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Les cartes, planches, tableaux, etc., peuvent etre film*s i des taux de reduction diffirents. Lorsque Ie document est trop grand pour etre reproduit en un seul cliche, il est film* i partir de I'angle supirieur gauche, de gauche A droite, et de haut en bas, en prenant Ie nombre d'imeges nicessaire. Les diagrammes suiva.-its illustrent la mdthode. 1 2 3 1 2 3 4 5 6 MICROCOPY RISOIUTION TEST CHART (ANSI ond ISO TEST CHART No, 2) [flB IIIIIM ■^ la. 12.2 34 40 ^ APPLIED IIVMGE I ^^ '6bi fii! Ma'f SUer-'. S TJS ftocheslc, New ^o'V 14609 ■ SA ■^S (716) 482 - 0300 - Phone ^S (^^6) 288 - 5989 - fa» A TEXT-BOOK OF PATHOLOGY FOR STUDENTS OF JIEDICINE BY •'. (iEORfJE ADAMI, M.A.. M.I) KRS KELI-OW OF JE»l-8 COLLErr ,.„„ MONTHEAL, CANADA; LATE LOLLEGE, (AMBIIIOGE. ENGLAND AND lOHN McCRAE. M.D., M.R.(;. R (Lovd ) v^..«oN. LA.E FELL..W .N '>'^'.:>>^^:::::::z:Tzz::z::z:, '-::::- - ILLUSTRATED W.TH 304 ENGRAVINGS AND 11 COLORED PUATE8 LEA & FErnCER PHILADELPHIA AND NEW YORK 1912 McGiLL UNIVERSITY, MOMTREAL, Canada Ijilcrrd urcoiiliiiK tu the Ai'l of Coiiun->s, in the year liU'J, Ity \.K.\ .v- Fi:m(!i;K, ill !lii' Otiicc ;o on*- of the authors of this work was ai)proacheo..k mii>t follow thr liiu-s of tlu- " rriiicipl.-.' must run the ilaiipr of app«ariiin to !)<• an al.i)n-viatioii of the same. I.iit must at tin- saiiif tiinr l.i- not an cpitomr of thr ilitf.n iit sections, liut a M ,,.(tion and .Iw.llinn upon what \v<- rejianl as mo-t important for the stn.hnf. anil this when the -.nl.jict is ^ \ . t an.l the innnher of men- facts ani.hTal)le, that the tc\t-l k of palholoi;\ of the past has often hein little hey.aul a catalo«ne of term- uith tlu- l.riefest linkaj;e of connecting Icttcr-prcss. lint facts and pht-noinena and their names an- only the hrieks with which the seien<-e of im'di.'ine ha> he.-n hnilt, and is still in the imwess ..f hnililinj:. We ha\(- to develop not the men- hodman, whose virtue depends upon tin- muni.er of l.ricks he can carry. I.ut tlu- en>;ineer- arhitect who, aecpiaintcd with materials aiul their emi»loyment, knows the use of each particular rc.oin or pa>-ai;e, knows why this construction is called for Iutc. that material there. If our l.nildin-: he s(miewhat lacking' in the elaborateness ot its decoration, wv trust that the founda- tions have l>een so devised that tlr n«.ms ahovi- will easily support what may eventually he i)laccn(l first aiul foninost to make <'lear aiul intelliphle what is known coiuernin^t tlu deeper meaniuK of nu>rl)id states, and have iu>t hesitated to sacrifice lists of data v>\^\ flu-ir nanu-s. The advanced j)atholop>t naiy hiok in vain for i,. ormaiion that will add to his kiuiwl- ed^e in jjarticiilar suhjc-cts; a s])ecialist is certain to find his i)articular specialty inadeciuately treated as re^'anis detail; hut to him who says that iniuh ha> Seen omitted we dare re|)ly that much has heeii iiu-ludeil. The all-important matter is to pn>vid(- and familiarize the student with the plan aiul workinn drawinjis of our science; once he has these in hi.s head it is a comparativ»-ly simple matter for him to pi.i;eon-hole meti- tallv lu'w fact- into their proper places as they come lumrinj,' in upon him ill tlu' wanls and dead house, in his n-adinii aiul lectures. This has Keen our aim and this is our a])olof;y for the iirescnt work. iL. I'l. hWCh VII TIm. fainili ;u w itii till- pri-vit.iiH vi)lii'iM"< w ill n-.' .LMii/.i- that ««• |,„^,. .l,"|.art..l littlr froii. ti»- t.-acl.mjj in I onKr (tl "If first, that upon (li-ii.ral l'atlu>li)>:\ . savf that there han hwu a.hli-*! an lU'iiuMiiary ■liaptiT upon pain and its M^'nifinuut'; on tin- other hand, from the verv fact olo^v \V( that it is .liftieiilt to Ik. oriKinal in the treatment ..f s,H^m l>ath- liave lMl,oniil uih' to that em I l.av.- writt.n it afr.-sh with little referen.i With like ends in m. \v we tn the eiirli- .oliime. have diseard.il most of the i! tn.tions ein| ,i„ved in the larmier work, introdnein^' soim two hnndu.i original iinravin^s from drawings nun \v l)v Miss K. S. Carrinnton fr""> »•'«■ |„. M.dill Mi'li-al Mnsenm and in onr deiiartment. an. material in t from the collections o' .air recti ,„,w of rittslmrtih, aii.l l'rof.-s.)r it l|.'a(;ii.'s I*rofcss.)r Oskar Klotz, I. iliea. ii.iw o ,f Harvard. T.> these, to o iir coll. allies Drs. Co ,Hn K. Hnss... llaiiford McKce. an.l naiiiilt..ii \,hitc. for their a.lvice with repir.l t.. si-ccia >iil)j If. ts. tl) Dr. Mac 'e Ahhott, Curator .) ,f the Mcdill Mclical Mnseiim. t.. Dr. Macl-a.lilhi ,1 I'ittshiirnh. an.l n..t least to our pu il.lishcrs. we w.nil.l here express „ur sincere thanks for assistance so wi itliiiK'l \ rem lercl. .]. V,. A .1. Md" M.INTHKM., I'll: ■■■ CONTENTS I'AHT I (MvNKllAL PATHOLOGY ('(■11.- Mild 'I'issiii's (;iiapti;h i I\TUI)l)l< TllKV 17 CHAl'TKH II The Cm sks of Diskasks InluTilcil Disease -Intrauterine Disease —Monstrosities and Al)norinalitips — Disease of I'osl-natal Ar The l,yiiipliatie Nes.vels-Hlood-fiirniinn Organs. The I.viiiph Nodes, Spleen, and Hone Marrow -Certain Orfiatis of Internal Seerelioii -ModilyiiiK the MIood, the Adrenals, Thyroiil, and I'aralhvroids aaa CHAl'TKU VII Till'; Hiitii'iUATorn Svstk.m (ieneral CoiisiihTal ions -The Nose— Pharynx and Tonsil- Larynx and Traeiiea-lSronehi -i.uiins— I'hnini— Mediafitinuiii -Thviiuis . . . 427 CHAPTER VIII TnK Nkkvois Sv.stjo.m (ieii'ial Considerations The Urain — The Spinal Cord—The Meiiiiiurs — Peripheral Nerves— The E\e— The Ear 473 CHAl'TEll IX Till-; I)i(ii;.sTiVK .Systkm The Moiilh and Teeth' lisophanus— Sto/vaeii -Intcstims i'eriloneiini l-iver- Call-Madder and iJiicts— Pancreas CHAPTER X Tilt; L'ltlNAItV SYSTEM I'he Iriiiaiy I'unclioii 'I'he Kidney— L'nMers—Hladder. .VJi) CHAPTER XI The Rti'uoDLcrivii Svstkm The Male Sexual Ornaiis— 'the I'einale Sexual ( huaiis -The I'rodiiets of Conception, Placenta, and Cord— The Maniniurv (iland 630 CHAPTER XII TiiK MoToit AM) Tecimkntahv Svstkms The M!isc!es--Te!,dan-< atid Tendon Sheath:-— Purr^a-Tht' Pi-iifs— The •loinls— The Skill, Hair, Nails ()73 ■iiL samm A TEXT-BOOK OF PATHOLOGY PART I GENERAL PATHOLOGY THAI TEH I INTRODUCTORY: CELLS AND TLSSUES THE mSTOLOOT OF THF CELL TiiK Ininiaii hody is made up wholly of cells and the jmnliicts of cells; it takes oriRiii from a cell, and carries on its life by cell activity; even its food is not available for its use save by the intermediation of cells. It is, therefore, reasonable that in ^eekinJJ to imderstand the iliseases of the human body one should study the diseases of the individ- ual cell, and not its disease only, but its health. This first chapter, there- fore, is devoted to the properties of the cell, and attempts to show how it is constituted, how cell interacts on cell, how a commiuiity of cells t'ornis an organ, how community reacts ujxju community — in short, iiow t' cell is at once a unit and a necessary part of a great aggrega- tion ot uiits. If the cell be regarded as an individual, it will be seen that, like a human Ving, it is born, grows, eats, casts out excretion, rests, is active, becomes useful, learns the work it is destined to do, fills its place in the community, falls sick, recovers, meets with acci- dents, is set upon by enemies in the shape of infections, enemies which it conquers or by which it is overcome, grows old, dies, and has its place taken by another like it. So far there is a parallel between a man and a cell; and it may be carried farther. The statement is made upon good authority that no man liveth unto himself, because a man's ilceds react not only upon himself but upon others, in however indirect a way; so the cell, as ])art of a comnuniity (the organ), cannot with- draw itself from comnnmication with its fellows, but will bear its share of tlic labor of the organ, and its ill or well-being will react upon the ceils that are near it or that depend in any way upon it. 2 18 INTRODUCTORY: CELLS AXD TISSUES The cell in health lies within the province of the physioI( """'■' J rr7 , A I /f-r Fia. 2 Vacunlation of nurh-i of fat crlls Fat cells of retroperitoneal tissue stained liy hematoxylin, and examined under the high power, to show the nuclear vacuoles, characteristic of this order of cell, o, nucleus seen from above; 6, seen in profile. Motor nerve cell from ventral horn of spinal cord of rabbit. The angular and spindle-shaped Nissl bodies are well shown, a, axone. (After Niasl.) The Constituents of the Cell.— The animal cell consists of two main parts, the nucleus and the cell body, and even if it cannot be agreed that there is in all animal and vegetable cells, a nucleus in definite form, we can at least, say that there is nuclear and cytoplasmic material. In the cells of man the nucleus has a definite form, generall.v round or oval; a nuclear membrane can frequently be made out, and inside this the substance shows an alveolar or netted arrangement. The miclear matter can be demonstrated to consist of (1) the linin or achromatic (non-staining) network in which is deposited (2) the chromatin — the material which is stainable by nuclear dyes. In the si)aces is (;?) the nuclear fluid. Xot always distinguishable are the following: {a) The mirlcuJii.^, an accuinulatic.n of nuclear material wliicli stains ditlVrcntly to the nucleus at large, and is j)resumed to b of a diflVrent, or at least, temporarily different comjMisition; (6) vacuoles, which are rare, but may be seen in the nuclei of fat cells, (see Fig. 1 ) and i .'•*•-;.<.'• ; ;~ / • » ■■- »*"•*. ""'v^^v; Cell briilgcs of vascular cndothcliun lAfll-T Kiilossow.) 2. The cell may have its prot< ])lasin developed into radiating pro- cesses, as in the infusoria; the luicleus and every y)art of the cell remains close to the surrounding medinin. 3. Tlierc may be great enlargement of the cell associated with the develoi)ment of multiple nuclei. It will be noticed that in all these cells, large though they become, every particle of the cytoplasm is near to the surface, if not to the nucleus, and that there is a rclation>liip a.> regards size between the inideus, the cytoplasm, and the sum nnding medium; this relationship is deter- mined by the size of the nucleus. The nucleus is the dominant i)art of the cell, governing the cytoplasm, and this governance must depend on the contact of nuclear matter and cyto])lasm; so that the nucleus which has the largest surface relative to its mass, will, other things being ctpial, be exerting the greatest effect upon the cytoplasm, will ''<■ the most active. If the nucleus be very large it is conceivable that r centrally situated nuclear material may be comparatively inactive, THE I'llYSlOLOOY OF THE CELL 21 M) tliiit wf ma\ say that tlu" small coll. wlidse nuch'ar mass is small (•(>iii])arc(l with its surfacr, will Im- active, and fittrd to siirvivi', wliiU' tlir - t'>- '#"/ K ^\^^r .- T DevclopinK egg of Aniuinn hifida, sliowlni: exlnisimi of nurlear mutter. VminK oocyte, the nuclear chromatin in the form of scattered branching threatla. The ilecply stained nucleolus is seen in the act of ejlruding cpherules 'clironiidia) into the cytoplasm, X i>(X)0. the mideolus, of granules, or chromidia, which stain deei)ly at first while they lie near the nucleus, and stain less deeply as they move away, until they aj)pear actually to become the secretory granules. The secretory gramiles are either actually extruded parts of the nucleus, me i,A'' THK I'liVSIolAKSY OF Tilt: (El.!. 23 (ir tlio pnMliictN of iiit»TH(ti(iii iM-twtrii >iidi cxtnulivl parts and (rrtain (oiistitiunts of tlu- crll IxmIv. The " prt'zx inom-iis" of the cell are Rivi-ii oil' from the iiueleohis, and in the cytoplasm l>eonme /ymogeiis, being again given otl' from the cytophism as specific secretions. Section from the liver of a child that dii-d from acute sepsis, to »how various stages of karyolyiia of the f^rst order: 1, unaffected nucleus; 2 and 3. paler staining nuclei, with some swelling and diminu- tion of chromatin; 4, nuclei still more swollen, the nien.brane only and an occasional nucleolar mass taking on the stain; 5, nuclei p-esrnt a» little more than unstained ve.clcs. The formation of fat in fat cells is evidently a tniolear process, for the vacuoles in their nuclei give the reaction for fat, and have some- times l.een fixed at the moment of extrusion into tlie central fatty globule of the cell. It is long since the changes were described which the nucleus undergoes in salivary cells during and after secretion, and nuclear alterations have been frequently observed in the ner\e cell bodies of vertebrates after natural and experimentally produced fatigue. The changes in fatigue in the Nissl boflics, which are of nuclear origin, are very noticeable. In general, it may be said that nuclear changes within physiological limits, arc manifested by (l) clianges in size and (2) alteration in the amount, and (3) the disposition of the chro- matin. In pathological conditions, still further grades of alteration are seen; such are reduc- tion of the chromatin (krryolysis), abnormal arrangement of chromatin, ledema, and swelling of the nucleus, vacuo- lization, nuclear disintegration (karyorrhexis), and abnormal discharge of nuclear material into the cell substance. Summary.— The following summary of our conception of the physi- ology of the cell n-,ay be given: the nucleus is the dominating part of the cell, which cannot act save in association with the cytoplasm; Leukocytes with disintegra- ting masses of nuclear material scattered through the cyto- plasm (karyorrheus). wi-.;r..\vtli. rr|.r.Mlii(ti(.ii. tiiul ol'tcn tiiiMti niiil n-mts upon tlu- <\ tupliism. tiikinj; siil„tiiiic.'s lr..iii it niul vicldinj; snhstaiicfs to It, l>iit not acting .lin-.tly upon thr mt-dinni wliidi sur- rounds thf (rll. The cytoplasm, on tlu- otlu-r liand, takes up and acts upon niattt-r from witliout. and >;ivfs out in turn otlu-r sul.stunccs; this It (h.es imrtly on its own account, and i)artly as intcmicdiarv for tlic nucleus. Thcs.- acts it performs in the proirsses of ahsorptioii and n-spiration, and it can he mohiie and contractile, as well. Lastly \ve only mention another im|)ortant class of activity, the prcxluctioii' of orjramc terments hy cell metal.olism; these can hi- discharged from the cell, and can act as intermediati- hodies hetween the external meduim and the cytoplasm, and can finally act, through the cvtoplas,., upon the micieus. THE CHEMISTRY OF THE CELL All cells possess, in common, water, lipoids, and |)roteins- the protems at least, are to he extracted from all cells as s.u.n as they iire dead, and exist m the Ii\ injj cell as such or as proteidojjenous sub- stances, which Kive origin to proteins. There are manv other sub- stances to he found in cells, such as salts, alcohols, carholivdrates, iind so on. and many of these we rej;ard as products „f disintejiration <)t proteins or as goiiij,' to be built up into proteins. None of them liowever, is common to all cells. Althoimh i)roteins are dead, inert matter, and have underj;one change before we obtain them, vet we i)elieve they are bound Mp intimately with what -e call "life." and when we refer to the active, living part of the . . as the biophoric' molecule, we mean proteidogenous mattei; that is to sav, matter which by re-arrangement of its molecules or satisfaction of its affinities becoines convert, into proteins. The lipcads above mentioned are, as will l)e pointed out later, closely related to the proteins. Proteins and Lipoids. -The Constitution of Proteins.— Proteins are comi)lex compounds of nitrogen, carbon, oxygen, hydrogen, and sulphur; some, too, contain iron and i)hosi)liorus. So larfe and so complex are the molecules that in general they are incapable of crystallization and remain in a colloid state; s.mu of the simplest proteins, it is true, are crystallizable, and can be obtained pure. The henu)globins (in the I)lural, for they are multiple) have been analyzed, and samples from rot('iii> arc tli<- iilliiiiniiis i>rriiiii alliiiiniii of lilood, t-^'^; alhiiiniii), the ^'loliiiliiis (si'ruiii ^'loliiilin, fil>riiioKirotciiis nn- in coinhiiiatioii witli various hmlics, iiu'liidiii^' otIuT proteins. Hemoglobin, for t'xainplt*, can he lirokcn u]) into licinatin or more lururatoly lifinoclironio>;en ;in iron-contain- iiiC liody with protein characters- and );lol)iii, an alimminoiis matter wiilch, accordinjc to Gamj;ee, is not a nlobuhn. The nucleins are com- pounds of protein and nucleic acid, \vhi;lol)ulin, myosin, etc., into peptones and albunioses, which are still ]>roteins but with smaller molecules; smaller molecules tliey possess, because they can ditl'use through membrane; the jjcptoues, etc., are dcj;radatiou i)roducts of the proteins, and we can infer that the ordinary protein molecule is a combination of like molecules, and is thus an examj)le of polymerization, or the formation of a larj;e nutleculebv the ajrj;re;;ation of a series of smaller ones which are alike, or of like order. The peptones and allnunoses atl'ord a still further series of degradation products, the >;roup of the amino-acids, which tojiether make up about three-fourths of the albumin molecule. These amino-acids are first cousii;s of tlie fatty acids, are indeed fatty acids with qualities tendinp to be basic by the addition ol" Nils molecules; which a^ain by iiydra- tion or by the addition of an Oil molecule become the hydroxyl fatty acids. These amino-acids, always j)resent as degradation jjroducts of !)rotein, are in reality the basis of protein.s; th" protein is built up by a linkinj; together of numerous amino-acid molecules. Chemists have now been able to obtain pure, and to study, a series of these amino-acids, and have been able to obtain optically active forms of them, the significance of which fact will ajjpear. It had been noted for a long period that if a substance were the product of vital processes, it was optically active, but if it were synthetically produced by the chemist, it was optically iiuictive. The optical actiuty of the now synthesized amino-acids indicates that they are, so far as hiunan observation can go, absolutely identical with the amino-acids of the body. T!ie antiito-acids arc amphoteric, that is, they pi/ssess both acid and basic jjroperties, acid by reason of their COC)H group and basic by the NII2 groups, and it is this duality of affinity that permits linkage. I>n iSTHOIHrroRY: ChlJ.S AM) TISSfKS To iis«' a lioiiu'ly siinilc, Ut lis iiniiKiiu' th«' plac«- of an iimiiiicacHl takrii hy a man. witli twi) artificial ariii>; at tlu' «iiil of niw is a liiM»k (tlir hasic aHinity), at tlu- nul of tin- otlitT, a rinn (tla- acid affinity); if thiTf won* a liirm' iiitinlH-r of such in»'n tlicy c;e colony (the comiMimid molecule) dejHMidinK for perfect cohesion upon the luM-k and riiij; men. These rings of varying innnher of amiiUMicuK arc tlic polype ptids, ami a linkage of eighteen individ- uals has heen experimentally ohtaineil ' is not even luwssary that the links should he the same amino-ac. ■.. just as it is not necessary that the men he of the same race. Tiie.c synthetic compounds prove hy their character to he all hut identical, if iiot identical with the peptones of the hody. Tiic conception we have here given may he erroneous in particulars, hut we have attcmi>ted to give the idea tliat the comi)lcte molecule is a ring, and that ring we have suggested hy the hizarre simile of the group of men hand in hand or "ring in hook." This, he it remcmhered, indicates only the simpler molecule; the more intricate proteins, l)olymerize l>< iiig surromided hy a concourse of individuals, who are constantly moving to and fro; such a picture, for example, as a hird's-eye view of a fair grovniil would afford; these individuals (ions or radicals) as they |)ass a group invite (hy their unsatisfied affinit> ! an individual of the group to leave it, and every now and then one of these free indix iduals is impelled to attach itself to a group. Ix>t us suppose we have twenty such groups, and this coiiii)ouiid group (or giant moh-cule) hy actual count has this formida : White2oo, XcgroMo, Indiaiito. Chineses,,. If a couple of children stray away the group he- comes whit«>2oo. negrosia. Iialiaiisi, Chinoiw, and tlie group is no longer the same. This is precisely what is occurring in the giant molecules of the 'oody; the arrival of a new ion of fooi.U-s i.. tl.fir comiH.situ.n. IV. H.k1u's of fatty imtiirt'. i.ot vft 'inalvze.1, «•. f/.. tlu Ii|m.- '''!i;"ont investigation in.Hcutes that the lecithins an.l ehdesterins are intiinatelv «ss.H.iate«king Renerally. m fats, hut un the contrary. .Iocs ! nt h. phosp'ho'rus ami "m«ked" iron (that .s, iron "' « -n;;>^'' •h.„). which a ,,»ear in the cytoplasm hut rarely and m small amo nt. -ria- proteins of the nucleus show some pecu uir cluiracters, Kastr c iuic. will dissolve ordinary proteins, hut the nucleus of a cell is resistant ;;.,;. „ecausc its nucleoproteins consist .,f alhumin and niK^leiu ami- hi„...l. and the latter is resistant. Nucleiiui contain 2 to 9 i)er ct ut of phosphorus, can he split up into albumin aiul !^/'"'^''^''"% •;;."";' "^ a.id, of which there are several. Nucleinic acid can be .^"rther d_i>- inteiiratcl into the x«ithin and ..ther purin bases uric acid, xanthin Kuanin. a.lenin, and hypoxanthin). These derivatives are ,m,M>rtant 'iini,.l'v because they exercise a toxic eflfect u,x,n tissues. esiM^cially the ki.inev, and it is these which constitute the drawback to a pro.e.n ,iiet in persons whose jmwers of elimination are imperfect Ihe exist- ence of phosphorus aiul the xanthin-base Rror-.)s onstitutes the ditler- ,.nce between ^he nucleus and other protopla. -s These groups and the "masked" iron and phosphorus are specially concerned with oxidation, tlv importance of which for the cell is absolute. Hefore leax r ^r this part ..f the subject we would remoitulate our idea that the •"..iophoric molecule" or mass is the active part of the cell; that .. is a huge molecule a>,,,re,iwted of many large groups, of which each, rnav be considere.l a ring of molecules with afhmties wnich are beinr satisfied by vari<.us other groups; that some affinities are c.nstantlv unsati>fiei(lc tlic cell, tlii' latter lu'inj; ('lal)oriit('(l ill tiif irll ami disi liarjifd. Kadi cii/.yim- acts upon a par- ticular sulistaiicc or series of siiltstimces in the external inediuin j)tyalin upon starches, niakinj; sugars; pepsin upon proteins in an acid inediuni, niakinj; ])c])tone>; trypsin n|)oii proteins in an alkaline niedinni, anil steapsiii ii])<)ii fats. It is not jiossihle to ohtain the enzymes free from conihiiiatioii with protein hodies; as the j)rotein material dis- appears from till- solution the enzyme action disap])ears. Finally, an extremely minute amount of combined enzyme and protein can convert a maximum amount of fermeiitescihlc suhstance, and yet the enzyme itself is not used up; the action does cease, however, when the i)rodiicts of fermentation, have accumulated up to a certain point. It will seem straiifre to the reader, at this juncture, to say that enzymes do not exist, hut such seems to he the case. Enzyme action does, but enzymes as definite chemical entities in all i)rol)al)ility do not. Enzyme action is an interaction hetwecn a jjroteidogenous mole- cule, and a fermcntescihle suhstance present in the same medium, l)art or the whole of the molecule acting on part or the whole of a molecule of the fermeiitescihie suhstance with the result that a new suhstance ajjpears- the ])roduct of fermentation. The Enzymes.- Enzymes are intracellular and extracellular; the former act in such close comhination with the hiophore, the com- pound protoplasmic molecule, that we have to conclude ttiat their action is j)art and i)ar(rl of the activity of the hiophore. This is proved hy the fact that such enzymes cannot i)e extracted, in fact, are not existent in the molecule unless it he alive. If this he true of the intra- cellular eiizynus, it is also true of the extracellular ones; these enzymes, in fact, are free protein molecules, divorced from cellular relationship, hut still manifesting a characteristic of life, viz., that of l)eing able to act upijii other molecules and cause their re-arrangement. Some hold that enzymes act hy katalysis, hut this view we do not advocate. They consider the ferment as a hody i)o>M'ssing active moleciibir vibration, so that, in ajijiositioii to molecules of the fcrmeiites- cii)le ^'.ll)stance, it communicates to them its vibration with the result that their particles are shaken into a new arrangement and the fer- meiitescihie becomes the fermented substance. This is the explanation given of the process by which finely divided platinum converts hydrogen peroxide into water and ox\ gen, and this process is katalysis. A more satisfactory explanation of ferment action seems to be that exem])lified by making sulphuric acid from sulphurous anhydride by the mediation of nitric aciil; the nitric acid gi\cs up an atom of oxygen which con- verts the siili)hurouH anhydride to sulphuric acid, thus: H2SO, HNO., = HjSOi + IIN()2 Til iinviiil i()nfil..-i()ii ui' i'iii|il(i\ llic liiiii tnii/iKi- III (U'Mniiaif ihosc fcrinoiits wliicli iirc pripdiiccd by the livinjj cell, to distinguish tiiciii frinii inorganic fcnnents, e. y., gold and piutinuni. EXZYMK ACTIOS 29 Tlic nitrous acid, so formed, exposetl to tin- air, coiiil)iiies with its oxygen and forms nitric acid, thus: HNOj + () = HNOj Theoretically, a single molecule of nitric acid can convert an infinite nunil>er of nioJecnles of sulphurous anhydride into sulphuric acid and at tlie completion of the action (if infinity could he completed) still exist as a molecule of ii'tric acid. In this process there are three factors— the suli)hurous anhydride represents the fermentescihle sul)stance, the oxygen the fermentator or complement, and the nitrous acid, which alone is i)resent in both reactions, the ferment. The process can he represented as follows: .-■liiinii "f f,Tinrnt-like ...lion of nitroiM oxi.li- in the formation ..f sulpl.urio ai'iil from siil- |,l„ir..us ;,nlivclricl.>. The coniplcte.l cirrlf rrprpa.-nts tl.i' su.T.'ssivi- .•.tuKi's of activity of the UNO; n.olorulo, first iittadiinc to itwlf ao O inolpcule from an O, combination, and then yiol.ling this to an un..ati.=ficil II ..-;0, molecule To the left of the (Imuran, it is souiJesteil that the .ither O molecole hlHrate.l from the O, c.mhinaiion may also comhitie with an IIw.SO., mol,.cule to form a second molccii!'' of .sulphuric acid. If instead of the hodies in the ahove picture, we consider that we are dealing with protein molecules with their unsatisfied affinities, we can conceive the process as heing instigated hy their unsatisfaction and concluded l>y their satisfaction. Knzyme action is one form of the interactivity' of the l)iophores. This heing so, one of our com- pouiitl ])roteiii "molecule- may he intermediary hody, or it may he tVrnicntc^cihlc luhst.'nice: or. since each iiulividnal ])art of the huge ring has got its own peculiar characters, and its own \msatisfied atfiiiities, the same huge molecule may he in a sense both at the same ■PP ■Vj?'- 30 ISTIiODVVTORY: CELLS AM) TL'teins; (iM cyt(ii)lasmic matter, capalde of indei)eiident metal)olism Init incapable of growth save in combination with nuclear matter, and {'.]) the free organic enzymes, capable of causing metabolism, but inea])- able of growth. .\re we to admit all these into our conceptioi of what is living matter? This is a moot jjoiiit. For ourselves, we are incliiu il to regard growth as the all-important property of living matter; but if this view be accepted, then it may be held that the biophores situated within the nucleus are the only truly living elements vimin the cell. This is contrary to the usual conception of the cytoplasm as being also living matter; the cpiestioii must be left open. The Reversibility of Enzyme Action. Since we count cn/ymc action so important for an understanding <»f mctai)olisin, we must indicate that it is reversible, and in fear of making the subject too cimiplex, we shall merely exemplify this. The enzyme maltase splits up maltose (<',..ll...j()ii) into two molecules of glucose (('ollijOel. but in the test tut)e the reaction is never complete— there remains a mixture of maltose and glucose. Maltase really can split up maltose into glucose or build 11]) glucose into maltose, and so long as the products of disintegration or of synthesis remain in the solution, neitlicr the glucose nor the maltose can be used iij). The enzyme will cease to ct when a stage of e(iuilib- riiim is reached, when the tendency to di ; .-egrate the one balances the tendency to synthesize the other. This action may be exjiressed thus: CisH-On + HjO + Maltase ;^ CsHiiOe + CellijOe + Maltase. Maltuse. Glucose. Gliiciisp. \\c have at the ])rescnt writing evidence to indicate that all enzyme action is potentially reversible (althougl; recently it has been shown that the reversed action may require a temperature ditl'erent from that refpiired for tlie original action), and this of itself is good evidence in favor of the supposition that an enzyme is not a chemical entity, but ft mnjiiKj state of not iaf act ion hit mm the affinities ri-:i.\ cossTiTrEXTS 31 inattiT of (litVusioii. Tako, for example, the plyeoKcnic activity of the liver cell. If the cell in its metal)olisiii has burnt up the <^\uvosn it has and heeonies deficient in carhohydrates. more jjhicose will diffuse in; the ferment in the cell will synthesize this to frlyco};en. and will con- tinue so to do till there is a local ecjuilihrium hetwcen the intracellular j;ly((>f;en and su}iar. Glyconen, heinf; insoluble, remains in the cell, stored up. There it remains until one of two tilings happens: until either the ceil i3 using up ghicose faster than gluc(»se can diH'use into the cell from tlie lymph, and the glycogen-glucose equilibrium is destroyed, w hen the re\(rsi- enz.vnie action begins to break down glycogen till so much glucose is formed that the equilibrium is restored, or until the ghicose ill tlie Ivmph is reduced, by the tissues using it up, faster than the iiliinentiiry tract supplies it, to a point below the amount in the cell. If this happen, the glucose bein soluble, diffuses out into the lymph, and the glvcogen-glucose equilibrium is again destnned; the ferment action will" break down glycogen again, and if the equilibrium be not restored by a fresh supply of glucose, the glycogen of the cell will be used lip. . This process we have just described, essentially an enzyme i)r()cess, is rciilh what we have been accustomed to call metabolism; the cell e(|uilil.riiim de|:ciids upon the enzymes in the cell quite as much as, ..r mure than upon the material absorbed. If the enzymes of the cell lie interfered with, the essential agent in absorption is lacking, and we find disturbance of metabolism. As free enzymes in the cell are a»()(iate(l with discharge from the biophoric molecules forming the iHiclcu^. we see how the foreign agents of disease, by disturbing the biophore, strike at the very foundation of metabolism, nutrition, and the well-being of the body. i ■ i Non-protein Constituents.—Water.— Cell activity is associated with the i)resence of water, water being the medium in which metabolism (.(■curs. If the amount of water be reduced below a certain percentage, hitencv of activity supervenes, and if the water be removed entirely, in.iieciilar death; 60 per cent, of the human body is water, and SO !)er cent, of certain organs, such as the kidney. The average cell of the Ininuin ixxly may be considered as seven-tenths water, and three- UMitlis proteins and other constituents. It is still debated whether living matter is existing in a soluble state in water, or as solid undissolved molecules suspeiide!\<'il lindy lie in the interstices of the solvent- in a colh.id, prntoi)lasni for instance, we have to imagine the molecules()f water as lying in the interstices of the huge protein molecules. The 5!i 32 ISTRODUCrORY: CKLIS AM) TISSIES question is ,.f importance lH- .Iroxyl ions in a watery solution, and these ions are most important in the prooess of metabolism. Simple Salts.- Certain salts without being built up into the protein „,.,kH..le are obvi.n.sly essential to the cell, for the protein molecn e does not exert its activity in a pure watery medmm, hut ni dilute saline solution. The salts usuall.- met are chlorine salts, alka hue rirbonates. phosi.hates, and sulphates, and salts of the alkaline earths, esneciallv sodium, p..tassium, ammonium, calcium, and magnesium. We know little ah..ut their disposal, hut we assume, from the mnuite nnantities present, that they probably are mostly < issociatetl into their ions and so help to promote activity ot nietabohsm. i he dis- sociation of salts, an.l their building-up into the hiophore an- accoin- nuued hv various phen..mena which we call endosmosis and exosmosis, which is the .litVusing. in or ...it ..f the cell, of water an.l salts in s.. utmn. \ salt oi high concentration in the cell will pass out ot the cell to a mclium where the oncentration is h.wer, an.l vice versa and at the same time a corre.'tive reverse passage ..f water oc.M.rs. I he colloidal cell substan.^e is sufficiently permeable t.. all.nv the m..le.-ules ot the salt in solution to pass. We believe, t...., that c. loi.ls ot . irterent compositi..n .litfer in their permeability, an.l. ther.'h.re m the time renuirci for the passage thr.mgh them ..t s..lutions I Ins relative impermeability ..f the c.Uoi.lal skin (ectosarc) ..t the .'.» per cent, sodium ciiloridei. Solutions with au osmotie pres- sure higher than this are hyperisctonic, witli one lower, hypisotomc. The blood serum must he very hypisotonie before hemo«lobmemui, from passage of the hemofilobiu out of the cells, eau occur purely from this cause. . Carbohydrates. Free carbohydrates as such do not enter mto the composition of the bioi)hore, and when found in the cell are true metab- oUtes; thev have been or are ready to l)e dissociated. It must, how- ever, be rt'calied that the dissociation of nucleic acid yields a pentose iMigar) according' to Levene and .lacol)s. a hexose ac'cordinj; t() Steiidel and Halliburton. From the ilissociation of sugars energy is liberated, and on the contrary energy is conserved when they are stored as built-up glycogen molecules. Fats, Soaps, and Alcohols. This is another grouj) of metabolites, which mav jm- 'biy lie s])lit off froui the cell i;rotein; they are not found in the n't.-lei (save, as already noted, that fat has been found in luielear vaci.oies;, and are to be considered as acted ui)on maiidy by the cytoi)lasm. Certain cells are found to contain insoluble neutral fats of which the most important are stearin, palmitin, and olein; these fat;-, aecordirg to their fornmla. contain a very small quantity of oxygen with a relatively large amount of c-irbon, which means that their dissociation and' combination with abs(.rbed oxygen is capable of netting free a great amount of energy; hence their value to the cell. 'I'hcse come from the food almost entirely as neutral fats; they are < iniilsified bv the action of tlie bile, and, to some extent when emulsified, mav be absorbed by the phagocytic action of the intestinal epithelium ,111(1 leukocytes. Hiit this is by no means all. It would seem that free liitty acids are to some extent sjjlit (.ff, soajis being formed and glycerin liberated; while again there may be actual solution of the fats by the cnlloids of the cells and body fluids. This matter is not yet determined. The presence of the fat-splitting ferment steapsin (discharged by the pancreas) in the intestinal contents favors the division of the fats into iree fattv acid and glycerin. The latter is jjrobably taken up by I he intestinal epithelium; the fatty acids are partly dissolved by the Kile salts, but most of them, in an alkaline medium, are transformed nto soaps of sodium, jjotassium, calcium, and magnesium. As soajjs ihcv j)ass through the intestinal cells and are to be found in the chyle iiid' lymph as neutral fats. Neutral fats are rarely found in the blood. \iiile' soajis commonly are; so it is evident that a second conversion Mcciirs; it is as soaps that the fats are ultimately taken up by the cells. -Microscopically, the cells of an orr .n, e. ij.. the kidney, may show n flit nor do they yield ft \y'*\\ to ordinary fat solvents; yet lie dry .sul)stancc "of" such a / -. v>rds as much '7 per cent, of at; this means that the fats ;. ■ not free, but c(mibined. Soaps are evidently very important as iin intermediate stage in the a 34 INTRODl'CTORY: CELLS AM) TISSUES utilization and synthesis of fats; lipolytic and fat-forming ferments have heeii isolated and designated lipases. Do proteins give origin to fats or tatty acids? They probably do to a slight extent, i)ut at |)reseiit it appears as if the fats of the body are almost entirely the fats of the food. Here it is necessary to mention the lecithins, which are almost constant constituents of the animal cell, and forr.j a considerable factor in nerve cells and in the cells of egg yolk. They have a fatty jx^rtion indicating a relationship with fats; they are nitrogenous s\iggesting relationship with the proteins; and they are richly ])hos])horized. The last two facts suggest that they are cleavage products of the inicleins, or combinations of such cleavage products with fats. Parallel to the lecithins as protein-fat compounds are the glycoproteins-or protein-carbohydrate compounds — chief of which are the nuicins. These are to be seen in the cell as globules of mucinogen, which by imbibition of water become mucins. They are modified, largely inert, proteins; among them are gelatin, elastin, chondrin, amyloid, and mucin, which are poor in carbon and rich in oxygen, and yield on dissociation carbohydrates. A few other " albumin- oid" materials occurring in and outside the cell are to be mentioned: such are the products (»f dissociation of I emoglobin. such as hematin, together with melanin, the pigment of the skin and hair, which recent observations indicate are allied to the lipochromes, compounds of lipoids with protein derivatives; these will be discussed with the infiltrations and degenerations. GROWTH In all our previous considerations of the biophore we have dealt with ipetabolic activity, but we have made only passing reference to -owth. If Wf think a little it will be seen that the growth of living matter demands a process whereby two molecules exist where there was one before. Our conoeijtion of the bio])hore is as a ring, or a ring of rings, and growth occurs by increase first of the individual smaller groups or rings. These grou])s, from their very inception present a series of unsatisfied affinities, and each or any of the molecules is con- stantly attracting molecules of a like order, and on the first of these is built up a second and a third luitil the group is complete. Along these lines we can imagine the development of a new ring of which each in«lividual component is the reflection of the components of the original ring: in its turn this ring attracts, ami so builds up other rings in due order until eventually there is produced a completed compound molecule, reproducing the parent molecule. We use the illustration of the ring to indicate a degree of completeness; the ring can break, it is true, and in its repair, be enlarged or be made smaller, or it can join with another l)roken one, but the mole-jules of the formed ring are less likely to be attracted away just 'oecause they are in a ring, i. e., in a state of relative completeness. GROWTH 35 The Relation between Growth and Other CeU Activities.— The c.nsi.lrrati.m of this siibiect (lenmiids a few words on the dynamics of the cell. In tiie perfonnance of function of whatever kind, t.ie cell is a machine discharfiiiifj potential cnerfiy. The body warmth means that cells are •lil)eratinK' energy in the form of heat; the nerve rell liiierates energv akin to electricity. On the other hand, growth and tlie accumulation of new molecules demand, not the evolution, hut ti storage of energy, and this comes from the food. The proteins, carbohydrates, and fats are carl'on-containing bodies the ultimate result of whose decomposition is a > ielding of much energy. The excreta of tlie organism, carbonic acid, water, urea, etc., on the other In nd, store up comparatively little, and the cells acquire most of the difference. Strictly speaking, energy is not evolved in the dissociation of matter; but dissociation and the "freeing of ions mean that combinations im- mcdiatelv occur which liberate far more energy than was lost in the di'^sociations of a moment before, so that the ultimate result of disso- ciation is, paradoxically, a storage of energy. The biophores are not to be compared to simple salts, but rather to nitroglycerin. A blow^ dissociates it, and though there is a theoretical momentary loss of energy, there is a vastly greater immediate i)roduction of energy— an exi)losi()n— brought about by the reconstruction of the ions of C. (), X, II into more stable compounds. Dissociation, then, tends t(. the liberation of energy, and growth, or building up, to the using and storing of energy, the conversion of kinetic into potential energy. The energy of the food is thus: (a) Katabiotic, dissipated in the performance of function. (6) Bioplastic, stored up in the formation of the complex biophore, i. e., in growth. Van these two contrasted processes, growth, and the performance of function proceed simultaneously in the cell? They can, as we shall show. . To digress again, growth is an intracellular affair, governed by condi- tions in the biophore, while the performance of function is a response to external stimuli of some kind. If the cell has abundant food, and the stimuli to function be strong, all the acquired energy may be used up at once, and no growth ensue. If the stimuli be yet stronger, all the food energy may be used up, and the cell substance be dissociated to sujiply the further energy required. If the food energy be little, the I cell may require to use up its substance to provide the energy needed for function. There is, however, a grade of adequate food supply and of moderate external stimulus, in which the dissociation of the food- stuffs provides more energy than the cell is called on to dissipate and the surphis is used in growth. The development of muscles under proper exercise illustrates this. Conversely, with adequate food, and not enough activity, muscles do not develop, but the contrary; a certain optimum of activity is necessary for the maintenance of nutrition and of growth. There are apparent exceptions to this, in a? -= >.», ■^i^aF'^'^B^-' 36 IXTRODrcTfiin': CF.IJ.K .1 V/> TlSSl'KS the I'liiliryn, in tiiiiinr ^'rnutii. an I in the Inct that undtT cxenist' and ailc(|natc nutrition tlicrc i^ a limit licyoial wliidi ^Towtli cannot >;o. Whereas j^rowtli and function liavc tinis a definite rclationsliip, there are fireninstanccs nndcr wiiich >;ro\\th is (piite in;resscs until the volume of the cell (and of the individual; reaches the point lieyoud which increase in mass is not only imeeoiiomical, hut harmful. There is a relation lutweeii surface area and mass, and when the mass exceeds a certain amount, the surface area is too small, and assimilation and discharge are hindered. The c<'ll has now the alternatives of cell divi- sion (hy which there is a rapid increase of surface area relative to inass) or of lessening its mass hy the ])erformancc of function, that is, of dissociating: some of its cell sulistance. As long as the cell or the individual is helow the economical ratio hetween its mass anf individual continues till this optimum is reached. In the dcvelo])ed cell there must lie a constant alternation hetween growth and functional activity; in ]!erformiiig function the cell dissociates some of its sulistance, and falls helow the state of oi)timum efficiency, and it is in a juisition to take u]) new matter, and grow; Weigert's statement is "the katahiotic use of material in function removes the ohstruction to growth." Physiological Inertia and Habit. .\ wheel set s])i:ming continues to s])in iifter the haml is witlnlrawn; a gland stiimilated to secrete contimies to secrete after the stimulus is removed. .\ resting muscle continues to rest (during the Icifnil jicridd) hefore it acts in response to a stinmlus. The cell, like matter in general, tends to continue in the state in which it is, whether of rest or activity. This inertia is the jirecursor of habit. .\ cell stinuilated to ]»erform an act. continues to perform it after the stinmlus is removed; on a second occasion, a slighter stinmlus suffices to make it rejjcat the act, until a period is reached when a niininnim stimulus will ])roduce an o])tinHmi reaction, and the cell, tending to emi)l()y its energy in one ])articular direction, tends to lessen its acti\ities in other directions. It hecomcs adapted to its work. OiK'c a eel! st.".rts to grow it has a ten1 ON th J^ ^^ ^.^.^^^,,,, ^, ,,,. '-» '•■'"""■^ •"";•■ * ^Hn!:; V hv Si tlu. energy that is put -nto ruxvtii iM'coiiifs, at tlu prop i ^,f fuM.'tioM an.l a .•o..t.nuan.'e of tht RESERVE FORCE All imp^rtiiut ( ■iiaracttr of living " attrr IS w hat is tiTim'tl reserve force; upon it (hMHMi.ls thf proi'i .f hi-al lui^;. Just as a \va ill, a hridttt" or a l,„iU.r. l.iiilt ou souiK il mei'hauical priunp IS an ihlc to stan< il a strain several time: Uri-ater tlian it is on liuarilv expected to earry hc "factors of safety t It there ,ftheeiiniueer).soarethece l)f tluM )rnauism; is a larj;e thev exert ww reserve i ,f force or energy hi them liT normal conditions. Illustratious o nl)o\ f th that whicli are knoNVi to cvervone. The patient \yho see ■ms so wta k that he can scare •ely his arm may raise heart can ' JuTome in .lelirium a m ,tch for two men. The lo thrice its norm ill work without overstrain three-(iuarters ic ran of tl it> iiurp< injury to t l.l)it"s hver m ise; t i\ he remove( ,1. and the reinainiiif; (luart he whole of the spleen ilth .f tl lie 111) ifj ma\ iv he exciset er serve I without he animal's health 111 the last case. ther related tissue take 11!) the functic )I1S o etr itv; yet vieariou. activity is ,f the a pure ,,„, .M-rcisins: a f^^)^';^^ "i; compensatory - - . example of reserve force, ^luli also v i„.,rv excretion; nim, will suffice ^^ ^^^'^:T'.Z^^^ "P th^ work of its wen in the hrain. one ot a pa - .J^- '^^ ,,„,,,,,,,/ .. t. possess .U.troyed fellow. In shor ^'^^^ ,,^ re.rne force. This reserve ;, ,„., „f i,.f,.nctn„. on ';^:;; ^^ ,' ^ ^,,.1 of immunity f. .lisease. ,„r.... 'ies at the n.ot ..t the »H^>ll% ••' •' ^ ,,vsioU,pcal inertia. I-de U..,.rve f..rce is yet one more "^ 'J.,,,\,nnternal con.l^ ha> hecn defined as the c->ntnumus . 3^ m "t ^^ ,, :;;T;;::-;;:u;;mS:i:::;.fr^r^^^^^^^^ THE STATES OF CELL ACTIVITY c.nstitute cell disease. , ■ ^,jp accumulation of 38 INTRODUCTORY: CELLS AND TISSLKS relutivelv little stimulati..n pass int.. an iiu-rt, latent state. Tliese el s with lack of sti.nulation, atrophy, «n.l son.e c.f »-> -t-l disappear. Not only .h«s this occnr w.th redum ant cells, hu oe S normal cells nn.ler al.n..rnml conditu.ns; th.s can he uell seen h he atrophv which an innnol.iiized leg underRoes; a.u the actua san trance' of cells is seen in the cases in which the lower ino ..r Z es roplly and disappear as a resnlt of lack of stnnu at.on from the upper ones, in cases where the npiK-r ones are destroyed. > Vegetotive Activity. Cells in the ,.roc^.ss of active growth present certain well-marked characters. The nuclei are large roimd or oval stall ng tains poorlj , the cvtoplasn. in the case of cells like those of th^ ney tubules may be Sntegrated an.l partly discharged; or ther. ..ay be abnormal clepoSs ii the meshes of the cytoplasm; or the cytoplasm may bec.me vacuolated. CELL MULTIPUCATION Increase in size of the individual is brought about in two ways: bv enlarirement of the individual cells, anrm, ^.^^^^j^j ^^j-g ,ts hall ':, borate '' q^mdrUle," but each daujhter^^^^^^ ^ L happens in hidirect dw^su)-^^^^^^^^^^^ ^j ^^^ biophores so that •,t.,.lf I (licates that there is a dinerem . identical with that „htamed by the other. »«= JO IsmnhfrToHY: (F.I.I.S W" TISSUES ;.;i..s .......rntratnl int.. ra.liatin, Hl.riU. f..rn..,.« a Mar -r aster an.l as tl..- tw.. l.alv... ..f tl.f .■rntr..>.m..> srimrato an.l J..ur...y t.. ..p -m.. ,„.l, ..f tl... .rll. a spindle ..f tin.' fii.rils i. s.vm ''\^'7.»"';/"'.'7-';'';, 'j ' . •• Metaphase. Ka.l. pi...ll.. TLi; ^i-li'f"');: "' "'»-■ ••It.."...-,...-s is the tiii..laiii.iital pr- iii <«'ll .,l., wln.l W..l,.u-; irn^nlarly sw.U.n ..r ,....l..lat..l a,..l f..rn,s tl..- ...twork ..t the r.stinn n.u-l.us. ADAPTATION Wo l.av. alr.a.ly n.a.le tl,. stat.me..t that the ..r«a..isn.^ran a.h.pt its - f to its surronn.rn.jis. a...l th. .lo.trin. ot th. s,.rv.val of tl.. hlU^t "li -ates that wh.r. th.r. ar. n.a..y i...l.v,.l..als ..,..l,-r,on., H a .^e ri.e.on.e l..tt.r snit..l t.. th.-ir ...vin...n..nt. th. on.-s wh-; .-.t vvH 1 e - r..,nir.n....ts an- th. ..n.s who snrv.v. a...l th..r progeny so n....liti..l f..r.-. out of .xisc... th. f.w.r. w.ak proK...y ..t those W V. I -..lante.l V larp- .U-n.ent ..f .hanc. .nt.rs n.to s,.<-l. a process T^;; V Awhile trl, is ..ot th. wh.,!. trnth, A.h.ptat..,.. .s n.^ . . Uve fortnit..,.s rn.KliH.ation of living' n.att.r .n a lav..ral,l. .lir..- li';; In.; an activ. pn.c.ss, wh.r.l.y a .han.c .,. s„rron...h„gs hrn.KS nlumt -i (-haiiu. in ."i. composition of ti.- hviiifr matter. " ..m s'i aoa.tation are ■...m.n.ns; l.actcria wl...;l. or.l.nar. y spli .,. .-arl.ohy.lnacs <-a.. he n.a.l.. I.y grown., n. >p.c.al m.-. 1 split up prot.i,.s; l>act.ria wl- vh can fernu-..t one J''^- '"V;:;^; ,^^ 1^^ m-,v he "traine.!" till thcv ferme.it the sccon.l a;..l not th. hrst, l.a t.ria :S-h w.^uot pathogenic ca,. he "'-le t.. !.ec..na. s... 1 ..s.- ahm^ .w.w.Ts .r. due to the ac.i.iirement ..t new (inahtie^ In tl.t l.act.ria , i .g 1 se V.S to their particular surroun.lings; th. alt.rat.on Jan • .'r i .. sh..rt a tin., as to n.ak. it certai.. that .t >s an act.ve i c. T .e a(-c,,.ire.l imn.unity \n ...a., against .hseas. ,s an exan.ple u aptati..... the cells a.laptiug then,sclves to ,.>.e --^If^-^;^^;;^; i„ this instance the toxh. <.f th. special hactcr.um. Ih . mlaptati, .,v remain f..r a long time after th. t..xin has ccas,-.l t.. he pr.s.ut nia\ reman. ..•■ ^ alteration n. constitution l).(-ause iher. is IIIlpr^■^^.e^l on t!K tt ii oim an- -,iu. l.i-for.-; /..--I, in the n.i.Mlc of; "■■', huckwunl; -',■'■■', afar. PLATK 1 A ;A I \'l> /V^ A A V V I -^ y ii Id Th HI Mitiisia. CELL DIFFERENTIATION 41 wl.i.l. =s ,.assf.l on even W the progeny of the cell. The capacity to .„l,nt itself is inherent in the molecules of the cell, an.l tlie molecules ;,,;,'„,, ..han^-ed in response to some aj;ent or agency n. the euviron- inn.f it is n..t that the tendency to vary -s mherent, but rather that th.. power to change in a particular <^\. -uo,. \- present, the change iH.in'' in response to the action of a i-ecific a-e-ii. '-.xpressed more ,,„urctelv. a particular modification u; ,l.e envir. r.aent is able to .■hange the pn.toplasmic nu.lecule in ^ .iTticular vay. It the cell remain in the same environment with .n. :..- ■ U.nds of food m(.le- ,,,U.> coming to it, the cell response will be to buiUl up the same side ..hah.s within limits; in short, the cell will not vary Hut as soon .,. a new foodstufl' is brought to it, and dissociated, an entirely new ^et of ions mav be produced, and new combinations entered int.) new side-chains may be built up, and the protein molecules in the cell itself therebv altered. This particular cell has gained a new .•haracter bv adaptation, by undergoing a molecular re-arrangement; .vrowth goes on at the same time, and the new side-chains may be detached into the surrounding medium or may remain and be built up into the cvtoplasmic or nuclear molecules. If then a cell has adapted Itself, and" has multiplied, the process of adaptation is not over, for its progeny will partake in the altered composition ot the molecules in tiie i)arent cell. . . i » 4.1 V.laptations such as these will occur m response not only to the fuodstutls. but likewise to toxins; and changes m temperature, vibra- tion, light, and other physical agents, not introducing any ne%y ions or molecules mav xet cause a re-arrangemeut of the molecules in the binphore. and so an actually altered composition of the cell, with altered characters. CELL DIFFERENTIATION \ corollarv to this is that a cell becomes adapted to its particular Mt of circumstances, its food, and so on, and thus becomes ditterent li„ni its neighbor; this is the reason that underlies cell diHereutiatioii; it we begin with a cell, which multiplies itself into a mass ot cells, it is ui.vious that the cells on the outside of the group are in a relation to the surrounding medium which differs from the relationship ol those ,1:1 tlie inside. I' >e begin with two separate cells, exactly similar .ach of which gi, s into a multicellular organism, if each be exposed t,, (xactlv the same environment the daughter cells will be ditter- , ntiatcd in exactlv the same way. But if the biophonc composition ol these two cells is ditt'erent, even if the environment be the same, •AC -liall have the daughter cells in the multicellular organism ditier- .ntiated according to a plan that differs from the (lifferentiation of the last example. To state this otherwise, we would say that eel .lithrcnti. ;ion is due to two factors, bioplioric constitution and physical intiu(-ue., and that in praclically every case, both are at w-ork Ac rnuid tluis understand, albeit in a hazy way, how the one adult iiidivid- 42 INTRODUCTORY: CELLS AND TISSUES ual differs from the other, even if we were to i)resuppose that the ovum was exactly the same in each case; the more difficult task is to determine why one individual is like another individual, why son is like father, and this leads us to inquire wherein one o\ uin is different from another ovum. Two ova, side by side, look to our eyes alike, let us say: why is one going to become an elephant and one an insect, and how comes it that the elephant is certain to have a trunk and the insect wings? Is there, in the ovum, a part of the protoplasm that is definitely of such composition that it must form a trunk and not a tail? And where is the protoplasm hidden in one cell which will determine that this particular elephant will have tusks like his grandfather, a trunk like that of his great-grandfather, and the temper of his great-grandmother? Is there a special piece of protoplasm in the ovum which has directly descended from each of his thousand ancestors? Xo, there is not; and we can prove, from what we know of the protein molecule that there is actually not room for them. The theory of "the continuity of the germ plasm," as it is called, which presupposes the descent from generation to generation of an infinitesimal part of the proto- plasm of each, is a physical impossibility. Such "determinants" carrying particular properties derived from one or other ancestor, which shall in due time be distributed to one or other tissue or area of the fully-grown individual and shall endow that particular tissue or area with the properties seen in one or other ancestor demands, it will be seen, that every separate feature in the body, even down to the particular markings of the thumb prints (which are alike in no two individuals), shall be present in the fertilized ovum, demands, in short, that not merely the microscopic nucleus of that ovum, hut the chromatin or whatever part of it conveys the hereditary characters, shall be made up of these innumerable determi- nants. Now, according to Weismann, these determinants cannot be simple molecules of matter, but must be molecular groups, and as we have pointed out that living matter is proteidogenous, each individual molecule must be of a size which, according to physicists, is almost visible by the ultra-microscope Regarded thus, it is a physical impos- sibility that the minute nucleus of the impregnated ovum can contain all the determinants demanded by this theory. If, therefore, we can- not accept the idea of determin.rts, is there any other means by which we can visualize the facts of inheritance and of individual variation? This biophoric hyjjothesis apjiears to us to afford the only means of explanation at present possible. The elepliant ovum develops into an elephant and not into an insect because the elephant ovum is made up, in the main, of molecules of a certain average composition, a ring made up, let us say, of small'T rings each represented by A: A A a- / A \ A / A— A— a / \ A A \ / I— A— A CKLL DIFFERENTIATION 43 A l)ir«l ovum, on the otl^ r hand, may be made up of X rings, thus: X / \ X X I I X X / A The biophoric- molecules of an insect ovum might be represented by U /\ U— R These may thus differ one from another not only in general com- position (as A is different from R or X). but also m number, and mode of apposition. The fundamental grouping of the molecule of all eU'pliants is the same, thus: A A \/ A the biophoric molecules of the ovum of one elephant differ from those „f another in certain slight modifications of one or more of the constit- uent parts of the ring, which may be represented as side-chains; thus for one elephant: a-A A- / for another elephant: A— a A; as no two individual elephants are identical or can be represented by the same formula, it is evident that progeny of any two will present a ni.Klification of the formula seen in either parent; these modifacations arising by elimination, interaction, or summation of the characters rep- resented as side-chains. , Having thus dealt with inheritance and the effects of fusion of the male and female elements in the new individual, let us now consider the modifications acquired by environment. , .. • j- Acquired Modification.— Passing on to the evolution of the indi- vidual from the ovum and the differentiation of his various tissues and ..rgans. it must be clearl>- realized that when the ovum divides ii.to two, each daughter cell has conveyed to it biophoric molecules, and that so these biophoric molecules while coincidently multiplying by the successive ■ISSWS\li' 44 ixruoDnroHY: ( i:i.i.s wo rissrKs .on UKi .nMlt.p! cat„.n ol t h,. .rlls „( tl.o «nmin^ i.ulivi.lnal c.n.e to iK-.l.stn l.ntcl to a. the fs.nos ,.f th. l.o.ly. So far as w. <,„. scv ti.ev I.nss to tl.f gmn (vlls „, an iiM,.l,a,.K.-.l «■ liti.m, l.„t i„ tlu' s,.,ressi„„ ot .I.V.S.O,,. wl.K-l. K.v ns(. to tiM. snn.ati.- or l.n.ly ,rlls, tlu- infln.-n.rs '.'Tit' ^•"•'.■^■^^'^•- «^->"-n'tio.,s of ,.dls an. ,-xpns,-.l in th. .linVrent part. n( tiR. Kn.win^r ,.,„|,rv„ ,),|iVr vrrv greatly. It is i\uv to the .liJlVr- once ... position ,.li,s tl„. ,iiffm-nce in foo.|stntrs a-ul phvsical an.l . ......<..l aKo.„.u.s to whi..I. tl... crlis arc- ...vposci. tl.at the containe.l l.iol.horr. ,ei-on.o ino.liho.l, until ovontnally, the n.o.lifi.-atio.. heeo.nes so gn-M that ...stea.! of these l.iophores l.eii.g able to repro.h.ee the whole ....livKliial. they now l.eeonie eapal.le of .ontrolling the formation ot only o.ie part.ei.iar d.lhre.itiated order of ceil Following ,ip„n this, the general staten.e.it inav he made that the more ,,mu„m,rd fhe (liffnentuition of a cell, tlir 'irs.s- n. cnmntij for rcproduchon. ^ et there are certain cells tl.at are specialized aii.l cin yet reprodnce; l.r,t they nprodnce only their ou„ .lilferei.tiate.l and n.odihed kind, gland c.ll reproducing gland ee.I, nmsc-le cell, nmsele- and even this in,iltipl.cati..n can occur only aftei th, ditferctiated cell has und.tJerei.t.ated itself again, that is. has reverted to a simpler less diflerentiat.-d stage. The cell that has lurome differctiated that IS loses the characters it has acqnired, an.l I.ecom.'s a "vegetative" eell ... ton,,, an. lyet when this cell reproduces, its progenv assn.ne onee more the d.Herentiated type eharaeteristic of the adult cell. FERTILIZATION We shall take ..p very I.riefly some of the fi;'ts .•oneerne.l with fertili- zatio..; that .t has n„t hitherto entered i.ito this text, is d,.e to the tac^t that growth, a.laptat.on. and cell ditferentiation can proceed with- out It; study ot the h.wer invert.-l,rate forms indicates that it is in them a means ot rejuvenation of the l.ioplw.re, l.ut tl.at it is not' an essent.al to the c....tn.ua..e.-oii,e marke.i .)ti' from the somatic or !..-.dv cells' the germ cells rema.ii rich in chromatin, none of « lii.l, is east .,,'it 1 he ..hservat.ons of Box eri and others indicate tl.at the cells .lestine.l FERTIUZ.VnoS 45 i,,, risf t.. the tissur. in Kfi.fral inukTKo a pnHr- ..I rf.luotu.M :,, ;|,,ir H.n.uiatin; very i...>sil,lv tl.is pr.Mr^s uf n;.lnftu.M rcn.lors ,,„,„ i,„,M,ahk- ..f Leing totipotential, >. v., <>t giving ri;.- t.. the ^^\u^c i,„|ivi,h.al, leaving then, earal.ie -nlv <.f giving ..ngm to u speeihe ,■,.,,!,• or tissues accnling to their environniei.t Nor does it seein ,lnt the eventual sexual cells are of necessity al.solutely i.lentical in ,1,, ,„,,„i.it of chromatin which tliey contain; a stu. ly ot the sperma- „„„•, c>peciallv of insects, an.l of the pollen ..t plants, has shown nrciiilv tliat in any particular instance their spermatozoa may he MiKiraUMl int.. two appn.ximately e.i.ial groups, ot which the nieml.ers ,,, ,,„i. .rroup contain either one chromosome iii excess i.t the numl.er ,„„tMine,l l.v memhers of the other gn.up. or one chromosome (acces- sory chromosome) markedly larger than the correspoiuling chromosome n, ,l,at other u-roup. No such .litlerence is ol.serve.l in eonnec ion w'ltii the ova, an.l as tliese species atlor.l approximately e.iual numbers V V ^ v^ '^^ Sf' 5i*L!_L*lll:Ll ■,]U. Difffrenliated tomatic (i'mcs of aduU. Srhnn.a of Kcrm an.l somatic ell .liflercn.ia.ion. (After Klcl.s.) „, ,„alc an.l female pnigeny an.l no other functional .litlerence ai Ik ,l,,..,t...l or imagine.1 hetween the two gr..ups ..t spermat..z..a, it i HM. .1 that the ..ne gn.up (that with the accessory chromosome) l";^e" Uilale. the otlu-r n.ale attributes. This conclusion is n..w 1 .Miiing generally accepte.1 l.y l.iohigists. . , , ,. .. ^. .. We l.ne state, that there is lu. re.luc-ti..ii m the chromatin of the ., IWcntiatcl germ cells; l.i.t we have n..w t.. a.1.1 to tl;- « a -nent ,!.,t tl,.- .enerati..n of germ cells imme.l.ately prece. Inig tl e ^ "a^^^^^^^ ,., tiie ..va and s,.ermat..z..a dor. uii.lerg.. a re.luctu.n ..t ^It"'"- t ,M,ring the pn.cess ..f maturation, so that the mature spennat..zo.,n or ;„, tains just ..ne-half he numher .,f clir..m..s,.mes charac ens ic „, the spe.-i.-s (aiul it will he recalle.l that this is a fixed numher f..r '"!,',Thrmaturati..n ..f the spermat..zo.iii. we may st.. oriefly the ht that a pairot spcrmat..zoa \i\ry 11 1 turn comes from a primary .-[v >rmatocvte, this fn.m a spermat.tgo- ^evmt^fmm -f^mrii-^^jiBRT wm 46 ISTRODVCTORY: CHU.S AM) Tlf^SVES iiiiiin, and this from a primordial Kcrm cell, and l.y the time the sper- matoziuiii is formed it has oiie-lialf the normal immher of chromosomes. The four cells derived from the primary spermatocyte all become spermatozoa, whereas, in the ease of the ovum, tlie primary ooc\ te gives rise also to four cells hut only one of them becomes a functional ovum; the other three are defiencrate. and are cast out of the cell as polar bodies, and this casting out does not occur till the spermatozoon has entered the ovum. This intracellular occurrence is for the purpose of reducing the chromosomes of the ovum, so that the ovum proper is the only one of the four which remains, aiul it functionates with its "hromosoines reduced to one-half of the number present in the cells of the adult individual. The steps of the process of maturation of the spermatozoiin and of the ovum we have omitted, but these intricate "nuclear dances" are evidently a means of ensuring that the chromatin of the original germ cell shall be impartially divided among all the (laughter cells— the spermatozoa or ova; and the reduction of the chromosomes brings it about that the fertilized cell, summing the two sets of chromosomes, each reduced by a half, shall begin life with exactly the normal number of chromosomes, and these contributed etpiallv bv the two parents. The cytoplasm of the new inflivldual is supplied liiainlv from the mother, but with the chromosomes (supplied thus with striking equality from both parents) must come the rnost important of all those factors which we are accustomed to consider in the problem of heredity. INHERITANCE Heredity is the conveyii . e to the ofi'spring of the i)roperties of the parents and of the parental stock, so that the child inherits familial, racial, and specific characters. Hut this docs not (L^scribe the child, because interwoven with heredity is variation, and this of several orders. (1) There is the variation that comes from one's course of life, as is seen in the type that is recognized as the sailor, the farmer, or the undertaker; variations so acquired are known as modifications and can be divided into those acquired in intra-uterine and in postnatal life. (2) There are variations that arise because the individual is the result of amphimixis, i. c, the fusion of the gerini)lasm of two individuals who differ op.e from the other. The chihl cannot, on this account, be an exa<'t copy of cither parent, but must show variation from each. (3) The molecules of gcrmplasm of iwo parents are so coini)licated that their interaction never i)roduces the same result twice; even the thousands of fish from the same si)awning differ from one another. Finallv, we must admit, that the biophores of the parent which supply the cerm cells are prone to variation during the individual life of the parent. The importance of the problem of heredity in disease is great, and we make no apology for insisting on its consideration. INUKRITASCE 47 I '""■ ''"'^r,, s r;nd'. ti\hl;; m<' i)r(.iHrties, MRU aistinctions. ,,,„„ from an ape, a.ul ^^-7.;^,^ f- '^"•^^ J^ „f fixitv in these characters. \\V see that there is an ««'<;' '""^;*Vr..to,-harcters are more firmly Z that. .leahn« .ith man. h.s ^^^^^l^^^^^,n\^. human, ,,as possesse.! longest he ^'^es up east r^a n_ • ^^.^^ ,,e,yone is Racial Characters.-To go n<. ^•' "^ ^j^^,,^. ^^^^ eolor of tlie skm ,„.,i,iar .ith racial < 'tt^"^?''^,!^',,^ ,' ft/n^ore strictly pathologieal ,,... shape of the skv,l^^a,u the s^^^^^^^^^ ^^^^^^.^.^ ^^^^.^^ ,, ,„, ,l..l.ls. one may recall t Ic tte enc ^^^^.^^ ^^^^^^^^^ ^^^^^, „.i,,,,,ie cl>seases; thus the^Ja^^^^^^^^^^^^ ^^^^^ ^^^^^^^. ^„^ ,.,,3 of are less susceptible to * »^"f r^' .i^t^tl with anthrax; negroes and Alu'crian sheep can scarcely he i""^" atca ^ -, ^^^d so on. A,nerican In.lians are h>gh >" --^* Jj J;;l,, knowledge that 1„ ,H,n-microlnc "diseases, it is am ui functicnal nervous ,,„. Ih-hrew is prone to d.ahetes the ^^en J'^ ^^j^^^^j^.,, „f ,,i,es- ai..a>es; the luiglish, t.. gout, an t e Ame^^^^^ ^^^^^^^ ^^^ ,jf^. . I ,he outcome of T'^^t*-"'^; ^^'^^l^he niemhers of a family tend to FamiUal Characters. Not _.n ^^"^^^ distinctive traits that are HMnihle one another, but there are urtau . j ^^.^^,,^6, a f -Hi in many successive ^!^Z.lr^^^onr said Falstaff. I,,,,., of some special part^ that thou ^^^^^ ^^j^g^ .... a 1 have partly thy mothers won. ' _ ' ^^jj condition such as ,„,i,l, hanging of thy ^f^'^'^lr^^.'^^^l^^^^ .Ihuiism (deficiency "V""'""rt' f^re (.It of insignificant injury). ,,.ility to excessive I'eni""*^,^ t ,.sess on of an extra .ligit. When r a.tu. 1 malformation such as tin P"'^^^^;^"" , y^^^ _ traced in a .,e consi.ler that such peculiarities - ^^^ ^^ ^ctio^^ of new blood, it n.ilv for centuries, ^'espite the c,.nstant mtn^^^^^^^^^^^^ germplasm .-, iii.nt that these are do°^>^* I'"^' ^^^^rHomc of thc<^c characters iSS^uS tS: r^: o; Ihem which appear in one sex 4S iSTiionnroiiY: cells .\si> t/ssi'ls ami arc traiisiiiittrd l>y tlic otlicr. Hcriiiipliilia, lor t'xaiii]>U', rarely apjH'ars in tlu- t'ciiialcs of an aircctt'd family. l)iit frc'iiiciitiy in their sons. ( liaraeteristies may ski|) a p-neration or more, so that the appear- ance of sneh in eliildren \vho>e i)ari'nt> were free from l)nt whose grand- parents or pre<'edin^' foreliears were atfeeted l>y them, is desijjnated atavism. Parental and Individual Characters. The charaeters that descend from the i)arents to an individual may lie blended, that is. he m.iy possess a n-.ixture of the paternal and maternal features, intermediate between tiie two, or they may he particulate, that is, lie may resemhic one and not the other. Tiu-re are certain parental charaeters that ordinarily cannot hiend, and sex is the most striking of these. Less important is such a character as the color of tiic eyes; one parent may Inne l)lne and one hrown eyes; the children fienerally do not show an inter- mediate color, lint either Mne or hrown eyes. One of ♦he two parents, in properties that are nnliUe or antagonistic, is apt to he dominant, and the other is then recessive. Mendel's Law. VVithont piinj; deeply into the particulars of inheritance in the matter of antaijonistie charaeters, wt ^.lall indicate the exactness with which nature works, as it was ohserved hy the Austrian monk Mendel, whose work has in this century heeii revived. Let us take for exami)le, as he did, the flowers of the pea; some strains ha\c white flowers, others colored. Color is a p<)siti\(' accpiirement, and whiteness means latency or loss of this acquirement. If now- red and white flowers are crossed upon one another, the hyhrids which result follow a law in regard to manifesting this particular character and the first fxeneratioii is red. The red color is (lominant, and there is no indication of the white color — the white heinji recessive. Hut in this experiment the white color is only latent, and this fact will appear if this first generation (red) he allowed to fertilize it^^lf; among its progenx' one-(|uarter of the individuals will he white, that is, will show the recessive quality. If this white individual he self-fertilized again, all its ])rogen\' will he white. Xow of this second generation of four ])lants (three red and one white), of the three red, one will give only red jirogeny. the other two of this second generation will have the characters of the first generation of hyhrids, that is, they will give rise in the next generation to one dominant, one recessi\e, and two hyhrids that again will produce this same percentage of dominants, hyhrids, and recessi\t's. This will he understood hetter from Fig. 12. The formula may he set down as follows: if 1) represent :i plant with the dominant red and its gcrmplasni and K one witli the recessive white and its gennplasm. then the first generation of crosses of 1) and H will all he DR. and if these DU individuals he crossed the result will he .r(I)I{ + DU) = .r(I)I)-f 2I)1{ + HH), or in other words, a dominant crossed with a recessi\-e gives in the second generation, as regards this one particular feature, one dominant, two hyhrids. and one reces- si\e, and of tliesc, each dominant uii! gi\c nothing hut dominants, MEXDKL'S LAW 49 ,,,1, r..r>>ixf notWm »><'t recessive., an.l eneh hybrid the same pn,- ,„,rtinii of dominant, hybrid, mid recessive. Fill 12 l\pih>iijf tissiks to indiciiti' liDW ii(rtil>lcins of licrnlitv in tlic liiiinaii s|)C(ii's. Atavism. Tlii> i> thr iipiMiii-jiiKc in a pvcn K('>>*'>'iit><»> <>' traits not itrcsint in tlic parent lint cliaractfristic of ••arlitr m'ticratioiis, anil is ^vv\] to lie in aci'onlancc with Mcndi-rs law. If, liowcxcr, we find traits appear which are cliaracti'ristic of an earlier state in the pli\lo>;eny of the species, wc designate this reversion. In reversionary inheritance or reversion wc have always a return to a lower typo a development not conip! 'tely np to the ])resent type hut attainiin; a stage eliaraeteristic of an earlier period in the development of the species. An example of snch is the a|)pearance of a niicrocei)halic child or of a chilil with indications of ])ersisteiit );ill clefts; not all such cases are true reversion, for some may he merely examples of intra- uterine disturliance. .\ jierfeit exaiuple of reversion is found in Darw in's experiments and those of others, in which when widely ditferinj; breeds of pigeons were crossed, the progeny, disrcfiardiii^:, as it were, all the recent ac(|uirements, have a|)iieared exactly similar to the form of wild ])ij;eon from which all the different varieties took their origin. One seems to see. froiu time to time, the ofi's|)rin>; of parents of widely diverse stocks sliowinj; this reversion to a lower type. Familial Degeneration. — This is a form of d«'t;enerati()n which we ascril)e not to the interaction oi' two antaj;onistic >;erm]ilasms, hut to a defect in one or hoth i;. t-d hy toxic intinences, which modify the constitution of the piirc jrerm cells. The class so produced we desij;nate degenerates the prodtict of those leading; vicious lives. The de>:enerate is of ])oor hodily development, the hrain is smaller than normal, its convolutions less marked, there is little cai)acity for prolonged tiionjiht, and a lack of moral sense in all these j)oints, then- is a res'-mlilance to a lower, less-developed race of otir sjjecies. .Such art- apt, in turn, to jiroduce children who are idiots, stillborn, or monstrous. Spontaneous Variation; Mutation. We have previously lueii deal- ing with ronditions a])])earin}; in the ancestor, ami conveyed to the oti'sprinji; hut there a])pear in the offsjjrinjj conditions and relationships tliat are new to the stock, that have «r/,vrv, and these are called sponta- neous variations. Tiie clover has a tri-partite leaf, Imt a four-leaved clover is ( ccasionally found, and does not luean that the ancestors of the clover plant had a cnuidri-partite leaf. Wc describe this as a spontaneous variation. We find the same thinj; occurring; in the human species; su])erniuuerary luaiumie, fingers, or vertebne occur, and, once present, tend to be inherited. The first of these in any series to happen, was a mutation, a spontaneous variation; and botanists have been alile to show that a new variety will suddenly arise, and self-fertili/ed, remain true to its new ty])e. .'^ome say that evolution works ill this discontinuous way, and that a new variety or i.;'w sjiecies does not come by slow gradation, but by sudden genesis. It luay be, of eour'^e, that we have here an exami)le of cumulative inheritance; that is, w here a blend ili^tead uf rvhowiiig a feature intt^^fiediale Ijctween FORMS OF ISIIKRITASCE 51 „,., .litr.ri..K i.i.nM.tal featur.-s. slmvvs tins t...tnn- .xanKerattHl in the . ' ..f l'..t far hoyo.ul that t.atnrc i., ...u ,.an-nt; hut wj- have L tn r.na.Mlur that .nutations hav.- h«vn ..htauMMl hy various phv s.cal ',t\V,ts ,■ '/ th.-i-fhini.r..fchi-min.lan«'ntsac'tnijr upon ova. The Theory of Inheritonce. ThtMonsi.ltTationof f.rtih/.at.on an.l the „r.,.r~M > that ,.r..r.l»- it lea.ls us to suppo ..• that oach parent c.ntr.l)- .' .Hu-half to tlu- ,t-rn, ;ro.,p tlu- various forms of mheritanrc, most of vshuli |i:,\ !■ hccM refemd to, as follows: ( I) rre>entin>;itsrlf alsoin theoffspriii);: ,. i . j- 1. Dominant, wholly replaeinntheeorrespoiKhnglnitdivercent feature seen in the other parent. •> Blen.led, this particular feature in the oiVspring hein>; inter- mediate in character iietween that exhibited in the two :i. Ill' mosaic form, in certain cells the ,,aternal, in others the maternal feature heiuK dominant. 4. IMeiided and excessive, the feature heiUK more pronounced tliiin in either parent. I /,'i riirecognizahle in ihcotVspriiiK: , • , 1 IJccossivc. and replaced hy ((.rrespondinp feature deriveci from the other parent, hut as such latent, capable of rcapjieariiiK in hiter generations. _ •1. .\hsent, wholly wanting in siibsecpient generations, the absence being due either: („) To casting out of an inherited condition, or xh) To the feature seen in the parent being an acquire- ment and not an inheritance. Or on the other hand, considering the individual, we note that as r.-ards anv particular feature or group of features, there may be: " 1^ S,',rwiO Inlwritfinrr: The offspring not being in this respect advanced beyond either parent, but at the same time not fallen behind. . , . /,', I'mnrrsmf InheriUuice: The offspring l)eing advanced beyond themoreadvancedofthetwoparentsandexhibitingeither: 1. Excessive development ot the condition or conditions alreadv observable in one or both parents, or •1. Spontaneous variati:)n (mutation), i. e., the appeorance of conditions not i)reviously iiote rissi rs It will !»«• still tliiit (|iiiilitir- iKiiMvi'tl l>v (lie itiirtiital liii)|ili(irrs may Ik- retaiiitti «\eii if in ii rtiTssivf, latt-nt lomlitioii. Tin- fact that tlu' Mt'iidrlijiii li\liriil att»T a iiuiiiIkt of ^joiicraticnis ran pnKlncf a pnrt'Iy iloininaiit or imrcly rrcc^^ivc imlisidiial sIh>\\>> this, aral con- jiiHatiun caiiiiot, tlunfurr, l>f a ilniiiital nniori nf two l)io])lu)rt'S with a n-snltiiij; \w\\ liioiilioric siil>-.tanit'. Nor can there lie sojiarato Kiophorcs repriMiitinj; ca( li iiiili\iilnal ance>tor. Tlu' following is our ySfM MOTHt/f CLLL KtfrBffiO). ^ini,i, n^e i( four if)trif>utoioa. F.I,. II COCynS iHrBHID), iivir.t,' ri.tt each tci'ne Cviim,fy nducticit. S', /. 1 a*'"^ \ (i^ (^■■^ ■Sj,£ Dnminar.:. DD <••> 1 DR I Jh brill. D!i Scliema to illuBirtitc .Mt.n.l.l's liiw rfiiarding the wcnmi liyhn.l Ki-nrrrition to illustrate the pffecu of reduilinn i.f the chriiiTiii».iirii'» in otiiieDcsi* an.l .'■permatourncMs K.icli germ cell (Brst rowi is originully provided with rl.roiii„9oi],i-3 ui!h. as ahnvc noted, the hiophores may in their Rrowth and develop- ment have attracted side-chains formed primarily by the .)pp..sed ..rder of biophorcs, to tlte exclusion of those originally belonging to them. coiiceptitm of the process of conjugation 1: -en parental Itiojihores in the fertiliy.cd ovum. We may picture thes. i)ici)horcs as lyinj; side hv side in a common cytoplasm from which they extract aiid to which they give ions, so that some side-chains are heing huilt up and some dissfjciated. Of tliese side-chains many are identical, common to the molecule of each parent; these possess the fixed characters of the species, thf.- race, the order; others arc unlike, and liic.-,f t\Idently mark the isni:Hn.\..' t »y \'Vi iui:i> ai \iiA(Tt:RS 53 <.lfmuerK.i"'i> '^:, " .l: ■,,, i,,.,ait„rv. tr ' ■■ni^dTrr lon«-arVu-a question. ;-"^™7-^,;'' .f./^v t teichim: of the mon.lu.loKists wc think that sonio. but not all, ma> t e U ■ . n halioat'ea before that we picture the -f ""^. J "'^ < in interaction with the cytoplasm that surrounds >*. pmg P to H';5rth:^cr:^r;^Sl-,!^';;';- .^ ^^,^i,, ,,f indivi.'.uals, in ulmh ll,i.. IS a«|UirC(l, unless t In tin '''•'''' , ,, ii„n.,i„„ „t „.„,„.l,.-n, ,.t one ..r "'I'" l»|;™' ,'^ ,, '^ ,' ^ |i,i„,, is m, i„heri,«l ,|,,s,.. II It I.C siuli ;. result, tlK l'''" "'"1; ' |,,,,,,,,i„i „„„|i,i.,„ te ;:tii;';:i;-,;:s,;:!;';s:a.y;.s«.ssc,i.n\ns;ure 2'^^^^^^^ antenatal or postnatal, aiu tlu.^e te%N xMu , art '" l„p,:,.„inn to the i.ulivi^ ,^ 'J ,,,i..h .litVer from one another in the ..hk '";,':., \,^,^^^^^^^^^^^ „.„t .,..t^ it is nece'^sarv to nc icate what these causatnt ai,'ents an, ^in t' s n ^^Xsomd .netho.l to consider them as direct and pre- ii^ . ™r -rs aKo. physicia,.s knew nu.ny P- -P-;;;;;!;;- hune^-hrect ones; today we are hndm, ont '- .1. c . s, after another (witness the speiilu- mun-orpim-n,-., <' ^^^^^ ;- , . ^ight of the predisposing or assisting causes. H.r exampk. manx 56 THE CAISES OF DISEASE iiulividnals carry in tlit- tliroat the gfriii wliicli \\v coiiiit the direct or exciting cause of j^ieiimoiiia; tlie assistiiij; cause a])])areiitly must act before a man is attacked l>y jincinnonia, and tins assistin>r cause is not the same in all cases, and frecincntly is entirely intangible; we hide our ignorance behind the term "lessened resistance," and although this may be as yet only a name, we must not fail to keej) in mind that assisting, indirect causes exist. It even happens that the same agent may be at one time an exciting cause and at another a i)redisposing cause; such is cold, which at one time frc 'vs a tissiie, and at another, paves the way for tlie inroad of pneumonia. Predispositions are thus the result of the presence of assisting causes, or of the absence of i)reventing properties. When we say that there is in an i., dividual a i)redispositi()n to tuberculosis, we mean this. We have in our mind a series of generations of a family in which cases of tuberculosis arise mofc frequently than in the same number of individ- uals taken at random; in this family we note certain j)eculiarities of build, of habit of life, of constitution, which we susi)ect have a relation to this increased tendency to tuberculosis. An individual i)ossessing all tliese peculiarities may, it is true, escape tuberculosis, but his chance of escaping it we hold to be less on account of his possessing these peculiarities and the history of increased incidence of tuberculosis that has arisen in conjimction with them. We say that such a person possesses a diathesis. INHERITED PATHOLOGICAL STATES It may be rei)eated that the results of all the morbid influences which bear ui)on the foetus in the womb are accpiired; mutilations are never iidicrited, and the statement may be safely made that infectious disease in the parent cannot be iidicrited by the child although it may be com- municated to the child in idem. The cases in which children are born with tuberculosis, syi)Iiilis, smallpox, or other such diseases, are cases in which the child has contracted the disease while in the mother's womb. These diseases arc transmitted by some germ, known or yet to be discovered, and to say that they could be inherited means' that the germ nnist be in the spermatozoon or the ovum as a foreiiin body, for we cannot imagine it as being incorporated with the protoi)las'm o* the s])ermatozooii or the ovum and retaining its individual power to cause disease; but it is not conceivable that a mimite germ cell with a bacillus or a ijmtozoiin inside could i)erform the delicate function of fccmidation. .\s readily should wv look for good time keeping in the hatter's watch, which, it will be remembered, was full of the best butter. It is true that in animals where there is a large yolk with the egg. the yolk may become infected almost innnediiitely jifter fertiliza- tion, as hai)pcns in the ticks that cause Texas fever, and as is seen in the eggs of exjjerimentally tuberculous hens; but the human ovum is <:-j. ViKi Ati.w-r-f i=ifr^-;-'^ INHERITED PATHOLOGICAL STATES 57 1 e (,...r^ volU thrtt infection of it can scarcely happen r "'r: ,:;Js"rs\ tuS « happen, «ouid i. !«.»„ .1. ;';„;i; ';;; ii.;: "«< *« u incomes »„ c,a„,pie ..f > pati.oK.gK-ai "■;;''•'?• ""i^li'^LrsVcSSase. ■» tnl«re,.U»is ,.r syphilis are „c,t sti^'niata, snih as tlutcmnbon & it-c because i,..lirectly due to syph.hs; these .^J^^ T,f c^l eH n^^^^ syphilis has existed in the P«^^"*- •"'\\f;' ,;;",,^"''.:^ ^^ ,vav k-cogm/e a\ least. parasyphiUtic '-'^^ ^^.^j.^" Jj;'^, ^ ha^^ r a .eak fn.me. ^tt;rf;:::er:;.siits:n?di:t;^^ ,.It Sai .manifested in various vs^^l;.|end.n,^^^ of the disease in the one parent, and the relatu t actn u> plasm of the other parent: 1 Sterility, no off spring being produced. • * r«^ intra- 'V I nperfV^ development of offspring, g.vmg nse to a) nt a .' ^ntl, r (b-) nhvsical malformation, (c) lowered resistance, iiternie death, v,r W pinsicai • ,,, ..j^" ;„ ts nature. „r s„ Frequent occurrence as to he callei parasijecinc u :;. Imperfect development of offspring, appearing later than the succeeding generation. 4. No apparent effects. ..hereis undesiraWe qualities may I'atel the quality of o„mha,i„B u ""«";■ ;?-|X!^„«t ti Generations.-lf abnormalities can be transmitted, f ^ " ™\^^ uenemwviua ,,ftener thev appear m a series »)f progditors, tne mil erstood that the outlier tiitN 111 j wwimnt •itteniDtini' ™r,'"* ",' ■^ r.::?eX.T™wMinis'-;:,»i wmo. S i^ll;:':;;: ; , • .;;, l heri,a„«s, bu. .l,oy pr„l,al,ly are. To ^ a premature exhaustion ..f nerve-cell groups, but M^V* '/"'l " " en ;,l',o function may really have a strictly anatomical, if >et unseen '"itheses While we deny the transmission of infectious disease l.'^J'^^ipl^n Ve admit'that an attack of jn^-tion ma^^moch^ ,lH. nexr gennplasm for better or worse. - ^he 'hreaion of gnu^tle i.lVspring greater protection or greater liability. We are unable •t8 fiik (\\rsh:s OF disk as i-: lociilizc this quality, jiiul prohaMy \\f sliiill never iin(lerstaii(i what it is, l)ut as a result of it there is the existence of "raeial" diatheses, or, stated otherwise, the ahseiiee of raeial iminmiities. The Hebrew has a eertain racial freedom from tiihereiilosis, and a raeial liahilitv to metaholie distnrlianee^ sneh as dial)etes and, in the female, oliesity; the white rat has a raeial freedom from anthrax, and many eariiivoroiis animals from evil results of septic wounds. A man's oH'sprinj; inherits from him (|iialities which render it lialile to or exempt from a eertain disease jns^ as it inherits a likeness of feature. We cannot take two needles and tease out of an ovum the i)articular i)iece of protoplasm that i)ossesses these potentialities; hut there is scmiethiiif; actual in the germplasm, in the relation of one part to another, or in the mole- cular };roui)in>r, that constitutes a real hasis for the "diathesis"; and when we k<) farther and find that diseases such as hysteria and epilepsy, which we fretiuently name functional diseases, are inherited, we realize that there may he a chemical and celhi'ar basis for the transmission of "nervous diatheses"; but if we cannot find the ortranie change in the tissues of the diseased individual, it is yet more futile to attempt to find it in the germplasin. INTRAUTERINE AND PARTURIENT CAUSES Morbid Conditions Acquired in the Womb. Wuh-lv var\ ing results accrue from influences acting u|)on the embrvo or" the "ftetus, and although the morbid states will be discussed ironi the standpoint of causes rather thai, results, it is well to indicate what these results are. 1. Death ol the embryo, with abM.ri)tion or "blighted ovum" or abortion, the ffvtus l)eing imperfect: or premature labor. 2. Monstrosities. ■ \. Malformations of excess or of defect. 4. lm['aired vitality, with imperfect development, without gross anatomical change: ui) Ceneral infantilism, etc. (b) Svstemie— es|)ecia!ly of the nervous system. 5. Cachexia, b. Infection. 7. 'JVauinatism. On the other hand, if we classify the causes that lead to the above results, we hn ''-^/y ■; ,;ralU-l facts i.. the ca..- c,f the '- ^" --^''-- '>^'^ ^^Vt; know Cover, that when the a.nnmn •"="'"""'"'" *"'"■•"■ \. .... ,n pressure hn.ui^ht t.. hear uih.u .„ i„....,n,.lete there .nay ^^^^^'^^,^,,,, ,,„hry.. an.l ann.u.n ,,„, ,„,,,ry.,. ..r a.lhesu.ns ma »^ "\ ;^,,,,„^l,, the movements ot ,.ru.hu.in, n.alf..nnat,ons; "-» j^ J;;.;,;;^;";., u.i.t hn.hs are thereby tl'^' t"tus may rj-ul h' K. ^ <^ .^^^^^^^^ ^^_^^. ^ ^ traunu.t.sm. „„,.utateil. l-.etal iratturcs "^ fraeilitv of the hones. not so caused. ,j.w.,.„t-. also nutritional defects in ^Vhc., there is .hsease ot the , au U ^^^^'^ ^^^ j^^^^i i,,,„„, ,he fcetv.s are very rea.liU ^^^^^^ ^^ Fvt where a monochorial „ imperfect, and ^'^al .Jc.ah n.^^ J^nsn^^ 1 -« ^^^^^^^ ^^^^^^.^^^ ^^^ nvin pregnancy exists, that is, ^^^^^^^^ ^'>^;^. \ „,,,re than its share lu>edVlacenta. the more -S^'"™^^,;;,*;;," £,; • ,,U,ocl by anastomos- "'■ ^''^' '^'"■"•^^"' ^'r''^"'";';;-;'; 1? ev o ts weaker companion, w^iose i„. vessels into the umb heal '^^^^"^ ''', ^^j^^^;,,,, ^^es rise to aulema '"rUcations.- U has been experime,..dly r^^^^^J^Z snch as lead, mercnry, arsenic, carbon mo ox dc, nrp^ • .^^^^^^ j,^ p;,.s through the placenta and can ^ ; '^;; / ;,,,ne or epileptic; l„.l ,,ois..ning the oHsprin, IS "'^l" >,^;;^^,^ V expose.l to lead ,,.., it has been shown that wht>re -^ J^ ^ ,^.,.,,,,, .iu.lren; in :r2 Mhsorption, NS presinanc.es resulted ' exposed to lead poisoning pregnancies where the lather :'l«'f Z/;' ' ;i;7,''J^^^ in a lar.e series !„.ly 3 of the olTspnn^' survived » «•"• ^'^^ , .'Rentage of aborticms, of dcoholie mothers, it w>^ Unuu\ t''"^;';. j";.^ J' %,,, „early two .tillbirths, and children dying before the tli d tMr >^. ^ .^ „,1 one-half times as great as normal ^^^.^^ ^ ;: /f^,,^. ,,ter offspring .ressiyely a victnn to .dcohol^ h h death . ^^^^^^^^ ^^^^^ niul the lowered vitalit\ ol ^"^ "'"*■,. . infect bus tal t'-"^.!'' »'",^ ^'^^^^^ ^" I cTrefuUv excluded. T' f:'::'^i:::^.n^\r:^ -y of syphius there ^ et r.uuim inst.ir.< es V , ,. tuberculosis, varicella, variola 60 THE C.WSKS OF DISKASH typlioitl fcvtT, (lidlcni, «|)i(l('iiiic (•on'l>r(is|)iiiiil nifiiiiijiitis. infliu'iizji, rt'lapsitii; IVvt-r, inalaria. and yellow tVvcr. 'J'lic fX|)laiiati()ti of these cases is i)r(il)al»l,\ that a ^ross lesion of the harrier lietween the maternal and fcetal circnlations oecnrred, and not that the eausative agent "filtered through. " The Effects of Placental Disease upon the Foetus. I'he placenta is essentially a part of the fietus, and is a mass of finger-like i)roj»'c- tions (tlie villi) of tiie outer coat of tiu- f(etal sac into the uterine wall; the epithelium of these finger-like projections has great phagocytic power, and ahsorhs the tissue of the uterus until each finger-like pro- ces ines to lie in a large hlood sinus of the maternal organ. Kacli fir.,,, like process contains a vascular loop and the f(ctal hlood flow- ing in this loo|) exclianges wit!i the maternal Mood, oxvgen and other difVnsihle materials through the wall of the villus. Jt is ohvious that these finger-like processes, with their phagocytic power tend to weaken the walls of the maternal sinuses, so that hemor- rhage is apt to occur; in fact, normally, hemorrhages do occur, forming accessory sacs into which new villi make their way; with heiijhtened maternal blood pressure or with maternal tissues ill-nourished, extensive hemorrhage may occur. .Such hlood heing effused gives no oxygen or nutrition to the f(ctal hlood, and hy its very presence prevents wholly or ])artly, the normal circulation, so that the Actus may peri.sh from asphyxia. This is a cause of premature labor and stillbirth. If the hemorrhage be not sufficiently severe to bring this about, it will, nevertheless, be followed by thrombosis, and finally, by fibrosis of the areas affected. This will reduce the area availahle'for the nutrition of tlie fo-tus, which will necessarily be imoaired. Impaired luitritiou ot tlie id'tal structures may be cxcmpliHed in disease of the finger- like i)rocesses, the villi themselves; they are at times a-dematous c.xstic, or they may become i)artly fibrosed, anv of which conditions inay give rise to i)rcssure upon the vascular looi)s, with consequent li-sscning ot the efficiency of the circulation. The nutrition and growth o the ((ctus thus ai)i)ear to depend directly upon the amount of good placental tissue, and the more numerous the villi, and the more active they are in i)liago(ytic proi)erties, the better will be the mitriti(.n and the greater the growth of the child. Of iiifecti(.ns of the i)laccnta the most important is svphilis In this there is cellular overgrowth of the villi with o'dema, .•uul both ot these leaturcs tend to increase the size of the i)lacenta. Thus in syi)iulitics, the placenta max weigh half as much as the chil.l, althouuh m normal persons its weight is about .mc-fifth. A pmn chil.l, of eourse IS partly rc',p..nsibie for this altered rati... Multiple small abscesses are als.. frequently f.,ni,.l in the sypliilitic pla.rnta, an.l the co-existence ot these with the changes menti..ned above is characteristic To the eye, the p acenta i^ large, pale, an.i may have yeii..wish-white Hbroid areas. A turtlier .hara.ter in syphilis is the leukocytic infiltration of the umbilical cord. ■.\ai ^^o^■STRosITI!^:s and abnormm-itiks 61 Hydiamnios (excess of an.ni..fu- ttnu\) often arises in syi.hilitirs, ,,?S. .-.li"'' .U-r-ts.of t..e f..;t..s .nay ^aiso •-- . ; .p;.~ of anmiotic Hiiid) is also sometimes a result of syphilis. i("((i(ieii'>''t ^--t^'^ „r .li^locations of hones, or l.irth pals.es or hydrocephalus. The ch e i,„,.,ious cause is the presence of pathogcn.c organisms m the gen al tra.t especiallv the gonoeoccus. leadu.g to ophthalmia, tnallx, i.nproper treatment of the uml.ilical cord may lead to hemorrhage, 1„. al suppuration, or to general hactenemia. MONSTROSITIES AND ABNORMAIJTIES The terms denote grave anatomical departures from the normal, either general or local, and the term monstrosity is applied to the more pronuuneed of these. Departures from the anatomical nornia co.^^t ;,t V nriations either in the direction of excess or ot .letect. or ot altered relative i)osit ion of parts. ,•.!•• ^t +!,„ Abnormalities of Excess.-This may show itselt in excess of the iii,|i\i(i)ial or in numerical excess. /n i *„r.ji i„.livi.;ual excess may be («) universal, ,.r. giantism; (h) lateral . , where one side is larger than the other, as if there had been unequal ,ru isi..n when the first two hlastomeres were formed; or c) oc"'- ^^h^ „„e n.eml.er or organ is markedly larger than the stand, rd set by the .. .t of the bodv. Giantism applies to those huinan individuals uho :,„. more than 200 cm. high, that is. (i feet ^ inches, a height tha is MMllv due to the great length of the legs, (..ants usually spring l„„n tan.ilies in which the individuals are of medium height. Lateral M;,„,is.n cannot well be extreme. Local giantism may either be true . ,. ,„.,,. ,,,. ;„.o„ired bv disturbed nutrition, in which latter case it is ,i,e„;,f <.ongei.ital origin. Thus, localized elephantiasis of a limb or macroglossia or macrodactyly (where a finger is abnormahy large) may mjf. ^■^' ■STT ^mi^m-*m^?^^mm^mi^i 62 THE CMSKS OF [)ISi:.\SR 1)0 due to ohstnictinii of tin- Iviiipli (•liimiicls. and cDiisi-qiirnt over- j;r()\vtl) of coiiiHM'tivi- li--Mif>. Wlien-, li(.\vf\tT, tlu-rc is not only marrodactyly hut diiplicati. f tiiipr^ or a tcndrncy tiuTcto, it i> -ate to assunif'tl'iat tiicrc lia- Imcm a ri-diuidamy of vcuttativc luattt-r at the jrrowiiij: point. Hypertrichosis (hairiness) ami lipomatosis (,i;encral oht'sity) ar,' to he explained liy a coiuiiination of inlu'ritanee aud nu'taliolie Modifications; precocity in the ilevelopuicnt of the nuiscnlar and ne;' ve systems ai)pears also to i)e associatetl with al)errati(tns in deve,u|.. .lent of the ductless irlanils. Nuinerieal excess inelmles a wide ran>;t' of al)nornialities from midtiple hirtlis to i)artial du])lication of a phalanx. Twins. Twins may lie dichorial (heteroi'iphal) or monochorial (mouo- oi)lial). In tlie former, each child has its own membranes and placenta, although the two placentas may ultimately fuse. The chiltlren may or may not he identical in sex; they may or may not closely rescmhie one another; in fact, they ohviously arise from two scjjarate ova fer- tilized at the same period. Should the dichorial twins he of the saine SOX, and very much alike in characteristics, it may he that two ova from the same follicle have heen fertilized, for multii)lo ova in a follicle do occur; there is even one other possihility, that a siufjle ovum after fertilization has divided into two, and that the two halves hecome sei)arately implanted in the uterus. Superfoetation, in which the omhryos are of ditl'erent apes, ohviously can arise only from ova discharged and fertilized at difTerent ])eriods. Monochorial twins are rarer than dichorial. Thoy have the same chorion, the same i)lacenta, are of the same sex, and if ei|ually developed, much alike. .\s the chorion is the outer wall of the ovum, it is evident that here the same ovum has jjivon rise to two indi\ iiluals. Such twins may even have identical ahnormalities, stuh spina hifida or hyi)os]tadias or right-sided hydrocele. FAi)eriineii' u])on inverte- hrates and even upon the lower vertehrates has dt uionstrated the possihility of one ovum giving rise to two individuals, and the eggs in development may even he shaken apart, when dwarfed individtuils arise from the fractions of the original individtud. The possihilitios to which monochorial twins are due are, then, these: (1) the two nuclei of one ovum may lie sejiarately fertilized, or (2) a fertilized ovum may hreak in two at a very early stage, as for exami)le, when it is two- celled, or CJ) a cleavage of the germinal area at a comi)aratively late period may give rise to two primitive streaks ui)on the one germiiuil area. r>iiiiiiiil Twins.- Thi> covers a numluT of cases in which a common fciuure is that one of the twins is nornudly formed; the other may he a iuni]) of flesh, with smaller warty j)rojections on it (not unlike a ])otato with small suiieruiunerar\' tiihors upon it), whose only claim to recognition is tiuit the umhiiical cord is attaclied to it; this is the fcBtus amorphus. .Sometimes there is a fair indication of the lower limhs hut no head (foetus acephalus), or the tu-tus may consist of little MoSSTROSrriKS .. /> .lW.VOff.Uir/ 77 /^N 63 tl.n, tl.r cli.Tn»>-lik*' iH-a.l (foetus acormus); tlu- nl.snue ..i a hiart '".,.■ asses U-a.ls t.. tluir U-\n^ calU.l m> ar.l.ac ... a.1.1.- '" "•""■. r.l t ...tive ..a,..es In s,„„r s. ;i;;;^;;;;!r;;':;ii;;iy ;;;:.; rpia..n.,a wit......! ,.,. i..t.rvo..ti.... .. "'^■rltl' ;rth.se acanUa.- .,.o..strositi.s is that th.- c-in...latio.. Ihc (aiiM r..v..r^.Ml oiif hera..sr t .o strniim-r ot the '" ^''^•';;" ;;r;';:: .e . i .;^ e i;!;;.;.i u.r....,h i...th; the aiia,.t..ic ;:;ni:; ";;;;.; ;^::irL....e Uy a,.ast.>.n..sef tlic embryo.. t.in .irives hi 1 ,.n.gressiv,.iy i..to ...ore a,..i ..u.re ''f t;-;;;;-^";;;:;;;';;- ,i,„llv. i..t., the weaker ejuhry's u.iih.heal arter> "'''I ' ? ' J ;;.^^^^^^^ i, i, .listrihute.! i,. the hra..ehes a.al ..mmshes the ,ss..es o^ -^ik , n.hrv.,; it ...av he suttieie,.t t,. .amr.sh a part '7'> ; 'X*'* X,, ■ he weaker e.nl.ry.rs fra.„e ...uU-r^yes aplas.a a,..l ;' ^l'' .^jj ^.'^ ; ,1 th,- we'.ker e i.hrvo hv arreste a.... :.! e m;.;^! no..rish.ne,.t fails to .l.wel.M., ^S'lV^Jn "Jvo ,).- it vet l-ep'^ as its ..w.. provi.iee the hea.l e..(l ..t the tm. r> o, ;,;; t' ,m, ri hes t^,is so ha.Uy. that the .vphalie e.ui .> ...-re pru.a- lu i:„;ai;rdope.l tha.. the caudal e..a-tottis acardiacus anceps. ^m^. 64 THK (wrsKS OF i)ist:ASK Triplet, and Other Multiple Births. Triplets ...ay Ik- .n..„.K.honul. or^!'Z\^l\ an.i .li.l.orial. ..r evc-n ..oly.lu.nal; tl- ruU-s as o em tv of sex an.1 si.nilanty of .l.anu-U-ristu-s w huh apply to t«n.. Sv lis, to triplHs. S.V.M thiMrn. at a h.rth .s rvporte.. upon Slhle 1" Jmh^Hty. In tin- .at. the n.onoehorial .levelop.nent of ftve ''S: Sli;^: There has heen for ,„any years nuu-h .liseussion up^" e rV^sons for .li,.l..,'enesis, an.l in a Hel.l where so >-■;>;. t^^;;^- iist ^ve venture to i.nt forwar.l l-ut one. which we term the growing- p^^t" t K^ rv This is hasea upon our knowle.lj;e of the growth of a ,„ ,.r„n .,( ..■.,,„„ of ,l,o «r„«,nR p.iin. ..f a plant. A. A. th- npicl .-ells, which contmually divid... scctmdary groning point. pluit If we consi.kr that the first cell is divided into two and then four and each of the four again int.. two, we find that the two poles ten.l t.. l..r..n.e separated. .)ne from the other, and each pole is advanced l)v the c,lls thitt arc l.uilt in l.ehiiul it. There are in the plant, from an earlv stafie, two prin.arv };rowing i)..ints-the supen..r f..rmiiig the stalk an.l the inferi..r the root; the <;ntire plant arises fr.mi one or other of these "ii- V L^rK g^^^^^ to the different ;s;n: tiXt^^^^^^ --- ^'''' ''' ''' limbs. „ ,. . u„ noted between the plant and There is thus a close parallelism to ''^ J^^^? , j ^y the fact that t!.e animal embryo nor need this be undub d-^V^X^^^i^,^ lateral. svmmetry in the plant is g^"«^«'^.';ff„' ^oth rules, and the lateral ,;,,„use there are "r^T, ?hecau^ cell division is binary, svmmetry is the fundamenta ""«. Jeca^se cell m ^^^^^^^ ■ Hut there is u ""''•''"^^^IfSsarlacUve through the whole i„ the plant the primary frowmg points are «ct ^^ ^^^^ ^j^ ^e i^roT't -; itHndU'SeTeTciVhe nervous system have been '''^H^iTiperiorandi^eriorgrown^IK^^^^^ ... would have the following «t«^^,°^ JX^^^^^^^ have already neural canal which form tje ventricles of he bra.n^ ^.^^^^^^^ f.,rn,ed themselves, and the '"'^'l^'lShL^Tout into a mass of near the site of the pituitary bmly ^^^^^ tom ^^ ^^^^^ ^^^ tissue. This may actual y happen Jf^^^^^.^^through the roof of i,'> There is none available, and it forces «s ^^ »J » j,^,, r,;. mouth to the outside as a ^-f .PJ^^" n tun^^^^^ ^-"'• epignathus. These masses h^ive a times been ou ^^^^ „na tissues representative of «" * ^ Sro^^-J^oT uch a mass lends hvpoblast. Thefactoflimbsactualb deNeloT^ ^01 ^.^^^j^^^u,, ailllitional weight to the supposition that . uf the original superior growmg point. ^^, ^^ A precisely analogous case "^^^^.f , \^" ^'.^tum at the extremity ,„ass of tissue sometimes "'^f ^^^^^'t^^^J^'Tmong ros^^ ..f the sacrum, called congemtal «'^"«J;"*^"j;-,t^tk and head develop a similar happening when an imperfct flower staiK -oin the centre of a flower. 5 66 TIIK CM SKs O! l>'St:.\Sh: Polar Dichotomy (Mnincliii j nf >\u- dowin^; I'oints). In plants there is a liultiliiy for thr jfrowinc [M.ni- to hranch, as whfii a fir ^.u.,K p,„nt; II, r, -nit of c«,lv d.W,.... ,mv of superior r.-o».ng p„int. the scparaii.m :,lI,.,iM,g al,o the U.fral ro»» of nlis t.ien ofl from tl ■ Krowin« pent: III, l^.te .h.-hmomy .,f su|Mrior Kr.minit |.-.int, only the , . Il» Kiven ofT mo. from the two siiperh.r growing points afTccte.l; IV and ' .ii„il:.r reaulls .1 ■ irly i,n.l late nf ihc inferior sr:,T,:.-.s poim; VI, i.ialu.l, iaie u„.i,o,.,my 01 ...„h .u,H;r.ur "a,„l ,„'f,T, points -anakala.lidymus; VII. early (eomplel, dichotomy mvolving both growing p, double monster,, lateral fusion; VIII. mesodidymus. the izr wing poinu remaining sinci series ■ ( cells derived from them on either aide undergoing =iti(>D. inferior ■ntly >niv wng ..sad xmxsrnosiTiES axd ABsofV. ities 67 trcf. Iii>:li 111', ilividfs ii.n» tsu. ..r tlir«; trunks; tin- roof f ilv« radihii mii> sill, iliirlv fork. Ill -oinf plant , a «livi>ion mto i nuroiH stems b lit' riilf. A pliiiit ma V t* IS uniHTjfi (lichut »ui\ at IHTIU I .lur- ing it^ urowtli iiiiiiiit laUSf It; itwiiij: iHHiits ar»" always active, Init an III 1 ■% niaiiimal for t mpU m\b tliat nil it«Ml linn tluri -i whirh «ii' Fia. iMth le 111"', t irrcw iiiji iMiinls are aetive ;;»:, it has liteii r\|K>rinieiitally sli.v.i! ■ hfit as long as tlie li('« trnwinK iMiints, (iouhl- monst'Ts can I'l i>nHline«l l>> t)!trti:il physic. ' (iivisidii i the exg, 'h h a> may \ '•rniiL'lit alx'iit li' the re-siin .t a ha Mfil armni'l it After tlic kTimii t; • Mii-its eease, tlwit , when ihf iii''«1illlary \c iiJiK-ars, III,- <'an iluh, Kveii thei)eri(Ml, - it>rt as i \Miiili tiichotoniy n, i ili\ iili'il into its early ai ? i the ilicliotoiny tK-enr - very cell horn fruin t poi'.t ill iTfes fr in it loi er he is, riiij; I ni.i he [m- . If i\ cmaii'' tiiat i|)eri< - ii'" 'i)W, i<7itioi >f tr entire a litii-Hl, a fii 1 from the ii rinr grov ng poiit. K' I), .i vcsict,- ■ pan »,(»» I fU; .ot<: 1 P.v< f right half 1 ,,w vc!i,. f w'th '■ ft half of riih.1. as the cells which have nti a (iichotoiny has ot'cnrred iin n ironi tne ii ri'ir gn'^ ngpt.u>ii.. un.^ „,,., ...-v j ..«-. .^ .^■. tliii^ earl\ , thediv erKeiicf nf ^he two gn. ps of cells hriiiRS it ahout that i\v(i .li\. rt;ing])riniitivc - ikh arc foi l.'iid (1(»«! smd in tiifn, ortrait the duyilicate of uios- thai ari- ll, hov ' \ er, a relatively late ■ •I ciirs, ' ic en<''!i;h will have -par -d fpnm one a ' ' her 1 mtivc and thus two anhgeii vill he li^' from each aiilage will he ot' !'r. .,y o! ■• of the growing points for I: two growing; points to ..^ ells, w ich give rise to a normal ■id til. iichiitui, V can atlVct only certain parts of x.l. l)i( iiotoiii' K tadidymus; t A^ g nse to fusional duplication, thii ^: a fiuure which dilfcrs from anakata.li.lymus iu that the trunk has two c-'mplete i-ngitu.linal axes an.l the skclct- 1 parts of two complete ^There follows a larjie class of .h.ul.le monsters, to which the last- na.ne.l .livision is the key; first of all, a cou.p ete c eavage has occurred an d a secondarv fusion has l.cen brought about between the parts of Fin l!l Fio. 20 If .'J>1^, X« Apicopolar fu»i..n: dUymmelrical J.ni-rp^ .( V„l.,|.,il,ura™,.uB.is ais.vn,.„.uo8 (Schwalbc'. c^-)- The two serondary frmit ..r (m. iai aspeds are Blwolut.-ly siniilbr. the bodv which arc contiguous ; the iignre last given indicates the "Siamese Twins" form, but it will be understood that there arc many possible modifications, as head t(. hea.l. waist to waist, in an axial direction, buttock to buttock, breast to l)reast, and so on. home- times the directions of growth, and interference of tissues w.th one another lead to the suppression of certain organs; interesting as this subject is, it is scarcely in place in this volume. Possibly the strangest MONSTROSITIES AND ABNORMALITIES 69 Fio. 21 Fia. 22 ;ree». Monouymmetrical Janiceps _„ the perfect .econdary front view ',( eplmloliioracopagus .uv.uu=j ...". ,..>-...- - /• - -- 1 .g. 22, the defective aecondary front view, with ajnotia (fu«on of e. m). Apa-opolar fu,ion >.t an angle lew (or greater) than 180 dcgre. 'Ceplmlothoracopagua monosymmetro.) (VroUk. case): Fig. -1. t, ; .» ^o .K. H.f„Mlve Becondary front view, with aynotia (fu«on of face, two arn.s. and two legs (Figs. 19 and 20). It is to be noted that sifcl fused monsters may be equal, or -^^^r^.^iJ^^u^ Inequality becomes so marked that one has its frame parasitic upon liie other, the so-called teratoid. 70 THE CAVSKS OF DISEASE kt - DupUcation of Organs- Just as tliere is cleavafrc of tlie axial ^row- iiiR points tliere may hv cloavaKf, also, of tlu; stroiidary growing points, whidi ordinarily give rise to the liinhs, so that ahnormahties ot these arise. .... . , Those ahnornialities of execss may arise in (1) longitudinal series and (2) lateral series. Kxeess in longitudinal series is shown by the develop- ment of extra \ertel)ra', or extra rihs; extra verleSra- need not have extra rihs nor need extra rihs arise from Fio. 23 extra vertehne; the rihs even may show- excess in lateral series, when for example, the sternal end is bifid. Excess in lateral series is oftenest exemplified by Polydac- tyly, in all grades from a double nail to an accessory a .licl».t.,n,> , an.l the existence of two growing pon.ts. Fio. 23 Vll VII the niulilli' line. instead of one, so defect at the gi.wuig ponit nia\ result in cessation of its growth, a pre- ,„ature civing out of growth; at the supenj.r pole, if tlie growing point die out, and the cells luliind are constantly "'ishing it forward, and there is no new growth . cells in the middle to keep the lateral parts away from one another, thev never leave their state of ap- proximation,' and it may thus happen that two eyes may develop as one (cyclops), or even that no facial parts may tlevelop at all. Siinilarlv, at the inferior jMile we max hiul I, st-ries of defects, which in its simplest lorin is si-cn as defect or absence of genitalia, and ii, its more extreme grades, fusion of the lower limbs or even the representation of the l„Nver limhshv a fuswl f-vL s stump (sympua apus). Rv a similar def r. ,.-.. lateral growing points, arises syndactyly : r Ai of fingers) or ri'duction in the number ot ...gits. Local Malformations.— Imperfect Closure ol iia. 26 Sirenouielus. (Synipu* apm, Forster.) the Dorsal Groove. T^^iral canal originates as a longitudinal depression in the epiblas . ,1 \! • L'lt lining the depression being .liflr.^entiated into neuroblast, 1 icl is the precursor of the nerve tissue. When the heaped-up edges 72 THE CAUSES OF DISEASE I'j if t of this depression meet one Jinother they enclose the neural canal, as if the banks of a ditch o->thiing it more and more until they met over it. At times, this closiire fails, either throughout the whole length or in some part of it. II tht iriiire to close be at the head, the vault of the skull and the scalp arr absent, and there is exposed congested tissue which appears like a mass of vascular membranes. This con- stitutes anencephaly, acrania, or hemicephaly. It has been supposed that pressure upon the head by amniotic adhesions at an early period causes some of these cases; parental infection in others is the i)asis for this vicious development. With such cranial defect there is often associated a failure in the closure of the spinal canal proper— the so-called spina bifida. Exencephaly is the condition in which, while the frontal region of the skull may be developed, though receding, the imperfect brain hangs out through the back of the skull. In iniencephaly the occipital bone is deficient and the spine bifid, so that part of the brain projects while the occiput and the sacrum are approximated, the body being bent backward. When the lamina; of vertebrae fail to unite the condition is called spina bifida; clinically, the important point in liiis is to know to what extent the spinal cord is involved in the defect. Cases of spina bifida may be classified as follows: 1. Complete Spina Bifida-Uere the groove fails to close and the superficial layer of nerve tissue is continuous with tiie skin on each side, lying as a broad plate. If only a snudl part of the canal be thus open, the condition is compatible with life until the canal becomes infected or until so nuich fluid is drained away that the child dies. 2. Incompii'te Spina Bifida, livrc there is failure of the bony struc- tures, but the skin covers the protrusion or the gap. This form is classified as meningocele, myelocele, meningomyelocele, syringo- myelocele, and the least scriotis form known as spina bifida occulta. The definition of these fornix may be left with surgical text-books. Imperfect Closure of the Anterior Body Surface. — Tlie embryo is at first fiat, spread out over the surface of the ovum, and with time the edges turve in to meet, forming the Ixnly cavity. For some time this closure does not take place and the viscera actually protrude, as does the uUantois. The vinion ultinuitel\ may be incomplete, and according to the region in which failure occurs, we have: 1. Sternal Finsiire.- If t!ic defect of closure be complete the thoracic viscera protrude; if the lungs do so, they cannot expand, and birth is death. If the heart alone be left exposed, ectopia cordis results. 2. Abdominal Fissure- Th'\s causes eventration, the protrusion of the viscera. 3. Hernia of the Vmlilical Cord.— An incomplete closure of the wall at the umbilicus may result in the proximal part of the cord being enlarged to receive a portion of the viscera. A condition not unlike this arises when the o!nphalonic>;cntcric duct, wliicli originally connects the gut and the yolk sac, remains open. MONSTROSITIES AND ABNORMALITIES 73 4. Vesicorjenital Fmiire.— The allantois de\eIoi)s from the hind gut iiiul runs through the umhiUcal region; the part nearest the urogenital sinus widens into tlie bladder, and the part distal to this closes, and extends as a cord (urachus) to the umbilicus. The urachus may fail to close, and may remain as a tube; the bladder may fail to close, constituting ectopia vesicae. Associated or not with this, the urethra may fail to close, constituting epispadias. Fia. 27 Development of the face of the human embryo (His): A, embryo of about twenty-mne day*. The nasofrontal plate differentiating into processus globulares, toward which the maxillary proceswjs o( first Visceral arch are extending; B, embryo of about thirty-four days; the globular, lateral frontal, and maxillary processes are in Bpp<.8itioni the primitive opening is now hetlsr defined; C, embryo of about the eighth week: immediate boundaries of mouth are more definite and the nasal orifices are partly formed, external eat appearing. D. embryo at end of second month. (Heisler.) Imperfect Closure of the Facial Clefts.— The accompanying diagram will remind the reader of the different fusions that occur, with obliter- ation of clefts, when the face is formed. When the fusion of these apposing surfaces is inhibited totally or in part, we have produced the Jeatures of an earlier developmental stage. Of such failures, hareUp in .WJH -.«.,aMH:'.-HU1 ' -, ' .^, 74 TIIK CMSHS (iF DISHASE its various decrees, with the acioiniKiiiyiiij,' palatnl iiiallormations, is thf oiif of most clinical interest. In its sinii)icst forin. Iiarclip atVects onlv one side of the uitpcr li|); a severer form is tliat in wliieh, m adides (lniihlf rhft ixilatr; or the intermaxillary hone may he wanting iiictlian rlrft palaic; ijr e ler- nally, the cleft may extend alonjr the side of the nose to the orhit. Imperfect Closure of the Branchial Clefts. In the ♦■i.ihryo the second and lower hranchial clefts pass from the outside into what ultimately will he the pharynx. If one of these do not close at all, a complete fistula remains; if it close at the end, a simis is made, and if it close at hoth ends a cyst; if the cyst he formed from the i)art of the cleft nearer the skin, its epithelial lining is stiiiamous, if from the pliar\ igeal end, columnar and even ciliated. The Eustachian tuhe is the first of these clefts, of wliich there are five; the second is the one which ofteuest persists. Rectal Malformations. The emhryonic cloaca in the course ot develop- ment is transformed into certain external jreiiitalia and the rectum. If the separation hetween the ^'ciiital and the rectal parts do not occur, we have the condition of persistent cloaca; if it occur (mly partially, a fistula is formed, the cavity of the rectum commnnicatinj; with some l)art of the n^'nito-urinary tract, such as the vagina, the bladder or the urethra. Also, the septum between the hind fiut and the outside may not he broken dow n, and the condition of atresia ani or imperf( rate anus may result. There are various grades of this, according to the distance from the surface at which the end of the hind-gut lies. Hermaphroditism. The matrix tissue {avlaijc) of the genitalia remains the same in the two sexes up to the fifth week, and alike struc- tures b(>come transformed into the apparently widely differing (frgans found in the two sexes. Kach part of the male tract has thus an analogue ill the female. It is not so strange that cases of blended sex should occur, as that they shouhl occur so rarely. True IlermaphriKlitiwi.- This is very rare; there may be an ovary on one side and a testis on the other, or both on one side, and either or neither on the other, «r finally, both on ea<'h side. The secondary sexual characters (the conformation of the body and its parts; are mixed. Falte lIi-rmniilinxlitiKm. This is far more common than the former. In it the genitalia are actually of one or the other type, but the second- ary characters are those of the sex other than that to which the genitalia belong. The male individual with feminine characteristics is the more common of these (pseudohermaphrodismus masculinus). POST-NATAL ACQUIREMENT OF DISEASE Classification of Causes. The f disease, or injurious substances, living or dead, may he introduced into the system. The agents which thus prwhice disease are: 1. Mechanical -in(hicing "trauma." 2. Physical under which can he inchided: (a) .Mterations in tlie pressure of the atmosjjhere, inchiding !)oth diminution and increase. • , ■■ t i ill) .\lterations iti temperature, local and general, indudmg Ixtth heightened and lowered temperature. {(•} Ktfects of electricity, hoth atmospheric and induced. id) Kffects of light and of other forms of radiant energy. {(') Ktfects of soil and climate. (/) Sociological etl'ects, hahitation. clothing, dwelling, occupation, 101(1 other environmental conditions. ;{. Chemical Causes - under which, hesides («) the gross effects ot caustic and other agents ui)on the tissues, we should include (6) the main effects of vitiation of the atmosphere hy various gases, and (c) the main deleterious effects of imi)roper food, as again, to some extent, the deleterious effects of certain occupations. 4. Parasitic- under which heading are to he included the deleterious effects of: («) Mimite vegetable parasites- bacteria and fungi. {!>) Minute animal parasites- sporozoa, amcehip, etc. ic) The larger animal parasites, including worms (cestodes, trema- todes, nematodes) and arthropods (arachnids and insects). As one reads the foregoing table, he will he conscious that many of the agents nieiitione. Section. 4. Contusion, with which may be included lacerations and teanng. 5. Compression. (1. Distension. 7. Atmospheric pressure . 1. Concussion. -This is the effect produced upon a s(>ft, fliud or Minifluid body by the momentary application of force; familiar examples ire l)lows ui)on the brain, or ui)on hollow viscera with gaseous or fluid contents, such as the lung, the hliulder. or the stomach. The brain 1^ a soft substance lying in a bath of ffuid; if a blow of sufficient force I.e struck upon the skull, without fracturing it, the brain may be iamaged hy being proi>elled against the opposite side of the skull, inasmuch as, being (ienser than the iiiiid In ^^hich it lies, it takes mure momentum fiom the applied blow than does the surrounding mer the initial paralysis of the vessels which are the Iieat-regtilatii.g mechanism, the vitality of the cells is arrested, and they miiy die. or at the best may throw into the circulation deleterious materials; in addition the sensory nerves of the part are profoundly irritated. It is thus evident that while heat or cold may cause death, yet short this the effects are primary and secondary; while the disease-causing .! -nt operates, the primary effects are produced, and after it ceases to operate, we ha\c yet to reckon with a train of secondary effects. Here exists the ditierence between physical and parasitic causes of disease; in the latter we have the continued effect of a constantly present agent, while in the former, we ha^■e to meet the after-effects of a temporarily applied diseasf^-cnnsing agent. Light and Radiant Energy. — The most definite evidence that radiant energy can cause disease is connected with cases where the tissues are 78 rut: ctrNKN '"•' /j/.'^a'-^'S'' ) ..,v,,t..,l hv tlu- .r-rav s n>,.l ra.li.nn ...«anati..ns It l.as lurn •-tunatod a . M- ..f ra.lin.n r.nh\ U .•..ll..t...l ... on., mass, inen > t; wi^;^.. ;; .■.-rtai,. .Usta..... ..f it woul. .aus. '^;;; ;• -I „ '^-, ""•' i;:^'";"!; r/ 1 ' ^ "m ' ::i":,.s ti. ....... ....tnu a,... ..f ti,. Zt::.:z.;::^^\':^ ■... .iti.... .„.-. ,.r..,.r ...s ..r ti n V.1 s^^^^^^^^^^^ its .•o.nl.inati..,, with .rrta... tm,.u-nt aco.n- ;;;:;;.'in;';:S;if ; i. as i.npnre air. .l.. i.. ti,,.. ,.nKl.u. .ld.t.nous '■'S::tS''l ' i"'a-S^;S-ult to .ive .nuch .lofinite infor.natio.. .,ho rS 'W. ..f <-I.;tricity upon the tissues The ertn'ts of he f .. ...rr M.t -.re .litlVrent fn.m those of the alternate; it seems that ^,, M, , 1 fr„M, .■l,«ri,i.v tl«- »„rst tl,i„« th,.t .■«.. Iia,.|.™ t,. thv |»t .■■,t i I. . 1.1 1..- .'■.."i.-.i ..II t.. ■■' l...»i.i'»l- .I;"/""'/"-/;"-" ";" ;;:;;;:r,: ;';r ';" ^m. ; i -"it.. '*, ,i,m.' .vv^- i.i«i., ,....e...ia. "■„,"!;■ |.™.l .l,r„„t.h .!.<■ i;.l...a1. l..«l.v «i.l'."« '"J'">- "I'I"'"SI' '*»» ..(•tion ..f a caustie. or ot :'. more n.stro>e.l. have tlu-ir functions .hstur he.l Any snl< li r;.r .as which is capal.le of heing incorporate.! with the ho.l> Zls. an.i thercl.v conun, to a.t .leleteri.,usly upon tl,e cell substance. ,nav Rive rise to morl.i.l changes, and thus he a pois.m Poteons \Ve Iku- jn>t stated that chenucal sul.stanees that ac .U-UneSsh mav .lo I, either as caustics, that is. as substances that ■^TZm M\. l.y .lirect contact^ with them, or as .n ox.ca^| s^ that is, as .ubstan.T> M.at act harmfully >,:„.„ ctu. by rca».m of l>emg ...rp^rated w h bouy flui.ls and exertmg the.r ''iflf^.^;'!'"" ^^'^^ any Aerc i.i the luuly, even at a distance from the point of first contact. POST \.\TM. ArQt'llit.MKST <>F ni. t also siil>stancc-> in tlictn- mIvcs harniU'ss whicli li> reason of their anionnt can interfere with the orderly and i)roi)er perfomiance of the duties of the cell. .\ poison i, not onl\ that which imlucc- molecular distnrhance and disonlerly clu-niical change in the cell, hut also that which interferes with or inhihits the normal molec\ilar ihanjtes in the protoplasm. .\n example of this poisonous action hy a suhstanee in itself no poison, is found in the case of water, which is essential to existence, and constitutes 7(1 per cent, of the IxMly weight; if it he introduced into the tissues ahovo a certain amount (tiO c.c. per kilo of l.ody weij;ht) it may kill. This will indicate how wide a meaning w liestow upon the term piiiniin. . . I'oisons may he at once divided into two jjroups, exogenous, arisuij; outside the .system, and endogenous, arising' wifliin. In dchninj; what is exojrenous and what is endogenous, we must he careful; fom, and is as yet external to the lining epithelium of the hody; yet many wroii>;ly sjjeak of the absorption of decomi)ositio!i |)roduets of it as luito-iiitnxication,^ as if such poisons were endop-nous instead()f hein^, as they are, exofjenous. The strict and useful definition of the two terms must he held to he: endoj;enous poisons are substances actually deri\»'d from the cells; exogenous those set uj) hy suhstanees forei>,Mi to the cells. Thi:^ latter will include even the products of haeteria in the tissues. The intoxications then may he j,'rouiM'd as follows: I. Elxogenous Intoxications. 1. Xiin-imranitir.' Intoxications due to the actions of poisons not produced in association with the organism, whici sjain an entrance into the system throujili the .skin, di^restive, resj)iratory. or urinary tracts. 2. I'arunitic. — in) Paranitlr prupcr, ;rowth within the tissues of parasites of vari-us orders, animal ,ind ve>;etahle, which, arrowing, give rise to to.vic sii!)-tances. [h) Saimiphytic, due to the growth of parasit( nf various orders on one or other surface communicati'ig with the exteri<)r of the organ- i-ni, the products of growth l)ecoming absorbed and diffused into the tissues. n. Endogenous Intoxications. Of pure ty|)e; auto-intoxicatu)ns pro])er. !. Internal xrrn'tDrt/, intoxications due to altered intenuil secretions (.11 the part of the body cells affecting (ti) the secretory cells and tissues tlieniselves. and (h) the other tissues of the organism, through diffusiim of the altered products of cell activity. > (irr<>c, self. iCP m • CMSKS OF DISEASE gQ Tin: CM Sh.-^ «'/■ ""- unit exert 1 1011 EXOGENOI INTOXICATIONS N0N-PAEA81T1C . ■ tl... l,n,lv or ii' M.rJ)e«l l>y it act (1) Foreign i.^ta.ur> vntvnu, tu o b r ^^.^ locally, at , h- vf'^ f 'X^/! Hw!.;;^ ^.generative or necrot^; sufliceiit tii.ieela )>e>, tliir. i^ t "' 'l,.,,,..:,,,, If u poison like ;i',. ,„„> ,,.. f...n.;«" ,:;:;; 'r,; ::.:-:;. .1.- .™!-»' *-«; :;;;';;,■ i:;,:;:V.i:4ii- .''"'«»' '■«-" """ '"" •"ivSnrmav hri„„ .1..,,. O^ir „e„en.l eff...» W. >l,c t..llo.i..« »«>»: of function. ,;,•:. v foUowedhv ,. By increase of (rll a> "^^/>; J' ;;''',,,; ^.^,^1,1 he merely to rata- To classify the po.suns un. er s . i^^^^Z l^ne selective etfeets loguethein; it is better tojah^^^^^^^^^^^^ ^,,^^ ^, , , !;;:::;;:;r;;;r:;^^;e';:::i^.:*s ..e ...rence to ti. tr^^ies of on account of its ''^''"-^^X fore at .iitlerenees according aHVcted by poisons ami ^^J^"'\' f ^J^ ,.' T,,, ..f tlie high degree .>f to the intensity of the dose. 15> M ^^.^^^^, ^. ,. ''-•'•'••"""'■'V' ^'rr^tr^lli"- us CO reT n^^ for severe cerebral ;i;:;s;;;:;;S:;in;;!;)^;nS u;:ip ^^ -- »» -^>— ^^-^ ^^^-^ little or no ettVct on lower animals. prouned as follows: "^Wisons acting upon tl- --- ^^^ ^^^I^SX. .. ... hydro- 1. Th<.>e "nued.at.>^ r. , l^P^^^j;^,,^^^.,,, i,,- .nminution o Those causing increase ot cell activiiv i of "function, c. ,.. alc.hol. ''I'l^'l^f^J: » 7;,^;, ^ ^j bv exhaustion an,l 3. Tho^ causing increase o^ ac^n t ^. ^ - ^ ^^^. ^^^^.^^ ^^^. _ at times disuuegr:. urn- f..sr " ,,^.,, test activity, parts of the nervous system as tht sitts ot inc « •'7^n;h:^cm'b:^Ventres: Hypnotic, carbon dioxi.le. of potassium and ammonium. EXncKSC'is is'Toxr \Tin\s \n\-r\i; \sitk' si I. l'cri|>luTiil luTvi F.fluT, ( hldrcforni. riiiK U-ctr..in..l.ility), dii.litli.rin »«.xiii. iiikI. po^sil.lv, U-ikI mid alrohol .'). N»TV«> ttTininatioiir- Cirart', rncaiiu-, vrratrinc. iiicdtiiu- (■((iifroiitiMl l)v tin- iiiH'stit.ii liow this seU'ctiv tinii is hroiiKlit that it is siijrjjcstivr that flu- liypiiotics, an a Kroup iui>'l»"i"i fats and lipoid ^nhstaiui-s, and tin- ahuiidanc' ..f by thi> partunli'.r class of »'•*>«'«' Poisons Acting on the Muscular System. Ai)art from the .■IT-ets prodnee.1 ui)on striated nnis.le hy the mnliation of the nerves, there yt remain some poisons whirl, appear to ac* directly ii|M.n the muscle iell- these either excite inc-reased contract 1 ■■ or make the coiitrac- ti.m' more feehle. Of the former, the IrrtUUve examples are (lUMuno. catVeinc, veratrine (small doses), hypoxanthine, and creatine, as well as the toxins (.f the MaciHiis coli. Of inhibitiTe poix.iis may he men- tioned the potassium salts, the alkaline earths, and copper. It is suppo-^ed, too, th.it certain jKHsons pnHliicc definite effects upon uiistriate.1 muscle, aiul it i. with this i.Ica that atropine is admin- i,tered to excite peristalsis 1 ; cases of so-called "paraiytK- distension .,f the intestines" oc.MrriiiK in peritonitis; mori)liiiie appears m arrest pcristalsi-, l.v a the muscle of the arterioles to contract. These points still retpiire (•um|)lete verification. ,, , i Poisons Acting upon the Blood Corpu8ci«,i. I lie blcMxl corpuscles arc protecte.l from in iv injurii.us substances 1.'. t ." alteration that Midi Mil.stances iinderp n the i>rocess of heiii);al)M. ;/'i. '"it it injected directly into the I)1o(m1 stream these arc effective. 1. Hemolytics inemodastics).— The destructio. (.ir|)uscies may be .rou^'ht about by physiial mea; the tonicitv of the plasma by the injection of wate l.\ thawinj!' Some ;s. such as saponin, abriii, aii.l ricin are effective, aiul manv Imcterial toxins and animal venoms. .\lso daiifjeroiis to the hodv tliou^h without there necessarily beuiK hemolysis, are those ^tal'.lc c(mibinatioiis of heim.jjiobin with carbon numoxide, carbon dioxide, cvanojren, and the cyanates which i)reveiit the pror-r absori>- tioii <.f oxygen and carbon Leukolytics.- There af some poisons which can cause destruc- ri.m' of white blood corpus* Ics, but one must be careful to note that l.ukoiH-nia (lessened mimlxr ofleukocytes in the circulating; bloo . ly not be destruction <.f leukocytes so much as to altered .listri ;.;• tiun in the IxmIv at large. I'ancreatin can, however, cause tli.>ir destru. ; i.,n,as also can the i)res.uce of bile salts in excess. \N here the destruction < im be recoguizetl, it is cpiickly followed by the appearance ot a leuko- . > tosis, which is, again, at first not so luucii .lut- lu regeneration as tu redistribution. 6 |.;i;' blood .. 'i ,is alterir.g ..eeziiig or ^ 82 THE CAUSES OF DISEASE Poisons Acting en the Organs of Circulation. I'oisous may affect (1) the heart. ..r (2) the vessels jmrticuhirly the urtenoles, or 0^) the nerve centres that control the canliac mechanism; it is extremely diHi- cult for the observer to know which of these is being acted up n the most, because their relationship in function is so intimate. Poisons Acting upon the Heart.— It has been (letermined, however, that certain substances such as digitalin, digitalein, digitoxin, strophan- thin, anr (2) dilatation, bv direct action. Ergot and ergotin cause contraction of the arterioles by direct action, apart from their influence upon the heart. Adrenin iuid barium chloride do the same. Dilatation, on the other hand, is directlv i)roduced by the nitrites, chloral, quinine, and atropine (small doses). It is a strange fact that some of the drugs mentioned liave a >elective power upon the vessels of certain organs. Quinine acts especially upon the spleen, digitalein upon the kidneys, nin\ 1 nitrite u|)on the superficial facial vessels and upon the respiratory tract. Adrenin, while it causes the vessels of most organs to contract, when applied to the surface of the i)ancreas causes vasodilatation. Poisons Acting upon the Digestive System.— It is necessary when examining the elVect of a juiison upon the digestive tract to ascertain its effect when introduced into the digestive channel, (a) with the vagi and svmpathetics intact, and {h) with t'.ie same divided, and also, when iiitn)(luccd snbcutaneously. It will be seen that, by reason of the intricacN of the mechanism, the possibilities of error are great. Apomonihine, to induce eniesis, must be injected snbcutaneously, ipecacuanha must be put into the stomach with the vagi intact. If the vagi are cut, even large doses are ineffective. .Magnesium sulphate introduced into the blood or snbcutaneously will cause only moderately increase('crction rccpiire first to be absorbed, and their action is thus reflex. Poisons Acting upon the Stomach. \'oiniting is a process in which the nervous ^vstcin is dominant whether the impulses be originated from the meiinlia or ui>on the nerve enilings in the stcmiach. There are many irritiint jHiisoiis which can set u]i irregular i)eristalsis, con- traction, and relaxation of the . toniach walls. Poisons Acting upon the Intestine.— Diarrhea is tc) be recognized as a term which may refer to two distinct processes. These are: (1) the premature discharge of the contents of the small intestine without due EXOdENOUS IXTOXICA TlOXfi— NON-PARASITIC 83 alis(»ri)tioii and incMlificatioii, and (!') tlif discli.Tjje of excessive secre- tion from the mucosa of tiie intestine. The first of these is due to increased peristalsis ("roton oil produc.-s this directly; rhubarb or senna injected into the veins will cause it, and aloes when injected, only when there is a free flow of bile. The second process, the increase of secretion, is produced by the saline purgatives. Actual lesions of the intestinal wall are pHnluced l)y poisons in two wa>s: (1) by direct effect, and (2) in the process of being eliminated nito the bowel after l)eing absorbed there or elsewhere. The former are most likely to be situaie- .■loiwly or more severe degeneration, or even actual cell death local or general necrosis). 1 The pro.Iucts of .lestructi..n ..f the red-bl.,...l cells (hemolvsis). t iia. iHrn lonn.l that as a oiiscqiience .)f certain t.)xemias the'liver I" < oni.s in.apable of dealing with the excess .)f bl.).).l pigment given to " ■ ■md althongh the original t.ixemia may be partly to blame, the excess '" pi^Miunt itsflt api)ears to take a part in causing the damage. H g4 Tilt: CMSES OF niSK\SK i.u- viArtava -T\\o iriMUTiil Statement just Poisons Acting upon the K^Jney". ['^^^^^ j,,^ ,„,„, it,,,f nu^le. that the <7'''[ ;;•'"'^^ " > /. ..^t, I ' liver; the kulnevs must suffer, applies f. the k..lne>> as t ' ;^" ";, ^;^,^,„i, ,ireulation; bear t!.e hrunt of th.- toxu- ^" '^*"' ,; '"J , f Jj,, ,i,.,r are equally certain cf the n^ta^ ">-^-;;:,; ,;, ^,- '^tWr sul .t^nces. sueh as distinct predilection for these organs. EXOGENOUS iNTOHCATIONS-PARASmC CAUSES f ,rw..M^.> -ire- (1) mii-roparasites of vegetable Bactem "«'»"= J^ ,,^,,m t.K. small t.. be *,■„ bv thi- micnn Zl;i;,;;,.n:r l,in;;;i;' ".lal c«xi, ,h. nnUke b.* an,l the sp.ral J ,',„,, i„.e ,„„iia .,;■ .;t-r;n'rr ;,;;.r:r;e;s ;:f free- ,";.>, .bU.«„ -'"'"j;;,;;^-^ ti; t Tl bin" H, ,-..ur.r ..t tin,,. b,v ai-bU. ..f t,.nnent,.,K .be.n. M -t i,™„„'',„ ..f all. ,1.. ,«tla*.ni.- ba.teria |,r,. n,e «mm. .nl~a,ue» that .MTt a |...i»oiK.a. a. ti.ai i "til" bvniK tlimi.-. MPH RxoGExnrs intoxica tioxs—pa uasitic cacses 8- Ilavinj; in view tliis power of pnxlucin}; toxins, Imctcria are divisible into three groups: 1. Tlie non-toxic. 2. Those oniiiiarily ineapahle of miiltiplyinj; within the tissues, hnt j;rown outside the b(Hly capable of pnKlucin); toxins which, if al)sorl)ed, are injurious. Here belong many saprophytic and putre- factive bacteria, which may become hnlged in wounds and set up irritation there, and may give oVl for absorption their tcxins, without themselves gaining entr> to the tissues. Here also belong some of the normal inhabitants of the intestine, which, in excej-s, may give ofT toxins that are dangerous to the host if absorbed. Some of these last, at times, are converted intr members of the following group: li. Bacteria capable r>f growing in the tissues (and giving off toxins) and there setting up infection. From the foregoing it will be apparent that a bacterial intori'ution is the ccmdition in which the action of the products only (.: bacterial growth is considered; while an infection is that condition in which in addition to the intoxication, the bacteria themselves are in the tissues, and are multiplying there. Toxins. — The term toxin is used somewhat laxly to indicate the jMiisons which owe their existence to the bacteria; but this does not mean that they are necessarily manufactured by the bacteria. An example will make clearer this statement. In iliphtheria a highly toxic allumose is found abundantly in the spleen and other tissues, but very little is to be found in the membrani in the throat. Th- membrane is toxic enough, it is true; the mode of hajjpening is, probably, that an enzyme manufactured by the bacilli, and present in the mem- l>rane, diffuses out and acts upon proteid substances, which l)ecome (■(Hiverte° to (iO° '., and they diffuse slowly. Tlic discharge of toxin in the active metabolism of some pathogenic I'Hftcria is very small in amount. If cultivated outside the bcKiy, ili'M' organisms set free but little toxic niateriai; but if the bacterial iiiilits are broken up. toxin is .set free in adequate amount. Such I'xiiis arc evidently truly intracellular, and are directly comparable 111 ii.tracclluhir enzymes that have l)ccn discovered in tissue cells. We tiiii> divide the i)athogenic bactpria into (I) the endotoxic, such "L';inisnis as those of typhoid, tul>ercuIosis, cholera, etc., and (2) the rtctotoric under which are included the b. diphtherite, the b. tetani, I'. |>yocyaneus, b. botulinus of meat poisfming, etc. gg Tin: CAUSES of disease The Nonnal Defences of the Or.ranism.^-It b ^^J^^ the ways in wlm-h bact.-r a pun I"''*"!;"; / \' .^.'^m T»'^ h"»'^" „osses;ed hy the lunly ot '^^''-'/l-^ ^^i* f.' ur,n"e of which is to „Kly has a continuous external ^^l"'^'^^^ „„,,. the skin, but prevent t^.e -trance ....|..n.....--^ ^^ ,^^,,^^^ alsothehnn.gofeve^ a -^^^^^^^ l^^^^^^^^ „f eovenng m vipon the surface. Ihe ..nl> Dr ..k . ^ ^| pallopian tube to the human bmly is in the case ot ^ '« "^^^'^.^ j^ ,„ ,,eeplv situated, the peritoneum; this has s.. hne a ^'-^T'" yet this opening has that it is, to all irtents and purpo.es clo ed Yet t ^^^ ^.^^^^ proved, even in «l>P^'-^"\,!?f;;'; 1,' ' reUptU^/the human body peritonitis being set xip., ^)) '\,\^ou sWe, ^ he skin, in the mouth, is a "close corporation. Un the ouisiut , ^^^^^^^ in the upper air passages "> '- "'^ "^^^ :\ "e Tuccefd in getting are cuntless billions ot ''>;;• ™;,,^;J/j d.. so constantly, but their tenure of existence within is a very -hort one. The mechanisms referred to are these. constantly 1. Surface Washing.- Ihe bacteria on tiit sk n j^ jj^d removed by washing or by '-^-'''.f":',^^*;^^ \c^l g^^^^ kills r" ''> f fz^^ s: muc iu -uu^^ ^r- the majority of tliem. l lie mucus i" ,,•..,, |.„„t while t catches the alimentary tract, and the J™^'^'';,„^J " ;' ,, '^^^^^^^ ro their times are almost, it not quite, f "'f- , ^ „ „f t,,, stomach or that most peritoneal l"'- .""^ J";';"*. ''^i^^^^S^ the upper part of the intestine are U >> ^ "-^ \ , \ ,> killing of many „f the ileum or colon, which is ^'''\''^\7^. "^. „!,,, '"vit^ diminu- and the attenuation of other »;«^'^\'"^' / .^^.'^^^^ this no tion or absence of the hydrochlonc. XtT^l^^ak pass down ^2^rbowcl,whereth.rnu.lti^tj^nia>;^^ of cours.', enunnons m.mber> .f '"i^,^"'^;; ''^^ •„, ^he intestines As an indication ot the extent "'»,;« ^^^'^^ ,,,^. .,ried feces it may be said that on an f •■"^^-;^ ',',^;' !;,,,' d of bacterial bacteria dis.^harged rrn,:»m ,/ grams, orotlu r%M>t ,ostr - EXOGENOUS INTOXICATIONS— PARASITIC CAUSES 87 li. Physical Hindrance in the Respiratory Tract.— If air roiitaiiiiiig (lust and otluT particles impiiijrcs upon a moist surface, the solid particles a.lliere to it; the breath that is drawn through the nose, l)assin)j through the devious maze of the turbinate bones and reflected by till- pharyngeal surface is very thoroughly purified before it reaches the trachea, and in health the expired air is again relatively free from orgif ■ ms. It has been pointed out that the varying caliber of the larynx and trachea inchices a spiral motion of the inhale<| air, thus bringing each successive portion of it in contact with the lining nnicosa, so additionally ensuring the arrest of solid particles. The particles that Uulge on the surfaces are either expelled again with the nasal mucus in blowing the nose or by expectoration, or they are swallowed, or, in the case of a small percentage of them, absorbed into the tissues that surround the upi)er respiratory tract. These particles are of many sorts— bacteria, dust, smoke, and so on. Among them there are sure to be many that are a menace to the individual, and it is for the disposal of these, in part, that nature has provided so large a mass of lymph tissue in the neighborhood of the upper respira- tory tract. Between the level of the roof of the pharynx and the top (it t!ie sternum there are very numerous collections of lymph nodes, . aryiiiK in importance from the tor.sils to the smallest cervical nodes, all togither constituting a large amount of tissue. Just as a country places most garrisons near the frontier that is most open to attack, the Ixxly lias its garrisons of protective lymph ntnles around the road l.\ wiiic'h the invaders are most likely to come— the upper air passages. Partides on the surface are constantly being deported by the mucus and >aliva, in which they lie, being carried toward the entrance by the (ilia of the ejMthelium lining tho tract. 4. Protection by Leukocytes. — On mucous surfaces there are fre- (|ii.iiti\ free leukocytes that have wandered from the bloo (aj)ti\e, the foreign body is thus imprisoned, and for the time being not (•ai)able of doing hurt to the body. No commonwealth fears very LTcatly criminals or other enemies, if each criminal is handcuffed to .1 poIiV.tnan. The leukocytes which wander back to the tissues are larric.l by the lymph stream to the nearest lymph node where the intruder, "if a bacterium, is killed by the leukocyte or if the leukocyte Ik wcikeiied by its struggle with the bacterium both are engorgeil !>> line of the large endothelial cells the macrophages— which line the 1,\ iii|ili sinuses. Haderia are, thrrrforr, cimstantb/ findimj thel, way nitn the tissues, but under such circumstances do not cause infection. hi liHilfh they are destroyed soon after their entry. Tins process is going on coi\stantly in the tissues underlying all the iiKii-t surfaces of the body, and in none to a greater extent than in the intestines, It is scarcely credible that the absorption of so many 88 THE (WrSKS OF DISEASE leukocvtcs- tl.c s..li.l internal ornans spleen. k..lne>, it(. Iism i t- .V . ..ntain l-aeteria. hut ap,.reeiahle «n.wth tr.,m 'j"^" ^ ;;^-; e unml.h l.eeause .n..st ..f the haeteria u. a given or^an at the m< m nt ■mm the cireulating 1.1.....1, an.l after an hcur pn.hah > none at . . S e ot elh n -t the hlu.-.l vessels ..f al! the organs has l.een aetue h Urn vh K t e haeteria. the ieukoeytes have hen. e.ujulhng U,e,a, a u the Inuteri.i.lal snhstan.e. of the hlo.-l ^-"'"^ .^'-"'-^^ ^,^^ h rs h.ter however, the l.h.o.l is again teennng with them. Ihis m". :rsorattem.ate.l, half-kille.l. or nninjnre.l haeteru. tneked awVv in some .-orner with insnfti.iently powertul t, a...l .t swee s er thh.g hefore it. It is possihle to fi... ... m.eroseop.e r^-'-f< ' ^ liver .lots. si.,gl.-. .l.mhle. or trel.le. wlu.-h are the re,na..,s ..1 hacttr a, a,..i ..tte,. wh.'.ie ha.teria the.nselves. Granting all the h.reg.nng e^.- ,ie.H-e. nevertheless. //,.■ hrnHlut tix.m. are potrnhnlhl f^'l^, j Modes of Infection. Sin.r th.re are many ways In ;^ 1"\'\ ' •»^^; "^ e..t.T the tiss,...s. it is evi.le..t that th.Te are ma..y ways hy wlueh mfec- tio.. ean arise. Infe.tion i.,.plies n.-t the .nere pjTsenee ..r^ the s,.e . sv- f„l muttiplieation of haeteria ... the t.ssi.es. I he ta.t..rs that makt po»ihle the latter are these: EXOGEXCrs JXTOXKATIOSS—l'ARASlTIC CMSKS SO 1. Traumatic Solution of Continuity of the Surface Layers. Hen' an ingress is i)r()\ ided for the l)a(tt'ria. and tin- damaged tissne is a fa\iich cases, but we cannot refrain from indicating the methtKl in which such an accident iiia;/ occur. '2. Alteration of the Surface Discharges and Secretions. — When in " tV\er the salivary secretion is lessened, the mouth becomes foul and liiicteria instead of being swept away remain /"/( nilii and multipl.v; tlieir toxins cause necnt.sis of the underlying surface epithelium, and mi: nicer results, so that there is now jm)vided a suitable medium for yritwtii of tlie bacteria in the damaged ti.ssue and an entrance into the l>ii(ly. Similarly in the bowel, if an obstruction occur, the bacteria in tlie contents above the obstruction multiply, give off increased toxic linHiiicts, and rapidly increase in virulence, an observation that is niidiiy verified by exi)eriment. '■'. Growth of bacteria and infection in an internal organ with no recog- nizable solution of continuity of the surface — "Cryptogenic infection." All osteomyelitis of streptococcic nature, for exami)le, is seen to iri--f without any surface injury or recognizable trauma, or a joint 111 rlieiiniatic fe\er is aspirated and a coccus is cultivated therefrom. 1 lli^ is clearly a case of cryptogenic infection. Why, then, if bacteria :irf ill tile circulating blood, is it not a constant occurrence? There Jirc (lonlitless several factors which nmst be concurrent, but one of 'liiiii is that there must be the requisite quantity of infection. Ju.st go THH CAUSES OF DISEASE "" -;-V""- . -'" 'r'T'i:;.' e": 1 S rule." can har.Uy set up an by a leukocyte, umU>. '^^ "^ ;V, '^^l.e leukoeyte, are al.le t., over- i„,Vet.ou, .e.ause tlu ^'^'^ ;•„.;„,■ .^^.^iate.l eircumsta.urs are eon.e .t. .^^^Xlt^ • a^'o-lly "-nn'- c.f haeteria up..u some neee>sarx : (1 ) t a 1 ^^ "^ '^^^^ K ^^^^^^ U-ukocytes passu.K .n.t au. nu.cuussurfaee; (2) Y'"' ^ •. !' u-cumu ati.n. of so many bacteria at -t""''T;i't Ih^ii r"it ce uZul^s exhauste.1. and prohahly one spot t hat t u ''^f '\p^ ^^^ ^i,-,, ,,,,., Move the hactena were S.= ^M^^i::^ is\h:;r^>: >n.on.e of. a contest between the Etoria an.1 the tiss,.es> whicl. t»^-- ^ ^^^,, ,,,3 difTereut How Bacteria Enter the Body. fW „,.y,r „i,i„s. others in whi.li to siroNV lhe> can »« ^" • . ^.„ts, in dust, ui water, nulk, or too.1 taken h}, an"t"«'J , ' • ^^ bacteria do mmmm ;','r;,i;r"a..aM,„it.,t .1,..,„:,K,.< »t ,. ,».i.it ..t l..wer«l rc,„mnce EXOGENOUS I SrOXlC ATI! >\R— PARASITIC CAUSES 91 in an t-ntirely diircrpiit part of tlic Ixwly. Kereiit oh^tTvatio.is luive show II tliat a imriiial lymph ikmIc is not a lu-rfrct tilt«'r and lliat within a ven few minutes after inoculating bacteria into the tissue of the lejj tiiese ha' teria may be found in the circulating IiIixkI, past the inguinal iHMJes; if, however, a preliminary inflammation of the lymph ikkIbs be caused, the bacteria are wholly arrestetatements, it is true that bacteria of allii-d species pro«luce multiple toxins, some of which are common to all the members of that group of allied species; yet others are specific for each member of the group. With reference to the second statement, it is necessary only to men- tion the gonococcus which is active for man but not for the lower iiiiimals, and members of the group of the hemorrhagic septicemias iif various mammals and birds which are without ett'ect upon man. Nor are these the only variati.-.is. It the same organism be isolated from two individuals, ttie virulence of the one strain is never, or hardly I ver, exi)eriniv ntally identical with the virulence of the other. Further, ;ilt symptoms of disease ]T(.sent themselves, the body fluids cnntaiiiing the bacteria be inoculated into a second animal, and so on, tin- \ irulence can be heighteneiiiailer dose will cause d'sease in a much shorter time than was at first till case. It has been occasionally noted that this jjrocedurc, while increasi-ig the \Irulence for the species concerned, lessens the virulence tor certain othci' species. Ill II iniiiiiKr contrary to the above, there are certain methods at oiir (li>posa! by which the virulence of a bacterium can be lesseneil. rhii>, by iiolnnj^ed growth upon media, with transference at long iiitiTvals, the \ irulence of all i)athogenic bacteria is lessened; bacteria "stewing in their own juice" rapidly lose virulence. Certain other iriicedures eil'ect the same end, such as prolonged growth at a tempera- l»i TIIK <-.\rSKS (iF l>ISK.\Sh: to a.lva.ur ; if to., .litH.ult >t »";-"-; '"'n , " ;,.llv hijjh.r i.. th. s.h|. Other Pathogenic ▼•K«»»Werornu.. H" -Mn '^ f,,, -,. i,,,,,,,^. than the hactoria ..r s,lu/....ny.Hf>. l^'^_l^^;j^ ,„„;,, Umus ..f t„„.v an- s,n..lrv Kvp!u..".y.vtos a u .la t ^ t^ .U,ll„p„u.n, of l.„m.hran.-hin>r fih.nu-uts ..r l,yi>ha', tho la U '^'^\ ,,^ ,,,„,,,; „, wfll as l.y sp..rul.it.on. 1 h •>. t. rn > an j^ ; ,,.,,;,,,, ^.„, first orpinisin of J.laston.y.rt.c '»«'"""t'^'r;, ! ;^ ' ^ ^ ^ 'Uhihits onlv tho ,,Lv , i.. N.,rth A"u;"- -^- - ^ ^ ^ri;; im^lia outside the n.un.le.!. l.u.l.l.nK form, al h..i U. ''\\l^ ,■ ,^.twe.-n these and ,„„ly it develops .hst.nct hvplue ^f'^^^^^^ ,„,.,h nu.re the hacteria pn.per are tlu- ^«7''"»''' /" '' V\^. U^,' he rav funpu> or ,„i,.ute than the -«'"X ' :|'' tvl ; 'H, t^I" f.-s whieh.'while aetiiu.inyees may >e taken ■'yM"; ' . . .„j ,,,,,1^^. those haeiUi. H,vi„, the sanu- .Ijameter as he -«^';'^^^^ ^ to form eshihit true hranehm, and V.! "'S.;' "!v"v closely relate.! t<. a .ny.elium ..r telte.l mass. l'>7'' ""'; V/' ". -.h also under favorable th.. tuhenle l.ac-iHi «|"l '"••^l"'^ '""-t*""" . ^ ^' ^/r,; . tfere,>tiate.l ,„„.,iti.,n^ n,ay exhil.it true hranc-hing. ^, »^; "^/^^^i . ;".,f .lisease. :r ^^'^'^^V"":; '; SJr: • /r.te Jirl's^n^rtina. ..evelo;.- linl,. or ,u, ,,...» t„ f.,n„ t„x,ns. Am„„B '"'"^J", ";„;„,„!, the t.>s e. It ^ ',/',,„, i„tra.tal.lefonn..f inflammat.o..,thou^'h ;;„ ,;,l,';,';iJ ™,,.r,. r.,,.n,l.li,.B i.. many „•»,«* tl,.«. ...,hu,..l l.> ""Mibii'Tit: ,„ ,„„,„ „,. „„,v ,.>„. ,ha, 'i-<<; » ;;-«^' iierkefel.! Hlter. Ol thes. .lis.uses we may mention >ell..w k^.r, PROTOZOAS PARASITES AS CACSES OF DISEASE m ploiiropiH'iimiMiia of cattU', vaccinia, scarlet fever, ami pruhablv measles. It is |K>ssihl<' that here we «leal with ultrarnicrosciipic orjtanisins of more than one Mnier. Tims, the carriage of yellow fever by mosqitit(H>s suiTKcsts that this disease is caused by an orftaiiism of protozoan nature, v 'ile, on the other liand, rewnt researches u|mhi the cultivation of the oPKiinism of l)ovine pleuropneumonia indicate that this is allie fetes. PROTOZOAN PARASITES AS CAUSES OF DISEASE ^4^ There are certain parasites Itelonpii); to the division of the protozoa wliich can cause disease in man; these belong to different orders of protozoa; thus, for example, the entamceba is one of the sarccKliniie, the trypanosoine of the flagellata, the malaria orpmism belon>;s to the sporozoa, antl Balantiul.ipl:in« by amitotic division; 3, appearance of ohrom.d..l 11X1 in cvtoplasm which enlarge and bocon.e the spores in 4: these spore, become d.seharged or Tbe'tld (5) and develop («, 7. 8) into the adult amoeba, or (U) under other condtt.ons the amcBba passes into an encysted stage. (After K. L. Walker.) Order Flagellata.-^Of these, the trypanosome is the most important tvpe This is an elongated, spindle-shaped parasite, with an undu- lating membrane along one side, which is connected at the head end with a refractiie grannie, the microniicleus, and beyond the tail end is clongate.1 into a flagellum. There is a nucleus, and sometimes a con- tractile vacuole; multiplication occurs by longitudinal division, ihe dimensions of this protozoa., may reach 30 or even r,0|x, with a breadth of 2 (.r 3 M- i»"'l '" »"rp^''l^ ''rii"" ''''">•' 't "!">' ^'^ ^<'^" l«^n»"K ^" and fro in the Held among the l)li)orin in the cori)uscles. There is evidence that the trypanosomes of disease have a minute latent intracellular stage. Tliesc forms of protozoa are conveyed to man and warm-bloomes int.. the stomach, syhence they reach the tissues and ire .U;char>je carrier of ihe trypanuaonic of sleeping sickness. Order Sporozoa. -These (.r^anisms are characteristica'ly intracellular. The parasit*- enters an individual cell, arrests its function and causes its death the cvcle of life of the parasite bein^' such that the spore formation roushiv corresi)onds with the time o! death and disintejtration of the host cell. The spores set free >;rovv into small amcrboid forms, which enter other cells and repeat this asexual process. Hut a sexual cycle also exists especially in the process of transmission from host to host, and this sexual cvcle is carrie not occur the disease gradually passes • ill'; young children seem relatively resistant to the disease. Yet it .ippears that the parasite may lie latent in the tissues for long perio^' f ' f^ ^tsence of terminal flagtjla, spirilla ^^ro,>er^r7l ZmI^^^^^^ both extremities They Fia. 31 :4 ti„ :,s that this IS l..nptu.lu.al. »^ '^ J'"^ that transverse division staten.ent,hyotherequaUy c.nnp t n^^^^^^^^ ,„ ,,,,t of the obtains. Their behavior to^^a^l ^^^^^^^ "^^^ ^ ^j^^ pin.plasma. trypanosoim. to ^^^^ -^;;il^::^^;,X to trypanroth.and the ;;;;r^Sr;:rd^;^ni:,^ to wel^h downthe scale m favor of their protozoan relationships. METAZOAW PARASITES AS CAUSES OF DISEASE 1, .. v-lufh are of inirortance as The parasites ot .ho ■"«»»■:; !',*;».<*« ..r flat-worms, sr'"^-ss;;Vr';;;l;;:r:..n.:;: ti'e '-«« -<• "« -"«""'* "V*;t,..a».a„ ,>ara,it,.s in «--«! take ..eir feed » a J^par^l state horn their liost, so that iheit d.6l^.tl^e =.M< iyjwr*nwrt s, ?s A. m a, ey ne erva- e the >f the asma, id the favor lice as ivorms, repared only of PLATE II 1 llyiliril' fiTITi „'. I'imiii'iitr"! niii; fMrn ;! tii li. I'lLMiii'Tiic'l f"rrii Fic). 1. -Tertian Malarial Plasmodium. i,,^ forms. '' Noll fl:ii:i'll:iie f'Tiii. (Macro- , . >t'jriiieiitinir s. 1 liiL'ellMli- fiinn. Mii'P.iru- IlllMnt'Vte.l l.MMH'tC.1 111, SciiiiuMiliim fi>rMi .'iftpr cle- -inu'l'oii ii-fU\ 1. l|y;ilinc f.irni. J I,. .".. I'iniiic'Hti'.l fi.riii- i; ;ili.l 7. .-(•u'lm-nlih!.' ("nn- Fig. 2.~Quaraan Malar'ial Plasmodium. -, Sem,»..,linL' form after ihe (1. IImki-:!;!!.- l..n„. (Mirmm- ,l,.,lriicli(.n of re.l .-..rims- ■nci..i-Mr.i lie. III. Ni.n-ll:iKi'llcite form. iMucro- guiiiete.l Fig. S.-Teriiaii ^suvo-autumnal Malarial Plasmodium. s VoiiMi: ,i,tnw..n.iiMMil:.rcr<-- 111, lla^.-llalo f..rrii. AUrmua- ,.,.„, ,„..l..c.vUM (I Scu-in.-ntinL'f..rtM-. u m 11, (>..-.■.■,.,,. '..rnis. , :,tv\ Ir I'lL'liuMilc'.l l..rni- ! ;1TI.1 1 ll.^Miilll' Tim: I'TIll, J, ;):m. , I'i-mi-mi-il rimr U'f Fi 1. 4. -Quotidian /Csii vo-autumnal Malarial Plasmodium. S,.ir,,„.niiTiL' f..rm. SeL'mpn- In. 1 1 .. l:i aii.l l.V (■resr....iic laii.ir iii'lcic \ntliiiiin- lorm-. i.fli..i ri'd 1)1 Icori.u-i-lc | _. iK,,i,lf,,rm 1 I,, 1. lUalimMim-'lorm-, >"mc ,.,.1U sti'iw ilili>i-li,.ii uilh nil ri' lli;iTi "iii" uriiaiii-rii. - 1,1 - I'ii-im-nn-l f'lnii-. Ill " " I l:iL'|.nai(' f'irrn. iMicroua n Non-llaL'cllaic f-irms (Ma Nou. Mark til,. lari.-.-r -\m- an.l t'rvai.T am.mTil ..f i.iirmi'i.t in tl- tertian xi-ln.i. auiiiiiiiKil i)la:*i>itMliuni, Fro. 1 PLATE II li.i. •_> 4 7 1(1 V *. 10 /) < Vu:. 3 11 13 f^: Vu:. J i^. 3 5 ' ■ * . 4 f parasites. The capability of causing disturl)ance in such forms is not great, a state of affairs which is to be expected with parasites of comparatively slow development. Such disturbance, too, is brought about in several (iifVireiit ways, as: 1. Displacement or Pressure Due to the Presence of the Parasite. — Although this is in general negligible, a Filaria nocturna may block a lymph vessel and cause elephantiasis of a member. A cysticereus ill the brain may cause death, or the cyst of Tania echinococcua in the liver may be very large, and may menj.ce life. 2. Injury Caused by Migrat'in. — The filaria migrates through the tissues but cause'- little or no damage in doing so; however, on the contrary, there may be much pain and inflammation of the muscles ( aiiscd by the passage of larval Trichince. :>. Destruction of Tissue. — This is of very slight importance, and I inly to l)e considered in th« case of a parasite like Ankyhatomum iilitiiing up a large capillary, causing hemorrhage, or where a parasite like Trichocephabis boring through the bowel wall leaves a hole through u liich infection may pass. 4. Loss of Food Material Used Up by the Parasite. — Contrary to a common belief, this loss is so slight as to be negligible. .'). Disturbance Caused by the Excretions of the Parasite. — It has been su])posed that the metazoan parasites excrete toxins as do bacteria; -oine of them certainly i)roduce substances which protect them against the digestive juices of their hosts, and in many cases the bodies and l>i)(ly juices of the parasites themselves re toxic, but this is to b» expected, and does not give any additional proof upon the questic. it issue. More important is the %ct that all verminous parasites ft up eoslnophilia, an increase in the number of eosinophiie leuko- >tes in the circulating blood. This undoubted fact is evidently due ■ ' an excitation of the bone-marrow tissue by some irritant produced the parasites, and it may be surmised that the anemia and the idition of ill-being are due to the same or parallel intoxicants. Fiu. VZ I,),, Tin: cAisKs OF i)isH.\.'seharne internally into the Ixwly juiees secre- tions of sreat importance to the b(M myxoedema, the latter arising from mechanical removal of tW J« ^ Srchexia thyreopriva) as well as from more obscure ;-"--"-«;;: its atrophy, or intertering with its proper action. ^et i.sm i. con L'cnital- the cretin is ,,hysically and mentally m a stale uf rr.anlation Se achilt in years remains a child in intellect, or even an imbecile. Cretin, main, ngwl l»eniv-<.ni- yciirs. tBournivillc and Union.) THE KSlH)(tES(HS IS'TOXKWTIOSS '01 ilfiititioii is lute, hikI the scxiihI orf;Hiis hikI fiiiu-tioiis lieliiycHl ami iinpcrfVct; tin- stutnrt" \< smnll, tin- liirihs sliurt him! thi«k, tlu- ft-atiires nmrsc iiixl fx|)r«'s.si(inl«-s.s. ,Myx(rr tissius, gradually rt)lil>iii>; tlu- fmv of its oxpn'ssinii; the foaturt's lucoriu' lu'a\\ , and tlu' sulxiitaiu-ons tissiu' siitft-rs a cunnt'ctivo-tissiu' HVtTuruwtli. The skin ht'conu-s dry, tin- hair <'oars«', thick, and tcndinf; to fall out; the mentality becomes slow and the memory defective. The same train of symptoms may Ik* set up by complete removal of the thyroid Kl»"d. Thyroiers; the ;\illary bones become thick, the nose broadens, the lips, the ears 102 THE CAUSES OF DISEASE and the everuls enlarge, the hands and feet become big and clumsy, it p ogres oVthe malady i., slow, and the extract of the pitu.tary Ldy'of m. benefit to the patient. The extract fron. t-e m ernajd.ae •ind nosterior portions of the pituitary body causes a rise ot bloo(l pl^ssure sSar to, but more prolonged, than that of the extract of tK^ nrlmnal iiiul ill addition, induces a marked polyuria. ''D^tb^c R^^^^^^^^^ to the secretion of the Adrenal and of the Chroma^ SysteT-The medulla of the adrenal, apparently the more unporta.it StoTthe organ, is related embryologically to the sympathetic ganglia iCextract of it adrenin) leads to great increase in blood pressure; it ac s di ecSv on muscle, .ven if the nerve endings are degenerate.1 Ihe eitr u' of the sympathetic ganglia has the same effect upon Wood press- ure and the effect of ailrenin upon a part is identical with the result of sthm la ing the sympathetic fibres to that part. Both in the medulla of he adrenal and in the sympathetic ganglia is to be »-•';! ^"-l;- able series of cells of sympathetic-nerve origin, the chromaffin cells to-eal d because ..f their affinity for chrome salts, the cells taking on a strong vellowish-brown color after immersion of sections n potassium Wchromate. The indications are that wherever those cells a eTresent, adrenin or a body having like effect upon the arteriole Tal . p^^^^^^ Wc use the term adrenin rather than adrenalin or epiiephin because the latter are names of proprietary ^"^s ances^^ 'There are several pathological states which, acting ^^^^^^^'^^ inrr the adrenal give rise to the disease known as Addison s disease, it^s^hlclle'd by great physical weakness, feeble heart ac.on and pulse, nausea, vomiting, and pigmentation of the ='^"- i»^ pigmentat on is most marked upon exposed surfaces, and m regions normaTlv pigmented, and varies from a yellowish tint to a deep brown. Xcaseiu! tuberculosis, atrophy, malignant g-f^^;-. '-^^f £; nnd inflammatorv changes of the adrenal may produce it, and it has ^eVbeeTkntn to exis? where the adrenals are healthy but th^^ ^^ thetic gangHa diseased. It may well be imagined that the lack ot Solli-presslre-raising material due to the destruction of the orga"^ accounts for the cardiovascular depression. As regards^ the cortex rS gland, it is interesting to note that just as overdeye Opment of the glandular portion of the pituitary body is found associated with acromegalv and increased growth of skeletal tissues, so there are severa ca esCfi record in which hyperplasia aiul tumor growth of the axlrenal cortex has been found associated with excessive and premature obes tj precocious muscularity ("the infant Hercules"), and premature virihty with precocious devel.)pment of the external organs of generation. Disturbances Related '.. Secretions of the Testes and Ovj.nes.-it is known that in castrated animals the secondary sexual characters fail to develop, and this is due, in the male, to the loss of large^.i.terstitial ce 1. in the testes and of their internal secretion; there are hom<.logou.s cells in the ovary, although the proof of the effect of their secretion is by no in me ova j ^ i .. ,. .^^ p^g^ratwl animals means us clear as in ini tii^c oi mc nm".. THE ENDOGENOUS INTOXICATIONS 103 can he produceil by the injection of the ovarian extracts. Not only do interniil secretions of the testes and ovary affect sexual maturity, but tiiey are also evidently concerned in the full physical development of tiie bod,\. The function of the corpus luteum is of another sort; the secretion of the interstitial cells that lie external to the Graafian follicle is evidently j)otent to stimulate the uterine mucosa to respond to the presence of the ovum and permit its fixation; where the ovaries are removed after the fertilized ova are set free, these do not become adherent in the uterus. A secretion acting in this way is a good example of a iiormone. Disturbances Related to Various Other Internal Secretions. — The Foetm and the Mavimary Gland. — It has been proved, according to Starling and ("lay])oii, that the hyDcrtrophy of the mammary gland in pregnancy is due to the intern.., secretion, so to speak, of the foetus. Watery extracts of rabbit foetus injected into a virgin rabbit caused in a few weeks hypertrophy of the mammary gland and the formation of a thin fluid secretion; in multiparous, unimpregnated rabbits this was true milk. To disprove the supposed effect of nervous influences, a nianmiary gland in the guinea-pig was transplanted to the region of the ear, where it underwent hypertrophy in pregnancy, and, finally, produced milk. It is thought that the substance in the foetus which does this acts upon the mammary gland causing anabolism and growth; wliiMi the child is born, lactaii'»n begins because this substance is no longer present, and. the cells which before, under its influence, mani- fested anabolism and growth, in its absence break down and form milk. Thus lactation is apt to cease with the onset of a new pregnancy. Doubt has recently been thrown upon these observations, other observers associating the growth and activity of the mammary gland once more with the corpus luteum of pregnancy. Disturbances Related to Secretions in the Intestinal Tract. — It is but icceiitly that we have discovered how intricate a system of internal icretioiis exists in the alimentary tract, and we shall rather try to iinlicate what these are than to deal with their derangements. The H id contents of the stomach passing into the duodenum cause an iiH rcase in the flow of pancreatic juice; this hapi)ens not because of n Ilex nervous stimuli, but l)ecause of a chemical suir-t as vet at all exphcable. of suhstratunr, (-') by ncrmal secretion w.th ^^^"^l «^^ "^^ I ri> hv ■ilweiue or .liniiinitioii of the hormone without wUitn ine and t.i) b\ aDsnue or " "" , , ; i,^ ,,1 the organ that m an ^""i '^ j. , , ^ f^.,,. ..^.^rs is inihcatiiiK that Uiel^'Sn ^ - W lu: h t llidy depen.ient upon t^.e interaction ;\):'s:c?eti:;;;s of tm. duc.less .lands; that. ..a -r^aiii^ex^nt^^ but thev cert;:i^;iy suLp.-rt the view tliat there is much interdepe.ulence '^N^elllSateTproducts of Katabolism.- Intoxications may be , JeM h™e in Uvo uavs: either the excretory organs, being diseased, : Uo m ate pro.luctsof katabolism or even if the secretory organs THE ENDOGENOUS INTOXICATIONS 10') eliminate, there may he resorption of tlie excreted material owing to ohstruetion in the (hicts. The Resorption of Excretions. — There is a normal resorption of excreted material constantly going on in the hody; the feces solidify in the lower howel because of resorption of fluid; the increase in solids in gall-hladder hile over that of hei)atic- be that cause uremia is yet unknown, though many different I'Mc- have been suggested. Disintegrative Intoxications.— Autolysis. — This is the process of self- liHiittgration that tissues undergo; if, for example, liver tissue be n iiiiivcd from the body and protecteil ''•nm septic infection, it becomes "tt, by reason of enzyme actions, the , .ost important of which is that M which breaks up jjroteids. To illustrate this, on" may take the fol- ing figures (Wells): a liver in which only otie-tenth of the nitrf)gen ^ ill a soluble form, after being kept twenty-two days aseptically, 'aiiied ix-tenths of its nitrogen in a soluble form. The enzymes ii li bring ai)out this change are elaborated within the cells them- 1 ■', and all soft tissues behave in this way. the liver and renal cortex "iig the most active, the brain substance and skin among the least Autolysis occurs most readily in a slightly acid medium and at nipcrature slightly higher than that of the body. The tissues are rally alkaline in reaction, and the process begins only when this -f^'J^"^^.^"^' "..JT ''.MSM..) ICG THE CAUSES OF DISEASE [« p: alkalinity has boeii neutralized by the product..... of carbon d.oxide and or,L.ic acids, such as lactic a..d l>utyr c, wh.ch are or.ned m dying tissues. This process of autolysis takes place ... the hv.ng organism. Thus, if a piece of liver have .ts blood ^«PP'y f^^ f ' autolysis will ocur in the n.ost , ,tral parts but ..ot "? the per- ipheral because the alkaline lymph d.tf uses ...to th.s part of ,t. 1 here is. however, an exception eve.i to this, viz., wherever leukocytes gam entrance i.i large numbers. Leukocytes possess enzymes, the leuko- proteases. which act most powerfully upon the leukocytes themselves, but once liberated act also upon other tissues. Ih.s explains the softening of septic h.farcts, and of the outer zone of simple infarcts, into which areas great numbers of leukocytes migrate; it explains also the softening and absorption of the exudate in a p.ieumomc lung. The softening of a tissue by the effect of this leukocytic e.izyme is called heterolysis. as opposed to autolysis, where the ce Us themselves supplv the enzvme. But, to prevent this universal heterolysis wherever there'are leukocvtes, there is an antibody m blo,Ml serum which tends to neutralize the enzyme of the leukocytes, provided these be not present in overwhelming numbers (Opie). „ , , . Autolysis is seen in the liver in cases of acute yellow atrophy, phos- phorus and arse.iic poisoning, chloroform poiso.ii.ig. and in the group of cases characterized by pernicious vomiting (oftenest cases ot prtg- nancv) In these the end-products found in autolysis are present, viz., leucin, tyrosin, etc. The operative toxin has evidently destroyed the cells without destroying their ferments. There is a partial explanation possible at th.s point of gangrene as it occurs in diabetic cases. Acidosis, as it is called, is a condition of heightcMcd aciditv or lessened alkalinity of the tissues, with the production of acet..nuria; such is freciuently present in diabetes, and this lessenef severe superficial burns. Impaired Metabolism as a Cause of Disease.— At times the cells of certain organs of the body do not carry out the process of metab- olism to its normal termination, and discharge substances that are toxic, or, through deficient oxidation, there may accumulate in the system, bodies not themselves toxic, but obstructive to the proper activity of the tissues. At other times, although metabolism can scarcely be said to be impaired, yet the metabjlites fail to be excretee they are endogenous. There is normally a certain small output of < mlogenous j)urin Ixxlies which represents the natural wear and tear "i tissue. The muscles are constantly putting out hypoxanthin, and t xcreise increases the output of uric acid, suggesting that one purin '■"ily is readily converted into another in the body, as happens in ' ">. If the pancreas be chopped up and allowed to act on guanin, ean c invert guanin to xanthin by means of a ferment which has ' n called guanase. Similarly, adenin can be converted into hypo- wiihin by the adrenal, the thymus, the pancreas, or the liver, by the •kmi of the ferment adenase. The different glands, in fact, contain tiients or groups of ferments; and in this series a ferment, an oxidase, oiind in the lungs, liver, muscles, and spleen, which can convert alloxuric bases into uric acid. Yet another oxidase, found in the le.Ns, the liver, and the muscles, can oxidize uric acid into urea. 'Ily, or perhaps one should say firstly, there is in cells generally * rE."«Pf*- 108 THE CAVSES OF DISEASE a nuclease l.v which nudeoprcteins are disintegrate.!, liberating the ^"step J»v step the foii..wing process can be seen to mcur: (1) nudeo- prcteins; exogenous fron, tocHlstufls, or endogenous tn..n the ImkIv cells acted on bv L-lea.e, yield (2) purin bases, wluch, acted on ^y 'luana^e orllemm' vidd (:i) xanthin and hyp..xanthu. which, acted ..n b> an arXi yield (4) uric acid, which, actetl on by an o.^da.e, yields ^""Thm- are ..ther much more important sources of urea; but this will indicate the variations in the amount of uric acid that may be derivxMl from the same diet, and the importance of the action of certain ferments that are constantly present in the body. « * ^t t is necessary to know, m..re fully than we .lo the toxic effects of the purin bases', for they are toxic, and it is perhaps the purin bases tat are responsible for gout. Gout, therefore, is probably the outcome of iu.„ficient oxidation, wherd.y the precursors of uric acul and similar bodies, are not fully oxidized, and by their accumulation anT their toxidtv. set up morbi.l changes; and the uric ac-id formed L i^i its turn imperfectly oxidized, and accumulates; this dimimshed oxidation b dne to a constitutional deficiency of oxidases, inherited or "'cystiluria.-The appearance of cystin in the urine is an unimportant matter, save that it may lead to calculus formation; but it is worthy Tnote at this point, as somewhat paralld to gout. It tends^ to be a familial disease, characterized by the appearance ot cystin m the urine (Tstin is a sulphur- containing amino-acid. and the evidence seems to show that it arises from an abnormal disintegration or conversion of the sulphur-containing part of the protein molecule. Alkaptonuria.-This comlition, in which the unne turns dark on exn(,sure t.. the air, is due to the absence or deficiency ot a specific oxidase with the rcsul. that final ,.xiff, and the salt, once more basic, is prepared to take up more carbon dioxide from the tissues. Where there is excess of acids in the blooil these combine with the basic salts, and as a result the ciirhon dioxide remains in the tissues, causing symptoms of asphyxia. Before leaving this subject, it may be recalled to the reader's mind tliat this condition of acidosis seems to underlie the disturbances iiiund not only in diabetic coma, in certain cachectic diseases, and ill starvation, but also in che pernicious vomiting of pregnancy, the (Nclic vomiting of children, chloroform poisoning, and certain other less common states where grave hepatic disturbance has been deter- mined; at the present time we can do no more than state the "t)stTvation. Dyspnoea and Asphyxia. — These symptoms, it will be seen, depend upon acidosis. It was for a long time debated whether they were < iiiiscd by deficiency of oxygen or excess of carbon dioxide, and the Itcision is m favor of the latter. The tension of oxygen in the inspired Mir may be reduced from 20 to 8 per cent, without inducing dyspnoea, but ill! increase of tension of 0.5 per cent, of carbon dioxide in the inspired air and so in the blood, leads to such increased activity of respiration that the volume of inspired air is doubled. Be it noted that the increase i-; not in the amount of carbon dioxide in the blood, but in the tension of free carbon dioxide in it; for in diabetic coma, as has been said, acids 110 THE CAUSES OF DISEASE combine with the alkaUes present in the hloocl plasma an.l less carbon dioxide is actually taken up; but it st.ll diffuses in the bhuKl, and is present in a free state, gh ing rise to the asphyxia. Eclamp8ia.-There is a most grave conditu.n which occasionally shows itself during; the last few .lays ..f pre^M.aney or in the few hours immiatelv fc.llowin^' parturition. It apjK-ars in the form of con- X rollowed by ioma. and frequently is fata . Postmortem examh ation shows that there are two orders of cases; m the one there "extreme degeneration of the ki.lneys. in the other, the Irun of the Maucv is seen to have fallen up.m the liver, which exhibits areas of degeneration even to complete necrosis of the parenchyma ot the organ The condition is essentially associated with childbearing. is ,„,t of infectious nature, but has all the ear-marks of a grave intoxica- tion but as to what is the exact nature of the intoxication, we are still' whoUv in the dark. While some attribute ,t to the foetus, others bring (inadequate) evidence that the toxic material (originates from the placenta. Others, again, ascribe it to want of balance between the internal secretions of the maternal organism. We are not, therefore, in a position to classify properly the ccmdition. Ptomaine8.-These form a large class of substances obtained from the decomposition of animal matter; they are the results, although not the ultimate results, of the disintegration of proteins, for if the decomposition be continued beyond a certain time the Ptomauj diminish in amount, givins place to simpler s"b«tances. The wdl- known ptomaines are methylamin. di- and tmnetliylamm. chohn, neunn and muscarin. While some of them are non-toxic, others are intensely toxic It is possible that the symptoms of constipatu.n may be due to absorption of small quantities of these toxic ptomaines from fecal matter fermented by the agency of bacteria; bacteria are "ecessary, for these substances have never yet been obtained from foodstuffs without the action of bacteria. The same holds true for a group "f substances of a lower toxicity than the last, which are formed from carbohvdrates bv the action of bacteria; these are the organic acids- formic," butvric,' lactic, etc., and the interesting point al«ut these is that if thev are repeatedly administered, they cause disturbance ot a chrc.nic tvpe such as , irrhosis of the liver. This is evidently not the sole cause c.f cirrhosis of the liver, because it can arise from some such circumstance as this; the obstruction may tend to increased bacterial activitv in the intestine, which irritates the mucosa permitting to enter the portal svsten: bacteria of low virulence, whose endotoxins are liberated, causing hemolysis and irritation of the liver. From what has been said, it will be gathered that these intoxicants-ptomaines and indol and such others— are rather exogenous than endogenous. BODILY STATES AS CAUSES OF DISEASE 111 INTOXICATIONS NOT PURELY EXOGENOUS OR ENDOGENOUS Oastro-intestinal Intoxications. Constipation.—It is a common obser- vation that constipation, in a person whoso habits are regular, induces a tVeling of lessened well-being, and in some, actual headache or malaise. What is the actual toxin or toxins at work we cannot yet say. In acute obstruction of the alimentary tract, where vomiting, weakness, or colIai)se is present, we are in a position to be more explicit, although not dogmatic. Obstruction of the upper bowel is more grave than that of the lower, and the possible causes of this severe intoxication are two: either (1) the blockage lets unusual bacteria bring about abnor- mal fermentation, or the bacteria produce their own toxins, or (2) tliere are elaborated in the stomach toxic materials, .nich are in normal digestion modified lower down. Both these may be true, although the better evidfence is in favor of the former; obstruction does permit increase of virulence and increaseil multiplication of the bacteria above it, though it has to be admitted that the toxins of intestinal bacteria grown outside the body do not i)roduce the marked symptoms found in obstruction. It is true that one group of toxins— the indol group — > ' ;;;;^^j,i ^ tre is a .laily .Iraft; to which there is a .la.ly .nenme "" /" '" ^ ';\'^, .cc.n.e. the aeeount if .lav hy day the a.n.mnt 'l>-»^^'\;' ,*^Vl ^^ ,, will equire many .H.„ii,ishes. an.l a sud.le,. '7«'-^' .^I'^o^'^.e am..int ..f the aays of ineonu- wrth --'^^-^^ l^^'^ „^ ..ther a-.alo^ies i,, the aeeount is restored. II. rta(ur .a '.' r .j ij^ress ,)n if we same line of thought; and ^T^^^^./^f ;','-' student to rea.l the r 'Tuest -S' Er :" n£ whU-h tellently demonstrates how ^'"^^' Va ;^;;;;;l'.tie prmnple is iudicic^s ina...ty. . ^^^^^^^, droppe.l .lea.l at Athe..s alter P^^'^ ;; ^^^^,,,, „f ,„m.cat- Thire are all gra.lations from ^''•%*'';^';, ,t' , hIV "> n... har.l t<. cateh i,„ hreathlessness of the "^•">"""- '^,;\^ /^sser grades ..f superacute his morni..K train. The sympton.. ol » .^^^^^^ ^^^ ,,,„rt n..t l.ei.ig overstrain seem lar,ely due f. c;ard.,K- ';^^'; Jg;,^";,,,,,. The eases able to pass on the hlood as rap.dl> as t k J^" '^^ ''^ ;,, ,,«,. "' whieh death follows ...tense I- ^ J f .^ pn^^^^^^^ «>f muscular that tl.m> are discharged .nt..t^uW^^^^^^^^ ^^^^^^^^_ ^^^^ ,,^,^l^ activity, (adayenc "«»> . , T Sa^^^^ The acute vcous hlood fa.ls to eoagu ate » e a,, a ne ^^^ ^^^^^^ ^ ^^^^^ .legree of ..verstra.n may he excited smn ,5^^,, ,,^ ],,,, anorexia, fever, pa.n in the l.ml.s. am is re _^^ ^^^.^^_.^, ,onger-<-o,.tim.ed. but less extreme c^w^^^ ^^^ ^,,^^ p, „„, pianists- c-ramp. "'".fj;^",';' general manifestations of dis- ;;;;l.r fn: reSrof ^h:\.;iUe.es in th^r attempts to kc>ep accommodation i)erfect. TH<:ease —It is long known to > Ov.«.„, i. .ho „h,.i,.,l ™.. ove,«,», .he bodily s,... p»i«<«d by it. BODILY STATES AS CAVSES OF DISEASE u:\ more lial)lc to infection, that hard work, loiij? hours, and inadequate rc^t make men more lial)le than normal to aciiti- diseases, such as iiifhienza and pneumonia. If resting animals anti animals under- KuiiiK forced lahor are subjected to the same doses of bacterial cultures, tlie resting animals resist much the better; if into any such ammal, aloMK with the culture, lactic acid be intrtKluced, the bacteria grow the ni.)re readily; this is interprete nerves concerned; it is one or the other or both. The muscle ii-dl' can l)e fatigued by direct stimulation, because the substances !.ro,luccd bv contraction inhibit further activity; when the nervous I i.rliaiiism is considered we cannot experimentally fatigue the con- ! h tiiii; iixoiie; nor can we fatigue perceptibly the reflex centres m the ..1, htit what we do observe is this: if a reflex centre for a particular I !M If be selected, a centre that is amenable to influences from several ..rent tracts, and we stimulate one of these tracts, we produce in ' !i,c the phenomenon that the muscle no longer responds; if, now, tlur afferent tract be employed, the muscle at once responds. ' >liows that the muscle itself is not exhausted, nor is the axone m.tcd; what is exhausted is the synapse, the junction between the . M lit nerve tract and the nerve cell of the reflex centre; these two . parts of different neurones. Let us here digress to give a " working .." of tlie connection between neurones. One nerve cell does not 1 'liy join another n.^rve cell, but we may say that it is in contact or 8 JJ4 Tilt: r.tf.SA'.S OF DISEASE almost i.. contact wit!, if. t.rininal Klaim-nts of ono .-.•11 are in "nlmost c tact''\vith tlu- .Un.irit... of uhoUut. likr tl..- .ranc- u-s o one ree h .r m n«li..« with hut not actually tonchinK the hranches of another; . m e^^i^ acr.,.> ti,. spu<-e fn.n, twi,' to tw.K. when they are .n a " e of "ah .ust eoMta. ..•• Fatigue of a nerve eel may he praetual v t «ht of as a shrinking, hy which tl - twjKsor »'--^- ;>^ ;-;;- ,lra«.. a'sav fron. the ..ther. so that wn|»"l^«'^ have fa ther to jump r u one to another than hefore. an.l .io so U-ss rea.h y; .f cells are at Lue.l the in.pulses pass poorly he.ause of tins withdrawal from CO frc «' h sKh-p we may supp..se that the rested .len.lr.tes or axones arf ;xp;n.linK oul on.e n.ore to a p.-sition of almost contact; so ha o waking, the impulses (or thoughts or whatever they may h -ass ^„.|iiv on'c nx.re. Hevertin,' to the spec.hc example we are c ...k^- Inl'. ie uui> iM.ap.u- that the cnstant stimulation of one atferenc t-act Fio. 3;) ., re,„nK u.-rv.- .,11 «i.l. luU- r,„.,„l..l nu.l-»-, .h-wiim .■hnHnru,,, no,w.,rk ll.o Ni»-1 . I,'.. In he ,vtoDl«-in (.leriv,-,l from tl„ nu. l.ar nmi.T.al. uU. large and prom.mnl; B, ex- ;:ui:.H nerve VI :. J,,," .,r,l..r. » hrunk-n ,rre« nuHeus, chro.n.Uin uetwork .nd,.- „n,-., .N,s,l 1,.«1,.., .1 u.M,..,l in si»- .n,l ,>„..rly staining. processes ..f that neurone draw away till the impulse no longer rea.lilv jumps the sap.mi susceptibility or predisposition. As was shown earlier, this predis- I'l'Mtion may be inherited or acquired. 1 1. hcrited predisposition may be (o) specific or ex specie, as is shown l'> the predisposition of cattle to pleuroi>neunionia, dogs to distemper, iii.Mi to gonorrhoea and typhoid. Or i may be (6) racial., as seen in I'liropoans and yellow fever, Hebrews ai.*: diabetes, or it may be (r) familial, as in certain exanthemata, piUiiciilarly neuroses and r>ut. it IS necessary to digress at this po.Dt, 1.) indicate that error may • I il.\ occur here. A family may rea'lv- be comparatively immune to I I Incase because, by survival of the fittest, the stronger members of '! « fatnily have, by virtue of some characteristic, been able to resist 1 'iis.ase to which they were liable and have been enabled to hand • ' fi this characteristic strengthened. But where a disease has been ' I' inic, there are many individuals who have acquired, in an unnoticed ' iiMT, their immunity. They have had unrecognizable or unrecog- ! ■ '1 !!!i!d attacks of the specific disease which h.-ivc siiflTiccd to protect '' • ni. Tins is seen in the apparent immunity of the natives of manv ' : itnes to malaria, the children when examined having the malarial ■■>■ J J, J 77/ A' CAISES OF DISEASE • xu • 11 A V..V iiiort' tht'V niav only Have taken in stimulate them t(. build up an immunity to the disease. Ckssifi^tion. --Predispositic.n may be classifiec aceording to : ? Sex -The female I exposed to a series of disorders connected anL^(to tl^^nd of fir;[ year); athrepsia, various forms of enteritis with diarrhoea; meningitis ,• wi^^rlo Childhood - Rickets, measles, scarlatina, diphtheria. Srt-'i 1^W^«^^««-^'W"™^'« (i" female); acute rheumatism and Snatic heart disease (ten to fifteen) ; typhoid ; tuberci.losis irfllS Typhoid (twenty to twenty-five); tuberculosis (twenty to ^^''uiddle lo<'-G..ut, lithiasis, and chronic Bright's disease (thirty- five ontrd' arteriosclerosis, aneurysms (thirty to fifty); cancer (forty *°oKfl« -The same continue.1, along with atrophic conditions 3 HaSit of Life at Different Life Periods.-In the years of infancy when^rowth is procecling rapidly, the digestive system is under xno^t tress Med power of locomotion prevents much exposure to nfec- tousdi eases, which occur at a later time when the child ^^f^^^^fj S, is fellows- the age of work produces often a more sedentary hfe „ mo e cnifiuHl and often less well-ventilated -"oundings ( the nerio.1 of tuberculosis); with increasing age, lessened exercise and yet Ee sedenarv life ten.l to constipation, gallstone fo^^^ion, etc 4 ^evlus infection. -Although in some diseases an attack con er. immunity there are others in which there remains a greater liability to as"; md attack; such ar. erysipelas, furunculosis, acute rheumatism. Z influenza It mav be that the germs of the disease are not destroyed and hat a low stat^ of general health permits them to flourish once more Not onh" this, buc an attack of one disease is frequently followed ran infc'etion .>f a different kind, as when one exanthem is imme- Hiatelv followed bv another. . . ,. , t Malnutrition.' To exemplify h..w malnutrition .P- -P- t^^ disease it is necessarv only to cite the severe epulemics of infectious disease' ihat. at dilVer'ent times, have followed upon famine m Russia. '"Se ^ceSllliy of Particular Tissues, l^f-ence is ma.le here ijot to the susceptibility ..f an area that is injured or badly nourished, for I ^ PREDISPOSITION AND SUSCEPTIBILITY 117 thih has 1>« (Ml already dealt with, hut to the fact that certain tissues are prone to pirinit the growth of certain infectious agents. The channel of entrance has something to do with this, so that inhaled germs often attack the respiratory, and ingested germs the digestive tract. In foci that are clearly secondary, and evidently selective, we find the tubercle bacillus growing readily in the pia-arachnoid, but infrequently in the brain; infrequently in the stomach, and often in the small intes- tine. Even if injected into the blood stream, colon bacilli are apt to set up enteritis. The fact of the susceptibility of special tissues remains, but we have no adequate explanation for it. Consideration of these data brings us to an important conclusion that an injection does not involve the whole body. Coincidently with the growth of the specific lirrms in individual organs, there tends to be a reaction to and destruction of the same in other parts. We find typhoid bacilli in a patient suffer- ing from that disease, in the spleen, liver, skin, and kidneys, but with much difficulty in many other organs; yet we know that the infection is a universal one, and that these other organs have their chance to i)t'Come infected. It seems that in susceptible regions the bacteria are winning, and in others losing their battle with the tissues. Idiosyncrasy. — This term is applied to the exhibition of extreme susceptibility to the influence of substances that are not hurtful, and even beneficial to the average of people. Strawberries, shell fish, certain fish, in some people cause urticaria or other skin eruption, headache, and in fine, indications of an intoxication; idiosyncrasy to drugs is familiar to everj' physician. Hay fever is an idiosyncrasy to one or more particular kinds of pollen; and the presence of a cat ill the room, although unseen and unthoughf of, produces in some lieople a state of nervous apprehension, explicable by some unper- (cived olfactory impression; these as yet are curious facts lacking explanation, save that the recent study of the phenomenon of anaphyl- axis has introduced us to a possible explanation of at least some cases. I'lie administration of minute doses of protein followed, after a few ihiys, by larger doses of the same protein, results in a general systemic 'li-turbance resembling that seen in some of these cases of idiosyn- I riisy — malaise, profound depression, coryza, erythematous and other ' iiiptions on the skin, or even in some cases severe respiratory distress I an asthmatic type, the phenomena, in short, of "serum sickness." I I is evident that the system may develop an extraordinary suscepti- 'iiity toward one or another protein, by the exhibition of relatively I unite quantities of the same. The food idiosyncrasies, hay fever, and ' lie eases of asthma seem thus to come into line with serum sickness i iiiiaphylaxis in general. m CHAPTER III THE MORBID AND REACTIVE PROCESSES PROPER THE LOCAL REACTION TO IRRITATION-INFLAMMATION It is verv necessan' for the student to obtain a clear understanding of what inflammation is, and how it begins, progresses ancl ends because a hirge fraction of all the pathological specimens he will exer see and a majority of the clinical cases he will be called to treat involve n some way his process. He can become conversant with the thousand specTl cases of inflammation only by knowing that the same general laws underlie them all, even those most diverse in appearance. In whatever member of the animal kingdom wx- examine it. the response to an irritation is similar; if we scratch the tissue of an inverte- brate with a needle, certain effects are produced; if we scratch the skm fa human being we fin that makes it possible for us to construct certain rules which underlie everv case of inflammation. ... • j.- ^u^t Infiammatkm is the series of local adaptive changes in tissi- that result from actual or from referred injury. By injury we mean all grades „f' stimulus, from a mere irritation which only quickens the activity the cells to a damage which kills or all but kills them; and we sist upon ome such understanding of the term inflammation; because S ;. who work in a special fiel.l are apt to restrict the term, and here t e phvsician, the surgeon, the physiologist, and the medical student musrmeet on a basis common to all; the tissues behave after the same manner whether they are injured by the aseptk- knife o the surgeon the i)oison of the Staphylococcus aureus, the flame or the frost, and i would be wrong for us to lay T friT, some being joined loosely by cell processes, others wandering. I I an irritant body be introduced into this cavity the cells travel toward I! and stick to it; its very presence irritates to reproduction cells in ' iitact with which it lies, and thus new cells are born; these cells, new ■Mill old, surround it and if it be digestible, they digest it; if not, they 1' nee it off and render it as harmless by this isolation as they can. III re are both principles illustrated, positive chemiotaxis, or attraction, a'lil cell proliferation. This must be kept in mind later on when we find 'lit the wandering cells, mesnh!a.stic in origin, .are the cells that 120 TIIK MORBID AND REACTIVE PROCESSES exhibit chen.iotaxis an.l rally to the site of injury, whereas the fixed cells of the bodv tend to proliferate and regenerate. . , „ , As we advance farther up the /.oiiloK'ical scale to those animals that have an open vascular system, hut no proper vessels, we hnd another fundamen al princii)le illustrated; if the ectoderm be punctured, the Ivmph which bathes the cells of the body coagulates and temporanly sVals the hole; this is to be remembered when we hnd m our studies on the human body that a scatlol.l of fibrin is construt-te.1 throuphout the injured area. As we advan.e once more to the higher animals, which have a closed vascular ..ystem, we hnd that these same simple features persist, and that the vessels serve to convey more readily and more rapidlv lymph ami wandering cells to the injured part, there to carrv out their functions- the same functions that we find their counterparts performing in the lowly organized ccelenterate. Fig, 30 FoTtifu hrnlv giiint cells in tliyrmd vesicle, to show similar plaamodium formations sur.ounding foreign body, .'.r its equivalent, in .nan: a. remnant of mass of colloid in centre of vesicle; 6 g.ant cells attacking the colloid; c, giant cells that have air fdy dissolved colloul. (From case of chrome interstitial thyroiditis, Ilr. Rhea.) The detail of the inflammator\- process must be dealt with farther on with more particularity. _ The Causes of Inflammation.— 1 . Bacterial. Bacteria are most tre- quentlv the exciting cause of inflammation, whether by their direct cctionin originating the process, or as an adjuvant to trauma, as in infection after a wound, or as in secondary infection after a burn or after the action of some corrosive. It becomes at once evident that this admits a very large number of bacteria to our consideration; there -TT' ■«««■ » THE LOCAL REACTION TO IRRITATION— INFLAMMATION 121 arc the pathogenic organisms, such as the Bacillus tvphosu'^ or the Strcplococcus pyogenes, which can inaufiurate inflammation; there are the saprophytic organisms which cannot grow in the body normally, l)iit wliicli can multiply in surface discharges or on mucous membranes, mid there liberate toxins which can be absorbed and cause inflamma- tion; the non-pathogenic forms are able to do nothing of this kind and tor our |)urposes are negligible. If we are dealing with a microbe capable of setting up or of assisting to set up the process of inflammation, it is by no means certain that tlie inflammation will be of a definite, fixed degree of severity; every case of bacterial inflammation is a problem in which it is necessary to gauge the virulence of the organism and the resistance of the patient; and we shall see that varying grades of intensity and rapidity of the l)rocess are thus set up. Bacteria may attack the body directly, being carried to and im- |)lanted upon it from the outside, or from the mucous surfaces of tlic throat or intestine, just as the ^sopian viper bit the country- man who warmed it in his bosom. Another form of infection is of Rreat clinical importance. It some i-nes happens that an operation wound, made with the most careful asepsis, becomes infected; it is l»)ssibie that there may have been some fault in technical work, and till' bacteria may thus have come from the outside; but it may also liappen, and does happen, that the patient supplied the infection him- M If, and that bacteria were carried from some of his storehouses, the tiiroat or the intestine, by way of the blood to the wound, because tilt wound is at the moment the part of least resistance in the body. This implies that there are bacteria in the blood; such we believe actually to be the case. It is true that blood cultures of the healthy yield no LTowth; nevertheless, there are indications that from time to time liacteria are being picked up from the upper air passages and from the iiit( stine, and that under ordinary conditions these are rapidly destroyed li> the agency of the blood and endothelium; but if living bacteria be arricd to a part where the resistance is low, as a wound, then in place ' I undergoing destruction they are able to make a foothold and multiply. One very important function of the liver is to kill off the bacteria carried I 'III the intestine in the portal blood; for the portal blood picks up : t only food particles from the bowel but also organisms, whose iviiiains can be found in the liver at any moment. It is true that the I ' ttria which escape into the blood are quickly destroyed by several !i(ics, and the internal organs are potentially, if not actually, sterile. i: I'' these "chance" organisms which cause the latent infections ■> i the terminal infections, which last so often supervene upon some ' ! ■nic disease; an example of this is that a case dying slowly of heart i^c is generally found to harbor some inflammatory process such •iieumonia, which arises not by infection due to highly pathogenic i nearest, causing the bio-necrescent process with subsequent death ill .hose a little farther away, the same process with recovery in those . ' I farther away, and cloudy swelling in those still more remote, while tl "M' farthest removed, yet within the sphere of influence of the toxin, i:v merely irritated to activity of function, phagocytosis, chemiotaxis, •1 rcijpoduction. In every composite picture of inflammation, the i lent must keep in mind that although we may lay stress upon ' ' r more macroscopic features, yet in each field there may be cells i: all stages of "sickness." Inflammation in a Vascular Area. — Let us consider what hrippens ■ I'!', a tissue as the ordinary lax -subcutaneous tissue, plentifully - i'iilied with bloofl vessels. In this, let us suppose that the irritant — ^■i' n :i£i.^' ' '-^. :^^^^^ 124 Tin: MontiiD asd rk active PRncE^^Es sav a clump of hactoriii is imiltiplviiin: tin- toxins arc hciiiK K«vcn off in all directions. The first step which is ohservc.1 on the jmrt of the tissues is that tlie capillaries -..f tr..g: «. n,nrKin«tinn „f l,.»kooyt..s in tl,e .lil«..-.l capiUuri..,; h, mi,irati.,., of leukocytes; r, ornHp.' of red corpus.les; ,/, a.L-».i.uhi.i(.u of Icukorj t™ ouUl.le the oap.llanox. (After KibU-rt.) What is now going on is a struggle between bacteria and serum aided by leukocvtes and sometimes by tissue cells, for if the last are not too severelv injured they will proliferate, urged thereto by the irrita- tion of the toxin. The leukocytes and the newborn cells of the part are activelv " phagocyting" the bacteria, and many microbes are thus destroyed.' In the meantime the blood in the capillaries is circulating, and the Ivmph outside of them is also, in its own slow way, circu- lating, so -Ihat it will readily appear that there is great activity in sucli an area; the area in question is now a mass of leukocytes, of cells of the part, old and newborn, soggy by reason of the excess of lymph which has exuded from the capillaries. Up to the present moment, then, we have a preliminary dilatation of vessels, margination of leukocytes, ■3jr-r- ''Wl »«»»"B^ ~ *-« r.^xs WrvvT? IXFLAMMATinX OF VASCULAR AKKAS 125 I'ui. 38 (liapedt'sis of the sium-, t-xudatioii of soriim, and phagcM-ytosis. At this stane the part iiiHamed will show tiie chtssic sijjns of' inflamma- tion, dolor, rubor, calor, tumor; ;reater bulk of blood in the vessels, 'i'his mass of leukocytes and other cells is now on the i)oint of hecominK :iii abscess; if, however, the resist- jince of the body be successful, tile bacteria become eaten up by the cells, or attacked by the lysiiis iif the serimi, and the leukocytes, which have not died, wander away ii;rain or are carried by the lympli, the excess lymph itself disappears, the bodies of the cells which have • lic.l are disintegrated, and the pieces "scavenged" or cleared iiwiiy by their living fellows, and the tissue becomes as it was at first, with the exception of the proliferated cells of the part, which rciiiaiii. These fibroblasts in time Ixfuiiie true functioning connee- ti\c-tissue cells, and the total n Milt of the inflammation is that th( re is a fibrosis, an increase of thcM' fibres at the spot where the iiiliiiinination existed. This con- >tUiitcs the process of repair or iili-iirption in an inflamed area. 1 1 . liowever, the fight is not won l'\ the cells but by the bacteria, H i.> .onsider what happens. We revert to the stage at which we have 1, iulhi-aion of leukocytes to tlio walls of a Ciipillary in an inflatnr.l area; 2. nioili. of miara- tion of a polynurloar leukocyte seen under higher magnification. (Lavdonnky.) ,1 - ill (ill iiiL th; (i\ iin> ri',' 111,1 ill- ■ ■ "■ ••"'- oiff^t til, niiifii we nave uy mass o leukocytes, new cells of the part, bacteria and serum, Mt, the mflammatory mass." As the bacteria multiplv and give More toxms, more and more leukocytes die by reason of bacteria ted or of toxin absorbed; especially those leukocvtes and cells Mrc most in the cc-ntre of the mass are apt to die," because their "I and food supply ,s cut off by the dense crowd surrounding them 'heir excretion is not carried away freely from them for the same ■): when they die ^ye And that the centre of the inflammatorv •"■comes a mass of dead and living leukocytes and bacteria float- ^erum -m other words, pus, and the whole area with its containe7 sistcncc of clufsf. atHi finally, dry or inspissate«l. .Meatitime tlu- surn.iindiMK tissue has b«'» fonniriK granulation f ssuo ahoi.t it. and this fjranulation tissue Iwcomes iti time sear tissue, and the scar in of hluiK uf) tho nap where the original l<.ss of tissue ocurml. sur- n.,n.ds the dnetances, the pr.Klu.-ts .lirect an.l in,'r.<> of cell diss..luti..n. especiallv 111 l.'iik.>cytes. '^ In all the prece.ling paragraphs we have sai.l nothing about fibrin t-ni.ation. winch is so obvious an accompaniment .)f inflammation on ;| Mpons or a mucus surface. Vet even in deep tissues it mav exist. Hi.' s.T a in contact with them, an.l they are a.tive phagocvtes. It is ""le, th..ugh not provtMl, that the large mononuclear cells of the 'I' .1 arc the progeny .>f these en.lothelial cells. Wht the capillarv is •' r.cted. the spaces between them are small, but when the vessel is I ';"< , they are large, and it is through these spaces that diapedesis "1 ' nkocytes occurs; it may wcur that red blood cells are pusW-d out S,i':Et:X.'r£'^^::/ar' '^f i.i.i»^ is -.Ua. part "V^;XSt,. t. the. .n....u.al .^^^^ H,,„, ,,-„,ph SP..;- -;: ,, »';,^''t':V trn fn^-n tl.nn ale lar^e. repnHiuc-t...n; ami *»^*',;'' ,',„f' '^...""^.tivelv phaK.KVtic. Tl.esr <-ells aci.lophili<-. liyahne cells that « /'J J^'^ » J",, .".j ^,,,. ,«„»■ ..nler we find lyiMK mM the t.ssue ••^'l • «" '^'^\,;", L-e. The fil.n.ns as the l«^P^^O•uU^e eel Is Kuen c, b a ;-;;''; „f ,,„.,,.,,ive coiineetive-tissue eel wh.eh ^^^'' »' * V' ' j \, ," .. ,„„i the .ells that 'PI. ..■•..(<>»> ii matters not wlietner ii" i""^>".' • ir {.; 1.S strean. the lymph stream, the t^ue spaees .. ""tT-'b Jd'i;ttr'"Th. lH.k,«-.vW ar.. c»ll.,l to tW part tlmt is inflam^l the 7^^'''^';"'\^*'™ ;^V e^^^ ooneentration; it implies. t..o. . ccn- '"''Phrtnk.,evtes that take part are the polynuelear (properly poly- proteolN tie, and bacurRuiai . ,,-i ^v the endothelial PLATE III ',' ^# J . Jt * «s; ^ *# * ^' '^' n- w ilci inc) Colls in ihe Peritdn^i il Fluid of a Rabbit Twemv- I'un Hoiiis aller^ In.jet udh of B. coli into the Peritoneal Cavity. (Beatlie.) -K'.w til.' i-.'hitiv e |ir« ip~toi|enoli« ur liyiiline) 1 iitul et)**iii(jphi le lei-ik( |ihiu|<>i'vi(i-sl-.. |><>lyniii>lenr». eosii ■ hil eiikofiytes. There 'Hi nm< U'jir- iloiui with hiiilllmy |>h!i.|o<-y' e*<. red <_'t>rpvi«cle** hy hy the polyniif'leHi'?*. FACTORS IX Tin: IXFLAMMATOHY PROCESS 129 w.iikly phagocytic, it yet lias lu'cii seen to wander through the vessel Willi, and to ingest particles, Init not tiie bacteria of suppuration. It may he that tlie lymphocyte can give rise to the plasma cell, of which r.inre anon. The important point to not. is that while in a verv acute inflammation, tiie result of virulent toxin, they are rare, in a low grade mllamination, caused hy a less active toxin, they are common. So much i> tins the fact, that in a serous-sac inflammation we are in the habit of <<>nntmg the cells in the exudate, and of concluding that a large per- I'litage of Ixmphocytcs speaks for an inflammation of second-grade intensity like tuberculosis, and not for one of first-grade virulence like that set up by the pyogenic organisms. The lymphocyte originates Fig. 39 •M iij ji /. nf -nil Tl:. tll, til,. Ik,', IK, ■ IM^.m.l,■.r l,.uk,,..yt.'S infil.rutinK Ih.- riroular mm,-\v \:,y,r of an aruflv inflan,,.,! apmmlix- «. a. rn.l.,th..lml ,;Mx; b. h. pnljimcloar IvukcMytrs- r, nuHrus of nm»..|<. .-oil. uiyiitcst abundance from the lymph nodes; it has, however, to be " ni iniiid that in the sheaths of most veins there is normallv present "I ' "t lymphocytes, and that those which accumul - in an area "-laiiimation are not necessarily all derived from j blood, but " It least are the result of proliferation of these loca. Ivmphocvtes eosmophiles we cannot yet rank in their proper place; thev have ■iiic |)ower of migration as the ordinary leukocytes, less" power " -Lr(»'\ tosis, and appear early in some acute inflaiiimaticms. Like "I.Muiclears they originate mainly in the bone marrow and they • .I" part 111 the formation of new tissue. We may sav here that " ith multiple nuclei or a partite nucleus does enter" into tissue 130 THE MORBID AND REACTIVE PROCESSES l.uilding; these eells, as we state.l before, are marked for an early death, and are already on the downward road. Fio. 40 Aiuic l.Miipha.lonitis, showing a lymph »';;;'" ,<'°f '*'"""; down, others (i) acting as t.K (ri) large endothelial cells, some breaking phagocytes. To the left are numerous lymphocytes (6) for comparison. Vw. 42 ri*> >»a^ * 1 •.^-^ o •<^l ■^. ^^ -CJ- # 1 «? 'iHui Cells (Mononurlenr Hyaline Histogenous) (rom '"■ Perit.>neal Fluid Forty-eight Hoins after' Intra- I'eritoneal Injection of B. coli. (Benttie.) ''•'^^ r'iia,|... vi..~i-< an. I , 1 . , |,.-.i ,, ,i i ,>l ] .oly nu<-lea r l.-iiU. ..yie^ iiiid ilii|i'->ii vo vaiMiole-.. I Laler MlHue.) FACTORS IN THE ISFLA^fMATORY PROCESS 131 The Fixed Tissues. — These play a very important part lu inflaniination, (Itsi)ite the fact that their eells are h'ss j)r«)niineiit than the leiikoeytes, if the irritant be one of sli^'ht dejrree, proliferation of the stroma cells ai)i)ears from the first; if of high degree, the stroma eells at the centre (if activity may be killed, but those in the surrounding areas are excited to phagocytosis and to proliferation, and the degree of toxin that is Fio 43 M * iranuiulion tiswuc Been from the ficeper toward the upper surface: /, spinK ether areas ,, , , Hu.n of tl.os.-rH.u.., so ^;-;-,.:;^,(,,,^,,,, ,,, this of the ho.ly <-«"'^'<"'- tl • t ^IpL ; ■ ' .ti,,,,s of phajioeytosis we have The FibroblMts. Ilu»,. ""„'""':,, *^„H.,.ti,ms with the c-lls cells snch as their parents were. F '1. 44 ^ c .''' — f^ "■■■ ^ 0^ ^^ ^ ' liascmcnt iiieiiibraiip. *f rX'h";;:.; MuxI,,,.,., a v^y c,,„.bU. .bBen,r. M. . o„n- PLATE V deh. mlHiion Tissue. The Upper- is toward the Outer Surfnoe. (Maximow.) ' . i)ly mulear leukocytes: x, the polylilasu nliiui " polyhUist." I i-^) , dth.t tlehi'l of t\' leiikoirylea ; dtQ,, a m^^^^- TJT FACTORS IS THE ISFLAMMATOIiY l>l{OrESS 133 siderable following in siip|)ort of tlu- vii-w that the plasma cell is hut one phase in the lif»' history of what lie terms the "polyblast," a cell that is, which may originate either from lymplioeytes (»r connective- tissue cells, which may develoj) into fibroblasts and so into eoimective tissue, or into clasmatocytes, large cells with pr«)nouiice(l processes, which are constantly she I'i* Hi H 134 T//K .WO««/i> -lA'O RHACriVK PROCESSES y ;.. tl... exudate for such is the name appHed to the miiterial. now he in the exuaate, lor n „.,•,' if the e\u< ate con- i„ most striki„K t™"ir,. Ins. '^ i^'^^. "„. ''^."^ .iv.lv numcmus „, inimeroih. tlu t .'I". n™' '» >'. ' , j ,.|| „|,p„.oial.l<; quantity, ""l* '.:'•<'';"« iS' n 'an"! «1» pu,.' Jbttaopim....; it « serofibni ^us, ii tiitrt is mui.ii s,,.f„pp slouchs away, necrotic ine.nbrane appears, membranous .1 ^ ^„ ™ „S K st or «n^ sueh at closely, all are at ooiimu i ..nr^nrentlv ditterent forms of come about that we speak «^ -\'J^«'; JJf ^ f ^t eclueated to dis- inflammation; the truth is that tht tissues "« "« j , ^j ^^^^ taxis, in and around the '"^ured a ea Ii se ere ,r^^^ ^^^^^^^ s?l; r j:ntff::'»™"=7';llvf ^^^^^ j^«---: organisms, successive- stages may be made out. As in the course IXFLAMMATIOX /.V \()\-\ASCULAIi AREAS 13.-) few hours the inoculated niicrohes begiu to proliferate, it can he ohser' 'd tliat the surroundinjt corneal corpuscles become distinctly swollen and sliow evidences of defeneration. With this there is a s:'"iilar accumula- tion of leukocytes out (»f the surrouiKling I\ni|)h spaces toward the focus of irritation, in a few hours more, the circular vessels at the perii)hery of the cornea hecouje dilated, and with this there sets in a migration of leukocytes from the vein. While this is prr)ceeding the corneal corpuscles in the immediate urea of bacterial growth break down, and the proliferating bacteria infiltrate over a larger area until such time as the accunndation of leukocytes from all sides forms a harrier arresting their further escape. From this poirit on, the inflamma- tion is similar to that seen in a vascular area with this notable exception, tliat obviously the chemiotactic influence which led to the migration of the leukocytes, exerts itself also upon the wall of the circular vein, so that now buds or processes pass inward toward the affected area imd then become develoi)ed into true capillaries, which may persist weeks and months after the acute itifiamtuDtion has subsided. In the heart valves a process similar to that in the cornea is seen; tlic area here is exposed to the double insult of a toxic or bacterial irritation, and seventy-two blows per mimite, so that ulceration is likely to ensue. Oti this is laid down fibriti and in it leukocytes, for in iiiidition interaction ensues between the ulcerated surface and the blood uliich bathes it. There are thus proiluced fibrinous vegetations, and the lilirin, in the course of repair, is replaced by fibrous tissue. In those iMses in which the irritant is not very powt-rful, it seems that there is ;i i)roliferatiou of the connective tissue of the valve, without anything (l>e, so that a heap of new fibrosis arises from the edge of the valve, mid constitutes a vegetation of a fibrous kind from the very outset.' Chronic Inflammation. — From the wa\ we iiave insisted upon the uniformity of the process of inflammation so far, it may be inferred that we are not in favor of building up a barrier between so-called ;iiiite and so-called chronic inflammations; and such is the case. Arc we to call an inflammation acute if it reaches its height in one, t.\i>, three, or four days, and chronic if it takes five or ten or fifteen? W I do so, but it will be seen that the distinction is arbitrary. Or, if we ar( ill doubt, as clinicians, whether an inflammation is acute or chronic, ;iri we to compromise and call it subacute? As clinicians, yes. But tinin the pathological standfwint, it is unnecessary, because in all we - . the same mode of reaction, a, b, c, d, e.f, as we have said above. Ii the irritant be of low degree of strength, there will be less killing of '! Hie and more proliferation, if of high degree, more killing and less 1 iliferation, more serum, it may be, and less diapedesis, but in everj' ' I' the procedure a, b, c, d, e, /, runs through all, as the theme runs in ii I'itce of music all but hidden under variations. \ fre(, .ent mistake of the student, is to confuse ^5roiM &ndfihrinoti8. The term ^nous can be employed only to designate ^.he result of depo.sition of fibrin. ' 13(i TIIK MORliW AS I) REACTIVE PROCESSE.^ TIh' sHlu-i.t ftatnn- ..f an ii.fla.ni.iati.m cans,.! I,y an inttnsf irritant is .xiKlatinn; .lia,M-.l.-sis .K.urs l.ut littl.-. hrcaus.; .lu.inH.taxis is iu-km- can .HTiir only at tiu- outskirts, whore tlu- toxin is nuII .1. ntnl; at tl, mitro. cvn, ilu- stron«.-st e; the student shoul.l take heart from tin- c..nsi.lerati..ii of the simplicity .. the mflam- niatorv pr..cess; if he im.lerstan.l tlu- invariahle reactmn ,.t the tissues he will see it in every case of the .liscase. even it it he f..r the moment c.)n(rale.l hv tin- pre.l.)minan Hhn.hlasts an.l, it may he, ..f plasma cells, an.l lar«o hyaline cells, it nnist he re.alle.l that the vessels ,)lay an a.tive part m the later repara- tive stag's of an inHainiiiati..n an.l this particularly where there has heen active .l.-stru (l.-rp woiiimI ImmiI in a li.Nilthv, Krowin"if .liil.l can a|.|.r.ri«t,. tlu- trntl. ..f tho a.lHR.-. "Tlioro i. in tlu- tissues an almost .n>u|MTal,le t.-n. nuy to heal." Th.- j.hysician niav suc-coe,! in ov.t- •onnnK this ten.h-nc-y if he he me.l.ll,some and foolish. If there he a Krannhitnig surface. ren.emlK.r that antiseptics will succeetl in killing Vm. 40 I nr nw.on of new ve»«.N ,„ granulation u,,ue: 1, from a Z».^\ex\ cl,a„,b<.r (form«l of two rovor- -li>-) l-ft ,n tho pentoneal oavity of a ral.l.it fo, forl.v-<.iKht .ia.v»; portion of fi,-!.! lx,uml..d t,v ,„o > forn„-,l new ,-ap,ll«r,e8- l^two-n ,h..n, can 1« aeen the »oli,l l„„ls ami pro<-..>«,., of dev.-lopim, • Ti^K :'."'"■ "• .k"!" r "'""" P"""^"""" «" "h"*- formative ell,, or fibroblast., ,„ .lirect eonncT- ' -1 with the endothelial processes. (Ziigler.) ti.se tender, newborn cells, that a stream of water mav wash them awas '"'\ nature may have to do her work over again on vour account If .v-'i see pus on the surface give it a chance to drain awav if possible, "i:t remember that granulation tissue presents a ver>- strong barrier to •y ^Tpuon, aii.i die pus may do less harm than the clum.sv sponge It removes it. The pus from a granulating wound was called bv our I' fathers, who understood the drainage of wounds as well as we do i 138 THE MORBID ASD REAVTIVF. PROCESSES L- i.f "fxuberant jjriui illation ;;rS^t;tC:VCU"n W trL..trate ...; .—ions -^: SJ^irOr^Sas,-- The n^^^^^^ ^^JZ ,,,JeHects .rou.ht by '^^^I't "^1^ sB- lepra-, H. mallei, forms of plant htc, ^"^■'\ "r.,*^ jl;. , Ini.hun, ami even the larv^ actinonnees, ''l'>^t"'"^■^■^■^ J "i;",4e tissues build up a Nvall around and eggs of certam paras, c V^^'^^ „evv-fornuHl tissue we call the the irritant, so to speak, and ^"J "''»;^;;\,^ ..,,, ,,,,,y he. It is evident li:;Sr^of1;::^Set ^r of tl. tubers or ShJJSS by the bacilU ancUlieir pr^ua. ^^^ .^ .^ ^,,^^^ , A word as to the f.^^f^^^^^, J^ «rthe irritant of tuberculosis ago it was realized that the /^ 't m aforetime called a tumor, Xs a "lump," the t"^-^^ ,*^ ^^.^^ was foun.l to be of fibrous and was classed among tun or., ^^^ ^» J '^ ,,^,i .^, .'tumor of granu- Lue, i. c, of *^'--">«t";"Jf;;>,^'irt"^nation-o»,a which we lation tissue," or ^^'^f;^''^^'''^^ 'l r. NVIhm. it was discovere.l have nnule to sign.ty the i.lea '^ J » f ^,,5, j,ranuh>ma, it was that the «. tuberculosis ^^a. t'l^ '.V'^*; ^,,^. „„,, the class aesignated an •*i>;''*?-^l-/^":;";Xh.s bee discovered; and now we has grown, as each infective agent '^'Y, "'^^; ,^. „„ inHammatory one, a?e iible to state that the proc >> P ^^^ j.^„„, the ind that the grauuloma ^^ ^^^^^ ^J^, to the toxin of the proliferation of the c' Is ot the part ^^^ ^^^^ . i„Hamraa- organism concerned. In /"•^•/^".^^'^^^Vt ,„ of the granuloma, although tory area" above is true tor ^^; ;^' ^ \ in ot'the B. tuberculosis the process is a longer one >» /"" ,•/ ^^^^^..^^.^ate exudation of serum causL a dilatation of the ^^^^^ ) '^^ ! ^"proliferation of cells of a slight diapedesis o ^^^'^^^o :*»;;,; ^ ,i,h\erm we mention only the part-the ^r''V^'^ £^L^^^^ ^-^-"^ "r the proWerated to reject; they should be ^•"""' J ''^^^^^^^^ cells if the part; while the -f e ^ -;;'-^ ,,,,„ ^api-Uy into pus and serum ami badly "^^^f j,"^, ."^ "th granuloina breaks down slowly an abscess is tormed, the ctntri o ^"^ |^ j j^^^j ^ cascated granu- ,to a formless mass o dry necrosis ^^ a Uon a ^^^^ .^^^ ^^^ ^^^ ^._^^,^ loma is the r^ult. J>''--» ;;j;,^' , ] ^^^^l' , rallelism betw.;cn these a subacute inflammation. '^•«7;;' '""^tion is this: if tubercle bacilli ap nts and those causing acute " "' » " f ^^^^Jcute iuttan.mation not to are in sufficient numbers they J;''';^^^ ^^^^^f^ ,,acteria. The same he distinguished ^;o"; '^^^^ ^ U lenders bacillus, while in man ,„^, been shown to be tnu ^^]\J^ commonly a central area ^^lth the mulule o «^'t>!»'"^>f ^ v cs n Set. contains true pus, while ahun.lant polynndear »f »^"' J:^' ^i-ue '■*'"^- around this is a /one of proliteratid ti.,.uc INFECTIVE GRANULOMAS 139 Tlie tubercle, the gumma, or the nodule, thus, is a mass of new-formed connective-tissue cells, and these cells are the essential part of the tubercle; the trained microscopist must become used to recognize the granuloma by this; the giant cell, of which more anon, is unessential; the caseation is an unessential, save that if sufficient time be given it is an almost inevitable sequel, at least in cases of tuberculosis; the ring of leukocytes external to the mass is also unessential, although tiie more acute the process the more likely it is to be present; the inolif crated tissue forming the "lump," the tubercle, the gumma, the nodule is the essential, and the only essential. And in most cases of these maladies the unit is tht grainiloma, and a cavitated lung is merely the final result of necrosis, secondary infection and what not (in an aggregation of small granulomas. 1 [III re If from a ease of tuberculosis of medium severity of the lung: a, central caseation; h, a liiant itll. c, endothelial cells; d, conaective-tisaue lone infiltrated with lymphocytes. Giant Cells. — Although not a necessary character of a tubercle, the -iaiit cell is very frequently found therein; this is characterized by a I iru't' body, made up of ill-staining, acidophilic, necrotic material, with crescent, a ring, or a group of ordinarily stained nuclei; this is some- • iiics clearly the result of fusion of a grouj) of cells to form a plasmodium round a small mass of necrotic material or of bacilli— in other cases : 11 re are indications of actual nuclear multiplication with incomplete inplasniic division. The giant cell is often found close to the necrotic irt of the tubercle, and in this edge, or in the giant cells themselves, <■ bacilli are to be most readily found. Interspersed, too, with the ■ '■ liferated cells of the i)art are lymphocytes and rarely leukocytes— r former are the "small, round cells" of inflammation— and on the i-ide is a more or less pronounced ring of lymphocytes which have ■ n attracted to the area of inflammation by chemiotaxis. %W^1Si?'.. THE MORBID ASD REACTIVE PROCESSES , .a. be useful to recall t>K.-»;^^P-— Jj^^ J^jf ^iJl t „ --leans limited to tul,era.l..>.s:_«ocnuUr^.^^^^ ,,Umyc..sis. oiher infective granulomas, •";:'''•';; t.Vce is seen fiUe.! with the nnrl Lrkuders. A somewhat sinular tM)t Here bv no means and glanders Fig. 48 •f Giant - « ..". -^ r ^;"=r ;^i^irzrr;,;- ;.:;r ^ — ' type; b, b. the same in proccs Flo. 49 -i A„wn u, FiBs. :«i a;; ^;;1 ; r 1'; " !»..;.., and »,„«re„.ly ■l;;;;i r. r r^ 1,"' ii. "'lis -' •".«"■" - >=■""-•""' -'-■""• CUROSir IS FLA .W.U.t T/O.V 141 Yet other mnltimiclfiitt'd Ki«>it cells are not infrequent in other forms of sarcoma, while in certain cases of Ilodnkin's disease we may encounter relatively hu>;e cells which are truly giant cells, hut have only (me or two nuclei. Diffuse Inflammation.- Sometimes the organisms of the inft'ctive firanulomas do not set up the localized nodule, hut we find a diffuse fihrosis such as happens in the pia mater in syphilis; nor is this con- fined to the jiroup of orpinisms which cause the graimlomas, for a good example exists in cirrhosis of the liver, wliere there is a general increase in the connective tissue of the part without there being &\y particular localization. It may be, however, that this diffuse fibrosis Fio. 60 '.9 V 'V^' /•' <^ y I 3 W e 9 ^3 J \%^\ o^ t S.I lion from n syphilitir livrr wlii.h presonto.I mimmnta nlonK with n- ' nsivf cirrlicsia The mv. I Mi,.-.l ronnoftivc tisKuo is wen .xKn.ling Iwtwpcn ami rutting off i ' of liver coIIb, which u a -uli aro shrunkun ami iitrtipiiit'il. i iiii ai't«-r result of the existence of small n • granulomas. At Mines it appears to be caused rather by the tox the organism than I \ the organisms themselves. Such a fibrosis a cirrhosis— is common •I the li\cr in syphilis, as well as in cases where a long-continued expo- ire of the liver to the bacterial and other toxins of the alimentary • iict leads to the fibrosis which is known as "cirrhosis of the Hyer.|| iitre is a further class of cases which we term "chronic inflammation," liieli arise in a way similar to this. Such are chronic nephritis, vroiditis, anil hepatitis, all of which we recognize as caused by an itant, yet in which we think faulty metabolism and imperfect nutri- 11 are also of some cH'ect. It is supposed that under the influence of turbed or excessive activity the secretory cells become degenerated W^ rr, Avn RF ACTIVE PROCESSES 142 THE MORBID ASD REAL iivi^ .„„ „., *,. ..«;.» .--,*-'-^ *:i.r™r Se*- «5 lower-class supportive cells. j er.th has the proliferation of Fibrosis and mflammatoon.- S ^J^^^ -^.^^^^^ ..^h inflammation, connective tissue been .^fj^^^, X,vs the result of inflammation? that the question arises, I^fJX formation of a fibroma or a ne^^ The answer is in the negatiY , ^ torm ^^^^^.^^^^. ,,j fibromatosis growth is, of course, a case " P" "V ] ^ ^^^ the readiness with which ^.f elephantiasis, o '"«;^''^'^";X; mcttn to the exit of the lymph by fibrosis occurs f there be a ^^^^n^^^^^ ^^ ^lie lymph prevents the its ordinary ^"'^"""•^^^ J^xh s o t e eefls, which toxins, remaimnp, free ''^*[,;V"".^ result of stress, to be presentlv and the process imy be re^ard^l as^ e ^^^^^^^ ^ ^^^^^ .^ ^^ ^^^^^^ mentioned. Final y.therei tfe^" i.f arteriosclerosis. Here we by fibrosis of the intima of ^^'^ ^^ f j.^arily f- r site of change, find two forms: >" 'I'J^'^'/^V irrU-ition, but the ot(urs are a.lapme. an.l this we may attribute to "tation ^^^^ „,generated; t.> strengthen the -"'V f .^ ^^^^.^ £ev ic infiltration or formation such fibrosis occurs -'^,^«"* '"^^tlv ^plained by what we have not of new vessels, and ma> ^^^ P"/ J^^ ^^.tion, namely, stress. It cells previously adduced as a ^«;' ^ «;|^'f t/^eh, or even are intermittently are put upon a constant ^^?;^^l,^,A, proliferation ensues, exposed to such a_stress, i* h^J »'t ^^e^ ^^_^^ ^^^_^^ ^^^ ^^^^. ^^ ,^ too ;i;;.l to such astress, ^^ ^hey be we no..n..j., .^^ .^^^^ .^ . ,^, th' distension acting as a sfm|dant^ 1 r ^^^^ inflammation. great a stretcli of the ""^P"'^*';'" \" 'X 1 1 Hcation than is gen^-rally ' We feel that tins is a principle of ^s u^^-ppc^.^^^^ ^^_.^.^ ^^^^^^ appreciated, the P"-f P\^; "«"^; f ', ^ is able to cause the growth either as pressure or traction "P^i a ce ^^^^ ^^^^^ ^.^^^^ ^^ a„,l proliferation of that ^f 1- ^" J^'^f^/ ho force acting on the cell no i.'erference -th vts u^rmon a^^^^^^^^^^ ^^^ , to je is not excessive ^'^/'f'f^ "' .yhat apphes to the cell mdniduall> opposite condition of atrophy, ^^f^ '^PJ „f experience, it is found Sies to cells in t^- ^--f^''-i^^,fn "bony'ri.lge is followed by thit the constant pu hug f^Ti^ i creased bony growth, increase in the size ot that ridge, *. -, We mav thus classify the fibroses: I. Of Inflammatohy <'"><';^- , f.,,^,,,,, tissue takes the place of 1. Re,>larave„tfihro... -^;;:^^ t"" scleroses" of the nervous other tissue that has been < ^ ' ;, ^^ i„,h,ae.l, as well as m part svstem, arising from glui; "re lure to nt _ the fibrosis of "nephritis an. '^^'P"" ;; ^^^^,^, ^f the graiuilomata. 2. rrolijeratire Jibr ,^ „ost-inflammatory and those around foreign, inert bodies, . W I SYSTEMIC REACTION TO MICROBIC INJURY— INFECTION 143 fibroses in which the fibrous tissue continues to grow even after the irritant has ceased to act, as in keloid. ■'}. Post-fihrinous fibroses, which replace fibrin in a thrombosed blood vessel or on a serous surface (adhesions); these partake of the nature of both the above groups. They are replacement fibroses in that they replace the fibrin, and proliferative in that they occur where previously no tissue proper existed. II. Ok N'on'-inflammatory Origin. 1. Due to strain, as in some cases of fibrosis of the inti: of the \essels. 2. Neoplastic, e. g., fibrous tumors. THE SYSTEMIC REACTION TO MICROBIC INJURY— INFECTION The term infection is used in different senses by t\\". pathologist and tlie hvgionist. For our purposes, infection is a process; it consists not ill the mere presence of pathogenic bacteria in the mouth, skin, or intestine, but in the growth of those bacteria in the tissues, i:> the diffu- Mon of their products, and in the reaction brought about in the body li\- their presence. Infection is the interaction between the body and the iiiicrnonjanism (jroimuj in it. This interaction may be local, and the process will, in that case, be one of infective inflammation already dis- nissed; but we are now concerned with the general disturbances which tullow such local growth, or the effects of a widespread proliferation of the microbes. The hygienist, on the other hand, considers infection as the mere linsence of the harmful microorganism; thus water, air, or a community may be infected; he distinguishes (1) sporadic infections, where isolated 'i-cs occur; (2) endemic,' where a notable number of cases of a given ili^ase occurs year after year in a certain area, and (3) epidemic, where i!h' disease suddenly affects a large number of people. Similarly, (li -cases of animals are sporadic, enzootic,- and epizootic. Causation. -We have already considered the question of suscepti- li!iit\ to infection; it may be repeated that there are various ways 1! liich susceptibility, inherited or acquirwl, may show itself, so that i! . ()])])osition to the bacteria is less than normal; on the other hand, li . l)a(tcria may be of so great virulence that a normal power of opposi- li. II on the part of the body is not enough to protect it. Each case of ■I • itioii is, therefore, the resultant of forces which are always varying; \' I-, tliere may be great susceptibility and virulent microbes, or great ~ rptibility and microbes of low virulence, or great i)ower of resistance I •vi\ against highly virulent microbes, or great i)ower of resistance II. iiist lowly virulent microbes. The result differs in every case. The Course of Infection. — To indicate the course of an infection a i ill may be given of a +ype case of typiioid fever. The patient on II CD ilate has taken into lii alimentary canal some typhoid bacilli. ' i'',"o'. , tho pt-opk'. animal. mt'^^m;^^^^ 1,, THE MOHBin ASU REACTIVE PROCESSES , • • t.wl till svmntoms of malaise appear— F..r a few .lays n.>th,n, - ";f;"' , ,,^^,7 ,onstipation. pain n the lassitu.le, slight bu P^'^j^;;^^ " ^.. ^^ ,a » of Letter, an.l ten days.or hack, an.l so ..n. 1 hese Kro% ^^ '^^' ' i^.,,^ i, ^o weak and feverish so after the ingestum oi ^1- »»« '^ »-^f , ^J^ ^he stage of incubation, that he takes to bed. ^^'J'i^'^' J! symptoms declare themselves, during which proilromal or PrTre^of rilehnite febrile state lor the stage -»"t>n'"">^ ""^'^ ^^^'"^^ t„ . ate the illness from the hrst clinical purposes, it is ;"^*«J",: Trrespon.l with a recognizable prodromal symptoms. J't^^^SS has f^^^ S-neral weakness, rise of temperature. Ihc patient i different systems: 'L\ various sympt.>ms or sign --j^bl to^^ ., ^,^ ,,i„ ,ead- (a) in the nervous system he e JJ^> . ^^^^ tern, a rapid pulse, ache, and chilly ^^"^^^'""^ ,,^.^^ ^," J^'S ; (c) in the digestive system, vasomotor disturbances such as ""^'^ nution of salivary secretion, dryness of the mouth, by -«f;- ^^tTod 1^^^ lo^s of appetite or a P^ l^^^^^^^Jj^^-ith foul stools. Day by day nain const pation, or at times diarrnceci« ^^^ urinary ?h 'fever rises, and the -y"^^'";i^ZZ:S^^f^^^^^^^ the chlorides, secretion is evi.lenced by '''";"':;\':\llirthe urates; the character- an.l increase in "t^er con tituents notaD ^^^ ^^.^ ^^e istic eruption may show ^*7\."bW.l, ami later tlu- serum begms bacilU can be found mthej^rc...at.ngblo^^,^^^^ ^^^ ^^.^^j^^^^l ^ ,11 to gain the property of being a'''^" ^J;^ ^1,;, i^ the stage of high, Thi' is the stage of i^ryescence^ l^^ t . ^^^ ^^^ ,,„ptoms and continued tever or lastlgluxn ^ > J P '^sten ^^^^ ^^^^ j^ , increasing weakness and loss ot tltsn. i . , the stage of S^, aLr which t)-/-- begnisj^> iaUj.^^^^^^ ^.^,^ ,1 defervescence, which m turn IS t""^"^;;' ^^^^^^ ,,hich are morbid condi- return to health and strength. ^o'^Pj^*!'"^^^ ,^, „f „ther causation, ions, either ass.>ciate.l with he oripn^l ^au. . ^^^^^ may occur durhui ^f''^'^%'t.ZT^Zi\i original infection, and niorbi.1 states due •'•^«^^t > ;; '"'^ ., ^, B. tvphosus or inflammation :rr^a:is- ^^ '— ^^- »-- -^^ '- ^ '-''''' -S^^e^:nf'lncub«^ou.-Th^^^^ during which the growth ;f . ^ ^1 \ S;\ hich the diffusion of the ,„,„,, and that tune ^f '' , ^f ^^.^ ^"Siently great to g ve rise to toxic products ..1 the bactcr a " y;;^^ ^..-e accumulated suffi- general symptoms; as soon ' ^XniS^lTmptoms. It is to be remem- eiently they give rise to ^^ P^~,t: be^due not only to the toxins bered that the pnKlromal ^> ^^^^^r-j ,5^, (albumoses) ma«lc from %S;L\ the rcAtunc ot the orgamsm. SYSTEMIC REACTION TO MICROBIC INJURY— INFECTION 145 Grades of Infection It min'it appear as if a line of demarcation Wire drawn between 'ot; ! infections and general infections, and yet tlie differences between the i/\o are diHerences of degree, rather than of kind. The bacteria w'liel !,. hoiee are of hical oeenrrence may be found in tiie blood; lately, the diphtheria bacillus which was supposed to be strictly local in its habitation has been repeatetlly found in the blood; the seat of election of the pneuniococcus is the lung, but it also is found in the blood; the tyy)hoid bacillus works its local effects in the bowel, but is found in the blood stream. It may be considered that every organism ca])able of local proliferation is theoretically capable of being found in the blood stream, and that in the ca.se of organisms like the i)yococci their presence or absence is due to the number of them that escape at a given moment, and the antagonistic power of the blood and the tissues. Further, with regard to the toxic products of bacteria, we are accustomed to designate their i)resence by the term int05dcation, sapremic intoxication, or sapremia. This, again, is a rnatter of degree of intensity of the t()xic products; thus, a mild local infec- tion gives off a certain aniotnit of toxin, and this is carried into the blood and tissue fluids, but is so diluted that we see no general bodily change wrought thereby; we neglect such a mild intoxication, but it is nevertheless present. Hefore leaving the subject of terminology, it is necessary to define the terms generally used; bacteria mtdtiplying locally, and giving no \i>ible signs of their presence in the blood, ev -n if there be indication of toxemia, constitute a case of localized infection. If the bacteria not only nuiltiply locally, but are also evidently in the blood, and are getting toot hold in the tissues (metastases) the case becomes one of bacteriemia. I'.M li of the metastases now becomes a centre for the production and .liiliision of more toxin, so that with the bacteriemia the toxemia iiilxances equally.' I'or clinical purposes we are in the habit of making certain rough ili-tiiictions, dividing infections into: (1) fulminating; (2) acute; (.'i) IM T-isting; (4) subinfection. !. Fulminating Infection. — This type of infection is characterized I' ~o i;reat a Hooding of the body by toxins, and presumably by the !! !. rtive organisms, that tlie resistance of the tissues is notably ineffect- lil The symptoms are those of great intoxication with depression ni ilie luiK'tions; the heart beat becomes rapid and feeble, the blood lH' -lire is lowered, the respiration is shallow and rapid, the patient II cmrcxporipiu'c tlicrois surli painful confusion in tho niind.s not onlyot student.s 'f nuMJical men in RoniTiil betwwn tlie terms sopfirpinia, sapremia, pyemia, iikI (ji'iioral sepsis or blood poisoning, that for the sake of clearness we prefer ■ ii septicemia to bacteriemia, sapremia to toxemia. Pyemia iii'.nv uscfl ;is a term to de^crilie seplireiuia with metastatic abscesses, and ! ["lisoninn" as a euphemism for any or all of the above. 10 UO THE MORBID ASD RKMriVE !'ROrESS,^ „«,. If tlH> .Hseaso is .>m- '■■; "^^ ,, " i.Htv .H-n'!^ <>" " ^ i"*''-"^ ,„;,;, is present. M.ch an o^ '7^"^, ,,,,,; „r a low n-istanc.. ..r Uanism. or a larp" n.wnh.r ot '^^^" ,'^; ,„ i,, „.„K.n.luT...l that ,11 tlu.se inlhu-ncrs w..rkmj; toR.tlur »;.'", ,„^.,ssary virulenc-e. tlH-r.. are ...>!>■ certain . 'i-^^- .^ l^^^"" ^'u tlu- virulenc-e of the It has never I.een possible '^^ _^^ ''^^ ^,, .„.iuce this f«ln,inan<-e ot tubercle bacillus to so^reat an J^ " * ;\^ ^f .^. .„,a epidemic cerebro- .vn.pton.s. (n-neral bactenenua' ^^^ f;* ,. So rapidly is the spinlil nuninptis provule ^^r^l-'fj^J^-' ^ ^^-es a .le^eneration of tI,xinpro.lu.e.l an.'sol,.v^tM.t ..t hat^.^M^ _^^^^^ ^,^.^^.,,., the ...uls of the cap.llanes. ^ »'• .^^ „f ten.pcratnre bnt even a ^;'';'';^'';i ;;";;;i,^ ,,,.'e ^vhich is evidenced .,f the bodv are not stunnlated to ^''^ ^:}2v\yvnvvssvs instea.l ..f V an increase of heat P-''-^;"'^ •;^:\n::'' ! u^^l to a low eW, ,,-i„« rendered .nore '-^j- ''X- "-^ j ,' form of infection whch has 2. Acute Infection.- 1 his .> th, '-"i ' ■' j ;„,! „f incubation, ,„...„ aescribed. .;here m a -^ ^l^'^n -^^ d^----- ''''''' f^'^''""' ,f tVrve..ence. ot con mned t^'^ '•;J^^^' „ .^^^,,^, pneumonia, the te.n- ,U.fiTves. a ,.„„valescence may ,,n.ture falls sud.lenly, by c"S^- ., , ' ,/ J, ,..,.,. of the symptoms l interrupted '^X/^'^P^^ '' ^ ^1 , I .l.^urs before the ten.perature .,f the prin.ary m\vvUou . it t . ar ^ relapse. l,,s reached the normal l-;- -.;;'. , .,• i„r,,tion p'ncral y called :, Persisting infection. ;' '„ "/.....tinnanc.e. dnrin, the ^vhole chronic, which .> <1';'7'- V"''^ , , ^ '.' ' .^s to be at work. FAan.ples '>'■ ^^ ''■"•'' ''""• ''"■ '"''" n, i,; tErcul..sis, svphilis, etc., as wc' 1 ..f „.i, type of di>case arc 1"" ^ ^ ^ !^^^' „,;„:,;, pyu.cnic coco. .,, in ...■casional cases ot n.tection ">/"\ ■ .„ .^ , i.,,^., ,,nd we note ; t line, the -^^^^^^-^YV?::^:^tZ^^ U> .Uvide these inf..- ,n exacerbation. ( Inncally ...t •> J " t" ^^^^ ,,^ ,„,. ti..n> into stages, as ,s .l-ne n. > ' '^^ '^Vh,,, ,,,n anu.n, dinic.an. nc-ss in tlu- pre-ent connect..... '""';\; * ".,,•„,, i„t., n.t ^v.th leU r - m I^.^ ^^^^^^^^^ ,.^^,^^,,,^, „,, ,l,..tructionotthcor,>:amMn;tl.e!:trm . . ,,,,..,. ,..U ., ,1.0 ,.r..s..n, .inu. ... sp..k ;;[. I-'--- i-'l;;;! s;:tn:'rn.:xi::;;.;;;:h..n...-...of .....wo..... TllERMOdKXESlH AND PYREXIA 147 from time to tiiiu- into an iitiitc form of inlcctioii. The gmiis appvar lo work fotiipiirativi 1 . slowly and to di'Viloj) ncitlicr a very lii>;li (l(j,'ree "I intoxication nor so active a resistance i i ilic part of the hody as «.■ lire accustomed to see in the acute infections. We now recognize more and mi)re f ly the frecinency of latent infection, of conditions, that i>, in whicli for moinli> and it may he years, puthop-nic hacteria (ht- -i>t in the tissues or cavities of the hody, setting' up no disturhance, liiit capahle at any moment of so dointc. We may instaixc the now u ill-known "typhoid carriers." Subinfection. This term indicates a -li^dit de^'ree of infection such :i- is e.\pressed hy the presence of liactcria in tiic Mood, which arc not potent ciiouj,'h to cause ^ross symptoms of infection, yet which do nrtiially wear out the cells whose duty it is to comhat with and kill iliem. Normally, of course, hacteria are heinj; carried away from the intestine and killed in the mesenteric nodes and in the liver; when, in addition to this constant action, we find that hacteria are locally active, and that there is a local inflamination in the howcl, if we examine the Mi.Miiteric node cell:; and the liver cells we find renmants of bacteria, (iltin mere granules; the constant destruction of more than orilinary iniinhers of these means the more than ordinary wear and tear upon ' icll>; liver cells, for instance, are thus the more quickly destroyed, 1 in many cases of cirrhosis of the liver, we helieve this is a causae of c(.iidition, thoiish not the only one. It is not necessary that the Ml miniums he verv virulent; we think, in fact, that the ordinary bac- t' rill of the intestinal tract can and often do constitute the agent in till M' instances of snhinfectiori. Terminal Infection. -It must have struck everyone who has had ' ■ ! niodcrate amount of e.\])ericnce at the post mortem table that 111 I - of chronic disease, such as heart disease, where death has been i;m ;,iiil, there is frequently present some infection, such as a lobular • ' Minoiiia, or turbidity, from infection, of a lonj,'-present ascites, or ' i ir not. These infections we call terminal; and they arise not so much !• \iriilcncc of the orfianism as by weakness of the body. We mean ' I'-iLriiiite by the words "tcrininal infection" those cases in which '■■ n;is(.ii ,,f failing vitality a germ, powerless at ordinary times, is " 'ilcd to fasten ni)on the tissues and set up an acute infiammation. " ' : II process means that by reason of weakness of the body, a sub- i i; linn becomes an acut«' infection, the terminal infection being set I'i' . the chance microorganism which may be temporarily circulating i'i ' I' blood. Ilii ail' .1,, THERMOGENESIS AND PYREXIA fei F.rexla is a heightened bodily temjjerature; the state of body in a p\rt!xia exists, with all its concomitants, we shall call the '". state or, briefly, fever. y^m^-.Ti'r'- 148 THE MORBID AND REACTIVE PROCESSES Heat Production. Hont is liberatcl from the organis.n under the ''''I't^'bS; /. e., from the re.on.bination of .lissociated food- Metahohs,n breaks .own ^1- J-eU s. tou a ud^ ^ J^ obtain.! conU.n.e with own^^jnu.^^^ ,„„, ^,^ the Fever is accomi.anio.1 by in( rta>ul a I .^ intake of food is generally 'l"';"- ^ / . JJ^^ be .h.e mainly to than norn.al. tins increased heat '■'•"l I " y,;!^,^ ,„,,. ,,,u think of ti.sne disintegration an.l <7"';'*;;; '.JJ; , ! ■, , '-hnrned up.'' thefebrilestateasonen.^vln. . he >s« U ^^^^^^^ ^^^^j ^^^ Heat Discharge.-- Heat s lost f"' ";"''";;,„„,. ,,f ^xereta. The evaporation from t - ^ 7;-'\^J ,1^; v'l^nl^rature lowered by discharge may be mereasul, «'";"'-. -j „^ount of sweat. an*l which the dog unable to P^'7\'-,%^:;;;VS calories, a calory being the We express hent freciuently m t^^^^^^' ''j"*,^.^ ^ r at normal amount of heat -^^^^ ^ dS S>n f^^m the human body, atmospheric pressure. . per in tlu- oxpire.1 air. . per ^^ " [^ ,/ ^ '^ p,, eent. is lost by radia- eent. in evai)oration from the skin, ^^n u /.) pir tion and con.luction from the '>;;;^> ™^^^ j,^ ,.^„tact with the body, The lower the t-ni-J'. t'- o tl m d un n ^^^^^^^^^^^^^^ ^^ ^.^^^^ ;l;:/roft Wyrlndt airt :o .tnratedUh moisture that S^ltion is prevented, t'^/^ >-;;Xr'Lr fheat .lischarge In spite of the variation ot > ■« * J' '" .' ;,„„.,.,oode.l animal is at different times. tl';\ tenipc|aturt t .r ^^^^^^^^^^^ verv constant (save in hiliernating animals '"""'- , , ^ i :old-bloo.led animals Iwive a t-'P-'; l^-,- f , !^' ^l^niperature ,ne. one I"' ™' 7„''„™'^^^^^^^ „«, or Lnvors the Inxlily te.upera- ":,r^"; *or., tL'™: "o:::. roa»,„ ... »up,»s. ,i,.. .>«= are » *« FEVER, THE FEBRILE STATE 149 liraiii, or tin- cord, «»r in iMitli, evils, some of which on stimulation cause ill) iiii reasod prtMhiction of litiit, others an increased loss of heat; these cells arc aheetetl in various ways, for example, reflexly, or by the tem- perature of the circnlatiuK 1)I(mh1, or by sul)stances in the circulating Mood that act upon them. So perfect is the result that it seems hard to think «)f the mechanism otherwise than as controllei' hy one centre or a pair of closely connected centres. It must always be rememl)ered tliat the thermometer jjives us information only as to the balance or resultant l)ctween heat income and heat expenditure at a given moment In a particular i)art of the b(Kly; we Rain, therefore, by the use of this instrument, no accurate measurcnuMit of the amount of heat developetl or lost. FEVER, THE FEBRILE STATE Fever, or the febrile state, is the train of symptoms and changes in ilic orjjanism which constitutes the reaction to infection, which changes, iiltliough associated with increased heat j)rcKluction, may occur with or without rise of temperature (be febrile or afebrile), and the rise of tem- piniture itself is best known as pyrexia. The febrile state is dissociated u itli changes in the circulatory, nervous, muscular, respiratory , digestive Mild "xcretory systems, which we shall take up in order. Pyrexia. — In an infection we can frequently recognize the fervescent or pyrogenetic, the continued febrile, and th;' cefervescent stages; the \a-x iiaiiied may be very short, the temperature descending sharply, liy crisis, or gradually, by lysis. We are wont to distinguish the varieties of fever as continued, in "liiiji the changes between maxiimim and minimum are as sHght as III litalth, but at a higher level; as remittent, where the changes in a day iiiiy range over several degrees, as happens in bacteriemia, suppura- ti'ii, and tuberculosis with secondary infection; and as intermittent, uliirc a succession of fel>rile attacks, each with its fervescent, con- tiiiicil, and defcrvescent periods, occur separated by a continuous ill' rval of normal temperature of a day's or more duration — as in III iliria. Where several days elapse the fever is called recunent, as ii 11 l;i])sing fever. The Associated Disturbances.— Disturbance in the Nervous System. — ' '' /.v and Chilly Seiimthns. — It happens often in the fervescent stage "I inttctions that tlie patient feels cold, the teeth chatter, and yet, i iiiiUi, tile surface nuiy be hotter than normal, and the temperature ' ' i. and increasing in height. The face and extremities may be pale. 1 ' iiallor or local anemia suggests that the blood is attracted to other ' " us, making a corresponding congestion so'^^nvherc, and that there '- -inrage of heat in the body for the time. The chill is evidently ' iiunicnon incited from the central nervous system; in fact, the < ; may occur without exposure to cold or infection, in which case it ^r . S^^Pffsm' 'tSs jf 150 TlIK MOliUlD ASD REACTIVE I'ROCESSES appear, to b. .....Uy a ,>art ..f ti. ^''-^'i^;;;;;;,;:!;::; • ^^ir • ...illary .■..ntn...t...s ;;-;'-;;. l:, .^t...... .la- ...ti .ur- riL'or; ii. fact. .-i-poMn^' mii>.'U-> >>"< ""-..i .. '. . • • ;,{. 1 7' '';^;;:r''v,:;*"r;:;.s::':;t;?"" >"!>»-•"■■ :- (Ti.tral nmous sNstfin. Hust at. 1^ , hea.lad..-, im- „r iiotu-e till- pasbap ot .xtnt.i. cp j^ , ^ ,„, .onsi-kT that the^e phen..nu-Ma arc '';,; "^;' ^ ./^ ^ , ..rtain toxin> the c«-lls ..f the l.raiti an.l conl. c^Kriall a^ m "^ ';',., . ;;:... a direct anmity f.-r the nerve Ml Ik;; > -» ' r^ . ;„ ,,„,„,,. Disturbance in the Circulatory System I ht> I V,,,,^^^.., isa..oonM.nnie.ll.yanK.rkc.hm-rcj. m ^ i > ^^ ^^^^^^^ ^^^_,^^._ ^j^, l.y incrcase.1 pulse rate. ^^^'Vi .ti , . .1 'lowcre.! M-....! pressure. .Hcrotis,.,. iu.licati,.K artena .hlatatum a. Um n ^^_^^ .,r a full l.uun,lin, pulse, so that .t is eve .t U ■ ""^^^ .,• ,;,,,, h,to the sthenic - those ^'I'^'^'^'^'^f^^^'' ,, ^ '"i'nic T»'<'- '^^''''- ..specially circulato^ encr^- a.al he . n.r>. asthe^ ^^_^^^ ^^^ .^,^ mu.ations are usua 1> n.a.l. " '> '• , ^,j f,,,.t„rs th ' our is atVecte.1 in any pvcn ease U> so la. ' ' , ^„„,,, ,,„,ever. deleet,on j' «; ^^^^ f J Hk tvphoi.l fever. i„ the leukocytes in the peripheral '•''"f ' ;"\;;' V', ,,;•,„,, „ rapid are atten.-d by a h>werin, of tbe mini . ■;-^,; ;^' ;,,^,J,,,„ [,. Hse i. the leukocyte count "'''"•^ '^ ^ ^^,:^, ;, , ', ,' ,..,„lary infec- superNcned; but it must also u- [^••''' '*;'!:,; ^,,^, ,,,,ti„n of tl. tion may supervene vvithout a ''■;'1^"''>!;^' j ' \'.; .' j .,,,e of a leuk.- h,,!v r..av be insuHicient; m >u.h a case, t h y'^> '"^^'^^^^ prof^nostir cytosis in the pres. me ..t . ' .' """^> , .,,,. ,,ecuston.e(l to fin FEVEIt, ntK FFAiklLK ^M //; 101 liifk iif rcfictioii (til tlif |nirt of tin- |>atiti,l. Tin nun ,i- in the while ■ I'll is usiihIIn ill tin- polyiiiiclcar ii acuti- «'it>«-^. in tin- I r>lii», I in tlit iii-^iii(>ii|iil(- ill <'(Ttaiii stat«'s uIkto iiiiin!Jil parasiti art- i >|)iii):-. uu^l Disturbance in Respiration. -The n-spmitory iiiu\ciiu-nt i- i|iiickci' i III inlirtions. This (|uickcf;inj; i hnnifrlit !il>oiit liv aiiytiiinjr win ' iiicrcd rs tin ti'iiijHTaturc of the i"iMl hitiliin^; the respiratorv ceiitr' The rapid l>ie ctFect of P r i- i.. din ish water of the nriiic, and the chlnridcs and phosjiiiates. and t;s; the diiniiiut'oi ii'i -utisfactorily expla'neii. The iiK reas. in iiot rsinin '111 lar.ue miinltcr of t d cells ihat 1 c Ik-ci iiroi- • np; tin .''\> acid iind otln 'oj.'cnoiis dcii>ati\c', art- ti isnlt i ■ti, Tiou rn chlo'-'U ilts isi mf :<} ^s "ii-rn ti it i- more acn\ i tian u>ual and i the hn tiiiis, \\ii,'-h protci ;- an ;.ot all food an'i reser\t' 1 irtly tlu, ■■ of the tissue.-, in this sense, < iifcti ip" the patient. Ill most severe inic- tions the urine conta' :'v tile seat of a cloudy swelling: '>r worse: tin kidney is prol)abl.\ due ti> L'ei alimnunuria," and the iirin. M-cn' dnr- toxic to animals; the luxin on ' and tiic>' damage the kidi; .n tiieir o-.inu jiiatcr m 'itet iir a a- 'l iiieta ; >- 'if pro- liiit iire ••l.iir - alhuinin, .liid the kii > l)ar' ichymatoiis cL nKighi on ti cpitht-itui.i ■■-- 'i« us prod 11" ' nf tissu'' lily (k'scrih- "febn a (Ii -ctioii is .IT ■■ in the )isturbance of the Digestive S> icm. It i- < u th.r 'lite aim dista.->tc for f( od arr ; (•cjiu lit re>t. intectio , • \i' i'i|og\ of tlic pr(H(~> is not y.- 'lear; the ;.'i; liiihir secretii '\ iiess (if tii( mc !ith and t s Ol ned in am( iiit, as i> seen in tin ' -sory dip -tive glands, in fact I'liced by ^he toxins, and clciidy Tespondir ick of efficiency of tii tie Cause? r Pjrrtxia. — The n - 'lire is ino Kin, but there. ■ :re iiK ';ti(cii. 1 he uifectivt iiu' ■ \ia can • irnduced exj>erin nU' il the l' lids of the body, are -welling -ilts with, no doubt, ' gh' d i ,ie time being, pre 'M cause of febrile tem- "^ '! auses of pyrexia which through their toxins, for ■■ 1} ns, as well as by enzymes .| im^^^^^ 1o2 THE MORBID AND REACTIVE PROCESfiES lu.nu.rrhaL'f, or up<.n tlu- in i.tu.n ..t l.lo.«l mt.. tin- >>. Um r up ' The s erile extracts of tissues or t.ssi.e jv.urs ""•;""'"• '^' nn^ :;xii::-rri;;j;:;;:l";;r;:;;^;;f.^^ ;;-::;r;L;;"Sof:!:;;^;^:^t.;.n>eJ.re.a.^ t !::i!; olVltlu-r otder. We l.ay. alrea.l>- refe^ed to tl.e .^^^^^ evidenee of the existence of this f..rn.. Chnieally it i. to tu ^'".|>-^/ a 'certain injuries to the central nervous system and 1-- '> ^^ XI lains the px exia of su.otroke. We are not yet able to supph tlie ' la nti ns mlssarv for the .ronpin^ to.r.ther of all these yaryu.g cases. i:;ftheiSive,th;enzyn.e.andthetissue-extract.ea^^^^ what similar, and all of these are cases where reaction lea* 1^ to the ro dSr of "itihoclies ; just as hiHanumition IS the reaction^ an ar^ t exceptio,;'. in whiy™. "-y be !.L in whid. a specific action on the heat c-entre ,s pn.d c^ It is perhaps unwise t<. attempt to hn morl) ph .omlnon when our ignorance is still so a nsn.al; "-'- ^^ -^ the fehrile state, knowiuf: how iucr.-ascd heat stimulates the cdb to :J a:^;Sve metld-oUsm. it is .lilhcult m.t J-'/l'^^;^^ ^HhTn ,^^ hoth the nervous disturbances l.^adrnj,' to heightened h) iil> t<."'P;j' U e .u r direot action of the toxins upon indivi.lual t-sues. m ^ict. a Uhc phenomena of fever, lead up to and favor that --:;5"»;;;^^^ substances, the body .leveU.ps certain antibodies b> ^^' •^'' ^''^ ^f^^^. are neutralized, so that the d.sturl.ance '7•"^^t«,«^:'f •, * ; J J nroccss of immunization. It has already been indicate.1 that the bm .rr^rt in immunity., absolute or relative, to deleterious outside rn« Jl of many kinds, which immunity is only another name for the em IMMUNITY 153 acciistoinance to surroundings; the body, furtlier, lias immunity wliieli is inherited. We know of certain acquisitions of immunity which are };ra(hial; and when we study the question of immunity experimentally, it is only those cases in which the imnninity is jjroduced in the course of a short time that lend themselves to our experimental study. We thus know little about imniunity, save as it is produced in connection with some toxins, enzymes, and tissue juices. Non-specific Immunity. -In our discussion of the defences of the iinily we i)ointed out that if microbes of various orders be intnxluced ill small nimibers into tlie tissues, unless they be of extraordinary viru- lence, they are destroyed in a very short time. In other words, the cells of the body have a defensive power which may be used indifferently Mi;ainst various intruders. And even where we deal with the devej- npmeiit of an acute specific disease, we notice this strikiuR fact, that the microbes of that disease are not to be found growing throughout the uhole body. Take, for example, a case of malignant endocarditis; the \ try fact that the heart valves arc singled out, is in itself an indication lliiit the microbes, streptococci, or what not, ha\e been circulating ill the blood, and the very nature of this disease necessitates that the microbes are from time to time being swei)t ofY the valves into the Mood stream and carried now to this, now to that organ elsewhere ill the body. But the remarkable fact is that in such cases we never fiiiil abscesses forming in the nuiscles, and very rarely in the brain, «r ill the nuicous membrane of the alimentary cimal; aiid yet all these ti>sncs have an abundant blood supply. Numerous similar instances will l)e tailed to mind, and the only conclusion that we can draw is that uhilf certain tissues or organs are peculiarly susceptible to the inroad of one or other species of bacteria, coincidently f)ther tissues are char- :i< tcristically insusceptible, or, in other words, are engaged in destroying tlir.e organisms and preventing tlnir growth, or in yet other words, |"'>>css a local innnunity. The muscular tissue or the endothelium of I lie \ essels supplying the muscles may hv cited as a well-marked example "1 tins non-specific immunity, because no matter what bacteria attack '!" Ixxjy they that attacks the body this non-specific immunity is constantly ■I' "rk, liand in hand with the specific immunity that is gradually I" - ilt'vcloned. Immunity against Substances of Known Constitution.— It is known '' liie so-called "arsenic eaters" of Styria can, after a few years' 1.-.4 Tilt: MORBID AM) RKM'TIVI-: PROCESSES a.l.licti,..., (■..ns.mu- witl...i.t ill cUV.ts four ti.iu-s tl.e onlinary latal .l,.s.- <.f tlu- .Ir.m, ami vvl.iU- tins l.as n..t lurn .•..nhniuMJ with annimls M.-vortiu-lrss. tiun- is .-vLlnur ui a (vrtai.. !,Ta.lo ot ..nmumty that ,ai. ho cui.f.rrr.l .... th...... If a., arsn.ical salt h,; inj.rte.l int.. tht ,,..rit..iK.uin in s,.s,.c..si.... or soh.ti..... a fatal tr..yi.ig the p..is..n. Ihe scrun. of tl.e a.tivelv i...muni/e.l animal contains s..metl.ing that it kill a niillinn iiikI a lialf L'ninca-i)ij;s, and tliis not suddenly, hnt after a peritid of fdiir or five days, siil)se(inent to wliieli ledenia, inflainniation, and necrosis of the lissnes near tlic point of iiijction set in; this snf;j.'ests the existence of ,1 ferinent-Iike action with formation of some second siitjstance ahle to act upon the cell substance. If animals lie fed cautiously upon -lowly increasinj: tr()yed. We may assume the latter, and show what some of these iliaii;;es are; if lieatcd to 10(1° ('. for two hours, it loses all its toxic pciuers, yet animals treated by it beet nie innnuni/ed. I'he so modified ii'xin (called a toxoid) is no lon<;er toxic, but is capable of setting up t!.t.' ' iiaiii;es in the body necessary to the formatioM of an antibody. If, a-aiii. ricin be ailded to the serum of an imnumi/ed an-'ial with it- antiricin, so that the mixture is inert and unable to i)roduce toxic I tl, !s. and if ilie mixture be injected into an animal of the same s[)ecies a- yielded tiie antiricin. it still has the jjower of proil . ' j; active iiniiiunity; from this it is evident that in the mixture of toxin and antitoxin the toxin is not destroyed. < luce an animal is innnunized ajjainst ricin it may be bled again and a-.rin and the blood remains antitoxic; the tissues seem to have acquired 1* . power of discharging the antitoxin, so that it does not seem likely li I the aiiTTicin is derived from the ricin. The vast jjreponderance lii i|i"i'itity of the antitoxin over the toxin also tells against such a -!i; position. Kvidaith/ the untitoxin is a suhstttticr irholh/ new to the ' 'II ism, ])roducc(l primarily by the cells as a reaction to the presence, in iliiui, of the toxin. Immunization against Substances of Unknown Const" Vu'on.- En;'ymes and Anti-enzymes. If a foreign en/yme be injected , ' -dly ii ' the body, a tolerance of it is ac(|uiretl. Iiy means o' : n nti- I! inc which is formed. For example, gaats injected wit., ennet I'! Hc a serum which has the power of neutralizing reiniet, and this 'I iiiiantitative degree, so that a fixed amount of senun neutralizes ■I inite iinioun*^ of rf nnet of a known strength. Hut just as an animal "! iiiized against a cert.TJii microrirganisni is siot rendered iinmime '" liier, although closely related, microorganisms, so in the above f-.-.-ir*. mofr-^sin ■ 156 THE Momnn and reactive PRorEfiSES I ? I oiise i\\v hloiid siTiim will not lu-utralizf tlu' ctlVct of " rcniu'ts" .htainod from i)Iaiit.s. Thus tlif aiiti-ciizyino is strictly spt'cific. T! ■ imici-ss .)f iiiiinuiiiz: tie n ajjainst animal and vt'j;ftal)Ic cnzynios cenis at first sifilit \ ,\ Ukc the pnurss that exists in innnnniza^ion Utt^inst bacteria; ! lit 'utc is this important ditlVrence, that the de\v!"pn!cnt of anti-ei /Aiu<- '.-, limited. The supposed reason for this is that the anti-enz\ is e t t free in the hody stimulates the cells to set free an anti- anti-enz\ :iie. Anti-en-'vi' es exist in the body in the normal state; an antirennin is prese:'t ii. normal i)!ood, and antii)ei)sin exist> in the stomach mucosa, and an au'it'erment to tiie dif;estive action of the i)aiicreas can be isolated from that or^an. If it were not for these antiferments the j\iice i) the stomach would (lif:est the coat of the stomach as it digests meat, and the pancreas would digest itself in life as it does after death. Despit. the existence of antijjcptic and antidiastatic enzymes, they tannot l)e artificially produced by the use of jjcpsin and diastase, nor d(H>s the injection of fibrin ferment result in the pnxluction of an anti- fibrin-ternient. The reason for this jjrobably is that the enzymes that are produced all through the body (for pepsin, iliastase, and fibrin ferment can be i)roduce.l by the cells of all organs) are so usual to the cells that they (lo not excite any antagonistic action. Toxins and Antitoxins. One of the early discoveries in bacteriology was that of the bacteria-i)roduccd toxins; this was made out especially for dii)htheria and tetanus bacilli, which we now know are able to produce and give off difVusil)le toxins, the ectotoxins. Most bacteria produce endotoxins, which are not dill'usible. ''"he injection into animals of the dilVusible toxins was found to ])rodncc innnunity; the serum of an animal, so hnnnmized, contains substances which neutralize the diffusible toxins, either outride or in the body, and these are the anti- toxins of medicine and comnicrce. It became necessary to arrange a standard by which to measure these antitoxins, anl(ciilf action; toxin action is a physical property, .icpcndcnt upon moloculur arrangement and shared by some, at least, of tlie dissociation products ot the cell. Toxin action is the first essential in the production of antitoxin. If a non-Jethal dose of toxin l)e injected into an animal, it disappears Ml a few mmutes, because it is taken up by the cells of diHerent organs and by the leukocytes, and can in most eases be recovered from the ur^ans. And here is the crux of the experiment. If tetanus toxin, well known to act upon the nervous system, be injected, it nes this mean that the nervous system has none of iV Quite the .or.trary; all the other systems give it up readilv because their cells have not entered mto a hard and fast combination with it, whereas those of the nervous system have. This close binding or Fia. 51 anchoring of the toxin in a tissue is the condition necessary to the production of the anti- toxin, and it seems to be the ca^e that the tissues that bind tlf toxins closely are those that dccelnp the antitoxins. It is not necessary for the production of antitoxins tiiat thf toxins produce disease; the toxin may by heat be rendered liarniless (toxoid), and yet when iiijcetcd can cause the produc- tion of antitoxin. This means that there are in a toxin mole- « ulc at least two parts, one of which is concerned with pro- 'iiiriiig the toxic effect. If this "xi'- part be rendered inert by heat, of what .Iocs the remainder of the "1^ Mcule consist, and what does it do? Since such a modified toxin can -t lip immunity it is clear that it must have attained close union with 'I" 'cll protoplasm; therefore, Ehrlich concludes that there is a part '■1 the cell devoted to the function of fixing the toxin molecule to the '- n.. molecule and this part of it is called the haptophore; the part of thr n.necule which is actually toxic to the cell bodv when fixed to it 1^ ■ illed the toxophore. This is represented graphicallv in Kig. ,-)l. 1' 1- evident from proof that we need not here giVc, that the cells "■' n thus become combined with the toxin molecules are those that !"' i'l'c the antitoxin, and that the toxin is not in anv sense changed r ""^l^f'\ \^ 'tfY'^\*:"t tliat the haptophore of the toxin molecule " '11 I !'i [ ^1' ^'T" ">'" ''•'' '*"^'"'' "thcrwi.e it could fasten upon ■"' ' II ot tlie body, and this power it obviously does not possess. There futptophune group receptor i:.s TiiK Mni:niD wn rk.wtive i-nncHssr.s must In- a .l.'U'm- ..f rccrptivity on tin- ].art cf the coll. A s lUutiiiK (•iiL'iiu' iniv liiivc a n.iipl.T, hut it ciiMiiot coiipli- tn a car unless the car also lias a c.uplcr. Klirlidi lias .Icvised a conception ui graphic terms of the i,rocc». If we >a.v that a toxin niolecnle has a certain coniiler, it follow- that the cell mii>t iiavc one to lit it; l.ut the complex cell has to provide couplers adapted not only to the coiii.Ut ot the toxin molecule, hut to various otluT molecules other toxins, iood- ,,tuiVs of diil'crcnt sorts, and so on. . These adapted c.Miiilers of the cell molecule, a.lapted to many dit- fcreiit forms of couplers on fon'i,i;ii molecules lie has called receptors, or side-chains. From one's chemical study, it will he recalled that we depict these Mde-chains as reachin- out for certain suhstauces to satisfy them- thev are unsatisfied affinities. To go hack to the picture «jt the toxi- molecule, it will he mcu that the side-chain is reaching' out to sati'^fv its allinitv for the Impfophorr part of tin- toxi.i molecule, that coupler attracts coupler. It does not matter whether there he a toxo- Vu. ,-,2 1 V .?-'.---; •'',,>' F.hrlicli (i( tlu' tir (■nllipoun< I'li'iiifnis .t ..r.l. !■ ( > (,-i of til- ■■ ,„ ,,( 111, II ni..livnli-. Mol.-, nil- with varic.iis rc<-c-iit,.rr. ,,r li:i|.ti.i>li"r.>i i.lMptr.l t.. .■..ii.l.m;iti.iii witli till' h:i|)lii|>li"rc>ii^ i:n,ii|w ^'•' ..f v.-iriniis I, thilii It will !"■ If.t''l that thiTi- is un iiicili:illi-ln l).v which Ihi- liiv „„|„,.,i„K . :,„ i..- ,lir.. tly att:,.li,.,l t.. the c.ll. iM. r„rh,t,.l, .tftrr Khrli (•heinical .iphtiruiis h.) phore part of the molc.'ule or not; the toxojihore jiart of the molecule has no power of satisfyiiif; the side-chain, ami cannot couple with it; hut if the haptophorc part join with the cell the toxophore part is hr'oujilit into direct coimectioii with the cell, and the toxin cun thus hecome part of the (••■11; in other words, can attack it. To apply this to a practical case, let us take that of di])htlieria antitoxin; the toxin molecule fastens on a cell hy its liaptophore iiart and its toxophore part acts upon the dl; as a consequence the cell throws out many additional side-chains, antitoxin molecules, which hecome free in the blood; the toxin molecules pick these up, couple- with them, and so are satisfied without reaching the i-ell at all. There is a normal discharixe into the hlood plasma of a larpe number of potential antitoxins, (piit.- ai)art from the stimulus of special toxins, M) that OIK- is tempted to think antitoxins may not be so purely si)eeili<; as has heeii stated. Khrlicli's - >i.k-ehaiii" theorj- supposes that ;i cell once stimulated to perform a certain act does not necessarily cease >"< WftMf' S v^-^ ' Tfti: KIDK-CHMS TIlF.oriY 150 ■ loiiiKso wlini tliciiimicdiatc iiccl is pjist, hut kf(|)S(.ii prodnciii-r tinTii (■(iMtiiiually fVfii alter the stiimiliis lias Ix-cri rciiiovcil. Tlic toxiiriiiolc- ciiU' stiiiuilati-s the dl to throw out mri)t()rs like the rerrptor whidi first fix(- it. It is sii|)p(.s(.(|. in terms of the theory, that these fresh receptors are coiitimiallv thrown oil" and eonstitnte tiie antitoxin. It is eimvenient, htit dilHciilt. to understand how tliis tliins,' happens, and at this point .ve propose to indicate a mollification of the side-cliain tiieory as it is ordinarily mider>tood. .\s we hav,- indicated !)efore, tlie lell consists of cytophism and nucleoplasm, not to lay stress upon the paraplasm. When a toxin l>i-comes ahsorlied into the cell, we do not picture it so nnich as fixed to the hiophoric molecule, as lyinj; Ioos<> ill the cytoplasm and conihinin-; with tlie side-chains of t!ie hiophoric iiiuleculc, dissociatin-; them from the molecule. If there are enough ■t such toxii. molecules, the l)iophoric molecule loses side-chains so rMi)idly as actually to he destroyed, "pulled to pieces." This docs not mean that there must he a toxin molecule for every side-chain detached, hut rather that enzyme action, as we have explained it, nnist play a part, and that a toxin molecule, having detai'hed a side- chain i.s free to break itself away from it, and at oik-c fix ui)on and detach a new side-chain and another and yet another. Only upon some Mich assumption, we think, is it i.ossiWe to explain satisfactorilv the • uses where a mimite amount of toxin can kill lar<;c animals.' ',Ve think that poisons, other than toxins, wreak their etl'ects hv a sitijjle ;ict ()f union with the hiophoric mass, while the toxins nnist he able t(. .lit like fermeiiis, with a rei)eatinf; action. If we were to supi)ose that the toxin molecule made a single act of union with a side-chain, it is li.ird to see why the dissociation of a sinjjle side-chain should at Once -iiise the hiophoric mass to set free a lar-je munl.er of similar sidc- < iiMins; hut if the toxin molecule should he able to repeat this act in '|iiiek succession again and ajrain and yet ajiain, we can imaj;ine the '1 II establishing a habit in the production of the new side-chains. It "ill be understood that this implies activity of a lii<;h order in the l'i"|)!ioric molecule: it is i)re(isely this activity that marks the resist- 11- cell as diti'ereut from tin cell against which the toxic attack is at 'Mi.c successful in causing cell death. Let us dijrrcss here to jrive an iNainple: instead of the abstract toxin molecule, ri'ad tetanotoxin. iii-tead of the bioi)lioric molecule consider a sinjrlc cell of nerve tissue: |h' tetanotoxin joins with the receptor for it and detaches it, and free- II- itself from the receptor it has taken nj), there betjins a race between ''•Mil and cell, as to whether the cell can produce more receptors than il, toxin can (htach; if it can, the exci^s of them, continuing; to be "wn off, constitutes tetatio-aiititoxiii, and thus a relative immunity Hii' result of an unsuccessful toxin attack, just as the soldiers of a "iiMin become more efficient by reason of each occasion on whicli the ider attemi)ts but fails to ca|)ture their stron-rhold. It will lie seen M tlie above that our eoncejjtiim of inmnuiity depends u))on the I hovering, so to say, in the cytoplasm, and not upon it being part ' Tsawmmefwmesimw r-n. 53 .Y. II Tm „„1,„, .ho ell, an.l ,„,.s..,«nK si.l.'-Wuuns of vun.ms ;| ^' ^; ; ; J j ^ V„„ „„. ,„„ ,,j. d„soc,.ti,.n .„U.-l„nn.-. fro,, n.ol.. ulcB (X. V) .l,m,».. .no "- 'J, . '^^ „„,„;„„.,, „„,„„y of ,h.. b.ophor,.. .,, „„.r. ..on.plox n,ot,.,.,.l.., also ,,l..,rlH.,lK ';;-''^; ':;;;::;;:;;:':,„.,. ,„„,„..,. ,„.y boco,n.. «.,M..l H..,l aro lM„lt up by .. .0 for,,, tl,o ^^'''^ '■;■'•;. ^ ^. ,„,in^,he nght or.U-r of h.ptopl.orous ,ro„p- ,.y a..r.., u„. to a ..,l,.r U 1''"") ™''' ■':.'," fin , „,ol-ul..a of .he E order .„ay not n.erely i,,,, U i, , onreivable iK.eo,„e neutral,, d, ,t .» h '- -i ^ ^^^_ __^_,^_^, ^, ^^,, ,. „,„,.^.„„., ,„« s,de. ,„,„ii,„,e, .he ex.rae, llular ant,tox,n. 4. ^^ '^J'^^ ^ ,„ .^e biophore or free ,n the cytopto,: ,„„„,» .4 l«>eon,e .„nl. „P in .er,e„ and ''" ; V'^^^ ;; "J, „„,,„ Z.. .■ondi.,ons will bo the pro- .he ,nore ,h are treed l.y .he -""";;'_', '^^.^'.^^^^ , „,„„ula,e. .he eell .0 ,he prclue : .; ;■> ■::t:i^::::::::^^2::^^ ;;;h:';:aU>. .a.-eh.. era. upo. «h.eh it e«rta .pec. a^'tion. mmmi'*^mT"mm. ■ '^•-'^s.z^mws I'RKCIPITINS 161 .1' tlichiophoric mitlfciilc. Our u\va of antitoxin prixlnction is expressed L:riiplii.all\ in Fi^. ■');!, the tliorouKli >tii(ly of wliich we would counsel. The Mode of Union of Toxin and Antitoxin. If toxin and antitoxin lie allowed to unite, neitliir i< necessarily altered in the j)roeess, because ;it least one of tiieni can he separated uiiclianjied from the mixture; liirtlier. toxin neutralized by antitoxin may be neutral for animals of one species ami jjoisonous for those of juiother, which may be explained l>y the statement that there are. in the blood of the second animal, -ul.stances with so strong an affinity for the antitoxin that they unite uith it. dctachins it from the toxin, whiih is thus left free to act. If toxin and antitoxin be allowed in vitro to iict one u\»m the other, they Income niore closely boond one to the other, and in vim the lonpcr tlif toxin acts in the cell the more firmly does it become fixed to the nrcptors, and the more difficult is it for the antitoxin to detach it; thus the later in the course of the disease the antitoxin is injected, the lt>s chance it has of bein^ effective. The v< r\ fact that antitoxins can (liter the cell and arrest the infective process bears out the supposition that the toxins when they are setting up eel! disturbances are not actu- ;illy fused into the biophoric molecule, but are acting upon it from with- "iit. that is, in the eytoi)lasm. The action of antitoxin seems to be tliat: (1) it neutralizes free toxins in circulation, so preventing their 111 tioii upon the cells, and (2) it gains entrance to the cells and there (litaclies toxin molecules, thereby setting up the excess of receptors ni((ssar\-, as well as neutralizing the toxin molecules temporarily S''t free. Inst as enzymes cause the development of anti-enzymes, so other 'lillii-ible-cell i)roducts, particularly proteins, have a similar power. Precipitins.— If the culture fluid, in which certain germs have been L'ri.uii and from which they have been removet mark.'.! vvitl. tl..- I...in..l..^;..ns s.-ruin. tlu t i>. tlu -' run. . i u ':Z~ 'finally um-I in th. .Mu-mnn.ts. a>ul ;;■"■.,!""> J^^^^^ , , , „..,., „,,t tW ...ost M,ark...l pr... pjtatuH. of all w o.-nr .nl> the •' . it ...t i.rut.i,,. i.. a 1.I..M.1 sm.... Lave so....tl....K ... .•...........,, „„1 prrripit..i.l> aM.l ovn. a..t.pn-np.t.,.s ^^^^^.||. in . fSr^'li... r u-M th.n- is a.l.k.l to that ....-Ih.m the ser..n. of t t ■ . It H.ws .h.th.r the in.livi.l..al atVon 1...^' the seru.n has h. ., t .r,. i..reete.l xvith typhoi.l ImciUi. A,'^l..t..K,t...r> ests ' i . ...otile as w d as xvith ...otile or};a...s..is, a...l are 'r. •::.; Uhi: ' ' .^ tvphoi.l. .lyse..tery. t..l,erc..losis. plague. :; in , nil with HaVilh-s eoli. ,>yoeya„ens. pneun.oeo<.eus^ ' n , o... .s a.ul >ta,.hvlo..oee..s. A,'^h.ti..atu... .s spec-.he to t xZ 1 wi 1. rrlJrh, hujh 'IHulion. of the h,>...ol.,Kous sen..... tl ^t u r oruanis,.. <-o,..er,.e.l is the o,.ly o..e to show < '""P'^ j ' r u. io>, .••... l.e ..l.serve.l ii.uler the ...irn.seope ..r ... In.lk when .. 1 'si- fo n.ati.>,. of a Hoee..h-..t s...li..K-..t is see..; hv.,jK a... :::;;" h;;::^ '1;..- pro.lu..e.the H.e,.o.e...... a...l t . .....non of <^;.a ,,„.illi ,,,„ses the fonuatio.. ot a««h.t......s Ihe powtr <" '»"• ^^^ StinMio,, ,..ay re,..ai,. i.. the sen.... tor a hm. t,...e after the '"We'e'niuori uliat a,,h.ti..i..s are. l„.t we k,.ow that they are ;:;^':;;t;::^::;.it;;;;;;th:'f;;;.tthatthe^^ i„ ...tal 1.1 1 or in the tir>t years o. eh.l. hoo.l p^<;^ w^ght to n..;^?; V ev i H- eriolvsi>.s .bo.lies that ea.ise the .iestrt., t.oa of ba^ t'ri.;' i^ rther ^vi.l.ot tl.at o,.e or,a..is.,i ca,. ,.ve nse to m- e ;; .m :.^,h.ti,.h.. a...l i.. the .-ase o. l.aet.r.a ' -'' an^ rektjjl^ - me another so..,e of these agglutinins are the ^ame. ^\e think, there W^- A aah I • TI\I\S—C YTOL YSINS 163 I'cirr. tlmt M s|Kci«s of organism can jrivi- rise on tlic one hand to an luu'hifiniii tliat is sjicciHi' to itM'If. and to others tliat an- also capahh- >.l l>«in>; fomifd U\ other rehited orjranisnis. 'I'hiis luia(ilhis II can Inrni D, K, K, (1, and FI, and >o <.n. 'I'lie nature of the a>;>;liitination jirueess is prolmhiv that the ajr^-'Intinins lirin>; idioiit an alteration in I Ik inoh'cuhir attraction or tension l)et\vefn tlie liaeteria and the finid imdinin. W'v woidd correhite witli this the KatheririK into rouleaux of tin hlood corpuscles, and the jihysical experiment in whicli niutelies I.I repr»'sent hacilli) or disks of cork (to represent red-hlood cells) are in.ited with hard soap :ind floated in a tub or water; they float about ir.e till the water is faintly acidulated, atid then they gather to^rcther into clunii)s; if the water he rendered alkaline, the chunps if liroken uj) iUiuiit reform. First, there is |)roltahly a junction between the agnlu- tiiiiiis anil the l)acterial cell, anion il I lie liaeteria, a change with which the ^nlts are concerned. Cytolysins. The blood of one jmtsou inject«(l into the body of iniother may lead to the dissolution of corpuscles of the latter individual nr tu coagulation in his vessels. If an animal .\ be inolood cor])Uscles of an animal H of another -|ii< lis, within a few days the blood .serum of A gains the junver of Inking" the blood of H. that is, of destroying the red-blood cells of it uiili lil)eration of the hemoglobin. The injection of the corpusoles Ii.mI. to the formation in the blood of A of a cUoto.xin or cytoly.sin. U 111 II this was discovered, a series of similar lysins were determined, iiM hiding leukolysins, which arc made by the injection of leukocytes. iIm Iriikolysin being specific for the kind of leukocyte introduced. Miiiiiarly, nephrolyslns and hepatolysins were discovered, able to set iip'lt generations in the kidney and liver cells respectively; in fact. till ((lis of every organ seem to have their specific lysin able to act t~|..(ially upon that organ. The destructive efl'ect is most marked « 111 II the animals used are of widely ditlerent species, in which case till iy,ins are called heterolysins, but there is some interaction even '"'urn animals of the same species (isolysins). Hut it is not possible til iiiMiiufactiire exi)erimentally autolysins, that is, sul)stances derived I :m animal which can break up its own cells. This ob.servation 1 keeping with the impossibility of making anti-enzymes to the iiion enzymes of the body. Before leaving this part of the subject necessary to note that while a cytolysin ads most powerfully upon I lis of the special kind which constituted its antigen, and in reaction ■icli it was produced, it may have a certain lesser efl'ect upon other iind this is not wonderful when we consider the common origin ' I tils of the body and the likelilio(Ml that they will, therefore, have ill qualities in common. Just as occurred with precipitins, if cytoly- ■■' rautiously injeclfni anti-cytolysins can be obtained, and these 1 iitralize the action of the cvtolysins. Iri'i i> I Cl.l! it i- tli, ti. . cci: (iff It Ma. awiiw ] :w^ats» 164 THE MORBID AND REACTIVE I'ROCKSSFS The Mechanism of Cytolysis. If a Kiiiii«»-l''>t ''"^ raM.its' ((.riHisdes iiijcctf«l into it. its stTuiii (|iii(kly Iktoiius iictix.' in »»rcakni>; up the ral)l)its" corpUMlcs, uikI is tlun iin<>a-pi^s ^.rnni has .k-troyt-.i Mun.tlnnK' which tlic normal scrum can rc^tun ^r that til' n is stuiicthinK present in Fio. it unhcatc.l inminnizc.l piin. ;i-i.i- s.rnm an;am somcthmj; in normal sernm that is necessary to l.cinol.N --is. Tin re must l.c m..re t.ian one h(Mlv im;-ent, becnuw non-inimnnc Kninca-pijj scrum is not nhle by itself to produce the elf.'ct. //( fvrrii cm uf ,7//o///.v/.y the rxidence and covihinrd ariiun nf thcxv two fnchrx rmi he .sli the complement acting with the immune body. (Iraphically we express this by Fig. :A, in which it will be seen that the immune body is imagined as cai)ablc of a double attachment, hence the name amboceptor,' to complement on the one hand and to cell on the other. Nor must it be thought that complement and amboceptor are iiu relv theoretical names, for each has a dcHnite exist- ence and is as real as if it were a chemical enclosed m a bottle and visible to the eve. Further, in the interaction of complement, ambo- ceptor and cell an exact amount of each is necessary for a perfect reaction; an excess or la<-k of one or another leads to an imperfect reaction. ^ i j 1 1,. The Existence of Different Kinds of Amboceptors.- If a goat be doul)l> immunized to both guinca-i)ig>' and rabbit.,' ml corpuscles and this goats' serum be used upon guinea-pigs' corpuscles until no further heni()- lysis can be obtained, we find that there are \et amboceptors in it capable of hcinolvsing rabbits' corixisdcs; the goats' serum thus cm- tains two distinct sets of ambcKcptors, and many other such experi- ,„..,,to. |e.icnl complemenUs, identical at least in their haptophore (or coupling^ I'lits, although the to.xophore (or destructive) part may be different. Ii^t as was the case with the t.ixin molecule, st) the comi)lement may • imagined as of two parts; just as the toxin could be m. 'ified to a I "id, so the com|)lcmcnt may he miRlihcd to a complementc 1, which "ill >till have its old affinities but will have lost its evtolytic powers- Mill, such altered complement can join with the iminnie body and rUr toxophonc or cytolytic part being jww. rless, no d, mage to the "II results but other and active comi)leinent is pre- ented from joining. Lastly. It may be jwinted out that the amount '>f .implement present I' a variable quantity, and it may by various ex[)erimental means and "V ,lis.ase be reduced, or may, by the injection of substances like blood !'l.' ma and broth, be increased. BacteriolysinE, As inoculation of animal cells leads to the produc- |i 'H ut bodies causing the destruction of those cells, so has the inocu- lation of vegetable cells, bacilli for example, a like result; thus to '''•'■nil perlect immunity against bacteria which dceelop endotoxins two 'I' '!iHt processes have to be carried out: (1) the development of ■' uriniysis whereby the endotoxins become lilwrated, and (') the 1; riMtioP of anti- (en.h.j toxins. Nor is it by any means easv to attain two nsults; It not infrefiuently happens that having gained the 'i • a dose of the living germs will ' ingest it; the extent of this action can be gauged by noting under the micro- scope the average number of hacteria ingestiil by one of thirt\ or forty leukocytes observtd, and comparing it wilh the niiinbcr i!igcsrcpcars as if the virulent ba'illi excrete or discharge substances which are not toxins, hut which ha\c an inhihitive or "anti" action upon the body cells, substances which do not necessarily combine with the body ct'lls to destroy them, but either neutralize the ojjsonins or directly repel the body cells, the repulsion being greater than the attr'ction exerted by other hactei. d substances. Anaphylaxis. -Anai)hylaxis or allergy, is a phenomenon connected with the injurious effect that is occasionally wrought by serum tl e so-calleil "serum sickness' and "scrum death." From the early days of the employment of antidiphthcritic serum, there have been occa- sionally reported cases of death following suddenly the injection of the serum, ("ollapse, unconsciousness, and convulsions have occurred, death ensuing with startling suddenness. Less severe symi)toni-. the urticarial rash, with or without sy>tcniic symptoms of lack of vvell- being, and otlier milder manifestations following the use of s»Tum, are familiar to all. These untoward elfects are produced not by the toxins or antitoxins but by the scrum, and it may be said, by the way, that the risk of these is the price mankind has to pay for the blessings of serum ther.ijiy. Again we shall illustrate this phenomenon by a concrete example. If .') c.c. of a foreign scnnn he injected into a guinea-pig there are no immediate etfccts, and the animal l>ecomes soon inununized to that serum. Hut, if instead of ."> c.c, as little as , „„'„„., <'•<•• he given, and twelve da\s later a second injection of ') c.c. he given, the guinea-pig will almost certainly die, and that i[nickly. Instead of being rendered itmnune, the opposite result has been obtained; the animal has been "sensitized," and this process of sensitizatitin is (UKii/lii/ldxh in contra- distinction to I'roplu/laxi.i. In herbivorous animals, the same result can l)e uainiMl by feeding with the serum, and tiic blood (tf the sensitizeil animal ■ omes to contain a substance which, when the blood is injected into other animals, sensitizes them. In man and onniivorous animals a single dose sometimes has the ctVcct that the two doses ])()ssess in hcrhi\orou-~ animals, anil thus serum death may K'cur. This .-( nsitization appears at first to be oi)posed to our general icKiis of iiniuunit>, i)ut we have attempted to sliow that it is not necessaril} so. As >hitwn by Vaughan, the i)act(Tial proteins can be s|)lit up into a j)oisn!ious Hud a non-])oisiinous ])ortion; tlic same is true even el egg jibuinin. ;Mid its poisonous portion kills an ex])eriincntal anini;il ju>t as doc- tiic poison of a i)athogenic bacterium. The same is true, also, of niu^t viiiitable proteins. One may sensitize an animal with --^MS-^^ tTiK > THEORIES OF IMMUNITY m the poisonous portion, or with whole aihuniin. but not with the nou- po|sonous portion, that is. th. cell .substance has affinitv for he " - I.o.sonous part, an.l for.ns an.l discharges receptors s'uited o t is o'wZr;^ IT- i''"' f ""!:'' ''' ';''' ''""'■"'" f- '"-^-ti^"'. t^ .rt if we , ,• r IT" '^'"''t '"'' '"''^ituate.1 to the non-poisonous part, If ueniject whole c^k albumin, the cells with their excess of reccj.tors attract the non-poisonous j.-rtion of the serum to which thev are acnustomed and set free the ,,o.- ,.k,us portion in the circu ition winch acts u,.on the nervous system a.ul produces .leath. Tlu ' econ 1 . OM- n ust be large enough to supply a fatal .lose of the poisonous pa .itt.T .phttmg up. It seems, further, that the poisonous portion has a M>-ud affnnty for certain cells, an.l it is this local, rather ?han gen^l -non that explanis the anaphylactic phenomena. In the guiner-p.V or example as shown by Auer, the fatal result is due to direct nfluJ.^e upon the plan, muscle fibres of the f,roncin. causing a spastic cmtrat- .on w. h arrested respiration. In other animals als,> it is plain muscih r i. re> hat ai.i.eor to be specially implicated. What is true of the el' ; ""';.'- ^"•^:.«f ^'-' protein-containing horse serum, wl k-l o s tl ! I'.i^is ot the antitoxic sera of commerce This does not explain ^^hy a small dose sensitizes while a large one . ailed the dissociation ot ions; if a minute quantity of salt be put ntn a arge quantity of water it is onous parts, of which the former is in q , ity to., nunnte to produce any s.Mnptoms. and the cells are abl o^' ct -I.v to the latter. I the preliminary dose be large, the dss da ion . .Ks „.,t .,,,,., ,,1 ,„.. ,.,„,,. ,,„, ,,,,,.„„^. arruston e.l to the he ■ .. e n mo|c,.wle; the poi.onous action is thus expen.le.l upon the t^m V n .r 17 ?""""^ r ^'^''' '' '' '■'■'^^ '" *h« circulation It n.i> be recallc.l t iat m our chapter upon pre.lisposition (n 117) TZT^T r' ''!■ *'"■ ^'""'""^^- '-tween'certain t;' of •|l;->^.KTaM , ...tluna, hay tcver. -.tc. and these anaphylactic phe- THIOWEB OF IMMUNITY !■ N erynnc. who is in the slightest degree familiar with mclical litera- ; • > eM.lent that we can give as bri.-Hy as possible not an < • " t he various arguments in favor of ^ arions theories, but '!> .1 very i)n<-t explanation of a sinde nractieal ,„>.. VV in ''^- l'"ve seen that all the substances that can induce the prcxluction 172 THE MORBID AND REACTIVE PROCESSES of antibodies (i. e., all antigens) are either ceils or the products of cell activity, and that the antibodies, too, are the prwhicts of cell activity, and that one group is a kind of lookinR-glass reflection of the other. If we were bacteria we would regard the antibodies as toxins, and our own toxins as protective antibodies. Two living organisms, the animal and the microbe, are pitted against each other, ami the increase of virulence of the latter may be the result of its developing anti-anti- toxins (which, from the microbe's point of view, are simple antitoxins), corresponding to the development of antitoxins by the animal and tend- ing to neutralize them. The problems of immunity narrow themselves down to special problems bearing upon the assimilation or digestion of unusual or foreign proteid matter, the products of cell metabolism. We have given the basis of Ehrlich's theory referring to simple toxins, but when we reach the cytoljsins we are met by a new phenomenon in which there is not simple union of the molecule of the cell and the toxin or the complement, but wiiere tliis is brought about by the intervention of an intermediate body or amboceptor. We may here recapitulate the various forms of antigens and antibodies with which we have dealt : — Eniymes Fhytotoxilw Bacterial ectotuxin!) n ^ - /animal Proteins', . , (vegetable Bacterial proteins ('!) Bacterial aggrfaains (.?) Animal venoms Csimilej .\niniul venoms (cotiiplei, ri'quirin^ interiiiediatiun of conipleiuent foi action) Vegetable cells ^bacteria) . Animal cells of various orders .leailinic to the proiluction of Anlienjynies " Ami (phyto) toiin. Antitoxins Precipitins Agglutinins Opsonins Antivenins I .. Antihcmolysins, ( etc. Baeteriolysins C'ytoIyHius Uemolysins Leukotiixins HepatrljHins, etc. .\cting singly. Ucquiring in* teraction of 1 amboceptor (specific), 2 complement Cnou.*I)ecific) Reviewing this table, one notes that there is a progression from a simple structure of the absorbed body to a very complex one. Accord- ing to the nature of the body to be absorbed, the binding apparatus must differ. To tie a simple substance to the biophoric molecule we may presume that a single, simple side-chain is enough. When, how- ever, we come to the giant molecule of a protein, this will not be enough. Giant molecules, as such, are useless for the cell, and must be broken up, dissociated, by fermentative processes. This could be if the "seiz- ing arm" were of a nature complex enough to seize the molecule and to bring into contact with it the requisite ferment; to borrow an example from the vegetable world, the tentacles of the Drosera seize the object, and cover it with a juice that is digestive. Such a complex side-chain we can predicate in the case where the body to be "lysed" consists of !S»riB' a*?J*tdia THEORIES OF IMMUNITY 173 in cells. If there be such a complex siMen^hain, the nrwess of imnni- mzation will cause a reprodea. Ehrlich sLpioses that there are three orders of receptors for food nr tnvJn molecules (1) The simple toxin (/. b) is anchor Jby a re^pt^ Ta) of the first order, that receptor being a side-chain with a haptophore ro which the toxm molecule becomes coupled by its haXphore c (-> For protem molecules, a different order must be imagined The sule-cham must have an arm for seizing (//, .) and one\Td){oT Fia. 55 The three order, of «de-ch«in«, according to EhrUoh. tLlT is'"a hantoT'"* ^J ^^"'^ '^' °^°'^^"'« "^"^^ ^e dissociated. \t li,^ ^Ptoph^re and a zymophore (or ferment-carrying portion) re ^ thlT'^^T '' ^^"""'^ '" ^'^- ^^' "' '" ^hich e is^the hapti r tlvL??'"'''""' ^l'^'' ^' "«"P""S ^'^^' the zymophore I c t.) exert its ferment effect upon thebody seized. It wiU be seLn :Z T^ri^'t '"^%''' \' '^ '''' «>""*-P-* "f the attached „ , * "* , F- ^•'' {^- , (•^) ^'or the yet more complicated case of an < -t o„ between the biophoric molecule and a foreign Sll we must "•> M.pp ,se a complex receptor as in Fig. 55, ///. The receotor Z,f ;;;;;.pa.leo attaching the cell to be acteci upon (^IdZZ^Z ' >it /), the complement is figured as possessing a haptophoric Dart ' . ar.d a zymophoric part (.), which latter corresponds to th"tox2 171 THE MOlUilD .\.\n RE.iCTIVE PROCESSES I plmric pnrt of tlie toxin iiiuU-ciiK-. When fM>th these are fixetors are produced in excess and diseharg'd, they have the same i)o\vers of attachment as when fixcfi to the hio- phorie molecule and when free are termed hy Khrlich haptines. Ilap- tines are thus of three orders, those with a single hapt()i)hore, such as antitoxins and anti-t-nzynies; those with a haptophore and a zymo- phore ^rouj), the ajrj;lutinins and the jm-cipitins, and lastly, those with two haptophorcs, which are the amboceptors rir immune bodies proper, and constitute tiic cytolysins and baeteriolysins. There is a word of warning to be ^iven to the l)egiiir.er in intor- I)retinK the diagrams which we have reproduced. We are not sure that the toxin molecule becomes anchored on to the biophoric molecule and .-.o I)ecomcs a part of it. The interaction of toxin on haptine is direct- the toxin acts upon the biophoric molecule in a way that is less direct; we difft-r from Khrlich in not regardin>r it as becoming lirmly attached to the biophoric molecule, but as dissociating, by its affi'iity, tiie receptor, the toxin and iecej)tor liecoming temporarily a free unit, and imapne that there!)/ the condition of unsatisfaetion, in which the biophoric molecule is left, leads to the formation of a new side-chain or rece-)tor. When we cnsider the processes by which bacteria are destroyed, and their cell products neutralized we realize that these are but special exaniples of assimilation and digestion. The process by which an ingested microbe is dissolved in the vacuole of the leukocyte, or .t bac- terium melted in the body fluids is probably brought about by a pro- cedure of i'.'.t same order as when fibrin is digested in the gastric juice.' In .10 Pl.t of the whole subject can we neglect the importance of enzyme action \Ve readily admit nay. we citt^the different grades of ej!.-.\ ;i;e action with which we art familiar; how ptyalin acts directly on -larci), and enterokinase requires the mediation of trypsinogen. We think, in short, that toxins and cytolysins are of enzyme nature. Indicating the ^inilarity between toxins and onzymes, we have anti- toxins and anti-cnzynics, we have natural and cxi)erimentally acquired .•inti-enz,\ incs just as we have actual and exi)erimentally acquired anti- toxins, we h ive evidence tlial ii minimal amo\mt of enzyme may convert a maximum amount of the substance acted on, and a minimal amount of toxin cause dissociation of the cell substance, even unto death, or that, umicr favorable circumstance;, either process may be arrested; we see, too, that the action of both is arrested by the products of • lissodation: both work with chemical exactitude, so much enzyme nentraiizes ^o much anti-enzyme, and so much toxin so much antito.xin. ' Or prrhaps. inon' ■((•ciiiately, in the piinoroatic juice, for such digestion is lytic ;iin] w now rcconiuzi! that for the activation of tiie trypsinogen a second body is ncri ^^al■v. 'i ryp>ini)(jen is inert save in the presennc of enterokinase, which may be regarded as the complement, the trj pteinogen as amboceptor. mmmmma^mm - - .^^^ a.- - -i:<*.:Sfc^t.i4fer;^- THEORIES OF IMMVSITY 175 Ue f toxin.s, an.i we must tlierefore express the process l,y symF)oIs i.s Klirlieh has done. If we iire speaknig of enzymes, tlie enzyme molecule (eorrespon.lii.j: to the toxm mo eeule of onr previous illustrati.-ns) has a haptophoric (conph'nc) part, and a zynioplioric part, and inst.-ad of the cell IkmK we have this tun.- the substance to 1h ferment.«d (th.- fernientesciMe sul.stance) .Now let us digress to the consideration of tlu- chemistrv of fernunta- tron; lor example, dextrose gives rise to glucose thus: C„H,,<)„+ E + Iti) - (;ir,,«»e . (•Jf,,()e+ E. ()n«- molecule of dextrose + 11,0 = two molecules of ghuose. In the pre-^ence ol enzyme (El hydrolysis octurs. The moh-cule of dexfose cann..t he split into two equal i)arts, but 'li\ ides lui iqually, thus; ^''="^"" = {c:h::I]: Ijiid the hydrolysis gives i.w a fn-e basic IK) ion. and a free aci.i II ion I Ik next step is that we expand our last fornuila thus: The dextrose molecule splits into two parts, one of which has positive, 'lie other negative affinities, aiul when these are separated one attra.'ts ■^ I'aMc ion, the other an acid ion. Our conception is that the enzMue "IiK'h thus splits up the molecule into a basic and an acid part, must itMlt he acK or basic; thus, if aoi.l it detach.-s the basic complex C'JI„0,. I.nt the hydrolysis has 1,-ft free an II ion, which now exerts a great*-r ^ittraction h.r the ('ellnO, than does the cizyme; the two -..mbine aiHl the enzyme is set free to break up anoth.-r molecule of th. de.tro.e' \\c have indicatetaneeot the kinaf^e. \yhen we liken the a.tion of enzyme to that of toxin, we recognize "a then, is a frecpient sonn.. of r-onf.ision in the conception on the :'.i t ..th,. worker that enzyme aeti-n results ordinarily in the produc- '">' nt substances which are certainly not anti-enzvines, and there "IH-.rs at hrst sight to be n., similar action o,. the part of toxin mole- ■ •■>■ these, we are apt to imagine, pn-h.r ..nly antitoxins. This I ««^.•^ IS a mistaken i.l.-a. The process .,f juncti..,, betwe>en toxin ■• "I antit..xin is associative an.l self-limiting. .....1 there is an identical "-.ss occurring between enzyme and anti-enzyme. What we wish 176 THE MORBID AND REACTIVE PROCESSES espwially to point out is that, ci -rrespondinR to the process inanifest- iiif; itself In-tween ferment and f( iientesoible si l.stnnfc which is y tiie eniym*' or tcxiii iiM.ieculc F ^^hiell thus joiniiiK with .1 lieconii--* ip-utralt^rd. and recurrent proc«'ss t)ccurrinj.' b< t^een the toxin and tlie biophoric molecule. The one essential '!ifft,roi( e is thut the enzyme may mani- ■PI SYNCOPE, SHOCK, AND COLLAPSE 177 f.st this .li>s«ciative acti\ ity ouUide the cell, the toxin tan manifest u only within the • v\\ and in asscH-iation with livinjj niattcr. It is when th«- enzyme acts u|M>ti the living cell that anti-enzymes iirr iir.Hhitr.l, just as antitoxins are «levelniH',l untier lii^e circumstances. AikI ti. explain the reliitionship Jn'tween the fcrmentescihle or disso- riative anil the antilnMly or ociative activities of both onlers of >iil)stitnces, we siiK);ist an addition to Professor Ehrlieh's conception >'\ 'I'll Imin acti\ itics. In toxins ami nntilxMlies he takes no note of I he ^croup of junction with the hiophoric moh-cule; when (lisstK-iatefl, tlirriMnust he here in the suic-chain coni|»h'x (which in our diagram, Vh. :.7, is Ni.lid black) a satisfiable affinity. If now we picture the toxiii nii.h'(iil( , nut as becoming attached to the biophoric molecule by one of the sidc-chiiins of the same, but fu detachhvj the nide-chnin, we can solve the difficulty; that is, we can regard the toxin as acting like an .nzyme, «letaching the side-chain, giving it up to the stronger affinity of the recipient 6'. and being free to detach another side-chain. Thia siilc-ckniu phis recipient in the antitoxin (Fig. ')7). Ill the cell this antitoxin cannot act because the toxin has affinities for the similar side-chains of the biophoric molecule still adherent, unless the point is reached at which wpiilibrium occurs by the accumula- tion of the products of the enzyme action and by the overproduction ;md discharge of side-chains of tli particular order into the paraplasm. Hut when the excess of side-cliain.s j)lus recipient is discharged into I lie blood stream, then circulating toxins, not having the greater attraction of the intracellular molecules, are free to join them and he iKiitralized. In this consideration of the subject, we have calletl in no external lactor save the "recipient," some simple but active ion present in all -nliitions in which the enzyme or toxin is able to act. 37NC0PE, SHOCK, AND COLLAPSE Syncope or fainting is the state in which the face suddenly becomes ched, the pulse small, rapid, and at times imperceptible; a brief • 'ill n I If! I uiiMincss or a moment of mental helplessness, is followed by unconscious- ness, the iridividual falling "as a sail falls the mast being broken." Tins arises in various ways: by the sudden assuming of the erect from I lie supine position, by the emptying of a full bladder (with probably a "' ehaiiical fillin;, of abdominal vessels), or by strong stimulation of iisory nerves, in other words, pain. Unconsciousness is usually brief. \-ain, syncope may be purely of emotional origin; many medical iMileiits will re himself all the sensations (and more) under- i: ne by the patient. Personal memory recalls vividly a football match, \Mili the scattered faMing, like pole-axoJ siters, of nearly half a score 12 ■Miii MICROCOPY RESOIUTION TEST CHART lANSI and ISO TEST CHART No 2l 1.0 I.I 1.25 ;- iiiiiM i2 IK 1.4 IIIIM I 2.2 1 2.0 1.8 1.6 _^ x^JPPLIED^ I M/IGE In ^^i ■♦■■':..! l2i[ V-j.n Street H y-S ^icnester, New ''ort. 14609 uSA *■= ''6) *82 - 0300 - Phone ^^ ''6) 288 - ^989 - fa- 178 TIIK MORBID ASD REACTIVE PROCESSES of undcr-ra.luatf ..nl....ktTs. .•..nsc(,iKUt iiiu.n tlie loud, sharp snap of al L'boue ofciu- of the i)layt there is the einoti...ial shock that may pr<..lu.r .l.ath. iho case is cite.l ot a mock trial con.h.ctc.l l,v son,.- stntn.ck on the neck with a ^vet towc'. and picked up .h.a.k In less extrenu- ..ases recovery may take davs or weeks, instead of minutes as m syncope. 1 her.- is hlanch- ini: with a w.-ak. feel.k- pulse; the eyes l..'come sunken th. jheek l.ones pnm.inent; the muscles are lax; the l.reathinf: ,s irre-ular, the tempera- ture lowere.1. lletehin^- an.l voinitiuf; ar.- tretent vomiting or excessive diarrlura. \Ve are ai)t"to count the two latter as collapse, the others as shock. In svncoi.e. shock, aiul c.llapse, there is a combination of cardio- vascular disturbance with -rave iirrest of cerebral activity. 1 he primary xascular disturbance is sometimes easily understoo. . / ''^ ,y*"'^"^'^,^ „f the splanchnic area, or even of the liver, are capable of holding a.l the blood, but thev do not onlinarily do so because ot the tone ot the abdominal walls, comi.ressing the viscvra. and the tone ot the vessel waIN bv which arteries and v.-ins are in a state ot partial contraction. If fn.m" anv cause there i- rapi.l .iilatation of the abdominal veins the blo..d in the upi.cr half of the bo.ly may gravitate there in increased am.>urt, vvith eorresi.onding an..mia of the brain. ()nc can even pro- duce 1 neonsciousness by eo:npression of both carotid arteries. Ihis abdominal vasodilatation may be cause.l by a blow upon theahdomen. which produces inhibition of th. splanchnic vasoconstri<'t..r influences, whereby the ab.l.)minal veins become dilate.l, or stimulation ot ttu' canliac inhibitorv centre (vagus) whereby the heart beat is arreste.l. One ..r both of tlu-e influences may be at work to constitute tlie ettect of the "'^.'lar plexus bl.>w," known to the prize ring, \\here by aii> „f these means there is produced merely a temporary cerebral anemia, we have the eondilion .»f .^vnc()pc. '■.■'■irmi^^-3'. PAIN 179 \Micn ail attcinpt is made to .l«-fiiic tiie condition of shock, it miist l.(. ninonilKTcd tiiat depression or cessation of fnnction is a j)roniinent t.ainrc Tins sccnis to apply t.. the individual cell; for it has been noted that drn};s like alcohol, ether, and strvchnine, administered liuring shock, are inert, although they dilfuse perfectlv; vet with nroy.Ty of the cells, the physioloj;!,,.! dicct has been seen to assert II Mil, indicatm;; that the actual metabolism of the cell was, for the tune, suspended. It has been observed, too. that in shock the specific jiravity of the blood falls, and that of the tissues rises, indicating a l..issai;e ot tissue juic.s to the l)loonted by indivi.lpal surgeons. We doubt, however "Ixilier acapnia and shock are identical and whether this diminution '" ■ :irl.on . loxide is to be encountered in all cases. The rapid on<-..me "I ' I.; cnduion in some cases is evi.Iently a reflex act, and a general ni. ilutiun ot the activity of the higher lerve centres must, in these 'l'-- at least, precede any change in the carbon dioxide content of t!i' lilood. if .loervcs to be notcl that it has been determined practicallv that !!'• conrs,- of surgical operations the exhibition of carbon (jioxide t^ the dcveloi)inent of shock, even more surelv than does Crile's •ration ol the old method of compressing the extremities and "■ >n as to bring about filling of the more central vessels. There "■k ot any evidence that in shock the arteries undergo dilatation PAIN < IS the cry of the tissues. The infant cannot explain its dis- •ts and expresse.; them I>y crying; equally the tissues have no "t expressing to the individual that something is wrong, save i)re.s,iRc of the sensation that need not be <' .fined because III Ml'! lilt I,.. m 180 TffH: MORBID AND REACTIVE PROCESSES 9 •I universally experiencvd- pain. Paradoxical as it seems, pam cannot exist in the tissues; a pain in the foot is ii ilisturhance of those nerve cells in the brain whose function is to receive stinnili conveyed to them by the afferent nerves from tl . region. In this connection we mu- . recognize two orders of tissues, irrita- tion of either of which may set up the sensation of i)ain, but in the one this process is accurately localized, while in t'.ie other the sensation is localized by the brain as originating in some other area or areas. Of the former' may be mentioned the skin, the mucous membrane of the mouMi and pharynx, the skeletal muscles, the i)criosteum, and the tunici vaginalis of the testis; of the latter, all the viscera, with the exception of the testis, or more accurately, of its serous coat. This may seem to be a sweeping and unfounded statement and one contrary to personal experience, but as a matter of fact, the individual viscera may be handled with impunity and even be cut in the unanesthetized individual without any sensation being induced. In such organs there are no sensory nerves for pain, no direct paths whereby the conscious- ness is informed of disturbance in those particular viscera. Stating this, we do not mean to indicate that pain may not originate from the viscera; every schoolboy knows a stomach-ache as a yery real thing, and undoubtedly a dull"heav> pain follows pressure or serious traction upon these yiscera. though here again we are unable to localize the pain in any particular area. At most we liave an obscure localization of something wrong inside. When, for example, the oesophagus or stomach, or the colon is overdistended, there may be painful sensa- tions behind the sternum, in the upper or lower abdominal areas respectively. u i • i. i If we analyze the pain associated with disturbances ot the^ internal yiscera, we encounter some points of remarkable interest. Take for example, the organ just noted- the stomach. An ulcer or other acute lesion of this viscus' is found to afford a pain which, if the patient be asked to localize it, is situated in the ahdominal wall in the epigastric region. We mav e\en oV)serye that if the lesion be in the cardiac part of the stomach," the i)ain is in the upper part of this region, if toward the i)vlorus in the lower, and this irrespective of the fact that th.' car.liac and pyloric regions lie somewhat transversely, rather than vertically one above the other. In addition, the patient endeavors, and if he be at all stout, endeavors in vain, to touch an area in the dorsal region between and rather below the shoulder blades; more accuruielv on cither side of the seventh and eighth dorsal yertebne. With the heart, as, for example, in angina pectoris where the pain is extreme, it is noteworthy that it is complained of as existing, not in tlie organ its.-lf but over it. There is frequently felt ;. -> a sens(' "f extreme constriction along the line of the second rib, and with tins, further, a pain extending down the inner side of the left or occasioiia y the right arm, or both, most often as far as the elbow, and occasionally as far as the little finger and the ulnar side of the ring finger. PAIN 181 It is to English-speaking observers more particularly tliat we owe tli<- study and elucidation of these so-called referred i)ains. Hilton, in his well-known lectures on "Rest and Tain," piiblishc, P''^^^^^ «' nutrition •e assimilated, and assimilatiris nmlfil hlfl. TP^' H"?'*''^ *«"^« *" .""ction is necessary as well th!! '^ *''^ ""*"*'on ««" occur. I^its, the more actiVe the absortirnf ""'''' '^' /""^*'«''> ^'tf'i" tl'e function the less the demand S • ".^ .'"at«ri«I. and the less '<'od and function are seen t^h • f'.«™''at'on. The two factors Although the subS has b^'en'ST^'^' ^"""'^ *° «"« «nothe .' ^'■"cral principles to l^remZC:r^tior'''''u''^^^^ .f'.t. inadequate nutrition or laTof ' rctj^ ff ^"'i" recapitulated; ";an.tion and shrinkage until arresf of fnn 7 """*'"" '"^>' '^"^ to tl.a^ .xce'-sive activity mav so rSv ,,1 .u ""' f.'\" ^^"t*^ ^"«"es; ■;-',tr.t.on may lead to growth and Zit' ^^^r^^"'"^^ ^>' ^^^"ate ''"^ time on a higher level f-^.'^fa^ ^"'^'^num be once more reached r-'l'" on which it w^rks w ihou ?oss' oTT " *''" ^"l'"^" '"^-««- t^e t-; between cell mass and ceU surfLe anr"'^V '^'' '^''^ '« « '•^'«- >''r ace, so that increase becomes sdfinhy. 'f'^' "'^'' «"^ »»«'«" P-l' eration occur; that grow hanfnn.T »"^J^ar " I'l'l' can occur simultaneously oXtilh?" «''^.°PP«««^ Processes, ^"-n of the cell for and th S the nl%"^''""^ ^'^ srouth and proliferativrcanaS^ht ^f ".f^M"", '^^ ^"°^*'«n J^-'ts ""t proliferate, and that the rctiVev.l^'i^'^'''^'.?^^'^'«P«d cell does «^" ti..,se that have ne^er £^^^11 Tff ''^ -"""^ "^ *h^ «'-g«n»m ''>;'.' 'li'ferentiated, ha^e reverted fl^'^^^'J'*'"*^.^^ ^'^ '^ ^^^^ have '' ^ve pass from physfoloSlo L^^^^^^^^ ^^P^- ^ at once the qLstion f'to the'^autTf r^'*\"' overgrowth. -'• .rowth originates who^ fnTh/cite ^^^^^ ^^ tiuit l!AU .,t .. 180 PhOGRKSSIVE TISSUE Clf.XNGKS '4 :J -'i cell growth, i. e., ^stimulus to jcrowtli outside the cell d(K's not exist, a fmiiit of view v.hich we cannot share. It seems lik«'Iy that ^trowth depends somewhat ujjon tension of su rnundinR cells, or In'tter that growth is restrained by the eH'eet of siirromiding cells, hut it appears that this cannot be all, for. more powerful than the restraininR effect of the surrounding cells, an external stimulns may arise that is powerful enough to more than neutralize these influences. We find that there is a c'onsid«'rablc numl)er of circumstances or combinations of circumstances tliat may lead, on the one hand, to cell overgrowth, or, on the other, to cell shrinkage and degeneration. Thus overgrowth may arise from: 1. Normal activity with increased nutrition. 2. Increased activity with iiicrease«l nutrition. :{. Ueduction in the external forces inhibiti i: diminished tissue tension. These changes in tissue we call progressive. .*>hrinkage and degeneration may arise from: 1. Normal activity with rcfluced nutrition. 2. Normal activity with pervi-rtcd nutrition, being of the wrong kind. 3. Increased stimulation or overstimulation relatively insufficient nutrition. 4. Arrest of function. 5. Increase in the external forces, arresting growth. These changes are regressive. Hut these classes do not cover all cases. It w''l be remembered that there is a group of cases in which the changes are not so evident in the protoplasm as in the paraplasm (a single example is the so- called fatty degeneration j, and since these changes are either due to or lead to regressive changes in the protoplasm, they are includeil among the regressive changes. On the other hand, there is the important series of the neoplasms in which one cannot state what is the primaiy cause of the excessive overgrowth; these are naturally included among the jjrogressive changes. the aii.;m.t i'on^: Imt scientifically it means nothing of rnuiriuon, u.e sort; the term is so widely used in f.o. eo Its generally accepted sense that it would be inadvisable for us to employ it otherwise. Kinds of Overgrowth. — !. Physio- logical Hypertrophy.— The type of this is the jiregnant uterus, which enlarges by liM>erirophy and hyperplasia. The total Mze in cubic content, of the hyjwtro- plK.-d muscle, is many times in excess <»t the normal; a great increase in blood supply also occurs, and muscular con- traction begins from an early period of pregnancy. Increased nutrition cannot 1)0 said to be the chief cause of this mergiowth, because the presence of a fibroid in the uterus for example, unac- • ompanied by any marked increase in \ascularity, may be associated with «reat hypertrophy. The excessixe de- \ eiopme.'it of muscles by exercise, as in tlie blacksmith's arm, is certainly due partly to activity, but with increased nutrition, because a muscle during exe tS.f SlT underr'"^ "TJ"''"" '^''''''^ '*• ^^^''^^' '« "«* t^e only just as ih u trthe fibr Jh"*^ 1 '^' ^T ""' ^'^'^^^^ •" ^'hich. I'cart weight is >50 to -S^l become larger than normal; the normal Longitudinal section through muscle of calf of leg in pscudohype-t-ophic paralysis. The muscle fibres exhibit atrophy; the increase in bulk is due to the eicessive development of fat cells (Orth.) PROGRESSIVE TISSUE CHANGES 188 times calle.1 compewtory. a t.-rn. M ought t h- «stnctenly a jiart be taken, the rest may proliferate and bring about regeneration; if a whole bone be removed, it is not replaced, but if the periosteum be left, a regeneration may occur. •_'. The hinlier and mure specialized the tissue, the Jess is its capaciti/ for rnjeucnitiou. A part of a nerve cell or a fibre may grow again after destruction but not the wiiole neurone. Tiic muscles regenerate, but imperfectly. Xor is it remarkable that regeneration in the higher kinds of tissue should be a difficult matter, because not one, l)ut several, orders of cell deveh)|) side b\ side, and the more rapidly develoiiiiig new-formed connective tissue, for cxamiile, is ajjt to bring ])ressiire to bear upon the new acini, or lobules, and to cause their atrophy. The salivary glands and the thyroid regen- erate moderately well by a process of budding from the duets, but mcst of tlie other coini)lex organs and glands can scarcely be said to regenerate. In tlic li\cr it is to be noted that the part most ready to proliferate is the l)ilc duct, and this is (juite in accordance with our knowledge, for we find tiiat wiicre different cells of tlic same order are differentiated to varying degrees of i)erfcctioii, the le>s differentiated arc more apt to regenerate than tlie more differentiated; in an ordinary gland, for cxaniplc. the cells in tii(> neck or in the duct are more likely to pro- liferate than those of the acinus. REGENERATION 191 3. Tulnilc's in tlic kidney, and lohnles in the liver of the adult rewner- ate only to the extent that lost cells are rei)laeed. Onlv in the verv young are there indications that new tubules or lobules mav be formed llepencrntion in the wore miiiiMr the i/oiiiifier the aiiinidl. There has been a good iiI)portive connective tissue, two kinds of tissue whose close similaritv vwn wh()se absolute identity we have previously uphehl. (Joing farther' many hold that the plasma cell also takes part in regeneration. There are several .liHerent cells found wandering in the tissues winch Ma.ximow includes under the term polyblast, and fV.llowing Ins observations, there is an increasing tendencv to believe that all ■-iicli cells, having a round or oval nucleus, as distinguished from those liiiving a i)artite nucleus (polynuclears and eosinophilcs) mav take p;irt m tissue upbuilding. Elastic Connective Tissue.— Thvrc is no (lou})t that elastic tissue ngenerates. It is to be found, newborn, in areas of new connective n^sue, and m such places as the intima of arteries; but we have not >.t settled what kind of tissue gives rise to it, nor do wc think it likelv t lilt Its origin is different from that of the white comiective-tissu"e li Tc. i! IS to be kept in mind that elastin, the component of the 'l.istic-tissiK hbre, is a relatively inert protein differing but slightlv !'"iii the more active albumins of the -upimrtive cell. Fatty Tissue. — It is uncertain whether we should speak of the y -.ncration of fatty tissue, because wc are not vet certain if fatty 'i -lie IS a distinct entity or is a modification of connective tissue- re IS much evidence in favor of the belief that it is not a distinct '^ ne. AMiat is the fat cell? It is chiefly considered to be a connec- ti .-tissue cell, or a number of connective-tissue cells, which have "' tiphed in the neighborhoo.l of a capillary; in the cvtof.lasm of -: li cells fat droplets appear, fuse, and push the nucleiis'to one side '; !l we see histologically, the huge fat droplet, surrounded bv t ' rane, which shows at some part of its circumference "" ■i.itteued nucleus, representing the seal in a signet ring looked at 192 PROaRESSlVE TISSUE CIIASCES from the broad side. Some ^yX^l'^^^^^^^^^^^' smaller cells, and in places where t^f/f/;;, f 'iy ,,v'^^,f the difHculty times see a nun.her ot closely at,'prej^i. ^.^^'^^ ^^^^ f,t cell as growth IS slow. Un> occurs in i\m n ' „,.,-,...,ti„„ direct from the (1) perichondrial regeneration, and (J) regtn.r.itu.u aspect of the perichondrium, and these ^f^J^^^^' iColdct. which in their forms of r.gcneratum. '^^»^^"J" ;'^,,,,,,^., , ,.,,.,. reniarkahl." REGENERATION 193 tlio entire process of growth; all these forces which are thus seen to Imilil uj) the bone in the first i)lace, take part in regeneration after injury or destruction. Periosteal Regeneration- X.-is of bone denuded of their periosteum have been seen to obtain a new layer by continuity from the adjacent P' riosteum; mere stripping of the periosteum from the bone does not necessarily render the bone liable to necrosis. When periosteum regen- erates, it occurs firmly attached to the bone, and separated from the n\erlying coimective tissue; the direction of the fibres, too, suggests that the growth is from the periphery of the area destroyed. The Jiegeneralinn of Meditlla.—lujuTy to the marrow cells is quickly followed by the ii ual degenerative changes, which quickly give place to mitosis and proliferation; equally readily the connective tissue around the capillaries begins its proliferation at the margin of the injury, whence fibroblasts are pushed into the injured area. It is remarkable, however, that there is little migration of leukocytes; new (■aj)illaries form and a new fibrillar network pervades the area of injury, in the meshes of which are the constantly increasing yoimg marrow cells. Pieces of injured bone are seen surrounded by osteo- clastic giant cells. The Healing of Fractures. — It is scarcely necessary to deal here with the mode of repair in bone because this is so fully considered in works upon surgery, but it may be noted that considerable variation in the process occurs, dei)ending on whether the apposition is good, and tlie nutrition of both fragme.its preserved. The more perfect the :il)positi()n, the quicker is the repair; the greater the amount of riding of one fragment upon the other, the greater the irritation, the exuda- I i( III and the callus. A poor blood supply will mean a delayed or arrested union. The callus forms as follows: (/() Hemorrhage and exudation around the fracture, with coagula- tion. (/)) Invasion of the coagulum by cells — polynuclear from the sur- ronnding soft tissues, fibroblastic from the periosteum and marrow. I') Absorption of the fibrin and replacement of the clot by tissue fiiini the periosteum and medulla, which iV/) becomes converted into cartilage, a step that may be lacking if the callus is small. (' ) Then begins the process of laying down the osteoid tissue with 't' pn-it of calcareous salts in the matrix, either with or without the |r. liniinary intervention of cartilage, the subsequent absorption of the - nic and its replacement by lamellar bone. In the lapse of time, the ' M ( ss of bone is removed, and the callus remains just suificiently strong Tm Mciire stability of the part. Regeneration of Lymphoid Tissue.— The specific cell of lymphoid '-III' is the lymphocyte, which is constantly regenerating, and the Mijiiortive structure is made up of the comparatively unspecialized 1' luhun, which we have indicated as the most readily proliferated 194 PRoanEssivE tissue changes of all tissues New Ivn.pl. nodes npp.ar in various sifs in the sub- ;^^on;S ttue uhere il.ey have n..t '-" J'-'^ >; -;'^-^- his is doubtless .Ine to lyn.phoevtes eounn^ ■'';-^., *^\ ^.^'^ £ as regards food supi'ly, to their ,.rolileration ..r pe uips to a su.u en acSn of ..owtll on the part of lyn.phat.e 1,>sue that has been ^""J*;^;:.;;!"^' Our ideas of the U-nk.-eytes ten.l to the supposition, tlu^t tl.^f tm^^re.' erate; they ari.. in bon. n.arrow fron. the niyeh.cyte, t n e a le then.s .h es to institute any process ot repro.luet.on, and t ei enranee in nun.bers apparently ,rc-ater tlum v.sual m ?hc bloo not aUvavs or necessarily due to increased rt1»roduet.on. but iTv be lue to a dilVcrent .listribution of K.-koeytes a.ready u. lltZZ The production of ,.ew leukocytes .s a process tha |;oe^ on coust'ant throughout life under physiolo.trical stuuuh, and thus can scarce V be properlv in.ludcd au.on, patholo;.u-al regenerations. ''Lgenerln oi^Blood-vascular Tissue.- In the -'';>;;' '.^.f-.^, methods bv ^vhich new vascular tissue can arise: (1) in intraallular for no. of ul chann.ls, by which cells hoUow out and ,ive rise rheir interior to blo..d corpuscles, the spaces later luroni.ngeon- Ltel (Ta pn.eess ..f bud.liu,. in which certain endothelial cells of eaSh n wall pve <.tf Ion, protoplasmic- pn.crsses, withou nude,, S- connect one capillary with another; these processes hollcm out and 1 passes into aid thn.i.t:!, the process; ultunately nntos, Jlu oi.'inn end..theHal cell occurs an.l the new nucleus Passes in t wail of the tube ^vh..n;Ws the <.^^ n'^i;ron:ti::i: :tl it'-rb;.;:. -llready ..escribed in the process of vascularization of granulation tissue (see p. \-M. Regeneration of the Mother Cells of Red-blood Corpuscles. 1 he re - l,l,^T™cles arise from muleated. lH.no,lobin-.-on ami.g c 1 s e b r marrow, the hematoblasts. Whether these hemafblasts "n- bl t a ise from prcformc.l hciuatoblast> a true re,enerat,on-- is d ibtt^ul- it is more likely that, un.lcr the stimulus ot neec.Mt> S. e n^'be an h.creascd produ.tion of hematoblasts tnnnj.s d tU. entiated "mother , in the .picen and. it may be. the lymph or hem..lymph no.les. ^Regeneration of EpitheUum. Kpithehum can re,.nerate and m v epitheUum arises onl> from pre-exi^teiit ^'l»tl-{'>' ' ; ^ /^^^^^^^^^ .icention in which epithelium appear, in the midst o -ranulation tiss u \^^M bv aeJidental trans,.lantation of I'P" -'•!'"';, ^ '^^ , ncii tcHce ..f epithelial elements deep down, as in the depths of a lia fol de \notler apparent exception oc.-urs in ,d,omata-^new gnnvtl Sfmm he supportive tissue of the nervous system- in wh h 'c^^ coi to be lined by a regular layer of rather c-..lumnar cells, U is no rr ain that this is tnu- epithelium, f..r one searches m am orU^nnent membrau... the c.l!. lying do.-ly upon tl- - inml^j ndividuals of the next laxcr. Were it proved, however, to bt true r- y'*r..^:ii^ mamemt:' REGENERATION 195 I'IG. HI ^^■:<- :i-itli(>liiim, it would not jtovc the origin of cells of one order from Inrehciirs of another order, for the ^va is of epiMastic origin. The epitheliinn, like the endothelium of bloodvessels and serous • Mvities, ean regenerate compl.^tely. If the epith.lium of the skin he im.ken, the lower layers (not the keratiniz-d cells, which are inert l-ccanse deg(>n«Tated) become active, and these cell?, her .minp rionpted, slide over one another, still preserving protoplasmic con- nection, until they form a soinev hat flat skin over the demided surface the new skin forming at the expense of the old, whicii can be seen f. he thinner than normal at ilie edge o.' the injurv. INIitosis quicklv I'lgiiis in these flattened cells. There i- as yet no basement membrane, but this is soon supplied, evidently by tlie fusion of fibrils from the uiider- i>iiig connective tissue. I'ntil this I'liniis tiiere is free passage of leii:.o- iMcs through the superficial cells, and cxen ph.igocytosi.s of leukocytes l>> file ei)ith(iiiim. Ihiirs, swt-at, and sebaceous glamls may grow again if their deeper parts lia\c lint been destroyed, and it is ■^t(•^(•■^tillgto note that in such cases iImtc is sometimes .i downward -inwth of the superficial epithelium t' meet them, an observation that -iiuiicsts that tissues of the same iianirc iiave a reciprocal attraction i"i nn(' another. If the root bed of 'ill' liair be destroyed there is no n -cneratioii; and the same is true "I the nail bed in the fingers, although tiii^ extends l)ack farther than is commonly supposed, and a portion "j It being left accounts for the appearance of a nai: after a terminal I'lialaiix has been removed. This can scarcely account for the appear- i ' <■ .,t a new nail- or an attempt at such- when two phalanges ha\e regeneration necessary in the uterus after menstruation, •- '■-'•r t:w i>!;ieriital site after purturilion, is said to be assisted bv I'-Tsistence of the remains of the deeper portions of mucous glands. "rsi'iiilii-epithfliiiiii." or si'coiulary cpithc- liuiii without busiinent mpmbranc lining a cyst in a glioma, formed by moditiiatioii of the suiKTlicial inyc-r of glioma fells. (Saxer.) t^m-rt- PROGRESSIVE TISSUE CHANGES [if m 196 « w«j«th«Umii —In r wav similar to that seen in epi- Regeneration «*, ^'^''^f ^^^ "mI of "translation and proliferation thelium, endothelium b> a "f '^'^ '\ \ ^i,^;,, „r tin- cells of a quiekly covers over ^ demuled a v c en hbrn^ ^^ ^^^^^^^^ ^^^ .^ new growth t'';"^!^'""*^'^ ^I^'.^t H^"- ^"^'^""^ ^''''' ^'"" '^-^' The view usually acceptc^d s. hat m ^^^^^^ ^^^^^.^^ existing superficial ,'^"[''f ^^'T' ^fiSalts and connective tissue, existing between endotheha '^;"^,.'^'";^7;^^^^^^^^^ area may arise V::trZ:^tZ^^ as endothelium has l:;;;S:.t5^^Htto,n..er^n^^^^^^^ ,, , , Regeneration 01 G^^d. \f\ [J, structure, such as the regeneration. 1 u »'''";' /'^'tj,, ^ uterine and salivary glands, Lieberkuhnian follicles of the »"t^f "^ '"^ complex gl?nds the ducts ao present --^^^-^^^l^^'^^^^ ^'"^ ^'^^ °^^'"^"; are mainly or entire > the source j ,^„d, have a great Se'rrXrt r „ oTthe'» co„,pa„M,. ..e„e..io„ .. .he supportive structures which e«'"P'^'' *j;Tin the laboratory by chloro- JTver.-Where, as in poisonmg ^";"™'/;he fiver cdbS the centre form, there is induced a state ot "^"^'"^ . " ^J''^'^^^^^^^^^ of of a lobule, regeneration «-'-,^^ '.^^^ i^^ ith ^^^^^^^ g-wth the more peripheral cells, ''"'/ ^ ^^.4",;' ^^e cells have disappeared, so come to occupy th^^^P»/'^^^;";^^X'eNm^^^ comy^lete regeneration, that in the course "^ ^/T ^ .^^^ V' ^'^ Sgone n- rosis from one or So also, where ^•^^^P'^^*'^^^"^"'^^ '^^^ V'^^^^^^ of new buds or other cause, there has been •^^-f^-'^^j^JM^^^^^ the framework of S r£rr;Sl:t rr^-^ at most, the remaining liver tissue exhibits some hyP^'-t'-^Phy- -.^^^^^^ ^av be rerlothed i,„,«tect an,l . .h»"t 'l"f ■™„,''l!V.3il.d tubules appear injuml, but ,„ *«JI'Sev it n, to contain more than the nonn.l :°ES'^:;p: i-.l'S/'netti.e corte. a,e »nsi„eted to be the of the view that regeneration d"^^ "^^ *X thrn^^^^ mueoseeand ..rr.Trrr^ii'-^^^p-ri-i-o-, «„.. >« »... animals, new fibres have been seen to form. REGENERATION m striated Muscle.- If the substance of a muscle fibre be partly de- stroyed but the sarcoleama sheath left, a complete regeneration may .Kcur; but where there is actual injury wrought to the fibres, these rontract away from one another, and the regeneration of the inter- l.l.rillar connective tissue tends to check the regeneration of the injurert of the muscle, and gradually become first longitudinally then transversely striated; the old sarcolemma sheath ....mes absorbed •' - i new one appears. When the sarcolemma is ruptured, as in a cu or a laceration, the capillaries are also ruptured and the picture 198 rROGRF.SSIVE TISSl'h: CHASCES III % ..f.w..,l Tl... riii)ture«l fibres contraot into clumps, eSt; Jll^munlHT of nudoi hecon..s ro.hu.e.l, the eyto,.las,u .n.-reuM.. '^C:;:;S:'of ' N:^^^si;r''i;^o,Ua. -TI. neuroglial ti^ue Is pSSat t is a eounective tissue au.l yet s of epiLlastw on«.u ;:];;;tfaet .. eloseU- rolatea to „en. ^^^ r.^-^l/'lt^-eS f u't^rSl^gSa'E:::^. u tl^ llJXre is no .louht ti.at .iial S ^euetra ana Su-v^^r^^ able to for.u not only tunu.rs hut rep aee- m^t^^'isln L cas. of loss of ,».rve eells. ^<7- V^^ fm. 'Ion thouKht thev have seen them RivinR rise to eel Is wh.di take the urn t of mivl. cells, but this can be deternjine.l only u. the very >oun, an.l even then seems to oiler ground for doubt. Nem CeUs-It mav be definitely state.1 that the nc-rye-eell bodx a preSs?rng axis c>'inder, and then only when u. connection ^Mth a '"S?nerve1bre ..r its axis cvlin.ler be severed there is .legeneration ^|;:.:SLd^erian degeneration- distalw^n^ltl...^ axis evlinder, and on the proxunal side, as ''^V fl,!t itthe esult nt tlie iierve-ocU bodv, ami tlic pruxinial portiun iil the aMmi. leu i : Lt„ ;ra ■ ...., ■,« *!,» dU,.! ,»« .,t a e t4ted through the fibrous connect.ve-t.ssue "^i^^m i>f mdi^irt^::^^':^^^ --^ --^'^v -'-"i-r Ncry "^'^^V ;.,-'. .j,„, ,n„ltiplvinj; close underneath the shear i.. ''lf"rlSre be hJuJed Jhe ^is iiindtr stains imperfectly, becomes .^■n- mf GRAFTING OR THANSl'LASTATIOX 199 fihrilliitcl and (lisitit(Kniti-<.ine sort be placed between the two ends; sudi a guide may be a liollow piece of bone or a bundle of catgut threads. In spite of" a con- Mderabie distance between thf^ two ends and the piling up of .scar ti.ssue a> an obstacle \ery remarkable regenerati(.n of ixripheral nerves has M.curreIiow a great readi- ng- for growth if they are grafted; with the w aim-blooded animals, n-uevcr, this is by no means the ca.sc. One niav make a general state- iiM lit to the efi'ect that immediately after grafting the tissue inserted n.ay gn)w, yet in a comi)aratively short time die planted tissue becomes ii'-orbcd and a cicatrix alone may remain, although sometimes the uritt forms a framework upon which the regenerated tissue fills in the a:- 11. Even in this short i)criod of growth after transplantation it is "Mm notable that the proliferation of the transjjlanted tissue occurs ilnMiigh g. derations of cells that gradually become less and less specific. 1 Mrcsserl in other words, there is at once a reversion in the type of '! ' '(lis transi)lanted. Considering this fact one would naturallv con- ' ;; that if embryonic vegetative tissues were taken in the first place, t! implantation would be much more likely to succeed, and such is v^ijqrjw-r-^-^^ 200 PROGRESSIVE TISSUE CHANCES \ii the case. But even in these oases, as where portions of ^^h'^k ^'J' "iSX the t™"pla".o;?'" Pf »' *', ?," MalSan lav.; are ,»n to Aow mitosi« K^;,ysp"":,itt.inla^ent.e„.a.^^^^ j^,, ,.av™« actually a^^^^^^ ESiS€b?:t"'^rE;;:T:;e^tJj3^ ORAFTINO OR TRANSPLANTATION •^01 hut subsectuently will bocomo piRtiiented. This may mean that there is a siihscquftit r«i»liRfmt'nt of tlie graft, piecfmeft'i, by cells derived from the orijriiial epithtlinm c.f tlie host, that is, that the permaiieiur of the graft is only ajjpareiit and not real. In support of tliis it may l)f said that in no j-«se is the skin of another speeies successfully jcrufted on man; nevertheless, the mere presence of an animal graft seems to stimulate the skin cells of man, causing them to spread more rapidix than usual over the denuded surface. This may be another instance of that i)henomenon to which we have previously referre* I, namelv , that cells of like order attract one another; that is, that the presence of epithelial cells in the centre of a denuded area by homotropism attract the epith«'lial cells of the host around the edge of the denudcfl area. It may be that the diffused prwlucts of activity of the graftet,ite of affairs is found in the implantation of bone, sterilized bone or ii( calcified bone; such l)one, like any other porous material, is merely M framework which fulfils the functions that the fibrin fulfils in the I'liKid clot with tile additional quality of rigidity and consequent pre- ir\ ation of the contour of the part. Transplantation of Periosteum and Perichondrium.— Osteoplastic traiisi)laiitation of these is very successful, especially if the periosteum lie retransplanted upon an old bone, or into an area where bone has • xisted. Even isoplastic transplantation may be successful, but it i> notable that in any experiment a good many of the periosteal oells 'iia,\ (lie, the burilen of proliferation remaining upon those that survive. riie bone marrow lends itself perfectly well to autoplastic transplan- i.ition, giving rise in its new site {e. g., experimentally, the anterior < liamber of the eye or the abdomen) to true bone. In 2„2 I'Ronnnssivh: rissvt: ciiasges " iran.pUnUtion of V.s..ls. ,•;« ^W Ut f.^^ y;;^ ^it.; i;^.- short leM,tl.s ..f art.m.s or v..... n ^ \ ,„ ' ,,,,r, ,1.,. otlKT an»-iit:.. NMh" / " ' "^-i , ,„.,,, ,„.r,Uteut vitality ami ..(uration has lu-eii 'V'*''1'^'^^'^'. , ;, ' .1 iM.rtu.ns of tl»- auto- ,:,,. ,rovvtl, ..f the .ntro.hur.l »';;";^ ,';;/;; .*X,w prom.un wiy.anlr\ ol » arrti m u« i"' i ., ,. itli ^iii-c«'ss hut fvni orpins Not only ha. la- transplant.;.' tn.h -[;;;;; 'i'Vir'^ular an^to- that have- iK-en pn-sorvnl tor '';=''>' 'J ^f'.^, that snc.rss has METAPLASIA AND HETEROPLASIA IS an a.lapta ion on tlu part oi ( n ...-ucrsion <.f or.h- a c.on>tant phvMo ..Kual I''••'^•^•7^"^ ?; '^^ . ;'^\,,.. transformation Han .on.a..t.v..-t.s.u- "-l';;- ';; ^^ ; ,r D.^into hony .••■lis an.l f"'t t '■' Va L;:i:.^ > ''-''^^ <-tain ri.i.l la..; epithelial hoi.y tisMU . \ tt "'y-' "• ,'• , ,. „f ..pithi'lial tissue, nieso- tissue can he .-onverte.l onl> mtu otlu ^^ , , ' ; Kpitheliuin an.! ,,,as,ie ti»n.- ..nly .nt.> other f..nn. »^.;-^'^^. J ' i,.t,, ,„„.. or .lan.l cells tor eNa.nple, can ^^^']\''^^^^^Zn .A on. U.vm .>i cartilage, or vice ver.a; an.l j^'''; ',,';, .''^;'"t.e ^aps ar.- hri.l,.-.l. ^"'••^'''■'''"" '''\ "'u; r^ hn,; : :;;t . i-u i- ri".- 1., ......ipiex "r Y ""'tlW r e ; ;.ati.>n of hair roots. Fihr.>us .•....- !;l:;:;t ;^i i:.!! ;.-; ..een .... t.. ..han.e into nnisele, str.ate.l or non-striatcl. . . . , ren.lere.1 function- Ifflf^ METAPLASIA ASD IIKTKROPLASIA 2(Ki (1) tliiit tin- hoiH' foriiintioii is dur to tniMliticd function iid nutrition of ctTtain clioroidal (•••lis; tln'so (tIIs Imvi- normally a drli. itc fnnrtion conticctni with tlio n. tivinj; of li>;|it Uy tlic ryo; this function ' "itif; intt'rru|itt'(|, tin- vascularity (»f the choroid is in;ivc tlicnisclvrs omt to the prcMluction of hone; i'2) that in the process of formation of the eye u few cells destined to form hone, lieinj; accidentally carried into the eye, remain latent so loriK as the eye performs its proper functions, becoming active when these functions are interfered with; (.'{) hone-forminR cells arc carried to the part l>y the blood. The rcinarkHblc fre(|ueiicy with which this bone formation wcurs in tin- choroid of eyes which have been rendered useless by injury is strangely op|>osed to the two latter hypotheses. Hefore discussing metaplasia specifically, it is necessary to separate one or two conditions which arc not true metaplasia, but which might be confounded with it. The first of these is heterotopia, which may be congenital or acquired and consists of the abnormal snaring of cells of an wrgan from the organ proi)er, and their siibse(|uent growth in another place. Kxamplcs of the congenital form are the various cell rents of Cohnhciin, aberrant adrenals and accessory spleens; examples of the ;i((|uired forms are periosteal and bony growths from displaced perios- tiuni. It is to be noted that in none of these cases is there tissue transformation, for the tissue continues to grov along the ordinary lines; further, one sees the same process in the invasion of one tissue into the territory of another, in such a case as where, after tracheotomy, tiie epidermis may not only cover tlu; wound but grow some little distance into the trachea. Heteroplasia. -This is the condition in whicli we find in the middle of the (esophagus normally lined by squamous epithelium, islands of cohmmar epithelium like that of the stomach. No -Mnvcrsion has occurred from one ty|)e of ci)ithelium into th(> other, but lere is merely ii persistence of niisplac-d and ordained tissue. The same explanation 1m 'Ids for the occasionu' islamls of squamous epithelium found in the n spiratory passages, and the stomach, without any evidence of past iiidanimation which might accoimt for the change. Anaplasia or Reversionary Atronhy ("Undiflerentiation").— To be • listinguished from metaplasia is tne loss of diflerential characters by nils which h.'ve become subject to abnormal conditions, for example, the simplification of the tubular cells of the kidney in nephritis, or the ubical form of the lining cells of the pulmonary alveoli in interstitial |'iieu...oiiia. The same jirocess is illustrated by the development of !iHK(iid tissue in the adult body, for mucoid tissue developmentally ;- iiii intermediate stage in the growth of another mesoblastic tissue. A similar process is the morf)li(>logical cha..,;e of cells due to mechanical " tion, c. .y., the flattening of a cubio] or cylindrical epithelium in a : -t on account of the pressure of ito contents. Af n we must not •iiftiiuid with true metaplasia the ditferentiation of a tissue under ' i'ldified environment without any change in the function, as occurs, F.'-i--a-,^^<-'-. 204 PROGRESSIVE TISSUE CHANGES m for exiiniplr, in the coniification of the rpitlu'liuin of the prolapsed vagina. Metaplasia, in oi)p()sition to this, comprise hoth a inori)ho- lo;;ieal ami a functional ehanfje. Epithelial Metaplasia. The nnicous nienihrane of the uterus is a coluuiiiar epithelium; if the or^'an he everted so that it projects from the vagina, its muco'^a becomes smooth and dry, and in place of the columnar there is a stratified squamous einthelium with horny change of the external laxers. Here, it will ho observed, there is a change of function as well as of structure. In the bladder we find changes of two sorts; normally it is lined by polygonal epithelium in several layers. We may find over an enlarged prostate, as a result of inflammation, areas of typical squamous epiderm, with prickle cells, or, on the other hand, we may find jjapillomas de\cloped with epithelium that is now distinctly columnar. Fill. 03 Stiiges in Uie nielapliistic r<>gcni>r;ition or furrnnlion of u new Ions from the iria, 'n the larval newt: 1, ed^e of iris lincominK swollen, 2, :!, 1, progrosaive overgrowth of the edge; 5. separation of the hypertrophicd in;i»3 of cells to form the len.i. (.Kischcl.) In cases of ecto])ia vesica- simpli' glandular crypts may form from what was a ■.! any layered epithelium. Kveii more remarkable is the metaplasia observed in the regeneration of the lens. In the larval newt, if the lens be extirpated, a new lens may be ileveloped from the iris, as will be readil.N- understood from Fig. (')'■'>. This is not very remarkable when we reineiiiber tiiat the normal lens and the iris though differently formed are both epii)lastic. Mesoblastic Metaplasia. Here may be seen the metaplastic forma- tion of bone from cartilage, as occurs in the tracheal cartilages in advanc- ing age, the one tissue being merely converted into the other. A similar process is the replacement of cartilage by bone in the callus of a fracture. A more striking exanii)le is the forniation of bone by metai)lasia of con- nrclive tissue (Fig. (m), as occurs in the formation of masses of true bone in the lung, or of plates of true bone ir old pleural and pericardial =1^.. -v^i. n:.' METAPLASIA AND HRTEROPLASIA 205 adhesions, whcrt. tlicro has Ihti, an excessive formation of granula- tion tissue. Hoth hone and eartilage further have been met with in Kki. ti-J ••■•Nv^;^.=^:5.1 Me„„.la»i,. fr„n. a cu.„. „f ...,„pi,. „f ,..., l.l.,l,|,.r; the ordinary gratified .pithulium bee replaced hy a columnar epitlieliiim. (Afler Knderlenj Via. 05 " ^ciis nM'ta|)Ia.-.ia in il.n wall of a br.iMclui.s (s„.ralled "oHleoni-i"!- n .,„„„.„■ t. v, . ..;uo„^ ..nd. .. cartilage; c, eonnec.ve ti.ue; , , r^^l^^lL : r^Zli; ^T::: ^l'- nrt.Tial XV.!! .^d in the thi.luned valves of c-lironi.- en.ioeaniitis. ''•' '"'■t'"^'" •'•XH'i'J'''^ l^e necessary it exists in the replacement by 206 PROGRESSIVE TISSUE CHANGES 1- bone of the toiidons of orifjiii or insertion of the muscle, ns in the so- called "rider's bone" of cavalrymen. This is purely local, but the same process is probably at work in the production of that remark- able condition mistakenly called myositis ossificans, in which the tendons and bodies of one set of nnisclcs after another become replaced by bone until finally the patient is unable to mo\e his limbs, rotate his head, or bend his back. As has been referred to above, the devdoiiment of the provisional callus of long bones after fracture is an example of cartila<,'inous meta- plasia, and the same is seen in the occasional islands of cartila<:e found in new growth derived from the connective tissue, esju'cially in the mixed tumors of the parotid and the testis. Wa are fully aware that this is generally ascribed to the presence of cell rests, but there seems no reason to separate it from other cases of metaplasia. Hitherto the examples given have dealt with the metaplasia of less specializi 1 into more specializerl liissues, but the reverse occurs, as when in an inflammation of the joint with immobilization, the cartilages disapi)ear from the joint surfaces and are replaced by fibrous connec- tive tissue. This is not a purely tlegenerative change, because inactivity of the joint would tend to atrophy, but results from a change of function, the immobility of the joint doing away with the necessity for cartilage. In true metaplasia, finally, we have no new process, because bone arises first in the fa'tus from mesoblastic cells; even in the ])eriostenm of the adult the future bone corpuscles may be indistinguishable from fibroblasts and in delayed union they may actually be con^•e^ted into connective-tissue cells. In foetal life it is their environment and rela- tionship to the vessels which lead certain mesenchyme cells to become osteoblasts and mo '•row cells. Why may not the same reason be in existence later? A 'ifficulty does present itself in the idea of fully formed cells of one order becoming directly converted into cells of a difl'erent type, but this does not happen; metaj)lasia is not direct, but can be brought about only by a preliminary reversion to a vegetati\e type of cell, or, where mother cells are present, by the development of cells modified by environment. When we speak of the direct conver- sion of cartilage into bone cells we mean that in these histologically simple cells there is at least a functional change; that this is not merely a supposition is shown by the change in the matrix which they govern, and by its exhibiting a regressive modification. THE NEOPLASMS Tiie term "tumor" is i)roperly applied to any unusual swelling in the body, and includes (1) dislocated parts; (2) collections of fluid or gas; (3) tissue growths, either physiological, as the pregnant uterus, or hypertrophic, and others "-iich; ohvinu'^ly, then, it can b.-ive no useful specific meaning applicable to the class of growth we wish to describe, v«r'^m-:^9m^i?fP!'jmiKa^B!mafi:!3^mm n^^xl^^^^SrvS^ THE TERATOMAS 207 a class which Thoina called the "autonomous tumors," that is, tumors winc-h are, or possess a law unto themselves. These are now generally named the neoplasms, or new growths, and the process b\- which they arise is known as neoplasia. But even these terms are not" satisfactory, since there may be new growth set up hy known agents. The tubercle! for example, is an inflammatory neoplasm due to the action of the Ij' tuberculosis. Despite these limitations it is usual to emplox- the term 'neoplasm" to indicate the autonomous tumors and "infl'ammatorv neoplasm" to indicate tumors due to the action of known agents, and in the following pages we shall fall in with custom. The neoplasms proper, therefore, are to be distinguished from inflammatory neoplasms l)y this autonomy, by their growth indei)en(lent of function and of the needs of the organism in which they grow and from which thev derive tiieir nourishment, and by the fact of their arising independentiv of any known stimulus. In the matter of terminologv we emplov the suffix -oma which cannot be exactly translated, but which col.ven- tioi.,.ily carries with it the idea f)f a swelling, and more specificallv, ot a swelling of the above-described neoplastic nature, although excejv tK.ns occur m the case of such words as hematoma. With more i)ro- priety than m the last named, the termination bears some of its full meaning in terms like granuloma and tuberculoma, for these are " tumors of granulation tissue" and "of tuberculous tissue" respectively. To gain an idea of what neoplasms are, it is by no means a bad' method to read over some of the various definitions that exist. Cohnheim 'l«s(Tibed neoplasms as "circumscribed atypical productions of tissue ' -"n ' f ■ •.< ■ „ ^■'"'"■>'0"'^' elements," stating thus that thev arise essen- tially from cell rests," an idea largely given iipat the present dav. Ziegler -tiites that a tumor is a new formation of tissue, possessing an atypical stnutiire, not exercising any useful function, and pre-r-ting no tvpical Innit of growth"; Lubarsch counted them to be "gro^^ i i ^ of apparentiv ^dependent origin, histologically correspoufling with the cells of th'e matrix from which they arise, but atypical in form . . "-von un.meisch characterize- ussiMl m series down to the case in which, of two individuals from k'^ll^i 208 PROGRESSIVE TISSUE CHASGES .1 4- 1 1 - ,.f t]>.. two hecoiiifs inf(>l»l»';,, ,,„t the parasite, l lie tiraioma i> m" _ i\.:.t„nl ,,( another itidividnal .hat kiiKls of eell in the hcnly m ;^ ;'^ ' -'^^^^^; ^ individual. Piviii, rise to all the "- ^-^^^ ,"^' i^^^^u ,„„ i,„e ean .lo this, At first jilance one would sa> that the » t'l/ ^ ,,„ ;, i,,,,. hut totipotentiahty is more V^t^"";'\f,;3i' „, that is. one that ean they remain in eonnee ion ^^.th ^'h ^ ^ ^^^^ "j -^ ,,^. forenumers taiuingno yolk); (4) the Kn-rmuial h as ni r l at . ^^^^^^^^^^^^ of the ova an.l spermatozoa, and U)) th« '"« '" ^^ , ' ^,^ ,^,,„,. after fertilization ^^e ^^^^ ^;^^:;^^;^^\Z.M: . t^r.- ^^"'"^ *" ^^'^•'"^S' .^m'ii "u. ;H^^ n;":f whieli have already toma can arise; the torms t h.it tan ar j. ^ ...nmiial been ,lealt with. "- '^ i;"^^ ^;,, ^^^ ' " ,^ monsters one of areas on one germinal xesicl , gum, nt i . , , ^o) The whieh undergoes inelus.on ,n ^.e ;^ -^ ^ "rwhieh become prod.etiou of ex-ess or inisi.laeed ^''^M <^^ "J' ^^ ^^ , ^^ , ..^Iv and inehule.! in the growi^ig "»>'^"1""V' :' i"^ 6 .« i .'/'. or may grow elaborately, giving "-;^-;;; '^ ;;^ ^ Sv Mo.l^^d inclu- d^^f^ihi^i-^d^^^^^^^^^^^^^^^ THE TERATOMAS 209 liinl)s, or sexual organs project from the mouth; less curious are those where projects a mere mass of flesh in whicli can he distinguished tissues of the various kinds that are ordinarily derived from all three layers of tlie emhrvo—the most common form of epignathus. Sometimes there is merelv a tun)or of the roof of the mouth, in which the tissues are simpler," and do not represent all three of the primitive layers. This last may have arisen not from totipotential cells separated at an early >taf;e, hut from nHiltii)()tential cells separated at a later period. Teratomas of the Genital Glands and Sporadic Teratomas.— 'Phis class comprises s(mie cases that are clinically very curious. Tlie cases mentioned ahove of cysts containing hair, teeth, etc.. hem); found ill the .)\arv, are surpassed hy the discovery of similar tissues in the testis of the male. Of such neoplasms we find thiit some grow in parts of the body hearing no relationship to the fissures or to the poles of the body, or to the generative ghnds, as, for example, in the neck, tlic anterior mediastinum, the abdomen, and elsewhere. No rule can l)c laid down for these, and we are able to say only that there must liave been a development of displaced totipotential cells. These teratomas called spomdircmhniomax—i-onsx^X generally of tissues from all three germinal layers; sometimes the tissues are of adult appearatice iind of limited growth, and these are called typical; more frequently, however, thev are atypical, appear about puberty, grow rapidly, and tciiil to form "secondaries. This, it will be noted, is exactly parallel to the occurrence of benign and malignant l)lastomas to be hereafter men- tidiied. Sometimes a tissue in a typical teratoma of this sort will begin I,, grow inordinately, the result being a neoplastic growth in a neo- plasm (tumor in tumore). A tumor of this order may give rise to distant metastases in the body of the host. Most commonly teratomas are found in the ovary, and are of two Inrins: (1) the large-cystic teratoma, commonly called the "ovarian dermoid," and (2) the "solid or small-cystic teratoma. The former is I lie commoner and may attain the size of several inches in diameter; its contents are fatty (Icbris and long hairs lying in a varying amount of fluid. It is lined by squamous epithelium with sebaceous and sweat laiiils, with bone frequentlv to be found in the walls and an area which ha> been called the "island," representing the head; from the island arises the tuft of hairs (in our experience, always red), and m it may !ir I. one in which are fastened teeth. In a small number of cases the . Atremities and genitalia have been recognized. T\ pical ovarian tera- t.mias of this kind may be found in young children. The solid ovarian n ratoma is like the sporadic teratojias already spoken of, and is very ■iHoinmon. With regard to teratomas of the testis, it remains to be said only 'lat the so-called mixed tumors of the testis have frequently been imd to V -long to this class, and close study is apt to reveal tissues ■ ' i:-rniinal areas. These are evint!y the product of totipoten- oio I'KOf!riF^t ^^f;!^:Z:t^Z i, them .1.. net rq^rpent all thm- g^^rmm^^^^^^^^ ^^^ ^^^^ ^^ ,nost striking exampes ot ^^^ ™'J^ \^ '^^^ one mentions them. A very fam.har ^7"J^\ . "^!,^^J^'^VSf have been noted so fre- the so^alled " sarcomas of the lodne , ^ ^ . , ;„ „i^,a „ucntly, growing to large f i;/" ^^^ Jt^^^^ „\ the IxhIv one must ;Xti;e £ai='^- rr^S -h a tumor only tissues I-Ki. 06 , . ' .. „t ,h.- ki,ln..x »l.nwi,.« Blan.1 tt.l.ulos ,i.l. st.rrnundinK surt-n.u-Uke Socti.m ..f a •■ ."ixptl tun.nr .if th. ki.lm x . n s (Kibbert.) sueh a. „%ht ,h.veh.„ ..an the "'f-' -;*,;li*^":?IU'^vh» we n,™n that jnst "» *;;,';';^^;1T;S«^^^^^^^^^^ «< *e W'«>. " eve rise to various structures in tit iuik . ^ 'impossible to find in a renal mixe.1 t""--; ^ ^'^j,^^^ potentially represente.1 in the myotonu. ^ '^j,"",!,: .i.-es origin undergone growth in its normal position. . It must be kept in nunti that the^ ^^^^^^J^S^X'^^-^ ^S^t^, i:^ 1^1r^.i;^~-atode. proper ,>. 266). -MB^^P^P^IW 4P TEliA TOGENOVS liLASTOMAS 211 It is ohvioiis ill such u tumor as this, that is, one arising from the iiiyotiiiiu', that all the eontained tissues are necessarily mesohlastic. 'liitsf neoplasms are large, localized, soft, sareonia-like, and bleed and ntcntse reatlily; on section, the body of the tumor is sarcoma-like, but there are in it elements that recall a kidu'-y tubule, as well as muscle. lihnius aniinif ii hvilatid iiiolf nutiinil size. l)v the maternal blood urow actively aii;Krenated tojtether in enormous numbers, the mass distentlinR the uterus as much as does a full-term foetus (hy- datid mole) . The \-esicles are \ello\vish and translucent. Even in an otherwise n(.rmal placenta u small portion of it has sometimes been found to consist of such a mole. Chorio-epithelioma. — In the case last mentioned it will be seen that the growth remained within normal limits, and was, therefore, of beiUK'n nature, but this is not always the case. Such a mole may continue to grow and fill the maternal uterine sinuses with polypoid masses, the so- called "destructive placental polypi," which show a kind of transition to the full-blown chorio-epithelioma maliR- Kiii. fiS ^>: rh„ri„..pi,h..li.,n. .rlwin. wlhln ,ho ru. V, .,.1, „f ..onno »inu^N««., .nultinucle... ,. H^ of *^ -vnevtial typ..; /.. .-.. .■•■lis ..f I.iumhan.-.' t>pc. (Teacher.) num. We have said that theouter surface of the Vl'f ^^'•"^tH!Tde.■'!^y epiderm, becomes fused to form syncytium, wh.ch ,s made of du ,.li ! c i "i THR BLASTOMAS 213 >taiiiinK cells whose hudies huve fused, the mass renmining multinuelear. IJclitw the syncytial layer the cells of Langhans' layer remain unfused, individual, and less deejjly staining. The syncytium possesses erosive plmgocytic proi)erties, and it is these masses of cells that tend to be -\\(l)t away in the hhuxl of the maternal sinuses an.\ IK ytial cells growing actively- either in the uterine sinuses or in tissues tJM where, the active growth of the syncytium being secon(let*'^ JOi jinicess of growth is increased by ,*•'*** *'|^ fl elinding of this growth in the testis '^ €>^^ ^.'.-H tlie male. Here the explanation '«,/^*' '*." > Cells of a chorio-^pithelioma maliKDum, hiKliiT nmKDificution.' a, syncytial cell mam; b, ii'll.i of LanKhans' type; c, brukon-down erythrocytes (Von Franque.) iMiiNt he that cell masses of this type lia\e developed, not as the outcome 111 the fertilized ovum and uterine pri-iiiincy, but from a teratoma. The teratoma must develop or tend to ih velop a chorion and so gain its nourishment through this chorion, nix.i.linj; the veins of the testis; the chorionic cells so developed may lirnlitenite in the testis just as they would in the uterus. I'i like manner, a few cases have been rlescribed within recent years III I'ol inch Si .1 li sporadic teratomas in various regions of the body have been examination to afford chorio-epitheliomatous areas. THE BLASTOMAS (ORDINARY TUMORS) bhi-^+onias include all tumors, that are not teratogenous, which ' i!. independent, localized growth. This gnnvtli is practically ■ of one order; yet neoplasms contain a stroma (just as do the m. E^J^^SP?i^s:^^^Si*iW^lJ^jT^IW^AW 3 5^' ■.':». iiaii^-. '\L ^SEs 214 PROGRESSIYE TISSUE CHANGES ....n,al tissues) in ^.i;h ^t-n.a r.. . jU^n^^^^^^^ witl, tlu- exc-epti..n ..f tlu.sv ["r;^,,^ ',''\J ;"",,!"' Wih his exception, tissue like that win. 1. '"""'* *J"' ^^T'"-'.. .ml r ..f tissue, ami are in the hlastoraas are ,r..wths f''™;;;,;',:'\i.;;;;nt tissue.; ..r example. nuinher as nu.ny as an.l m„re * ""'^^''^/'^'^i^J ,,,,,, ^ ,„a „ste..nms fihr.,n.as of fibrous t.-»;y^'- ^ ^^s gl^^^^n^^^^^^^^^ of h.,ny t!=^s»;-; >«>•;•""-'' ^^^'^'^^J^ „fbln.tou,a than there of (secretnijj) ^lan. s. Ihin are """.'/' J •' ,„^,n or Ki»«t- i,,^. fn.ni a speeial kuul ..f .ell, '"»> not prisi ,,f ordinal crll fully .lifferentmte.1 J '^^ » ^^f^ '\^^^ appnm.h to the fully f.-rnu-.l an.l fully « '♦^^ "/^^^^^^^^^^^ fonn .>f the .ulult tisiue. Wh-n the "-'['•''-V^'^Cicrwht" lu nei^ m this r*"""''T'r;Cu:c:!ii:a "^^ hut uni)erfe(tl\ , w hen tl i ct us an i . (.ounttr- „,oplasni is like no a.lult "«>;'""\«' f ^^'^^ "^ *''%Sher^ as a general pari eells seen .>nly in the ^'">*;5"; '^'^^^^ f^^ , Jara.luU tissuts, the rule, the blast..nms that a e "^ t^^^\\f„^,, ;V";'™ the .ells that e.W als.. tlu- maUgnant neoplasms. ,.„.,„. ;„ eomnose.1 of cells and su.-h. have «r..vn s owly, an.l Ins ^ "^ - f ^-h is essentially a by pr...lucinK a ssM ar.mn. ^^f'':'\''^^2sm\^onn'ih^u^^,^y^<^^^ p,rt ..f the b...ly tissvu-s, an.l "' ^/J^^^^^^^^^f^Tergowths, an.l .lo not as brain or b..ne, are n>«ip * ".'' nerd ru"e, most tissues are able rea.lily pr...luce a capsule I. '^^''^^''J^^^^^^^ ,,„ often be shelle.1 to .•ir.un,scr,be the growth so that. uchne..pa^ m which It lies, lirowin, in ten.lencv t.) increase forme.1 of inipertc.tl% *""*^r'",*" ',..•., rpiiev snen.l little energy the num- to expen.l .m mere growth, '^^^'.^ 1^' f™, ' 5,;, time f..r 1 Tilt: BLASTOMAS 215 si^ii <»f eiK-npsuliiMon; «'vt'ii if a capsiilc ap|M>ar to the tiaki' all atypical tumors, for there are malignant tumors (such as tlu- malignant mouse ' Micers) that do not readily form metastases and, «m the other hand, there are tumors of benign t.vpe that form se«'(indaries; we have, in fact, all grades of transition between tyj)ical and atypical neoplasms. Yet it is useful to gain the general iriea that tumor-cell diHerentiation for specialixatioti of form) has a definite relation to benignancy, aixl the lack of it, that is, a tendency to the vegetative type of tissue, has a relation to malignancy. It is upon such evidence that the decision is made which (U'termines the removal or otherwise of the tunu)r con- ciTued. This being so, it is very essential to have a clear knowledge of what is the adult type c " ell from which a particular tumor springs; for example, the so-calletl giant-celled sarcoma arising from the bone marrow, exhibits cells of a vegetative, undifferentiated type, and might on that account be called very malignant, until one recalls that the jidiilt Ixme-marrow cells are of this type; this sarcoma, as a matter of fact, is one of the least malignant of all sarcomas; whereas, a mela- noma appears to be made up of more diffjTentiate*! spindle cells, an riioaREssivK tissue ciiasces correspoiurin^ (flls of tl.f embryo. •J. Rapidity o! growth. , ^^,, infiltrnfum of the H. Periphor»l exteniion. with huk oi «ap. siirroune readily ''t Tendency to Central I>««*r:^; ,,SJ "arts teiuls to e,>nstriet „,ulerstoo.l. f..r the pressure "''/""'" f,,\i,^. best of the oxyt!*'" ill vessels, aiul the outermost eells >|^' " * \.,i „,• ^Hese. an.l uls.. ll foo.l supply, while the "'"-^/Xlnets" degenerative chan,.. .,f H free outlet to their ^^""^^'^l,^,^ so that the central part are atn.phic or necrotic or at »"',^ !",'.; „„face tumor, the most '^'fli^bSr^ir recurrence aUer ^^^^1^^^^^^^^'^ that the removal is not .;omp lete ;' ; JX "nels of chains of cc4 s ii.g, with the characteristic yellow ish-gra> readily recojinizaUe. . j ^.^^^.\■,^^\.A, for which indeed S. Anemia.- This ««-« hand •} ' " ^^/^ jossof red corpuscles, anemia is partially '^'fl"'"^'t.cnera ion show that the blood picture is an.l sometimes the ^>P"^ "^ J'^^^^'/^JVa^^ anemia. Cachexia „ot very different from that «^;^ ;^;^^^^^^^ ^^^ .j,,. or the rate of growth however, is n..t necessarily mpnnH^^^^^^^^ ^^^ accoinpaim.! by very of the t... or; a very small [/'^'^^.^^^ if situated in the severe cachexia, and ^^ain hough s«^> V ^,^^ ^ .j^^^ the crsophagus. may interfere with "J^* ^^m" ^^.^ .^ue cachexia, hut rather cachexia is therebj increased ^'"^^^terrn "cachexia" to describe starvation; nor is '\^'*'"^'^.\f ,fle fo-l proet Icumg me cancerous cachexia. ,„*;r.n? The auestit)n is of impor- Have tumor cells an internal ^^<'^^^'^^ teen "ong consi.lered as tam-e because cachexia and anemia have »^^^' '"J^ Presumably Sts of a specific toxic --^J^ ^^^^^ Xn discharge soluble these in their growth ^^i" ^Iku- f g j ^|,, „„ture of cn/.ymes, :^::^ ;^m!:^LSproSy in some cases cytolytic as well, TIIK HLASTOyAS 217 so that we nmy iissnmi' that tlif cacluxia is «lin>-called) to consider. We liave sometimes heen tempted to t(Ki (1 ig. .0). I'm. 70 Vm 71 , , h Croup of Do.lular scrnmlary growths C-ar.inoma u.lvHn.md aloriK iIh- ,„r.v.s.ular lymptt ^^ rouncl-...ll,.,l .ar.onu. P<'.'1«1 off from ,l,au..cls of the hmt! fro... a pl-u, al L'row.h s,•oon.lar^ ^^^^ ^^^^^^^ ^ ^^^ ^^^^^ p.-rilontu... in a ca-se ,o ,.ar,.ii.o.„a of the l.r,a.st. iDr IU..-a . a P-r.- ^^^^^, ••.,.,.,li„«" of the pcr.- va. ular ..v...ph ves..! .l.s,....,l.,l »i. , ,a,.,cr ,-.11 ^ «h J ^_^^_^ ^^^ ^^^__^ „lv,.ol„s of lun.; c, l.lo.»l v..ss,.ls, ,/. «..o.,.lar> 1 u k,„,vti.- ...filtra.io,. of the p..riva»cular eonueet.^.. "T ,,,. ti..n..r in its ,n.ut1. may -'''IV,-;" -i^i^^l^^ir' sIS pass tlimtly into tli. f'^-''^ /''rea. ^^h^^^ ^^^ ',,lls ^vill iH- liable- to arn-st •'> ^lu" ^ ■< - inlW> nto n ^^ ^^^^ ,,f THE liLASTOMAS 219 cavity hvlun rarriod to the stoiiiach, and tumors in the stomach hciuK carried to the intestines. It is not safe to junii) to the cone Insion that a secondary in the small intestine has found its way there by trans- phmtation even though the primary jjrowtii he in tlie stomiich, for n hert' tiu- extension may have taken i)Iace hy the lymphatic channel i'\t 4. Transplantatii ■ceurs hy a/iponitioii. Cases are recorded HI which fa) one |, Iwing invh -! in cancer, the corresponding point on the other lip h s he. iiiiic iiifc' d; (h) the skin of the arm in contact with an ulceratin, c; rcinoniii ol the breast has become involved; and in which (c) the \ le pleural, opjjosite a superficial malig- nant growth have become tlie site of transplantat ion even wiien no esions !)etween the two have existed. The jjrocess of nibbing ha;- rom the first have (Ih bared the second surface, on to which the cell's f become engrafted. Retrograde Metastasis.— While the cells are generally carried by the force of the lymph or blood stream and the secondaries are tlnis situated farther down the stream, nevertheless, it ma\ or carrying of neoplastic cells is in the directi occur that sucti growth . . HI precisely opposite to that which might be expected. Thus, in cancer of the breast one mav find the head of the humerus of the same side infiltrated. Yet the head of the humerus sends lym[)hatics to the axillary nodes and not away from them, so that part of such extension nnist have liai)i)ened against the stream. The explanation of this anomaly i)robably lies in the supposition that some direct channels are blocked and the neoplastic cells seek out collateral routes. We have to remember the possibility that the extension may occur by direct contiguity of growth which we can imagine jjreyails against the lymph stream' as well as with it; while where there exists a negative i)ressure in the inferior vena cava, the cells may actually fall back from tlie inferior vena cava into the hepatic veins. Unicentric and Multicentric Primary Growths.— It is ordinarily not !)ossible to follow a tumor to its earliest beginnings, but we have good reason for supposing that most blastomas arise from one cell or from a group of cells in juxtaposition, and lu'oplasnis which thus grow from a single focus are unicentric. Others, liowe\er, appear to be pluricentric, that is. it seems that of a number of cells or of groups of cells near one another, each gives origin to an independent mass of new growth. 'J'his fact tells against the theory of cell rests, in that the adult cells an organ are sometimes seen undergoing change into the neoplastic i. pe. We have also to admit that it is possible for one body to be the seat of multiple neoplasms of dift'erent kinds at the same time. It is hardly likely that these deijcnd one upon another; more likely is it that a lowered bodily resistance permits cells of various kinds and m different parts of the b(Mly to undertake active proliferation. It is perhaps due to the same cojiditiuii that we sonutinies find bilateral organs affected by new growth of the same or similar kind. It is, of wmi^s^w^m:^^. 220 PROdRESSIVE TISSUE ClIANaES course, possible tl.at one of these •X;::^^^::^ '^o;th:;r 'i::^n wS'^^Stl tl.at'in sueh a case ^^f^^l^^Z^^or. some Tissue of Predilection.^ It .s notab e ! "^-Xrl e alL.st sure to tissues are very likely to be afleete.l, ^^ '' '^ \; ;, ^^^^^^ eseape; an example is seen m the ^^^^^^^^^^ZtJ in the appear in the liver, an.l the seeonc ar> ^^^^J^^ grmvths. The hones; the muscles are '•»"'>>V"'f't,,,.rent parts of the meaning of this is tl.at not -M -";;.«Xl.r^ h^^n ll ,f the bo.ly l,o,ly are able to prohterate, tor if/'' /^^ "J' ^ J ,f '.treugt^ of the bo,ly fluids, as is sh.mn by *''•;;; ^"^f^i.^t-t.nsplantation tion of tumors there are stajjes, .luru.g ^'' ",;';,/ ,"i„^,n(> doubt, c-an be made, while during others sueh an «"^ "f^. ' ^^^'^tanc-es in to the existence of antafionist.e, presumablx extoht.c. ''m"prii;^lL of Metastases by So-caUed Bemgn Tumors. .Certain uZrof^Un type are able to ^-^ -j;;- ^Jlmi ^.S" dromas. Here we have mult.pW ^^^ , > ^^^^^ //^^^^^^^^^^^ make not dangerous. It is not possible that 1 ^["^^j^^.^ ^^^ the peri- their way into the pulmonary ^''MJ'll'""^ ; J ^^^^^^^^^^ elumdrium cells (small actively growing eel s t ut >• :"j*^,^;'^ J„,, \,,,;, of a chondroma) which are -"f \»": ™"V ke ex mjle occurre.! pve rise to their normal pn.du(|t-cal^^^^^^ A 1 K. ^ ^^^^^^ '„u, climcl knowlclee .-omp,!. » «" "^P- , '„i:S ' ^l ' the THE HLASTOMAS 221 satisfy; however important it be from a clinical standpoint, it is necessary t ■ find some other basis for classification. Latency ui Metastases- It is seen from time to time that a neo- plasm, successfully removed, may break out in metastases years after the operation. We have lately seen a case in which recurrence appeared eight years after removal of a melanotic sarcoma of the choroid. Have cells from the origi' " neoplasm lain latent all this time? Presumably so, for the same pmnomenon has been observed in transplantation experiments; the transjjlanted cells of neoplasms evidently either (1) grow immediately in their new surroundiiifts, or (2) lie latent for a long time, with or without eventual multiplication, or (.J) degenerate and are absorbed. The variance of these happenings indicates that metastasis depends not only on the inherent growing qualities of the neoplastic cells, but also upon the resistance of the tissues; the latter may be merely another way of saying, as was said above, that there is a preflilection in tissues. The Nature of the Stroma.-The blastomas gain tlieir nutrition from the host and possess a blood and lymph supi)ly. In what degree the intervening tissue belongs to the host and in what degree to the neoplasm is a matter for consideration. The capsule of the typical blastoma is formed by the tissues of the host; even in a typical blastoma the cells at first make their way between the supportive cells of the host, and the connective tissue of the host thus becomes the stroma of the neoplasm, and its cells grow side by side with the neoplastic cells. Just as in inflammation, a neoplasm infiltrating an organ may kill off the specific cells of the organ and at the same tim imulat'e tlie more lowly connective-tissue cells to proliferation, a. ' this at times to so great an extent, as in scirrhous carcinomas, that die con- nective-tissue overgrowth acts as a flirect check on the neoplastic growth. In an atypical connective-tissue growth (sarcoma) a double process is at work; the stroma itself multiplies, and again, as the sur- nmnding tissue is infiltrated, its stroma becomes part of the stroma of the growth. Blood Vessels and Lymph Vessels,— The blood \essels and lymph channels of the host are retained by the growing tumor, by which means the tumor is nourished and gets rid of its excretions. "As the tumor grows, the vessels also grow, but never beyond the stage of capillaries; there is never formation of muscular walls, or of arteries or veins proper,' and even perfect vessels that become enclosed in a growth are sim- plified and lose their specialized characters. Thus it is evident that a hlofitomn hfi.t uo pow.-r of refiulatiti(/ its blood supply. Nerves.— The host supplies no nerves to the blastoma. A few fibres may be seen to pass into the periphery of a tumor, but they c\ idently quickly undergo destruction and absorption, and the deeper |)arts of the tumor are without nerves. There is thus no trophic or \ HMHuotor control exerted on the tumor by the body, and the activities, vegetative and other, of the neoplasm can be influenced only through »n>; ^'ji#33irni& -:5??^«*2^ 222 riiocmssivt: rissiE chasoes t,„. CO nposition of the l>o.ly Hui.ls an.l ..y alterations in the resisting powiis of tlu'snrn.nn.hnu tissues. j,, ,^ Degenerative Charges. ^^^^^ ^ l^'J^^ extent control neoplasm, espeeiall.N sn.ee the ».•"»*"•!' ^* , j . tumor .-ells have its 'own m.trition; apart »-;" 'i;:;; '^ ^^ ^^^^ no other s.,uree..tmn.nshnu..tl ant Hn.^>^<^^^^^^^ ^,^^ ,^^.^^ ^,,,, ami of this the peripheral V^^'^V ,. t Iv lit off tor f.Mnl ami ..xvpn. most, leaving the centrally situate 1 p. t •;»'>;" ,j ,,j t,,^;. ,,ts N„t only this, but the peripheral cells a> f,e . ^^^^^ hv .liffusi..n into the snrroun.hn^' 'Tt ^V n Le or kille.i tnerehv. niust "stew in their own juice^ ^^^^;Zo!ln internal neo- b: J:r;^^ ^:/:r .i;^i.r.!t5!^::Ue liahle^ .upture and permit hemorrhajie. Fic. "a 2 Irrciiuliir iiutoscri in ,:uacr cells: 1, hypo.hromatic mi tosis; 2, asyinrnclric niUosia, the upper (liiunliler nurli'us liyperr hronmlic; 3 I" 7. various forma of multipolar mitoses. (Galcotti.) given tumor >et m. n^ "^^ .^ ^-^^^.^ hvpochromatie (that is. H''ffiBfi^«KrJKir"*'^,^|rn.gs. Considering the earliest stage that has been recognized ' in H. development of the fertilized ovum after it has begun to segment I :.t IS, the morula, we have merely a cluster of undifferentiated cells' l-pidly these cells arrange themselves into two layers, the epiblast ■■r'\ hypoblast. Hetween these the hypoblast and, to a less extent, the •1 1 .last giv rise to a jxx.rly diflVn-ntiated mass of cells hardly to be -j lc no longer stratified. As the dorsaU'roove becomes infolded this portion becomes cut off from the rest, the only part recalliiiK' the original epiblust being the epcndymal layer arouiul the central canal, these cells having originally been outer layers of Fig. 73 OiuKrammatir ropresontiition "f portion through vcrt.-bratc body to show r.ntogenct..- rchition- ,hip of tho varin,i8 orders of tissues. .1. Of lepUli<- type: 1, epi.lcrn. ami its glands (epi .last";! : - murous momhrane of digestive canal and its glands, liver, etc. (hypol.lastic) ; 3. endothehum l.nmg serous cavities (mesoblastic) an.l glands, like renal cortex, of moso, helial origin; 4, vascular endothehun, of late n.esoblastic origin. B. Of hylic type: 5, spinal cord, b.ain. an.l nerves (ep.blastic) ; 6, n.>l..- rhord (hvpoblastic) ; 7, connective tissues of the body (mescnchymatous) ; H, myotomes, atnatcd musck of body Unesothelial). C. Cavities; 9, lumen of digestive tube; 10, body cavity. the dorsal groove. A similar ingrowth of cells occurs from the hypo- blast to form the notochord. We find that these ingrowths from the epiblast and the hypoblast come into most intimate relationship sub- sequentlv with mesoblastic structures. The mesoblast in its turn undergoes changes; when it splits to give origin to what will ultimately be the primitive body cavity, or ccelom, the cells lining that cavity ms^trr ' VS..''S.«'.*-«»,»r-i* 'Sis.'' CLASSIFICATION Of THE AUTOCHTHONOUS BLASTOMAS 225 '.icomp arranged in a layer, the mesothelium: tin; rcmaiiiitiR part of the nifsohlast, which dot-s not become so ditlVrcntiated, constituting the mesenchyme. From the mesothelium again, there occur ingrowths into the mesenchyme wliich are comparable to the ingrowths from the epiblast ami hypoblast; these are the myotomes, the anlagcn of the luture striated muscles of the body. Further, a mass of mesenchyme wiiicli will ultimately l)e recognizable as the heart ami trunk vessels are seen to develop a central cavity, and the mesenchvme cells Iving upon this cavity become differentiated into a definite layer, the endotheUum. Ue thus find that th" embryo becomes divisible into collections of two orders, which may be termed "lining membranes" and (for lack ot a more expressive word) "pulps," the lining membranes being persistent epiblastic, hypoblastic, mesothelial, and endothelial layers, the pulp being the main mass of the neuroblast (of epiblastic origin), the notochord (of hypoblastic), and the mesench\nie (of mesoblastic) 15riefly expressed, each layer in the original embrvo becomes differ- entiated into lining membranes and pulps. To the former we apply Lr',.*''™ "^•Pi!"c." (from /.sr/c, a rind or skin), and to the latter hylic (from 'J/.r^, crude material), both words being used as adjectives. 1 he characteristic of the lepidic tissues is that the cells are arranged 111 layers or clusters in direct apposition; they are not separated by h/niph or hhnd tesseh, an.l they possess a supporting framework or stronia of liylic tissue in which run the nutrient vessels. The features of livlic tissues are the opposite; separating the celh there is a matrix of inter- rrlhilar substance, either homogeneous or fibrillatcd, while lymph spaces "11, rrsseh and blood capillaries tend to separate and run between the nidimlual relk. If in the lepidic tissues there is a stroma of hylic tissues, so in the hylic tissues there is lepidic tissue in the shape of the emlothehum of the bloo'"" *"'"■ or niav not he hlood and lytni)li vossi-ls: 1 'l-'i,lhl(i.''tlr: Nerve cells, nenronha. T !Kw>^ '—-•.• tissues, cartilage, hone, reii Jmn ::f hnM.h .lands, hone n.arrow. fat eells. n.v..luntary muscle tissue spleen, hK.od vessels, hlood corpuscles. 4 i/,lo//,Wm/; Striated nu.scle. in.ludu.. canl.ac nms, e Kollowing this sehen.e of classiHcafon ot the -"- J ;^' ^^^ .X now divi.le the tnn.ors arisinj; from tne ;^l'^'''f'y,:" '^'•^";.'' ';!„.;i*Jl^ various tissues into t.„ n.ain ,c-nera- the l^'^'- "■-•;- ^^^jf,^^ oripnatiuK fn>.n the ahove "luuug-n.emhrane ^'^r^-,*^; ' \. ^^^^^^^^^^ tumors ..r hylomas. originatinK fn.m t,ss u s .lenve.l '>•''"! ";>;^^^^ '• ,uh. '• Wo can further .listin.nish tvvo hroad groups <>t lep.du tmnors puip. ».»>' derived in d rect descent irom the tlw nniiiarv those ^^ io>e (en> ., ha%t passed, .Uu course o devc-lopnu-nt, through a n.esohlast.c or mesenchyma- uZ^^ lu-f..re conung t<. forn, portions of a '-^n-;^--^ ,,^^^ The coinage of new tern.s in a suhj.'Ct .s "•"'*'^' '' '^;'\' '^^^ ' " r";',",. or new relationships are to he expresse. . unavo.dahle. ^1''- -> * ' /^'^-^ e circun.stan es un.ler which lepi.lic an.l lep.doma and h.xhc ad 1 V were su>^gested. Thev are necessar> for the expression ot tins ;: ;;i:;of ;^mor relatiou;hip. hut at present, we ;^-;i,;'>- - •, fruiework on which the idea of tumor growth is t( he l.uilt, rath r ; ; erms or everv.hn employment; in fact, we .io not personally 'nCin hlr daily dinicai purposes, for which t-- hke car.^^^^^^ sarcoma and en.h.thelioma are adecinate. ihese terms (••'"»»•" J; w ';: nile that u.m:.rs of id.nti.-al type may ..rigmate trom any .^ he u rn la^ors■ thus, a lepi'li^" .aninoma can arise from ep.hlastie. ; ..^:h;:iic:' :; mcsohlastic'stmctures, and, what is -- -"^^^ in ts malignancv according to its origin; we think it nece>s. r. , th r r t PI Iv an a.lje.-tive which will indi.'ate its tissue relatmnship, : ; iXllal ;arci,u.ina. mes.>the!ial carcinoma, or n>.tlu-ln. a, ei.oma liulotlulial adenoma, and so on. We are aware 'V''^"; 'h ^V Z nients which can he urge.l against this method ..t nomenclatun , hi "n .,: allowe.1 to sta^- its chief advantage, v- the recogm^ t,„: secialary or traditional f-''P^- '^,-:/j;;; !^ ^ rcw!^-. lepidic tum..rs wiuch are liai.le to prisitit tn"'^"' „ tnmor .„ ,1 t.. cause therehv the greatest contusion. I'or exampU, a tumor ottlK adrenal, a "hypernephroma" of the kidney, an " ovarian tumor, ini.OMAS AM) LKPIIiOMAS <>: 27 iiiiiy. if of slow ^n.wth, prcsi-iit all tin- cliaracttTs of a carcinoma— a ;;lim.liilar tuiiK.r and if rapi.lly KrowinK and activciv vegetative may he mori)liolo^'ically a perfect sarcoma. Such a tumor was often culled carcinoma sarcomatodes, and in some instances has actually Im(ii proved to possess certain characters, su|)posed to he distinctive, ct each; for instance, sarcoma cells are separated hy fibrils of stroma,' ( iircin«|ma cells are not, yet a comparison of V\iis. 71 and 7.") will shew' thiit FiK. 7:> shows a tumor that is in this regard at once a carcinoma iiiid a sarcoma. Fui. 7' Km. 7.1 'I'll "f rarriniiiiia sir^ \ i>f lirnaist, I «itli Mallory'M cunn* iiM-tissuc stain, "■"risirair a (•(iiniilcK' abxhri' of passage ' I'lllular filiril.« hrtwrrn llic itiiliviiliial " i~"f llicaivci.laricll Knmps. ( Wi,i,ll(.y.) .S'ctinn iif an ciKlnthclioma similarly tn'ali'il. The hIv..i,Iii» Im>I.,w rcarts almost wholly liki- an rpithdjal ,ari intiTci'iliilar ronni'i-tivc-tissuf fibrils, liki' a sarcima. (Woollcy.) Tl /■'■ hit tin ri : ;■ reason endotheUomas (for example) are trmmtmuiJ .seems to I'N. We have insisted before ui)on the fact tiiat the rarlii'.tf. arqiiirrd ■ rlivx „j c'lh, or of individuals, arr flic laxt to he Imt; properties of '■ ac(|iiiri'ment are yielded up with greater ease. The i)rimarv lepidic >r^ are derived directly from cells that from the earliest eml)rv()nic "I. have been lepidic and of the nature of lining membranes- "while Imimtnwal <,r secondary lepidic tumors are derived from cells -'■ from bemj; lepidic (in epiblast or hypoblast) have become vjlien the mesoblast was formed) and yet later have ajiain taken ■1' ic characters. These colls, „r their prt,scn\ in neoplasms, revert ' t" the hyhc, sarcomatous type, which the primary lepidic tumor 111 ii>'t, l)ecause these last have been continuously lepidic. This 228 rnncREssivE tissue chasoes h not to state that primary U-pi.lic tiiinurs ijomt rryrr . for tlu>> .K „ot..ri..usly in tin- case of tho .o- . It niav he h.i.l .iown as a ruh- in all tn.n..rs that tlu- nu.re rapul the ^n.vvth. the ,n..r.- .lo cells lose those featnres that were fornierly specific to them as the constituent cells ot this K„. Tii or the other tissue; the in«li\ iiliial cell ^v inav thus atl'ord little or no chie to ^/V' :••-.:• •; the tissue of oripn, hut hy the Ken- ^^ii;.*:-lj- "•' eral arrangement of cells it is pos- ^^'^<^tl^''.'. sihlc to see at least reseinhlances ■*" ^*-- • to connective tissues or to glandular tissues, and thereby to know wliat kind of tissue pive orij,'iii to the tumor. We note, in any case, a reversion to a simpler, earlier, more •'embryonic" type of tissue, in which l)roliferative or vegetative activity has replaced functional activity and caused the tissue to lose those features that are distinctively connected with the performance of functicm. With this loss of power to perform its function, we ht-iieve the tissue to he incapable of repiininf; the same; a hvlic tumor, beinn comi:)sed of tissues of less specialize*! type, cannot take on lepidic characters. An apparent assumption of such ;:';»>-';;;tf';;;.;; seen in Fij;. 77, but even here, although the cells which line the c> s cavitv that has .U-veloped in a ghoma, have the appearance, at first glanJe, of epithelium, they are not so; there is no '>''-";V"\;";-^,'- and the case is merely one ..f a.lai.tation ..t jjlioma cells to tulhl the function of lining cells. ■•l'siiiil..-<'|)illi('li\lin." or fu'cimrlaryopillii- lititji nilhiiut biiwiiiinl nii'inliniiio liniiiK ii cyal in h glimiiH, fi.nncil by in(.ilili<-!iti.m nt the HillKTfirial hiyor of islionja rc-lh. (Suxcr ) TYPICAL HYUC TUMORS OF MESENCHYMATOUS ORIGIN Bef..re dealing with the large (piestion of causation, we shall pass in review the various forms of tumors. Here it is necessary to .lra^^ a distinction between blastomas proper an.l blastomatoid grovrths. The blastomas are well-;r..ui> tlim .!> havinj: n.aiiy n-s.-inMaiHrs t.. tiiiiior f<.nMatioi,. Tlu-s.- ov.rirrovvtlis '" l.last...„at..i.l naturr (of whi.h lipoiimtusis. film..nato.sis, nnin- il.ro.natosis, kIu.s.s. vW., ar.- .•x,.n.plc.,s). as « class (1 ) am^t one par- ti.nlar t.s.s,u.; (2, ar,. niultipK.; are of .-oupMHtal. if not here.litarv. nriirin. froqnn.tlx I„.„,k n.ai.ift-st in ,-arly life an.l affectinK several ni.n. KTs of a lannly; , J) may InMliHuse, or if not .liHuso, at least mertje into the snrroun.hn^^ tissue; (f,) may appear to he e.uapsulat.Hl, hut this apparent eneapsnu.tion is merely the limit imposed hv the houmlarv ot the tissut- afleete.|; ((i) are (.f slow growth. exten.lii.K "ver, it maV :"•. years; (/) eventually may take on malignant characters, which 1^ n..t a characteristic hut is merely an example of the priiKij.le that n>M,e winch has develoj.ecl m excess of function is alrca.lv nu.re than M t-vvay t..war.l a , errancy, that is. tlu> stinuihis. whatever it is. that 1"! t.. hlastomatowl gr.wth may lead to true hlastomatous growth. Fibroma. -The fibr.>ma is a typical tum..r of fibrous connective ""■• I ^Ti" .;/" *'"'* *'•'' '■"''-'' ^*'"' *""""•) '^ " ^'•"«' i'nitati.)n of the or,:;mal the hl.r..us connective tissue); the origina! tissue lies wi.lelv M.it.nd thr..ughout the body, so that sn.-h a tunmr niav arise iii jM.iny situations. Just as .•onnective tissue varies in its exposition, I" m^' m some regions l.mse an.l are.,lar, with rclativ.-lv frt^uent cells ""'.', ^f'"^' ''^•';«" "»"' ««•"'. ^vith relativ.-ly few cells, 'which are neces- ^;mlv .•oinpressed, s.. the tunu.rs vary, an.l we liave soft and hard il.ruHKis from these tissues respectively; the soft aris... for example ro,„ snb.utane..us tissue, the har.l fr..m dense tissues such as tendons' t.i-i;r. an.l i.eriosteum. All alike, however, are composcl of con- n- t.v.-tissue cells, connective-tissue fibrils, s..me elastic tissue, and -.vessels. Lymph spaces are seen in greater .,r less prominence . 'ord ng to whether it ,.e a soft or a hard fibr...na. The fibr.,ma .n. rally forms a well-,lehned no.lule which gr..ws slowh-. an.l ,,resses P'.n and replaces the tissues near it; if tluTc be rapi.l growth, however, '1^' 'His instea.l ..t resembling fully .levelope.1 comie.-tive-tissue cells ;|n N e hbr.>blasts. The greater the- ten.lency to r..s..mble fibnlli^t:; "I li... I,.ss .liHerentiation there is in the .lirecti.m .,f perfecti.m of .||.me,.tive-tissue ...lis, the nK>re .l..cs such a growth 'approach in >trM ire a sarc.ma; the .M.ly sure differentiation between the benign ;" > I..; malignant (sarcmatous) growth is the absence or presence of ;t. ..n, an.1 mvasion .,f surrounding tissues. Lest .,ne should be - • .1 It IS well to remember that all fibromas are n...re cellular than is r ,1 adnlt c.)nnect.ve tissue and the growth .,f a fibroma of the ; locent kind occurs by the proliferation of such fibroblasts, and ""' inlly formed connective tissue. I . Hbrum.-, is pale on section, and the firmer ones are glistening, n appearancr that recalls watered silk; this is .lue to the bancls - that run in all varying directions, each band bting originally ■ ■'^'SW^JSBi>iiS^^jm *-rrV' r:-i*4 kJZ '^n' W ..jI 230 i'H(K;iiKssi\ F. Tissrh: ciiASdES |„i,l ,|o«n imn.11.1 tn .,r iumn.l a I.Io.mI x.smI A Mcti.... tl,ronK». tV..> tui.H.r will sIm.vv M.Mir Imn.is .ut transv..r>.l> , ..tli.rs l..„«m..lmall.v. „,„1 otl..T-> nl,li(,n.lv. Ill tlM- Kn.>s. tl.r »il.r...,.ii is uvuvrMy sharply nmiinMril«.l. aial .an mi.iilv I.,- .nu.l.atr.l, i.ut tlu' >l.arp l.nmaiarv liiH- camu.t I..- s.. w.ll Mrii mul.-r the ini.roscop.'. lw(aii>f tlu; siir- roun.iii.^' tisMif is of tin- saiiu- .ml.r, aixi tlu- iiormal aii.l tum..r tissn.-s pass rnulilv into om- aimth.r. i i „ . I),'H.-n.Tativi- ihnuiii's arr i)n.m- to occur in hl.roinas. an.l l.v arrest of hloo.1 supi.lv . or l.v tci»ioii they im.lcr»io necrosis, an.l m tin- n.-.T..so.l area is inn.l. chol.-st.rin an.l fatty material, whi.h snhse.pi.iitly may |„.,.,„ne .-..nverf.! int.. .•al.-ar.'..ns n.Mluh's. If th.' lymph ..uti.ts Ik- ol.strn.ted, the tnn...r may hec.me .clematous. lymi.hannie.tati.', evsti.', or niu...i.l. , , ^i i ' In certain situati..ns. as in th.- mammary nl"'"'. " hl.roma ma\ h« fo.m.l to have in its mi.lst jrlan.lular el.-m.-nts; this pn.hahly m.-ans that an inflammat..r^ fihn.sis has taken ..n tnm..r h.rmati an.! t a- |o.ali/e.l fibroma thus f..rn..-.l has iu.lu.l.-.l ulan.ls that were ..riKmally n..rnuil; su.-l. a tum..r is a pnr.- fil.n.nui. an.l n..t a fil.r..-a.len..ma; it is a fil.ro-a.l.-n..ma ..nly when there i> a i.n.liferation ol tlu- n.cin.l.-.l dan.lular .-l.-nu-nts. Asa mutter. .f fa.-t, there is a p....l .h-al ..t loosen.-.s in ..ur us.- of th.- tern. Hhr.>-a.len..ma; s..me ..f th.-s,- are pur.- h .n.nu.s with iilan.l tissu.- in.-lu.le.l. an.l ..thers are not a.tual ly tru. hl.n.nias at all hecanse the fihn.us tissue is n..t (-ircmns.rihe.l (haston.a), hut is general, an.l .litTuse. ..f the nature ..f a l.lastomat..i.l ^r'-wtlj. True fihn.mas .io i...t form nu-tastas.-s an.l .1.. not r.-cur att.-r removal; if rcurrence .l...s happen, it m.-ans .-ither that the s;r..wth was ..nuinally sarc..mat.>us or was fil.r,>mat..i.l. in whi.h latt.-r .ase th.- n-cnrren.e is simply the exi.r.-ssi<.n. ..nee m..re, ..f the .lilVuse overjrrowth whu-h was orijiinally wholly t.r partly remt.ve.l. Hard Fibromas. Hani fil.n.mas are f..nn.l in many .iifl.-rent situa- tions hut m..st ..ften in .•..nnc. A vari.-tv ...-ciirriiif; in .•onne.tion with th.- jaw is epuUs, a term oft.-n impn.'perlv ^iven t.. ost.-..i.l and osti-..sar< oinat..us j;r..W s in this situation;" it .leveloi.s from th.- i.eri..st.um in .-..iiii.; is a h!a .tnn.it....l ovcr|r_ruuth of the medullate.1 peripheral nerves; it is asserte.l that the "i>tH • « „lfact..rv nerves, whi.'h are .levoi.l of sh.-aths of Schwann an.l .)t tlie Hlilir.-ciirsnr> ..f tl.,- sheaths, an- ....y.-r iiivolv..] i„ .-hs^.h "t iniiltii.lr n.Mir..hl.r..ma. vH thr upti,. imtv.- is thr m at of tnu- Hl.ro- n'at..s,s. i„ xUvsv casrs. th.Tf is .s.mir rch.f i..i,>hi|, l„.txv,.,n fh.- til rs I' I.I. :r Kici 78 ■■'Hi ' "^^^-Ik- • ■Hi "-' .; <^i ' 'Ks^y. t M;int fihrorin, (ItiM , * 'It tihroriKi iii'l •■t ruction of the lymph channds. \vi lr.,iii tl If system of tht- tis lurvcs arc distinct I Ills to lie (hic to s( th isiics they traverse; tl,. (iistiirhed niitrit hundred or more n jinrted cases of fihroma- imc vice of ih'\elo|)ment hecaust ion many, if not all. tn.iN .f th urred e optic nerve 7!) in carl\ lif (' or "•re familial. Cheloid.i Althou>;h dis- iiiMt ill its I'tiolo^'y, aim I what in its liisto!o>;y, I'id is closely related to -Hill illiatn^ It consists III Aces-i vedeveloi)ment of •iitaiieous fihroi IS COll- i'"n\c tissue, sometimes i-Tcat as to produce '-'•>>\('rlappiiij; masses of l;i Liniwti d ski 1 covered hv coar™. hyul Section fri)tn a ttrnwlh in a rn«- of clitloiil n. Two fi line ronitfrtivf>-r)KNiic V )nn sufier from it. a slijrht cutaneous injurv is liable to he fol- I'V its (level opmciit. In a case studied in our own laboratory, •iiii' aiitliorili-'s write this k-i'l<>i<| from »'>-. ■) jT-ih'- -l-.w "- '1 .> m «iii..|, „„. ,,r,„.,..ss..s spn-acl i„t„ tho st.mMm.iinK <' \ . ^^^^^^^ cumulative, borne ,uul the con.lition beconu-s progress! ^i^^^^^ -^^^^j,^; few, even nasal polyps ^-';^^;;^l''^TvJ.n.h\^ is not to be found The tissue ^^1»«^^\ ^he n.vxoma most r ^ j j.^^,,.,, as in the adult body, but is the tissue " ^Tt^^^^^^^ fattv tissue of the Wharton's jelly, an.l t -'^^'vehW '^^^^^^^^^^ ;^,,„,, i„flani- f„.tus. In pathological states. ^^ 7>; ^j,;^, ^trix; we realize, in matory areas, fibroblasts y.ng ma -^^^^^^^^^ ^^^ ^^^^ ^y^ fact, that mucin which IS a '°^,«IJ,';„„,Vissue, and we recognize a connection with the development of fibrou t^s ^ ^^.^^^ ^ connection with this ^«^'*^'"P™f"* ^^ „^Xd mvxoedema. but in the generalized «^"^'"7^J* ™^^ '^te cells, or polyhedra V true myxoma >«/"'"P«^''; '^ .!t°„£ cell" ' ) , which are separated ftt:: =ri?^::;:^Snt:£ U^, t.. mucm ta^mg a LIPOMA 233 In the matrix run large, thin-walled ilifferential stain with thionin. vessels. The tumor is slowly growing, soft, and fluctuating, so as to seem at times cystic. It forms no metastases; a certain number of myxomas do become sarcomatous, and when they do the metastases are purely sarcomatous, and show no myxomatous characters. Lipoma. — The lipomas are sharply defined tumors composed of tatty tissue; even if situated in the midst of fat there is no difficulty in recognizing the tumor, even if its color be not paler than the sur- ruuiiding fat, as it often is; there exists some difference between normal fat and the fat of a lipouia, for where a large lipoma is present the botly may progressively emaciate and yet the fat of the lipoma will not be taken to supply the botlily needs. The lipomas are usually single but may be multiple, and vary in size from the very minute ones observed ill the kidney to the G3-pound retroperitoneal mass which has been described. Generally rounded, they may have finger-like processes radiating into surrounding tissues. They grow slowly and do not recur after extirpation. Modifications may occur, such as that part of the tumor \vhich becomes jelly-like and mucinous, the lipoma viyxomatodes; ail unchanged lipoma may even be so fluctuant as to be taken for a localized collection of fluid; at times a kind of necrosis is followed by the development of oil-containing cysts; cartilage and even bone have been found in lipomas, a phenomenon which is probably to be accounted for l)y metaplasia. Most frequently the lipoma is subcutaneous, especially in the region of the shoulder and arm; a curious clinical fact is that one of these tumors under the influence of gravity may change its position and lie, for example, lower down upon the arm than was at first the case, internally, they occur in the submucosa of the intestine, in the kidney, ill the brain, in the omentum, and as enlarged appendices epiploicse; liponiatous processes may develop in connection with the joints, pro- jecting into the synovial cavity, as in the knee. Lipomatoid Growth. — More or less generalized, often regional, lipo- matosis occurs. Steatopygy, an excessive development of the fatty tissue of the buttocks is counted a point of beauty among the Hotten- tots, and is so frequent that it must be counted racial. Lipomatosis atl'eetiiig certain areas may be familial; and the good results sometimes <>l)taine(l from the use of thyroid extract suggest that the occurrence 1^ due to a nutritional disorder; and in fact, a diseased pituitary has I'teii found in at least two cases of adiposis dolorosa, a disease in which tlie presence of the excess fatty tissue is associated with severe pain. Xanthoma.— The xanthoma is a small, benign, fatty tumor of a yellow color, subcutaneous, sometimes multiple (X. multiplex), often toiiiul near the inner canthus of the eye (X. palpebrarum). Formed "f connective tissue, it contains yellow' fatty globules, in which the piKiiient is of the nature of a lipochrome. Jt is probable that the xaiitlionia is not a tumor but a fatty or lipochrome degeneration of ^%m13 234 I'ROaUESSIVE TISSUE CIIAXGES II m [■ii {'i'i ill m Li ri.i. s2 tissue. The iniiltiplt- form is found associatfd with diahi-ti's (X. dia- beticorum). Chondroma. (Iioiulroinas arc tuuiors of cartilafii-, liyaliiu" (hyalo- enchondroma), fihrous (flbro-enchondroma), or ri-ticulatcd (reticulated enchondroma). Tlu-y may lu- sin^h- or multipi*-, and in fit'iioral have a (hstiiiet fihrous capsule. There are two varieties, tlie ccchondroma, and the cncliondroma. of whicli the former is an outj;rowth t)f cartilage where such is normally i)resent, as in the costal cartilages, the larynx, the trachea, and t-lsewhere; they are truly local hypertrophies, and are to he considered as chondro- nnitoid. In the chondroma proj)er, or enchondroma, we have to tleal with a mass of cartilage having no connection with a parent matrix. Such occur in many regions, notably in coiuiection with the !)ones, the parotid, the submaxillary glands, the testes, the mammary glands, the lungs, and more rarely in the ovaries, the corpora cavernosa, and otlier organs. They do not arise from the cartilages of joints, although they may deciop in the fringes of the synovial meml)ranes, forming the " loose cartilages" of joints. Fl is lobulated, the intervening connective tissue carrying the blood vcsmIs. In the large growths, the deei)er |)arts give place to bone (osteo-enchon- droma). or calcareous infiltration occurs (enchondroma petrificura). There is also considerable tendency to central necrosis, and if a necrotic area o|)ens to the exterior it is apt to be very intractable, and leii (^llOXDRO.\fA~OSTEOMA 235 eniK.. an.l slowly Kr.,vvi„K as thvsv tumors arr. novortl.oless th.-v ;-■. m„„ ,„ 1„.,H.H, a„,l thm- ,l,..v „ri „re,.„ .'.m ,„to ' w h V^ * usreoma.-jJsti )mas, defined as tumors havinc a crowtli ,,f tL\^ Mr.„.,.ss "*' ""'"' "^ *'''' '•"""'••"lis examples of this ,^ip9.;;;xf Kr^';;x^s;™ sls^''i:z 236 PROGRESSIVE TISSUE CHANGES often shows no cartilaginous fore stage. Ossifying chondroma serves as a further example of the heteroplastic form. Osteomatoid.— This, as was stateil above, includes all cases of localized or general overgrowth of hones in which the growth is not defined from the normal hone, is not independent, and is t>f unknown cause (save, perhaps, that heredity plays a part). Such are: 1. Idiopathic hyperplasias affecting one or several bones, especially the long bones. 2. Enustoses, localized and circumscribed growths within bones, not independent of the surrounding bone. 3. Exostoses, processes of various grades arising from the surface of a bone, not of traumatic origin. The ivory exostosis of the skull, or the ossifying ecchondroses at the ends of long bones serve as examples. It is difficult to separate from these, conditions such as myositis ossifi- cans, in which bone gradually replaces set after set of muscles. This last should perhaps be considered as an example of the following. Metaplastic Ossification. — This is an alteration of some part to bone, accompanying inflammation or senile changes in a tissue; examples are: (1) the "nders' bone," where bone is laid down in the adductor muscles of cavalrymen, from repeated trauma of the muscle; (2) the like case in the deltoid of the infantryman, from pressure of the rifle; (3) in the choroid; (4) in the pia, after inflammation; (5) the bony plates developed in the dura are even better examples; (6) in the heart valves and arteries; (7) in the lungs; (8) in old pleural and pericardial exudates, where bone formation often follows calcareous infiltration; (9) in various tumors — lipoma, fibroma, etc. Odontoma. — Pure odontomas are rare, and odontomatoid conditions commoner, the growth not being independent of the cement substance, of the dentine or the alveolar periosteum of the tooth. Bone-marrow Tumors. -Myelomas.— The m\eloinas are tumors of one or more parts of the bone marrow; morphologically they are like the sarcomas, but they are not malignant, do not form metastases, (lo not infiltrate; they are m-de up, not of cells that have become undiffer- entiated, but of cells that at their highest development are of a relatively simple tyi)e. Hecause the tumor tissues do not depart from the type of the original bone-marrow cells, the m\ elomas are typical blastomas. The different elements in the bone marrow are these: on the one hand the cells directly concerned with the bone— the osteoblasts and the osteoclasts (or myeloplaxes) ; on the other hand, the erythroblasts, megalocytes, myeloblasts, and lymphohlasts- the mother cells of red-blood corpuscles and leukocytes. The cells of these two orders, widely divergent in kind and in function, can give rise to corres- ponding tumors, and not oidy this, but each kind of cell can give rise to its own overgrowth. If we realize this, anjc«/ fi/„,..I.s of he jaw; they grow expansively, causing absorption oTur roundmg bone, are vascular anr! do not form r«.La...,, save b the cases where sarcoma spnngs up in a hitherto benign growth; they do not '•eour; nor do they require to be very "wi' M,./o,„«,. These are, of course, the sarconuis, wlml, mav i- (. pnmanly or (h) Irom typical blastomas. such as the alW, II ! '>'«/tomatoid overgrowth, such as the following : l!la.sfow„to„l Orergrouih.~Myelom&toa\a (Myelovm Mnltipkx) -This a I-nihar form of growth th^.t affects the ret! marrow of bones, such K ertebra., nbs or cranium, converting it into a .lark red or ■ Hl.-^-ray. or gra, h-yellow tumor mass. It is a primarv multiple .-. arising simultaneously in bones widely apart; at 'times the ," 's are soft and j.ulpy, at times firm; they mav project up to urtob;;' *';.'V»-""«^eum and fractures are thus' common, or in Mrtebne, distortion. There is no sharp definition to the areas 23S PKOdRESSIVE TISSUE CHArOES of hyperplasia. Yet with this progression thi< m> ith remains con- fineci to the hones, and there are n«) met. stii iS in lymph nodes ()r elsewhere, ("linically, there may be fever, pain, nnii Nc-vere inemia, with albumosiiria. Some of the names umler whiih tlk u iiarkable condi- tion has been known are mahgnant osteomyeHtis. myelogenous pseudo- leukemia, sarcomatous osteitis, lymphadenia ossium; and our conten- tion is that even "myeloma" is incorre't, in that it is a myelomatoid. Histologically, there are the pure cases in which there is no cner- growth of the myeloplaxes nor any indication of the osteogenic ele- ments t>f the Ixme being implicated. The tumor cells are derived from the cytoblastic elements of the marrow, and are myeloblastic or lympho- blastic in type; this means that we may have h)calized blastomatoid overgrowth of the lymphoblastic elements of the marrow without leukemia. Myelogenous Leukemia. — The cell growth in the above is local, but we have similar diffuse overgrowth of the bone marrow with at)undant discharge of the cells into the circulation— myelogenous leukemia. Here there are in the blo(Hl great numbers of large mononuclear cells with neutrophile granulaticms, coupled with the presence of increased eosinophiles, "mast cells," and normoblasts. The ordinary red cells are reduced in number, the white cells greatly increased, and the myelocytes may be one-third or more of the total white cells. The bone marrow is seen to show hyperplasia, and is reddened. The main elements present are myelocytes, nucleated red cells, and numerous cells with eosinophilous granules. The great enlargement of the spleen is not primary, but is clue to an accumulation of hloi.'I.K-ytes. namely, myelomatoi.l (mjeloma multiplei" 3 'enou l.uke,„,a an,l chloroma. This leaves us free to ,ieaU it the m n He i;;e,l3 ' *'""' •" *'^ '""^^ ^'""'^ ^" *h.;se of lymphoid KLmsS^Jhifr'"'*"* ^^•'»'"P«':«'>le with ehronie inflammatorv it.:ss-;-;sii- ^-^^^^^ -- '- --- w.'il.VMJTh'.f"*"^ (c-omparable with cheloid). I„ the last group -!<.' . \Mth eases where a known irritant is the cause of the ivmnh «rpias.a; here w-e have a hyperplasia of the same sor v 1 enthe ;:;:.;^::u;i;;:^iS:'" ''- ^""'^^' "•---"•- - -- — I li«' ly.nph-node groups «,f the b«Kiy are successivelv enlarged often r mng w.th the cerv cal, and finally, the spleen follows S tZI t;; bT^^r^r'''^''"''*"" •" r ^-"^ ^^•''"^' -'•-vtomieally node, a : Mribe.l. 1 he lungs reman, free, and the bhxKl shews no nr..- ' fh^Stf""'''"'^""''-'' *'-. ^'---ters are .liHVre.:; fZ. s= rn , Vl t ' •'''^"'■' "•' "^"' "* '"filtration, as occurs in hmph.n .r :; " rr^l^r*!!!:''! .r-T-^t''- - — i- the pre^'ious l.o4t.. an.l I., same characters are foun.l in the spleen, there being no excess '^i ornt the ^s"T '^' r^^^'"^''^^ ^"'"« '»"• •'•-" . iron. I tlu \essels. Ihesc collections are provided with a " ". ... connective tissue, and do not infiltrate, thougl he m.v 'I.on and cause to atrophy the surrounding issues We hT^^ ' '• a l.mph h!,peri>Uma mid m,f. a mcUu^tasi, ' "narked contrast between the involved no' ^fie results of chronic irri iLl^hiJo T \ "''f "^^ *° "" "'"-^cogni'-ed irritation, .i. Lymphatic Leukemia Lymphocythemia). — There mav l>o o^ developn^ent of typical Ivmph tissurthe r;ticu[urth7^n.ts a tJie cells being (levclojM'd prop *• tionately— a real lymphomat( overgrowth. At times this is i stricted to the spleen or cert« groups of lymph nodes, at tim more widely developed, even i fecting secondarily the liver ai other organs. Of inflammato overgrowth the indications a slight; the capsules of nodes mi by distension be thickened, but tl reticulum shows no correspondir overgrowth. The hvperplasia n spccts its boundaries and shows ri signs of infiltration. This can exi; without escape of the lymphocytt into the bln, dm.aso to .how v„ri.,u3 or.l.T, of -eh prc.«,.,„, ,„a„y of ,he„ ^f |,,i„.,i^.^ mflammajorv ..v,«... a. larg.- .mlullulial rHI- 6. fihrohlast, r. 0(Jsino|))]i lymphocyt..; e. pol> nuilm, niiTsion lens.) '/. oct'aMinnal iikiirytc. (Ini- recede, ther- b» ing. >nnect . \ e LYMPHATIC LEUKEMIA-LEIOMYOMA 241 AM these . u ,s,ons ,t will be see... fall into tl.rt^ mni.. classes- (U III'' sple.i.c e,.larKe,..e..i may W the o..lv sic..- there m„vK '^ |.anyi.,R seco..,lary a,.e.nia. a..|.l.n.. w.th accompanying anemia an.l icteroid state whSmiv be r.™re.l from completely when the spleen is extirpated ' Myoma (Leiomyoma).-The uterine fibromyoma or '^broid " is the -"•"mo.,est„f tnmors. \-ery freqnently thev are multiple exTst.^^ - "'fmes ... arge numbers, a,.d in situation" («) intTrsS' (hu2 I . i.Kulate Ihe ...dividual tumor is sharpiv defined and somn ;! ...ut easily while others are firmly anchored hv a Suse cap uTe I I .are two ^oneral types a..d all stages ,.f tra.isitio.i between t^hem 1) the pure .nyoma. reddish gray and softer than C>) the ''fihS'" .;-,«. a n.ost white, and showing the watereSlk ipp ara..ron ;...; T-T ""•' '""•"fi^«tions occur, the following be ng se^i tla„jj,,c.tat.c tumors. ... which the bloml vessels are greatlvdnate-' - l>n.phang.ectat.c. in which the lymph channels are istended '>.n Trims, hemorrhag.c; (4) necrot.c, an actual liquefaction nt ' ■;- occrnng; (.5) calcified so that the mass can be J onlvl^ the ^ii tc ; ' K'''^^"t^* ^y fatty orhyaHne degeneration. ^ -." rfih,;.;:^' Kra,les ex.st from pure myomas to what are ■ ui h ItL? ;• *" J>eg.nner generally finds diflSculty in dis- St. ? ^'^^»es. but if the nuclei be exan.ine ; h, a bundle of muscle cells cut transversely; r, fibrous connective tistue around bundle, with (i) spindle-like nuclei of the same; - obstruct pregnancy, and the demand fo' tluir removal is by no means so negligible as their histological nature might suggest. ^^ :!mmff^^j3M LKIOM YOMA ~RIIAHIH)M YOMA t.. su,,,L. that LVI ndZr ii; ^ ';■ ""'"' "''T^ «'"«i'Jerable reason arr: CI ) other parts of i\u IJT • '' *'"''' ""' ^'^Pt-f'aH.v seen -•!' '!'<■ skin. wluTe A- „T ^-sp nully the stomach and intestines; "•—.nee ii. oth p'^s " th;";:^^'."" wf f • r "^^^'"«^"' -^h '> •--'«•"■<« it seems tr^ S^J^X'- l^.i^^ JS. ^-'^ TYPICAL HYUC TDMOBS OF MESOTHELIAL ORIGIN Fia. S7 ton musrle fibres from a rh.iM..r.„o~., ^, ,v- ^ ^ **^"' "oP'-.i,..-. (Wolfensberger.) lomifl, generally small and capsulated, yet stUl •*& •JM ruii; Hpart frntii this, Imwrver, ll .1 ill ;ir(iiN svliiTf striiitiil iiiii>ilf i^ ni>rinjill\ pi M-iit, ^mh a- the ;irt, the txtr<'iiiitif>. the iiiUcs, thr <»rl>it. i III nil ; II'*' ciiscs the Hlin's art' of cinltrximic. iiniifrfci'tlv ilill'i r- « ntiiiitil iijitiirt', soiiictiiiH's >li(iwin>r only lnii>;if uiliiiiil ^rintion, «>r traiisvcr i- strii ti >ii nf oiil; a part of the crll, aini other > liiructt-rs, all of wiiitli |M>i'it to the likcliho...! that they arise from etfl rests In s..r of t' . ic tiiniiir> the eells are eomparative' imiliH'eretitiHteil, and l'' e u .turally liifKciil* to (listiii>;iii>h froii inuniis; in faet, niali>;i.i.ii ha'i omyoniii lias t/een n-jmrted, ' "Imh the iii'tastases sliowfil %!ri;iii'ii iiisele elements; ill hotli flu- -e last foru- tlier»' is ronsif' ' (i>l'- IW-t'iImmhI »liat the tiiinors arise from sarcobUau. lifhouuli tlie.v II ; hi' e !)ri;,'iMiite litr'NiM". TYPICAL HYLIC TUMORS OF EPIBLASTIt JRIGIN The Neuroblastomas. • > il.\ such tmnor as i mtaiii nerve cells should he classed a.> neuromas; further, if tlu -e he inrve fibres in a tumor whieli are in ckimh ction with a !,cr\e dl outride the tumor, these iire not iiidepemi t, and o fiir ji tlu',\ re concerned, the tumor t^X ^S ("fll« frnin ■. iiuti ;itii! :i tjjliif rijinf m-tU' I'liiia 'v! ! ; iif ni'iiriTii:!). ii'i-ti\.'ly, lln- -r trcint ihf Hiicrui tfifK.n. !ii»' Lint"- lit. in llit- ro(H-rn.'ll.:il n'^inti :»t th- ■■! i»f the [ttil" '• ' lit Hrh.-kr I is not . neuroma. \ltli;li i 'nie neuroma or liiii.^'lioi'Un i'* one of the rarest of tumors, .\ it ni. 4 he remeuiif red li ^ lie neurones, .lust »- jii the "\ arv th .iii tlpi c; (is and % \El /»t.\fA 2 IS --^'^'^^^^^^^^ ;li)i ( (.||, ' '"' ••l*^'i.lymiiJ nils iinintr tli«- can,. f t\ ■ i r "' , ,1 ; *•"»'»» "Muiirniua, or uiirocxtdini' r*\ ♦!. !• '■■ '■■' •'""•'^"" '"". »'kI (4) lu. ,H.,.nnon,;; • ^^ "" ^'''""""^ Hiiors ■> lur ' ..iiiip! , IV,, „ f ill (oii- '>iitain '■•iiijriion Koiind levdoi • 1 ' ■'" iim, itiKi (■ Meuroin*. Tru«- Neuromas '"■I- i.' ". f||. al. .„„.„, f.,r IM-lltjl!:, ,f tin ,ldr.: il,!,, Hl.n ills I fi, tyjje 11^, vi fl by : fiiu- 'OS); (Ifspitc this fact siich toiind to nWv ,„,.ta^i tscs, >•♦ arc practically iiciirosar- ih til 111,1 ■ til.fil. iiiiIk I f'riiii 'ilc< rnputation neuroma is ••••"la. H it the proximal end "Tve i conifs -wollcn into a "lavs, oft,.,, stronjily united hv to Its siirronndin^'s. 'I'hjs ""^'^ts of h„„dlcs of „,.rvc ^''irviiiK iip<.n themselves, and '' "I III an over>:r(»\vth . ; the " generally lack me than the surrounding brain tissue, with a bluish tinge, and pidpy by reason of the glairy fluid in the matrix. These last are found in the cerebral hemispheres and the corpus callo- sum, and may be of large size, replacing and compressing the bnuii tissue. Neither hard nor soft forms give rise to metastases; and recent studies go far to jmne that many are strictly forms of gliomatosis rather than gliomas arising fn m a single focus. Retinal gliomas show more definite signs of nmlignancy, lM)tli in their capacity to infiltrate and to give rise to metastases. They are II Fig. 91 GLIOMA— SEURl SOMA 247 Mnall, soft gray masses projecting from the retina into the vitreous "a> .nvade the se era an.l extend into the orbit; or filling the bdb eumorrnay erode the cornea and project oteniall^t a fungating ...iss. Histoiogieaily, they are forme.! of small cells, without processes TSenrt:';""""' l""' -^'-^'^ ^""' «'-'-^ may or maTnot •pneiance Tn^'Tiv'"'": "7?"^^"°""t «"KRests a perithelioma r LI. • n " iuhhtion to this grouping of the cells, there are gest the retinal cones. These retinal gliomas are formed of cells little dif- tmntiated, and are. we hold, properh gliosarcomas. In attempting to determine the itioi(,gy of gliomas, we are helpei"d .;, the white as well as the grav matter, they seem t., be misplaced in- fliisioiis or overprutiuctions of nerve tissue, evidently developmeiK II I. This and the liability of the voung to the - Pithelium of tlfe „at nre Tttt "'. '1' r '*' T '^' ^^« °" *« f"™ ■Hurones and S cells dlt ^V"^"'' '"'^^ *''*' "^'"-al canal. That --r o? gliCatlHis nair"'"""' ''''' ^^'^^'"^ "^ "" '-'"-" '" « fwclion of reUnsI glioma, showing re- lationship of cells to vessels and forma- tion of "rosettes." (Hihben.) 1^ 248 PROGRESSIVE TISSUE CII.WOES that interspersed aiiioufj the fibroid tissue are individual nerve fibres, and this relationship has necessarily caused a ^reat deal of debate. Regarding: the tumors as brought about by overgrowth of the peri- neurium, they have been considered fibnnras and wrongly termed neurofibromas. Others have recoj^nized that the fibroid tissiie is due to a proliferation of the cells of the sheath of Schwann, and believing these cells to be mesoblastic, have again held to the fibromatous theory. It has, however, been fully established by Kohn and Vero^ay that Fio. 92 -I Multiple fihrimiiitoid ovi-rgrowths along the course of the cutaneouM nerves. (Herejel.) these cells are of neuroblastic origin, that the growths are formed from a neurogenous tissue, and are derivtHl eitix r from the sheath of Schwann or from precursors of the .sam«'. These tumors, therefore, are to be descrilied as nenriimnns^ or, more aecuratt'ly, as neurinomatoid, becauM' characteristically the tumors are multiple, they occur without shari) delimitation, and along the course of the peripheral nerves. There ni.iy indeeI«>rtarK. which renre- "'f' r ntial substance are f, m , i ^h • ' T^"'"*;''' \'^' " ''«'n">Ke..eous • ' ■n'al.nc.rmi ow h fl^^^^ '"^ks; nu.st com- '""l> 'he site,.f the ™ ;„irTl r?""' f ''* ^'^'''""' t''^' '"tu'tarv ^•^ "" '"Irosis. i.rth "bone ttllLT- !^^^^ f '^^" spLemvoccipital "' '1^ l-iisilar arterv. ^"' "^**'" '"t'^'ately attachwj 2:)0 I'liOCRESSIVE TISSVE rHAXOES i ATYPICAL HYLIC TUMORS Sarcomas. -While it is logi.-al to discuss the atypical tumors with the typical tumors of each tissue, it would he cumhersome l.y reas.m .,f the nudtiplicity of the sarcomas; they are, there Ore, here dealt with as a class, the members of which have certaui characters. Ihe term has primarily a histological siguificauce ot which these characters '''Vhrsammms are richly cellular tumors of the connective-tissue t>pe, the cells hcing vegetative, imperfectly d.tferentuited, reseml.lmg he emhrv.nic mesenchyme, and developmg a characteristic interstitu suhstance-the " hvlic" arrangement. This arrangement can apply not onlv to tumors derived from the mesohlast (whether raesenchymatous „r mesothelial). but also to certain tumors (.t epiblastic and hypo- h astic origin; that is, .>n,e atypiral e,M.Uc tumors nrust ahobere „aakd a. sarcomas, .nd artkely i,romn,, tumors of tra„sUionaIlcp,d,c charact r. are also to be considered as sarcomas, ^uch tumors are mhltra- tive and malignant, hut the malignancy depends upon more than the mere form of cell present, for two tum<,rs ..t etiually small round crlls nav differ greatlv in malignancy; the tissue of ..ngm is of the greatest mportance:an.l it may be said that the more nearly the cell approache the cell of embrvonic mesenchyme, the greater is the presumption of malignancv,but'more important yet is this: that o two «uch tumors the one that has departed the farther from its adult type of cell to rl^ch this state, the one that has "reverted" the more, is the more "S'sarcomas are not capsulated, but grow peripherally m.d invade the surroun.ling tissues by growth along tissue spaces Ihis leads to progressive destruction ..f the preexisting tissue, '"» , ^''^^''P^'"' °' all that tissue save a supporting framework around the vessels and capillaries. Thus, the tumor cells are frccpiently arranged m masses eparated bv well-marked strands of cnnective tissue. J^ sareo.a cells nnne In the immediate neighborhood of the cajnlanes, and the n essts are compose.1 of a single ea.lothelial layer beneath which are the turn . c lis; the capillaries are wide and the tumor abundantly vascular. It is pn.bable, but not certain, that there is a new formation of eap.HaraN and that the sarcoma cells grow along these, just as the fil>" '-^ appear to extend outward among the growing loops of granu a n tissue. In some sarcomas there are channels that have "o «ndot e- lium, so that the blocKi seems to make its way directly between e tumor cells. It will thus be seen that hemorrhage into the tun. s "apt t.. occur, and that sarcoma cells are liable to become free m te blood stream, so that metastases almig the blmd stream are charactmdic of these growths, and the lung is apt to be a common site o secondarj sarcoma. Of course, metastasis can occur aU> along the lympiw- - so that involvement of lymph notain deeply, and ijossess round nuclei with little cytoplasm; the KiG. 07 -iimII roiiiul-.-i-lliil sarcoma frnm akin. (High iiacuilii-atiiin.) (From Professor KK-I».) "^ ICuund-ocilcH sarroma intiitrafing the heart- wall. (High iiiaRnificaliuu). Fio. !I8 S. D !• iii.l-iclU.I >!ir<-...na, iiifiltratiuK livi-r, ailvanciiig aiitig a portal sheath: V.I', portal vein; H I), liili- (liiet ; A. II, h< palir artery; /.. liver cells. iitiiil rcticiilimi is at a niininumi. These growths are vascular '' .kIIIv iiiulcrgo hemorrhage; metasta.ses occur hy the blood stream !!i«' iyinphatics. -* cdK .irc cuiisidered to ari^e from connective tissue, the growths, ' '. tH'irtg not unlike a (('liuiar granulatitm tissue; it may be recailed 254 PRnaiiKssivi-: tissie cuasces as thut the siinpU' vcnotiitivc iifiirohlast colls, us seen in ii retimil surcoma, were of this sort, and it may well he that this is the least ditTerentiateii and the most actively vegetative »■<■ »••• of all cells. , The ordinary round-cellepindle-rplled minimui (sH-ondarj . non-i.i«mpnted growth of melsnotic «ar ■■ ma— or clironiatnphnronia — of skin): o, ci'll with two nuclii, roerntl., dividud; 6, pigmcDt contniiiing leukocytes in stroma; c, neptum between alveoli. ( Iliith power ) The Oat-shape Celled Sarcoma.-- It Is jjcrhaps overcare which seek> to differentiate this sarcoma from the si)indle-celkHl sarcoma, but in ■as?. >-^ *.-».•'« SARCOMA 255 (■(iiitrailistinction to the lutter members of this ^roup have long oval niiriti lying in blunt cells. We are not prepared to state that they (iri^jiiiute from any special form of tissue. Fio. 101 Kiu. 103 Spindle-eelled aarronm (rcrurrunt, from fon-arm) : Oiit-shape celled sart-oma of unknown orinii, o. delirate-walled blood vessel in tumor. (From (High power.) (MeOill collertion.) Professor Klotl.) The Small Spindle-celled Sarcoma. — The cells of this form are rchitivdy small spindles, 15 to 20 fi long, with oval or spindle iniclei, the ((lis appearing in bundles around the capillaries just as occurs in true fibromas. The relationship of these to coimective tissue is so marked that their xHirce is evident; in fact, the fibrils which ncdir ill connective tissue may be found in till -(■ tumors, which, compared wiih round- 11 III (I sarcomas, arc far less malignant. Large Spindle-celled Sarcoma (Fig. 103).— i he nuclei are large and clearer than in til' last case, are often vesicular and the (1 11- vary greatly in their size and shape. >i'iiie arise from the periosteum, recalling tlu large spindle cells which occur in the viint-cellcd myeloma; this is to be expected '" i-,i(lering that both originate from the me tissue. i t will appear that there are not very sharply cut distinctions between • ^iiilcrent groups of cells that have just been dealt with; this is due 'lie tact that undifi'erentiation has gone on to a different stage of Large spindle-celled sarcoma. (Ribbert.) ". >"%-■«.■ laHis. 2.*)r. I'H(K!RKSSIVK TISSIK CII.WaKS !!■ li' c'«>iii|)lt;toru'ss ill i-iuli casr, just as tin- Kriiwiiij; ci-lls attain ;rowinj;. Liposarcoma. .\n ol>vions lipcmia ^rowin^ slowly for a loii^ time may take on rapHJ jjrowth and show sarcomatous areas where the fat cells are replaced liy a tissue that is richly cellular. Such a tumor may, nf course, ni\«' sJircomatoiis metastases. Chondrosarcoma. In a rapidly ^rowiii^ chondroma there is some- times found a rapid transition from unmistakahle cartilajte to richly cellular tissue that is evidently sarcoinatotis; this is a gradual transi- tion from highly ditferentiated cells to tiiose less ditferentiated, the reverse of what occurs in tlie normal j;rowth of cartilage. As the vas- cular sarcoma tissue becomes formed it can he seen to advance into and replace the more typical cartilage, so that we have the j)ictiire of cartilage formation and, superimposed upon the neoplastic cartilage, a sarcomatous modification. Osteoid Sarcoma, Osteochondrosarcoma, and Osteosarcoma.- Tluse three terms indicate ditJerent types of sarcoma exhil)iting varying grades of the process of ossification. The osteoid sarcoma is malignant, grows rapidly, and forms metas- tases; in it are areas intermediate between cartilage aixi b(>ne, that is, there is a homogeneous matrix in which the cells are more like bone corpuscles than cartilage cells; sometimes there are several in one space. These cells are seen to surround thickly the osteoid lamella or mass; they are polymori)lious, and sometimes giant cells (M-ciir; in studying such a tumor one is convinced that the osteoid tissue is part of the tumor, and that the tumor cells have laid down the imperlVct bone. The osteochondrosarcoma is more perfectly ditferentiated, and tlitre may be a deposit of calcareous salts in the lamellie, while yet other cases show both true cartilage and true bone. The osteosarcoma proper shows lamellie and masses that consist clicmi(;ally of true bone. Flistologically it is imperfect, the bone Ik ing in isolated spicules or in thin, spong\ irregular masses. Or, juiiii, especially where the periosteum is concerned, radiating osteopli-tes ajri-ear. This is true bone, although in a tumur, just as there nK\ f>e true muscle cells in a myoma. ■-X ■iPP :..rV;^ ^^Pf I'AriLW.y.i 25: llHTr ,.r su,m i.utlu.nties who are .inwillinR to lulmk that true -.,.. .;,„ t u.s rxrst „s a p„rt of a t..m„r, l,„t the fact is ac-t..allv so. 01 .. urse, tlu. mor,. p^rfc-rtlv an.l fonsi.hTal.ly this l,„„y si.hstan'c.. is i^H. .low,,, the less mal,K„ant is the tumor. a„.i we ac-tuallv fi,„| '" ".'- "•"*'f ,"^ W^^tl's wuleiy .hfTereut powers of .„aliK„a„..v. just as - Cm. I wulelv ,1, erout h,stolo«ic„l pictures. The sa,..onm"eleme.,ts '"■'.; I- -!..". I.Ydls. pol.vKoua ,ells of various si.es. ^iant cells (espe- rK,ll> .-. ceutral Krowths). an.l over the growth there is Keuerallv a |.ri.,>teal forn.at,,.,, of l.oue which is thi„ au.l rea.lily l.roken, ghiuK r^r ... the fanuhar •cKK-shcll crackli,,,.." As a rule, they .|o not form III. t;i>t;,M's iiutii the superfical periosteiun is hrokeu through Rhabdomyosarcoma This form appears in the ki.lnev and els.-wl,ere. .■;p.,,Mi . as part of the pluripotcntial tumors that have Let.,, meni ti'-i.. . J hey niay show unperfect nmscle fibres, transverseh- striate,! i'ln-li.' cells with lo„«,t„du,al fibrillation, or large polvmorph'ous. o te "H tmu,.|,.a e cells of sarc-oblastic type. althouKh it is not' noceksari^J >.itc t.. say that all such tumors arise from sarcoblastic ceIN onlv GUosarcoma.--\\e have referrt.l t,. these tumors in connection with I- n. „,a, an,l ,t w, I be recalle.l that the .letermination of such, as , Mm.t fn,„. a s.n.ple roun,l-c-ellcHl sarcoma, often .lepen.is upon the rit. Ill I..I, ,.f a few unperfect glial fibrils and cells. PRIMARY LINING MEMBRANE OR LEPIDIC TUMORS (LEPIDOMAS) it ..iiist b.. u.idcrstoo,! at the outset that while these tumors show jl-.i.l.||iat,.M, ot tissues yet the essential part of them is the epithe- I 'T ,'la,Hlular, that ,s, the hning-membrane element. It is essen- ' to have a stroma, and the very ,,resci,ce of the lining-membrane '-'-nts render the stroma more ,,roliferative. but this growth is not --ir,l^ „,ore than .rritative, that is. it is not truly blastomltou TYPICAL LEPIDIC GROWTHS Papilloma. 'lUv term papilloma conveys to the min.l nothing but ' """f ' •J«:-^^T;pt.on of the form of the tumor, and makts m ^' i;:i tti'*^ ';"'"'"T'i '"^"^*^' ^-^^ ^^-^ ''■•■ ^-'-^ «^ ^--"o I" r..t< re to utilize h,s term, couple,! with a qualifving adjective ' li-t" the nature of the papilloma under discussion. PapUlomas are 'It :.''']. Z;"'"''' T''^ '•^' ^^"*'^^'"'"^' «'-^'-^ famous or '•• '■'''"« '^. ^on»ect.ve-tissue core to each in.lividua^ process lt^Pc^. U.7 T "'^ outgrowths of the corium covered bv a thick .1'-^ ■vine,! epulerm; they arise apparently from irritation, are 'WllfiLi^iii&/a^ii:^ 258 I'RoaUHSSlX K TlSSfH ( ff\\an>! «oiiiiii()ii ill cliilillicxMl aii- ease arising as small red masses, hecominj; warty, underfri.ing central necrosis, and discharKiiiK triuiKt'-lf>(.kiiij, ii-iH-t from till Mulp ul) CuUneoiu Homa ( ll;,i>rdrratmis). '11,. pr..,,>M'> of homy coriMitiitir.ii w|,i,|, proj.rt rii.l till- filer; tlii-y are liioviihlf. the l.iiMf iMiii); soft, 'n,,' horti is ail o\tT j,reserve<|; it MTiii 'erefori, a.-, if \\r |,a,| to do with .1 j;rowths may arisefrom irritation we iMii> Mote the oeeurrenee of papillomas diu- I" the (-omdnim. whieh i> one of the sporo- zoii. This parasite appears to he alim)st de- ^""1 "I n.arked irritative power, and vet,as H n -lilt „l Its very slif;ht irritation, there is .M.-Mve proliferati..n of ■""« --■«.- ,i,„„ .\;i,'™;,;;:2;;,i ™o!"t,uI,:: Km. 100 »"n.l.vloiiiula„f Ihc vulvu. ((Jnti.) ih a bile duct becomes pajMlIomatous, and if projects 2(i() i!3^ i'i{0(!i{h:ssivE rissi'K <'ha\(ies ill (Inidrifyiiii; inassrs; at first Jiliiiic*' siicli truly new jirowth. I>iit tin- coiitimiiiiicr and the fiirtl a cmKlitioii apfH-ars to Ik- \vr irrowtli of the I)a])il!:itt' niassfs oc( ur only with tin- contimu'd pn'sciur of the coccid and nn'tastasis lu'vcr occurs. I/) BilharsiasU. la, Th V fir: %'^ Klu. 108 •vt'ii more blastoinatons in character than the last IS this condition, in \vhi<-ii (Fi>;. 1(»7) growths in the rectum and the Madder are initiated hy the ova of Hilharzia hematohiuni. of this parasite haviuj; a s|)ike, are alile to tra\el throuj;h the tissues and in the Madder and rectum induce hematuria and melena. In hotli these or^'aiis we find papillomatous i)rolifer- atioii of the nuicosa and not iiifrecp: Mitly this irritative over- frrowth jrives place to definite carcinoma. It is evident that the stimulus to growth and the ii)it of frrowth are ac(niired l)v the ei)ithelium durinjr the loiij;- contimied presence of the |)ara- site, and that the final assump- tion of carcinomatous process is the expression of tliis hahit of jrrowth. and is not de|)endent upon tile continued presence of the ejTK. lihiMfiiintitoiix I'dpilli (ii) Soft Papillomas. growths tiiere are main forms IIIIHI.I. Of tl U'se Tk;. 1(17 HiUiarzia.si..4 nf (hr rcrtiim, to slutw papillntn. i» , , ' lii'iiialc.liiiirii, i.vnvriiwtli i>f tin- iimc(),Ha: '!. nivilii'n tillid uilh I" sl,„» ,.,!,. rr„i.mi, h, l„t,.r,,l s|,ik... iI'itIs.) I,1,„„|. (I,.m.,».) <>vu..f H^n,:,r^.,•,(S.■l,i«t..,• f^oma mere n..dular protnherance of the mucous membrane to a mass of delicate long fiiiKcr-like processes; the nodular process, and eii.li of the hnj;er-iike growths alike, has a framework or stock of eoiinc( live tissue, III whicii run the vessels, while on the outside the coveriiiir is of the einthelium of the part, often with ahimdant mitoses and niten, too, showinir the utmost specialization, as when, in the intestiiii', it showri abundant goblet cells; on the other hand, it may be modified by PA PILLOMA—A DESOMA 201 ■l"1.l«;crH„f tin. v.,i,,,l li„i,',g. ' '''" """ """"•■'".>■ f»"i"l ii. Ih, may the I'm. ll)!» I'Ki. I Id ^t=*^^.' "" ""';;""l-''l"^'-h"wtl,..|..n«,fi,.«„HH.e l>"|)in.iinat.,ii« „iilKro»tlis. (Hibhcrt.) Ono of „,e fine „„,„„„„ „f„ «l.- « ll„. ,.,.nlral (il.r.M.s ,,,p. ..^ „,„.,k Willi VfSwIs. '* '-li'^K to fill ,„, the^avi^ . ' r .". ''"r "/^ ti-"-. ami vessels is JcZar i Vhe ni^l i'?" '"'■' "^ ^-""m-etive '''••'■ i^ to he eo„si.lere,l t'le LT ''^'* '^ ''■'' •'V^TKroutl,; this, in ;j'i;;"'i=^ activity ap;:i;;i;;; n;:tSt:^the?;r:':>/ ,::""'"-• *"^ S:.?;;;;r-:s;?'!;;rs Adenoma. An adenon -, 1 ' "'^'*'^''*'">'' »''•' •■"clerlvin^ tissnes ''"'•nNtly. having its^pitTeHmn • rr^^^^^^^^ .^'-V-'^^"""'' «^ "prosse, "'• • 'I "f Klmulnlar aeini ^^^ ' 2 " "^ . : ' ^fl'^^^'* ^''"* tissne he eou,- tiiii , '" \vith hi.nina- if -.s n, t u I , thea.fenon.a is in the form '"■'• of a .i.Kt. There is thus , u! "'^'•"•'»" t :t is n,...essary to know f'n. . w ,t . ■•';"" •"" .f •^"'•'"' " ^-.n . .....ever, are eo.„r l.rilfUk: '^' '^ "^'^""'"^- ^'=--- ^-.;4arith;^::ii;^^ 262 PROGRESSIVE TISSUE ClIAXGES goblet cells and discharge mucus; of the thyroid, some form c-olloid, and of the liver some pro(Uice l)iie; and as sucii growths are sometum's encapsulated within the tissues, and are iiicapahie of discharging their secretion, the secretion is apt to accunnilatc, distend the structure or the tubule, and form cysts, the cyst-adenomas. In studying such a growth as tiic adenoma we come at once to tin- difficulty presented by such a fact as this, that two tumors of the same organ mav develop histologically similarly, and yet one wdl form at the most a benign cystic growth, and the other a solid tumor Fio. Ill 1^r Odfc- ■•Z,^' ^#4* ■^P. !-...,■ ; v»'- 1/ • • vr V - * .■■•*. ■' ■.■■■■■ . -ic'V- • ■ ■■ -^r-:^ ' -^"t^X-:.- .. ■ -r::. »^^:v; '.! '/^.-^ •'lit'' '■^•V''-' ■ ■ '•■t'„--^r- 1.'""- ••• - .■ - 4 ■■■' • «•'• " A.k-nonm ..f liile .lu<-t^. f..rnii'.l of ar-ini r,.s,-n.l.Uim th..«- of nor.n.il l)il.- ilucts. (WiU..>l.l ) mass, having some of the characteristics of the carcinoma. We have, in l:.ct, to recognize that in the adenoma we have a grade of overgrowth, ('■ifTerent only in degree and not in kind from the inflammatory or irri- tative hyperplasia of epithelium on the on<* hand, and a malignant glandular carcinoma, on the other. As we have done before, we can divide the overgrowths of glan.lular tissue into (1) irritative mii< (congenital glandular hyperplasia, (2) adenoma (encapsulated), and (.ij adenomatosis (non-encapsuiatetl). We Iuim; said that two adenomas may grow from the same onran, one being cvstic, the other not; ioic being capsulated outside ot me mother-tissue, another being -apsiilatcd within tlietissue; oneniay lia\e ducts that oi)en and dlow secretion to be discharged, while th cr is closed ui) and mav become cystic. Because some of these adenciuMs, like normal glands, connect with the ducts of tlie organ, it bc-nies very difficult to separate them from inflaininat('ry hyiH;rtrophies -i tiie or-an For example, a difiusc Hi>roi(i induration of the mammar.v _ ma mmm'mmsmmmm ADlCXO.\fA 263 >l...un in succession bv the Im , . r«. *"^''' '"'"^^ ^"^" '^e cccs of degree and not of kind "' *'''' ^''^'"^''"'^^ '^'^'"^ J"^^^- t.:/!;de;i:f:^^:'^,,^';!2,s't';r t'r'^""^ ^'-^ '^^ - -^ wlnehlmve never attaillfulldl r""'' "'"' '* '•^'"'^ ('" ^'^'"-^'^sts) take on independent a hh^f't "",'"• '"'^^' """'" ^''"P'^ ^timnli -lone bv full vdifferenti Id it^.^^^^^ characters, the same can be Histologically, the stroma is an imDortint ,v.rf ^# .u i E';h:xrESi£F^^^^ tla. lormer'is the nufre iml^^^^^^^^^^^^ ""'i "P«" ^^e ether, t'"'l"«s that of the ephhd mn ,;/ t ' f ^'^^'^'^ "* *''^' ^^''^'na ""-"Hs in mice it is the tra in . /l ''T'f'T'"''' ^^ ad^""'H'arci- ^'"' >troma being fuJnL'S ^f ^ .^^ll^^ '\\ ^^f "V'^V""^ ^•coiidarv to the irrowth -♦• •' ,■ . ^'"' ffrowth of stroma "'•• '-".u-ctivc-ti sue ™ '••-""^tion. then ''•■^•'"pi'iKiicoulasm Tl , n ' '""* "" *''*^ nutrition of the '''••'-H..p.op:^;rs'tt.!^;n:r'^;Nn^^^ uit Ml:l en! t'\. ' "<-• .liffcrent degree, of overgrowth Congemtal Glandular Hypertrophy \,, ,.v.,m,.i. t .i- . - ^-rovvth of the nnnnZnZul w i< , Vn " 't' "■y development of niih,.rt\.. V ■ • '' ""^^ "P"" the '-"-vn t,.^;il n^f' , y;"^-'' *«''»'" "lar overgrowths have ■'n.>rnnd mirmarv gland *" '"•""• '-^"'»*'--"y. to l>. „„ ''ian.i.\ to hbrobis, as occur frequentl.v in th^ breast. 204 PROGRESSIVE TISSUE riiA\(iES Glandular overgrowtli, thoiiKli to a moderate extent, does apparently here exist. A similar condition is tiie overRrowtli of the mucous memhrane of the di^estiv.- tract at the ed^'e of an ulcer; prostatic hyi)ertrop!iy prohahly helonjjs to the same category. .'5. Adenomatosis.— This is the condition, closelv' related to the last nientioned, m which i)ortions of a gland or a surface become the seat of adenoma, the overgrowth occurring, not from a aiuyW focus, hut sunultaneously from many foci at the same time. Kxami)Ies of this lorin are the multij)le jwlypoid adenomas of the alimentary tract, or nnilt.pic adenomas of the liver. 4. Adenoma Prop«r. 'J'hese are the demarcated, encapsulated, benign overgrowths of glands. They are not numerous compared with the examples of adenomatosis, and they ai)pear to originate from cell-rests Wiier the cell-rest is formed of gland tissue normally comnmnicating with the exterior. comj)lete eiicai)siilatioii results in cvstic formation and the cyst may become the seat of intracystic pai)illomatous growth.' An absence of secretion indicates either origin from non-secreting cells or a highly marked grade of anaplasia. Here also lielong the encapsu- lated cystic adenomas of the mammary gland, as well as the large group ot .idenomas which arise from the remains of th,- Wolffian duct, although f^''." ' adrenal a.lenomas are related very cioseiv to the transitional lepidomas. THE ATYPICAL LEPIDIC 3ROWTHS CARCINOMA I p to the middle of the nineteenth century, an\ malignant growth was desigiiate.1 a cancer. With the developni tit of morbid histologv, pathologists came to use the term cancer as svnonvmous with car- cinoma and as sharply contnisted with san-onia." Within the last few .years, with the development of "cancer research," and with workers ill this dej)artiiieiii studying both carcinomas and sarc.mas, we are reverting to the oUlvr use of the t.Tin. We shall thus emjilov the term cancer iMdiscrinuiuit<'ly tn iialicat.' a malignant growth of anv order, tlie term caniiioina to denote niily cancers of eiiitheliai and glandular origin. Carcinoma. We here consider atypical growths of both covering e|)itlielnim and of ghuid tissue, and point out fhat the properties of both are alike, to such an extent that the most atypical form.-, are scarcely distinguishable. Here if anyxvhere are found excepti(.n-> u> the ruh- that the greater the .Jcgree uf anaplasia, of depi rturc from tiie adult normal histological type, the -reater is the malignancv, for M.ine of these carcinomas in the primary growth defiart but little and .ire exceedingly iiiahgnaiit, while some that are greatly anaplastic ar.' <>! relatively mild malignancy. A good e\anii)le of the latter is rodent ulcer (called basal-ceUed carcinoma), a viiant, as cxcninlifipfi K,. - N.M„i„atio„ will show s S" Cnrt e^^^^ «< enocarci„omas. caref,,! ■''-."<- ••'• " ''.•'snnent Mul.rau ,%;.''" ^''^ ""••'"«'' «"«el. as tlu- ■""drdh, aUiinral ,r!h. ' "'"' '*'•"' "'"■^'"■>- "f ''iml „r Relations of Tumor Cells and Stroma - \ « ; ,, ♦ i i niMtinn IS cften u-rv well niark^.! /..'""' •'•""^■«''"'- -Stich -". ^.ppoanuK.. with a -aiWen.:;;;;^;;;;;^,:;^ ( j,^^^;;;^'^^;:; w tin. ^uhI,-, tll,.; ilMlic, prir\ i'n.li:, ;t..;;m.l7fc;t^'-|--!l^.-tnuethe,. I'l""'-;• Pr.1 .n" Chiton' r"- ■*'""• ''^^ -^^--l'"l«r "' ^'"' fi-^^ne is „se.l t., f„ , f. u'. s ! ' ""/''.*" '''^''' ''=""'• t'-e .'"' ^'- '-""- ...av sti, "t, s„,h T;' "* "'■ """•"•• «"•' ♦'•-' -'^^•nr uui 2fif) PROGRESSIVE TISSCE CUASGES order of ti?e excited to an atypical overjjrowth itself, giving rise to what is a true carcinoma sarcomatodes. According to the degree of reaction we are accustomed to use certain descriptive words to denote carcinomas of different consistence: (1) medullary, where the cell growth is abundant, and the stroma incon- siderable, the resulting tumor being cellular, soft, and like marrow (medulla); (2) scirrhous, in which the stroma is abundant, the tumor cells being scanty and compressed; and (li) carcinoma simplex, where no marked predominance of one over the other is noticeable. :r.-f.:^*|^yv^^| Kpithcliimm of lip: a, n, epitbi'liul "pt'orl':" '>• Bmall-rclled infiltration of Burrounding tissiu' at iwriphrry of nrw growth. K At the edge of a carcinoma the cells generally stain deeply and are intensely vegetative, and while less so centrally, there may yet in this position l)e mitotic figures, indicating that the growth is not only peripheral. Generally, degeneration progresses fairly rapidly in the deeper parts, and this degeneration sometimes varies according to the function of the tissue from which the tumor is derived ; thus fatty changes are common in mammary gland tumors (recalling the active part taken by the cells of that gland in supplying absorbed fats to the milk), and mucoid changes in tumors of the alimentary canal (in evident rela- tionship to the normal function of the goblet cells of the nuuinis membrane). "Cancer Bodies." — These are bodies, found in and between circi- nomatous cells, which have often been supposed to be parasites, ami the cause of tumor growth, but which are at present considtTnl to be cellular degenerations. Thus we encounter small, hyaline, s|)li' -^ical bodies of varying size, the mean size being that of a red corpuscle \ hich stain intensely red with fuchsin, and lie singly or in little groups attuhed PLATK VI '\I\'mIi Ii ,,in E"' im.-M ,,l Pr.,1,. — ,,, Kl •IK ,|, rive-rl In. Ill tl M"l -: '.. 11,1. .Ill ■I/'. ,1, .■,.||-. cli^l..,nl,-.| Willi .l.-\..i.l ..I II, -111 ■ '. i"iniiiii~ ..1 y . ^^ '-iy^its?-. CARCINOMA 267 to Olio iinotlier, hotli intracellular and free in the struma. They are known us "Russel's bodies," after their disatverer, ure met with not only in mHlig- iiaiit growths, hut iilso in inflaniniHtory areas, and are consideretl to he ('\iinii)les of hyaline dej{eneratii)ii, hut >. hither of re' products. (Greenough.) ilcs(rij)tioiis recall ihe successive stages of a protozoan, with progressive tiil.irsjement and final setting free of spores, yet the study of the tiiii rochemical reactions of mucin, hyaline, amyloid, keratin, and other iliKciieratioii products shows that the same reactions are obtaineti in ilif case of these bodies. It is, t>f course, possible that some one or more of these bodies may eventually prove to be [)rotozoan, but in the present -t itc of serial sections it has been possible lo see that although in a single ' tiun tlie alveoli of tumor cells apj)ear separate, yet in different iiic- they are i.I! connected in a series, or a Si't of series, I'or it may be -mI.Ic to determine that there are more centres than one of origin, ^^:^-. '\'P^-^.iS^ ^^. V*<^ «■ ■:' mi ^mtmmmm. h^ ^h- i-4* - d%. m 1 "v^ *** "' ''''■ ' ' "iSi ' v^H' .*■ ^1!* -^^ I m W^ 26.S I'RocRFs^nK r/.-sTf; rii.wofis thut the urowtli is iiliiria-iitric arising fruiii st-vcral ii siiiiiiltaiu'(iiisl\ . (kca-iiiiiully si-M-ral primary urowtlis, widtly M-paratfd. aro ni- couiittT'-d, as tM-nirs in tli*- niiilliple sn)MTK<'ial );ro\vtlis of chiiinicv- -ivveoif or of workers in paraHin. and U'st (»l all, in tlio frwinency with whicli iKith nvaries arc aM'trtcd l>y larfinoniii lairly frwiuently, t «liiiw ('i) ri'llimi <>l "riniii hy ili>» l>-ltrii»tli from prrtxistillK ipillic liilln; '■, h. i'pillH'li:il i«>arls; r, Kiiiiill-t'illi'it iiitillratioii ill mirrouiiiiiiiK ti.wii". (IVlenh'n.) iio farther than to state that the same instahility of tissue that iM-nnits the overgrowth of tissue in one plaee in a typieal (henign) way, afi'ectiiip numerous tissues, allows atypical overgrowth in another, or even sub- sequently in the same plaee; that is, the nudtiple growths arise as a sequence of a vii<> of development or from the developn)ent of multiple cell rests. The develoimient of now si.i;,'l(' now multiple tumor- is paralleled hy the state of afi'airs we find it infection. There, generally, we fin N ra.M.,|. .....i furthor .nvHsi,,,, „t nt\wr ,M,i„ts is n-sisUNl I„ „ " pnv,.,., f„r luT .l..v,.|op,nn,t ..Im-wIut... .Uhou^U nut strl^Zl ... ..vfn„„,.. t u. t.nnur Kr-wtl, alrc-a.l, i,.stitnt,.|. That his 2 :m. .■ .s r....,l ,s sh„w„ ,y th.- fa.t that a mum.s,. i„.K-nhm.. w th r- rri. . , m :i.:"i;:;;;;;;:;;;r;;;-:.::;'t;^''''''-'^^ Sq.ianioua-ceUe(l Carcinom. (EpitheUom.). Tumors uf this onler ..rid .-..; Iron. s,,„a,nn„s .•pithdin..,. a„.| an-, as sn<-h. ehit.r,, ?• i , . f. on..n; h„, snu. hvpoMastic linin, „„.„.l,rane .nay h. ^^„ ^ ^ t Mnh.,..sopha,..s.tlnsals.Mnayuiverisc.tos,pun„o„sHdo^i<^^^^^^^ .i - th. sk,n Kh.n.|s of ..pihh.sti<. oriKin can «ivo riso t X, ^ I .-..-.s It .s c.v„|,.„t that MO ahsoh.to .listi.utior. nn, ho ma.l i , t J «.,v .. .•onsuh.r.nK one o cpihlastir an.l the othor of hvpol.K • or Jin . . . unhMK to ,ts roh.t,onships an.l its functions, a jrivo,,Ii „-,«,,„ 3 ' 1^ '|".^t,pc oi tlu. ...other t.ss„e ,s the ,n«h«na„t growth that arisei Fill 117 III lull .|Ua.„ous^.eIh;.l eareino.na ,,resents soli.l eohin.ns of cells ,,-,ss •-'.e tint tlu. I- "' ?"'V'"; "^ *'-'^' ""'"•' ^•"" '- "-"lerstoo- «>'»^'^'>-- The outen..ost projttte,! part would be those of the .Malpighia., laver MtCROCOPY RESOLUTION TEST CHART (ANSI and ISO TEST CHART No 2l 1.0 I.I i^ i;;. IIIM IIIM i;^; 1^ 12.2 1- 1^ II u U£ 2.0 .8 1.25 1.4 1.6 ^ APPLIED INA ^GE Inc ^P^ '•■''■'i Lost V'j'i Street rJS "Ocheslef. New 'o-k U609 uSA JjS '16) <,Q2 - 50G - Pt-one SSS -le; 288 - 598^ - Fa. mm 270 PROCRESSIVK TISSUE CHAXGES and the innermost ones the normally keratinized cells of the surface. If the imaginary finger were now withdrawn, and the projection later- ally compressed to ohlite Ue the space left hy the finger, the solid column so resulting would show precisely what is seen in a down-growing process of epithelium. In less tyj)ical growths, the difTerentiatioii between the cells of different layers is hy no means so clear, and with greater degrees of anaplasia the cells may he round, j)oIygonal, or even spindle-shaped, as may happen in rodent idcer (Fig. 11!»), and in this coimection it is to be remembered that the extreme anaplasia is not necessarily a sign of extreme malignancy. These tiunors which show a failure of differentiation toward flattened and keratinized cells have been called the basal-celled carcinomas, on the ground that such arise wholly Fkj. lis ill Impurn or Iransitionnl opithclionia of nntruni of Highmore ("basal ceiled carcinoma"), in which instead of central keratinization and pearl formation, there is central rccrosis and autolysis in), with production of lunicn-like space. from the basal cells of the I\Iali)ighian layer, although, as a matter of fact, as this is the actively growing part of the epithelium, all the tumors arise from it; it is the degree of anaplasia, the incajjacity to develop beyond a certain jioint into the flattened and keratinized cells tluit determines the existence of such tumors. There are certain difTereiiccs to be seen in the squamous-celltd carcinomas according to the site of their origin. Skin and tongue tumors arc apt to give well-marked pearls; oesophageal tumors are not so apt to show them, just as normally in the a-soi)hagus the keratin development is not marked. The nitire rapid, too, the growth, the more atypical it is, and the less apt are tlie differentiations to appear, just as the process of keratuiization on the skin requires the lapse of considerable time, and a constant slow pro- gression of removal from the dee])er. better nourished layers bel<>w; CARCINOMA 271 wlure the growth i. rapid a.ul the cutting-off of the cells from their n.itntion correspondingly hastened, more active degenerations (even ii.cTosis) are liable to occur (Fig. 124). Bcncruuons ^e\en Fio. 119 Fio. 120 l''irlic,n of edge (.f a rodent ulcer. Part of the same at a more hipihly magnified, to show assumption by the epitheUal cells of aspindle- shaped type. (Krompecher.) S,,,umious-colled carcinomas are found occasional' in regions which Mormal y possess columnar epithelium, such as the larvnx. broi chus ...nach, uteru.s. an.l gall-bladder. It is in these verv r;gions hat "e .Mc.unter. either as the result of metaplasia or otherwise, islands Fia. 121 Aberrant s,,uamous epithelioma of Rall-bladdcr. (Von Han«>nmn„.) '' tlKi"'tuZ!^T' 'f^^^^""' '^"d apparently it is from such cells ' ' nit I. llorn ou T "l a7 "■' ""' ■"f'«'"«»t'.v ™-ed- showing : ti< ..oniatous an.l glandular carcinomatous constituents. 172 I'ROaiiKSSlVK TISSCE CllASdEti Gland-Celled Carcinoma.— Tliesr tumors differ somowhat iucordiiif; to the structure of the mother-tissue; from tuhuhir Rhmds we are ai)t to obtain tumors that show, or attempt to show a tul)uhir arrangement; from acinous glands, tumors that have a grape-like arrang ent; from the liver, a tumor of cells arranged in solid masses runn" g in irregu- lar strands. As before stated, it is necessar.v to consider the tissue from which it arose, before one can say how typical or atypical is a certain tumor. In the tumors which show a distinctly glandular form, there may be a relatively orderly arrangement, with an attempt to form lum'imi or, on the other hand, there may be no such attempt, so that we arrive at the forms in vhich the gland formation is lost and solid masses of cells occur with more or less abundant stroma, according Fia. 122 ,4^ I'f •;••■■'•■ .•-aLM-*- m V^Tll Aclcnocariinoiiia of rrrtuin (from pnpiiralion of Proffsaor Klotz): n. hoction arrnss tul)ular ilinvn- growlli with largo luimn; 6, more solid iiiasn of aberrant gland cills forming multiple luniina to the amount of which, as alrtar . \aini)lc, we get pure adenomatous and carcinomatous growths! \vt, though rarely, it does happen that a tumor of one of these areas may show most marked hylomatous characters (as in one of our cases of prostatic tumor where the primary growth was typical carcinoma, but tlic extension sarcoma-like, in the judgment of some well-known patho- idsrists). Such tumors have clearly transitional properties. 1'. Tumors of the Ovary, Testis, Adrenal, and Kidney.— In con- >i(lcriiig the tumors of the kidney, it is necessarv t j remember that the Wolffian duct provivles the distal, collecting part of the tubule, and the nicsenchyme the glomerular epithelium and that of the main part of the tubule. In the ovary and testis the primitive kidnev, intimately connected with the Wolffian duct, is involved, along with the germinal inesothelmm. Thus it comes that, while in these organs we meet pure adenomas showing no sign of reversion, we also find a series of transi- tional tumors which in places appear to be adenomatous and in other places sarcomatous, and yet other areas where one passes into the other and the cells in the sarcomatous areas may even be spindle shaped' Mich tumors, once for all. dispose of the idea of the strict bounds that were tonnerly supposed to exist between carcinomas and sarcomas, and tliat such tumors can exist is due to the common embryogenv of the I>rinntive tissues. ' Adrenal Tumors.— It has been said that there are in the ovar\-, testis Mil. ki.lney, tumors of fxed type, which fixity is perhaps due to the stahihty ot the W olffian epithelium. Tn the adrenal, however, there is no Mich ( oubttul origin, and yet we f n.l in it transitional tumors. I li«' ndrcnal, it is true, arises from two sources: the medulla originates 111 ".nneotion with the sympathetic nervous system, the cortex from nuM.thehal elements. In the mwlulla originate tumors that are true I 'iromas with rudimentary ganglion cells and non-medullated fibres ^^liKh evidently arise from cell rests of the sympathetic system; the •"rtical tumors, however, are entirely different. Iir>t there are accessory adrenals; they are composed of cortical " '■«■. lying in the adrenal capsule or in the adrenal itself or outside ' ■ -T even in the kidney and more rarely in the liver, while at times "'|,^ liaxe I.een earned down in development and appear in the ovary y '<-tN. U hen such are found to hypertrophy, we deal with an adent^- ";""n.> phenomenon. These tumors show the typical cortical tissue, ■■"',,„ ot cells lying „, a meshwo x of capillaries, the cells wiiiK I'vcry transition from n, cpIIs UPdistinxuisliublo from the Burroundinn cplls of the cortex to small cells with deeply staining nuclei of sarcomatous lype. (Adami.) similar conversion or molated embryo^ K'lcally so that tumors arising from them must possess closely related ",*'*'"»■.•, ^'"'' '^''^^' '^ supported by thelatest workers on the subject namely, Wilson and Dayis. When such a tumor of the kidney tends t.. form tubules instead of solid columns of cells, its renal origin is a riasonal)le supposition. Tliese tumor, are apt to be yascular, the cells being in close contact with the capillaries, and they are prone to hemorrhage; metastases l.v the blood stream readily occur, and especially is the tumor apt to Sirow h\- continuity along the yeins to the yena cava. A useful term to describe all these transitional tumors of the adrenal kKlnoy, oyary, and testes is mesothelioma. A mesothelioma is thus: I. A tumor arising from tissues which, while of mesothelial origin piissess in the adult state lepidic characters. ' riT ^Jvu" *'^P'^"' **"*' ^' s'ow growth, it is an adenoma. IIJ. When atypical and of rapid growth, a sarcoma, although transi- 1 1. .lis I K-t ween adenoma - ' -.•-. coma are to be seen . I\. The secondarie. .; . natous •!. Mesotheliomas _^ Surfaces.-These are flat, nodular t.iin..rs, si.rea.i.ng locall.% er tiie pleura, more rarely the peritoneum or iHTicardium looking ^o tLe naked eye like a localized inflammatory 'i"«k.;iiing and under the microscope, like a carcinoma. They evidentlV arise Irom tiie endothelium lining the serous cayity affected. A relatiyelV ■'>M-i(laiit stroma is present, containing elongated acini, formed of irreg- ■r swollen often cubical cells. Here we deal with a carcinoma-like i nor t>,at has originated from the part of the mesoblast that has T.||^<■l| lip a liiiinjr-mcmbrane function. t Endotheiioma.-The endothelioma is a tumor arising from the ' n^ «lls of a vessel, ana may be a hemangio-endotheUoma, from a o Vessel, or a lymphangio-endotheUoma, from a lymph vessel; in a "" r of long establishment it may be difficult to make the distinction. ' M-nssing overgrovvths of blood vessels, we have to consider first J' '.ma! ones, and this leads us to the consideration of some tumors '■ ^' ire not blastomas, along with some which are ■iu;rr!!rsti;^nJr^rr"t'^ angiomas (tumors having vessels as their "■"■.u.nstituent). whether hemangiomasor lymphangiomas, arenot true 278 PROCRESSIVE TISSrK C II. WOES l)l)istoinu.H; ////•// /«).w.w no jmwrr of iudeiH-iidnii (jwuth. Mt-rc (liliitat ion of spiins, fvoii if pmrded In aplasia and fulJowtMl hy atr()|)liy of tin- siirr()uii(liii>; tissues, is not Krowtli; nor I the iiitToasi' m length of a vessel (as in a cirsoid aneiirysni), nor im-rease in tlu> tliiekness of walls (as in cavernoma) to he considered as more than physioloKical. We find widening of preexistent vessels, either congenital, due to a lack of c(M)rdination hetween the amount of tissut- lo he supplied and of vessels to supply it, or postnatal. i'iir> in them. Their congenital origin is a-crihed to the failure of the original c'lipilliiries to become clotheeiiiKn angioma. Cases which show -|ii('s to (ii-eliarge the lymph. ;i. Cystic LymphangiectJwis.— The most striking examples of this are ""|"I Ml eases of "cystic hygroma," where multiple large, clear cysts ""iir hdow the ear, or submn:dllary, or above the clavicle. The «' ilinj; is tense, and the large cysts often do not communicate with ''''•yn.,,tht.r; tlu-y a e lined with endothelium and have strong, fibrous ■ p I lis is not due merely to obstruction, but the secretory activitv ;>' 1 He eiMlotlielmin is likewise responsible. Not to be confounded with -> cervical hydrocele," where a cyst, lined by epithelium, arises from I' n nt a eervical duct or fissure. A true hygroma may appear in the ' a7 •''*'T"i' " '"™ ^^ ^^"^ congenital sacral tumor. tvpical Angiomas. Hemangio-endotheUoma.— The most character- - > > ^aIlll,lt■ i> that developing beneath the dura mater, where it forms 282 PROGRESSIVE TISSUE CHAXOKS I!? ; i II nofliiles tliat displace hraiii substance or spread as sessile masses. TI uppearunce of the inicrosc(»pic field is strikiiij;; the tissue consists ruinierous whorls of concentrical disposed cells, which are flattent but not tightly i)acked, especial at the centre, where one may oft( distinguish the lumen of the blo( vessel. If cut in a direction m jjcrfectly transverse, the mass( ai)pear oval or curved, and in an case there may be between them good deal of cellular fibrous tissm The whorls may show hyaline r calcareous change, in which last ca; the tumor is called a psammomi , ^ , The psammomas, sometimes mu Hiiiianitiii-tnilothclKmia from nose of child . • i j. u I i (Dr. KIntz), showing devolopment of new ^'P'^' aPPCar tO liaVC alwayS thl capillaries (o). endothelial origin and the rapidi growing ones are sarcomatous. Lymphangio-endothelioma. — ^Vben there is no perfect whorling c cells around the capillaries, growths of this nature may be considere as arising from the endothelium of lymph channels. S«i-iion froir. a pirilhi'lioma or perithelia! angiosurcoiiia (from the eolleetion of Dr. Rhea) .ihomni the relationship of the central bluovth and lose the habit of function before they can originate a neoplasm. A cell that is ready to be the starting-point of a neoplasm diti'ers from an embryonic cell; the latter has the ])otentiality of dirterentiation still before it, the former has lost it. As suggesting how tlie cell has lost it, we ])ut forward Oertel's hypothesis that as in the protozoa we find in some cells two nuclei, one associated with rei)roduction and the other with the functional activity of the cell, so in man and the metazoa there is chromatin of two orders, of which one governs the i)roliferative, the other the functional cai)acity of the cell. A tumor cell is a cell that has largely lost the latter; when lost the cell is unable to replace it. Such a cell can give rise only to daughter cells that lack this power of dift'erentiation, but are still endowed with full vegetative properties. That such is the case is not yet i)roved, but the idea is worthy of preservation in tlie i)resent state of our knowledge. It seems necessary to recognize among the blastomas some change in the biological i)ronerties of cells as an essential for neoplasia. It is not something outside the cell, neither an external stimulus nor a diminished external resistance; it may be that an external stimulus starts tl j cells on that path which leads eventually to their assuming neoplastic properties; it may even be thot the malignant growth affords a secretion which depresses the vitality anrl inhibits the growth of surrounding tissue cells, but these are subsidiary. The essential point is that the cells giving rise to an autochthonous new growth are so modified that the energy acquired by the accumulation of food is not discharged in the performance of function, as in the healthy cell in normal relationship, but is retained and accumulated only for purposes of growth and multiplication. This is far from denying tiiat various stimuli assist the modification of the cell; it may be that in one case the cell's position, displaced as it is, tends to retard its function but not its vegetation, or in another case that a micTobic or parasitic agent begins an inflammation that acts similarly, or in yet another case that a senile loss of function paves the way, the change being accompanied by ;in alteration in histological characters. There is not oiic specific agent, but many and these at the most begin the process. The end-result is a cell mutation. What is the i)ractical bearing of this? It is that the cure of cancer does not lie in the discovery of a parasitic ?ause, for, judging by what we know of the nature of malignant cells the mere removal of a microbic or ])ara- sitic cause will not suffice to stop cell activity and the propagation of the properties that the cells have assumed. We have rather to seek agents that will influence the growing powers uf these cells. Two possibilities, at least, lie open. ';;^raih CYSTS 287 The first of tb( se is y till- tissues, parallel to that seen in various infectittns, and it seems l>()ssil)lc that tumor or even normal cell extracts mighl exalt the defences (if tlie body against tumor growth. Yet we must not be blind to the fact that many incjulable tumors induce but a very slight general rc'ii'tid... The second mode of destruction of new growths is ])arallel to the iinployment of the agents that produce passive immunity. It may lie that drugs or animal substances, or mechanical af:rits like radium (ir the Roiitgen rays, chemicals such as salts of selenium and tellurium, or body ferments may be found, to which the neoplastic cells are more s(ii>iti\o than are the normal ce!is, their growth being arrested and atrojiliy and absorption ensuing. As a matter of fact it has been fully (hinoMstrated tiiat radium and a^-rays especially arrest the activity of \(i;ttati\e cells. As this work has been passing through the press, \Va>MTniann has aniunniced partially successful inoculations with com- pdiind^ of selenium and tellurium with anilvi dyes: these ha-e resulted ill the destruction and disapj)ea ranee of the cancer cells in mouse carci- iKiina witiiout injury to the tissues in general. We say partially suc- : (1,1 retention cysts, due to abnormal dilatation of preexisting 'ii!(N of the organism as a result of secretion outstripping absorp- -i hemorrhagic cysts, dut^ to escape of blood into the tissues and ipient encai)sulation; Qi) necrotic cysts, due to the death and lique- .-^rm^s^ 288 PROGRESSIVE TISSUE CHANGES m im faction of tissues with subsequent encapsulation; and (4) parasitic cysts, due to the development (in itself normal) of metazoa.i parasites within the organism, such jjarasites possessing a cystic stage. A. Secretory or Retention Cysts.— This group may he subdivicled according to the nature of the cells lining the cysts into (1) cysts with cubical or columnar "glandular" epithelium, (2) endothelial, (3) epen- dymal, (4) squamous epithelial, and (5) composite cysts. In all of these, when cellular activity leads to secretion into a cavity unprovided with an outlet or when the outlet is obstructed, the fluid is secreted against piessure, Fio. uo which, while low, is above that in thi cai)illaries; as the secre- tion Is continuous and the ah- sorjjtion less rajHd, the cavity is gradually distended, and under this gradual, not excessive strain, cell multiplication is favored, Kici. 141 Section through a retention ryst of mucosa of under aspect of epiglottis, due to obstruction of a mucous gland. (Professor Klotz) (low power ) a, blood vessels: b, compressed acini of a mucous gland: c, cartilage; d, artery. From the same section under higher magni- ficalion to show the flattened epithelium liaing the cyst. and not only the lining cells multiply but also the underlying coniiectjye tissue. Eventually the lining cfHs become flattened by pressure, (Fig. 141), and ill-nourished by reason of the pressure on the vessels in the walls, so that atrophy and final disappearance may result. The watery contents of the ceil sire absorbed, so that the less diffusible products (rf secretion become more and more concentrated, until the cyst may be filled not with watery fluid but with inspissated, thick, jelly-like, or colloid content. ■KilllMIII CYSTS 289 I. Of Antenatal Ohuhn.- Congenital Cysis Due to Persistence of I'lirh ,if Embryonic and Foetal Ducts—TWis is a large frrouj). In the un.wtli of the cml)ryo and foptns, certain passages that onlinarily hccoiiic closed and atrophy, may not become completely absorbed; tikse rcriiiin isolated in other tissues, and either immediately, or after years iia^e elapsed, their cells may take on secretory activity, giving oriu'iii to cysts. Some of these are as follows: [(I) Thyrolingual cysts in the median line of the neck, from the thymlingual duct leading down from the foramen ccecum of the tongue to the thyroid. V) Branchial cvsts on the side of the neck, between the angle of the jaw and the stewioclavicular articulation, from t!ie branchial clefts. The contents of this series vary from mucous flui«l to sebaceous material according to whether they originate from the inner end, lined with mucous membrane, or the outer end, lined with squamous epithelium. (' I ViteUo-intestJnal cysts, near the navel, from the omphalomesenteric duct which communicated between the small intestine and the yolk sac. ((!} Urachal cysts, in the hypogastric region, from persistence of parts of the urachus. (c) Ci/xtn of the Primordial Gen ito-urinary Passages in the Female.— FIr. 1 12 will serve to recall the relations of these ducts and the changes liy whicli they arrive at their finally destined purpose; cysts are liable to arise from imabsorbed portions of those that atrophy. Cysts of the Wolffian body are apt to be multilocular, growing in the broad ligament. Tysts arise from the lateral (free) tubes of the paroophoron; thev are of siiiall size. The cysts that arise from the connp?ting tubes of the iwroiiphoroii (connecting with the ovan) may be of large size; they are often single, and are lined by various kinds of epithelium, though tins may be lacking in the larger ones, where also cholesterin mav be toiinil. Cysts of Gartner's duct occur in the broad ligament and in the vajrinal \yn\\. Hydatid of Morgagni is the term which describes the nstic dilatation of the long fimbria of the Fallopian tube. i.fi ry/.s/.v o/ the Primordial Genito-iiriyiary Dncts in the Male.— Stalked hydatids are found at the upper pole of the testis arising from WoHhan tul)nles. Encysted hydrocele of the testis may arise from the ^iisi (ti(rentia, while from the Miillerian duct may arise at its distal ciKl a sessile hydatid, a cyst in connection with the globus major of the Cl)l(|l(|y|i|is. '' ifn rnniirnitul Cy.sts Due to Arrested or Imperfect Development of i.laiuluim- (hf/ans.— This class is well exemplified bv the congenital cystic kidney. I„ the formation of this organ, the glomerulus and the mHii, proper arise from the mesoblastic nephrogenic tissue, while tiie coliretmg tubules take origin from the Wolffian duct. When a proper iimetion between the tubules from these two sources fails, the Jei" '" '""" "'""^'^ distends the upper parts of the tubules and cysts lit ' -=w» . I ..c 1 'S.^.'^CA '* 290 I' Ron II ESS I VK rissi'E cuaxoks III II. Ok Postnatal Omc.is. ]. Orinlndfiiitj in Tiihuhtr (Unmh ihrnufih OI>»tnictii>ti of their Duds.- Tlit-sf art- the ordinary "retention" eysts, arising from pluKjii'iK <>f the duct hy mucus, or a calculus, or from stenosis of tlie iluct fntm previous injury or i)y the prrssure of surroundinj; fihrons tissue or of near-hy new jjrowtli. Examples are very numerous; ranula of the floor of the mouth from obstruction of the suhlinnnal thict or that of tlie ijlamliilu incisiva somewhat in front of it; salivary cysts from hlockinj: of a saHxary duct; mucous cysti Fid 112 m J\i ro(V/>/ioi'(>?i or ycpiifif lit. of M'ulffiu'i Biitly. Iirua I. II S ,: a a _ i o -I s B I'diailidijini yephrif lit. I'f Wolffian Holly- III. '{plationsliip i,! the sixii:il iliiil.s and tijiir ruiliiiirnts in tin- luci sixis: /, Ihc indifFircnl priniars' typo. //, thf iliflcrcntialiori in llic fi'nialf. ///, Uic iliffcrcntiation in llie male. Ilyd Morg., hydatid of Morgagni. I'cd. Ilyd., pedunculated hydatid. I'lff, vagina; Seasile //i/J, sessile hydatid. )f the intestinal mucosa from Ijlockinjj of tlie crypts; i)ancreatic cysts (ranula pancreatica) ; cysts of the mucous jjlands of the epiglottis, the trachea, of f'owper's jjlands, and the glands of Bartholin; hile cysts of the liver; cysts of the kidney, of the bladder mucosa, of the glands of the cervix of the uterus (ovula Nabothi), of the lacrimal gland (dacryops), of the ducts of the mammary gland (galactocele) ; wens and sel'iuemis cysts of the skin. Here also belong cystic dihitations of hollow organs, such as the gall-bladder (hydrops vesica fellese), of the appendi.x, and CYSTS 291 tlir r,.ll..,,iHn t.iho (hydrosalpinx); tl.r n-tn,tio., „f ..toriia. .iischarges In (i< rhisKm o\ the cervix jjives hydrometra " .-/'^'•''V'"/'"V'" ^!"fr ^'/'""/•^•- (JIa-xis like the thyroid and pitn, ;.n . heinK f«>rine,l at closed vesicles, are liahle t.. distensi,;,, of these MM.Io so that thyroid c.vsts (thyroid goitre) or pitnitarv cvst.s (K-cur; .„.! 11. the ovary, ,.ysts of the GraaHai. follicles «„d cvstsof the corpora li.t.M .,.;iy arise in some of the former an ovnm may persist, thoiigh jr.hcniljy It undergoes disinte);ration. III. ( )K Xkoi-lastic OHKiix.- 1 . Cystadenomas.- Adenomas of tuh- nNirj:liMMis In tliecontinned pro.lnction of (ahnormal) secretion become .li^t.i,, i...l aiHl <.ystic; especially is this true in the ovary and the mam- m,ry i^liind; and in snch cysts there is a tendency to the multiplication Fio. 143 .nL',r,r!' ',' ?,"■'",", ''r ^''^'r '""" " "'■"'"'"' •■''"'' '■■""« "'"'■■'Iv "f" birth. Each orRan Rrra.lv '-!Xx'"r::.,.!;r' u'"";, r ^''^^tl'^Pi'^'na^^''^ i">^rowths of great li.K . f , ,r iw '" '•'' "■'"'''•'■ '""'"Stood that here the horder- ; - nr.. prnl.lerat.on ,s readily passed an.l neoplastic growth •^;/' •'' ■' '.rciMoniatoiis nature, instituted. fe™vMn. ol the lining membrane) is a relatively small one. Tht ,^^V'-M..> .re serous cysts-sacs .listended with serous fluid or ; . • ...c sacs are normally lined by endothelium, either of r . on ot a .serous c-av.ty or of the lymphatic system. Ex- 1 " ..e ioriner are scrotal hydrocele and cysts o«Lthe cknal of Nuck 292 PROGRESSIVE TISSUE CHANGES ',f the latter buml cysts, ami "fMiflta" (rysts fonncil l.y the tuttinn-oir Bun^il and Ivmph cy.ts in ge..eral ..we the.r crigm tc, a e..mh,nat...n of c cumstance'; there is iricreased activity and lessene.1 ahsorp u.„. and n manv there is no doubt a lew Rrade of .nflajnnmt.on whuh. Sling to a progressive thickening of the .al!. yet further interferes with the pn)i)er degree of absorption. M ero us c Ists of congenital origin the niost stnku.g are the hyromu. which are most common in the neck (hygroma co h) \et l^e » commo CYSTS 293 form i)f uc|H'rt Ht a (the palifiade layer of the rete Malpighii); the stratified flattened cells of the epidermis i:it t" iKivf l(»Nt the power of growth; 2 and 3 show the continued growth of the celts of the rete Malpighii, ulii'li Iritiii the wutit of growth of the <-ells at h must come to surround those cells, and form as at 4 a -cili.l. MiKJ lutir. us ut 3, .1 hollow sphere. ."). Composite Cysts. — ^These are cysts whose walls are composed of iiKirf than one kind of epithelium, whose contents are from glands ili") hiir^in^ into the cyst; sequestration cysts of the skin are such, as i> hydronephrosis. Sttiucstration cysts occur in the line of fissures of the body, where in the process of joining, some cells of one or both surfaces become de- prissitl, and sequestered in the underlying tissue, there eventually ^'i\ inj; rise to a cyst. This may occur at the dorsal groove, the thoracic- iilidoiihiial cleft, or the facial clefts, and in the part cut off there are j;( inriilly sweat or sebaceous glands, and hair follicles, which determine the iiiitiire of tiie cyst contents. Such cysts may not only be superficial liiii (itrp, and because of the comparatively late development of the -kiiN, t'lcy may be found attached to the dura mater. Hydronephrosis ("(ur> when the urinarj- passage is obstructed; the kidney continues to -(I rite, and the urinary canal to be distended, especially the pelvis of till kiilncy, so that ultimately the kidney itself may be transformed into a thill-wailed sac. Of the nature of composite cysts, too, are those ill lii>ions of tooth sacs or remains of the enamel germ that are found iii 'iic jaw. These may be lined by epithelium, and may even have til til ])r(ijecting into them, in which case thev are true dentiferoos cyst". i '•■ Hemorrhagic Cysts. — In the brain, as a good example, we find f; 1 torination following upon a hemorrhage; the blood outpoured ;i' ' :i^ a foreign body and the tissue makes an attempt to wall it off ' tiiiniiis capsule, while at the same time leukocytes and autolysis ;ir r. .p,,iisil,|e for the removal of the corpuscles. The blood pigment, 291 I'RmRKSaiVE TISSUE CllANaBS m t(M>, in (;ru«liially removed, so ttint ii sninll amount tirouiui the capsi may be the only inchcation of the faet that McmmI has been pres«'i and even this ultimately disappears. The cyst fiiuilly contains a clei serous fluid. A like prrmin layer; t\ d, r, dcvclopnicnt of Ifie heads accordiiiK to Leiickart : /. 3, h, i, k, development of thi- hci according to Moniei; /, fully deV4'loiK'd bnnjd capsule with heailH; m, the hroo. 4. r tnodc of formation of wcondary exogenous dauKhler c\st ; /, daUKlitcr cyst, with one cndoKcmtuB a onu exogenous grund-»i without infection, as in a large infarct, it may happen that, after tl mmmm CYSTS 205 ti>MH> has liecomo li(jiH'fie>i i> Mii)i)lied, in part, by the parasite, althoi- jh the irritation of its pr.M IK I' leads the surrounding tisRiio to build a nbrous capsule on the |"itM(lf of the hyaline cyst wall proper. 'I'lii> .-(.-called hydatid cyst may be single or multiple; its wall is hva- li'" inil larniiii.l'MJ, lined internally by a granular (cellular) '-^yer from «li:!i project t.ie iieads of new individual parasites, with character- i-ii( liotklet Secondary heads ar- constantly being buddeii off rmii the vvall :.,id thrown into the fluid; these it is which render the "in.l likely t . infect the peritoneum if allowed to come in contact "itl, It .lur.! , remt.vid. The secondary heads mav give rise to the "H, at toil ot daughter cysts in the primary sac, or less frequentiv, til' 'liiUL'liter cysts may form on the outside of the mother cvst in-^-ad • iiiMile, causing a multilocular cyst. :i: I CHAPTER V THE REGRESSIVE TISSUE CHANGES NORMAL HISTOLYSIS AND CTTOLTSIS For a proper understanding of the regressive tissue changes, it is necessary to consider how the tissues naturally decay, for however rarely we pay attention to this phenomenon, it is going on constantly. Tissues and organs in the embryo, representing ancestral structures, appear and disappear. The thymus reaches its maximum during the first two years of life, and undergoes absorption; the lymph nwles, at their largest in youth, become smaller; the milk-teeth disappear before the inroad of the permanent set; after pregnancy the uterine tissue undergoes involution, that is, the cells which were hypertrophied, atrophy ; the ovaries atrophy at the menopause. Red blood corpuscles and leukocytes have a life of but a few weeks; they disintegrate and are eaten up by other cells; even so solid a structure as bone is under- going constant change. All this is but the analysis of the popular saying that the tissues are renewed every seven years; the particular definite length of time has no foundation, but the principle is true. The destruction of cells in the ordinary wear and tear of tissues is doubtless a complex process, the result being due to changes in the cell itself, as well as to forces acting outside the moribund cell. We are not in a positixjn to recogni/A' the signs of approaching cell death by any special histological change, but we can tell sometimes that cells are growing old; in senile atrophy, for instance, the cells grow smaller and often lose finer details of structure, such as the transverse striations of muscle fibres. A cell in this state of senility is not as capable as it once was of carrying out its functional duties, and sulistances which it ab'^orbs are not properly or completely converted and tend to be stored up; the products of its own cell disintegration, if not solul)le, in a similar way tend to be stored up, so that by the presence of paraplasmic material in the cell we may recognize its senility, either natural or pre- mature. An excellent example of this is seen in the so-called brown atrophy of the heart muscle cell, in which the cell is seen to be smaller than normal and to have at each pole of the nucleus a deposit of fine reddish-brown granules, which are thought to be the final insoluble [nod- uct of the breaking down of myohemoglobin. (See Plate VII, Fig. 1) Ecjually good as an illustration is the change wrought in the muscle of the uterus after i)arturition. During pregnancy the muscle fibres have undergone i-'inu-nse hypertrophy, and during the first w«'rk after delivery they shrink in a degree no less remarkable; from I ing un an .^ite ..: ' .. J nam WW PLATE VII Brcivvn Ali'iipliv. lli..^M, -,lr..,.hv ..I I,,... lit. Ii...,i -.,-, iM.n -Kiin...i l,v Kil..x>lin. 1., -I,,.w ''•■■"'"'""'■'' ' ■••■l.h-h- 1 ,i( ,^\ II |, I, nil, Mil ,|l;iiiiil.--. .It ..|lli.-i |„,l,. ,,r •■■• I'! "I 111.- nM'ii|.liM mil-. I.- hill-,.- Fiiilv DefifMUMiiIlc >n. 'ii'i-.'- ,,r li,.;iri rr,,iii ,.,,„. ,,| |„.rui.-i.iu-. ;iii..iniM, -,u,iiiM,l l,\ I "I'l h. -111,11, ,x^ 1,1, .,, -!,,,„ liui\ . 1 'a ^Ita ^25^E^ri»71?SE^SS^S ATROPHY 297 a\ truije 20S li long, they become reduced to 24 m- (Sanger.) In addition, tluy look more cloudy, and sometimes show refractile globules of fat. 'Ihis is fatty degeneration, and a simultaneous fatty infiltration is \ i^ihli- l)et\vcen the deeper muscle cells, this fat disappearing with con- >i(l(r:il)k' rai)iult from tiie inunobilization of a limb by mechanical means, or if the IK r\t' 1)1" severed. Disuse atrophy is very well shown in the nervous systiin, ill which it was for long thought that when an axone was severed, a (It'jrciu'ration only in the distal severed part occurred; but there is MKiri' tliaii this, for a disuse change occurs even in the nerve cell body, ami tliis is especially so in areas where, in health, there is a constant HKccssioii of stimuli reaching the cell; in the absence of these stimuli there is atrophy. L'. Atrophy from Overwork.— Overwork, carried beyond a given limit, t( ,i(ls til induce cell-exhaustion, if continued, to produce cell atrophy. it is difficult to bring forward clear examples, but we would suggest that certain of the professional palsies belong to this category. ;;. Atrophy from Malnutrition. — The alteration of the body from general starvation is a case in point, as well as the atrophy of special areas whose arterial supply is pressed upon and lessene(l; even the airupliy causeil by pressure is another example of the same, the most ih ii-c tissues, like bone, tnidergoing atrophy when subjected to constant lire-^nre even by a fluid mass. Senile Atrophy. A closely-allied form is senile atrophy — the natural >i;irini; out of the tissues; but there is another factor concerned, for !'i -oiiic ])copic tiie process begins at an earlier period than in others. >iime tissues, too, grow old more quickly than others, and as a general I nh tiic first to atrophy are those that become functionless during the I itiirai lifi': next to tl .-se come the lymphoid structures— lymph nodes, Maliiitrliiaii liodies .it the spleen, and the red bone-marrow — which iiilerp) ^rptat diin'.nution; next to these come "store-house" tissues, ■ h as the fatty tissue. Nervous tissue, ordinarilv, shows atrophy ' it of ail. \\^--n) fatty tissue atrophica, tlic fat gradually melts away until the ' !ia- once more become a connective-tissue cell, but sometimes ^i^^KT«<>^^^.ar-< Y*'>M*EfiHV ' ;'(^-i^^'-6*:;i..:;W" ^^s^^Kr^r^^^Tv^ 298 THE REGRESSIVE TISSUE CflAXGES m instead of this the phice of the fat is taken by a serous fluid, so thai H large mass of fatty tissue so altered apjjears translueent and jelly- like. This so-calle(i serous atrophy of fat is not definitely known t( be a purely senile ehanRe, but may be so regarded. When the cells ol the active tissues atrophy, we have first the diniiiuition in size, tnit atrophy, then in more extreme stages a diminution in number (hypo- plasia), and along with this the dejjosit of pigment, especially in those cells that normally contain pigment. This pigmentation occurs in brown atrophy of the heart, as we have already iiulicated, and it happens similarly to a marked degree in the liver. In bone the process of atrophy is a rarefaction whereby there is an actual loss of bony substance, the individual bones become lighter, and there is an increasecl liability to fracture. The loss of substance is largely central, the medullary c-vity and the Haversian canals being increased in size, and the tral)ecuhe .-.iid lamella' thinned; the red cellular marrow becomes replace*! by fat, which again may undergo the before- mentioned serous change. The characteristic changes in the senile skin are due not so much to any epidermal changes as to a loss of subcutaneous fat and fluid, accom- panied, of course, by actual tissue shrinkage; the elastic tissue of the dermis is also altered, bet oming less resilient. This elastic tissue change becomes very important in the senile degenerations that occur in the arteries and the lungs. In the arteries, as the walls lose their resilience, the arterial tube dilates and is unable tf) recover itself, remaining per- manently e.xpaixled. At this stage, when the expansion is permanent, we may find so difl'use an enlargement as to constitute a fusiform aneurysm, or if localizeiic around the arteries and bronchi. Throughout the tissues of the body, with the exception of the nervous s\ stem, there is everywhere to be seen, along with the senile atrophy of tiic specific tissues, this relative increase of the lower, supportive tissues. This is partly relative, that is, as the other tissues abate, the fibrous tissue conies into greater prominence; l)ut more than this, there is actual incnase. a replacement fibrosis; and this is more pronounced in the li.ri\ascular (periarterial) regions than elsewhere. The nervous system wiis stated al)ove to be an exception; here, it is true, there is peri- iirtcrial increase, but there is relatively little or no gliosis; the place of lost substance is filled not by tissue, l)ut by fluid, a hydrops ex vacuo, which is the reason for the oedema of the pia so often observed at autopsy in those far advanced in life. Abiotrophy.— A condition allied to senile atrophy, called by Gowers alm.trophy, -equires mention. There are certain "familial paraplegias, diseases like i iiomsen's disease, and the so-called parasyphilitic diseases tliat lack explanation, as well as paralyses developing in the most exercised limbs. Certain cells and systems of cells degenerate, and ultimately become disorganized, the rest of the system remaining uiiphaiiged, and this often in a way that suggests that the trouble is (■(jiin.ctcd with heredity. The conception of abiotrophy is that these ctHs begin life with less resistance, with less potential energy than others, s(> tliat tile stress of a toxin, such as that of syphilis, uses up a consider- ahlc i)art of their energy; later on, they quickly become exhausted under ii stress that is no greater than normal, even although this stress be no (itlier than the usual work that is demanded of such cells. An i\|)(riiiient that exemplifies such a general abiotrophy is to expose fro- --pcnnatozoa to the .r-rays; the ova are fertilized, but the larvie, atiir a few days' growth, expire prematurely, cell-exhaustion having sniHTveiied. Reversionary Metamorphosis; Kataplasia.— While studying atrophic •liiiniris, It is necessary to mention a regressive process that mav some- tinus I,,, found accompanying them. In this, highly organized cells are stcn t() (liange to a less specialized state, to become more embryonic, a Kindition of aftairs that has been well observed in muscle fibres; just ii- tlic sarcoblast by slow transition becomes the muscle cell in a'pro- ^n.MN (■ way, so the muscle cell may become the sarcoblast in a regressive ]'■■'>} The most commfnily seen example of the process is i-i the liver 'II " lii.h the bile-duct cell and the liver cells have a comjion origin, and ■1 t'i 'iilar arrangement of cells is the earliest grouping that is seen; in thr . t\,l„p,„j, liver there is a time during which the liver cell and the [II. -'Inct cell are not to be recogni. id one from the other. Wh^n, as in cirrhosis of tli. '' *> > 'iver cells ber:i to atrophv, the trail ifion from liver cells ti cells become. , heaoing-np of what we term by-pro.lucts must tell deleteriouslj upon the cell and its activities. It was thought, but now seems less ctrr.a n, that we could distinguish two processes, which might accompany ea.n CLOUDY SWELLING 301 (itluT, one the chaiiKf wrought in the cytoplasm itself leading to the iil)|)carance in the ceil of such changed products, and the other charac- tcri/t'd by the appearance in the cytoplasm of substances obtained from iiiitsidc the cell, and, it may be, imperfectly handled by the cell. It was thought that the former were degenerations proper and the latter infiltrations, but further study shows that it is becoming increasingly (iitficiilt to separate the two, that, in fact, they are too closely related to jHTinit of being considered apart. Kspet-ially does it seem to be that triH" infiltration, by itself, is a rare occurrence. Cells, it is true, become infiltrated with or contain the substances in question, such as fat or ^'l>(uf;fn, but it is doubtful if this is secjuent to a process of absorption of the fat or glycogen as such; it is more likely that these materials art" the result of synthetic processes, the activities of the cytoplasm Ix'ing responsible for their appearance. For example, fat as such is IK it to be detected in the blood, for it is to a great extent saponified hfturc its absorption by the intestinal mucosa, where it is converted into a soluble compound. This the liver absorbs from the blood, ail' I reconverts, by its ferment activity, into fat. When globules of tat appear in the diseased cell, it is not likely that these arise from tiic lireaking down of the protein of the cytoplasm, but rather they ajiiKar, perhaps in excess, as a sign of the lack of competency to deal witli them on the part of the cytoplasm. Whatever be the source of tlioc ])araplasmic substances, de^'eneration and infiltration are so closely linked that they may well be considered together; in many cases, in fact, thf.\ are inseparable. Cloudy Swelling. — Perhaps the most common morbid change seen at autopsy is that of cloudy s^\elling or albuminous degeneration, in wliidi the cut surface of the organ has a dulled appearance, as if, to tiiijiliiy a much-used phrase, it had been momentarily dipped in boiling \vat( r. With this, there is d certain amount of swelling, which, in the ividticx , causes the cortex to rise above the level of the medulla and makes the cut edge to evert. The individual cells have lost transpar- tiu \ , anil an unstained section will show, by transmitted light, the cells (ir urmips of cells that are cloudily svsollen as shaded with gray, con- trasting' with the clear white of normal tis.sues. On close inspection, the mil 1( i look as if obscured by the deposit of a finely granular material in the (yti)])lasm, and they stain less readily than usual. Weak acid or weak alkali clears up this cloudiness, apparently by dissolving out the prei ipitated proteid or albuminous material. < liiii.ly swelling is found in the cell under many different conditions, iliiet 111 which are acute infections and high fevers; it is seen also in varimi- intoxications, after chemical poisons, in burns, and even in star, uidii; the granular material which appears is evidently a product lit' ah. red cytoplasm, and seems like the granular material ordinarily iks( ri'iieil as Altmann's granules, but with this distinction, that it seems aRi.T. .licii into larger masses, and there is none of the regular linear arraiL rnent seen in the normal. It is not possible to say definitely ,j.'*r^.,|,„*iiF^-. 302 THE REdliESSIVE TISSIE (H.WdES what this matcTial is; accnliuK t.. Martin Fischer, it is to be reKardecl as the result of conversion of certain coHohIs of the cytoplasm from the soluble int.. the soli.l or "^el" state. It is evi.lently either material (lisintenratcl fn.m the cytoplasm or material absorbed an. not com- nk-telv •• han.lle.l" bv the cell ; ..r finally, it may be b..th. The increase in si/.;- is partlv .lue to the increase in these paraplasniic materials, but mainiv t.. a hv.ln.pic oiulition aiul increase in the watery constituents. (■l.ui.lv swelliiiK is n..t t.. be c.nf.uin.le.l with granular .lefieiierati..!., which is a .lisintegrated state ..f pr..t..plasm. an.l a precurs..r of cell death- the .In.plets. at least the larger ..f them, are .lue t.) hquefactive necrosis. The process <.f cloii.ly swelling thus seems t.. be the expre«si..n „f overstimulati..n of the cell, with .lisonlered metab..lism an.l the heaning-up of paraplasmlc matter of an albuminous nature; apparently it is n.^ a ncc.>sarv cause ..f cell .leath, is frequcPl y recovere.1 from, and yet is pn.bably the earliest stage in what may be the progressive deteriorati.m of the sick cell. Fia 149 Kio. 150 Clou.ly awpllinRot ii'llsof coiivol-.ite distinguishable, but in many cases the two seem t.. be blemie.1 "Fatty Infiltration."-Neutral fat is a c..nstituent of m.«t of the tissues of the body, but in a state unrcc.gnizable ^-^1^";'^^ ^^^^^ chemical means. The ki.lnex- tissue ma>- be dem.>nstrated tc^ possess I;;" the extent of Z^ per cent, of its s.>lids, yet may by «tammg -- tions show n.) trace. On the other hand, certain regions such as he subcutancus c.nncctive tissue, the omentum the appendices p phnca., the car.liac gr.,.>v..s, an.l the area armni.1 th^k«!"^>. "'^ jj'^ c.,ntain fat in large amount, the cells being distended - f^ i. /J' ;; not fattv infiltrati.,..; that term shoul.l be onfine.! *» ;»f' "^''^^/J", lective tissue elsewhere, especially in the interstices of tissues, ^^h.ch xmvB^ m7H3"'™)wvB«!»'-"'*'w»'^:/T,'iaj ISTRACKUAJLAR FAT ACCUMULATIOSS 303 1„. „.s thus laden. Tnu- fatty infiltration may thus occur lietwecn the , inliiic nuiscle fibres, in skeletal nuis<-les, or in an orfjnn like the pan- , rri> The liver cells, too, may become the seat of a notable fat-fleposit, |„r(\ample, during pregnancy, and this is perfectly properly spoken „f MS fatty infiltration, it niav be very extreme ni such states as chronic „l('oholism, where four-fifths of the total solids and 41 per cent, of the ,rll Mibstance (including water) in a given case have proved to be fat. It i. to i)e remembered that in aU other parts of the body fatty mhltration atlVcts the connective tissue; in the Uver, the ci)iuiective-tissue cells are ii„t involved, but the liver cells proper. liitty infiltration may thus arise from a number of causes: 1 Physiological.— There may be a heaping up of fat in the liver .liirins; pregnancy aiul lactation apparently as a preparation for the ' ■>. Ovemutritioii.— The "foie gras" of the overfed Strassburg goose is a fiiiniliar example of this. . , . ,1 :; Substitution.— Fatty infiltration, and not cirrhosis, as pop larly MipiMHfd, is the most common affection of the liver in alcoholic-, not- witliMiiiiding the fact that the confirmed alcoholic is not a heavy eater; al((ai.,l, being a foodstuff capable of easy oxidation, probably rej)laces tlic fats, and these, nt>t being oxidized, remain and accunuilate in the ' '1. Diminished Oxidation.- («) Congenital.— There are some people iiaiiirallv obese just as tl'.ere are others naturally spare. The former lurlnrn." tlK-ir metabolism slowly, and the defective oxidation of their tatt\ acids leads to a gradual accumulation of neutral fats in the cells. Tli>'n,i(l extract lessens obesity in such people, probably by reason of it^arirlcrating the oxidative processes. >/, ThmiKih Dlitease.—Vatty infiltration, of the liver often, and of til. .itlur tissues sometimes, occurs in those ill of a wasting disease (iiotr,! ill tuberculous cattle), because lowered vitality and low func- tiduu! activitv of the tissues mean lessened l)urning-up of the fats taken a^ 1u,m1, while fat from the subcutaneous and other tissues may be trail iMisfd to the liver. "Fatty Degeneration."— In the cases of fatty degeneration that apprir to be trulv such, there is primarily a cell degeneration, the fat : (i.posited as a result of depressed cell activities. The nuclei may liooriv, and in the cytoplasm are minute, dust-like fatty bodies -^tained with Sudan III or Scharlach R, give to the cell a diffuse -red color, the hisrh power showing that this is due to abundant .' t'att V dots. The tissues so affected are: (1) those liable to cloudy !!'.: (gliiiid cells, especially of the liver and kidney (see Plate VIII, . and muscle fibres, especially of the heart) (see Plate VII, Fig. 2) ; i, lutliclial cells of blood vessels, and (3) certain cells undergoing '■ rc;;rcssive changes (cells of the sebaceous glands, of the mam- Iv ■■t;ii; will-'- cr.'ii' mil.: Fi.. liii tii; V\ at first sight appears to be a like accumulation of fat in the form ■m: Via. 151 304 THK RKdRKSSIVE TISSUE CIIASGES of minute ulc.l.iiU-s. I.tit without any nu»;ratinM. occurs ,wrmall„ iu ti.c cortex of thea.lreual. an.l ui ti.emusclecellsot t he uterus undcrjioiuK involuti..n after parturitiou. ( )m the contrarv. vvuh nuclear '^ ^ dejjeneratioii tlitre may Lc Uir>,'e globules of fat in the ceil, as happens in phosphorus poi^m- ing. Histoh»Kieally, it is there- fore not saf»- to say that the minute gh'hules indicate a de- jjeneration aiul the larger ones an infiltration; there are evi- dently intermediate states. Typical cases of fatty degenera- tion can be divided inco: (1) those Fio. 153 Section showing fntly .'. . &ff m ^ % Fntty .legeneration of liver cells: h, fresh cells. cl.)U(lvaml gr.inuliir, nuilei not clear; a, the fine, fatty globules seen more clearly after treatment with acetic acid. (Uibbert.) Fatly degencrali. . of hci.rt-niusrlo fibrcK. showing diffrnutvr-"lesuf involvement of iIk individual fibres; fti»h specimen. (Ribberl.) following cloudy swelling, therefore the second stage '"f /^"/''Y*^; "" inflammation of organs, and (2) sm.ple V»<'«'^P;^'^t'^'^/5'^*>^ ! ;, T^j ation. (n) j.hvsiological, an ^^'^ ' ' ;' " trition of starvation or of the extreme anemias. 1 here xs no cert.unt>, LII'OID DEPOSITS 305 (if (i(iir>f, that any or all iif tlit'st- fatty (If^jt'iu-mtions ar«' not pri'crdtMl li\ I liiiiily s\velliii>{. Lipoid "Infiltration" and "Degeneration."- \\v imve said that the ai'iKiiniiKf of the (rlls of tht- cortex (>. acln-iial appears at first -i^lit to resemble fatty (lej;enera'!on (see Vlate V'llI, Fijt. 2). The work (i( the last few years upon the lipouls has denioiistrated that here we (Icil not with the aeeiiiiiiilation of neutral fat. hut with globules whieh, unlike iliose of the neutral fats, are found doubly refractive under the IHiliirizinj; niieroseojH'. Some neutral fat, it is true, nwiy be present, but tlicM' cliiiracteristie >;h)bules are, aecordinn to reeeiit investigations. f(iriiitf;<'neruti(in: epithelium Irom 11 snijtllpdx papule. Tlie epideniia) cells greatly (twolten, difltended by large vacuoles. X 300. (Ribbcrt.) toll- .It-, ' tir- 11 I.- ii,,„: iifti' I' flic Ixxly in tlcgenerative processes, notably in the atheronia- icins of the aorta, in degenerating cancer cells, and in areas of :!ii()ii ill the nerve tissue. In fact, more than one of the lipoids •vi\ the ajjpearance of double-refraction.' One of the simplest ' -t f.\aiii])les of the existence of these doubly-refractive so-called ■ lrii|)l(ts to study is in the sputum of adults coughed up M inoriiiiig. It seems, therefore, that just as we may have I tatty "infiltration" and "degeneration." .so also we may have iiililtratioiis" and "degenerations." This subject is being 'uilicd at the ]>. ^ent time, its chief interest lying in the ' twteii the lipoids, and the proteins, many of the former See also p. 20 for cla.isification of liiwids. ^f ^^^ii*: ;{(Mi TIIK HEailf:SSlVt: TISSrK (IIASaKS n-simhliiiK tin- iiiu liiiis in posMSHiiiK lM)tli tiitrnK«'ii«ms ami phosphcric riulirlfs. aii.l sunp-stiiiK stroiijtly, staK»'H «'itluT in tlir huil.hiiK up or «liss«K-inti(m of IkmIIi-s of the lattor onlir witliiii tlif roil. Glycogenous Infiltration. \\v liavf littU- kiiowltMlm' of tin- sijtmfi- cance of Kl.vio^jfii in tin- tissm-s in ahnonnal situations or amounts. It is found inu oonsiderabU' nunihtT of rapiilly Krowinn (TJIular m'oplusnw, as again in HtnU's tuhult-s of tlu- ki.infv in oases of (lialn-tt-s. It has h«rn found also in pus crlls. • i ■ i Hydropic Degeneration. Cloudy swilling U-ma ass(Kiate«l with an incnase in tiie watorv contents <.f the .til. then- art- oxtrt-inf khuU-s of this in whioh actual vacuoles appear in tlu- cyt..i)lasm; these watery vacuoles nn.v increase in size till the cell hursts; the accuniulate.1 fluid from the hurstiuK of several contiguous cells may then form vesicles. The m.)st extreme examples of this are the "imkUs" in smallliox, where the deeper layers of the epidermis Ix-come hydropic, swollen, ami disintegrated. ... , n • i i ^ i The explanation of siah absorption is that the colloidal outer laser of the cell which repres«-iits the cell merahraiie of plants, ordinarily prevents the diirusion <.f crvstalloid niole<-ules; that crystalloid mole- cules do appear hv some .lisorganization of the cytoplasm, and as Ioiir as these exist in the cell hody in greater c«)iicentration than in the surnmiiding metliiini, wat.-r will diffuse inwanl until equalization omir*. Thus the cell swells up and Lccomes hydropic. In addition, Martin Fischer calls attention to the fact that increased acidity of a colloulai menstruum leads to an increased imbibition of water. Vacuolar Degeneration is seen in muscle and nerve cells, and is char- acterized by the ai.pearance in the cytoplasm of vacuoles, which are presumablv caused by an osmotic absorption. Serous Atrophy.- This has alrca- T,,,.,xs —There is a series (.f ill-understood degenerations in which apin-an in the tissues material that in 1- • unstained condition is trans iK^nl or glassv; when colorless and firm, we call this hyaline; when eolor-i-s^ and fluid or semifluid, mucoid; when semisolid or solid and of n» appearance of glue, coUoid. Hyaline and nuc.i.l were ""fe/;-*""'"'^ as specific substances; but we know now that what is calleo hyatine for example, mav be pnMluced in difTerent ways. Amyloid is an evcep tion, and from its staining reactions seems to be a separate entiiv These substances are proteins; and in a molecule as large as e\.n in simplest protein molecules are, it will be readily understoofl that J comparativclv small change such as a few more or less carbon Mom or a few more or less oxygeu atoms may be the cause of a oonsule am change in properties; and these lower proteins are only thus far reuu>Ne( from ordinary protoplasm. Pl.AI'E VI H Fntt V Dt*qf'n^r'Mi i< >n. ' !t-.t,.tift:ili.»n < .( . «-ll-. i>t ? .t ; H 1 tie , -III tfrv»Mi 1 1 u| n 1 1' >l I V < Jt I Itc I t I I till If if lli»» ki() tii»v, InnM ■^tni iiecl S\u III KUi U Li |)(>i(l Infiltr'aiion. i(» JKJreniil ireHtetl willi Smhiii III, to -,h«»w a 4M uniiiliil iMi 1 III the *"itt"-. ;ire aht iiirlniit ircc from lipoid iiUihuics r*. cell rotmr. u- 'iWML-.m^f^i^^^^^m ■«!J MUCOID— COLLOID— AMYLOID 307 Mucoid Deposits. Mucoid Degeneration and Mucinous Deposits. — The iniiciiis arc filycoprotfins, coiiinoiinds ht'twi-fii proti'in and car!)!)- Ii\ ilniic; tlu'v arc laid down in the body intracellularly and intercellularly. I-Aiiinplcs of tlio first are seen in the salivary filands and the jjohlet (ills of the intestines, and of the second in Wlirrton's jelly in the iiiiiliiiical cord and in the nmcinons intercelhil'': 'h..:i!\ of embryonic li--iit s in j;eneral. In either ease, nuicin is vise. I, swells iii* uii i water, i- Miluble in weak alkalies, and is ])recipitat< 1 b. aistin of the enlarged colloid goitre; similar material may show itself i I -ides of the pituitary The next most common site is in the i: iiry tubules in certai. ases of chronic nephritis, the tubules ' ' 'iiiiig plugged with dense hyaline, or more accurately, colloid casts * !i tiike on a deep stain with the ordinary staining n-agents. ' myloid. This is a material allied to the matricial matter of cartilage, ' 't found in normal tissues. When it is present, it has a character- aiii)earance and well-marked individual reactions. It may be ' ili/ed, affecting several organs, or localized, affecting a relatively ' area of inflaminatury or neoplastic growth. W- 808 THE RKaRESSIVE TISSUE CHANGES Generalized Amyloid; Amyloidosis. When advaiurd, this affects a larjjo mimlHT of orj^aiis, fsi)e(ially the spleen, Hver, and kichieys. Tlie only tissues that have not heen t'ound affected are the epidermis the cutis, hone, huij: tissue, and nervous tissue proper. If tiie spleen and liver he free, it is useless to search other or^'ans for it. The affected spleen is enlarged and more dense and firm tiian usual. On section it lias a semitranshicent, waxy ai)pearance (hence the terms waxy or "bacon" spleen), this being ditFuse; or rounded areas are seen on the cut surface of the size and appearance of sago grains ("sago spleen") the affected parts being the Malpighian bodies. The ajjpearance of the liver and of the kidnc\ is by no means so characteristic, but the reactions can be readilv demonstrated. Fia. 156 Fig. 157 ^ '^ \c Ant\l<»iil lii'i^riicratkin affi-ctinK tin- liii-r; sliKlilor grade; the cells are .•.till preseni with hut inoHerate atrophy; the irremilar depo.^il iihied liver eella; h. tran.sverse section of a (;apillar>- surrounded liy a hroad ringof amyloid material; r, a capillary c»it longitudinally, (liihhcrt ) Rf(i(ii(»i.~ On tile cut surface of the organ washed free from blood is poured diluted tincture of iodine. When the surface has assumed a pale yellow tint the amyloid will ha\e a brownisli-rcd color; if now a ."> or 10 per cent, solution of suli)huric acid be poured on, the amyloid becomes violet or black, the rest of the tissue remaining relatively unaffected. The same method may lie applied to the microscojiic examination of sections cut from the frozen tissue, the affe. T?d parts showing clear and yellowish by transmitted light. Kveii more distinctive in sections is the use of watery methyl violet, followed by washing in very dilute hydro- chloric acid; this applies to fresh or alcohol-preserved material, mid shows the amyloid as ii rr)se-pink mass against a slaty backgrouiul. The deposit of amyloid occurs in the walls of the capillaries, just external to the endothelium, and in th" larger vessels the connet tive tissue of the media is th«' iiart affecteo. The amyloid is laid down (piite irregularlv , so that a ves.sel may look iop-si ELASTOID—H YA USE 309 m- twofold: the lumen of the vessel is encroached upon, and the* ti-iics are thus ill-nourislicd, as u II as subjected to pressure by the l>liysical presence of the amyloid; ultimately the original tissue may be iiliiiost destroyed. Amyloid deposits are made in the body during thr course of long-continued drains upon the system, especially when till-; is a sociated with an excessive product' ■' and an excessive waste III' iciikocya's, altliotigh a protein discharj,^ y.! any sort will produce the elfVct. ChrcMiic bone tuberculosis with cold al)scess, osteomyelitis, ^xpliilis, leukemia, Bright's disease, or even prolonged lactation are -I line of the states that produce it. Localized Amyloid. — This is seen in localized granulomatous masses "f tuberculous or syphilitic origin and in coimective tissue tumors, Imperially (tf the head and neck region. In such sites the small blood- ussels are relatively unaffected, the amyloid being laid down in the interstitial tissue, perhaps along the lymph channels. The Nature of Amyloid. The blue color with iodine and sulphuric ;i(iii led to the supposition that amyloid was related to starch, whence Its iiiiiiie; but its protein nature was soon shown, although the name iHT-istfd. It is a glycoprotein, containing chondroitin-sulphuric acid. Tlii- material, brought by the bloofl or lymph, probably diffuses out tliroiigii the walls of the vessel and meets a local protein with which it iuiother form seen often in the uterus after delivery and involution, in winch, especially at the region of the placental site, arteries more or le>- (ihlitcrated are to be recognized as glistening, hyaline masses. The remit studies of our colleague. Dr. (ioodall, have shown that, associated tt It li the narrowing of the lumen of the much-dilated vessels, the internal dustic lamina undergoes a most remarkable process of swelling and t'll'liiii; upon itself. At first the swollen elastic tissue reacts with Wei- j-'eri s .lastic-tissue stain; in a later stage it no longer gives this reaction. 1 lie remarkable fact is that within these swollen masses a newer, smaller iirteiia! lumen is developed, which may become surrounded by all the :irt( riiil (^)ats, intima, media, and adventitla, whereas to the outer side, til' prcMously h.\pertrophied media undergoes complete degeneration jiii'i al.s<>ri)ti()!i. In this way the arteries adapt themselves to the I'- 'lied demand for blood by building what mav be an entirelv or iwrniillv new artery within the lumen of the old. Hyaline. Of the other ortlers of hyaline, which still retain this name, th. III;! ti- iiip. tihr ■ini.iDncst is that foun!) Hynlinp deueneration of a ((lonierulus. from a kidney showing ebronic interstitial nephritic. ■jp'j^j^xcjsnp^.i IIYM.ISE 311 li. re we (leal not miToly witli a lihroiis tissue which has n |.lii(i-(l (lead inusclf fil)ros, l.ut with a hyaHiic traiisroriiiation also of nnixlf trils whose imtrition has hccii cut otV throiijrh ohhtcration of the arterioles. Jn several orders of tumors there is a siniila. hyaline ii(( rohiosis of cells farthest removed from the nutrient vessels;' these tiiiiiors then assume the appearance known as cylindromatous. A like hvaline change may also affect the organized fibroid deposits on serous Mirtiice:;, the new connective-tissue growths of granulomas and even ."il)iilary walls. Of this last, the most noticeahle example is seen in the hyaline chmips which represent the glomeruli in cases of chronic interstitial nephritis (Fig. 1.")!)). Fiii. KK) J.G.A. Ill ilir,. tl.ri.iHhus in diluted vinulc of hemorrhoid. This was perfectly honmgeneou* Ueichert. ol>j. 7a. oeular i. Camera lucidu, rediieed one-third. Hematogfenous Hyaline (Hematohyaloid).- Of this form the type >le is seen in hyaline thrombi due to the intravascular and intra- "iigiiitination, either in) ol the entire red corpuscles, as under the •if agglutinin, or {}>) of the ^ me after a preliminary disintegraticm iiiidler glo^ ular masses, or {r) of blood-platelets." Oc^- • • onally, nnog..|!.(.,„itainiiig serous exudate, instead of forming . .e char- i lie fine fibres of fibrin, undergoes coagulation in the form of ciiieiiis hyaline ma.s.ses. This seems to be an allied condition. tWIil vli.ii 111''' 'I (I ill'! I; ho;,;, r,,-"--^,, Z*»f«>—'!5f^^ »' 312 THE REORKSSIVE TISSUF! CIIASGKS 1-; m Hyaline Casts. There is still ilclmte ri'jjHnliiij: th<' luoile of origin of the tratisi)areiit. scarce visible casts seen in tlie urine. Some autlior- ities reftanl them as the result of coagulation of oonstituents of the bloofl escaping into the tnhules, and in favor of this view there is that at times those have been seen in parts to take Wei);ert's fi[)rin stain. (Hhers regard them as more commonly the result of fusion and inspissa- tion of discharfres or broken-down matter from the e{)ithelium of the tubules. Where there is more extensive disintegration with liberation of coarser portions of the cell, a granular cast is produced; where the t'utire cells in the course of acute infianunation become cast off, there is formed the cellular or epithelial cast. Where the disintegrated material detained within the tubule undergoes progressive inspissatu)n, there is developed the colloid or waxy cast. Intracellular Hyaline.— Especially in the study of cancers there have been noted small globular or irregular masses within the cells, having the appearance and reaction of hyaline. A series of cases has been described showing various gradations of staining power (and therefore of chemical composition). Of these the most familiar examples are the Russel's fuchsin bodies (Fig. 11.")), so-called because they fix fuchsin with con- Iderable intensity. These originate, apparently, within the cell in cases not merely of cancer but also of chronic inflammation. Often through degeneration of the cells they come to be extracellular. Pathological Keratinization.— This is an allied condition. The normal epithelial cells of the skin, as they come to lie farther and farther removed from the :\Ialpighian layer, exhibit when they reach the level of the stratum granulosum fine graimles of keratohyaline. These stain blue with hematoxylin. In the stratum lucidum these become trans- lucent and are seen to be evenly diffused througliout the cells (eleidin). Further outward is to be seen a second development of granules of keratin which take on a puip:ish-blue color with Gram's stain. Passing still farther outward, as the cells become completely necrotic, with non- staijiing nuclei, they become represented by flattened scales of compact keratin; this stains yellow with van Gieson's stain. Occasionally we encounter massive accumulations of these keratinized cells, as for instance in the middle ear, forming pearly masses known as choles- teatoma, and in the cutaneous horns which may show themselves on one or other area of the body surface. These are not true hypertro[)liits. but abnormal collections of matter not properly cast off. At most, the underlying rete Malpighii may show hypertrophy and indications of increased cell proliferation. Hare allieliition of bubbles of gas-carbon dioxide- indicating the presence of (•ar<:nni (and magnesium) carbonates. Sulphuric acid causes the ap|i«iuaiice of fine crystals of calcium sulphate (gyp.sum). ''.•il.ification may occur in tissues that contain "living cells, not in the lirnni a//* flwrnselvps, but in the inert interstitial matter between the cells; It iH ciirs. that is, in dead or necrcscent material, and the statement may •'•• niadc that it does not occur in living functioning cells. The state- 'II' HI 1 iiat calcareous deposit does not occur in living cells is made with a kiKiw I. (Ige of the apparent exceptions. I' niay be said, then, that calcification occurs in dead or dying cells, anj 111 (crtain interstitial substances such as the matrix of cartilage, ulln^ tiastic tissue and hyaline, this latter change being especially NMth other senile alterations. Belonging largely to the former an those instances that happen in the interstitial tusue of I ir organs like the thyroid, the testes, or the ovaries, in the lungs, mhranes of the brain, and in scars, and most of all in the arterial !'i the artirics, calcareous deposit follows hvaline and fattv ' ition (necrobiosis) of the media and the hypertrophied intima, ' 111 the elastic tissue; these changes may be shown by the specific alli'< till II \M!!I- ain' 314 THE REHUKSSIVK TISSCE ClIASdES Km Kil tests wlu-n wo :ue, Klotz. Obviously, 't is not a pre- cipitation of the salts norniiilly j)r»'sent in the affected areas; the lime salts are brought to the i)art by the lymph, and in dead or dying cells or in the interstitial material of low vitality, are ren- dered insoluble anrl.v individual, treated by von Kossa'a nielliud, to demonstrate ealeifi- cation of media, and moro particularly of tlie muacular bauds. (Kloti.) ■pHi IHPP«P CALCIFIC \rios .\si) ('M.c.\Rt:ors DKrosirs aiT) I i'lly 11 rt'diictioii in the iiinouiit of carhoii dioxidf or soiiu- otlier ;i-i iKv iiidiKTS tlif prfcipitatioii of calciimi salts in a colloid matrix. Concrements. In aildition to tins deposit of caliari-ons niatcrial ill the tissu s, tliiTf may Im- a deposit of tlit- sanu' in ducts or jiassancs, li;iilinK to 1 (If formation of soli(l masses, round or oval or taking tlie >liiil>c of the duct in which tln-y arc found. These are termed concre- ments or calculi, the same term, unfortunately, heinft emj)loyed hoth lor I he almve calcareous deixisits and for deposits due to the aliiiormal |in( ipitation of specific excretions. Concrements of the first order will 111 I'nund to contain an amount of calcareous salts in excess of that iiMiiilly [)resent in the fluids dischar^red alonj; the passage coticerned. On dissolving out the salts, there is left a matrix of mucinous material, iiMi.illy mixed with fatty acids, soaps, and cholesterin. Such concre- iii(iit> arise generally as a result of a catarrhal inflammation of the passage ill (|iicstion, wherehy nuicin is exuded and some of the cells exfoliated. Tin (li>integration of the latter affords the products of jmtteolysis and the ffitty material, and in this as a matrix, just as in necrotic tissue, there i- ,1 deposit of calcium salts, hy diffusion into the mass, of serum from till inflammatory exudate and of the secretion nornud to the passage. Of these concrements, the following are worthy of note: rhinoliths in the M.iNil i)assages after ozena; tonsillar concrements forming in the crypts; salivary concrements formed in the salivary ducts; l.icrimal; cutaneous tonned in sebaceous ducts); preputial, following phimosis, with accu- iiiiihited smegma as a t\)Uiidation; and appendical concrements which lKi\e as a base rolled up and compressed fecal matter. Pancreatic con- iTi inents are of widely varying c(mstitution, this depending probably ii|>iin the length of time during which the concrement has been retained; I nient line will show abundant products of cell-disintegration, while ill! "Ill one will be largely composed of insoluble salts, a distinction wiiK h may be considered to hold not on' for pancreatic but for ail • iiiMTi-ineiits. Phleboliths. These are small oval stones formed in veins, chiefly in till uterine ph'xus in the female, and the prostatic plexus in the male. itions may be found from a comparatively soft to a hard pearl- ; the i)hlel)olith arises from the deposit of lime salts in isolated t irunibi that have not undergone organization, and thus lies free in '111 Ininen of the vein. Calcareous Incrastations.— Deposits of various kinds upon surfaces niii undergo a similar impregnaticm with salts derived from the bmlv llMhK The commonest exami)le is the tartar of the teeth, of which • I'ltM hid debris and particles of food form the foundation; in chronic <;> in. a deposit of jjhosphates may occur ui)on the mucosa, while tor. i,„ iMMJies i„ the tissues or cavities of the bodv are apt to become >iiiii rl> encrusted. ' ill nr concrements of the second order include four gioups— '"" ■ .'. I'lliiiry, and yrunhitic calculi, and coriumi aiiiulacea. Alltrai like liiidv ^W" :\]i\ TlIK RtUHlKSSIVK TISSUK CflAXdHS Fir. ir.L" Urinary Calculi. Urinary Lithiasis. Any of tlie usual or nnusiial salts of the urinr may lie precipitated to form calculi, ami for tliJN formation certain features nuist l>c present, \vlii
  • ;n matter, such as hlood clot t)r an intr(tiluce(l foreign body, in ami uiuui which the salts are tieposited. Tlu- rate of this deposition will depend \ipon the rt'lative amount of salts present in the solution, that is. the eoi'centration of the salts; as in the urine this is very variahle, the rate of deposit also varies, so that piriixls of i)roj;ression of (lei)osit may alternate with |>eriods of arrest. As a conse(|uencc, most calcidi are seen to he formed of concentric lamina. ."^ince, too, in the urine, at one time one salt may he present in excess, at another another, it pnerally happens that layers of more than one sort enter into the formation of a calculus; mixed calculi are the rule rather than the ••xccption; and in iirinary calculi, the jrrowin^' stone acts as an irritant, infection occurs with ])roduction of alkaline urine, so that th«' most superficial layers may he j)liosphatic in luiture. 'I'he mere pn-seiice of salts in excess in the tirine is not ade()uate to explain calculus formation. If the salts he dissolved out of the calculu>, there is left hehind a matrix of organic matter of f^elatinous ' >• colloid type, yellowish or other- wise |)i>rmcnte- nd if calculi he jiromnl liape of the crvstals, the crvstals tendinj; to he f*liai>c with pr. ■. srn i i • i . i ' . i . (ivri») roinided mstead ot anjj;ular. .^uch a mucmous or colloid material is thrown off in inflammator.x states, ami the greater its amount, the greater is the liahility to precipitation of the salts. Thus for the fornmtion of urinary calculi it seems necessary to have three fa( tors: ( 1 ) the presence of a cr.\ stallizahle bod.v in excess in the urine, and Cl) irritation of some part of the tract leadiiij: to increased discliarj;e of nuu'inous matcTial, and {:>) some solid body wliicli will act as a nucleus on which precipitation occurs. The irritation iiiei! not be bacterial, but no doubt it is so in a considerable nunilxr of cases, and if not so at the outset, the irritation caused by the stone will readil.v lead to a passinji infectif)n beinj; picked up. The most important groups of urinary calculi are the uratic (inclnding uric icid), those formed of calcium oxalate, and the phosphatic. Uric Acid and Uratic Calculi. I ric acid is the commonest coiistitiK nt of calculi, wiietlier a.^ llie Uiain or a.> u subsitiiary salt, and is n./ri- common as uric acid than as amorphous urates. The typical urii miil calculus is rounded or oval; its surface is smooth or finely mamniiilaltranehes. F(U. 163 Kio 10.". )"io 164 .'M'^ ^^tri^^ I i'. RU ^Cul. iilus formed of uric aiiii followed by oxalate; appearance on section, l-i.. I'.J — c>i:,|„t,. of linjp calculus ("niulhcrry" calculus), exterior view. Ii'. n:i .\innioniuin iiraie followed by oxalate and eventually by mixed phosphalea (These inri'c t:.-,j:.^ .-.r.. from thu ralaloKue of the Royal College of Surgeons.) Uratic Inspissation in Infancy.- Autopsies upon infants a few weeks "I'l !rM|iuiitly show the calices of the kidneys opacfue and whitish or I' finitely streaked with yellou, while in the pelvis a few reddi.sh- ^r.iiiis can be collected. The collecting tuhtiles contain a large ■ "t inniute doubly refracting spherical masses of urates in a iiiatri.x, and the condition has been usually calles suitable term than uratic inspissation; the masses, chemi- '■"inposed of quadriurates. Why there should be a relatively • iiarge of uric acid aiid urates in the very young is not und-r- fVfl! iirii'A llllll,! mill i .ally yrcar tld'f^'W .~c I«i 3IH THH HmiHKssivh: tissik ciiwuks Kli; liiii sttMMl. Imt tluTf scfins pMxl n-a^oii I'nr Mi|)|Misiii>; that inassi-s of tins sort an- in part rrs|Kiii>ililf for tlic uric ariil calnili ln'(|u«-iitly fduml i?i the voiiiijr. Calcium Oxalate Calculi. Tiu- nid-^t cnniminily seen of caicimii oxalatr calnili arc tiiosc that arc callcfl "mulberry calculi." Tlurc is a" ho^c.l" or iiiiill«'rrv-lik»' appearance with brown or hiack color, and on section the lami- na- apjM-ar laid down like the plan of a fortress with bastions. In compositidii it is founil that most of tlie oxalate • alcnli contain uric acid, w ith suhstaiuis dcpo-ited from acid urine. Phosphatic Calculi. These niii.\ !>*• formed only of calcinm phosphate, or of annnonimn nia>;ii<'siuni phosphate, or of pure ammonium phosphate; of thcM' the mixee sin>;l»', Iar>;e, and barrel-shaped, the ends beinj; face'' ', or there may be a Mnall number of relatively large stones faci' I to one another, forniinf; toKcther a cast of the gall-bladder; or there may be multiple Mnall stones, even hundreds in number, all of relatively the same size, p iitr- ally faceted, the faceted surfaces smooth. The color varies Irom black or deep brown through reddish-brown (bilirubin) to green bili- verdin), or may be i)ale yellow from superficial layers of cholestcnn of white from calcium carbonate. The cut surface shows coiKtuTric layers of varying color depending on the extent of admixture wil!; tht calcium salt of biliverdin or bilirubin; the nucleus is often of cholesterin. A stiiK-horii ralfiiliiH in) In |H-iviH of tlif kiilncy. GALLSTOXKS 2. I'lirr (or nhiiont purr) Chnhiirrhi Cnlnili. .'ilO Tlu'sr ari' init very niiiimuii, Hiiil arr usually siiiKl*'. oval, pair ydluw stom-s, with a waxy- jookiiijr. Hiu'ly niHliilar surface. Winn l.roktir. tlit- siirfact- is crystalliiM-- liH.kiiik', ami tluTr is little or no sijjii of stratifisoliit«-ly piiH', luit !».*) jmt out. or iiion- of tlu' contents nmy !>«■ (Iiolesterin. Ki.i 1(17 Kiii 108 *'iiii.ii ..f I'Miiiiiiiin tnixi'd liiliniliin falciii t:;illMtuni*. IN'iiuiiyu.) Kiu. IWI C'holri'.rin cult iilu», cut tuid rxilislied lo n ,.\ rniliale crysittllinc .Hiriiiiiiri'. (.\buii> Km. 170 "MiriDrphoiia" I'lioli-Micrin K.-ilNtnup iiiK r. niral rnvitaliiin. (NaiiiiMi ) Pure hiliruliin ..iliium <-»Idili; bile (travel ': N'iiuuyn.) ■'■ I'lnr Hilinihin Calrliim ('(ilriili- Thvsv are sometimes termed "bile gravel," and are miiltii)le hiaekish >jrannles, lying in mucoid li'l' ; Oiiii fresh they are soft, and break under the finger; when drv tlifx rniiiilile apart. 1 ' •ilriiim ('(irhoimfr rri/r(//i. -Comparatively rare, these stones are ^»p i ml: more often nodules of calcium carbonate occur in the mixed •'alciiii. (ir coininon gallstones. Etio!)gy. In the difficult problem of determining the cau.ses of ;'|ill^'. ■ , .. there are certain well-recognized facts at the outset, such as thfs, i,;it they occur most often in or after middle life, in females ''"•■n. Miiiii males, and in those of sedentary rather thai: of active nalMt- .„! that the cholesterin of which they are formefl i.s not excreted to an; .Attnt by the liver, but from the mucous membrane of the 320 THE REGRESSIVE TISSUE CHANGES gall-hladder and the bile iJassaRos, especially the former. Tlie increased production of ciiolcst«'rin is due to a catarrhal state of the Kali-bladder wall, induced by some bacterial aRcnt, often of a low grade of virulence; the readiness with which the gall-bladder is infected in general blocKl Fio 171 Fia. 172 n Corpnrii aniylaces from brain, to »lio»- hiniiiiHtnd character. X SSI) Fui. 17.) S(M'li(jn throujrh an amyloid hody from a eternal tmimr, \ft more highly ni!iKuifi<'d, ti> sliow the subcrjs'talline (If'pohit of yiu-c'ssivc liner'* of rlowely parked needles of aniyliiid material. At a the needles radiate from a small foeiis. (Ophiila) Fig. 17-1 -"i^ n • >%^ Aiiiyloid liody (rnrn lung (immersion lens) to show radiate crystalline formation similar to that w'en in figure precedinft. Amyloid body lying in a pulni' nnr>- alveolus from a case of chronic pi.^'ive congestion of the lung (high power! : o. large "cardiac" cells, containing pisnient; h, ml corpuscles. infections, such as typhoid fever, will be recalled in this coiincttion; finally it is necessary for such a state of aflairs that the bile be staunaiit, the ci,utent> of tiiV K"ll-f>laddcr not being quickly drained <■•••! as quickly renewed. mkk o^mgm «B* PIGMENTATION AND PIGMENTARY CHANGES 321 111 gallstones, as in urinary calculi, is a mucinous matrix in which the Milts arc deposited, and such mucinous matrix, here also, indicates that for their production there must be a catarrhal condition of the gall- Miiddcr, with increased outpouring of mucus into the bile. The studies (if tlif last few years have shown us with increasing emphasis the fre- (luciuy with which organisms of low virulence, notably the B. coli and H. typhosus, exist for long periods in the gall-bladder. It has been shown, indeed, that cultures of one or other of these organisms added t(. sterile bile leads to a deposit of all the constituents of gallstones. '1 liiis, both by favoring a low form of catarrh and by acting on the bile, these, and other organisms, directly lead to the production of gallstones. As to the cause of the great variation in the relative amounts of the (lillVrent constituents we are still in doubt, but pure cholesterin calculi art- most frequently found in cases in which, through obstruction, the pill-I)ladder or its duct are cut off from the flow of liver bile. Their tlidlcsterin appears thus to be derived mainly from the mucous mem- hruiic lining the gall-bladder (and ducts). The deposit of calcium salts ai)i)(ars to be associated with the breaking down of cellular debris, as in other concrements. Prostatic Calculi.— Section through the prostates of most men past niKldie life shows the presence of minute, dark-colored granules in the suhstance of the organ; these are sometimes called prostatic sand. They are situated within the lumina, are hyaline-looking, generally polyf,'onal, and of concentric structure; they are so soft as to be capable of eiitting, and give imperfectly the reactions of amyloid; they are sometimes called amyloid bodies of the prostate, and one of them' may l>e the nucleus for the incrustation of salts. Corpora Amylacea.— Closely allied to the last are minute concretions toinid in the brain and spinal cord of the old, in lung alveoli in cases of (lironic congestion with hemorrhagic discharge into the alveoli, ami ill certain tumors. They have the general appearance of hyaline "iiattTal. The growth of some, at least, of these bodies in the lungs and II tumors is by successive deposit of layers of obscured crystalline iiecllt ^ of protein nature (Figs. 172 and 174). croi, ]ln-.. pi-l; is. ,! exo, aiw,. >ii El and icir ill) r PIGMENTATION AND PIGMENTARY CHANGES relative unimportance is the chief excuse that exists for the pigment changes of different sorts together, because the 111 of color is no adequate ground of relationship. The s eaii be divided according as they are: (1) endogenous, that 11' direct products of cell metabolism or disintegration, or (2) s, that is, are colored matters foreign to the organism and I from without. The endogenous we may further divide into ■Mnn and its derivatives, and (6) other metabolic pigments, enous Pigments. -Abnormal Pigmentation Due to Hemoglobin Jerivatives.— It will be remembered that hemoglobin occurs ;}22 THK RKdliKSSIVE TISSUE CflANGES i ! in a solul)lo form in thf blood corpuscles, and especially in the portiil system (including the si)leen) is disinte;jrated, hy the liver cells espe- cially, with discharge into the hile t)f the iron-free portions of the pigment as hilirnhin and other hile i)igments. The urinary pigment, urochrome, is prohaMy also derived from it. Exj)erimentally, hy many chemicals, l»y foreign blood serums, and other agents, such as thermal changes, the red corpuscles can he broken nj) and the hemoglobin freed into the serum, whence it diffuses into the tissues and is absorbed by v<..ious cells. In diseased states, es|)ecially sepsis, hemoglobin imbibition occurs, the heart valves ami the surface of the iiorta showing a bright-red color from absorpticm of the pignif "t, a condition to be distinguished from postmortem change of the same tissues; in sepsis the staining is partly ante mortem. When the pigment is set free in the blood in large amount it may quickly appear in the urine, unaltered as in hemoglobinuria or modified as in methemoglobinuria, in the latter having a firm combination with the oxygen with an acid reaction. If the red cells are destroyed in the tissues or serous cavities, the pigment before its discharge may undergo a further change into hematoidin or urobilin and be excreted as such (urobilinoria). Paroxysmal hemoglobinuria is marked by the sudden appearance of hemoglobimiria for a short time, after whi -i^ again the urine becomes limpid. With some i)eople exposure to jold is enough to excite the state, and the attacks are most frequent in winter, the red corpuscles ap|)earing to be abnorniiilly sensitive to temperature changes. Modificil Ilemixjlohin. — Where there is jjrolonged hemorrhage or h)cali/,ed hemorrhage in tissues, we are ai)t to find the hemoglobin extensively modified, a fact which is graphically shown l)y the succes- sive changes of color of a "black eye;" the substances eventually obtained are hematoidin, hemosiderin, and hemofuscin. Hematoidin is identical with bilirubin, and is red, iron-free, and to be found in the central part of a large hemorrhage. It is crystalline, in which it differs from hemosiderin, which is always found in the form of amor- phous granules. In the anemias, and diseases where there is extensive destruction of red corpuscles, hemosiderin may be deposited extensively in the liver, as hai)pens also in the condition known as hemochromatosis; it is an albuminate of iron in which the iron is relatively loosely com- bined, and hemofuscin probably represents a yet more stable conil)ina- tion of the sanu' sort. Pseudomelanosis.- This is the dark greenish to black colonition seen post mortem in the liver, the spleen, lud the stomach wall, when these organs ha\-c lain against the intestine, sulphuretted hydrogen set free therefrom combining with the more or less mtxlified derivatives of hemoglobin and leading to the dejjosit of suljjhide of iron. Hematopor- phyrin is an iron-free derivative of hennitin which is set free in the urine, c:-i)ccia!!y after the use of certain drugs *^iiiained appearance. This staining is jaundice or icterus; the accom- panx ing symi)toms, such as itching of the skin, slowing of the pulse, mental depression, and melancholy (literally black bile) are entirely suliMdiary, due to associated absorption of bile salts, etc. The blood, the urine, and the tissues show the chemical reaction for bilirubin iir the inoro highly oxidized biliverdin, and the liver is the first organ t(i ^Imiw this coloration. < liiiically, the sclerotics of the eye, the mucous membrane of the iiioiitli, and the hard palate show pigmentation early, the skin quickly >lin\v-, it and the connective tissues throughout the body; cartilage, till n.riiea, and in general, the nervous tissues (save in infants) are nlaiiuly unaffecte«l; the secretions, the urine, the sweat, the saliva -iiou it; tlic milk more rarely, and the tears (it is s.,;d) never; the pale (iilor nf till- feces indicates that little, if any, is discharged from the i:\i\utru the pigment injects a fine intracellular network of channels, lU with the bile capillaries. This network surrounds the t the cell but does not enter it, and if distended, throws back !|H>n the cell, where it is at once absorbed by the lymphatics; '1'-^ less rapidly, but surely, the pigment makes its way into the ' !o(m|; the latter process is much hastened if rupture of bile IoIih! niirri Willi for. prr- Wii!. nltiii I'oni- niir!. thr ! aiiioravli,ii of the skin in hemochromatosis appear to be of this order. Other Endogenous Pigyiientations.—'Sa.ela.notic Pigmentation.- Of the autochthonous pigments not derived from hcinoglobin, the most important are the melanins, bodies poor in iron but rich in sulphur, which exist normally in the choroid of the eye, in the Malpighian layer of the skin, in the hair, and in the membranes of the brain, and are lacking in so-called All)in()s. Increases of pigmentation are seen in pregnancy, in exophthalmic goitre, in certain neurotic states (melasma), in Addison's disease, and in melanotic tumors. This deposit of melanin appears to be due to a process in which oxidases act upon the chrom- ogen grouj) of the protein molecule, with the pnxluction of pigmented substances allied to tyrosin and the mem)»ers of the aromatic series of protein dissociation i)roducts; these fail to undergo lurther conversion and so accumulate in the tissues. Llpochromes.- These are colored fatty bodies, which give color to the fat, to the corpora lutea, to xanthomas and chloromas, and under certain conditions, to the cells of the nervous system. Present indica- tions are that they are fats combined with ty rosin-like bodies. Exogenous Pigmentations.— These consist of colored substances absorbed by and deixisited in the tissues, or colored derivativis of substances not themselves colored. Tattooing is a familiar exnp;|)ie of the first of these, where insoluble j)articles of vermilion or another pigment are rubbed into fine punctures in the skin; the particles, I'lose at least which are not carried away to the nearest lymph ntnles, vvvM\n in the outer layer of the corium, whence some of them are graiii aii.v removed, producing a fatling of the color. A superficial inflamin mm iiiH^^-SKHMfHi !*?■ EXOGENOUS PIGMENTATIONS 325 lasting some time may almost obliterate the tattoo mark, because Icukdcytes are called to the part and engulf particles of pigmer t. More important are the pigmentary deposits in the lungs from inhalation, the pneumonokonioses (from /''wc, dust). The commonest of these is anthracosis, the deposit of coal dust found in the lungs of city dwellers and coal miners; these dei>osits are black, whereas rather gray in color are tlie deposits of siliceous particles in the lungs of quarrymen, stone- cutters, and workers in „.anite (chalicosis — X'^^'^< a pebble — or silicosis). The lungs of knife-grinders, glass-polishers, and others working with iron or iron-oxide dust lu'come a rusty red (siderosis) ; those f'o i76 of pottery workers show dirty-white deposits in the lungs (aluminosis), and those of workers in tobacco dust a rusty-brown deposit (tabacosis). Dust j)articles in the air May not all lie entangled by the moist wall of tlie nasal cavity, the pharynx and the trachea, but some reach the pulmonary alveoli, where, lying upon the e[)ithelium, they are picked up by wandering leukocytes, which, in turn, if not discharged in the sputum, make tiieir way back into the lymph stream; once there, they may dis- integrate and leave their pigment to the endothelial cells or they may ("irr.\ it to the nearest lymph node. 'I'his explains the deposit so abun- dantly present in the lymph nodes of the respiratory tract of a city dweller; but it is well to remember that a node that appears absolutely black to the naked eye may under the microscope prove to be a fairly normal structure, the pigment being M t ti in scattered masses. Wherever such insoluble particles find lodge- uii lit they act as mild irritants, giving rise to a devek)pment of new (niiiitctive tissue in their neighborhood, which may be so localized ariiiiid a large collection as to appear like a tubercle; a lung so affected nil infrecpiently falls a victim to actual tuberculosis. I 'i ( lian>;es induced by bodies that enter the system in a colorless form iiii'i ;^i\c rise to a colored deposit, the best examples are the "blue line" "t ! ;id poisoning and the deposit of silver in the tissues, known as argyria. The "blue line" is due to a deposit of lead j 'phide in the gums at a ed^is of the teeth, which is a result of the combination of the '^i ! !i suit of lead, circulating in the blood and lymph, with hydrogen sii!; 1 jc jriven off from the decaying food material lodged in the inter- s' i '■ It ween tb<.' teeth and the gums. When soluble salts of silver are p! ' in the body fluids they become reduced and metallic silver is d' !i (I in the tissues, especially the connective tissues. From section of an luithracotio lung to ahow fibrous areas eocloaing deposita formed of fine coal d'jBt particles (high power). ■ ■ I M F It-UB 1 JJ « I MiJ,J«iJ J 32G THE REGRESSIVE TISSUE ClI.WdES NECROSES :i-i; ' r Necrosis is death of cells, of tissues, or of parts composed of many tissues, in spite of which «lcath the organism as a wholt continues to live. Causation.~It has already been shown that there are many grai.ii- tions of cell disturhance, in some of which quick death of cells or tissues occurs (necrosis) while in others the cells undergo a slow degeneration whi' erminates in death (necrobiosis, bionecrosis). Those forms of nee . s and necrobiosis which occur as a result of degenerative change induced in the cell have been dealt with, but there remain those con- ditions of necrosis set up by circulatory and nervous disturbances. Circulatory Disturbances. — Necrosis is induced, on the one hand, by arrest of the bloolMTnd6rfTer.) Fia. 177 M ; :!i' focal necrosps in the liver of a rabbit subjected ti, experimental glamlers. (Duval.) For T of Necrosis. — Distinction, partly clinical, may be made bttw . cliHVrcnt forms of necrosis; there arc (1) necroses of individual 328 THE REGRESSIVE TISSUE CUANGES cells; (2) those affecting small groups of cells, focal necroses; (.3) those uffecting circmiiscribiHl areas, as a result of vascular obstnu tion infurcts, and (4) necrosis affecting parts rather than tissues — guigrene. 1. Necrosis of Individual Cells. In adtlition to the degenerat-ve changes alieady dealt with, there is the waxy degeneration, known as Zenker's defeneration of muscle, seen es|)ecially well in the recti muscle? the abdomen in typhoid fever, in muscles after trauma, and at ...-..^s in the heart muscle. The fibres lose their striation and become waxy or glassy in appearance, the sarcolemma still intact. It appears to be a coagulation of the muscle substance, the myosinogen becoming converted into myosin. 2. Focal Necroses. — In cases of se\ere infections there occur, in various tissues, minute areas of necrosis scarcely visible to the naked eye; such are seen in the lymph follicles in diphtheria and typhoid fever; in the liver in typhoid fever and other forms of sepsis, even chronic forms, and most marked of all in the liver in eclampsia. The causation of these focal necroses is yet unsettled; there is con- siderable evidence in favor of thrombi, sometimes hyaline, which may be formed by hemolysis of red cells, or by alteration of capillary endo- thelium which has been killed by toxins and cast off into the lumen. Fat Necrosis.— Of quite a different causation are the necroses which occur when the fat-splitting ferment present in the pancreatic secre- tion comes in contact with unproteded tissues. These are opaque, whitish-yellow islands of small size, seen in the fatty tissues, generally in the vicinity of the pancreas; any circumstance which allows the pancreatic secretion to act upon tissues other than the pancreas or the intestinal wall, may lead to their formation. 3. Infarcts and Ck)agulation Necrosis. — The produ( on of infarcts will be more fully considered later, but it is needful » mention here coagulatit)!! necrosis, a process best seen in infarcts ol the kidney and spleen. In addition to the death of the cells, there is a fibrinous coagulation of the whole area, fibrin being demonstrable; besides this, the dim outlines of the tissues of the part, dead and without nuclei, can be seen. The blood fibrin is one of a group of coagulahle proteins, and this process is evidently comparable to that which obtains in Zenker's degeneration, where myosinogen is converted into ccjagu- lated myosin. Closely allied to this is colliquative necrosis, in which there is liquefaction of the dead tissue as a process of self-digestion or autolysis, not to be confounded with putrefactive necrosis, wliere the liquefaction is the result of proteolytic powers of bacteria, 'i'iie for-ner is seen in infarcts of the brain and in the centres of tumors iind large thrombi, especially in the parietal thrombi of the heart cavities. 4. Oangrene and Mortification. — ^The death of large areas mav lie brought about by many agents — by vascular obstruction, by a( iite infection, by burns, frost-bite, corrosives, and physical forces such as radium, the x-rays, and electricity. The results of such necrosis \ iry widely. Where the necrosed area is small, and not infecte:i; from tliis zone a formation of K^uHulution tissue and vascularization of the same arises. In some areas, as in the brain, where reparative process is comparatively sh)w hy reason of the rehitively small amount of supiM)rtive tissue, and where colliqua- tive necrosis is i)roi\e to occur, instea«l of a solid cicatrization, there is likely to he (li) cyst fonnbtion. In tissues such as lM)ne that are so dense that (!isintegration of dead matter is a long-) moist fUKrene or sphacelus, or (7) dry Kangrene or mummificatioii. In moist gangrene, a.s in the lung, intestine, or an extremity, hlood enters the part and evaporation is preventetl, the dead tissue becomes waterlogged, and l)y the entrance of various microl)es l)utrefaction sets in; the aflfectwl tissue is swollen and livid; on the skin large blebs form filled with fluid; the discharge is foul from bacterial growth, and the soft tissues gradually become decomposed and liquefy, the bony jjortion being the last to yield. Dry gangrene may occur in the extremities and the ears, the necrotic iM)rtion becoming shrunken, wrinkled, and dark brownish black in color, like mummy flesh. .\t the boundary between the living anil the dead tissue, a zone of intense inflanunation develops, the line of demarcation, at which, by leukocytic and cytolytic activity, a .separation and ultimately a detachment nuiy be made. DEATH Why does the body die? Apart from any jjhilosophic pronouncenniits we call find some definite knowledge on the subject. Death is not an inherent (piality of living matter; ilic schizomycete— and this is true of all protozoa— within certain limits of heat and cold, moisture aiui dry- ness, grows, divides, and adapts itself to change over long ix-riods of time; accidental death ma., supervene, by desiccation, by physical and chemical means, but in the processes of such life there is no suggestion of death. In the hematozoon of malaria, its disappearance is not death, but a division into many new living individuals, and all of the original body save some parai)lHsmic pigment appears to enter into the new individuals. With the multicellular organism, death appiars; the germ cells alone carry on the continuity and the somatic or Ixxiy mrmn DEATH 331 ((■ll> (lie. Ill tlio jierni <«'lls ilt'iith is iH)t inherent; in the somatic cells liKiiiiM- of their s|M>ciaii/iition of function, death becomes inherent. II ii nitilticelhihtr organism or a cell republic could \h' inuiKineil in wliidi all cells arrived at maturity sinmltaneousl\ , and in which each ((II (diitributed exactly to the needs of others, there would be no need for -.(iinatic death. IJut such an individual d«K's not exist; different (iriltr> of cells are required to be mature and active at different times. III I lie case of man, there are develoi)ed in the enibryo, organs, such IIS tlic yolk sac, which are merely of temiM)rary use. When their pur- ]i(>M' is accom|)lished they atrophy and disappear, and their place is tiikiii by other «irpins and a new cellular e(iuilil>riuin has to l)e c.tal)- li^licd. The heart and kidneys Iwconie functional early; the jjenitaliu n liitivtiy late, and the latter, too, cease their functional activity In-fore tli( iir<;anism in );eneral. In the cases in which orpins sup])ly internal N(( ret ions to the bloo«l anf those (irf;aii> lcu\ cs the I»Io

    tr(^N tiirown upon the remaining cells until ultimately somatic death (if tlif ti>sucs in general is brought about by the failure of one or other ti^>iic that is absolutely indi>pensable to life. In tilt- interaction of tissues, the circulatory, the res|)irat()ry, and tiif iMT\()us systems are indispensable, and cessation of the activity (il :niy out' of tii. m will bring about somatic ih-ath; organs, too, at first ^ifilit insignificant, such as adrenals or parathyroids, have been proved t" lie (if |)rinie importance. With so many organs, essential to life, it i> I Icar that there may be many different ways in which somatic (Iciitli Mi.iy supervene, because the exhaustion of one single system or iirmm will be enough to permit somatic death to occur. Somatic death, win II it lilies occur, is a ces.sation of functictn of these three vital systems, fnlliiw, il i)\ the disintegration and decomposition of the body in general, till Tt iKit necessarily being imnuHliate death of individual cells. Signs (it tlii> somatic death are the cessation of respiration, and of the heart litiu. ' iDiidiiijrof tlu" cornea, the development of rigor mortis, and, finally, iif :;rt ilcconiposition and putrefaction. Rigor '■s" *is is due to coagu- liitiiii iif niyosiiiogeii forming myosin, the ci>agni..iion being brought iilmu; li\ the lactic acid of the muscle; the i)assing off of rigor mortis I'' ilm III aiitolytic change; its onset is rapid in those engaged in violent iiiii-.ii'ar clldrt at the moment of death ami in cases of tetanus or striliiiic poisoning; whereas in cases widi prolonged wasting or of itspii \i,i (ir litinorrhage it may be delayed for a c>onsiderable peri(Kl. llii' I iM 1. too, -A' decomposition is variai)lo in time according to tem- IMTaiix , the '.i .rmally moist parts such as the intestine show the ••Isani.. .;!!!ckly; tiic IxMlit's of those dead of acute infection and of I'iiiiiii iiiia cliangf rapidly not only because the bacteria are present jmt a! '.I cause the jjrotective substances that inhibit bacterial growth liivi ) 1, cxliansted. 1 ,1- 1 I •'■I mss/i s|»K(iAL ANT) SVSTFMIC I VTHOIAXJY CilA/TEii 'I IHE CARl»IO\ ^CULAli SYS' n K'liM tlu' discussi' " of the rir> lu tlr it Systemic I'litholij;. Our !mi-. 'lie i.uiiiliar • ith I ^ari> ; or . lint, alizfi-' always ths^i pa^ho iii.M..iii«', to kt'fi) . ind b< ihest iesi ill. iMiicnuii of tin st( .' which th iiiimIun iIu- nctiviti' - "C '' 'hhIv as « \aliicto!'. pnH'titi< !UT II. for I ;i-f "if iv\..i)l»thaiii»ic ^ litrt- to hi ' ;!i\ri>iil el .'njtes tlmt tu'cur in ti I ii(oii>]' ippreti ttes what the tv ttif ti,\Toi(i Us, il' Tt creaM! oxidati d tff«ft- •fd to ■■ cons'i' .,1 Spe ke im. •on >r, ■• III .<- orj{ ..^ usua. ; prefer to ten. ■ lid si< iain ! ral 'li. ■! i he .r pai ' " a Mh lufori ,je<-t. ! -tudy 'liat oft! ' I .1. iogist IS not merely tfi it nia\- affect each special the handmaid of clinical s t>i particular organs mos with this he simul- iges ii !)ly, namely, increased ■ d disclnrge into the hlm the 1)1os may be produced equally by an increased proal<' < Hl<.r. but that the amount of the blood in the heart and vessels i> iiotahly small. Like reduction in quantity may follow extreme or ri|.. Mt.d hemorrhages or, again, great loss in the fluid part of the blood as orjurs 111 cholera and pernicious vomiting. In this latter ca," the tliinl left 111 the vessels is thick and tarry, owing to concentration of the • orpiiM escmtrary to what occurs after extensive hemorrhage, when "li^'t Nond there is is singularly pale and thin, owing to the passage into ( |„ vessels ot tissue fluids, in order to make up for the loss of blood pro]i(T. Plethora. .Adequate nutrition, with active development of the mus- «Mli'r ^Nstcm. ,s f,„uid to be ass.)ciated with increase in the amount o I.I00.I above the normal. There is thus, contrary to the teaching tnat I,,,. pn-vaile j.lso exists pathological plethora, as seen in obstructive heart ;i'Mi<- . uhere the bhunl is apt to l)e darker than normal, owing to ■iP'T. t uxKlatioii, although estimati..n of its specific gravitv shows . t It ! more dilute than normal (hydremic plethora). We do not wholly " T-.:,. ,1 what are the conditions that lead to this hvf the blood with, as a result, a {jru^ressive accumulation of blood -m the venous side of the heart; overfilling of the veins, whether of the lungs alone or of both lungs and the various organs; relative deficiency in the arte- rial blood supplied to the various organs, and lowering in the arterial blood pressure. The effects of this we shall discuss under the heading of Passive Congestion (. 33S). Where the left ventricle v.t vahes of the left heart are involved, the pulmonary veins exhibit distension and increased pressure with congestion of the lungs and all its attendant disturbances of respiration. This throws increased work upon the right ventricle, which undergoes hypertrophy and dilatation, and eventually, the right heart becoming unable to overcome the obstruction, there results also congestion of the systemic venous system. Disturbance of the cardiac nervous system, whether acting more particularly upon the vagus paths, the accelerators, or the intrinsic nervous mechanism, lea is brought about by two main agencies, namely, arterial contrac- tion (tone), and muscular tone, the compression exerted by the partial (diit ruction of the muscles in general and notably those of the abdom- iiiiil wall. The existence of muscle in the walls of the veins shows that tlicM- also are capable of variation in caliber. The recent researches of Vaiiilcll Henderson demonstrate clearly the existence of a venopressor mcclianism. It follo'vs that, by the action of one or other factor, the lilood may find itself in relative abundance on the arterial side of the (inulation or on the venous, although the close interaction between till' licart and vessels may bring it about that opposed states of the arteries may result in the same general eH'ects upon the distribution (if tlie i)lood. Kxtreme contraction of the arteries and arterioles, for (Nainple, may result in an obstructive heaping up of blood on the right -ide of the iieart, but so also extreme dilatation of the arteries and arteridles may be followed by such a 'owering of the blood pressure that tli: cireuiating Huid caimot bt forced through the veins, but, stagnating tli( r( , atlords a similar picture of passive congestion. We have already (IIm ii-sed the effects of vascular relaxation, when treating of Shock and <'olla|)se Ip. 17S). Local Alterations in Bloou >dpply. — Increased activity of an organ or liart i^. as is well known, accompanied by increased passage of blood t(i the same. .Such increase is largely determined by the vasomotor a|)i)aratiis, although at the same time there are indications that the n a( tidii of tile lymph in the part has a direct influence upon the muscu- lature of the vessels. The lymph may become more acid with activity of the tissues and, further, may come to contain other diffusible cell Iinducts (•ai)able of acting on the vessel wall. Many other influences ill '.irinine the arterifd supply of a part, as again the passage of blood o'lt I if it through the veins. We thus recognize the following states: .ocal) active hyperemia, due to increased determination of blood part through the arte. • ^ Ileal) passive hyper. ' widening of the abundant capillary channels of an organ. ! ! iii-alj anemia. Ac- .ft Hyperemia of a part may be direct, due to dilatation of the art. - "iipl>l.^ hig that part, or collateral, due to contraction of other an.; v hereby the blood pressure is raised, and as a result more t. tli( ol i!'i III 338 THE CARDIOVASCULAR SYSTEM 'I t blood is poured into tlu.nf arteries which are not actively contracted. This latter we see in the Jevcloijment of a collateral circulation in a limb or other region after obstruction of the main artery. The direct form is brought about <>ithtr by stimulation of the vasodilators (neuro- tonic hyperemia), a paralssis of the vasocontractors (neuroparalytic hyperemia), or direct local action of physical or chemical agents on the part (warmth, diminution of external pressure, after-results of tempo- rary ligation, atropin, croton oil, etc.). Such arterial hyperemia is characterized by increase in size of the affectefl part, bright red color, increased warmth with, it may be, throbbing and pulsation. Capillary Hyperemia is usually classed as arterial. We are, however, inclined to hold that the " active" hyperemia of inflammation is due not so much to dilatation of the arteries going to the inflamed part, as to physical changes occurring in the capillary area whereby the onflow of the blood is hindered. In all viscera possessing muscular walls or capsule, expansion of that muscle and lack of tone of the same, pas- sively permit a dilatation and hyperemia oi ihe capillaries within the viscera. Venous Hyperemia or Passive Congestion. — Obstruction to the onflow of the blood or closure of a vein necessitates that the blood propelled from the artery accumulates behind the point of arrest, unless, that is, there be so extensive a collateral network of veins that the blood can escape through these. If, however, the obstruction is beyond the point where the veins of a part converge, then accumulation must occur. If, for example, the ()l)struction oc.-urs in the right heart the whole systemic venous system is apt to show the comiition of passive congestion. If, again. thV obstruction is in tiie left heart the whole pulmonary area becomes intensely congested. Thus (1) cardiac weakness, (2) hin- drances to perfect inspiration, as from jjaralysis of the diaphragm or accumulation of fluid in the i)leural cavity, and (.3) arterial dilatation with lowered blood i)ressure, all lessen the onflow of the venous bloixl, aiK i , to a greater or less degree, favor venous congestion. Such overfilling of the veins tends to show itself, more particularly, in those regions in which the veins receive little sui)port from their surroundings. It also must be remembereii that a forward passage of blood through the veins is aided by muscular contraction, as again by the negative pressure on the thorax during inspiration, and lack, or relative lack, of these is also a factor favoring local or general congestion. It is, however, where there i-' obliteration of the venous channels that the passive hyperemia is apt to be most marked. As a result of this damming of venous blood in a part (1) it becomes enlarged in consequence of the increased amount of contained blo(^, and, secondarily, as a result of increased transudation from the distended capillaries; (2)" it becomes of a dark purplish color, owing to the dis- tension of those vessels whose blomi, by long continuance in thein, has become intensely venous, and (3) where superficial, the part is coolw than the surrounding parts, owing to the slowed circulation and increased ■■■ A -.vfi'i -i? UUM4 iJHi PASSIVE COXGESTION— STASIS 339 cells iilso, Stasis. oil flow is (if --tii^is. niiliiition. Tlu- 1)I<)()(1 may bwome intensely venous, and this explains till cyanosis of suHerers from passive congestion. The vessel walls are apt to show evidences of malnutrition, the epithelium becomes abnor- niiilly stretched, and may exhibit fatty degeneration, and, as a result, there is increased transudation into the tissues, resulting in oedema. Where there is venous congestion of large areas, as in heart disease, this (edema is one of the most striking features. There may be accumulation of fluid in the body cavities (ascites, hydrothorax),' and in the sul)- (utaiieous tissues (anasarca). Perhaps the most rapid accumulation of fluid takes place when the portal vein becomes blocked or obliter- ated. This leads to a very quickly developing ascites, presumably heeause the portal blood coming from the intestines is more toxic and hariufiil to the lining endothelium of the vessels than is the systemic Mood in g»>neral. With extreme congestion there may be multii)le cajiillary hemorrhages. Lastly, malnutrition is apt to ati'ect the tissue and these may show evidence of degeneration. Slowing of the blood stream may become so extreme that its c<>rni)Ietely arrested, and there is brought about a condition Tile capillaries of a part are found intensely distended, as al-o the veins (if this condition is caused by venous obstruction); the arteries also are distended, as n result of the obstruction in front. As a eoii-t (|uence of the malnutrition and dilatation of the vascular walls the fluid of tiie blood tends to escape into the surrounding tissues, and tlie more concentrated corjjuscles become so compressed as often to ui)i)(ar as a homogeneoi.-s hyaline mass. This conglutination must not he iiii>taken for coagulation; with removal of the obstruction and re>uni|iii()n of circulation the individual corpuscles may again become loo-< !i( d one from the other. Prior to this stage of conglutination, the we,ik( iiing of the distendcfl capillary walls may result either in escape cf -oiiie of the erythrocytes into the :uirroundiiig tissue ., either through -^I'ac (- ill the walls (hemorrhage per diapedesin, see p. 304), or as a result of nciiial rupture (perrhexin). 1 ht causes of such stasis may be either (1) obliteraticm of the efTereiit \'"li' iiiducuig acute inflammation (see p. 122). Local Anemia. Local anemia may (1) be part of a general bloodless- after profound hemorrhage, or may be (2) coUateral or compen- ;i> wlurc the determination of blood to one region leads to i lie blood supply to others, as is well seen in the cerebral anemia pe (!>• 17S), or may be (3) due to local di'^turbance, as in the ' iitraetion of the artery or arteries of supply of a region (neuro- ' mia) seen in Raynaud's disease (symmetrical gangrene), and in ■ ;heial tissues under the action of cold, or again through the III' - >at' ' iiiii'!. of ,; >p;i-! tonic thr - i-w --^TW^'-.-wsriMr-. 340 THE CARDIOVASCULAR SY) by direct compression exertc«! • pon a j)art ( P'smarcli's bandages, pressure of aneurysms, and other tumors upon the surroniid- ing tissues). Pressure is, however, more apt, save when extreme, to tell first upon the less rigid veins, and as a result, passive congestion rather than anemia is the more frequent. It will be recalled that if a pressure less strong than that required to arrest the i)ulse below, is applied around the proximal i)art of a limb, the result is a well-marked passive congestion ami swelling of that limb, and thus an incarcerated hernia presents a similar venous hyperemia and not anemia. Itr.iiiltn of Loral .iHfwm.— These are primarily (I) pallor, (2) some reduction in size due to lessened filling of the vessels, (:i) firmer con- sistency, (4) lowered temperature, (.'>) arrested fimction. With these there may be subjective symptcmis- numbness, "pins and needles," agonizing cramps, and sometimes intense pain. The after-cH'ccts may be very serious uidcss conditions favor the develojjment of a collateral circulation. These results we will consider in some detail. Closure of Vessels and its Effects.- Arterial Occlusion. —The results of closure of an artery are influenced by many factors: (1) the rateof closure, whether sudden or gradual; (2) the existence of anastomosing arteries; {'A) the relative size of these collateral vessels; (4) the extent of the area supplied by the closed artery; (5) the arterial blcxnl piessiire; (ti) the venous bloo ||„>I brunch rccfivcs abunihint bloo.l throuRh the anastomoses between it and other artiri. -. '. ;,ii.l r. At most there in an arrested eireulalion in the artery itwif as far a» the nearest jioinl* "f I'r tiu'limir or ■-in:t>lonio»is abnvi' and below. Kia. ISl rccmi, rn-nlii. " riiiinal ariirial system in which the anastomoses arc only between the < apillary l.xtpii. 'luit a iicaiiire or obstruction at the poii.t a may cut ofT the whole blood supply of tba ! *'y the obstructed artery and its brunches, unless the eapilhiry circulati""• ■ - foinmuiiiciitioii between their oapiiiain ureas and branches :'• "'I ' arteries of like or different origin. We are of opinion that this '^ I'll I matter of degree. Careful study of the kidney, for example, ■M2 THE CARDIOVASCULAR SYSTEM reveals Dceasiniial anastomoses lietweeii branches of tlie cortieal arteries, and e\|»eriin«Mitally it ( rjitiire and muscular power. We know from dissection that anasto- iiiiiM s fxist between the femoral aixl its branches and the other arteries of the lower limb, i)ut obviously at first these cannot suj)ply sufficient IiIihhI to the part. The returning warmth shows that gradually these riilnr;;t' until the collateral circulation becomes comi)letc. The accom- pMiiving diagrams show how abundant and large these collateral cliiiiiiicis may become. It has l)een ii to the vena nzygos, through anastomoses between the inferior niescn- t( ric and the hemorrhoidal veins; through the veins of the round and Misptiisory ligaments of the liver to the epigastric and mammary veins him! >o on. Infarct Formation and Mortification. — Where, as above noted, the anas- loiiiDM's arc inadecpiate to restore the circulation before the tissues die .1111 1 Ihtc it must be noted that tissues vary in their vitality so that, tiT ( \aini)lc, glandular organs are more sensitive to nutritional changes tlian arc nniscic and connective tissues), then a characteristic series of iliaii^'cs manifests itself. Of these, paradoxically, the first is a swelling "I the ail'cctetl area so characteristic as to afford the name given by \ irrliiiw, of infarction or "stuffing." T'.iis swelling is due to great dis- tiii^ioii of the capillaries with blood. They become intensely con- j,'< -i< il, and at the same time the tissue cells of the part show a series I'l ' ii;,ni;cs ending in co(a|)lcte death and failure of their nuclei to stain. Iliiw docs this ougestioii come about? Cohnheim hehl that as with kjiig of the artery of supply, the blood pressure beyond the block ■lii'cd to nil, and as the surrounding veins have a positive pressure Muod falls, as it were, from them into the area until the pressure r n aches that in the surrounding capillaries. The matter, however, 1 ((iiitc so simple. It has been shown that in the ki;li tins*' collateral artcrifs is siitticicnt to tlistt'iiti tin- erinients Ity (ireenfield, of KdinhurKh, nnd his pupils, confirniiiiK earlier studies of Vulpian and Hardy, demonstrate that in its first stage — within five hours of the obstruction — an infarct is always intensely conj;»'i^ted, rt'ddisli-jiurple, and raised. Later, if not too large, as both the tes, tlie henioj;lol)in hecon-es diffused out, and the part becomes paler and of a more pinkish color. It is in the early part of this second fMriiMl that the infarct shows best the condition ternuHl coagulation-necrosis. The cells no longer stain; they bt'conie hyaline or very finely granular shadows of themselves. At first the individual cell outlines are still distinguish- able; soon tissue cells, cajjillaries, and their contents become fused into a firm homogeneous or almost homogeiu'ous hyaline mass. In this way the hemorrhagic or red infarct and the "anemic" or "white" infarct may be regarded as two stages in the one process. Hut here certain comi)lications enter: (1) the hemoglobin may not diffuse out of the centre of a large infarctous area so that there may be eom- j)lete hemorrhagic necrosis without pallor, and (2) in certain ti-sui'-. (lung, liver) the infarct does not proceed beyond the red stage, and that because, owing to the existence of a double hUnnl supply, the coag- ulation necrosis stage is not reacheil. Thus, if a branch of the pul- monary artery becomes occluded, the residt is intense congestion of the region of supply, congestion so intense that the corpuscles escape into and fill the alveoli; but sufficient blood still reaches the alveolar walls through branches of the bronchial arteries to nuiintain their vitality. .Similarly, if a branch of the portal vein be occluded, a like red infarct is profluced, but tlu> liver cells do not undergo necrosis, gaining sufficient nourishment through the branches of the hepatic artery. It follows thus that the red or hemorrhagic infarct is of at least three orders; and a fourth may here be noted, namely, that the local death of tissue accompanied by intense congestion and all the features of infarct formation may wpially be brought about by occliiitioii af the efferent rein of the ixiit, provided that there be no adequate anastomoses. While, for example, the majority of red infarcts in the lung appear to be due to blocking of a branch of the pulmonary artery, in a certiiin number of cases a like condition is produced by intravital coagulatinn of the blood in a bram 'i of the pulmonary vein. It can easily be imaginid how in these cases, o\\ ing to hi'k of exit, there is most intense conge>ti()n of, with hemorrhag< from, the capillaries of the affected part, and liow the stif^i- i- liji'-ie t< 'r followed by tis.-i-- :!eath. This venous f"r!M is always of the ' i nionhagic type. .\u organ in which it is apt to occur is the adrenal, .md this jjarticidarly in young chihlren, in them iKing lAM tSFANrTIO\' 345 ;i r.iiiM' of ri'intivfly smldfii roper. In the more central arc;! the dead tissue is removed by the agency of the leukocytes and ti"ii( IVrineiits, and now gradually the central deaart of the -iirriiiiii.linjr connective tissue, autolytic changes rest ; - in the necrotic ti~ 111 iicconiiiig eventimlly replaced by a .serous fluid, encapsulated \Miliiii ;i relatively thin layer of conntctive tissue. Such cyst forma- tion ii!ise(|iient to old infarction is most frequentlv met with in the -ec p. 2!»4). Suppuration. — .Suppuration may occur in small infarcts where the I 11-^ l>een due to infected material in the blood stream. As the ' r!;aiiisnis multiply and toxins dilftise, leukocytes may be attracted ircii ill such abundance that a true abscess replaces the infarct, trefaction. — Where the infarct is larger and becomes infected, riiiiiiiition of leukocytes to the i)art may be inadequate, and urnwth of the bacteria the cells arc broken down and liqutfif-d, 'f imtrefaction rather than of true abscess formation being or;ii: 1 1,1,.' lllilT, tot'- till' J' ki'l 'It. :vMi r///? CMiDKiV \S( ILMi SYSTK.M : 1 : -f r». Calcification. ISanly Mprophytic ..ruanisiijs from thf surfa<-«- ar. a|)t to ^row into and in\ail«- tin- .Icmj tissiir, loading to e> iisive i>ntrffaction. \\> havt- already desf the Idood in a solid form within the vessels. It is a process frequently found at |)ost mortems. Here we nmst distinfrnish between post mortem clotting and intravital, and at times this is difficult. The followinR are the main features: (I) bliMnl that has clitted in vessels after death (cmor) has done so by a prixrss identical with that which occurs in blotnl removed from the l)ody. It is a true coagnKition. with fibrin formation. (2) It shows no stratification; the blood has coagulated - /( iiia.y.ir, save that just as with blood <-oagulated slowly outside the b«Hi> . the lighter hiiko- cytes ma\ rise to the top and form a " bufly coat," so sometimes we find tiiis post mortem clot red througlioui, at I'ther times, notably in the auricles of the heart, we finosi ■ are •liflereiit. According to moilern teaching, coagulation is essentially liroiight about bv the formation of fibrin as a fine network. It is here necessary only to recall that this formation is due to the action of tibnn ftTinent »>r thrombin ui)(>ii certain of the proteins present in tlu' I)Iih) iilHTutcd in tin- hrciikinK wn itf IcukiM-yteis and IiIimmI plntflctH, iiitlioiigli tisMic (flls also may ; IFonl ti coftfnline which activates the tlironilM»j{cn. ()|i|mis*'(I to this tlirt>inl)iikiiiasc, there exist, accordinR to lliiickc, substances which hin( rth and .'< pnx'ess. Tliey intHNluced a fine needle point through the vessel u;ill, and observed u very striking process; namely, they fouiid that the tir-^t step is the accumulatioi. upon the foreign IxMly of UIihhI jtlntelrUt. Whiit these blo(Ml platelets are has been subject of debate, but this is -. ''.men may iixcptiic filled with (1) a pnr. hyaline blocKl platelet thr. :,: i- Often, linwever, tiu' leuk(K-ytes of the circulating blocxl also b. \" '••■ :, ri. ent to thr nias- when we s|,.ak of (2) a mixed blood platelet •! i. .livj -yte thr.iiibiis. Or, under ct rtain conditions, more particulflT ■'. • there i- irtiiiouriced st:i-is of the blood, a thrombus beginning 'hus passes on til the (nnditioii ukiu to eoagulaticm propt>r, and coarse hyaline bands !iiir example, is not uncommon as a compli- cation of tyjjhoid and other infectious conditions. In s(mie of these cases we deal with a bacteriemia and find (as in acute endocarditis) that there has been a primary injury to the vascular endothelium. Such thrond)i in themselves contain abundant bacteria. In other cases, however, the thrombi are sterile, and in these we must suppose that the circulating toxins are the imjjortant factor both in injuring the vascular endothelium and in bringing about an increased (oagulatior. power of the blood, this hyperinosis and the liability to throniltus formation appearing to proceed hand in hand. Forms.— Thrombosis may occur in all parts of the circulation proper. (a) Cardiac thrombi are frefjuent; the sites of election here are in the auricular appendices, and in the ventricles, originating either at the apices or in the pouches between the nniscle bunilles. All these are areas of relative stagnation of the blood, and, it may be aihled, of poor nutrition of the cardiac endothelium. Originating thus tluy tend to form sessile, more or less globular nuisses, and, under the action of the blood current, often i)resent a ribbed or coarsely netted surtiiir. They are of some little duration. .After a time these thrombi proiiit a comparatively thin surface layer, enclosing a turbid fluid, the cciitre of the mass having undergone li([uefaction through autolysis or ieiiki)- cytic heterolysis. More rarely such a globular thrombus, originiiting in one of the auricular appendices, be<()ines i)edunc\date with pro- gressive growth, and, being broken off, forms a ball thrombus. Irce in the auricular cavity, such ball thrombi iiave been found to hv ii cause of sudden death, acting like a ball valve and occluding a narmwcd mitral orifice. Yet another form of cardiac thrombosis is of first importance. '1 hose above mentioned are encoiuitered in cases of obstructed circulation iina THROMBOSIS 349 slowfd 1»1(mmI flow, whether through weakening of the eardiae miisele or tlinniK'li valvuhir disease. They are generally rejjarded as hhiiid and iioii-iiifective. The other form is that found in aeute (l)aeterial) endo- ciinlitis, in tlie form of vefetations, most often developing upon the cusps of one or other heart valve, but occasionally also growing as parietal tliriiMihi upon the walls of ventricle or auricle. Such vegetations may 111' ill the form of individual i)rocesses or outgrowths, or, at times, iimv develop into large cauliflt wer-likc masses, adherent to the valves. Fiu. :»« (;i .iHilar thnimliua of uuriraliir iipix'ndix: ii, (clobulur thrrjinl)u» filliiiK mid protruding from the auricilar upiM-ndix. mm / Fia. 1S4 I'n:: ill-n : leu'. Imt,. A VCIln aiiil ^'nl^^ (llobiiliir throinhus of apex of left vi'Htricli'. 'Iicir <(>nsist»-ncy, and from the motion of the blond current, as 111 the softening they may undergo through the actiot) of the 'I t'lrnicnts, vegetations of this nature are jMculiarly liable to l>rnktMi olf and be (arried forward in the blood stream. n;idy noted (h) arterial thrombi are not so fn-fiuent as ar»- Nevertheless, they may develop both in the pulmonary artery •lie iiurtii or its branches. More fnHiuently they are parietai, Ironi some diseased area of the arterial wall, and at times thev 3r)0 THE CARDIOVASCULAR SYSTEM rm Kiu. 185 niay conipli-tc'ly fill the vessfl, forming an occluding thrombus. It !> interesting to note that it is excejitional for such arterial thrombi growing downward to extend into the cai)illaries. Wiien (c) capillary thrombosis occurs it is due to direct local irritation or disease. id) Venous thrombi are relatively common, occurring in the pul- monary, the systemic, and the portal circulation. The slower flow of the blood, its poorer quality, the presence of the valves, the low blood pressure, and easy com- pressibility all favor thrombosis, and once the process has begun in a vein, it is apt to ex- tend in both directions, so that, for example, a thrombus originating in the femoral vein, may exten«l up int i the iliac veins and involve nil the brandies of the femoral below, while a thrombus forming in the eins of the uterus may progress until it fills the internal iliaes of either side. The Rcsulin of Thrumhosis.—Xn obliterating thrombus of a vessel produces those c(>ii(li- ♦^ions t)f arrested circulation, in the area of supply or origin, that have already been dis- cussed. If the thrombus, or part of it, be- '•onies loosened am! carrietes make tiieir way into it from the vasa vasorum, and foUowing ii|Hin these there is a passage in of f iJi i. vein. '■ WcC.iW M-'(h<-.iI Mu!<.nirii ) THROMBOSIS— EMBOLISM 351 The thrombus thus eventually becomes ropreseiiteil bv a shrunken ina.^ oi dense connective tissue. The networic of new capillaries, in this newly formuig tissue, may open above and below into the lumen i.t the vessel, and so not infrequently we find the development of canalization, one or several channels of fair size restoring the contin- iiit) ..t the vessel. At times indeed the only indication of an old thn.!iil...sis IS the presence of fibrous bridges stretching across a vessel (li Autolysis, as we have already noted, is liable to occur in old ciirdiac thrombi. (1) Putrefactive Softening.- Tl is rlso has alreadv been referred to Imt two processes must be distinguished. There mav Im- a simple iMintorni, but not truly purulent, softening of a thrombus. This for (XiiiiipIjMs not infrequentlv sjen in thrombosis of the lateral sinus'and iiitcni.-il jugular vem foil: wi.ig upon infective middle-ear disease The thro.nl.ns is liquefied tl.rough bacterial agency, without anv marked iin MH.m by pus cell.. Or, on the other hand, as we at times note after app. M.heitis, progressive thrombosis of an infective nature, involving the interior mesenteric vein, may either be the result of an ascending iNlertini, of the Wall of the vein, or may itself set up inflammation of t le wall (thrombophlebitis). Where this is the case there mav be an iil'iiii.hdit migration of leukocytes into the thrombus, and silftening ;i-<.ei;,te.l with true suppuration. (.-)) In certain regic.ns of the bo.lv' ^^li(re there are abundant venous anastomoses, as in the uterine -ind' prn.tatie pl,-xuses, we encounter phleboUths, somewhat elongated, oval l""li;-. lying hu.se in the lumen of a vein, which have undergone calei- ■M atioM. 1 hese are old bland thrombi, i.re characteristicallv unattached aii'l ui.t.a.l of being absorbe/ the '"N'i- :.^t. riusns. „r, passing through the heart, in some branch of the {"'"""I"-: artery, „r originating in the pulnionarv vein- or left heart "■""H. ;irr,.st,.,l „, slus, riding over the angle of the V ■^tending d„\v„ the two branches. It is apt to be 'I"" 11 the two branches by a prli. 4. Fat Embolism follows upon extensive concussictn of the iioiiy skeleton, sncli as may be caused by a fall from a height. So, also, after fracture of the long boiu-s, with rupture of the fat cells of the marrow, after forcible breaking down of stiff joints, operative handling of fatty tissiu's. such as the onu'ntmn and pamiicidus adij)osus, iiiiinenms ca|)illarics of the lung tnay be blockt'd by fat. Where only a few cap- illaries are involved, at most minute infarcts may be produced, witli no serictus results. There may be a small surroimiling congestion aiinw debatcas to the exact causeof death. Some cases arc evidentl> i.ir.iiac, - PfL EMBOLISM 353 (liM ti. tlH> expansion of tho wanned air and its heeoming churned into a In.i li in the heart, the froth impeding the action of the anrieuloventricular viihcs. In other eases the formation of abumiant eapiilarv emboli in III.' hiiigs or brain would seem to be the lethal agent. Tlius in these (iiscs the lungs have shown multiple hemorrhages, indicating obstruction (if a hirge num;, r of capillaries, with congestion and rupture. (1. Gas EmboU.- Rapid death may follow if proper precautions be not tiiki-n, when those who have been working under compressed air rttiirn to the ordinary pressure. There may be either pronounced ilyspiKca and asphyxia, rapidly fatal, or a succession of nervous dis- tiirhiiiKes, which may be recovercfl from, or prove fatal after a few days. Tlii^ caisson disease has been experimentally proved to be due to the iiK r.ased solution of air in the blood under pressure. The oxygen of that air is utilizwl by the tissues, but the dissolved nitrogen is apt to 1m IiIh rated from the blood in the form of gaseous bubbles, as gas bubbles torin III a soda-water l)ottle just opened, an cardiac or arterial hemorrhage in one suffering from disease of the myocardium or syphilitic disease of the aorta. Here may be noted a rare order of hemorrhage, rvgiiuiul, capillary, and apparently jwr rhexin, that, namely, of nervous origi:;, seen occasionally in hysterical individuals. The "stigmata" on the hands and feet of religious enthusiasts are of the same or-Ur. (2) Hemorrhage jicr diapcdcu.n occurs from the capillaries an- IhhIv cavity («?/ij, a tumor). \ hematoma is a localized i)rojecting, tiiiiior- like accumulation of blood in the tissues; petechise are punctate capil- .*^V«i a„awi %£:£«<^»i« HEMORRHAGE 355 liirv li.inorrliiiKcs; more (iifl'iisc <-ai)illiiry licinorrhnKes so dose set that tli..\ tfiiil to run tofietluT art- ecchymoses or suggillations ; where these li(iiM.rrha«es are multijile and siihciitaiieoiis we speak of purpura. General Effects. -Tlie gravity of a heniorrhape depends ujx)n (1) tlif iuniiinit of Hood lost from the vessels, (2) the rate at whieh it is l(.>t I that amount whieh, withdrawn suddenly, leads to death may be lost MV( ml times over in recurrent smaller hemorrhaf,'i-s), (:{) the region ot h.nK.rrhage (thus a hemorrhage of l.ut an ounce into the brain siil)stjmce, by pressure upon and olistruction of important centres and triKts may cause rai)id death, where a pint withdrawn from the vein (if all arm may be followed by a feeling of relative well-being). It mav !•<■ l.nd down that the normal adult individual mav suffer the loss of tw.Mty ounces of blood without harmful effects, and of less than half tlir total volume of blcxnl without necessarily fatal results; women hiiir ihc loss ol large amounts of blood better than do men. Tiiking these into consideration the general effects of hemorrhatre may I.e: I. .Sudden death within a minute or two, as after rupture of the luart, or burstmg of a thoracic aneurysm into the pleural cavitv, IMric.irdium, a-sophagus, or trachea. 1'. 1 )llaj»e followed by hydremia and eventual recovery. I S\ iicop( or temporary cerebral anemia with rapid recovery. .'. >... disturbances due to cerebral anemia, but, in cases of hemor- rliaL'K- . xtravasation into the tissues or cavities of the bodv, the devel- HiiUK nt ut a febrile state due to difiusion of the products of disintegration ot tlif . Mravasated blood. Th. mI-ox e nee.l little comment, save, perhai)s, to note that diminution ""' *"•;■'''";;"« ''l«od below the normal amount is followed by a pa-airr ol fhnd from the tissues into the blood vessels so as to restore in a i.w numites the amount of fluid within the vessels; this passage mnl. r. the ,loo,| hydremic. So, also, secondary to any considerable '- .'I I. .).Hi there is increased activity of the hematopoietic tissues, • "nH.i,,l,ly an increase in the red marrow of the bones (increased prn,lu. i,un „t erythrocytes). With repeated hemorrhages the marrow ') |--n,r cxha„ste, 1 |„,,s ,„ a case of vascular papilloma of the bladder with 11 "na ..xt.M.d.ng oyer many months, we have seen developed a " " ■- ,.|„.,ly resembling pernicious anemia in every respect, sa.e iM ,1 I,,,,., ot i,uTease It-Kl to at least temporary lack of nutrition of the Pi'l.v. In general, where there has been rupture there follows PHKcss whereby the escape of blood is brought to an end- I "M'scaiK. IS at all considerable the blo,Ml pressure Lecomes '1^ '"«^'red,andwiththistherate of escape is Iessenc.1. (2) \s tli( area r. a iiati I 1 i \( I iirii-n 3r.6 TIIK CARniOVASCCLAR SYSTEM ,;4 J in iil the hl()0(l oscaiM>s tliroiigli tlio woiiiulod \ osscl into the tissues, contact with those tissues, and their eoa>;iilins, iixiuees eoaKnIution, and this in its turn lias a hemostatic action which becomes more complete the slower the hlood stream, {'.i) The solution of continuity of the vessel wall, if the ruptun- he transverse, is followed hy contraction of the middle coat, and diminution of the vascular lumen. If it he itnxf^i- tudinal, on the contrary, the contraction results in the opening; remain- ing patent. But in Kcneral, besides (1) the directi(>n of tlie ru|)ture, the natural arrest of hcmorrhape (lei)ends upon these main factors, (2) the si/e anat«CT »gaap ■»- QVM.it ATI VK CIIANf!RS l\ THE BLOOD 357 The bactericidal jxiwcrs of the blood arc such that it is ra 'c for a 111 iiK.rrhajiic extravasation to become infected and terminate in abscess fonniition or putrefacticm. QUALITATITE CHANGES IN THE BLOOD 111 this section we have to pass rapidly in review the main data (oiKrniiiiK tise variatiteii(c of mechanisms which in the normal state keep their ratio txtninnliiiarily constant, so constant that, as A. B. Macallum has p'liiitcil out, the salts still retain the relative proportion characteristic <>t th.it ancestral i)eriod when, with free connnunicatioii between the \»»\\ I iivity and the external medium, the internal tissues were bathed "II Ihii slightly modified sea-water. Acvertheless, in disease varijitions iiri iii.i infest. Thus, as already indicated, i, condition of hydremia is ii"I niir qiient, of increase in the plasma relative to the corpu.scular •i"i!'iii- with accompanying lower specific gravity. This mav be tin lijii ;ilH.ut (1) by actual increase in the amount of circulating fluid, it- in .ii-tnietive heart .iisease, (2) by no in r-ase, but. on the contra.-v, 'I'' r. iH 111 the ti.tal amount of circulating fluid, as after severe hemoV- \\iiiii with loss of blood the plasma undergoes a compensatorv h, teiidnig to maintain its volume. A similar relatiM- hydremia ;i« ti ristic of conditions of grave anemia brought about,' not by ■!'a^e, i)iit by intrava.scular deatli and disintegration of the ■' vtes (;;) by increase in the .salts of the blood tending to attract lii'l. SI) that the hypertonic state of the plasma may be reduced niiiii. This process has been invoked to explain the hydremia ' iri>, \n will- li ti.ea' are evidences of increased retention of chlor- ' system, th()tii,ii here also the loss of the proteins of the blood iiiti) the urine may be a fact(,r of .some importance. Thus. \ ( h llrili! IT,\ I i iiinri tl.ll llf I,, illl- hv , !,ri,. ti\, ari;i .''K»B«MlK>p-S »*l.»k.>iSV«-Jf. 358 THE CARDIOVASCULAR SYSTEM tioiis ns.s(H*iutt>ar that we have to deal not so much with an excess or nnccted witl. cliangc in altitude, blood counts affordiiii,' from S,i)U(),(KH) to 1 1,0* :;• 'JIM) corpuscles. There is often an associateil enlarge- .£-!»-• J^i?" THE RED CORITSCLES 3:)9 in. lit of thf splet'i., aii.l a tnall (microcytes). alone uithcorpuseles exhibiting ^reat variation in shape (poikilocytes. froin .-■/:/((;, various). VariatlOM In Structure and SUIninf E«actlon«.-A stiaK- of the red MMrruw shows that tlie red corpuseles originate from muleated eells .rvthroblasts-by a proeess ..f gradual shrinkage of the m.eleus. with t Mattered mnnisses, gradually dilfuses evenly fhronjch the whole , "' fl'V corpuscle into small gh.bules from ^^hiell the hemoglobin |- . •..: -hMliarged so that as they separate they are searce .listin- «ii.-!„im|c tr.)ni blood platelets. Variations fa Hemoglobin Content.-There ma^' be great variation -lor in.lex of ti.e blood, i. r., the ratio of the hemoglobin ],er , •■ \",'^ ''•. f*>r example, found increased in per..icious anemia. ■ in c!,|„ro-,s. llu-re may be both a reduction in the henio- ! -". uce.' as in the latter case-a defective eonversion of the •■"'t. . „| tne erythroblast into hemoglobin, and, on the other ''illusion ol the hemoglobin out of the corpuscle or hemolysis - numerous agencies which can bring about hemolvsis both Ih I ri'ilui iiikI, lian :. W^^T^I^imSy^^ MICROCOPY RESOLUTION TEST CHART (ANSI and ISO TEST CHART No. 2i 1.0 I.I «- IM III 2.2 J- 1 3., i^ " l" lllll^ .8 1.25 1.6 ^ APPLIED IIVHGE Ir '•-'"■1 ioV Mjin SiffP' _ '-1^='..= -•■;hesler, Ne* v .- U609 U->A ^^'— ■ "6) ".82 - 03;/ p^ij"e ^'6) .^88 - b98^ -ai 360 THE CARDIOVASCULAR SYSTEM ti within the vessels and in the test-tulie: cold (as in paroxysmal heino- gl()l)innria), "leat (as in hums), tiie sera and tissue cxtrae'ts of animals of «)ther species, and sometimes of those of the same species, experi- mentally i)roduced hemolytic sera (p. 163), certain bacterial toxins (which possibly explain the anemia of many infectious diseases), notably those of streptococcus, B. coli, pyococcus aureus, pueumococcus; vejietable products, such as ricin and amanita (mushroom) poison. In addition many chemical agents bring about this diffusion out of hemoglobin ant, and evidences of hyperplasia of the red marrow of the bones In.iuently there is an accompanying atrophic gastritis, and evidence nt interference with the sensory tracts in the lower part of the cord. 1 liese various conditions suggest the continued action of a hcmolvtic ti.Niii ot gastro-mtestinal origin, leading to excessive destruction oi'the n.l corpuscles, increase m hepatic iron, and increased but imperfect (d.npensatory production of corpuscles. The increase in hepatic iron lor example, is a result of hemoglobin disintegration; the pigmentation ot the fat, a result of modification of the hemoglobin liberated in the . in ulating blood. Whether the fatty degeneration of the heart muscles IS (it toxic origin or due to deficient oxidation is uncertain. The cause of the hemolysis is still undetermined; there mav be more tlian one. Prom the frequent association of pyorrhoea alveolaris, a low t..rin ot suppuration involving the sockets of the teeth, Hunter inclines to the view that a secondary chronic streptococcic gastritis is the esstntial cause; one of us (Adami) has suggested that we deal with a sul.inlcction by means of hemolytic intestinal bacteria of the colon Kroii|); Herter would implicate the excessive proliferation of tht B \H.lm in the lovver intestine. Based upon the close resemblance liotw.ci the clinical picture and post mortem appearances in man and tlM>M. (,t surra and dourine in the horse, the latest hypothesis is that «<• .l.al with a condition of trypanosomiasis. The riddle has still to be solved. Aplastic Aaemia.— Rarely there is encountered an extreme anemia .'""■npanied not by hyperplasia, but by an hypoplasia of the bone Miiirrmv and hemopoietic centres. There is great reduction in the ".' '■'■ "f '■«'•, corpuscles, abr^ence of normoblasts and megaloblasts ' immature erythrocytes), low color index. Poikilocvtosis is not marked lymphocytes are in good number, but leukocytes (polvnudears and to>nM>|)hiles) fewer than normal. Instead of increase in red marrow tli.ro IS reduction, its place being taken bv fat cells. Chlorosis.-Chlorosis is an anemia of\ different order affecting >oiinir a.lult females; its presence in young males is so rare that many "<>i> Its existence. There is a characteristic pallor, the "green sickness" "I l.li/..il.ethan writers, lassitude with weakness following upon slight «^'rllnM (lyspopsia and capricious appetite, gastric acidity, constipa- 'loii .111(1 attacks of palpitaticm. 'I ' < I'lood exhibits definite hydremia with corresponding reduction N_. lumber of erythrocytes per c.mm. What is most marked is the r-'iM' ti(,„ „i the hemoglobin, so that the color index averages 0..5, and ' as l(.w as 0.1. The good effects that follow the proper exhil)ition I Hi^gost that imperfect production of hemoglobin is the essential ' \N hat leads to this we do not know, although several clinicians 11(1 stress upon constipatio.i and the good effects that follow a "t laxatives, suggesting intestinal intoxication as the underlving nthers see a relationship between the sex of those afft' ted lll;i\ of ir tV;il Clill! CM 11^ ■ 302 THE CARDIOVASCULAR SYSTEM ■f .. n m- i and between disturbances of the menstrual function and thtse blood disturbances. The Leukocytes.— Before proceeding to 'scribe the changes that occur in the leukocytes it is necessary to a.sifv these and to have some idea as to the relationship of the dif..'rent forms. Now this is not an easy -natter, and that because, despite abundant research, there IS still active controversy regarding many points, and to discuss the pros anu corus would occupy many pages. We can, therefore, but give dogmatically our own opinions regarding these matters, stating franklv tiiat these represent one view, and that they are liable to revision.' ' Briefly, we have to distinguish between the circulating white cor- puscles and those found outside the vessels and in the tissues, certain wandering cells being found in the one region and not in the other We can further distinguish between those white corpuscles, or wandering cells which originate from myeloblasts, those that originate from lymphoblasts and lymphoid tissue, and those originating from endo- thelial and other connective-tissue elements. I'he trend of recent observ; ,ns is to approximate more and more the last two groups, ihe dilliculties in making a classification depend essentiallv upon this, that the earliest and simplest stages of developing cells' show prac- tic-ally no differentiation, and thus it becomes a matter of extraordinarv difhculty to trace back the different forms of cells to their origins, par- ticularly when in the hemopoietic system the different orders of ceils are apt to originate s.de by side and not from different isolated centres. Forma of Leukocytes —Vie may, however, distinguish the following main forms: Of myeloblastic origin (granular leukocytes): (1) the polymorpho- nuclear, polynuclear, or neutropWle cell. This is the commonest white corpuscle of the circulating blood, constituting in general more than bo per cent, of the white corpuscles present in normal blood. In its cytoplasm are fine granules which stain with n.utral or more accurately weakly acid dyes. It is the form in greatest abundance in acute inflam- mation, and is thus the typical pus cell. The nucleus is character- istically lobate, so that under low power the cell appears to be multi- nucleate. It is actively phagocytic, particularly for bacteria. It rarely shows evidence of r.itosis in the blood stream, or again in the tissues at the site of inflammation. It 1ms nothing to do with tissue formation. The Eosinophile.— This is of the same size as the former, most olteii 'ts nucleus is coarsely lobate or horseshoe-shaped. In the cvtoplasm are granules much coarser than those of the former, and these take an intense stain with eosin and other acid aniline dves. It also mi^'rates out of the vessels in the early stage of acute inflammation, but is soon overpassed in number by the polynuclears, while again it is foiiinl in the tissues in fair numbers in certain forms of subacute inflanimalion. ' A ftUler discussion of tho subject will be found in the small work on •'Iiithmma- edUion" ""*" """ ('^'^'""'^- (Macmillan: I^ndon and New York, f.mrth LEUKOCYTES AND LYMPHOCYTES 363 III normal blood this form is present in but small numbers (about 3 ptr cent.). It is abundant (10 to 50 per cent.) in many forms of helminthiasis (parasitic worms), in certain cases of chronic skin disease, etc. Only rarely is it observed to act as a phagocyte. Studies made on tlii- frog and other animals show that these cells can discharge their j;Taiiiiles, which are of nucleoproteid nature. The cells seem thus to have certain excretory functions. Opie has noted that during the < nurse of certain acute peritoneal infections the eosinophile disappears liirKcIy from the peripheral circulation, but may be found accumulating III the mesenteric and other vessels, and there undergoing migration. The Lymphocytes.— The typical lymphocyte is distinctly smaller f hull the preceding form, possessing a relatively large, spherical, deeply >taiiiing nucleus, with a relatively inconsiderable surrounding layer of Idioplasm. This form of cell is but slightly amoeboid. It is not ob- X r\ ed to be phagocytic. In inflaramatory conditions it is found more partKularly accumulated around the vessels. There is still doubt as to wlicthiT these accumulations are the result, in the main, of migration, or are due to proliferation of preexisting lymphocytes of the region.' (Marchand.) In subacute and chronic inflammation {e. g., tubercu- losis) this is the preponderating type of cell present. In the blood stream 111 pathological conditions, what are known as large lymphocytes, one jonii of "large mononuclear," may be encountered;' these represent miniature lymphocvtes. In the tissues in cases of subacute inflammation the small lymphocytes give origin to cells of larger size, with excentric iHi< lens and a somewhat polygonal cell body of fair size, the vlasma nil ('p. 132). Mast Cells.— These cells, rare in the normal blood, may be occasion- :illv ciicountcred in pathological states, such as leukemia. They are of hiir size and possess abundant granules which take a basic stain and iirc so large that they may be taken for clusters of nu'crococci. The 'iiKicus IS generally degenerated. Whether the mast cells in the tissues iirr ,,t the same origin as those in the blood has not been absolutely 'i' t' riiiiiied, but here they may take on motility, and their path may be tr.i;|i occasionally by the granules which they have shed. In any |i"-iti()n tlicy are comparatively rare. HyaUne Cells.— Cells having a large body and an oval, pale staining [iji'l''us, constituting "large mononuclears," are encountered in the '' ' '" small numbers, and there are difficult to distinguish from the '•" -' lymphocytes already described. Their cytoplasm is free from ;;'•■!; 'lies. A similar type of cell is seen in conditions of inflammation of ;'.(KM). .\fter a rich protein meal there occurs a nmderatt' alimentary leukocytosis. I) ring the last hours of life a terminal leukocytosis is generally to be recognized. Polynuclear Leukocytosis is iliet with in iuflammatorv and manv intectious conditions; not. however, in all, for it is absent in tvnhoid malaria, and the more ordinary type of chronic tuberculosis and lepro.v save where there is secondary infection. So, also, it is wanting in measles' mumps, and in most cases of influenz. It is very pronounced in pneu- monia, where there may be a leukocytosis of even 100,()0(), with % per cent. ,.. .>o ynuclears. Suppurative disease and local and generalized disturbances (iue to pyogenic organisms exhibit this tvpe of leuko- cytosis. Jt IS of note also that in states characterized 'bv grave dis- turbance of the liver, and wh.ere there is a breaking down of tissues, as in tlie later stages of carcinoma, this form shows itself. Antipvretics and salicylates induce a moderate grade. Eosinophilia is seen in many difl'erent forms of helminthiasis (p <)0) in many irritative skin diseases, accompanying myelogenic leukemia, in bronchial asthma, hay fever, and allie.1 conditions of so-called idio- syncrasy in somr post-febrile states, and in a varietv of conditions it IS difhf lit to correlate. Lymphocytosis is fr.>c|uent in > oung children, particularly where there are gastro-intestinal disorders; it may be noted that in the voung there IS a relatively great development of the lymphoid tissue of the bodv. and especially ot the intestinal area, and irritation of the Ivmph nodes is accompaniec by a greater .lischarge of lymphocytes into the blood. \ similar lymphocytosis is f.nin.l in iidults, where there are enlarged Ivnipli nodes. With whooping-cough, lymphocytosis is so marked as to he pathognomonic. In scurvy, rickets, sclerosis, and debilitating discMM. a lymplKK ytosis ot moderate grade is frequently noticea5)le. Leukemia. -Leukemia is a disease characterized by the voidi'mal I)resence ot an t\ces< of circulating leiikoc\ tes— of more than l.'.ini" per cubic millimeter, although generally in the hundreds of thousnuis. Ifie state is characterized by progressive weakness and associ.iud *■ 'M;ll [- i.-i, I J;ii*: l^lpi 1^ I j LEUKEMIA 365 iih.rnia proptT, usually with a grnitly t'nlarn;fil ■ plt-in. Tli«rc arc, how- 1 \tT, two types— the myelogenous or uivelohlastic aiul the lymphatie. Myelogenous Leukemia.- This form is seen most often in early aWuit lit( , and more often in the nuile. The underlying feature is an alHTrnnt li.\ IH-rpIasia of the hlood-formiu): tissues. The hone marrow is always .illVcted, showinj; an excess of gray nuirrow, in which ahundant cells (iiii he found exhihitinj; transitional stages, from myeloblast to nnelo- (,\tf, to the neutrophile leukocyte. There is an associated increased ill M'lopment of eosinophiles, evidence of ii'.creased activity also in the liroductioii of red corpuscles, with increase in the number of mega- r;iry(>cytes. 'Pile spleen also reverts to the condition seen liefore birth, and presents indications of active formation of myelocytes. The organ may attain ;iii iiiormous size. There may be similar indications of mvelocvte tnrniation in the hver. In all these areas there is but slight indication <>l 111 increaset cell-, and the lymphocytes, although relatively in small numbers, n re present in greater ntunbers than in health. 'With this there is ii 'li^tiiict, though not an extreme increase in the number of red «'>ri.iis,ti .. • ire features of the disease, as again the epistaxis, ■■'""■''' ■'- liemorrhages. Associated with the increased pro- 'InrtK.n there ..e evidences of increased destruction of the leukocvtes, 111' il>l.\ an ixce.ssive discharge of uric acid, which we assume to be due t.- till disintegration of the nuclei of these cells. The disease is chronic, i.i tin- troni a few months to several years after its first recognition. Lymphatic Leukemia.— This also occurs in young adult life and mainly "I '' •• male, although found at all ages. In young people the disease t' !! I tu have an acute onset and course. Here not the spleen but the i>ii 111 glands are most involved. The symptoms and phvsical signs iirr tlurwisc much the same as in the other form, and blood films show ■ t excess of lymphocytes (see plate) of typical shape, with large iiiinmg nucleus and small rim of cytoplasm. In the more lirni they are of more atypical and embryonic type, resembling IK' lyniphoblasts, and showing a less deeply staining nucleus - 'liar shape, with relatively abundant cytoplasm. ! liiT all these cells are lymphoblastic is a matter of present debate. -^".■eMtly been shown that the presence of Altmaim's granu'es in tins order is not, as Schridde held, a positive indication of : '^i w^ 366 THE CARDIOVASCULAR SYSTEM .. 1 11' Ij'mphohlastic oriKin, for such Kruiiulfs may also he detected in myelo- blasts. Thus it is quite i)ossihle that there exi-*ts an acute leuken>ia, due to excessive atypical (h- rinpment of the myelocytic elements, indistinguishable by present methiKls of rc:.cnrcli from the acute lym- phatic form. Or, expressed otherwise, there may l)e an acute leukemia characterized by the overgrowth and liischar.'te into the blcKMl of cells representinjf the common primary stage of both lymi)h(K'ytes and granular leukocytes. Fnlike the myelogenous type, in the lynii)hatic there is a liability to tlic ap{)earance of multiple, minute, subcutaneous lymphoid nodules. Inlike the other form there is here characteristically an accompanyiii}; febrile state (102° to 104° F.), with severe sweats, and development of a "typhoid state." The condition is fatal, and of shorter course than the other form; and this, although the blood picture does not exhibit such extreme changes, the number of contained white cells averaging 200,(KK); eosinophiles and mast cells are wanting, nor is there any marked increase in the neutrophiles. Blood Platelets. — To the other constituents af the bloo>uc. Ascites is the accumulation of serous fluid in the peritoneal cavity: hydrothorax, in the pleural cavity; hydropericardium, in the pericardial; hydrocele, in the tunica vasiinalis testis; internal hydrocephalus, in the ventricles of the brain; external hydrocephalus, distending the spares %• m \ X / -■¥ "■«?&ii-' » > \. \ # f I"! VDA'A/zl 367 nl flic pin iirailirioiil. \Vr would lay down tliiit nrnmuilutions of stniiiH fluid in tonnininication with tht- exterior, and t'uis outsiile the l)n.ly,arenotstrietl.\ (I'derna; pulmonary oBdema, tli«r«"fi)n-, the nceunui- l.'hioii of fluid in the air sacs of the Uuig is, strictly s|H'aking, not a iiiiiiiiK'r of this elass. < tiir clMssifiention of these various conditions has so far heen faulty. lN;inate from the Miiuiis system and form a closwl, freely hranchinj; s«ries of ducts -I piirated hy aii endothelial liniuK from the tissue spans. ' < to the n Litioiiships of the great serous cavities of the Ixwly with ' s system thiTf is still dehate, .ome holding (from the ease and ra» ity with wlii( h inilk globules, red c<»rpnMles, etc., pass from the peritoneal i.nltx into the lymphatic vessels of the diaphragm) that there is a 'linrt coinnuniication; others, from histological considerations, deny the existence of any such fn-e communication. For convenience, there- lore, uc may regard the three are- ^ is distinct, and lay down that M n.ih fluid may become ace umula^- t (1) in the lymphatic chaimels proper, (2) in the serous cavities ot ihe body, and (:j) in the tissue M'iMrs. Na\ , more, we can go farther and recognize (4) that fluid r' H I Miiniiate abnormally in the individual cell-. (See Serous Atrophy and li.\(lr..i)ie Degeneration, pp. 29S and 306.) 1 Lymphanglectasis. — Little need l)e said regarding the first of ilir-c (onditioiis. We recognize that, in consequence of obstruction, ulHtli.r congenital or as the result of disease affecting the efferent l.viiipliatic chaimels of certain organs or area'?, there may result a huge iliM. iiMdii of the lymph channels behind the point of'obstructicm. a 'li>t(ii>i(.n so great that at times they take on a oystic appearai -. loriiiiiii; lymph cysts. Such distension is seen in congenital conditi. IK li as macroglossia and macrochellia (p. 281). HyKroma oT the n. niay he regarded as of similar nature (p. 281). As an arqiiipea con- 'liiidii, iyniphangiectasis is encountered in one group oi cases of
  • ii(li cases may sliow very little beyond the local effects of the thyroid enlargement and little general disturbance save when, through handling IIP operation, active congestion is induced ami the grave sympt mis of li.\ |)crthyroidism may supervene. If the condition progress still farther, with pressure atrophy of the epithelium and loss of function, symptoms III myxo'dema may show themselves. In yet another series of cases wr (leal not with geneialized but with nodular localized hyperplasia of till' thyroid tissue. These are usually spoken of as adenomas, a term whose applicability we doubt. They present not so much active ny.r^Towth as a distension of the individual vesicles with colloid. ^ Vt ill some cases there is evidence of true adenomatous development. We may thus encounter the foetal adenoma, so-called because in this (oiHlitioii we find areas formed of clusters of cells situated in the stroma, rcMinbliiig closely the cell clusters seen in the embryonic thyroid! Till X' evidently are undergoing active proliferation, an(i what vesicles an present among these are of small type and lined by small, roundetl iir (iibical cells. This form .iceording to Wolfler, jiresents itself as iiiiiltipic well-defined nodes, originating apparently from mother tissue wliM li has remained latcrit between the previously developed follicles. 111. >u-(alled sulenomas in their early stages are very vascular and liiiliii' to extensive »"-morrhages in their substance, which result in the Inniiation of cysts, .metimes of great size. Yet another form has Ihi II railed by \irchow the struma vasculosa. This is not a blastoma |'rii|ii r but merely a great dilatation of the superior and inferior thyroid :irti rits and their branches, leading sometimes to great enlargement organ with pulsation and the development of bruits audible stethoscope. This condition is often accompanied by indica- 1^ I't' hyperthyroidism. Tumors Proper.- The proliferative conditions just mentioned may give pliir, I,, true adenocarcinoma, or tiiis may (>riginate without previous r al)|(. goitre. Arising thus the condition is markedly malignant, iAt(iisi\e infiltration of the surrounding tissues, penetration of the 'I and of the :< :- ,/" the neck, accompanied by rapid increase ' i/e of the org. •' i! ; the formation of metastases in the lungs, ' 'I . Loeb and . • > .s have described both in man and the lower '^ a true carcinoma sarcomatodes, namely, a combination of the lit growth of the parenchyma with coincident sarcomatous rpjidsis ()f the interstitial tissue. Secondary invasion of the 'iv nuiligmint growths originating in other tissues is compara- rr; occasionally there may be direct extension into the gland r> of the trachea and trsophagus. Ot ill! liy till tiiih-, I iiii^, with tnii I ill tl lll;||. illlill Ili;ih lint, III-. ti\, lu • c I 426 THE CARDIOVASrrr.AR SYSTEM THE PABATHTROIDS R ' I We owe particularly to Sandstrom (1880), Gley (1891), Cristiani (1892), and Cohn (lS!*ro the recognition of the parathyroid glands, and from the stage m wliioh these little bodies were regarded as unde- veloped and latent masses of thyroid tissue, we have passed to perhaps too great a belief in the importance of their function. They are usually four in number, situated either immediately outside or imbedded within the thyroid tissue in the region of the posterior inner edges of the lateral lobes above and below, and, in their histological structure, resemble the embryonic thyroid tissue, with frequent cjst-like spaces. Embryo- logically it is found that they have a separate origin, being derived as outgrowths of the epithelium of the third and fourth branchial clefts, close to, but distinct from, the points of origin of the lateral thyroid masses. They are to 8 mm. long by 3 mm. in breadth. From their simi- larity to undeveloped thyroid tissue, it is difficult to state with precision whether certain small masses found in th.: tissues of the neck between the thyroid and the arch of the aorta are accessory thyroids or accessory parathj roids. Tliese are so common as to make the frequent state- ments of surgeons that they have removed both thyroids and para- thyroids without obvious results of little value. The obser\'ations of MacCallum suggest the existence of a poison in animals whose parathyroids have been removed, which enters into combination with certain cells of the nervous system, so that there develop *he symptoms of t-t'Uiy, a condition characterized by spasmodic contractions of the muscles, con\ulsions, rapid respiration, with dyspnoea and salivation, followed by coma and death. Accompanying this there is increased excretion of calcium salts with diminution of the calcium contents of the blood (MacCallum and Voegtlein), while, as pointed out by Erdheini, the extirpation of the glands in the rat is followed by defective deposition of lime in the large incisor teeth, followed by brittleness and a tendency to breaking. Fracture of the bones of these animals is followed by delayed conversion of the cartilagi- nous into bony callus, affording a picture that recalls somewhat that seen in rickets. If an animal showing these symptoms be bled, they are checked and can be made to disappear by the injection of emulsions of parathyroid. This condition of tetany in humankind occurs most often in infants and here se\'eral observers have noted the existence of hemorrhages in the parathyroids; these, however, are not present constantly and a further condition of gastric tetany is described asso- ciated with dilated stomach, etc., in which no lesions have been made out in these glandules. An attempt has lately been made to correlate hemorrhagic and necrotic changes in the parathyroids with marasmus of infants. Hyperplasias, or so-called benign adenomas, have been described, without much evidence of functional disturbance. Mim-^ mwi'MP-j ^ry, ■■jr'^^&&m. CHAPTER VII THE RESPIRATORY SYSTEM GENERAL CONSIDEBATIONS The chief function of the respiratory system is the intake of oxygen and the discharge of carbon dioxide for the benefit of the economy at large. This is accomplished by the filling of the air sacs with air on the one hand, and the capillaries and lymph spaces with blood and lymph, on the other, and the free interchange of the gases between the two, separated as they are from one another by the alveolar epithelium, the capillary or lymphatic wall, and what connective tissue may chance to intervene. It has been calculated that there are 725,000,000 alveoli in the lungs, exposing a surface of roughly 210 square yards, so that the air cells are lying close to a film of blood that has been estimated to be 10/x in thickness. The amount of gaseous interchange can be thus seen to be enormous, yet this is but a mall part of the process of oxy- genation of the tissues, for only a small amount of oxygen undergoes re(luctif)n in the corpuscles. The cells have an intense avidity for oxygen, and are capable of storing it to some extent, for the tissues have lieen shown to bo capable of metabolism for some time in an oxygen- free atmosphere or when transfused with oxygen-free saline, during \\ hiih metabolism carbon dioxide is abundantly discharged. The arterial lil(»o(l is almost but not quite saturated with oxygen, and even in a-pliyxia some oxygen can still be obtained from the blood. Of the lirocess of diffusion which the oxygen imdergoes from the time it leaves the ctjrpuscle until it joins and becomes part of the biophoric molecule \\( know very little, but we suppose the transference to be fairly direct. Anatomically, it may be noted that there are abundant elastic fibres III tlie aheolar walls which assist in the recoil of the lung, in the ex- iMiMun of air, and in the circulation of the blood and lymph in the alyrolar walls; that the right bronchus is larger than the left by one- iliinl, and that the bronchial tract has a capacity that is one-thirtieth t!i:it (if the lungs; that the varying diameters of the larynx and trachea a IV ( \ idintly to impart a rotary motion to the current of inspired air; fiii'l that a double blood supply from the right ventricle through the I'lil'ii.inary artery and from the aorta through the bronchial artery give a . ; V free collateral circulation in all parts of the lung. The Air Passages.— This term includes the entire tract from the i - ii- In the terminal bronchioles, a considerable dbtance; the effect "li" the insjHred air is that it enters the air sacs (1) at the body tem- 1 r,;iii,., (2) impregnated if not saturated with moisture, and (3) ,. ^bV^Br . 428 THE liESriRATORY SYSTEM \ i i It: I I! i (It-void (iiorinully) of du.st and fort'i);ii particles, and tlu-rofore sterile. The nasal passajjes have an important effect in l)rinj;inji this state of artairs about, and the large surfaces of the turbinated bones war i and moisten the air, and their moist surfaces, like those of the whole tract, entangle particles to an enormous extent. If the effect of this mech- anism be nullified by mouth breathing, it will be seen at once how serious may be the effects pnKluced upoi *ht lower parts of the tract. Mouth- breathing may result from nasal obstruction of many different sorts- from congenital or ac(|uired narrowness of the passages, from trauma, from the secretions of iuHammation or the thickening resulting there- from, from tumors, especially polyps, and from lymphoid enlargements. Of the last, adenoid growths of the nasopharynx are very common and very important; occurring in childhood, they may be associated with peculiarities of development of the nasal chamber, esjjecially a high arch of the palate. In normal conditions, there is a di.stinct |)rotective function exerted l»y the nasal nuicosa, which is at once highly sensitive, strongly vas- cularized, and richly supi)lied with mucous glands; as a result, irritation is followed by marked reaction with a!)U!idant nuicous secretion, which protects the epithelium, washes off' and dilutes the irritant, and supplies a physical impediment to bacteria. The Pharynx.- Assistance is lent by the pharynx in these processes, and while its surface is not multiplied like that of the nose, the sudden change in direction imparted to the air current assists actively the entanglement of foreign particles; the abundant jjrovision of lymph tissue (including the tonsils) is directed to this end, and it is notable that many of the air-borne diseases, such as the exanthemata, are connected with a preliminary infection of the pharynx. The Larynx. The main function of the larynx is phoiiation. The larynx, essential for the singing voice is not essential for speech; the "note" of the voice is determined by the tension and the rate of vibra- tion of the voca! cords, and by communication of this vibration to the air. The voice is therefore aff'ectet ini])ortant afferent nerves of respiration, and stimuli are ; ''irently geiitrated by the carbon dioxide tension in the blood, • 1 iimmI tension of carbon dioxide stimulating the centre to produce ' :i-e(| respiration, and reduced tension depressing it. Disturbances of Respiration. Sneezing.- This is a reflex act, caused i.illy by nasa! irritation stimiilatii!!: .-i lirap.Hi of <|i!> Hfth ju-rvo, and i-ts of a deep spasmodic inspiration followed by a strong, quick : lation. During the first part o* the latter process, the mouth is 4.30 TIIK RESPIRATORY SYSTF.M closed hy tlio approximation of the «lorsiiiii of the tongue and the soft i)alate, so that the first jjortion of tlie air that is expelltMl K<»es through the nose, tending to drive before it the irritant partieles; then the tongue and soft palate are separated, and through this relatively narrow spare the air is forcibly driven, producing the characteristic sound. CouKhing.- This is vohintary or reflex, the irritation in the latter case being in the nasopharynx, the larynx, the lungs, or the pleura-, although it may be in the external auditory meat us; deep inspiration is followed l)y closure of the glottis, which remains closed y venous hioml, hegins to fail and to distend, and the liliind pressure hegins to fall. Cheyne-Stokes' Respiration.- This consists, to (pKJte Stokes' own >Mir(ls, in "the occurrence of a series of inspirations, increasing to a maximum, and then declining in force and length until a state of appar- I lit apno'a is reached; in this condition, the patient may remain so long as to make his attendants believe that he is dead, when a low inspiration, followe*! by one more decided, marks the commencement 111 a now ascending and then descending series of inspirations." It was iiri;;inally supposed that this phenomenon marked onct.ming death, but ^li. !i is not necessarily the case. There are two main groui)s of di.sease in which it may be manifest circulatory disease without obvious (i'-rase of the brain, and intracranial disease without affection of the ill art; some cases of general infection and some narcoses may also show it. It is not possible in the ])resent state of our knov.Iedge to give any sitist'actory explanation of the phenomenon; it appears to be what Iiliy>i(ists call an interference curve, that is, it is the resultant of waves 111 line rhythm on which are superposed waves of another rhythm, the -nni.il at times augmenting, at other times neutralizing the first. The Air Sacs. — If oiic considers broadly the diseased states of the air sacs tliat interfere with the proper performance of the work of the luiii.'^, these fall into two main groups— those in which the ingress of air into and the egress of air from the air sacs is prevented, and those ill wliicli cliangcs in the walls of the air sacs prevent the proper inter- (liaiiL'c of gases. Diseases of the first order may lead to those of the ^I'Clilllj. Air iiKiy he j)revented from entering the air sacs because they have iini liccn (iisteiuled (atelectasis: 'ir£/!j'c, incomplete : .^'"a'^'C, expansion) , IT li.iviiig been disteiideil, they have undergone collapse. If of small I \iriii, this state is of no moment, the other air sacs undergoing com- |ini iitiiry cnlargeiiicnt; even a whole lung may be thus dispensed with, il i! 1 liiiinge be wrought gradually. " 'I met ion to Air. — The air sacs may become filled, and the air they iil'l ciiiituin be replaced (1) by serous fluid, as in the cases of acute or II congestion, (2) by blood, as in rupture of a branch of the pul- !> artery in a cavity or its walls, or in rupture of an aneurj'sm into ' :.ii lua, or in infarct; (3) by water or other fluid from without, as in ing; or (4) by inflammatory exudate as in pneumonia. The effects ! of these upon res|)iration depends partly upon the amount of lung iiiMitvcd, and partly upon the causative agent. In hemorrhage I II huts of hemolysis, or in pneumonia the toxins, may induce a >!;.: ci.r Mil.! tl,. ilrn of.! ti- tllC •-.•- '3W:*i 4:?:. 77/ H liKSl'l UA TOR Y N I'.S TKM r«l>rilf stilt*' whicli of its«-lf will afT«- (ruin luii« ^'h«iria. Nut.- the iirciil air.iphy ami thinning of iilvrdar walls nml thi- fri* inils nf ruptunil anil iilisorbiil inlcTulvii)lar septa. Emphysema. This ma\- Ik- local or generalised, hut the mode of \m>- duction is alike in both". The hronchus or bronchiole has its liinieii narrowed, either l)y ^pasin or hy inflammatory dejjosit, or by the pres- ence ill it of thick secretion; the forcible inspiration foIlowe interchange, dimiiUKion of the elastic tissue and ot the elasticity . t the wall, and atrophy. In this state, the sudden iiurease THE I'LFVRM. ( AMTIKS 4;{;{ .A I.hI,.s. I....IS u, t\w rnptnn. „f u ,.,.k..„..,| walls „.,.l M-v.-ral air m' ..r. .I.rou ,, ,„t.. n.u-. I vn. if tlu- ..Lstructi,,,, i,. the hronc-l, Z tZ n ..H.V...I tlu- .la,na«.. aln.a.l> .1..,,,. is ,H-r.„ann.t. an.l th.-n- is aw" M prup..r pn,,K,rt...M iM.tw.r,. .l.,- (iiun-as...!) u.huuv of air an.l .• >. Mnm.slu-.l) area ..f wall prrsnit.,! I.v ,1... „ir sa.tHa,...| at tlu. .s„rfa,r of tlu- Ium^. a.al ..sp..,.ia||v at th e hirXs ..".. n-lat.v.. V l.ttl.. support..! I.v a.ljoi„i„« 'air sa.-s suffer the Kr,-a es .li>t.;„.H,„. so that thev ,uay he ••hall..oue.l" to » verv lari;e sixe \N.- hav .ousKhr*.! m « Keuerai way tlu- .ausation of en.phvsenia- •t will he se, M that au.vthiMK whi.-l, .auses a hei^htene.! h.tra I u^ m v pre.s„re ,„ay uuluee this state, hen.-e the liahilifv of ,.lave' S ..ptnuuents o, ,las.shlow..rs. au.l of persons •sulfe'rinKfn.n. -Isease as whoopu.^ eo„,,h; a^e, too. has a .lefinit,. eff.rt. in tha h . a> u.ty of the alveolar walls is lessene.l l,y the atrophv .f the "last • ..ssue. an.l proper ..ontra,.t,on of the air .u- in expiration is , alt With this emphysematous expansion of the lungs, the .-onstant ; <'-..Hl f..r ..xygen ealls for an o^erfillinK -f the ain.u v full a s"e ntmg the state m whuh its maxnnun. inspirat<.rv eapaeitv is ,ttain«^• H ..xp.ratory part of tlu. ac-t is length ene.l, gaseous i tm- a ! is I - HKH-nt. the passage of l,|oo,l through the lungs is ,,h C e '.„ .■..^.arrassment o( the right si.le of the heart follows ' Bronchiectasis This is a ...ulition of the l.ronehus in whieh its l"-.Mn ,s .hiate. u, one or n,a,.y places; either hv pressure r.n it I , "{•"■' an atropM<. wall, or I.v traetion from u itn.ut le . r . j '^ I. .mus ,.oMne,-t,ve tissue, tlu- lumen of a hronc-hus ..r a . on S nm >l ou a Ins, .,r„. or .-ven an al.ruptly sa.rular wi.iening le ! ..m- 1 .n.n. M.s takn.g up spac-e that shonhl !.<■ ocrupie.l bv .t rll ai ^ n >nltn,g ni .lunuushe.l aeration of the W..o,| ' Interstitial Deposits. It is self-., i.lent that new fssue whetlur f-lTo..s granulomatous. ..r ne..plastie takes up n-om in the I ,',. „ , " ;;; ■•;".. .hsphues n.,rmal air spaee: hut this 'i- „ot al . ,r i .'h^^^^ j^^ ;l:;;t;;;;;'^;,;^i;|;r •-*•''-••- - l-'t ,, i ' .. V?. '"t'''"'T' ^'"^P""^'"" »"'! contraction would go on -ti;^ e ; wo 1 t;r; "f "••= ^'^y^, l*'' ''iaphragmati/eon. ■< iti, litt!.. of th. a le *-"■ * •r^'^V"^'"" ''f t''^ lower parts of the lungs 'I ''t reg ou The U "'^*'"''"".K'' "^ "i-" ^culcl he slight in .^."^Mon. Ihere ,s normally a negative pressure in the pleural 2b il i ' i li : i I I •■ I : !■ i i II 434 77//. UHsi'in \T(H(y .^)>irt:.M PneomotboTu. Tin- niirarur ..I nir or pi- into one or hotli of the cavities eliaiiges this ntnative to n p(»>iti\e [iressiire, aiul in rieiirly every cuse a (((inpression ot the hiiin is pr«Mlueeeen iK-elu(iee the cuse, ami the lung lies against tiic vertebral column completely collapse,l. In small elfu.sions, the fluid by its weight exert a lu-gative pressure, and the lung, instead of swimming U{)on the effusion, supports the effusion until its weight exceeds the lifting power of the lung; when this happens, the fluid is able to ex«'rt a direct dowu vard force on the diaphragm. In such a case, the partly compresserrhage (eputans). Of the passive sort are those hyperemias due to heart and lung disia-es, and to the presence of tumors in the nasal cavity. By reason ot the delicacv of structure and the elasticity of the mucous membrane ot the nnse, it is prone to be readily rendered hyperemic m a reflex ua>, and vasomotor turgescence. even of purely nervous origm is 'retjij.i.i, even so slight a thing as a change of posture in some mdivi.luais -TaiSTK.. THK \OSE 435 .nay rause the rlisaprK-Jiraiuv -.f hyiMT.-...;,, of on., si.lr of the nose |hhI >ts trnnsfm..,.^. to the other. Ken.orrh,.,.- o,.,.urs i„ ul.rration InlUnunation. -Acute Rhinitis. Coryia. or C.t«rTh.-This arises i.nmar.ly from barter.al ...fection, ami a,.,mrently from ex-i„,snre to ."M an. wet, as well as .rntatniK .hemieal x apors. Son..- Jrs..ns are M.MTptihle to (rrta.n iiHhvHual volatile s.:l,stancfs. sn.has irn-ctt,. nml ...any to the irntant effect of s,H>eial sorts of jH.ller.. the smell' nl ..Tt,.,., flowers or ammals; the most familiar example of this i, hay ever. wh„.h ,s evaleutly a reflex . .somot..r effeet resulting from ."i^U.hylax.s. I hat eoryza i. met wit. . measles, sc-arlatina. variola Mtlnn./a. ami typhus fever probably n.eans that a .lireet infection o til. mucosa by the spccihc a«ent .K-curs. The mucosa is swollen, hvper- .m.. , ot a .lcqM.ne(l olor, .Iry. an.! irritate.l. a state soon follow^ by lie .„p,o,,s secretmn of a clear, waterx-. sliRhtly viscid flui.l. containing In.k.Kvt.-s ami epithclmm. and possesse.1 of the power of ermling the 'km or anot u-r mucous membrane. It must Ih- remembcre.1 that such iM, mfectio,. has the poNN . • t„ sprea.l to the throat, th.- accvssory cavities an.! sumses, as well as to the Kustachian tube an.l the n.i.ldle ear In >.vere prunary n.tection.s, as well as after the continuance of mild f.rt,onstlu fluid may iH-come purulent, an.l lu-ing so mav be mixed « t i blood an.i maN possess a foul odor. Local abscesses or "the erosion <> l-nc or carflage may follow. Me-r.-..^anou« inflanunation is mos ■'tl.M due to the .In.htheria bacillus. Chronic Rhinitis, fli/prrtrophlc Hhinills.—r]. <"ii:restion. either h- i infection or mechanical , ; h iHTtrophic changes in the mucous meml>rane. >■ pla-r Ml the sul. mucous tissues, and mav. in ext • . I"'l l-i.l"! form he merely to the foldings of t^ . , . proper in ...n.. ... , suc^h hypertrophy is followe.l by a secondary contraction •■"l"ig t,, a dimumtion m the size of the turbinate, the so-called ......dary atrophy" seen in old persons. This process ho^-^ii -'H.tlnng ,pute apart from the condition of atn.phic rhinitis, as will ;■ . ^:;;n m the description of that state The old icL tha^ .n atrophic f.I'l!.tiom ^ ^' " hypertrophic .-ondition seems %, be without Alroj^lnc nhi,,ith -~rhUcoiu\h\on has been the object of innumer- l'';scuss.ons ami n.v.-tigations as to cause, and very variedTon- ' -n> have been reached. The condition p;esents a very nke -;al and also histological picture. The stn.ctures in the nos. " *' 1. shrunken and covered with .Iry. foul-smelling crusts (oz,n, ' ' • histological pic-ture shows m.rked thinning of the mucosa wiih . iinthfhuvi from c-olumnar to sqi-.-mou^. There are changes in ' .0.-S, which some observer, n ,ard as th. primary factor fn the !-"i ,.on of the disease, though this we are ,u,t inclined to admit i^t formation takes place for two reasons-there is abnormal air • Z continuance of t,M! , may lead to ' • •i^triifowth takes 1'; ''a.-. ., assume a proper. In i m m-' 435 '/•///; HKSriRATORY SYSrE.\f span- in tlu- ....st- tvuduMi to .Iryii.K' of tlu> sem-tions. ans probablv the result of some former se^(■re n.Haminatory process which has destroved the normal lining; of the nose, and this has been imper- fectlv repaired. Such seNcre .lestruction may be seen in congenital svphUis. and in the infec-ti.nis fevers, such as scarlet fever. In some cases a l..ii>;-coiitiiuied, latent suppuration in one oi the accessory sinuses mav be the cause of the disease.l state. The Granulomas.- Tuberculosis in the nose is rare, syphUis. how \er. is fairlv often seen, bc,'in.mm with the "snuffles" of the baby who is b..rn s'vpliilitic, with a constant i»urii!eiit catarrh; minima is apt to arise in the c-artilages or bones, and, when broken down, Jo K.ye .,n«in to the "sad.lle" deformity so often seen; pert<.ratioii ..I the septum aiKl of the hanl palate may occur. Glanders and leprosy may attack the nasal mucous membrane, the lesions varying according to the acuitv of the infection. , . , Progressive Changes. The most <-omiiion torm ot overgrowth is thi polvp^md.as has been reiharked elsewhere, the polyp is usually n..t a tu m.r pro!)er, but a mass of proliferated tissue, which thus becomes OBdematoJs ..r a myxomatous polyp. Both are gray, semitranslucent, and sparselv cellular; mucous «l..ii.ls may be enclose.l in the ina>s, an;landular parts may inuKe adenoma, of the Hbn.us parts, fibroma, and widening ot the vesse s telZiec asis. One must at times be ama/.d at the sr/.e ot .edematous or myxomatous polyps that can be taken from the m.stnl. arcinoma arising i.rimarily is rare, sarcoma ni..re common. New gn.vvths, ..ft.n endotheUomatous, arise in the acc»ssor\ sinuses. PHARYNX AND TONSILS Fauces. .\s the gate of common entry to two important systems, the .ligcstivc and the respiraf.ry. the pharynx is , lara.teri/.ed l^ wha would appear t<. be an extensive .lefensivc mechanism in the sl.aiK ;;; allndlnt submucous lymphoi.l tissue. This tissue is l-sen .. most of its extent, but is massed in the form ot ^ cry numerous to I, U in the two lateral pair of faucial tonsils, and m the ine.han super.u r nharvngcal tonsil. The structure of these tonsils is <-liaracteris ic 1 u ■niderin is relativelv thin, an.l .lips .lown f..rn.ing a .•..lle.tion ot .rvpts. t the surfaVe an.l imine.liatcly be.u-ath the epithelium hn.n ;;!: ..vpts is a,, abmLlant ..ollecti.,,. of lymph foUu es. A sn..r m with a swab rev.als fairly numerous tree p..lymorpl-. •»''''<';^^ ^^^^ ™ have evi.lciitly wan.lcrcl out an.l ingest surface bactena, etc. 1 unmi, ^■"«.'-» .<«. I'llMiYXX \.\l) TOSSII.S A'M ill . ordiiif; to Iawt, tlu- tliiii «|)itlicliiiin ci.n i-riii); the tonsils also posst'ssi-s pliM^rocytic proiMTties. By this means the surface is kept clean and lr."»). This teratomatous f;rii\vtli, which has its attachment at the base of the skull, projects into till' mouth. Circulatory Disturbances.- The vascular c..nditioii of this region iiiid its visibility make it a striking indicator of circulatory disturbances the active hyperemia set up by various irritants, with its scarlet reiii:irjincc, through the more l)rownish color of chronic irritative liMnriniia, as in alcoholics and smokers, to the passive hyperemia of (.iriii:ic disease, with its bluish-red livid api)earance and' irregularity III Mirfiice brought about by swollen veins. Pharyngeal oedema is not uiiiominon; most often it is associated with sjjreading inflammatory >t;it.s ,'. ;•., acute inflammation of the tonsils. It may be angioneurotic I'l 'M r may show itself in obstructive heart disease. Inflammation. Of this we recognize various grades. It may be noted tb:ii liKtd inHatnmation (amygdalitis, of the tonsil, or uvulitis) is apt to -!iri ail iind become generalized, setting u]) a condition of pharyngitis. \\r rii iignize the following forms: Acute Catarrhal Pharyngitis.— Acute catarrhal pharyngitis or angina • \liiiiits in the early stage pronounced redness and swelling of the iiinii.sii, witii later abundant discharge of mucus or muropus and >"i iimi; of the isolated lymph follicles, sometimes also of the mucous siNiii.k. OvtT these projections there may be abrasions and formatitm "t iiii.il ulcers, with gra.x ish necrotic bases, .\cute tonsillitis mav be "t iliili rent types, but in all, the tonsils are swollen and hyperemic.'aml lii'r, 1. abinidant secretion of mucopus. The inflammation mainlv ■111' IN tiu. crypts which become greatly swoPen ami filled with foul I'"' ii' nt material. From here the inflammation may extend into the ~iil !inc,. „f the (.rgan leading to tonsillar abscess, 'and, as an after- n ;i.i ,,t the follicular disturbance, the contents of the crvpts may til 'I Ilia Wl th, liii: IT. 1' Mi>pissate due most frc(|uciitl> to the (li|)litlHTia bacillus, such membranous inflannnation is li\ uo nuiiiis a nccc— -ary iiidication of diphtluTial inflannnation. The so-called "diphtheritic membrane" may be due tn (1) irdialation of steam and irritant gases; (2) the streptococcus pyogenes; ('.{) more rarely, pnciiUKx mccus, in addition to (4; the most important cause. Racillus diphtheria'. In gmeral it may be said that the use of diplitlicria antitoxin gives the most rapid difl'erentiatioii l)etween the diphtherial and other forms of inflammation. With this ti." leathery niembraiie induced by the diphtheria bacillus may loosen within a few hours. The antitoxin may have some effect on other ijiembrjincs. hut not so rapidly or so characteristically. The true diphtherial infection begins with a localized congestion of the fauces of the tonsils or back of the p!iar\iix; soon there appear grayish-wliitc, opalescent spots, which sprciid and become fused, and now extending over the pharyngeal wall, coalesce into a dirty yellowish t lembrane. At the edge of tlie spreading membrane is a zone of acute congestion, and characten'-tically the membrane in its early stage is firmly adherent. Removal of the i-dge or other part will be followed by bleeding. Lfit-T, where healing occurs the membrane becomes loosened and may lie ^TCr rswT'Tfvm rUAHYXX AM) TOXSILS 439 removed with ease. Such iiieiubraiie may extend from the pharynx into the posterior nasal passages, th«- hi.ynx, trachea, bronchi, etc. As pointed out already, with the superficial growth of the diphtheria hac illus on the surface of the nuicous membrane, there is a necrosis and destruction of the epidermal tissue, which is cast off, an intense con- jrcstioii of the submucosa with abundant exudation of serum and leuiio- ( ytcs, and now a fibrinous coagulation of the exudate, with, at the same time, a necrosis of the superficial layers of the submucosa. As the cells litrt! undorgo a coagulation necrosis the resulting membrane is due in l)art to the surface exudate, in part to these necrosed and infiltrated superficial layers of the submucosa. It is this that renders the mem- l)rane so firmly adherent. Later, with healing, abundant leukocytes pass from the ves.eis into the deeper layer of necrosis, and as these, through their enzymes, cause the liquefaction of the necrosed tissue the overlying mt-ni)rane becomes loosened. Diphtheria bacilli may be Mipcrficial and grow in greatest abundance toward the under aspect of the nunilirane, although from here they are not to any large extent taken up by the leukocytes and conveyed to the deeper tissues. Or, if so conveyed, they do not there proliferate actively. Almost con- stantly there is an accompanying abundant growth of streptococci in the membrane. These may invade the deeper tissues ai)d set up severe lymplieating disturbances. Harely the inflammatiim extends along the Ku-tachian tube to the middle ear, or through the lacrimal duct to the eoiijunctiva. A similar membranous infection occurs m very acute cases of scarlet It \ er. I !ere streptococci appear to be the main agents, and the tendency tor tlie process to extend into the deei)er tissues with ulcerative dis- tnrl.aneesaiid suppuration oi the cervical lymph glands is much greater. Vincent's Angina. Xincent's angina, dm-, it would seem, to the ;;r(A\tli of spirociietes with the bacillus fusiformis, is a rare affection, and may in tin early stages show membrane formation. This tends t" the de\tl()j)ni.-nt of siiperfici; ' necrosis of the pharynx with the tiinnatiun of ulcers. Chronic Pharyngitis. The chronic form may Iw due to recurrent or I'liu-eontiiuied irritation as by alcohol, tobacco, or may be the sequel "I a sn(cession of acute attacks. There is a congestion of the pharyn- ;:i.il wall, with dull, reddish or brownish coloration, a mucoid or miico- I'linilnit secretion tending to dry and adhere in the form of scales, and it !i l-erpiasia of the lymph follicles, gi'.ing the wall a granular, wartv iii'l'> nance (granular pharyngitis). More rarely with atrophv of the I'luro-a the membrane becomes thin, .smooth, dry, and shiny" (chronic atiophic pharyngitis). In chronic tonsillitis with advancing age, as again, •" '"iiii>: to r,on;e, as the residt of acut.> tonsillitis, the lymphoid ti.ssue "I II • tonsils may become diniinished in amount, and there may be It atrophy of these organs. The ojjposite condition, hyiHTtro'phy, ti-i, •lii i(-iilt from repeated attacks of acute tonsillitis, or from long- '"' : 'lied irritation, as from retention of inspissate|H-ak of catarrhal, membranous, phlegmonous, or ulcerative laryngitis, lis weil as of certain specific forms, such as tuberculous or syphilitic laryngitis, or those occurring in variola, glanders, leprosy, or rhino- Mlcnmia. ('(liarrhdl I Ji ry ti (jit In. --Thk represents an early stage of inflammation, seen often by the laryngologist, excitetl by a variety of irritants, arising III the infective fevers, and is a prominent feature in such diseases as influenza and whooping cough. Just as in the nose, a preliminary n ihiess and swelling are followed by secretion of a fluid at first clear, lati r ilouy imi means safe to rely upon this as a sign by which to recognize diphtluTia, because a membrane overlying columnar epithelium is more nadil: removed than a membrane of like density Fio. 218 -a iihritiu- rcphu'ing nuicosa; b, outer layers Serticin frnm ii cawe of n.cnilirannus tracheitis: a, meilili lit auliiiiueiwa. necrotie anil iiifillrateil with Uukiieytei., c-, iiiUMiul.iris mueojw; J. efiguried veimels iif mihimirosa. e, deepest layer'- of suhiniie- Suppurative perichondritis of larj'ni: o, infil- trated and necrotic inner wall of ahaoeas; 6, eartilaKc laid bare and surrounded liy abscess cavit.\. THE LARYNX AM) TRACHEA 443 latlen'sputum, with the result that ulceration or a diffuse infiltration results. A tubercle, caseatiug and discharKinj;, will leave an ulcer, (IP there may be shallow erosions whose relation to the tuberculous infection is not at once evident, or there may be a diffuse, granular overgrowth, definitely tuberculous, which may subsequently caseate ill it number of places. Syphilitic LaryngitiB. — Like tuberculosis, this may be evidenced by con- jcestion, a diffuse infiltration or the formation of gummas, the epiglottis iiiid the vocal cords being liable to show the lesions. The tissues some- times become rough and warty with the overgrowths, and in parts where there is considerable ulceration a good deal of deformity may result. Glanders, leprosy, actinomycosis, and rhinoscleroma are all able to j;i\e origin to ulceration of the larynx. Fig. 220 Curcinimia of the larynx. (From the Patholofncal Museum of McGill I'uiversity.) Regressive and Progressive Tissue Change. —Atrophy of mucosa, iiliiiiucosa, muscle and cartilage, calcification of cartilage and such • haiiKes occur in natural or premature .senescence. Of progressive ' liaiiges, the commonest is the papilloma or papillary fibroma, a warty excrescence often seen on the vocal cords, consisting of fibrous tissue "\erlaid by squamous epithelium, which often recurs after it has been I'lnoxed yet n(lary growth. Alterations in Siie and Shape. Obstruction of the lumen may he eaustnl hy crdema. inflainmatory infiltration, tumors, exostoses, and atresia, or narrowing, hy contraction of scar tissue, or as the result of l)ressure from the outside hy agencies such as thyroid tuniors, i)eri- tracheal ahscesses, enlarge*! lymph iukIcs, or aneurysms, most of which may idso cause perforation of its walls. THE BRONCHI The pathological changes found in the bronchi are diverse, according to the anatomical nature of the part affectetl; the larger hroiichi, approximating to the structure of the trachea and larynx, are likely to be subject to changes similar to the changes seen in those structures. while the terminal bronchioles are so intimately connecter(> may he (ies(|uamati<)ii of the epithdiiini, (•(iii>;estion, «eiirfa(;e there is an alumdant exutlate, fibrinous ami richly cellular, wliicli in sections of the lunj; is often seen to fill the bronclms completely. Such a microscoi)ic picture nchiole. Neither this, nor the "Charcot-I^yden' crystal, is pathognomcmic of iistlniiii. .\s in the larynx aninM»us I>n>h"« CIill Vniv'THity ) Chronic Bronchitis. — The point of most im|)ortance in whicli this ilitiVrs from the acute form is that it tends to be pnMluctiv, the wall liiiiiic dtfiiiitely hypertrophic; even the mucosa may l)e rough and piilypoid, due to the irregular contractions of areas of fibrosis. Vet in M very long-continued inflammation, the products may bo absorbed, ;inil tlif nnicous glands, muscles, and cartilages atrophy, s») that the l>r(.!i(liii> may finally be dilated and thin-walled. The specific forms "1 lin.iu ii';t;s scarcely differ from traciheitis and laryngitis from the same (iiiiscs tiilKTciilosis. syphilis, etc. — unless it be in their greater rarity. Foreign Bodies, etc. -A foreign body, inhaled, is likely to fall into 'Ik riglit bronchus, because il is larger and more vertically .situated 'liaii ih'- left; if it completv'ly obstruct the bronchus, collapse of the ■■«;■■■•■' -7 JW 44r. THE RESPIUATORY SYSTEM ■■««r:. -, Lt.. part of the lung suppliiHl will folluw if tlu b«xly inhaled be septic, or if the trauma he coiisiderahle, a putrid hronthitis and abscess may l)C quickly set up; ut the best, there is likely to l)e loealiztnl inflanimntinn and ultimately a fibroid induration BrouchoUths. masses of in>pissated secretion in whieli lime salts lia\e f>ecn deposite( the iiing is ^Tadually absorbed by the blood and collapse follow: , wlureas, if it be only partial, the alveoli are dilated, and emphysema ensues. Bronchiectasis. — This is a diseased state in which the bronchi arc dilated and often acc.i to be encircied l)y ridges, which represent the less yielding muscular and elastic parts of the wall, while the more yielding con- nective tissue has given way. 'J'he hypertrophic form is found mosi often in a highly fil)r')id lung in which an irregular, heightened pressure is found as a result of some parts of the lung being cut off entirely from tht ir supply of air and the j)re?sure in other parts being icrrc- spoudingly higher than normal; pleural adhesions, too, may be so situated as to pull upon a bmnehus in two opposite directions at tho same ti:ne. Tiii- . \istenci of a bronchiectasis is usually evident to the naked > ye; even if the dil.'tations arc not of \ cry great size, it may be possible to trace the tub.- .ilm()st I ) the periphery of the lung, and their mucosa iS m\j; ^MX^i' TllK Luxas 147 almost certain to show cvitlt-nces of tli« arcompanyirif; hronchitis, while cDJlapse, compression, cavitation, or itiduration of the neighboring liiiig tissue may l>e visible. THE LUNOS AbnomutlitieB. — The anomalies of the lungs are unimportant; vari- ations in the lobulation, esiwcially of the right lung, are often seen. Circulatory DiBturbances.-IEdema. Where death has been slow, tlicro is almost certainly to be found some (edetna of the lungs, which arises from the laxity of the vessels of a failing circulatory system assisteil by the toxic or infective manifestations that we have pre- viousl.v referre ill tjiosf who sit; this postural type is called hypostatic congestion. ')l)strii(ti(m to the outflow fnmi the lungs iray be due directly to a \al\iilar lesion, such as a stenosis of the mitral valve, but more often ' is due to an 'inemptied state of the left auricle, from whatever cause. '\ 1 <\ < i Uie heart is incc.mpetent, it is to be remembered that the step ' s incomplete empt;y ing of the left auricle is passive congestion ;iiir tollo ar« BRm MICROCOfY RESOLUTION TEST CHART (ANSI ond ISO TEST CHART No 2l 1.0 I.I 1.25 *- 11 2-8 lllll-?! ii£ rr ^ 1: ■- IIM I: U£ 2.0 L. ^ li 1.4 III 1.6 ^ "A PPLIED IM ^ GE Inc ^S". ''^^■' £°st Mam Street S "-S Rochester. New >'ofi. 1*609 uSA "*^S (716) 48/ - OJOO Pnone 448 THK RKSI'IHATORY SYSTEM ■'« i , 1 of the lungs. The coiim'sted luiif; is eiilarjied, firm, less elastic than usual, and of a dark red orpuri)le color; with lonj; continuance, a fibrosis of the lung occurs, and from the dark color and the increased firmness, this has been called cyanotic induration. Where much bloo*! is broken down in the course of a long-continued congestion, the pigment stains the tissues and the predominant rusty color I'^ads to the term "brown induration" being employed. In such a lung, there are seen in the alveoli, or in the fluid expressed from the scfueezed lung, large, flat cells, generally circular, laden with brown pigment graiuiles — the "cells of heart failure" or "cardiac" cells, which are the desquamated cells that in tin ir lifetime lined the alveoli. The microscopic appearance of the congested lung is readily interpreted; the vessels in the inter- alveolar septa are congested, tortU(»us and varicose, and seem to jut into the alveoli in a succession of bead-like projections. Blood cor- puscles are apt to apjjcar in the alveoli. With this, there is an increase of the fibrous tissi\' of the interalveolar septa, which are often richly cellular, the increase being due to the numbers of fibroblasts. Very characteristic are the "cardiac" cells mentioned above, and in long- standing cases the j)igment is not confined to these but is seen in the septa themselves. Hemonhage.- Blood free in the lung is usually from the pulmonary \essels, but it may be aspirated from the nose or mouth or may come in from an aneurysm external to the lung; one of us (McC.) has described an aortic aneurysm exjianding in the upper h)be of the lung. This, however, is a nwv oc«'urrence; the common mode of production of pulmonary hemorrhage is by erosion of a vessel in tuberculous or other ulceration or its rupture by trauma. In tu!)erculous cavitation the blood vessels being very resistant may be left ])rojecting into a cavity as a loop or even crossing from side to side. Such a vessel is unsuj)- ported, and its wall being degenerated a rupture may ensue, or an aneurysmal dilatation which later rujjtures. Death does not so often result from a single large hemorrhage as from the effect of repeated hemorrhages. Infarct. An infarct is the area in which a hemorrhage occurs as a result of the blood suppl\ to it being cut ort' by a clot lodged in the vessel supplying it. Thetyi)ical infarct is cone-shaped, sharply defined, the base of the cone usually situated at the pleural surface, the apex imiermost at the point where the clot is lodged; it is elevated above the cut surface of the lung, is dark red or purplish, and firm. The pleural surface is at first smooth, but becomes roughened by the fibrinous deposit that results from reactive infianmiation. The edges are usually sharj), and with the lapse of time may become gray from fibrin and leukocytes, while the centre may (rarely) soften. Microscopically, the air sacs arc distended with blood corpuscles, and the relation of 'he .septa to one another is unchanged; the nuclei of the tissue cells in;iy stain i)oorl\ . At the jieriphery of the infarctous area leukocytes ire usualh' abundant. THE uwas 449 Witli the lapse of tinu" the iiitiirct tends to he absorbed; with the lircakiiif; up of the corpuscles and the setting free of pigment the alveolar >p;i((s begin to be reestablished, and circulation restored. Should infection occur, abscess will follow, but necrosis and cicatrization are I II it common in the lung. Ari-ing as infarcts do, in val iilar diseases of the heart, it may lie tliiit the capillary walls are degenerated, and rupture is brought iilioiit by the force of the collateral circulation acting on the capillaries tliiit arc full (from the bronchial arteries). It is still (lebated whether the hemorrhage occurs per rhexin (ir jivr (liojH'desin. Embolism. — Although this is dealt with in connection with the vascular >ystein, it may be pointed out that fiit embolism occurs in the lungs in the ease of fracture of a long bone, vviiere fat is picked up by the iilood fr.iin the marrow; in fresh tissue the l;it ^'Idbiiles may be seen and stained in the vessels. Particles of fibrin 111- e\t"ii large thrombi may be de- iMched from the systemic veins, iiiid, passing through the heart, may Indue in the lung; if a large ves.sel lie hldcked, instant death may be tlie result. IHnidSfd States Due to Disturb- innf (if the Respirator}! Funetion. — Atelectasis. — This is the state in which the air sacs are partially or com- pletely mulistended by air. ("oinplete airlessness is called apneamatosis. The true atelectatic state is that in which the limgs have never lurn distended; in it the bronchi are lying in folds longitudinally, and the alveolar walls are in contact with each other, to be thrown a|iiirt and distended with the first breath inspired. A persistence of I lie foial state, with a failure of proper expansion, may be found 1" debilitated and premature children, especially those with such a ■ie\elii])mental defect as hypoplasia of the lung or a diaphragmatic l'ernia;or with bronchial obstruction by foreign body, by meconium, '1 liy secretion or by compression of the thorax. Not oidy in infants 'lies atelectasis occur, but in weakly or moributid adults it may .ii'Ne. \Mien there is a mechanical cause allowing the egress but not the i-Tess of air, the respiratory act is not of itself suflicient to produce a 'ite of airlessness, !)ut the resitbie of air that cannot be expelled is A\ly absorbeil l)y the blood until the alveolus, being empty, collap.ses 29 I ^ St'rti n from an infarct of the lung, show- ing cPDtrnl portion Tlie alveolar walls stain poorly; the alve jli are difliendcd with blood in which are oei usional pigment-holding cells, staining deeply. 4r)0 THE RESPIRATORY SYSTEM i ii ^^, completely, with what maybe resarded as a compensatory dilatation and congestion of the vessels of the alveolar walls. External pressure upon the lung or a part of it induces a compression atelectasis. Fluid or air in the pleural cavity, an elevate.l diaphragm a mediastinal tumor, enlargement of the heart or pericardium, thick' enmg of the pleura or distortion of the spine may all he effective not only by reason of direct pressure but also by indirect interference with proper respiration. When the whole lung is atelectatic it lies high up in the thorax close to the spinal column, possesses the bulk of a moderate sized adult hst, and IS brownish red in color, or if anemic, is gray. From its resem- blance to flesh It IS sometimes called "camified." It does not crepitate and It sinks in water; if squeezed below the surface of the water a few bubbles may be expressed, chiefly from the bronchioles. If onlv ,■ part of the lung be atelectatic, the surface of that part is smooth, dark and depressed below tiie surface of the rest of the organ In the f(rtal state, the lining cells of the air sacs are polvhedral or rounded, and project from the walls; with complete expansion <.f the ling they become flattene.1, and with a subsequent acquirement of tne atelectatic state, they once more assume their former shape Emphysema.-- The term interstitial emphysema describes the state in which the tissues of the body at large or the connective tissues of the lung are inhltrated with air, while emphysema, pure and simple, denotes the oyerdistensioi, of the air sacs. When this is generalized, there are certain w«^l-marked physical ppculiarities in the thorax. The accessory musclc>s of respiration are well developed, the neck appears short and tluck the chest IS enlarged, .-specially in the anteroposterior direction, so as to be barrel-shaped, whilr the abdomen is relativelv sunken. r.H.n opening the thorax the lungs arc ^•oluminous. relati^•elv of light weight, an.l do not collapse. The tissue is inelastic, less crepitant than normal, keeps the imprint of the fingers and feels like "a bag of feathers." On the surface the pigmentation is slight, the surface pale, and at times tlie individual air sacs can be seen with the naked eve like little vesicles. In a.lvanced cases, especially at the edges of the lungs. individual sacs may become of great size, giving the lung a bullous appearance (bullous emphysema). ^Microscopically, as seen in Fig. 217, p. 432, in a case of emphv.se.na there is marked atrophy of the alveolar walls, and manv of them ar,- ruptured; several alveoli are thus thrown into one, and" the resulting sac takes a shape approximating to the circle. In the thinning-out and rupture of the walls the blood vessels necessarily are flattened, thiniuHi out, and many are thus ol. terated; the diminution of space that occurs in the remaining vessels due to pressure throws increased work upon the heart and the right ventricle distends and hvpertrophies. Inflammation.- Pnemnonia. — Here consideration is given to the pathological aspect of an inflammation of the lung itself—a pneumonia or pneumonitis— and not to the manifestations elsewhere that arc a THE LUNGS 451 |)iirt of the disease that is termed by the clinician pneumonia. Yet we niiiy not, for a moment, disregard the fact that the reader finds his interest chiefly in the clinical manifestations of the disease. It is necessary that one see, at the outset, that an inflammation of the interstitial tissue of the lung is just as truly a pneumonitis as an inflam- niiition of the air sacs, though by no means so common. Even more iini)ortant is it for him to recognize that, numerous as the causative iifl'-'its are, and diverse as are the modes of infection, yet the air sacs resiMHid to irritations of all sorts in much the same way. Just as was said in the general discussion of inflammation, the process may vary in sixed, in intensity, and now this feature and now that other may be I)rnniinent, but at the bottom of them all lie the same fundamental (Kcurrences; the blood vessels become congested, there is an outpouring of >erum and a diapedesis of leukocytes, a formation of fibrin, a contem- Ijoraneous killing or injuring of the cells of the part, especially those that line the air sac, and e\en a multiplication of those cells that are mildly irritated- all this occurring in the dosed-in space of the air sac, so that the pruduets of the inflammatory process fill the air sac to the exclusion of air, and the disposal of such product.-, constitutes a step to be per- formed i)y the body in the process of healing, over and above what has to !)(■ (lone in a case of inflammation on a surface. Ahnost all the known pathogenic organisms have the power of eansmg pneumonia; the Fninkel-Weichsclbaum diplococcus of pneu- monia, Kritdlander's bacillus of pneumonia, the Streptococcus pvogenes, the Staphylococcus albus and aureus, B. tuberculosis, B. tvphi "abdomi- HiilK, 15. eoli, B. influcnzie, B. pestis, B. anthracis, and B. diphtheria' ■ iKlnde nearly all. While each of these is able unaided to produce the disease, it actually happens very often that the infecti(m is mixed. ■ |S to the maiuier of infection e' ryone of these bacilli can reach th<' Inng either by the bronchial tract (aerogenic pneumonia) or by the blood or lymph (hematogenic, lymphogemc pneumonia). As to what "liiiieal type of iiiiahie to cause a lobar pneumonia, Be this as it mav, lobar pneu- 'ii"ina 111 the e! laical acceptation of the term, is a very different kind " e haeteria gain power to attack the tissues? I'erhaps the body is ■ittaeked at a moment of chilling or at a time when resistance is in some • -; i)ecomes heavy, swolleiv firm, pits on pressure, and is more friable than normal It is intensely red. owing to vasciihir hyi)eremia rather than to the jm-sence of red corpuscles in the exii(i;iic, and the fluid scraped off the cut surface witn a knife is definitely tiirl-l. and ')lood-staine(l. Microxopically. the capillaries are congested, liic lining epithelium of the air sacs is swollen, often desquamated. m\A fibrin and leukocytes are i)rescnt, the fibrin threads mak ,ig a conipli te mesh ill the air sac just as a blood-clot adheres to the sides of a gln-s vessel. lu-d corpuscles are im-seni. rioin the red solid a|)pearaiicr ..i' the tissue in this state, it was likened to liver, and the term hepatization THE LVSGS 4.53 "iKir iiiii'imioniu (uruy lic|M(izalimi). The IciwiT iohc is involved (Pathological Museun MiGill University.) iKi. a24 sXn^ !•'•-. ■>t-nto Inter pmnmv.nis, =^tr,K,. „f f..,l hvp::iizati:m. The rcntro „i ih,- u.ieloscpi.- fiei,! ia >\><-'l by an air vosick- cnntainiiig a mass uf exudate composed of a network ..f Bbrin, red blood '. iin.l a few leukocytes. (Hare.) wm^^mmmim 454 THE RESPIRATORY SYSTEM Kui. ■^25 iippliod to it. To iiiKierstiind properly how this changes to the so-calle«i gray hepattiation, a consideration of the microscopic appearance is neces- sary. After tlie hipse of a Uf '- time tlie fibrin tiireads begin to break np under the action of enzviues, and just as the blood clot shrinks away from the sides of *.lic j;luss vessel, so the exunil)al)ility, the swollen alveolar cells, and these give to the exudate a ' iit tluy never succeed in producing the uniform solidity of the lobar t> ])e of pneumonia. With the possible exceptions noted above, a piece '!■ -11! the middle of one of these areas is microscopically iudistinguish- i'l'ie irom a similar piece cut from the middle of a lung in lobar pneu- M! i|l.fll| IMipf II 456 TIIK RESl'IRATORY SYSTEM nioiiia. Tlu' iiidivulual consolidation., pass throujrh red and jtray stages, iiiid tlu' sporadic distrihiition of these areas li.is led to the hinj? beinj; lii at a time of low vitality or complicates other ;;r;ne disease. Several of the difierent forms must be considered individually. Fio. 226 Twf> iilveoli from the lun*; in n<'ut" lobular pncuniuiiia, showinK loowr cell rollortion in the t^xiulatf Hud aliMDce of fibrin: u, disintogrutiniE Icukocvtos with gianiilar contents; h, same with fat globules. Aspiration Pneumonia.— A typical example of lobular pneumonia is that known as inhalation or aspiration pneumonia, arising from the aspiration of food, vomitus, or secretion from the nose and mouth during unconsciousness, as in the anesthesia of operations. PVoni the nature of the infecting agent it will be readily understood that tlie tendency to destruction of the lung tissue, to abscess, and gangrene is greater than usual. It is a frecpient ( ccurrence that in surgical cases ending fatally, especially where vomiting has been present, tin trachea and bronchi show a greeni h tint, suggesting bile-staineii stomach contents, and this usually indicates that such have been aspirated. Where life is sufficiently prolonged to allow the pneumonic process to supervene, the profuse sputum, often foetid, shows by the presence of elastic tissue that the lung tissue is being destroyed, ami at iiiitopsy scattered or confluent areas of actual abscess format!"!' will be found; the zone ?urr(»unding such areas is likely to show a '■•. ;^M^B THE U'xas 4i>< \(T.\ iiitt'iise conRt'stion '>eraiist' set-ii in s«) vascular an nrnau. St'ptio liiiiuiiKinia may hv caiist-il ii) other ways than hy inliahitiuii; the exten- -ioii of inflammation from nt iKhhorinit tissues, such as tlie ineiliastinnni (■r tnini snl)(liai>lira);matic stnu-tures, will c-anse it. as ma\ also infec- tion at the time of injury to . ' '■ Innj; as in jierforatinn wound of till' luim through (he chest wall. Womul of the lunj; hy a rii>, where III) external womul (\ists, is more lik»'ly to he followed hy an unmixed infection and a typical pneunonia, hecause the wounded area is the liliicc of least resistance for the time Ikmu)?, and the infection is Iiema- tot.'fllIc. Metastatic or Embolic Pneumonia. — This is allied to the last form. It hapi>ens as a manifestation of a general hacteriemia in such dis- eases as osteomyelitis, thrombophlebitis, arthritis, sejjtie endiK-arditis, iiiiil erysipelas, where a septic embolus becomes the point of origin of a laieumonic focus. N'-; part of the lung is exempt, anil tlie abscesses can he felt as indefinite lumps deep in the tissue or seen as yellow dwellings under the j)leura, varying in size from that of a pinhead to several centimeters in diameter. The inflanunation set up by the Mptic material brought by the embolus, although circumscribed, is of the nature of a localized pneumonia, but it |)roeetHls straightway to the formation of abscess or gangrene. Of pneumonic nature, strictly ^|)eaking, is also the effect of secondary infection in tuberculosis, aetino- iiiycosis, or other primary infection. Hypostatic Pneiunonia. — A pneumonic infection occurs very often in tliii-e who are debilitated, and because the posterior parts of the lungs are cDiigested and (edematous it is here that the infection strikes, ami a difi'use catarrhal pneumonia, definitely localizwl to this part of tlic lung, is set up; the general bodily depression h;is much t do vith tlic infection, for it is know:i to every clinician that lnn};s may r. iiiain conu'csted and (edematous for months without infect n; but w' ii the individual comes within a few hours of his di ith, th .o-called urmina' ■ifcction takes hold, and thus it is that so man\ patients -iitierim iruin lieart disease die irifh, if not from a pneumonia. Chronic Pneumonia. — ('are is nece.-isary in considering chronii puet*- iiioiiia not to incluoo the actual reparative process that may follow i^ acute pneumonia, unless an actual lesion of the alveolar septa occi, i'lie term chronic pneumonia presupixises that an irritant is continual and progressively at work. An "unresolved pneumonia" is correcily ., I lironic pneuuionia, and the infections of the granulomas, tuberculosis, -vpiiiiis, actinotnycosis, etc., set up an inflammati(m that may be so ii'^iiiuated. Chronic pneumonias may be divided into (1) the above- iiK'utioned secondary indurative pneumonias, (2) pneumonokonioses, the iiMases excited by the inhalation of various kinds of dust, and (3) pleurogenetic pneumonias, caused by the extension inward of the infec- tion of a chronic pleurisy, a rare form. ! . Sinindarif Iriduralicc Pitcumunla. There is a genera! substitu- i'lii of fibrous tissue for the soft lung sul)stance, the pleura and inter- IW^ plW^l^ »fp^ 4.'>8 THE RKSriRATORY SYSTEM lobular septa l)eing specially prominent. If it «Hciir secondary to a l)rouclioi)iieunioiiiu, the fibrosis roughly follows the bronchial tree. In an advanced case, seen microscopically, one is struck by the fact, that, when-as normally the ffreatest part of th«' section is air space,' and the least the walls, here the greater part of the field is sohd tissue and th. lesser part is air space. The Inng is heavy and hanl, cuts firmly, IS grayish in color, mottled with the black of inhaled dust. Areas of necrosis resembling caseation nuiy b<' seen, the pleurae are thickened and often matted together, and the lung may be entirely deformed. Microscopically, the air sacs show as small irregular spaces containing desquamated cells or leukocytes, lined by irregular cubi«aj cells, and Fio. 227 Section from ■ ae of indurstivc pneumonia (fibrosis of the lung), showing the extreme fibroid thickening of the alveolar walla ami the consequent rcluction in sise of the alveoli: a, alveolus con- taining desquamated cells; ft, somewhat cul... al epithelium lining the air spaces. separated from one another by wide masses of fibrous tissue. The bronchi are irregular in -hape from pressure or traction. Now and then in the fibrous tissue one sees large collections of leukocytes and young fibroblasts indicating areas of acute inflammation in the fibrous tissue, where some infection still continues to operate. This extreme grade of change never follows passive congestion; here, at the most, there is moderate thickening of the septa and the alveoli show many catarrhal cells containing pigment (brown induration). 2. Pnmmonokoniosis.— Little, if any, inhaled dust reaches the lungs directly in the air, but it imping.-s n;\ the bronchial walls, i- carried by the leukocytes to liie peribronchial lymph collections or to THE LVXGS 450 to a the alveolar walls. Wherever it Iniuls it may -et up a certain atn'^unt 111 itution, tiic more so if if particles are shurp-edKed, iMicatise these at tiially pierce the walls ami set up in the surroundinK tissues nodular reactive jjrowths, like tubercles, in which the offending pi-rticles arc >liut up. In a«lvaii(ed cases the peribronchial lymph tuxks m.-'y l)e gritty, and particles may be carried to ti.e alnicminal lymph nwles. |)itr»reiit kinds of dust set up differ»'nt degrees of irritation; the most familiar fo m is uithracosis, from coal du.st, found in all adult dwellers ill (ities. id unimportant; in the case of coal miners, however, the damage -«..ight may l)e great, and anthracotic tubercles are seen as uraxisli ..sses of fibros'a with blac' .iics, while the entire lung is soiiiewliat infiltrated and is heavy. ;< .ine-mason'slungCchalieotU) the infiltrating nmterial is grey an ' •- /; in siderosis particles of iron and steel do the damage, as is seen ...:ong needle-grinders, file-makers, ami iron-workers of different kinds. The lesions are not very different lrt)iii those of indurative pneumonia; calcification and even the forma- tiiiii (,f bone has l)een seen. Tuberculosis.- Tulwrculosis occurs in the lungs Iwth as an acute ami a chronic ease, the Bacillus tuberculosis, discovered in 1882 by Koch, being the essential agent. .\s to tlie mode of Infection, it may be stated that tuberculosis is not iureditary, and but few cases of intra-uteriieginniDg; E, a fused ii' li.nf lubcTclos, farther advanced that at D. (Hare.) f;i' t, a combination of caseous tuberculosis and '^npumouia, the lesion l"'>l^lns,r microscopically like the former and the in olvement resembling tliat i)f the latter disease. "Fibroid phthisis" is merely a very slowly I'lnirrpHsing ulcerative tuberculosis, in which there is ample time and Mmiiilu.s for a marked degree of protective fibrosis to occur. The !i 'rous solidification of lung tissue, with its contraction and consequent mr^fw at 'j« eo^^z-TK^-V.^*- . 4(;4 THE RESPIRATORY SiSTKV ddorinity of tlic liiiifr and i-\«mi of the chest are the itrikiiig features of this type of *^\il)erciilosis. Hematogenic Tuberculosis. This form of the disease is characterized hy the disseiniiiatioii of tlie haeilh hy the hlood either in the lungs alone, or in the lungs in connnon with all the organs of the hody. A caseous focus breaking into a vessel or intt) a large trunk of the lymphatic system is the usual cause, and the widesjjread occurrence of tubercles in s(t many foci at once brings it about that death occurs before any considerable degree of enlargement and caseation occurs in any one of them. Fio. 232 Fio, 233 Caseous hibiTi-iilosis (»n pussinK on to cusrot pmuiiioiiia. (Paili. Mils, MiGill liiiv ) Ht'iiiatoKonous miliary ttiiw^ri'Mlosis oi liinc (I'alh. .Mu». MrGill I'niv ) The lung so affected is hyi)eremic, heavy, and the tubercles are felt, or later seen, as shotty, granular particles in enormous numbers in the tissue, throughout both lungs in the generalized disease, in one or a part of one in the locai forms. The bronchi are reddened. From the small size of the tubercles (Fig. 2:53) each has been likened to a inillct seed {wili.i) and the term miliary has been given to them. Tubercles of the same small size and miliary appearance may also at times be encountered as the result of bronchogenic, not hematogenic infection; in such a case their arrangement is not uniformly dift'nsc; they occur in little grape-like clusters along the course of individual bronchi. Lymphogenic Tuberculosis.— Infection of the lungs may occur from a tuberculous caries of the spine or rib, and occasionally by direct extension from a lymi)h node; the most frecpient example, ho\vc\(T. is the secondary spread of the disease in the lung itself. Under this heading it may be jHiiiited out that there is still debate as to the j'iirt played by the pleura and its lymi)liatics in the origin of apical tubercu- losis. It is held by some that the i)lcural cavity becomes infected from the lower cervical lymph nodes, and from this, infection most ea iiy involves the apical region of the lung. Syphilis.- .Syi)h' of the lung is rare, and seen oftenest in the new- born. No doubt some cases considered as syphilitic bronchitis and THE TUNGS 465 pneumonia are merely instances of a mixed infection occurring in s.v|)liilitic i'ubjects. The disease proper manifests itself as an interstitial fibrosis or as gummas. Gummas are rare, found oftenest near the hilus, and if healed may leave a fissure forming a false lobe (pulmo lobatus). (irayisii, translucent whei. small, gummas may in their later stages iipjuar very like tube'-cles. The diffuse interstitial form is due to a ^'('iicral widespreii ' infiltration by inflammatory products that can be fiadily understood by anyone who has stt-n the enormous numbers of spirochetes that infest the lung. The anemic pallor of the organ !ias led to the condition being described as white pneumonia. Actinomycosis.— Actinomycosis o irs in the lung both as a primary and a secondary infection, conveyed from the mouth by inhalation, or l)y extension from the mediastinum or oesophagus. Sometimes manifest as miliary noddies, it ^lay, nevertheless, set up a broncho- imeunionia and consolidation with ca\'tation may be found. If very chronic and long continued a fibroid lung may result. Glanders.— Like actinomyces, the B. mallei may set up an acute pneinnonic process or a chronic state characterized by multiple miliary Modules, hardly to be diagnosticated except by the discovery of the l)a(illus. Various Infrequent Infections.— There are certain organisms that have Ixrn found infecting the lung, capable of setting up either caseacing i;ranulomas or diffuse pneumonia or abscesses. Cladothriz, streptothriz, some of the hyphomycetes, aspergillus, and even animal parasites, such as strongylus and distomum Westermanni, have been found. Echlno- coccus. carried from the liver, may form cysts in the lung as elsewhere. Regressive Changes.— We have already spoken of the atrophy of the lung seen i.i emphysema (see Fig. 217, page 432). Here we would iiKreiy recall that this emphysematous process is often secondary to a !ironressi\e atrophy and disappearance of the elastic tissue of the luni:. The «. b'-onic deposit of fibrous tissue around the arteries and the l)ronclii seen in the old, the so-called periarteritis and peribronchitis, is, a> the names imply, usually regarded as an inflammatory condition. It i- pt rliaps more properly considered as a progressive than n, regressive cli:ini;i'. Progressive Tissue Changes.— Hyper .y may be said not to ""IIP in the lung, increase in size being . physematous, not hyper- tn pliic. Tumors of primary nature are rather rare; of benign growths fibroma, lipoma, chondroma, and ostooma are found, the last named not t'l lie confounded with the metaplastic formation of bone previously iiHut.oned; adenoma and teratoma are of great rarity. While the lung I- I common site for secondary malignant tumors, especially those cirrud in the blood stream, primary malignant tumors are not \ory ' "iiinion. Sarcoma is found arising from the lung tissue, Ijrmphosarcoma tr.hi the lymph tissue, especially at the root of the lung, and endo- ihelioma from the lining of the lymphatics or from the pleura. Primary carcinomas may originate in the bronchial or the alveolar epithelium 30 4(i() THE RKSPIRATOHY SYSTEM or III the ponlm.iicliial imirous glands, und are important from tli fre(,ueiuy with which they i)rojeet into and J)Ioek tlie F)ronchi, wit resultant eoUapse of the lung tissue. All tumors that pro(lu( secondaries ajipear witn fai frequency in the liinj;, especially th chorioepithelioma, whose tissue of predilection it is. THE PLEURiE The i)leur!e are sacs composed of i thin, loose, connective-tissii menil)rane containing; numerous blooii vessels and elastic fibrils hik covered l)y a sinjile la> er of Hattened endothelial cells. These sac-wall henm normall.- m perfect ai)i)ositioii. ihe i)leural cavities are non existent. Any content, therefore, constitutes an abnormalitv Xoi very i.rone to primary disease, they often suffer by the contiKuitv oi the Junp, and by the relatively free lymphatic communication witl the pericardium and the jH-ritoneuni. The course of anv disease ,.l the pleura is influenced by the constant movement inseinirable from res|)iration. ' Circulatory Dwturbances.-Hyperemia.-Active hyperemia occurs in int^animatory attections and with congestion of the lung proper, and occasiona ly from relaxation of tension when th..racentesis lias been performed, ^^\n\v passive hyperemia is found in obstnicticm to the greater or le er circulation. Hemorrhage.-- Petechiie, ecchymosis, or even hemorrhage maA- arise from trauma, in suHocation, in renal and cardiac disease, in Severe intections and intoxications and in instances of the hemorrhagic diathesis. '^ The Existence of Contents in the PleursB.-Hematothorax.- «I„,mI may be efluscl into the pleural cavity in wounds of the chest such as fracture of the ribs, inv.'ving the pleura, or hv the bursting into it ot an aneur>sm, in which cases the blood mav be unmixed Often however, it is mixed with transudate or some product of inflammation,' as 111 the case ot certain forms of pleurisy-, with .lew growth, or when a tuberculous or gangrenous cavity ruptures into it Hydrothorax.- This consists of the presence of a transudate in the pleural cavity, occurring oftenest on the right, frequentiv on both si(..'s. Ihe explanation offered for its greater frefpiencv on the right is that a distension of the right side of the heart j.resses upon the veins of that side lenral adhesions may localize the fluid to a part of the cavity attected. 1 he fluid is usually pale, straw-colored, alkaline, of a specihc gravity of J(M)!) to 1(.12, containing 2 to 5 per cent, of albumin; microscopically it contains nothing but accidental leukocvtes and desquamate,! endothelial cells. The surface of the pleura^ renu.ins smooth but in long-standing ca.ses becomes thickened and even nearlv by reason ot overgrowth of the fibrou;; tissue. A small amount of fluid may t-ansude into the pleura during the TIIK I'LEIR.H 407 .ic.ili iip.ny, hilt j)leiitifiil transudations are found in nt-phritis, broken .niM|Hiisation of the heart, cirrhosis of the Hver. hvdremia. an (hydropneumothorax), or pus (pyopneumothorax). Al.chamcally it may he produced hy a penetrating wound of the cli.-t, even hy thoracentesis; most commonly it follows the rupture of a tiilMTcuious or gangrenous cavity through the pleura during a severe [.Mn.xysm ot coughing; an empyema may rupture into the lung or iiir lor «as) ,„ay come from the ,VM.pl.agus, stomach or bowel previouslv r.iid.nd adherent to the pleura or to the pleura and diaphragm bv new irrouth. 'ertain varieties of pneumothorax mav be difl-erentJated • Ml open pneumothorax, in which air passes freelv in and out. C>) val- vular pneumothorax, in which an oblique, valve-like opening allows air tn .liter hut not to escape, and (;i) closed pneumothorax, in which the "Pcniiii: has become occhuled. Pneumothorax, without i)erforation iirlnisn, "' ' "''''"* "^ **" '"faction of the pleura by a gas-producing The cticct of pneumothorax depends ujjon the cause and the l-rMstciice o the communication with the outside; while the fistula rcnmiiis, the ung will be collapseij..n. and more d:.te,.ded until the heart is pushed over and the dia- I'hni^MM .lepressed; If there be no infection, ami the woun.l be closed ilM' air may he gradually absorbed and the lung may resume its natural' Inflammation. Inflammation of the plcu-a (pleurisy, pleuritis) is ".'ll.v Mt np In extension of the disease from an organ nearbv or ;;• Nu.ta>tat,c at cction. part of a general disease, as i^ seen in bac nn „".„;. r"'*'^ ™f-''>'' ^"'»P»^te or partial, and is either exudative 'r Poduc ve; the exudative form may arise in a pleura alreadv the .1 t a prodiic ivc inflammation or the exudative form mav develop 1 e productive. These two forms ..re really expressions of a more •' '■' ■' 1'^^ '" ■ intectum. '-h'^^mS^'^ ''''"' ^'^^'"'^'' "^"••' ^^'^ '^ ^hut in, unable to Pla ac neuriLi ' "'""•' l"'""^ aPPearances; it may be fibrinous • rrln'i '"■""'' ^*""'^^""""^- fibrinopurulcnt, purulent, or lirli 4r»s THE RESPIRATORY SYSTE.\f Fibrinoua Pleuriay. -In this, the scM-allid "dry" pleurisy, the j)Ipnra is opatjue, and covered by a delicate hiyer of fibrin which s<-arct-Iy resists removal. This consists of interlaced threads of fibrin, with leukocytes, and bacteria; the vessels of the subjacent lung and of the pleura are congested, and fibrin may b«- seen in the tissues, which are a'dematous and show a certain amount of cellular infiltration. Fia. 234 b _ Section from a case of serofibrinous pleurisy (high power) : a, congested and infiltrated aubpl ural lung tissi e; h, fibrous layer of pleura also infiltrated and devoid of endothelium; c, c, denser bands of fibrin; d, d, loose nieshwork of fibrin, infiltrated with scrum and leukocytes. Serofibrinous Pleurisy.— Few pleurisies remain dry, and there is usually an outpourinK <>f fluid into the cavity (pleurisy with effusion); this fluid is yellowish, and if mixed with many cells and shreds of fibrin, turbid. In the dependent parts of the cavity and sticking to the walls of the pleural cavity are shaggy masses of fibrin, bright yellow, some- times gelatinous, and at times w thick as to form a regular blanket which it requires some force to tear. The amount of fluid may vary from a few cubic centimeters to several liters, it coagulates readily with heat and sometimes spontaneously on removal; its specific gravity is high (1025 or more) and it contains much albumin as veil as sdine uric acid, cholesterin, and sugar. Microscopically, it hows fibrin, leukocytes, red corpuscles, endothelial cells, and bacteria. The condi- tion of the lung varies with the amount of fluid; it may be almost completely collapsed, the heart disj)laced, and the diaphragm (and with it the liver) depressed. The collapsed part is tough, gray, or gra.\ i-li brown, or even bluish in color, and is non-crepitant. If not heltl by THE PLF.VR.E 469 iHlhcsions, the fliii«l moves with the patient's change of posture. When h.iilinj; occurs the fluid is Kradually ahsorhed by the lymphatics, the lil.nn l)rcaks up, and no sign of trouble may remain except a slight ilii( kcning of the pleura. Oftener, however, some organization of the lil.rous layer occurs, so that the visceral and parietal layers of the plnira r.-main adherent. With the lapse of time, the adhesions, being ( onstaiitly pulled upon, become thin and veil-like; such adhesions are otteii seen l)etween lobes and on the posterior surface of the upper lobe, and in some cases the pleural cavity may be entirelv obliterated. Purulent Pleurisy (Empyem*).— This may arise from a serofibrinous pleurisy, or as a complication, sometimes a sequel, of pneumonia, or from I hi- rupture of a tuberculous or gangrenous area in the lung, or more ranly, a subdiaphragmatic abscess or a diseased viscus may perforate uito the pleura. In children it occasionally seems to be primary. The • xudatc consists of thin or thick pus, and the action of the pus cells t.n.ls to digest the fibrin. If putrefactive organisms be present, the pus JMconies very fetid. If the condition be not relieved surgically, the consequences may be very serious; the patient may die of exhaustion,' ot toxcnua, or the pus may rupture into the lung with formation of pyopneumothorax, or through the chest wall (empyema necessitatis), or into neij;Iil-,oring organs. If unrelieved, it occasionally happens that the fluid IS absorbed, the pus becoming inspissated, and later, infiltrated with calcareous salts, so as to ft)rm a .solid plaque. Should the patient survive there is usually great thickening of the pleura and even deform- it\ ot the chest. Practically it must be remembered, in viVw of the serious nature of the disease and the readiness with which it may escpoe recognition, that the physician will oftener regret his delay than his I>re(ipitaiicy m the use of the exploratory puncture needle in a doubtful case. Hemorrhagic Pleurisy.— Bloody exudate is found in tuberculous pleuri>y or where new growth is present in the cavity, although not <■! iHcessity; further, it may occur in the very debilitated, or those sullerniK trom scurvy, icterus, or the hemorrhagic diathesis. Productive Pleurisy.— This may be a late development of a simple eMi, ative pleurisy, or may arise insidiously as a primary affection. Miulit (legrees of thickening of the pleura are pathologically unimporiant ;nid clinically equally so. In the more marked cases the pleura is "in.li thickened, even to a centimeter or more, becoming a white 'I'enil.raiie, sometimes of a pearly or cartilaginous appearance, and 'H extreme cases, resembling the icing that is put upon a cake (hyalo- serositis). On microscopic examination, this proves to be layered, and '"lierwisc almost structureless, save that in its deepest parts there !^ ^li^'lit vascularization; the lung is apt to participate in the state of ""I'lratioii, and often a neighboring serous surface is likewise involved, ' -I-eiially the peritoneum over the spleen and liver. With the lapse >'= -'lie, calcareous masses or plates of cartilage and bone are formed. 470 TUK HESrinATOHy SYSTK.Xf n • TJib«rcul08ii o{ the Pleura. \„t infm,.untly a patin.t pnvi..u.slv lu-altl.y .|,.y,.|..ps pleurisy with rtruMon: such a plnirisv. oominic "oiit of u .loar sky is likely f. hv ti.I..T.ul...is, aii.l ov.-n if "no l.>s.la(rs in which tubercle bacilli and other infective ajfents lie latent or Irnni which tlii-y set out to infect the Ixnly at larjte, the lar^e groups ot nodes \n tiicmcliastinum are those referrce lymphoirl tissue of the thymi. ., and of these s<.me at least, exhibit the characters of an inflamm -,ry Kranuloraatous Krowth. .Secondary maliKiuint growths ol)tainin« pla.c in the Ivnioli noy what »i)pear to be true fat cells. Occasionally it persists until the fifteenth vear or later and is of considerable size, with abundant lvmt)hf>cvtic'ele- nients. Diseased conditions of the thymus .re rare; them.ist important is the thymus hyperplasia generally accon ji-tiying the status lymph- aticus (lymphatisiD); this hyperplasia otcu-s in young children, but ha. been noted in you.ig adults, weights of .0., to ir grams being recordci, t..e maximum of the normal gland being '.il grams. In leukemia there may be marked enlargement as also ;.i <-ome cases of exophthalmic Koitre I{are cases of abscesses, tuberculosis, and of syphilitic necrosis nave been described. Tumors are rare, with the exception of lymphosarcoma. As ab(>\ e noted. It appears probable that a large proportion of the diffuse, locallv infiltrating growths of the mediastinum originate from the thymus glancl. <'n.\i*Ti:i{ VIII THE NERVOUS .SYSTEM GENERAL CONSIDERATIONS' UiiKN \ye recall the fxtruunlinary ecmpUvxitv of the finer <• —rv ..t the .rain aii.l c.rd, the relatively small arek of the .surffl.>' ,e ( rr. hriil heinisi>lieres ui which we can recognize the existet- - tres" .•H„tn.ll.nK one or <.ther function of the b.Kly, the vast ma- .Tehrum nn.l cerebellum, regarding the function of which we have n ure inili- «.iti'.„s, the remarkable system o' multiple associati.,ns between the nrurones. the great bulk of data an.l of hypotheses that has accumu- li.t.Ml, «e conft.,s that it is ^^ith trepidation we enter up(,n the task of .•..ini>r..ss.ng into a few pages even the minimum of knowle.lge require.! h tl.e beginner ,n niwhcine. As to the nature of thought and the .•.>^o,mt.on of uleas, the highest of all the cerebral activities, we know .ni.ti.ally nothing; the same is true reganling the essential nature of "Mnu.ry ; ,t is :.nly when we come to the relatiorihip between the higher •rntns an.l certain bodily functions that we find ourselves on somewhat >nn r Kn.nnd and thr because we can follow and recognize the tracks ■1 ^Miaton.u-al change But even here, although for lo,^ years investi- M ;r ' r" '*^*^y!"8 *»»« "*^'-^»»"* phenomena of such all-imi«,rtant I... tm as the periodic activities of the circulatory anura nerves are largely made up of axones. The neurones are together (or held apart) by gUa and fibrous tissue „ i,*ter, in M I o-antity, serving to support the blood vessels (. v.m.ou, ..'.,• ; i"itt ..mph vessels have not yet been proved for t v ^'" Tan,, although these exist around the blood chann- r-'H^ IS anato.nicall: ^dependent of all other neurones. '■''■ n.rye-cell body assumes varying shapes, has a ' I A '^^t'^.f ""^'eolus, and in its protoplas. LiDSttli.-., i/i Kuch i;e;i- v.\lX , Z f"^«^"«^ (chromophilic, tigroid, or Nissi • ^.L.^), ""'I' are presumed to be of nuclear origin, because their substanc^ ' :. ' rentr . ! ;!ll!.>Pt'i!i; <■ 474 THE XEinors sysTE.\f has stain iiffiiiitii's Mmmvliat like those i.f the mieleiis. The dendrite^ are tree-like proloiijrations of the protoplasmic siihstaiice of the iierve- eell body, taperiiij;, heeoiniiif; smaller as thev reeede from the eell very numerous and hrauehed, serving to hrinj; the i)rot()plasm of one nerve-cell body into "almost-contact" with other cells. The term "almost-contact" is used, because it is generally believed that actual contact does not occur, but that parts of two nerve-cell bodies thus lie m juxtaposition as do the secondary and the primarv coils of an induc- tion battery. The axone or axis-cylin,ler is a process of the cell, usuallv Slug e, containing no cliromophilic b.ulies (nor are there aiiv to be seeii 111 the part of the nerve-cell body from which it takes its immediate oriKin) and is of uniform size throughout; toward its emi it mav split It up into a terminal tree, of which each twig may end in an end-foot or end-plate which is in intimate relation (actual contact) with the eell ir. ;/., muscle) t.. which it runs. The axone, as it leaves the nerve-cell bo( y, becomes iinested by a myelin sheath, and axones so sheathed make up the greater part of the bulk of the white matter of the brain and c-ord. A number of sheathed axones, surrounded bv the sheath ot Schwann, constitute a i)eripheral nerve; the sympathetic nerves possess a sheath ot Schwann, but are not myelinated. On the Correlation of Neurones. It is duly the verv simplest reflex act apparently, that depent.n,r roo gansMa ot the spuml cord. an. 1 in certain corresponding ..-<• ne.l ce„ res ,n the bnlb ami pons, and even farther forwan i,! t e lm.e ..i the bran,. Cerebral sensory nerves, olfactorv. optic, etc .re s mular to the so.nafc sensory nerves in this, that a! a ike must tn.nsler their st.nu.h to other neurones which con.h.ct them, bv n"re o.ssdev,.,„s paths, to the cells of the cerebral cortex, an, to Sr 1. e.l cells of the h.gher order. The apprec-iation of sensation 1 es these ceils ot the h.gher onler, whereas the reHex act proc ce.l Tn e sunple arc may be accomplished without reference to the bain The Efferent System. - The erterent nerves of the bodv are represented ;.v ^. l-vcr Kroup .> neurones whose nerve-cell bo.li.' are situa e d1 "t tlu l.rani. Ihese, however, are under control of a higher jrroun of n.nrnnes, or ,„„re strictly of two groups of neurones, the ^ne vim e " I .tn. We stil are by no means informe.1 as to the full functions 't t cse two onlers of neurones. The cerebellum is presumed to be ' - antly responsible for the preservation, by meal.s of rh thmic ^ mm!,, ot the mteract.on of the muscles, that is. it e.xerts a sUtic •"•<■-'<•«'. <-<;"t.nues, so to speak, the .tatu. ,,u„ of the bo,lv m sculature I.;|rt„res trom tins state, such as voluntarv movements; are , .!^ftute th.- (unconscious) tone of muscles, to illustrate which it :Zn'ci::^v^t^ """^^^^ '' '•"^^'•" '-*- -tw ;^:,; N "^I'es thiss .f, ■ fT '•""^^"[•t"'.». .Pr-FH-rly coordinate, of manv i .'■ e el. "^,/''%"'"-^^-'^'-'' '^ "'. r-P'>"«e to constant stimuli . y. ,(rel,iilar cells; if, now, one wishes to move v..luntarilv the "■ : ot tl... .-erebral cortex take command, and bv sti.nuli reinfo ce the '■;■;- -m.. lessen the acticm of .,thers. intr.,.luce, IJt^ b" ^^ T^li\^,Ti'7 7*'''^"":^^"' "»-'-. a-l - alter the status r.itiis ot voluntarv activity The Sympathetic or Autonomic System.-This system is a verv craDli- • .that he abuulant investigations of the last few years by Langle - t u . ha e intr,,duce.l so many new p.,ints of view that it is ex- 'i.Mt luatew words t.. describe either its anatom orits '■ Hreflv, n, .„,n,ection with the brain, the main spinal cord I- t K,r lUTNc-cel b..dies withm the central nervous svstem leave '- r otTS';':;'-'' r-'''^ '^^^''^^ ^- ^'^ ^rain) correspcln. 1. '-'^.' . 11 bo f" "' " T'' "^ ^"^^ arborizations around the I bo.l e.. .,t certain ganglia, which, .save for these fibres are ' - . Z'c ;:tr;;;"V"'iK'" ^'f^T ''''"'^' ^^^ exampicXS • ...,,. • .r ^1 ^'"^ ^^'^^ ''■'"'^'' P''«^ to the ciliarv ganglia; the '""' '""1 "H.th hbres passing to the submaxillary and sublingu^ 470 "^llE XERVOrs SYSTEM II gai.gha and to the sphenopalatine and otic Kanglia; the autonomic or sympathetic fibres of tlie tenth and eleventh nerves run in the vagus and It seems probable that these fibres end in small ganglia situated in' or near each of the organs supplied by the vagus. As regards the spinal cord, the sympathetic fibres pass out by the anterior motor roots to the series ot vertebral ganglia, including the superior cervical ganglia; in the sacral region of the cord, slight differences of arrangement of the svm- pathetic system to the anogenital region are observed. These fibres running to various ganglia are the pre-gangUonic fibres which arborize around the cells in the ganglia; these cells in turn give oNgin to axones (the post-gangUonic fibres) which course directly to the viscera, or in the case of cutaneous fibres, return to join the spinal nerves and so course to the various segments along with the cutaneous sensory nerves. In whatever ganglion this relav is situ.-it . d, it appears that there is no further relay, but that the axone of the second cell passes direct to the viscus which receives the svmpathetic innervation l-or example, m the dorsal region we liave both vertebral ganglia and the conjoint ganglia of the solar plexus; sympathetic fibres from the cord pass through both of these to their ultimate distribution; their relay cells may be m one or the other but not in both. As regards the afferent hbres of the sympathetic system, these when present run in the white rami; it seems that the head and the skin have few or no afferent sympathetic fibres, these coming essentially from the thoracic and ab- dominal viscera. So, further, it appears that the sensory connection of the various viscera with the spinal nerves differs but little in arrange- ment from their motor connection. Pathological Changes in the Nerve-ceU Body.— What knowledge we possess concerning the changes that occur in tlu- finer structure of the nerve-cell body is largely due to the employment of Nissl's methiKl which uses a staining material compounded of methvlene blue, thionin, toluidm blue, and neutral red. Small masses and granules in the pro- toplasm thus become visible, arranged in different wavs according to the type of cell. It may be mentioned that experience and extreme cautu)!! in the observation and interi)retation of results obtained bv this method are necessary. In a general way we know from the appear- ance and arrangement of the stainable sul)stan(e what is the ph^si..- logica state of the cell; the stainable material (tigroid) is normaliv in granules, spindles, lozenges, rodlets, threads, or shapeless masses oceupv- ing the interstices between the fibrils; it is not demonstrable in the ernhryo, it increases m amount within limits in a state oi rest, and diminishes by activity and fatigue, in intoxications, in circnlatorv and nutritive disturbances, 'i..r. aiKl disappears. Whatever the course^,f^he aTo lu Z ■ e^ '"n=| e Its relations with other axones, its life as an ax m; em, ds -■;n .ts „e.r^e-cel body, and if it be separated therefrom i s u It. iMtti r> . i he one wire looks like the other ninety-nine, but no -IT l>. th e axone in a short time- twenty-four hours- shows a ■nu " he myelin sheath; this presently becomes changed into a - "t « .i.ules of various sizes, of a fatty nature, which S mate v '■XZ %^j:;r'rl <'5Kostion and absorption by the c^l^'onil' . hw..nn. he ..xis cylinder proper becomes irregularlv t. I. broken, and granular, and likewise ultimatelv disappears "I-'- 'H-'g taken by proliferated sheath cells an.l fibrousS:' 47,s TUK SKRVOrS SYSTEM m t m a rcplaceiiient diiniage the nerve-cell body to an extent, slight but sufficient to interfere with its initriticm as a whole. Under these circumstances, the most outlying part of the neuront^ the terminal i)art of the axone —suffers most, and the nutrition which did not sufHce for the wliole neurone may suffice for the neurone minus the most peripheral ])art, which is thus sacrificed to the welfare of the whole neurone, much iis a beleaguered and starved city might save itself by sacrificing its most outlying garrison. Where the peripheral part of the axone begins to atrophy in this way, we may predict that the entire neurone will ultimately share the same fate. A second kind of degeneration is that to which we have previously referred as abiotrophy, in whicii, l>.\ reason of some congenital lack of \ iiality, the stress of onlinary neurone wo. k is too great, and the structure atroi)hies under *'mulus tluit would not ilamage a healthy neurone; such a neuroiu' ' . a. ' .-^pt nds its life with so little spare energy at its disjjosal, t, ;1k, ...dinary expenditure of eni./v is too great for it and it atrophies j.eniaturely. Lesions of the neurone may be accomi)anied by a great variety of GESKRAL niSrCRBAXCKS OF THE SEKVOIS SYSTK.Xf 470 -.npt.m.s, and these it is not pcssiblo to particularize, co,npri.sinK. ;':,'"■>;'•'' !*" ^^""'V»^ *'*f"»te iiml imiefinite aberrations of function (I rlie .iehnite tunet.ons possessed by the neurone we are able to note tli.it ! , tlie stnnuh which excite muscular contraction mav be absent nr u.ak or, if present, inefficient, so that the muscle rests in a state of partial or complete paralysis; (2) or. contrariwise, the stimuli mav be so tr..,n,.nt or so extreme as to excite a iMd we .jcscnbe such alterations of the normal performance of the organs as functional. It is not ,)ossible to say that functional diseases ''..-called) are attende< by no ..rganic change in the neurones; all we <.iti say is, tiiat it ther.- be change, it is not to be detected bv our present Similarly in^ the sensory neurone whose iini)ulses pass from the per- ipiMTv „t the bo, y to the nervous system we find that certain lesions '• lii' .uMiruMc destn^y the conducting power completelv; or, again, "ith MO visible alteration, we discover that the ft.nction of the sensorN- 'H nrone is altere.l or abst-iit- that, like a ba.lly manned telegraph line > H r,' „,ay b,. n. messages at all (anesthesia), that the message initiated ■I' the skin max be exaggerated (hyperesthesia), or mav be entirely P^ir,,i.|,rase.lfrom its true meaning (paresthesia). To make the matter 'n-rr .,,„t,.sing. any of these deviations from the true function of the -nn„M. may not be due to inefficiency of the neurone at all, but mav ;■' in.ntal, just as the messages taken by a bad receiver from a good ;' - u'-.q.l. „„. might seem to in.licate that the line itself was inefficU-iit - ^N.n ot all this ,s that there is little known about the organic changes ' I'^'I'Ih;" .11 the neurone; that wi.erever we observe disordere.l ";"-' -ithout a correlate\MT: that, in health, each voluntary muscle receives stimuli reaching If -n tlic rate of from five to fifty per second. These stimuli are minimal I'iir -Mfhcient to set m action those associative and disso.'iative processes ^vliK h l.ad to contraction. When the neurone is fatigued, the rhvthm ~" tiis to l,e slowed, and apparently the rate of rhythm in coorc. .lated iMUMlcs IS subject to variation, that is, may not be the same for the liA.,rs an. the extensors respectively; in this wav we mav explain the reniors (4 cases of nerve exhaustion as flue to a lack of correspondence I" tN\.,n the rates of contraction of the flexors and the extensors of a I'.in. Ihis tonus then is a "state of preparedness" of a muscle; the 'I'ti'r.iue between tonus and voluntary contraction is a matter of 'I' -r, , 1,1 a normal contraction there is not a single impulse but a like ~'n,. „| rliythniic, rapidly recurring stimuli, apparentlv at the same a^ hut individually stronger than those necessarv to produce 'reserve tonus. " 'lescribing convulsive movements of the muscles, it is usual to nniruish tonic and clonic contractions; in the former the stimuli I'r M. ra])Kliy that the proper time of relaxation is not granted to the ' ':■ iincl a continuance of the contracted state happens- tetanic " 'ontraction; in the latter either by partial tiring of the muscle '.■I less rapid series of stimuli, the muscle goes alternately into rate ;ni,| til 4.S2 TIIK M':i{\()rs SYSTKM m ' tlif oni.tracted jind tlic nlaxed stiiU- rh,„lc contractions Tlie te cIonuB. hy nsaKc. has coin.- to i.avt; a slightly (lifr.-rcnt sisnifican by clonus wc nu-an tlic plicnon.cnon associated with tendon or mus reflexes, wf.ere in places of yetting a single response to a tap or n upon a tendon there is ehcited a recurrent series of contractions d to conditions causing exaggerated muscle tonus. ' The part atrected hy a convulsion may enahie tlu- observer to defi the site ot tile lesion, especially if it be situated upon the cerebi cortex; here the ceils of only one group or a few groups of muscl may he atlected, in which case the convulsion is called focal or Jac ioman (Ilughhngs Jackson having first described it). Even if t lesion be strictly localized, it sometimes .seems as if the excitation the cells imm.'diatclx- affected could sprea.l to others, in ever-widenii circli-s new cells being involved succ.-ssively, so that the convulsi. extends in that half of the body first affected, in a definite order Co yulsions are classified nccording to their origin, rather according their sup,.osed origin, for most of such a classification is pure conjectur t le difficulty of determining the - that the causes of convulsions are (1) mechanica as when a tumor or hemorrhage in the skull causes extra pressure up.. the motor nerve cells, or (2) toxic, as in alcoholism, uremia or lea poisoning, (.,) reflex, e. ;,., some cases of epilepsy, as when an inflamniii turn or irritation in some .listant part of the body (perhaps even pin worms) appears to be the cause, or (4) functional, when the stimiihi appears to originate in the highest cerebral cells, that is, the cells con earned with th..ught and association. Stimuli of this sort are calle. ideogenous. Focal or Local Changes and Their Resu.\s.-I)istinct from the state just dLscussed whieh concern the most important parts of the nervoui s.vstem an. l{..tw,.,.„ the e,.rtual cell an.l the muscle two neurones run- h.' upper mul the mver mot..r neuron... The upper motor neurone liiis .t> c,H uhIv in he cortex, an.l its me.lullate.l ax..ne crosses to the opiMMt.. sKle ami there runs with other m..tor n.-rves. especially in tl:.' .•rnss,.ll h.i,|v .,f the l/.wer .iH.for ...ur..,,,^. wh..-h ,s situatnl in the anterior horn^ ..f the conl. In.n. the .rll ho.ly ,n the horn the ax.,ne . f this secon.l cell run- by a I..npl,..ral >';;ry|".to the muscle. If the ,,eripheral nerve he cut near til.' .nnsd,. all this elaborate mechanism is rendere,l temp.,rarily u.seless ^o h.r M- the muscle is concerne.l, an.l the muscle is paralyzed; if the npi-cr n, tor n.;uron,' just below the c.rtical nerve-cell bmly be cut tiM' nn.^ .. >s similarly paralyze.1; how can one tell in which of thes; >i nations ,s the actual lesu.ny Th.- nutrition of the muscle depen.ls lit mi.it.'ly up.,.. Its ...miection with the nerve-cell [hhW of the lower .1. or m.„ro.,e; ,t the l.,wer motor „e«ro,.e be intact, nutrition is not rx -,..li h.,.|y of the lower motor neurone chooses to sen.l; and if ti.' l.s,o„ Ik- ,., the upper motor .leurone. the cortical cell body has no ^.^ |H'rt. flacci.l, hypotonic.. a...l. cut off from >"n -(.• I body, quickly deRcerates an.l atn.phies. To recapitu- Y','lr>uium of the vpper nwior veuroue allows h,periomis orTm^m ;;;«..;.. jA^..r.c.-o„ ofthe loreer nroior .Jol, Mcidit'JZd ■ 7. ;.d. 1 ".'""t,'-'" "" *'" "•' ^^•'"■^'^ P"t "f the tract is tr X d. t , .l,.term.ne th.s requires consi.leration .,f all the facts in I' - -.Much can be learned from the extent of the damaffe- if we - r tl,, ,„ „„ tor neurone, it will be apparent that f lesio. "•I' a> iKniorrhaK-e. tluKiRli .,f small size, might affect a great mTnv I l.a..ke,l cl..sely together, as in the internal capsule. A trn , , I • ■ ^^'""'"'•ly, in the lower motor neurone a .1.- l-v< I vher .? '\"''.P"*;'"t "f ^^rvice m.,st of the muscles of a „r ,;„;' 'iV;. ''"^^'""^-h"'"' ^^"«. «"-* -^-ther way in which the same n-MJt is T>r.i,ln^, I J ii ■'."."•'^'^"'"'^"*^'"»yinwmcn the same produced, and that is m the so-calle.l hysterical paralysis; here V«^^ 4.S4 THE SKHVOl S SYSTEM the musle is htvilthy, the neurone intiiet, l)ut the niiiseh' is i stimulated by its neurone, whose action is inhibited l)y tl" mind « in other words, by some Rroup or proujjs of eclis which are eoneern«' with the mental functions, and are the i!nilti|)h' K"verning power i the brain. Hitherto we have spohcen f)f lesions of tiie neurones, evidenced b paralysis or paresis of the nusch-s, that are (hie to prevention or (h pression of the function of ti e neurone -the so-caMed depressive mani festatlons, l)nt there is another form of lesion, the irritative. Hefor pointing out what these are, it may be said that a lesion can destro; some part of the neurone, so that stimuli from that neurone ceas entirely; or the lesion may merely interfere with the stimulus, whici reaches the muscle in a weakened degree; or the pressure of the lesioi may act as an irritant to the neurone so that it is stimulated. Heini stimulated in a wrong way and from a wrong source, the messages i sends to the nuiscle are certain to be ill-time- related to tremor is fibrillary tmtching of the nniscle, in whici the individual muscle bundles are seen through the skin to contraci (|uickly and rhythinicalix-. Tremors are readily observed in sonit alcoholics, in paralysis agitans, in multiple sclerosis, in lead poisoning and many other states. We have already referred to the mode of pro' duction of muscular tone (p. 47.")). If the rate of these tonic impulses to two sets of antagonistic muscles l)e different it will be seen that thert will be a lack of synchronism between the respective contractions oi the two sets, so that the liml) or part affected is drawn momentaril\ now in one, now in the other direction. Choreiform Movements, -("horeiform movements ar'» of the natiiro of intermittent clonic spasms; tiiey appear as irreguLi, purposeless, jerky motions of the limbs, face, or body, and are seen in chorea, Huntingdon's chorea, spasmodic wry-neck, tic, and hysteria. Convulsions. — Convulsions have been already considend (seep '•O'l- Contractiire. — These are the states of body in which the ni -ility of the limbs is lessened, and the position assumed by a limb is gradually Jt' Y^TT THE BRAIX 48/) fiv.l. so that It cannot be movo.1 from that position. This occurs in two « ays ^ a unh, for example, n.ay he f1exe,l l,y the activityTflexo; nn-Mles whuh are continually in a state of spasm, rr by the action of n..nK.l flexors. unopjMKm! by extensors. In-cause the latter are paralvze.1 uli.lr the former st. I remve the normal tonic impulses. This laui tnrin ot contracture IS termed passive. THE BSAIN Gross Anomalies -These may be .livi.led in the first place into I) those ussoe.ttted with inaliormation of the vault of the skull, which v.- .nay call cranial anomalies, and in the second place. (B) thos^ of the l.nm, alone, the cranial vault being intact. »«oirne (jl ) Of tlie former we have a remarkable series, associated evidently « th nnperect closure of the dorsal groove in the region of the cephal c lol..s .Ihistrating all stages in which this is either partial or complete or a,ro,npan.ed by a greater or less extent of imperfect closure of the ^o natu- dorsal groove (spina bifida). AnencephJiy or acrania is that Is''.').?"'', '^rV" •"""'P'"*" ^'^''' °^ '^' ^""'t «f the skull and o n ' Vr I ^'•«'";^,^r*'-'nt«i by a mass of congested mem- .u„>. II ebasal part of the brain is present and gives origin to the eye th.' ear. and the cranial nerves. In exencephaly the defective deVeK "-t .s partial; the vault of the skull is in part develop^ I, most fr^ n ly t^^^^^^^ frontal rc,;on; there is imperfectly formed brain substance h, 1 nerl angs. like a sack, the back of the neck, or in other cases! My MS. As a result of amniotic adhesions, the projecting part mav Ix' lat.ral and unsymmetrical. i J "fe par. may r...lf rk!.hl™''^"™"""'^ "^ ^^' ''™'" ^'""^' *^^ f""°«'"g "« the most «n GeneraL-Microcephaly, in the typical form of which the whole • l.ram ,s small and poorly .levelope.1, the cranium, while pe S li.' .orrespondingly small. The brain, instead of weighing OQO ; :."' '"T ^■"^'^ -^!' ^'-^T^ ""• ^'''- ^^^^' '^""dition is assoda^ S "li'Tx, and IS sometimes familial. nn'ir w.^lf '^ ■;, « T'^'^'T "*■ "^•'*"'"**' '■"^■••^"^^ '" '^f«'n substance. ■r^ . 1 M ^^,.|| uuthenfajted. Some, but not all of the greatest men in ^'0 ;■;;;;;' '";; "f ^^f r- -tal>lv Oomwell and Bismarck (ov r J^\u^!t7 'P'T.u'^l ^^^.P\^'^' microcephaly, the cerebellum being .■' doped and the hemispheres of small size and with poor convi ' ■ ^mZJ^T ^"^r V-^ "^"i'''^'^ development of por^on" l.rM 'it.h, ?tKv- P. Tj= ° ^^'' ^^' '"'^^^ characteristic form is ' - H or r^,r^T f r'^P'^f "t °^ ^y i»tru-uterine obstruction /e the in r 1 *'" 'V'*':"" ""^'^^'^^ ^""^^y- As a result ^ iitlur in the early stages a lack of development or in later foetal lii! re is l.H(i TiiK xKinnrs sysrhwr 1-3 f I: or early |K)stimtal life absorption of the ana supplie.! hv that vesse witli, 111 eoii.se. i.un.T. the formation .,f a evst-like spa<'e ...vereil h the iiieinhraiies. eontaiinii« rtioiKS of the Kray matter are aU-rrant an.l are f.Min.l in the whit, matter. There is e..nsi,leiahl.- variation t.. !«■ foiin.l in the .levelopnient an. numher of the c.)nv..lnti..ns; in s..-.alle.l degenerate., these mav Ix re.lnee.l in number an.l shallow, from flatteniiiK of the Rvri (a»^a) In those of hiKh mental .levelopinent they are f.,nn.l we'll .K.vel..WMi and abundant. ' Circulatory Disturbances. Anemia. The brain is f..nn.l strikindv )h)o,IK.ss, and of almost milky white e.,l.,r in eases of .k-ath fn.in hem.)rrhaKe. as aj,'am m eases ..f profonn.l systemie anemias. Hyperemia. Hyperemia of th.- passive onler is seen in eases of chronic general oonKe.stion, as in canliae .lisease, of obstruction to the ven.M.s outHow by way ot the jugular wins, as in hanging, and in eases of sutfo- eation or death in convulsions. The brain oozes more blcxxl than usual on section an.l the cut vessels are m..re than usuallv prominent. Active hyperemia is seen in cerebritis, an.l in such states as mania, delirium tremens, and to .some extent in ca.ses of .leath at the height of acute infections As in c..ngesti.)n, .s«. als., in (edema, the condition is best recgnize.! by the state of the membranes; cen-bral oedema is reog- ni/able by the pah' v vt, m:<] shii.v i;rfuce on section. (Kdema mav !,,. extreme m the vicinity of a new gn.wth, the infiltrate.1 brain tissu.- appearing actually gelatin..us. The cau.ses of oedema in general are those .)t extreme passive congestion. Hydrocephalus.— IIy..,.., nnir the hutUhv trii,tr branches of the mi.l.lle cerebral are almost in a direct line with t hr internal caroti.l and thus are subjecte.1 to the Rreatest f..rce of the I.I'hhI stream. From their position such henurrhaKes are likelv to .n\..lvc the anterior two-thirds of the posterior limb <,f the internal ;c lieinorrhaKe is transformed into a cyst (see p •^*r.i) EmboUsm and ThrombosU. Sn,hK.„ apoplectic attacks mav "be due "-a,»r> otIuT than hemorrhage. Of these the most importunt is enilM.liM.i. I he arterus of the basal reKi<.ii of the brain are eii.l- .■-rt.rio (sec p. :{41), wherefore it follows that it one of these becomes Mi.McnIy p!„K>r,,,| Uy ,,„v |-„r,.ijj„ substance circulating in tiie WchmI tnc.n,. IS ,,,t otf from its nutrition, and. as a result, the nerve cells ;". 'M.! the ... rve fibres passing through that ares, undergo disorL'an- i/jitioM. ( .Tcbral embolism may be brouKJit about, like emboli.sm else- "l-rc. I.y many aKcnts (sec p. IWA), but of these by far the commonest 1^ the thrombotic material constitutinR the vegetations of acute eiulo- 'jiMitH, which, broken off, may be carried into the caroti.ls and so to II' i>nnn. an. the .same reas.>n that le.l t.. liemorrhaKC beiiiL' specially nMii.rit m the branches of the mi.l.lle cerebral-namely 'he direct "MPM. nt the l)l...,,l--applies also to embolism; it is the arteries of the "•'- '■ the brain that are .si)ecially ai)t to be involved. The result " H. I, .iiibohsm IS encephalomalacia ..r -brain .softening." affectine 'I- ir..,-, „t .hstributi..., of the artery involvc.l. There is first .leveloped I" .inn ol nccn.sis. which soon uii.l• y^llo^v softening as the blood '^ HHt ditluses ..nt an.l is abs.,rbe.l. The .liHVrence between the ; H ..t ..mb..i,.,„ aiHl .,f hemorrhage is that the f..nn..r remains ^ 'tml.N cir.-umscribe,l to the area of bloo.l supply, whereas with ' ^npiv,. .,utp.n.nng of bloo.l the hemorrhage involv.s a greater :"; ■' ";">' >^ sni.plied by the ruptiire.l vessel. Svmpto.n:,fl,.allv tluTe- ■ lannL'Thr.'- ''•?,[""'■"'"'>' "'""' " '^•''""'•'•I'agc is apt to be progressive 'I'inii,,' the time following its actual beginning. 488 THE NERVOUS SYSTEM Thrombosis is secondary to disease of the arterial wall or to an embo- lus. In order of freciuency tlie causes of cerel)ral thrombosis are arterio- sclerosis, sypliihs. and acute infections (including those cases which follow embolism). It will be r.called that in the subjects of arterial disease the smaller cerebral arteries are peculiarly apt to show degener- ation in the torm of atheromatous plaques and of multiple miliary aneurysms Such thrombosis, originatiiiK at one spot in the diseased vessel wall, does not suddenly, but Rradually, lead to obliteration and closure; there is, therefore, in general, an absence of the true apoplectic or stroke-like onset. The results to the cerebral tissue may be identical with those just described. Aneurysms. ^Aiieur\sms of the extracerebral and basal vessels of the brain are not uncommon; they are saccular and of the size of a pea or bean, and may be the site of rupture. Of more importance are the multiple miliary aneurysms of the intracerebral vessels in advanced arteriosclerotic conditions; maceration of the brain reveals that these may be present literally by the hundn.l, just visible to the naked eve. It is the sudden gning way of one of the larger of these that is held to be tile most frequent cause of cerebral hemorrhage. Inflammation. — Acute EncephaUtis.— This is not a very frequent condition, save as caused by trauma, an.l as it occurs in the superficial IKirts, associated with meningitis, and locally, as an extension from disease of the mi.Mle ear and bones. Xeycrtheless certain of the acute inteetions are associated with diffuse and generalized disturbance of tlie hrain tissue. In rabies, in acute polioeiurphalitis, to a less marked extent m influenza, in bacteriemia due to staphylococci, etc., in typhoid, and other acute mtections, the toxic hyperemia is probably the cause ot those symptoms which ar. clinically grouped niider the term "menin- gismiM. Saye the hyperemia, tiie changes are microscopic, and con- sist ot periya.^cular exudate with infiltration of lymphocytes and leuko- cytes. Ihe nerve-cell bodies exhibit alteration of the Xissl's granules. in very acute cases, punctate hemorrhages may be seen (hemorrhage encephalitis). Abscess of the Brain (Purulent Encephalitis).— This mav be of various kinds, cryptogemc, traumatic, metastatic, and by extension from nearbv structures, especially the mastoi.l region of the skull. Or ..sionallv a wcl - » zone or intact, though -'.. '■'! bra„, substance: t.. exph.in this it is necessarv to ■„ sider t!'l-;Mb.hty Ota metastatic lymphogenous infecti.m ' i' m abscesses may be n.inute or multiple, as in metastatic cases I' .. ...ore frequent ,s the large solitary abscess, surroun.led b a In, erl ■-•• -lematous area, forming a roundel mass; the pus isVl a S- ;t .Hy green.sh and tlun; when at all old, there is presen a vvd - |"i..,l Innng membrane, with little or no tendencv\o s .sequent hl.rous repair; accordmg to its position it mav rupture ex ern" Iv ..using a purulent meningitis, or internallv into 'tlie ve. tric-kf *een ".the b Imd" an-a of the brain, such an abscess nuu ^^ n or v^S without obvious disturbance of cerebral function ' ' Syphilis --Kav,.rite site for spirochetes as is the brain it is to be re .nen. hen.,, that the most striking signs an.l sympton^ o '^ S.^I Mill... ar.. meningeal rather than cerebral; the meningeal X-s - ><■ -l-lt with ater. More^ than this, cerebnd infec.;" it m com I. I.N >econdar.x- to meningeal infection. The following are the most ■on.i.on changes induce.l in the brain sub.stance: (1) IcepVaU^ neonatorum, winch i.s f„un.l in newborn, often in stillborn svpl£s > ^tnking feature ,s a small-celle,! perivascular infiltration; C £ ;;;tl^.n. o.xcess of granule cells (Gluge's corpuscles), scattered /Klgh I >lnn 1 be invohement of the cerebral arteries and arterioles ■i.ny hose on the surface passing in from the meningfTh^ ron.s which .seems to be the eventual cause of those d i^nerat ve 'l'-i'''l« ol'lo!^;.: i'^^'r: ^''^^^"•^••f ?turbances, we encounter '"' P '.'<."t of localized solitary or mult j) e syphilomas fnimmft) --.vplnhtic granulomas may attain large size, 2 c m. o"n ..rfTn.s ' ,7; ;■"''."« >.'7'-..nes-in short, may present those svmptoms •!- c^"i;f':;:rr' ''7f- ^''-^ '^'^^ °^ the-brL^t 'I"' "t site, and the cerebellum is rare v involved In the ^t''^cand generalized, or local invo ving sharply defined areas of the brain and their associated tracts of fibres. General Atrophy.^ (Jeneral atrophy is best marked in the progressive diminution in size of the brain in the old. Here the brain in general shr'nks, and the si)ace so made is taken, both outside and inside the brain, by cerebrospinal fluid: the perivascular lymph si)aces in the base ot the brain are greatly widened so that cystic spaces appear in the bram substance, and the membranes, especially the pia, indicate their share in this change by aj)])earing (edematous. The nerve cells of the gray matter undergo a marked diminution, indiviclual cells shrinking, aiK losing their dendrites, becoming more oval, and flnallv disappearing, and this not in sju'cial areas, but here aiul there, appareiitl'v at random. Uith this diminution of the nerve cells, there is both an apparent an( also, it would seem, an actual increase in the more lowlv glial tissue and fibrils, so that there results an apparent dilhise sclerosis of the diminished (.rgan. Associated with this the convolutions ai)pear small aiK. the gyri between them much widened. Y'ry simil.:- appearances are met i)rematurelv in cases of chronic lea( poisoning and in some alcoholics. In botli of these classes, the gha and fibrous overgrowth ajijiears to be even more pronounced than in the senile brain. To another markedly atrophic condition we have already referred that seen in dementia paralytica. Here it is that arterial changes of syphilitic origin, affecting the arterioles, character- ized more particularly by a perivascular plasina-celle per cent, of cases of dementia paralytica give a positive Wassermanii reaction, Thi'* disease, therefore, '\uwnu->\ premature exhausfon of the neurones of particular areas of . -■ bnun. as also the .hsuse atrophy which n.ay follow the cuttiuR-off o Mcurunes from the.r d.sta ,,ortious, either peripheral end-or^aifs or .•.r!,nr, ,mo„s aro.m.l the cell bo.lies of other neurones. It is these IMPfal atrophies that are so characteristically accon.panied bv pec,hc connec-tue tissue, .he ueuro.dia. are of epiblasti,- origin lU' mooiast.c elements m .t ar.. comparativelv sight, consisting -n<;n .y ot he ^•essels and the small an.ount of connective ts"uec™- ■ "Ht,n, the.r ad^ent,tia. It follows thus that progressive changes ' ;— ly u, conuectu.n with '' epiblastic elements. Progressive la ue. m connection with the . ,els are comparativelv rare; These ^^' M.;,y f,rst d,s,.n.s, u, stating ti,..t angiomas have been rec, r |e in -;-m^w.h the cortex, and then of pial rather than ^'IS^^^ " .l! r r ""•' '"y^r*' Yr '•'"• '"'*-'" '•^^^■"'••'-'' tlH- former r T ,h, latter s.nall and roun.h.l. So, again, there are verv rare - -'t .rc-bral osteoma More frequently are encotmtered n.etaplaTtic - . M'lacpus of the bram n.embranes; these cannot be rcgard^l as ' H. s. sarcomas onginating within the brain substanc-e are 'innlv rare ■; we except the most anaplastic form of glioma the '„,''"''' ?". ''^' ""'>■ "* connective-tissue origin. AVe shall n,: ,;,l.;;nl;: ^"^°*^«^«™- -•'- *'---ing the tumoi of the 1.^11 Glioma. Here we „u,st in the first place distinguish between this ' ■'i:;Hv'd;:i;,'f^r" ^'^r'^r - -'-•>• - encou.;*:;!:':;? "-n,i 1 .1, ,1 • "T I '"' ^"V"""'"""^*' overgrowth of the piMl tUmn s. In such a case the tumor passes impercentiblv •'■ t ,,. surroun.hng tissue, and, what is more, if t alfect a con"ol ted ;;;;-; .onvolutjous are stdl maintained, although thei'a;:XS '--M in .; ' ': Vl""' '' ''""^'*';'"« ^1^>'>'"» ■'^ '"cre hyperplasia, . " ™e ghoma is usually solitary, tends to be spherical, and by '. "I'T and consistence is rerotrniyabiv di-jfinr-t fr^i,, tl. «""".> > -i'. in c.lor tl„. „r ;.-•"'-" '".^ ''7"^" trom the surrounding «'>l"r the glioma is grayish pink, somewhat more trans- ~ '!eif 'offsif ««r,'«»» ~riir ii[~M-mi 402 THE \ERVnCS SYSTK.V I.Kvnt than the I.rain sul.sta.u.o. a.ui ,„ay I,,- ntlu-r rdativelv poor in the .hoi. of the ttunor" ,. , •wln^L^^Z' ^" ""^^ ^'r^''"' l^l^t V ""' "'■""'' ■■>■""■ «iv ti,» lined l)v o cubloal irom tlic tourtli \ eiitrick- have l)een reported. Apparenth- these enen ;!=^;:- ;.:t;:"^'" '■'-'^■' ^-^^ - -^ ^pitheiiLnatc!^ ;:r :;s;;: hypernephroma and chorioepithelioma are ooc.asiomd v 3 't e ^ Cvt ''"'("';"";• '•"•'''^'^*'-: »■- this site than th^ two fomer ''riidcvsts; o^«nLH'"'''r "''''"■^- '";'-^' '"" "'^'"»ntere,i in the hrain; cy s rn;|.^r.T'!''' rV*- """'"'"•■•^' ^" '"■•^'^' l.enu.rrhages; necrotic 'h ,n..!' ; re 7 ^I'ttv-ng. appearing also i„ conneetion with pa aSic r r' ;""^'^^:;"^'"''''.'J porencephaly (p. 48(i), an.i h.,sth- coccTs S Vr ""'• "^'V'"'^ '^-'^'' "*' cy'^ticercus an,! echino- Xe of :? r ' TP' ^••''."•.""•^''^"^ f>y(lati.ls are large, even to the tumor '"' "' '" ""'"■ ''"'■ ^'''' ^^^ *''^- symptoms of a brain THE PITUITARY BODY (HYPOPHYSIS C REBRI) fnVC i''^*"'"r>' '""'y •''■^"^••^ separate mention, in that, while attached oonmM l""; ir """" ^•V"^t't'»'"t i^ "ot nervous tissue; it is, indeed, composed of three portions: the anterior glandular, an inttnncdi.te 77/ A' SI'lXAL CO If I) 493 una witli Klarid colls iiitoniiixod with muiroglial tissue, and the posterior juiKli.mid portion, also of jjlial tissue without nerve fibres proper. i.ittif is known reRardinn its function save that the posterior an.l inter- iiitdiatc i)ortions afford an extract wliich, like adrenin, greatly raises the hlood pressure, and unlike adrenin, induces polyuria by acting di- nrtiy on the kidney. The main pathological interest of the pituilarv \\v< in the relationship between hyperplasia and adenomatous growth's nf the anterior portion and the development of acromegaly (see p. 101). Chantri-. have also been seen in the jMtuitary in connection with preg- iiancN and castration, as again, secondary to removal of the thvroid sliind. THE PINEAL GLAND (EPIPHYSIS CEREBRI) Aiiatoniieally the pineal gland represents a rudiment of the median eve still recognizable in certain lizards; it consists thus of ptirelv nervous « liincnts; at most, it may be the seat of hypertrophy and gjiomatous timmrs, which by their size may press ui)on the aqueduct of .Svlvius and the vena magna (ialeni and so bring about hydrocephalus internus. THE SPINAL CORD AnomaUes. Here may be recalled some of the more important "m-nutal abnormalities of the spinal cord; they are relatively infre- qurnt an.l do not call for extensive description, ■jncomplete formation aiii >h.irtening of the cord is observed in cases of anencephaly combined "itli -pnia bifida as also in simple spina bifida, to which reference will I" "iide later, duplication of the cord has been observed both in '^iiM> (it partial double monsters and apart from anv clear evidence of '.hi|> i.ation of the body in general. ])ui)lication of the spinal canal 1^ alH, r.,„rde(l; this may be partial or complete, when it appears to "■ til.. \,Ty slightest case of somatic duplication. More important, '"'•inM' more ommon and more obvious, are the various grades of spina bifida (rachischisis). Here, anatomically, we deal with the various "'i"'i'i"iis ot incomplete formation of the laminae of the vertebrre but "■"•'flying tins, in the extreme cases is a lack of closure of the dorsal ■;''"'•, whereby the two halves of the posterior portions of the cord ■''I '" nnite and the ependyma of what ought to be the spinal canal "ii"'- vMth the true skin. W. iia\c >.'->ady referred to the various forms of this condition in '•-"i-mg t.., abnormalities (see p. 72). Here we repeat that the ';• ' ifKMi may affect the whole length of the cord, or mav be partial ■ ' "I'll; a portion thereof, and may be complete or incomplete. Thus] the eystic form of spina bifida, we may have a series of cases in "" "i^rely the laminae are defective, the cord being perfect, the n.-, I. 494 rilF. SKliViHS SYSTEM sliKlit.-st orm bcu.j; tlu- spina bifida occulta in which fattv tissue, in „ai ttv:;''7n"" r^"*"'^'?" Y'*'' ''''■ ^•"■'"' ""•■"■"»^'^'^' '"I'Hrt filling th cl.h-ct ot the Ix.ny an.l suhcutan.-,,,,. tissues, fur.ns a projeetinR n,as> wuci., .unuusiy .s ....vere.l hy a skin that is extra.lnlinarilv hain J h s torn. ,s ,nnst fre(,..ently Men in the hnnh.,saeral region and'appear to l,e cosely related to those cases of fatty pn-j.-etions c-overed hv hair^ sk n w uch consftute "talse tails." Fro„, these slightest c-ases we pas' t hrouKli a series ot eon.hti..ns of meningocele, in which the defect ii iu- bony vault .s oee„p>ed by a sonu-what cystic expansion of the men. n>ges hlled wth fluid, and in which the spinal ccrd s not involved™, "nourT.ra " ; " ' > "f''^'""^' "'^ "^■'""-^ «™ove remain, or«n; ^p.., epuicr,,,; •1, utur.n trait, pa.s., i)ia-aracl layer o nerve tissue c-overed posteriorlv and superficiallv by a layer ot epen.lyma. In these cases occasionallv owing to th" want of support, Hmd may accumulate in the anterior part of the pia-arach- noid space-, tormmg thus a tumor projecting backward, the myelo- menmgocele. ' v o , * TIIK SriXAf. COIil) 495 (V..s,„,.ally wholly unass..c,ato a .e; m general also.tlu.y are surroun.lcl by a layer of hvperplastic a ,ssue. I he .hlatat.on an.l cavity, being ..entrally loeate.l.^afTect t .• fibres passn.g over m the commissure and prod.ice .lissociated loss ; -MS. M.ty to pan., h..it, and cold. It is still uncertain how far h ,M> ,. t" '- regarded as o pri.nary. how far of secondary origin ..t .. part.cularly noticeable is the in.lication that this condition .n|> ot the existence of tactile as 0"haKe may occur in purpura and the blood ■ -.though It IS usually a result of trauma. It has been suggeste ' u,;^.;;';; ;;l^;; •; "-''->• «I--" arc not purely fuiictional,Kl^ ^^, ;^;;lt ..t .n,„It,,h_ J^^^ ,„to the substance of the cord with Inflammation. Inflammation of the cord is known bv the eener-.l '• '• r,.as. It may again be divided into the form which PoUomyelUis.' ''' "' *''"* •''^^'^^'"^ ""»"'^- '^^ ^^-V -atter, in I'bte" ;-"' ^"-^ l"^ *•-* P-^"-! ^y -npression. til ;ttl' .■IF, ■I- ' >nirr;.n !/^':ia!^!: ^«;" -"""^"-^ -« ^-te distinct. •M-rliti (ir l.i.th, a t'li'i:.'! ill i>r.,.,orl,-o ■ II I • . "'" '^""""^""is are quite distinct, ro erl so-called, is the result of infection, or acute trauma, s characterized by .lefinite reactive processes. It i ..cute general intect.ons and i„ certain specific infection gray; //i;/.ir, marrow. I'M) rut: sERvois system afFecting ospfciiilly tl.o cor.l, i)rtrinitient nmoiiR which is that knov as acute i)()h()inyciitis. Wtv important ah . are those forms in whi( infection occurs by extensi(.n. as in .liscase of tl:o meninges, notab cerebrospinal meningitis, or of the vcrtebrie. as in caries. In all cas- of true acute myelitis the aH'ecte."„|,k of ,l,e» «.c„„dar.v degenerations, let u, suppose that 49S 77/ A' XKHvors sysTim the .■..r.l Ims l„ri. iK.nnsct.d. that is. o.u-lmlf<.f it l.as I „ ,.„t tliroi,«lr tl.f kiiil,- l.as s,-v.T.-.l vun tra.t an.l ..very longitudinally disposwl fjlw in tl.a halt ..f tJK.-car.l. I'lu- .lesciHlinK fihn-s that l.aNe been ,ut show .leKem-ratu.,. /./,,„. tl»- section, that is. special staining methods will nt hrst show thes,. hhres n. their staf of .le^eniration. and later their disappearance and ivplaeen.ent l.y s,|,.rosis. Theaseendini;fil,res on the other hand, are relatively iinaHVeted l.el..w the point of inj„rv' It IS above this that the degenerations arc >een. Based upon these ;;,.neral consid.rations we ina\ cla.-ifv tiie main diseases afhrtinK the cord ac.or.lin>; to whether ii.e lesio"ns are .lue to (1) .lestniction ..I the iipp.r in..f..r ncnn.n.s; r2) injuri.-s affectlnE the axones ..f those upp,.r motor ncnr.mcs .Inrin^ their eoirse down the cor. ; (A) mjuries of the L.wer motor nenroi.es (.liseases of the axones of these, the periph.Tal nerves, will be c..nsi,|,Tc.l separatelv), an.l ( }) .liseases or injuries allVctitiK the sens..r> neurones fr..in th"e post.rior KauKhon upwar.l, an.l (.-,) .liseases allVctinR motor an.l sensorv neurones comeideiitly. It seems i.e.essary in a w..rk of tliis sco|,e to leave ..nt the i;r.-at mass ot chnica detail that is inv.,l\,..l in any full .lis,-ussi..n .,f th.s,. various spinal .lis..nlcrs; we .an m.r.ly in.licate the .Uderent tvpes with oiitstandiiifT examples. ' ' 1. Diseasfs Affrcfim, thr Cranial Distribution of the Upper Motor Ne,- r«»<..-Congemtal spastic paraplegia is a well-marke.1 on.lition in wl.i.h nerye-cell b...lies in the c.T.-bral c.rtex luue been .lestroved. usuall\- by trauma at birth or ayain by obliteration of ,er.-bral vessels .lurin'j: f.rtal lite, as m congenital porencephaly. Similar spastic paralvsis of like origin, nain.ly. thr.,uph .hstrn,ti..n of c.rtical nerve cells, mav he of postnatal origin, .Im-, f..r .xample, to the presence of tumors, infective granulomas .)r vascular ..bliteration (acquired porencephaly). As regards the cerebellar n.-ur.,n.-s, the i.leas <.f many authorities compel lis to include here Friedreich's ataxia as owing its in..st imp.)rtant svmpton.s to an atrophy ot nerve-cell bo.lies in the cerebellum. In 'this' rare familial .l.scase it must be remembere.l that there is also a spinal lesion ot botli m.)t.)r and sensory systems. Perliaps the commonest of lesions in the cord, secondary to priniarx insults 111 the l,rain, are those following upon cerebral hemorrhage aiul cerebral thrombosis. IIem.,rrhage affects most frequently the internal capsule an.l the p..ns, d.'stroying axones of onlv one side of the bo.lv. In multiple sclerosis with its sporadic, irregular distribution of scleros.",] areas ot primary degenerati..n, .Mthcr the cortex or the cranial tni. t. may chance to be inv.)!ve.l. an.l so l.-ad to secondary .legeneration in tli.^ motor tracts of the cord. 2. Disease Affecting thr Jj-ones of thr Upper Motor Neurone dnriwi I heir Course hwn the Cord.- The broa.l effects of such diseases m- identical with those ..f the previous category; we make the separation bccau>je here tlu- disease acts within the cord. Strictly speaking, we must here mcludc conditions of myelitis difluse or localized, because 1 , .^'^m^^m' THE SI-ISM I (nth 499 * : .*:vi;:;i;;r:,:r:i;;!:t;^:;.:' it^rr '>-" •"- '■"-" ^MiMii.trical sclerosis „f l,.,t < r ," ^'''•''•"^'^ '^ " I)riinary 'liM> >tri.tlv n.id.t l.av,. l.rr i, I I .. "'.'*'"" '"■'"•"'•i'. '""l :''- "'•1 i'.--'."'v„:j;;;::,:i ,:'•"' v;,:;:^^^^^^^^ i— << II 111 tic family tvDi» nf i«f„.i 1 • /'"^ ""tcra I .sclerosis sclerosis uvl.c^cX^!rr n t r .nmr,"'' '""T""'?'' ^*"*» tumors. Mi tlicinfecLirruiomls ^'""'" '''—'"": - «'- with '"'•> riu, in cranial lur c . ! 1 ! V ."* *''.'" '"•"""^ "*' ^'"■'^«' ^•^'"-^ "" .^n- here .1 / vit ii f. "■* •"''; '"■''"■'"'^' ^•'■•'t- «'tl...,iKh i'~ .-.x-M,,.. Ti.c i,n Jrcssiv . • tr • '" ''"'*"'' '"•'*'"■ "^'•"•'"»- ""iiiK. Ihrr, first and fomiiDst. In to l)(- n'('tlii«. hilt it is now >;eni-rally ae<'epte(l that th< m- are not sufficient to explain the extensive (ieneiieration found in tin posti-rior eoliiiiins So, also, certain observers have called attention to locali/«'d nieniiiniti> with thickeiiin>; involviii),' the nieiiin^'es of the jiosterior as|M(t ol the cord, and have assumed that the contraction of the filiroiis tissia around the enteriiif; |)osterior root fibres is sufficient to cause an as;ciieration that first shows itself pt iii)lierally and only with its projjressive ad\,ince l;s about a final atrophy ol the nerve-( ell body. It mijrlit be su^rKcstt-d that we deal w itli a sdeetivt action of the syphilitic virus telling |mrti;eneral lowered vitality of all the neurones thus in those showing' the early stages of tabes and accustomed ti jiarticular recurn-nt muscular movements (])olishers an; sleej) when the cerebral stimuli largely cease to act. If the vitality of both orders of cells he depressed, the sensory neurones are more liable to become exluuisttil than are the motor. Apain. as in all the fore>;oiiij; groups, multiple sclerosis, myelitis, tumors, gummas and tuberculomas, acting on some portion of the posttrinr columns, may lead to a secondary ascending degeneration. '). Diseases of the Spiiinl Cord Affecting Motor and Sensory Fihn.s. Here we have to take into account all those disturbances of the spiiiiil cord which result in iiiM.Kiil fciviiiu ris«' tu >r«in nil parrsis, tlirn- riia.v he a sclerosis (»f the hiti rill (iiiotiir) tract as well. Wlwrc, as in multiple iclerosis, luitnvrous jirri- 111' [iriniarv, localized ijcstniction of tin- spinal tissue have their iiiL'iii, not so inncli in connection with tracts as with vessels, which ill iliiir course may pass tlirouKli several tracts, there ne«-essarily w*- tiKiiiiiitir coinliined sclerosis, that is, a sclerosis of hoth motor and Hii-(ir\ tracts coi?irirlently. In Friedreich's ataxia there arc found atni|i|iic tracts iMtth ascending' and descendinj; l|M»sterior and lateral 'olmiMi-, direct cerehellar, etc.). A similar state is fonnd in subacute combinjd sclerosis, associated with peniicions anemia. H<'sides these, ill lathyrism and pellagra an- fonnd similar states of comhined sclerosis; llif lornicr of fluM- follows the |)oisoninj; hy several kimls of vetch l:itliyriis), and the latter is commonly attributed to a diet of mouldy ni,ii/c. though there is still nmch discussion upon this matter of <;ii|sitinn. Progressive P-'hances. Associated with the low rt-generative |"A\cards the tumors, the gliomas an- the only ones Miliii icntly common to deserve note. These ;;liomas oripmite most "Itcii in tlic immediate neij;hliorhood of the central canal, and frecpiently iirc (lilliise, hcinj; of the nature of jjliosis rather than sharply defineil ^.'li'iiii.i. If tile central jjlionm breaks down, a condition of syringo- iMMlia i^ produced. THE MENINGES, CRANIAL AND SPINAL. The Dura Mater Circulatory Disturbances. -The most imjiortant circulatory disturh- "1" ~ r b\ way of the emissary It lie petrous bone or in the cranial vault. The cavernous sinus ntti I flii- IlKl i lllr I'-,: II,.-. I" \l 502 THE SEHVOUS SYSTEM is less often thrombosed by extension from the orbit, or elsewhere. The sinus is distendetl by a clot, grayish-pink to dark red, firm or softened according to its duration, and at times even appearing as little else than a purulent mass. Such a sinus thrombosis may spread to a sur- prising extent into other sinuses, and into the jugular veins. The results of this softening are very frequently tlie development of multiple abscesses in the lung and pyemia, not to mention the more local develop- ment of meningitis and cerebellar and rerebral abscesses. Hemorrhage. — It will be recalled that the arteries run on the external aspect of the dura; thus while there may be small capillary hemorrhages in the substance of the dura, any large hemorrhage brought about by traumatic or other rupture of branches of the anterior or middle men- ingeal arteries, is situated between the dura and the skuH; despite their extradural position, such may naturally bring pressure upon the under- lying brain substance (cephalhematoma internum, contrasted with c. externum, under the scalp). Subdural hemorrhages originate from the vessels of the pia-arachnoid. The same principle obtains, mutatis mutandis, in connection witli the spinal dura. Inflammation. — Acute Pachjrmeningitis Externa. — This inflammation of the outer surface of the i ura is practically always secondary to infec- tion of the skull, the sii'iwt ,, or the vertebrae, or follows infected wounds ; it may be of any dogin up to abscess formation, and, by the firm con- nection betweei dura and bone, is localized, since extension is only obtained at the price of stripping off the adherent dura or burrowing into the resistant bone. Pachymeningitis. — It is not a little interesting to note that inflamma- tion of the pia-arachnoid may progress with little evidence of involve- ment of tlie dura, wliile contrariwise, the curious condition, pachymenin- gitis hsemorrhagica interna, affords at least in its early stages a picture of involvement of the dura alone. In this relationship or want of relationship we may recall that the blood supplies of dura and pia are from entirely different sources, and presumably thus, in connection with inflammation, the infection may travel by one and not by the other. In pachymeningitis lia;morrhagica interna the earliest stage so far recognized is that of areas of the inner surface of the dura covered by a thin layer of fibrin. What is the cause of this phenomenon we d.) not know, but we suppose that there has been a hemorrhagic oozing of exudate from the finer caj)illaries of the dura. The conditions in which this is found, viz., in alcoholics and the insane, does not help us to determine the etiology. Studies of cases of longer standing give evidence that with the organization of this first deposit the newly fornitd capillaries, originating from the dural vessels, again aft'ord a heiuor- rhagic exudate, wiiich once more exiiibits fibrin formation and organiza- tion, and in this way in the course of months, there develops a thicktnwl layer of new tissue wiiich may attain considerable depth, and by its pigmentation indicate that there have been recurrent heraorrli;!;;i5. The outer side of the dura is not alfected. This layer of new tissue .iMP5K-'5.'««'».i>' THE MENISGES, CRAMAL ASH SPIXAL 'm MiM> exteiKl over the larger portion of thedural lining of the skull, and m many cases may show little evidence of extension of the inflammatorv pro^s^^.s^^'^>i¥w^!i^. c'-i^:^:- lfeLijr'^K5&"^*«--ni6f "--^^ rf9^ lu'liomatous tiiHT aspect 11(1 produce nias do, of (1 these are ous tumors ibably more en observed either into )t to largely lid and pia; rds the pia- • membrane the meshes helium, the he cerebro- iches which the choroid L general or e hyperemia scularity of ing away if Passive con- e congested •y (hydrops ostance, or with ht'iiil , associated ay occur in tions of tiie i arachniiid nice. , fibrinous, infections, ;ed In' the y in young (id accutnii- tic atrophy- to bcn»me cts arc the THE ME.\lNGE,I-rs. as from the middle ear. the nasal passages, the orbit etc .to a h.v years ago conditions like epidemic cerebrospina Imeid. I ii" "'tSt^^ "''"'"''^r'= "^ '""^'""'« amountof'proof tcZ- m ...t.^ that they are secondary to growth of the specific organism's ■ upper nasal passages. There are two areas which are especiX labl,. to be the seat of purulent accumulations, viz., the base of the bra n ::;;;;: ;;.;:r""T"h""'""" f™.*?. «-« the'vert'ex, over one oMo Hun pheres The pus is specially apt to lie along the superficial c>>cl.. „, the sulci, but may be so abundant as to form a thick kver Md.ng all the convolutio..s of the hemispheres. In general, owing' to tree .onnnunication along the arachnoi.lal spaces, this purdent flu d . xtjiMls down the cord, where it is apt to accumula e aloiwhe anterio jHMl posterior hssures The ventricles, also, mav be sinlrK rnvaded . .•xtens,.,,. along the choroi.l. A local meningitis mav arise efthe t ison from without, as in mastoi.l disease, or from within he I. as in abscss. It may be laid down that through the intimate .'— t.on ot the vessels with the cortical substance, the out^ l^s '■ «n.y matter are apt to be involvcl, so that ^.e .leal T^re , ten ■I "uit that we owe the pareses and other nervous phenomena tiM irocn. hemselves after the acute attack has passe,l bv hhS?! !«P*«'«eni««fitis presents itself as a milky thickening of the •- ii c ,v tv'rr '."•■^''^''-hood of the superficial vessels 'I- '- .f u I ;.,! f ^T" •■ " ^'•'Vr''■'''"*' K^''«ti"""« material at 'I'" '1 a.i • er e f''""?^"""; *'•''""'"">' '" ^''^^ "''^ «"<' the alcoholic, "• '" • u m;;rH .Sit" m "" "'• 1 "^"*'" '"""'"'""tion, there ^re j^^^ _ l'-'-mt.r.d .lefinite ftbrous adhesions between the dura and "'^'''^■;X^' commonest forms of meningitis, aiul then - m'J^^ '!•''• , "':':^^; 7"-^^ -^ the tuberculous. This shows . . T OS s ' .^, " ".'"^^"*'''f"." "' P«rt of a general hematogenous ■ •• , .Jh;;^ •« recogn.zable on careful examination bv "along the vessels of the .Sylvian and other fissures anil I;; n .Jexiis ,>f minute pi,d,ea,l and smaller tubercir^lllch .'parent It a .rnall piece of the arachnoid be floated out in - «xan,,ne,I with a hand lens. Other favorite si el are ovir -.1 on the apposed surfac-sof the c-erebellum and the tempor" it- iiii tl), of l„, til, i-3'-.4S?.v •■ -aaiL^ic ' -^? 50G THE SERVO us SYSTEM ill- :# 'i : i sphenoidal lobes. More rarely the tubercles instea.l of being generaliz, may be few .n number over a small area, e. „., of the cerebrum Tl appears to bo an early stage of the cerebral ir' cerebd ar tube-ulom diffit^^fl '''T '"'■^''^" ™'^'^' '^PI'^'^^ '•^''^t'^^'y healthy and free fro diffuse mflammation one may disc.ver on lifting the brain that al Itl nitersfces at the base are filled by a yellowishf gektS tran^ce and oedematous n.ass, really the swollen and ii^U at d aSaet In general, the basa areas are the m.)st involved, and it is o be reZ bered that m practically all eases, there are he e n. onlf the mS tubercle, but s.gns of exudation and increased presence 7lymDh™ct '"slnl^'"TT' r^ "^■''"^'^ n-nonuclear'cellsrtheC stage' Syphilis.-Wahzed gummas of small size may be formS in th ^ZFa "• '\ ^r'J^^ of a greatly -thickened mSg of 1 arachnoid, m which the individual gummas are not to be distin ^v2 • ♦ 1 v^ '^f .''?'' '^''''^°"' ^^"f«s- More typical of cerebra syphilis IS the diffuse thickening of the basal meninges with firm adhe Thk r " ^T f^?'^'\''' «n'J thickening along the basa nenes This process of syphilitic infiltration around the vessels w;th\r=^Ki :ut:rs^feT";sr%f TT '- ^^^'^^^^^^^ may be ?I .^l?' f^'- T'"''' ^^''^ ""'^' ''«" "^ «>'PhiIis in the craniun Pro^esZ^ " «^ mesarteritis of a single superficial vessel, sion X!rT 5^«!--Sniall plates of metaplastic ossification occa- ii« p ', ™'* "' the leptomeninges as in the dura, the lZ™« /' •' '"'"""^ ^^' ^""'^" t"™"'-^ a'-e to he encountered commT^' f*"*™''"**^/ ""d lymphangiomas, as also flbromas. More common and more characteristic are the primary endotheUomas hese are of two mam types: the more frequenUs compose! TwS endotiiehom«; the other form shows cells of a more cylindricTlT^i and penthehomatous arrangement. These, it is supposed are srictl^^ lymphangi<«ndotheUomas. Both forms ar; aptTTw transS^ Hito niore purely sarcon.atous growths, though^occasirafpure S h "SnieTo'J'^irt/" '" ""'l- ^".— 1 tumor found espedalfy K r V *'•'; P''"" '"''t^'" '^ the true cholesteatoma, in no wise to be confounded with the cholesteatoma found in the mTddle Tr .lhe.e tumors form pearly, multinodular masses, occasionaly reach: Scu'iaT : 'th "b" '^ -p'". '''''''■ "^^ ^^""'^ orvrti^Shrpi . SbnalLvlrtl' ' /"u* ' 'T''''. "^ '^'^ P»"« «"J ^^dulla, and occasionally over the cerebellum, choroi.l plexus, or cord. They are to h vXke'n " n 'T"" ?^"°"'^' ^'"^ '"^-^-"t to their iSon of CD ttoM . ^'"^*«'""tous growth. The cells composing them are ot epithelial nature containing keratohyaline granules: the nearh SsXn 'i''"" '" ^'''T"^ ^^""' '^ ^^^"« coiftaining fat and^a -l ai d lien. i"' . " ^''"" T ''^'''''''' »'«^ found hairs in these, and sebaceous glands ha\ ; been detected. |p,>-m?^' PElilPUERAL NEUVES 507 PERIPHERAL NERVES unl'lL'TiTLdrtirr ^ ^'''^'"^ ^"*" *"^ systems-the somatic and tilt s>mpathetic, the former are composed entirely of mediillateH .u■^^ ..s and have a somatic distribution to the voluntarv muscle and skn the atter are composed of fine medullated and of non3uTlat">d • I r= their hbres innervate the non-striated muscles of the bSv b n e aborate.1. Briefly we may say that the nonlmedullated efferent h ers take origin from the lateral horns and pass out bv the ventral ro ot o a series of vertebral ganglia, where either they eifd. or pass in j 11 tinpnS, «^ • 1 ^ '''''*^ ^''"^' ''"em to these fibres, but we may «^i"i. and bring abot anes hesia, pallor, and atn.phy of the regionr, of supplv. so that fingei sc i ''n ' rf " " """ 1 "'rV *''"."^""''"'' ""'' 'J'"'' "«■' '^'^^••"K ^'^tensiv «s f ; •/ «u"-f"f- 'f * "■' '■'"■""'^ '"■"^•^■'^^ "' t*'« "erves is see, as fusiform fibroid thickenings ^long their course. Tuberculosis o peripheral nerves, while it occurs with similar distal degeneration i comparatively rare Lntil salvarsan came int.. frequent employmen the effect ot syphiJis upon the nerv'..s was overlooked by most path o ogists, but syphilis IS now held responsible for a large number of .lis turbances of the ..ptic an.l au.litory nerves which mav appear after th. use oi salvars.-,., .nd mon- rarely of mercury. The attention .Iraur to this subject has shown that lesions ..f these two nerves are imt uncomm.m in the course of untreated svphilis ne?r!f T*""® Changes.- Here must be in.lu.le.1 many forms of s.M-all..,l neuritis from al...,h.,l, arse;,..-, lea.l, erg.>t, diphtheria, beri-beri, an.! mnirrT''*AJ""'"*r. *"''"" "^ ^'"■^''''' ""*''"•'»«• t" n'''"ti«n ihe m„r.- l^^/vit T. .?' "i-*;T ^""'^ "^'*'"*^ '"^^■** ■■' ^'haracteristic selective actu.ty Ihus the diphtheria toxin leads t.) areas of acute degenera- tion an.l atrophy, picking out certain n.-rves in th.- upper respirat..rv tract, as we 1 as the vagus, the .legen.-ration of the latter being the cause of su.l.len heart failure. Lead affects the innervation of the extensor muscles .,f the f.,r..arm and K-g. causing wrist-drop and foot- drop. Alcohol may set up a wi,les,)rea.l polyneuritis, especiallv aff.Mting the peroneal nerves. In all the above th.- .legenerati.m of the periplural nerves ai.pears t<, be primary, they being directly affected. What is terme.1 secondary degeneration is seen in the peripheral nerves vvlu.se cell bo. les have previously un.lerg..ne .lestni.tion, .,r which have lu . n cut .)tt tn.m thos.. cell bodies, as in true Wallerian .legeneration. ^^m!\^'':':r.^m^ m^ THE EYE 509 Projrressive Changes— We have already referred (see j). 24.-)) to "false neuromas" or amputation neuromas, as also to what we have termed neurinomatosis or multiple neurofibromas or fibromatosis (see j). 247) Til. s(.-(i.lled elephantiasis neuromatosa or pachydermatocele, appearing a> a .onKemtal atfectioii, has underlyiiiK it a great irregular thiekening ..r the iier\»-s. of the same order. Assoeiated with this is a general .ieformity of the part with thiekening of the skin. Rarely gliomas have iK-en descnhed as oecurring along the eourse of peripheral ner\'e3 aiKJ still ni«»re rare are lipomas and rhabdomyomas. All of the gliomatous and nenrinomatous tumors show a tendency toward a malignant metamorphosis, the latter giving origin to spindle- jrllcl s(.inetimes myxo-sarcomas. Of secondary tumors carcinoma has Ihtii deserihed as occasionally ext.-nding in nerve bundles and bringing iihoiit atrophy of the same, but in general, nerves are little involved in secondary malignant growths. THE ETE Anomalies. -The eyeball may be lacking (anophthalmia), a state winch IS usually toiiiid in conjunction with other grave defects occa- si.Mii.ll.v there may be found tissues that represent the eveball, -mv\ i„ ,vrt other cases a small bulb may be present (microphthalmia) In .hthnnt kinds of cyclopean monsters, two eyes in a single orbit or a Hii^ic eye in a central orbit are seen. The cornea may be smaller o- larjier than normal, or its curvature may be more or less convex than ■wTiiiai; part or all of its substance may be opaque, usuallv in such states as microphthalmia. The iris may be absent, or mav lp<-k pi;:nui.t (albinism); the lens may show opacity, or tissue strands on til.' siirtace may represent the remains of the hvaloid vessels; the lens may 1„. dislocated. Any or all of these different parts mav be lackinL' 111 coloboma. ' "^ ' "loboma is a congenital failure of the cleft of the secondary optic ^.H.l,. to close, either wholly or in part. This may thus affect every -r ,,.,v part from the optic nerve to the eyelid; it is common in the iri;, ^ind IS tre(iuently associated with other congenital anomalies. Circulatory Disturbances.-ConJM«c apparatus. A common cause of local (T>,h:ma is the sting of nn ' . Hemorrhages in the conjunctiva are the result ot injury or '^^y''!m^m^^^:^Bm 510 THE NERVOUS SYSTEM ■4r arise durins,' the effort of violent coughinK or siiee/.iiiK, e.s|>eciany i chiMren witii wliooping eoiigli. /r/.'*.- Hyperemia is of importance as an earlv accompaniment r inflammation. CAofou/.— Hyperemia is seen as an accompaniment of inflammation c the choroid and surrounding parts, and in its passive form, as part of general congestion of the IxmIv in general or the head in particulai Hemorrhages in the choroid are due to trauma, and the hemorrhagi diseases. /ic; our colleague, Dr. Hanford McKee), Murax-Axeufeld diplobacillu: iiPPP«| THE EYE 511 stitpliylococcus, streptococcus, pneumococcus, Microccx-cus citarrhalis ^onococcus, B. McKee, B. Koch-Weeks, B. w.Ii, B. influenzae, menin^ (lococcus, B. xerosis, B. Hoffmann— while a large variety of saprophytes is seen, many individuals of these last being found in greater frequency than some of the pathogenic microbes enumerated. The character of the inflammation varies greatly but is in no way liistinot from that described in vascular areas; catarrhal, purulent, iiiid membranous forms are seen. The severe degrees of inflammation lire apt to jeopardize the integrity of the delicate cornea; the chronic forms may lead to considerable superficial loss of conjunctival tissue, the healing of which may be attended by deformity of the lid. Ptery- gitiin is an inflammatory overgrowth of the conjunctiva upon the eyeball, of triangular shape, the'apex directed to the pupil; sometimes It becomes quite well vascularized, and the superficial epithelium is |)roliferated and even at times folded. Chronic ConjunctiTitia.— The forms of conjunctival inflammation known as chronic are, in the main, characterized by proliferation of the tissues, which appears as granulations varying in size from those just visible to cock's-coml)-like masses of large size. The so-called trachoma is the most important of these, the overgrowths being not typical granulations, but small encapsulated overgrowths of lymphoid ami connective tissues. It has been shown that the so-called "trachoma bodies," intracellular Ixxlies found in the epithelial cells in trachoma, are not the etiological factor. Parinaud's conjunctivitis is a rare, but severe form accompanied at times by marked systemic disturbance. Vernal conjunctivitis is a malady of persistence, with annual exacer- Itatioiis, m which the granulations are hard, composed of thickened il)itlieiium and connective tissue, at times degenerated into a hya''ne mass. The infective granulomas are rarely seen to affect the conjunc- tna. Tuberculosis may spread from lupus of the face, and syphilis and leprosy are known. Cornea.— The process of inflammation in the cornea (keratitis) has already been described (see p. 134); from what has been said there it \m1I be gathered that the collecting of lymph cells and the production "t new corneal corpuscles will give rise to some opacity of the cornea, "cal or diffuse. This may be recovered from and the foreign elements l>e iil)sorbed, but on the other hand, a certain opacity mav remain "r tlie inflammation may become more intense, with loss of substance witlun or on the outside of the cornea. Should this loss of substance lit rei)aircd, the connective tissue which performs the repair mav, on tlH one hand, remain as an opaque body, and, on the other, by its "intraetion alter the curve of the cornea, thus impairing its efliciencv ■'>■' a refracting body; vascularization of the surface of the upper part "t the cornea may occur in trachoma, constituting pannus. Diffuse parenchymatous keratitis, evidenced by infiltration of the -rnca may lead to vascularization in the mbstantia propria, the forma- I •;■ of new vessels being deep. Should loss of corneal tissue occur on t e surface, corneal ulcer is the result, and if in the substance, abscess. ■n i%'ffiYW. 1 i r ^B^^H ■ K* "1 :)12 Tin: SERvnrs systk.v SuppuratiTe keratitis idhv he phlyctenular, generally close to the eorneci scleral margin, where riiiiuite pustules appear just under the surfaci .apidly l)reakin); through. A eonsiderahle number of cases of sup|)n rative keratitis are due in part to the ciH'xistence of injury. Corneal ulcer nuiy (M-cur with inHainniations of various intensity it may arise in ill-nourished children and progress slowly, or it ma; he the result of a fh)rid conjunctival inHamnuition and ennle rapidly The serpiginous ulcer is named from the fact that while the ulcer heali at one part of its ed^e it proj^resses at another; it is practically alway: due to pneumococcus. Herpes f)f the corn»'a may occur, associated with nuirked anesthesia The infectlTe (ranulomas are of eonsiderahle importance in the causa tion of keratitis; the difVuse form is frefpiently syphilitic, much les« often tuberculous, but the localized occurrence of the gumma or th« tubercle is rare. It was previously thought that there was a specific form of keratitis which followed lesion of the fifth nerve, but it ha> l)een shown that this is not neurotrophic, hut due to infection becaust the eye is less protected than in health. Iris. — Inflammation of the iris should always at once suggest tn the beholder systemic disease, and in the order of frequency is due to syi)hilis. rheunuitism, tuberculosis, gonorrhea, gout, diabetes, oral sepsis, ami trauma overwhelmingly the first two. Fibrinous exuda- tion from the vessels of the iris blurs its bright surface, and with this exudate there exists a strong tendency to a to the mode of transmission of the uifection, a century has not adiicd any certainty to our knowledge. Purulent cyclitis, or better, iriil<)- cyclitis, results from injury, an«l the iniectiou sets up paoophtbalmitis. THE EYE •)13 III this frravf state, there is su[>piiriiti(.n un«! diMiiteKratioii of all the )all, p'lierally acc«)rii|)aiiif(l by severe Mitt iiitcrnai structures of the eye! inlliiminatioii (.f the eoiijiiiictiva amF the soft tissues of the orbit Ihr mdaiiiiiuitory products may greatly .listeii.l the eveball. their -M ;.p,. bcit.K prevente.1 by the dense sclera, which in time mav Iw itself rnMlnl to the burstui.? point, when the contents escajM'. Shouhl the . w ball not l)e remove., there may be a gra.lual shrinkinR of the empty >Mc. and a more or less solid mass of firm tissue be left to represent the tfl..bc (phthisis bulbi). ' rAoro/V/.- Choroiditis is caused by systemic .lisease, svphilis, tuber- 'iilo-is, certain disorders of mitrition, or a bacteriemia; in other cases thr .ause remams undiscov»Ted. Sometimes in the granulomatous iiit.rtions.and always in the i)acterieinic, it apj^ars as an exudative or a purulent inflammation. These terms sufficientlv exjjlaiii themselves- t If .Niidatc may remain upon the choroid or mav be thrown out intci th.' vitreous which loses its transparency for the time beiiiK; even a mild frrii.lc ot choroiditis may. in healing, be followed bv atrophv. A sup- IMin.tivc choroiditis, as stated libove. is almost nect^ssarilv a"forerunner i>t iiaiiophthalmitis. Hy r. iison of the propinquity of the retina, this membrane is practic- i.llv ahvavs affected; in the acute type, the retina quicklv .lisappears, iMit in the more shnvly progressinR infectii.ns, the retina shows changes I"' iilii.r to It. and the disease is known as choroidoretinitis. In tuber- ' iiIomn tubercles of miliary size are seen in the choroi.l, lifting the retina IT MP-iT i.ggregate(s Its distinctive features as a result of anlema or exudation inl, .edematous, and cloudy. Ai)art from these cases, a like appear- .'M- r i~ >,.,.„, „,dH,itive. not of an acute local infection, but of a svstemic ^ar,- s,u.i, as Hrighfs disease, diabetes, syphilis, or arteriosclerosis. ' " N.>t named indicated by hemorrhage. Most important of retinal ' ijni-'<- is tliat known as albuminuric neuroretinitis, a description of "''I'll u,|| ,n ge„..ral serve for the changes seen in anv of these bodilv ,1 ■ ■ ^:'« ".'l.rt'qiifntly the retinal examination, undertaken l)ecause Ji" ^ iMnn ,s aihng gives the first alarm of the existence of the disease inn I. swelling, dou.liness, and lack of definition of the papilla; the r>tin. .hows pomts, streaks, or flame-shaped areas of hemorrhage •re are m the macular area, irregular whitish areas formed bv '""Illation of cellular debris which has undergone fattv, granular ';^'Nne degeneration. Withal, there is lymphocytic and fibrinous '""! into the retina, whose vessels appear engorged and tortuous. "Mst.nce of the hemorrhages and the whiti^i areas marks the ritlii:i illlll tile iir exni Til, stall ■| n. uroretinitis. ^^ hetJicr due to Bright 's disease, diabetes or a , ^, "^3 514 riiK \F.H\(>( s s)\-^i i:m transitory alhumirmriu of preKiuinc-y gravidic neuroretinitig ; he pM-tinr may Ih' the same, bnt Mic siihse(|iit iit t-mirs* • the \mu< ess niav reoivr ,vith the loroi-'-i- is i .ihs- >pacitir- be quite different; in tlie last nanieil, ffe n-tina i disappt>a ranee nf the alhuniiimrja after lahnr. When due to sypliili the It ..m is that renitii! or aequired, and ai-jxars in seeond stage of s\phiii ii-^ually in botli eyes. 'I'iie fun tiriet, the retina and t .lisk iire swollen, and fine, dust-hkv (cist-off exudate) app«-iir m the posterior part of the vitrrows. 'in tl hein<»rh»»ic form, .»-ca!leinulaii! the usual signs of -etinitis ar^ im-sent. am; m adiHtion, fi ^i is , series of recurrent I -•morrhages, th< wh'vle oft n heint in ind ■on of widespread vascu' disease (art« rioseler<.sis), an n i l)ral heinorrhiige. Eegressive Changes, '"le only regi !\e ehasiife^ arc those observen in the ■ cm. a, the ehon.i i th« retin; I iimea.--\n the first, the cornea, there i> a regres-ivt IS called arciu senilis. It c onsiNts of whitis ar( margin of the ((-ri). a al)o\e and below, ultin; ?<■! ver miniitr dn. of fat which lie in the sn -tantc of far post rii iiy as i Jescemet's membrane; son ' mes t' appears tc be a kind of hyaliie, whi!- in ( ^ r ca i r to be a depo-ition of lime Its m ctt -nsparent tissue ot th( which de]"'-inonth».ad\ai iigdcKenerat of the f Itxxi v« ^sel It is thus htii n'ore than a sign -4 arteri:'. age In the choroit times a> i >e(jP!"! to previous uHammation, ar ^ ot atropi ith irregular ],, ^'mentation, an. I >metinie- ull; tely e\ ■- ell a> aft( r various f.rms of lis« ase, such j. stibretinal heniorrhag''. The nx! obscure fatty or other eliantres. ;,;m»nt may in Teas* rrunn- m "er tal la layer attached x<> the e' .roid chanps in the separat'^ iayi r undergo maceration or ijeiierai depo-ition in it of c{.lca n. matert Retinitis Pigmentosa mator\ state of the retii males, especifflly those wh ars ■a, 'vors. >orae- 'ccur, pio- :'SU' tis ai uid cones niay atrop tiderg. ysts may ari«e. and i tk .iioiint w -'- casi of separaion of the away ving ■ e pigment »t ;" !' ae uipanii.i by grave i be. !es ( "matous and may of diii- rent kinds, ev- n to the -t^i no •1 inflani- , aiieets Hi parents. ais;-stnr!: :i jjressive J! which of( iir ill particulai fe the offsprngof consang ._ ^ In thi> rare disease, the roi a is degcficrated and atropnied, and then is a migration or a carryin of the i ,'raent from the external la\er, wher t normally lies, to the inner ers of the retina, where it is depi ed. ^Vehave previi.Msly |M>i>^ out that the pigment-carr\ in^- cell sa *he skin seen hat methoo re ill e mig ,y powers; it is not possible to ''1 -n^ changes its situation in retinitis THE EYK 515 li tin" formation of f t has lift and I illf IfllS ' be rt>niov«>( uch n lens h -<■, remaimd !.iu'in«nt«»sa, but a is laid d wn apparently in eiHlothelial . \h in the vicinity of blomJ vessel;- in fibrol;c areas. Lnis. The r ressive .hanges in the lens that are of importatue are th(.s, that give ^e to ojmeity- in short, the various forms of caUfMt. ( iiiFiiet IS of t' o distirx-t f.»rnis stationary and progtMsiTe In the forup r. a Cfirn.i inf. tu.ji may leail to a localized area < .paritv on t ,• anterior surfaii of the lens which remains tliruURi fe, but whi. IS of little iniiMJrtanre, Iweause it dcM's not increase in iZe. A hk. iditioi, ia\ ifict, though more rarely, the pc -eriDr surface or a Mn^i Ian.. Ila ih*- lens may Im- opaque, and of ms the extent !«■ imiM.rtanee are nt.fssarily Kreater. Progressive .atarnet is (]) ■ mi,-. (2) congenital (jn< .Miile), and Ci) traumatic. In senile cataract 'iKKt famili.,r form lie fibres of the lens undergo .' globules and myelin. Isually the opaque "extraction." It may happen, further, i«en removed, the po tcrior capsule, which tay itself bi«come opatjue secondary cataract pacity constitutes capsular cataract. In 'raumatic cataract patjue a,-", a direct result of an injiirv, ;.,id here it is that a 'ouMderalHc degree of absorption of the opafju. tissue mav occur- M"Mld til. lens fibres b- ome separated and fb.id be absorb^ (from' tlir a(|U('oiis) the lens n. v swell up, may be< .r.,f soft, and may even k' .oniplet.ly absorfjed if t'„. lens and capsule become Hxed to some il* zed, a considerable fiJ -ous proliferation I'T with the new blixxl rssels, constitutes -ransparency of the ler Even calcareous )osited. adiva.- Certain benign tumors, fibroma, re found on t!ie conjunctiva, but the -t— the squamous carcinoma and the sarcoma. Carcmoma is oltenest seen as an extension from the eyelid "r utli.r nciirby .structure. Sarcoma is less common, and when it "< ' Mrs, may be of the pigmented variety. ror//,y,.- Primary tumors of the cornea are \ erv rare. Isolated cases ;'i i.rnniiry fibroma, papiUoma, sarcoma, and myxoma are in the literature 1 ; rnctnre may be secon.larily inxaded from other parts of the eve "'•v. 1 igmented sarcomas are found, bnt by ih. means so commoiilv ii- iniilar tumors m the choroid. '//om,f/.- -The most common progres.sive tissue change in the choroid ^ melanotic sarcoma, of which, indeed, it is the most frequent site. Thes. tiiii>"r, are markedly pigmented, consist of round or .spindle ce!' firov, rapidly, arid having once grown through the .sclera, rapidlv f( I" ' i-cs. fhey are seen as flat, ses.sile growths, lifting the'reti. •>~ ' ' progress. Ii ''IKI nearby structure an ina.\ incur, and thi a vtr ;;reat detrini. tnatcrial may be ultin Progressive Changes lipoma, papilloma, or 05- iiii-r important an- m; gllon; ra '.-The only imptirtant tumor arising from the retina is t " ""• have nr- vjoiwly masle referpne*-. The tun- he globe, making its way through it and appearin • I 510 THE XKHVOrs SYSTEM m. % as a funjjatiiig luxuriant growth that sprcawing or obliteration of the angle of the anterior chamber Owing to the great intraocular pressure the optic disk becomes cupped which cupping, together with the hardness of the eyeball, is suflicieni to distinguish the disease. The Optic Nerve.- It is necessary to point out one at least of tht l)athological processes that affect the optic nerve. The most importani is choked disk, the name applied to the pa])illa altered in certain patho- logical states, as when there is a more than normal intracranial tension such as is produced by the presence of a new growth or an inflammation of the membranes of the brain. Some of the names applied to chokcil disk, such as papillitis and ojUic neuritis, imply that the change i^^ an inflammatory one, but this is probably not the case, although tlu' ai)i)earance of choked disk is seen as part of a papillitis or optic neuritis, (lioked disk is an a'dematous state of the optic papilla. As the ojitic nerve is contiimous with the brain substance, the cerebrospinal fluid surtaunds it in the ojjtic nerve sheath, and may press upon it; thus the central vessels which come to riui inside the nerve itself are likewise ci>m|)resser| and n-dema of the pajrilla and the most distal part of tiie nerve results. In a moderate degree of choked disk, the outline of THE EAR r)17 tl..' paiHlIa IS blurred and indistinct, the papilla reddened and swollen .■>I..c.ally .„ .ts nasal half, while the retinal vessels are enlargld and tortuons In more extreme cases, there may be splashes of W- rn,.. on the d.sk. Should cedema persist, atrophy of the nerve ft^es lit tiic disk may be the result. "vcnurts X.uritis of the nerve trunk may occur from an orbital or a meningeal nit.rt.on. \Ne have previously pointed out the liabilitv of the nen^ trmik to flbromatosm. and true neuroma has been found ' The Orbit.- The eyeball is siispen.led, as it were, in the bony orbit jUH be ween the globe and the bone there is, therefore, a coSerable l>ulk of muscles and connective tissues, not to mention fatVnd the v.^ular and nervous structures that are placed there. Inflammat on <\ tlH..e soft tissues occurs, as a diffuse ceUuUtis or as abscess, result Z run. rauma or infection; to the latter the orbital tissues a^e Scpoed tor .,t«,,„„ may spread from the face, the cranial cavitv, the Ees TumoirT ^''"^""'^ "' f^"^""^ mechanism, the lacrimal S' Tumors of many orders are found in the orbit, apart from those that nay spread from the globe: angioma, osteoma, myoma, and teratoma are '-'"•I. while sarcoma is fairly common; carcinoma is onlv seco^darv or y extension. Cysts of many sorts, including hygrmi a Tdo^Ks <>t like congenital origin, may be seen. THE EAB Abnormalities. -Anomalies of the different parts of the auditnrv 'M'paratus are numerous, but relatively unimportant jlnsiderSth^ ;:.:;:;:," '^T '*""*"'!f' '^r ^'^--^^ «^-t '»- middle and ntina! • usually associated with other defects, such as harelip and clef It., the auricle may be abnormally small, abnormally large or ■i-'.-x.ry auricles may exist. The external auditorv canal Zv Z a sent, stenosed unusually narrow, unusually wide o ^v^^rduScated Ik ..nun membrane may be absent or flssiied. The nifWle enr ^ I'l absent as may the Eustachian tube, or the latter mafbecJ^^i if f ''""l"^'"l'>.^- freezing is well known. Hyperemia is usuallv i^ -" u .>:=,!?:* !^:r'- '-- ""-«^ ^— in ;C t--i">mn K^S ^¥^?«*---^:i'-^-"'«tory changes are not of impor- ^^ . .|IMrt from the inflammations or traumas with which they are part, the enlarged individual vessels being visible in states of 518 THE NERVOUS SYSTEM i inflammation. Hemorrhage, of punctiform nature, may occur in membrane, and may show upon one or the other side. Middle Ear. — HyDeremia occurs as part of the inflammatory proo and as the result of general passive congestion of the head regi Hemonhage is usually the result of trouma or of a particularly virul infection — hemorrhagic otitis media. Internal Ear. — Hyperemia and hemorrhage occur under conditii similar to those in which they arise in the middle ear, but hemorrhi is of more importance, as it may cause deafness, and the absorpt of even a moderate hemorrhage may be attended by damage to delicate structures involved. Inflammation. — Auricle. — Any of the inflammatory processes wh affect the skin may afl'ect the auricle. The inflammation which folk freezing is familiar, the auricle becoming swollen, bluish red, and pa ful; blisters may form on the surface, and even gangrene may folic Inflammation of the perichondrium or of the cirtilage iiself may acco pany this or other form of injury. Perichondritis, secondary to inju as at operation or after hematoma, is occasionally followed by slij deformity of the pinna which appears wrinkled. External Auditory Meatus. — Inflammation may be localized, as the common furuncle, whose origin can be readily understood when is considered that the wall of the meatus is exposed to contact w; discharges from the middle ear, is liable to eczema, and does not read lend itself to complete cleanliness. On the other hand, inflammati of the meatus may be diffuse, from the same causes, especially in patiei whose resistance is poor; secretion tends to form upon the wall, whi is shed off from time to time and as quickly re <>ved. The infecti may be confined to the soft parts, may be supci-ticial, or periosti and implication of the bone may arise; in any of these cases an absc< may form. Membrane may form from diphtherial or other infectic and mycosis, or infection by moulds, is seen. The infective granulom ahect the meatus, tubercles being found on the cartilage of the auri( or 'n the skin. Syphilis may show itself in ulceration or in inflammuti of the cartilages; gumma is not unknown. Both of these infections ii rare. Drum 3/e7n6ran ed speech ; it ,s remediabh .y a simple surgical operation. A rare naltormatK)n of the tongue is macroglossia. or large size of the organ i-rou^^ht about by congenital .)bstn.ction of the lymphatics. ^ Circulatory Disturbances.-While not infrequent and easily recog- nzahle, these call or httle special note, save as a reminder thaTthe appearance of the hpsand gums affords valuable indicatio.,s of general anemia or hyperemia. '^'"t Inflammation.-According to the part specially affected we sneak ISr^tt ^.'""T-^f'T "f the mouth). Cheilitis (of The Z\^- pvitu (ot the jaws), and glossitis (of the tongue). Considering how^e mou h IS exposed to infection and traumt ii is remarkabfe on the on. haml how relatively rare are serious inflammations of this region n oth.T words the protective mechanisms are here highly developed U oun.ls of the mouth heal in general with extraordinary mpi.Syfi .l<..s not mean that inflammations of various orders are not met with- -J. l.e contrary. Some of them, too, are characteristic and Iservbg notice More particularly it would seem that the mouth is marked"? flu..nced by disurbances affecting the other portions of .he drges^ve espiratory tracts. Here may be mentioned the herpes fabui^ tt frequently accompanies lobar pneumonia, and the ca^rhaf gW ■t s acc..mpanying intestinal infection. As a class general infections i.l.-t an associated inflammation of the buccal mucosa, and the con ' -.. ot the tongue an. lips, varying as they are apt to lin theTf. ■ i kS^S™ • ""'''"''i^ ? ^ ^■'^'""^'^ ^'*^«""^*'*^ ^^^- We would II Kopbks s gn m measles (the appearance of punctate hvperem.V ^io > ot p„,h,-ad size, often with a paler bluish centre on th^ murv -I- cheeks and hps These may bepresent hours or days before k ■ -I'.p.nent ot the sk n rash); the strawberry tongue of sSfe er to intense congestion and swelling of the papL with loss o the M" !.-lunn over them); the catarrhal exudate upon the tongue lios ■ ;; ..n„,s of the typhoid patient, which accompan ed by e^'reme Ir ;c>s of the mouth leads to the production of sordes. dry dirtv " -, superficial deposits. Cases are on record of a ves culi' stoS^ "" <^ n^embing ,n its characters those of the highly infectious "ftSt ■•;.; n.,uth disease" of cattle and brought about by i Eg the mUk ,, , „j •'^••'^-tef!, a Vesicular and later ulcerative eruption may be ' "iKT characteristic forms of inflammation of tiie nu.uth are: ri24 THE DifiKsrnK system mi Hii Thruah.- This is a form of sproadiiif; iiu'inhriuious stomatitis, be| iiing on the toiiKiU' and imic-osa of the cheeks, foumi in infants i greatly (lebilitat(li-white, thin, rounded plaques sianding out against reddened mucosa of the cheeks, lips, tongue and bases of the gums I not on the gums themselves. These would seem to l)e of the nat of a fibrinous exudate. This condition is most common in poc nourished children at teething and after acute and weakening disea (bronchopneumonia, whooping cough, etc.), but also may occur pregnant women and in men after exhausting disease. UlceratiTe stomatitis shows itself most characteristically in the ja and around the teeth. The gums become (edematous and spon, easily bleeding and breaking down. With this the teeth are apt become loosened. The jaw bone may be exposed and undergo necrc and the ulcerative process become very extensive. The condit is met with in scurvy, as also after poisoning with phosphorus, If and copper. With phosi)horus the liability to necrosis of the jaw b( is very pronounced. Noma or gangrenous stomatitis is a very acute and fatal conditi beginning usually on the cheek and rapidly spreatat is the tongue, and here most fre pi( al epithelial tumor from this region is the epithelioma, or squamous 't ll.d cancer (p. 209). Such epithelioma may affect the lips and the toii-ne, more rarely the gums. The characteristics of these epithelial tiiiiiors are the formation of well-marked cell nests, with extensive sM|)( rficiai ulceration and the relatively rapid involvement of the lymph ikhIcs at the base of the tongue and in the neck. Kpithelioma may also arise from the upper portion of the pharvnx i'lMl occasionally from the lower portion above the larvngeal opening, 111 which ('ase the epithelial origin is from the sinus pyriformis. This toriii IS difficult to distinguish from primary cancer of the larynx. Kaiiliiiann lays down that while laryngeal cancer is for long unaccom- li'inic.l by any secondary growths in the cervical lymph nodes, pharj'n- ^'cal ( aiicer is apt to be accompanied by a relativeh ormous infiltra- tion ot these nodes. Teratomas are occasionally encountered growing from the pharynx epignathus, p. Go), or from the palate. Occasionallv within \he t'li-iic substance posteriorly may be cysts developed from' the primitive tiiv n,i; ,,ssal (l„ct or from an aberrant process of the same, the so-called ix'clMlalek s glands." These cysts may be lined bv a ciliated epi- tiic -ii.n. Other eysts may occur in the ducts of the salivary and •'"I "MS glands through obstruction and retention of their secretion. 1 II M,-called ranula occurs in the neighborhood of the frenulum, and is ■^ils: flbroo chondromM, UpomM, angiomas, and. its alreae overgrow of both the tonsils and the general submucous tissue of the pharvr Very similar overgrowth may be encountered in the preleukemic aleukemic conditions, while, further, lymphosarcoma may show its, primarily in the tonsils, and then is apt to be rapidly infilt-atir .Such growths are very vascular, easily break down, and lead to gangr. i and liemorrhage. THE TEETH A few words should liere be given regarding diseased conditions ( the teeth which the ordinary medical man is apt to neglect, althoue we are coming to realize that they are of material influence upon th general health. ' Caries.— Caries is the commonest of these disturbances. Tli I)rocess is due to a progressive decalcification and destruction of tli substance of the tooth. It is brought about by the agency of micr. organisms which, producing acids, dissolve out the calcium salts. Thes bacteria gain entrance through erosions of the enamel and grow alon the canals of the dentine. While this is the case, it has to be recognize, that the tooth is not wholly inert matter, and that its power of resist ance to this microbic invasion varies greatly. French writers, mor particularly of late, have called attention to the fact that during preg nancy, and in the early stage of tuberculosis, there is a distinct lower ing of the general calcium content of the organism and coincidently ; marked liability for the rapid supervention of dental caries. Pulpitis.— Simple caries is unassociated with pain, but where it i; present microorganisms have penetrated along the dentine canals v. the pulp and there set up an acute inflammation that is intensely pair: ful. Ihe exudate may be of suppurative type and so form an absct -, THE TEETH 527 (IrstroyiriK the pulp atui extending to the root of the tooth and so to thf alveolus, inducing aii alveolar periostitis; or again the pulp cavity remaining closed, the abscess may niaki- its way (I) through the hone of .ither jaw, usually on the outer aspect, and here either discharge Its." f or undergo absorption; or (2) abscess of the upper jaw, notably of the cannie teeth, may extend upward and set up acute inflammation (if the antrum of Ilighniore. Pyorrhe* AlveoUria.-Tiiis is a form of I(»w suppurative alveolar |..ri„stitis, origniatnig, it would seem, not from the root of the tooth l)iit at the angle between the gums and the teeth and graduallv working .Imvnward. loosemng and lea.ling to the falling out of tooth after tooth 'li.e condition is in general painless, and apt to escape notice, save on .Namination. This condition has come in for increaseikIi pyorrhea is said to be often preceded by tartar of the tMth 1 his IS a very common affection and easily set up if the mouth be not wa>he,l out after meals. Portions of food, cell debris, etc., collecting in the angle between the tooth and the gum become the seat of growth '•t hptothrix and other bacterial forms, and, as noted on page 315 •iileanous salts are apt to be deposited in the broken-down materiaj >.. that a calcified layer of extraneous matter coats the lower part of f le tooth. If left, as the epithelial scales are given off from the surface "I the Kuin and are prevented from being swept awav by the calcified ""Her above, these dead cells in their turn become the seat of a cal- ••..'.oMs deposit, and so the tartar appears gradually to push its way 'Inn Mward sei)arating the tooth from the gum. Tumors of the Teeth.-The development of the tooth as a differ- ' HtiMte.l portion of the epithelium of the jaw is a complicated j)rocess .{irint»- from noriiiiil <>;• anr sorv touth s or niispliu-»'rtioiis of sucl) k.tiiis. Tli.s,- cists, lii fd hv an v\ limn, nro most ofton iiiiilociilnr, l>iit ma\ Ir- multilocular, aixi tluv ••oiitaii! r(irits of tt-rth. Root cysts arc the result (»f periostitis of the nM>t. Tht miiltiloci'Iar cysts are thin walUil, cansitig absorption ot the of the jaw with ^reat swelling of the same. u i^ hi SAUVART GLANDS. Inflammation. - The most important (ondition i': associii with the salivary Klaiuls is angina ludovici (eynanche). This very acute inflammation <.f the floor of the mo'ntii and of the u portion of the neck, which is supposed hy many authorities to c)rif,'i from the suhmaxillary fjland. It is a rapidly extending infiltra! the surroundiii); tissues tending to suppuration :ind i.'anRrene, an IS liable to end in a general baoteriemia or fatal (ed( i.ia of the glo Mumpa or epidemic parotitis is a highly infection^ condition chara( ized by pronounced enlargement of (me or both parotid glands aecomi)anied by a mrolerate grade of fever and general disturba That the infection is not merely local and confined to the paroti shown by the frequent coincident orchitis in the male and by an inH ruation of the ovaries or mamma' in the feni, > . The disease n particularly affects the male sex before the age u 'wenty, and the parotid is apt to be more involved than the right. Tuberculosis and other specific inflammations of the salivary gla are relatively rare. Concrements (sialoliths forming in the di of the salivary glands are occasionally encountered. These re: from catarrh with obstruction. Progressive Changes.—Tumors, more particularly of the parotid, fc a complicated series of growths, nor can it be said that the exact relati ship of the series has been fully established. Occasionally we encoui pure adenomas and j)ure adenocarcinomas; more frequently then an admixture of cell groups of very different types, what appear be epithelial elements intermixed with fibrous, cartilaginous, or m actively .sarcomatous developments. As a rule, these mi \ed tumors gr slowly, and while they arc apt to spread locally, despite their maligiii appearance they show little tendency to recur upoi. removal. M particularly li.ese tumors are apt to show cells of the connective-tis: type, or sarcomatous, in definite relationship to the vessels of the py the so-called i)erivascular endotheliomas or peritheliomas (p. I'^l'). where the outer mas.ses of cells undergo hyaline degeneration (cyl dromas (p. 28.S). It is often difficult to come "to a determination wh. rl the alveolar masses of cells of these mixed tumors are of cpitii.I or endotheiiai origin. We are inclined to state that no satisfact' or generall\- accepted explanation has been afforded for the frequen mm mmims&::im. w^m' 77/A (KSOI'H.UilS r..'9 (.f ih.-o niixt.l Krowths of th |mrti«'iilar n-^'um. Tumors of thr same orl.r. thoupli rare. Iiavt- l>< (Ij-mtIIkhI in uss.K-iation with iIh> sub- in;i\illary ^'laml. on oi the bone THE OBSOPHAGUS .\otwitl,>tan«nn>; its ex|M.s«^l <-onrtaiiee. Hen eertain anatomical data may be recalled. Averaging L»." em. or 10 inches in ieuKth in the adult, the (esophageal tube is pressed ii|M)n a httir 1.1 low Its origin b\ the cricoid cartilage, then s em. below its (in-iii l.y the left bronchus which crosses it, and shortiv before its ttrimiiMiion m the stomach it passes through and is apt to be" compressed li> the diaphragm. It is at these |M)ints ol relative narrowing that irritant matter taken with the f I is apt to suffer relative arrest and tli.M', therefore, are the sites of election for morbid .states. In the Mi'lMT portion the muscle is striated, in its lower plain ami involuntary. A« throughout the «ligestive tract this muscle is arranged in an outer "iidiiiid and inner circular layer. There is also a well-developed nil ■1. iris miicosie The mucosa is formed of a s(iuamous epithelium *'M , . asional mucous glands. It, some J,') per cent, of normal indi- !.ii-i> small islands of cyliidrii j-celled epithelium are encountered ii|«per half of the a»s. ),-.;; it ;.'!!- {)„ section, these eloselv resemble tli< -a-tric mi cosa, and lu^ ■ be regarded as such by simie a'nthorities. Nhndde has pointed out, however, that the originally cvlinder-celled t|iithriiimi of the foregut gives rise to various orders of epithelium, iiiiil il : t III these islands it has proceeded to develop into a cvlinder- "II' 'Mdification rather than mto a sipiamousHclled; these "are not ;m~i riji-n'sts in the proi)er sense of the term. Malformations.— These are uncommon. There mav he complete absence agenesia) or in part the tube may be representwl by a fibrous '"r.l the ,,-ran thus forming a bliml sac. Oceasionallv there is '"""'•'meat with the trachea. Partial or complete duplication has '•' ! r, ,,,r(l,.d, I, dized narrowing or stenosis, and the presence of a i"l" ■ i diaphra;, i, causing occlusion. It must be remembered that till r, i.iratory system originates as a respiratory diverticula. 530 THE DIGEiiTlVE SYSTEM ■I !:! Acquired Malformations.— Occasionally in hysterical individuals and nervous states contracture of a portion of the oesophagus is brought about by muscular spasm. Whether from such continued spasm, or trom acquired stenosis (by pressure from without, by new growth in the wall, or by cicatricial contraction after an inflammatorv process), the portion above the site of narrowing undergoes dilatat'ion. This dilatation is sometimes enormous. Idiopathic dilatation has also bren observed. A similar condition has been produced experimentally in the dog by cutting both cervical vagi. In addition to this generalized dilatation we recognize also local dilatations or diverticula. These are of two orders, the so-called pressure and traction diverticula. The latter are not uncommon, their usual site being on the anterior wall just below the bifurcation of the trachea. They are dearly associated with tubervulosis and other inflammatory disturbances of the group of lymph nodes situated in the angle between the two bronchi. As a result of this inflammation the tissue around the nodes is involved and fibrous bands or adhesions are developed between the nodes and the a'sophageal wall. As a result with each peristaltic act, in swallowing, the oesophagus is pulled upon at this point and gradually a small expansion or saccule becomes developed. Tlu- pressure diverticula are rarer. These occur at or in the neigh- borhood ..t the middle line on the posterior aspect of the oesophagus close to Its origui. At this jioini the muscle wall is at its weakest. The usual teaching is that through the pressure of a large bolus of food the mucous coat becomes pressed outward through a defect in the muscle wall and soon a small amount of the ingested food or fluid collects in the lower portion of such an expansion, so that with the successive acts ot swallowing the divcrticnlum gives way more and more; more and niorc foodstutt' c(.llects in the lower portion of the saccule thus tormed, until gradually from the weight of this food and the irritation and weakening of the wall of the sac prcKluced bv the same, there is developed an clongat.'d, blind sac, ( vtending downward on one or other side in front of the vertebnd column, it may be for .-everal inches and even into the thorax. Isually no muscle fibres are found in the walls of this sac. In this connection we may iioic rertain other acquired conditions. Rupture is rare. Perforation may occur from swallowe«l bone, etc., IVoin eroMon, from syphilitic and cancerous ulcers, at the base of tri..ti.,n diverticula, by i)rcssiire of retained foreign bodies, or by extension of inflammatory conditions from without (caseous tuberculous glands, aneurysm, etc.). Post mortem st.ftcning and riii)turc may be brought about h\ the action of the acid gastric juice. This may occur where there is rela- tively sufidcn death, with full digestion. \ery rarelv mav this dig( stion occur intra vitam, with the production of ulcers at the lower end of the oesophagus of the same ord.r as the i)e|)tic ulcers to be describe.! k.ter. Tim (EmriiAars 531 Circul.tory l»mrbu,c...-Of these the ii,a,t iiote«„rthv an, the tr,.;.tly .hstended v.r,c,,« submueou, vein, of the lo." eS-emTtv J tl„. ,.rsan, y„ ,„ eonditi™, of obstruction of the poLdrcSon ml, ,, x.e,.ll,v, ,„ ca«.s of portal eirrhosis of the li%cr Thev™^ Ze -;.»iv,. pharynge^rdiSrSlTixl' inXnX Xi"r«rr °""' . an.ls. etc. These may lead in the milder cases to an ISe dtram ",^Z"nri,„^'r:-;;S7„"„t?" -■""■;'•• ■"""" '^- Tl,. f ^^v """"iiT'O''; «) also are aarconiM q«tl,,.|i,„i, of the o^r f^e^ r """'""""S '"■" the »quam„, , "f t ' r nobt? ff ''■^'''' ■"''' f *"™"'- '""•^ d«^-l«P. namely, or^ ^^^•^^^^Zk^:^r:Z^:^y:^7'^ "°^^^: J^^^ 'tatistic/from r-Tion i. in' Xed Oifrln^ ^'- ''"'''7 ^''^ ^'^'^^^ o"*- «r other - 'Ii- -M..S c m n..„ it. K /""P'"''"" '"'■^'■^ *^« ""'^'"^ region (■\t(l!.M., then i thcv H;it'i, llic V thii! IPW 5:i2 rilH DlflKSTIVE SYSTK.Xf astinuni .,r thoracic cavity. Tl.n.iiKh infiltration u,,wanl and down- ward tlie growth may extend a considerable distance. Softer adeno- (■arcniomatoiis growths, on tlie other hand, form lar^e n.asses projecting into and blocking the a'sophajjiis. The bronchia! nodes are especially liable to l)e the seat of s(>condary growths; metastases at a distan(-e are relatively uncommon. By direct infiltration the trachea lungs or vertebra- may be involved. It will be nnde.-stood that through the passage of food over the ulcerating surface, gangrenous conditions extending into the neighborhood are liable to supervene If. } V THE STOMACH The stomach is of the nature of a pronoi.n.i ' dilatation in the course of the alimentary tube. This tube in early fcrtal stages has a compar- atively direct course in front of the future vertebral column, but, with further growth, that portion which is to be the stomach both increas-s m length so as to ff.rm a loop downward with what is to be the pvlorie end remaining relatively fi.xed, and at the same time undergoes dis- tension and some rotation, so that what had been the posterior aspect comes to corresi)ond with the greater curvature tuniing to the left and lorward. J he wall consists of three main layers. From either side of the vertebral column the perit. iieum i)asses to it to form a mesenterv whose two layers separate to cover it and join again along the lowi-r asix-ct, now forming the great oment im, which passes down and n 'urns to the vertebral column, whence again it is reflected over the transverse colon. Beneath the serous coat is a loose connective subserosa. The muscle layers are well developed, consisting of an outer longitudinal, an inter- mediate, somewhat illxlcfined oblique laver, originating from the former, and a circular layer. At the .listal end of the stoi uich the musci-latiire undergoes a marked increase so as to form a sphinct.r, the pyloric rmg. The mucosa is relatively verv thick, consisting of ,i cyluidri.al-celled cpithcluim with abundant long, glandular invaginn- tioiis. Ihese glands form simple and (.ften in the pvlorie portio- forked tubules, ditrenng in tluir constitution in the cardiac and the py One regions respecti\cl\ . The cardiac region mav present two orders of cells, namely, the nior.' regular cylindrical chief cells. gi\ iiiij origin to a i)epsiii-c()iitaining secretion, and the angular or polvgniKil oxyntic cells, v.ith a more peripheral i)osition. giving origin to the ;.(i/ T on^in J In- t„rmer man fests tl'.' ^nm,a u. 1 et ' I "^ *-'"^t"'\<'''«trnetion, .lilatation of ^'-.tio„ \.UnZT^["l:^,^'^ "," ••''^'•"^'"" "• ''t antops,- the ol>- hyperemia fo lows the r.-i-Pnti,.. /• •? ' "' ^*''*''- Aetive «•; - i. .1.. e^lj ;;,X";i r,',,;:'^;;;;;,';:'" "■•■ *— ^^ f-.v. i„p.„,^. i, ,,.„,;,„,, ,„_.,,, ,„;,„,,^,^,. , .^^_^,^ .^^ ri/l +*. .. 1-.. , ^ Mill ;iM;. ;i I'., Vrin a !,,■. He iiiiili til, ''■-nw t,\,„. „f gastritis, *'" ''''^^''''P'^^'nt ol rrhages arc w,t iiifr. ,„i,., t TIihv mn, k -.i "I'linth. ..riiMs .;. ' • be either (1) minute, '"Hum J,em..rrl,«^^ oozing, from v.-ssels ho small as 534 THE DIGESTIVE SYSTEM ii to ,e invisible to the oye; or (H) solitary, gross and free, leading to great sudden loss of blood and tending to be rapidly fatal. Minute hemor- rhages, ecchymoses. are seen in many different conditions: (o) in hemophilia, passive congestion, acute catarrhal gastritis, where there has been severe vomiting, phosphi r^w and arsenic poisoning, condi- tions, that IS, associated with dilated or degenerated states of the capillap-, or (6) they may be the result of a nervous or neurotic dilatation of capillaries as in hysteria and (probably) the gastric hemor- rhsiges of pregnancy, or (c) th.-y may follow the erosive action of caustic substances that have gained entrance in the stomach or (d) they may be secondary to multiple emboli into the gastric arterioles, or throm- hosis of the larger gastric veins. The beginner must be careful not to confuse with these the common condition of apparent hemorrliage along the gastric vessels brought about by post mortem digestion, and due to diffusn.n of hemoglobin and changes occurring in the same. 1 he submucous hemorrhaKe is apt to induce necrosis of the immediately overlying mucosa by cutting off its nutrition. While the gastric juice can exert no influence upon the living cells of the mucosa, dead mucosa is acted on by it; there is In fact no difference between it and the dead animal matter that may bo introduced into the stomach as food. It follows, tlierefore. that the state of multiple hemorrhages tends to gi\e place to t; at of multiple hemorrhagic erosions. We shall describe these more fully under the regressive changes. We would suggest tentatively that wh.'tluT there be developed easily recognizable sub- mucus hemorrhages witli little evidence of erosion, or on the other hand .iif^use oozing with little or no indication of submucous hemorrhage IS pn.hably determiiud by the acidity and activity of the gastric juice. \\ Jien this IS j)owerful, so soon as a small area of the mucosa is of e brought almut by the rupture of a rela- tively la ri;r vein inpassive congestion (most often in cirrhosis the rupture attects not the g.istnc but the lower esophageal veins). Common.r causes are carcinoma and round ulcer. The verv nature of the can- cerous growth determines that where it infiltrates the surface the oiit.r- niost layers are apt to be poorly nourished, to undergo necrosis nnd ulceration. The digestion, therefore, of the necrosed matter is apt lo expose some ({..p vessel, weaken its wall and favor hemorrhage, in the i)eptic ulcer there is a similar process of necrosis, ulceration, i id exposure of a deep vessel (see p. o.'JG). Blood discharged into the stomach and mi.xed with gastric hure takes on rapidly a brownish coffee-ground appearance owing to tlie action of the acirl iii)on its hemoglobin. EmboUsm and thrombosis, as already indicated, may involv. the gastric vcsmIs; we y^hall take up their effects in di.scuss'ing the ]<• Dtic ulcer. THE STOMACH 535 Inflammation.- Acute Oastoitis.-The historical studies of Beaumont .m lu. toinach of Alexis St Martin have taught us how easilv ern^of ^.tHHluee inflammatory changes i„ the gastric nmcosa. an o3ose . alcohol bringing about acute hyperemia and even the development ot a vcsicuilar eruption, with discharge of greatly increased amoSrof nnuus. Acute catarrhal gastritis is characterized more particularly by t s pouring out of abundant mucus from the goblet cells, along lith ..tlur inodihcations in the composition of the gastric juice notlb v ...nnution of the hydrochloric acid. The mucous membrane is lK!'r.t'.''rrh.d".-lf!"^'' "^^ TY™"^^^" "-t«Io«i^-«ll.v. i» a.l.lidon to tiK- c.itarrh il infiammation of the mucosa, there is a small-celled infil ''■'' of the submucosa with marked congestion ™^"^^"^ """- Phlegmonous Gastritis -This is a rare and fatal condition character- .".1 l.x the formation of sub:nu<-ous abscesses which, spreading separate iK' mucosa from the underlying tissues. With its necrosis the pufi; ;t; T '"^."/h^ ^tr^^'' --^"^ ™S«^^ ^^^^- develop. Tn To c. s the condition ,s of streptococcal origin and is one manifestation ot the pyemic state; in others it is idiopathic, unassociated wi I abscess o . nation elsewhere. Drunkards show some predisposition to this form I.r^umably as a complication of subacute gastritis Membranous Gastritis.-Membranous gastritis is also rare apt to be .■n|o„„tere,l more particularly in the newborn and young chSen in «Im.„,. ,„,|,rd, true gastric diphtheria has been recorded. Folhcular Gastritis.-As rare or rarer is follicular gastritis with oro- Chronic Gastntis.--Cl,ronic gastritis may be broadly of two forms- > ..rrophic and (2) atrophic. The first of the'se is seen more r':;; ;';e'''.hr''t^'r"^ those sufl^ring from chronic St^S ■u -liMMscs, although It may result also from any chronic irritation 1 1: stiuf dXv'rT'^ ^"'^ ^rv^^-' rLntbirfood • r.-o.M i" h th ki H^ ""' ^v^■^'n^\ digestion. The mucosa is pi'M 'tioo u 7 u'V!'"^'-;'^ •"'^^'^ "«'"'•• ^^''th at times some u u ntat.on. the result of iinperl.ctly absorbed hemorrhages. There ; -i "HH-ous pnxluct,,.,. and discharge, but what is m'ost charac- -H . . wh n t^';;; 'u",;! t ■ ---V;^' ^-nukr appearance of the « .n tiK mxvn. has been washed off or otherwise removal '- - w h "lis;;;: tr -^.^ y-^-i-ti-t thickening of th/slib. '-'■ — I i ns fxt h ; 1^ '"^'V"*?"= ^« infiltration and ,' '"'r.^'^**'«l f^^tween the gland tubules, which are further I'"' 1 -.n s .f sill ^°'»'^*^'-\J?'-f""a^ appearance is ar. to the existence ot suhacute or chronic gastritis. Gastric actmomycosis an.l glanders have heen re..,r.l...l. n.-eration of the ra e sohtao- Mph f..lli..|..s .,f the stomach is one of tlJa.;- .^iLr:^ Regressive Changes.- Of .legeneration pn.per there is little that calls for furth.-r note, save that calcareous deposits have been descrM hange^ that may .,n„lv.« the mucosa an.l the various ulcerative pr..- there uZ '.! P'''*;P""";".^f ^tnt.s w.. have alr.-a.ly inlliiated that m.st,™ -'Krrati.m ot ,nflammat.,ry .,rigin in the st.miach: the 'K "'"■••s ^■.K'o.int.Te.l inthis.>rgan are non-inflammat..rv. lift ; ;' ;V ''"' 7 "" "■''"'" "'•r''*'^^'"!'''' ^"xaminati..n the e"k take« little note ,.f c,nr f i'-nn '': •'•' ''"""'''tt™! no less than six examples in the e t ^•^'l";;'"*'^ ^>7 f'K^-tl'*'- with others that appear to he the fi?i„ ; ^'L! ' '"•■^•^''•>P",V't. In this form there are foun.l from Jn^Tr *^''^V''■ "^'"•^' ^"'"" '"•'■"^ <>«• l'»^s .,f tissue of irregular sluipe and from 1 to o mm. across, most often in the middle zone of the or,nn. I nt at times m..re ,n the canlia.-. at .,th,-rs more in the pvloric n-io„. lhe> have pale, ch-an-cut clg.-s an.l in gcu-ral a sm....th base forine.1 of t le subn.uc.sa ..r at most th.- muscularis. Their abun.la.ur ami small size gne the lining ..f the organ a .l..ci.le.lly moth-eaten ap|..ar- ance \ery rarely do they p.-rforate. In n.me of the cas.-s nn, we recall that there were any sympt..ms calling attention to st..niach THE STOMACH 537 Iroiililc iio li' inatciiK'sis, no rncU'iin Tli«»- k ... i . . ;:" :^,:i'r;.r;;;:;:'Si XrB: ^^"^-^^ ("r «,. i,„v,. i„ Sr „ii.r r ^™ '•"ll-..unes. Dps. INk^ Jv /i 1.1 ^ its activity. Ijeoently onr ot ui,l,.<,.r,.. I •11 • '''"'^t^' ""ve (lemonstratiH ri one ras.. ;i:S:';;;i;; :Se Sc^ ' rn :5t- ''"''""■ r" *"-* »'- -'^ ■n;;. l;.st..an in'tlu-'t^H^^K Im.cor " °" ''' ^"^^"^ "^'"^ -'^• -St^";;;tSi,r h'"""'^ 'T'' "''^'- »'- t'- '^'"-•n« char. 'li« rr .nay I,,- two or tl.R-e nrose n • it ^ » '. u^*?' '''''*"^'' '^"^ ^""'11. is. if w,. niav s exnr^^^^^^^^^^ '^"'^r' ""* «'"' ^■''^" >|..MHk tl.at if V h t . • r l Tr't •I"'-""". ^"'•^- ^^^ ^'^^""t corre- ""i"^' to tlu- hr-t tV.„f -.1 :. • ."I tne ulcors fail to perforate fn i^'Ha^m t o^i" 'f, ^^"'H' *'".'"""« -f the stomach wall, adhesive I. r,.;, 1 ',;;', .^ '^'\ i'P •'•t^-^:^'" the base of the ,.Ic;r and the ■-I l-f .;;;.'' ;;:;'f '•"'"''« \'-"«- I» this case the digest o^ '•>" --toratio.tm.^'^'r"" '■**'•: "«>;'"^V the a.lherent organ. llM Tl til ' ''oration is m.wt ....^ * "" ^ "'". """ """ »<»"t"rent organ. '■" •' ^'"""' ^'''■''^-:^^ t" !»H. cause of this form of ulcer there '" i»lMn.(iant hvnn ." • ^"\''»"«e ot this form of ulcer there i"''"-ciou area tiL ; r'"^' '^"y'^^t' ^^'^^ ** --rresponds ■ irt.Tics \n I • ««i'!iision ot a branch of .*ne of the m :)38 THE niGKSTIVK SYSTEM w iv» Y often in individuals, man nn.l won.an. wl„. sh.m n<. sij;ns of enilmlism elsewhere For th.s reason othvrs hnu- suKKest,,! a local sLstic ,.»? htr u 7'"-''""' -t--.-'' y-t <'thei::seein;tlr;hr'Si^:; LTT •..'■"'"'"* '" ^''' ""'' '""^' "^ the stornach. ocrlnsion 71 the museulans winch occurs after nu-als. The solitary nature of the^ ulcers ,s opposed to causation by irritants-hot fo-nls. etc.- acting from w th.„ the stomach ; such shoul.l set up nn.ltiple lesions. XeSi " iLf'n' rl\ T '^"«" '"••>■ ix-'xii'"'"! the like order of ulcer« in the first part of the .luodenum l.y liKaturins the common bile duct Such hpature does away largely with the '•alkaline tide" in this rein a" favors thus the deleterious eHe<-ts of the aciditv of the eh me Now IS to be noted that there is a close associati<,n between ^ric hpe act.v.ty ar..l he deveh.p.nent of these jK-pti, ulcers, wt are inc ined to lay down he tollo^^i„K as essential factors in the proceL o 'vu- "'"'''^ ' »t'n of the hyperacid gastric. Juice acting ..n a s^lbmlripriVe^ j,ciMric juice l)y mtlammation. (3) A normal, or, preferably-, hyperacid gastric juice It may be askens. According to its concentrrtiou i . „ J ^ '' ''u'' -^'""'V''' ''"'"'"^' "^ ^ •^•^*""«'i«h brown. ( '.r- . i n ZL"-"'"' ^'"'"^ 'r'"'"""^' "^""*' «^'''' Kreyish-white disclor- eoDneV^. r? ^"'^''"'"t^^'- " f''-' '^^-white superficial precipitati..;,, copper sulphate a greenish discoloration tro^hT'"'"* Changes.- \Ve have already -vferred to simple hyp< r- mS\ r"'f '■''T^' '""'•'''•'' *'"^ larger proportion, of so-ca!K,l p oric hypertrophy of later life are not true hypertrophies, are n<^ tliat IS, example's of overgrowth of the main tissue, in this case of ti.e THE STOMACH 639 P.vlori,- musclar rinR. b„t are ,lue to fibrc.i.I hyperplasia either nf Of bemjjii Krowthg, siihnnicous and subserous flhmn... u i ■■»r.mo„,a I,., it, ™£ ' " " '™"" ™* "■»« ">'' '<"- of "• •!'. .HdervU tis ul^s Z " '"T"^'"* i-jfiltration and invasion .n.-. p-r';;?rSr:::^,x^Ssr^heS^-^^^ -« '2Ti,r^ ^''""'T'^ ^f ^ size) of^h^t^r .^:yi;;f ""'■ wkl lar« Ska" r ""r." ^''.^ "^'^"""^ «"«•"' -t'undantiv Simplex; f cSus cLe^^^t^^^^^^^^^ *?, ^"■^S^^^' ^^^ «*^^^^-<"n« «i'l^ litti,. emlen^rfnT !,''*"''''''' S'flall cells, abundnnt stron.a V u. , - ^'^^*'' ''"''"' «'"^**'' '««« "'deration, although > aM> .ievelops, and great tendency to infiltrate. The cau^ ' " ot glauir * I ?n-* 'f'^'"'' ^-- type and le.; " oi glandular relationship, lumen formatmn *.*« ti • -s orin IS niost cmmon in tfe pylori^ regSittginnlng often ' ' , hP?T' ""' "^*""^'"g '"*" the duc^enum butS ^ -li the ualls of the stomach from the pyloric toward the cai^diac will tlii rW ill.; sii; a >■■ o-H) Tin: DiaESTivK system r':- ! in.l,,;i tl ,. i , "„ ""Nm'H.i i-sLhs,,,,, tl,n„n.|, tl„, rtoiimch wall; as only t.. !„• .li.s,.ov..n.. I,v .an itUl tI '"'"'"' "^ sec.ii.larv irn.wtlis is in t ". . '™'-. ^'"" """'""'""'^t site for curvature next tl .. " " ' ,' ""t"' "*""**'*' ''"t'^"'^' *»'« l^-^^r J he m.,st strikmK tile most inij..,rtant seeti..n of the digestive traet Lut s > fo I , ' ' ; ' '■ ■ '/'^ '*"""^'' '•'"'"'""*^'' ""•' 'li««o<-iatingthe m... . CO i"t? e ;\ .•T''"''"*''''- '"-'^ '''"^■^' ^'••"" the stomach, in.l- ..I. ex- See T ' V'"*'""' '' ^''''^''"^>' ^-"'Patible with e<,ntinM,i •Mst.nti. Jiu. „,.n. absorption of foodstuffs occurs in the <..u.ll THK isrKsrtsKs Ml •- "• (-2) tlH. .mil latwto. u 1 "'• "•'"'""'• '^■^""- it P«^«'« "1 ;nf/K ' ""^ '«' impress,.. .«ve JWi^ <«n~j«; MICROCOPY RESOLUTION TEST CHART (ANSI and ISO TEST CHART No 2) 1.0 I.I 1.25 •IT IS 1: 1^ 2.5 2.2 2.0 1.8 ^ .APPLIED IM/1GE Inc g^ 16^3 Las* Mail Sl-eel F.^ Rochester. Ue*> vort 1*609 USA '^S (716) *82 - OiOO - Phone BSg ("6) 288 - "^gsg - fai- wm "IT 542 77/ A' mCESTIVE SYSTEM m -i .ill in the ascending colon undergo inspissation prior to discharge jier annm. In other words, the' cecum and ascencHng coh)n have physio- logically to undergo great variation in the volume of their contents. It would be to the oetriment of their function were they to be acutely susceptible to pressure changes, were they to undergo'peristalsis and void their contents immediately they became filled from the ileum. We must regard them thus as, in the normal state, distinctly unresponsive to pressure eflects. It is the appendix, we hold, that is the hydrostatic agent initialling peristalsis in the large gut. In it we have a narrow tube, \yith no such pronounced ^•a^iations in caliber, so situated that the weight of the column of forming feces is communicated to it, and we presume that when this weight reaches a certain point, the distend- ing force acting upon its walls originates muscular contractions wiiich sj)read directly into the cecum and so initiate the forward movement of their contents. Such a view explains the tendency to constipation in the bedridden, in whom this gravitational influent^ of the contents of the ascending colon can have little effect; it explains the normal tendency to empty the bowels, either shortly after rising and assuming the erect position or after the first meal when stimulating peristalsis of the small bowel has driven extra contents into the cecum and so in- creased the load; it explains the constipation that follows some interval removals of the appendix. At the other end of the colon we have another hydrostatic mechan- ism. In normal health the rectum is empty until immediately preceding the act of defecation. As Hertz has shown that act is brought about by the sensitiveness of the preanal portion of the rectum to internal press- ure, but this sensory mechanism becomes soon exhausted if the pressure continues, if, that is, the call to defecate be not attended to. Once, therefore, the rectum is loaded and not duly emptied it is apt to become overloaded. This rectal constipation with all its attendant ills and miseries is guarded against by the siphon action of the sigmoid flexure. The formed fecal matter does not gradually dribble into the rectum; it gradually accumulates in the descending colon and the proxininl lim!) of the flexure until a column is formed of sufficient length to set up the pressure necessary to surmount the curve and once arounorf pending excessiv,. pmstalsis. He™ »e mav d™l w,th a reSex *t up by ainiormal TOntnils r,f the bowel nr hv „,fll, Ji ■.•n.«ry „i„„,la„., „. ,6) ,he int^ind « a,„'^ C be unt" " tome ID consist of little beyond serous f^u d with shreds of - i»H,v a.,:ctT:,Ti„,''„ih'? per cent of our autopsies. Belonging to the same svstem are occa- sional abdominal cysts representing a persistent intermediate part of the duct, and the condition of persistence of a congested moist columnar epithelium upon the navel, or it may be an actual blind sinus leadinr down froiP ,c- same. More particularly where there is a fibrous band of attachnu.it, the diverticulum may become the cause of internal hernias with strangulation of coils of the intestine. We shall refer later to the acquired diverticula. The api)endix in addition to variation in length mav be abnormally placet!, and infrequently retroperitoneal. Another important condition of congenital origin is congenital hvpcr- trophy of the sigmoid and often of the colon-megacolon (Hirsch- sprung's disease). In this there is noted in the young child a progressive enlargement of the abdomen until it attains huge size, and associated with this there is progressive constipation. On oi)ening the abdomen the sigmoid is found of relativelv enormous size, occupying the greater part of the cavity. There mav or mav not be associated enlargement of the descending c.Jon, or "the colon in general, and with this pronounced hypertrophv of the coats. There lias been much discussion as to the causation. In two well-marked cases seen by us there was an abnormal mesentery of the sigmoid; the lower end ol the descending colon was closely bound down bv the peritoneal attachments, and gave ;.lace to a large, fan-like ineseilterv of the sig- moid proper, with similar binding down of the sigmoid-rectiim junction, a condition favorable to obstruction by kinking when the sigmoid becanie loaded and so to its progressive distension. One of the tuo cases had a similar close binding down at the splenic flexure with corre- sponding dilatation and hypertrophy of the transverse colon. Oth.rs, liowever, deny the e\ idence of this primary and anattmiical (lil\<-t, and p(.ssibly there exists another order of eases in which not potential obstruction but primary atony of the walls is at fault. The third important group of abnormalities is that of the stenoses and atresias. The presence of membranous septa occluding the diio- rt ' ! THE IXTESTIXES 545 of the omphalomL: aic due e rr'";^''"' '". *''^ '•^*^'"" "^ ^'^'t stenoses that can on ^be ex hined nlT "f;'"'' contractures and |H-rit.,nitis. The most freauen sir •' "^t" /'^^«»'t« "^ antenatal onhrs of atresia^^ a nra^^il;;* f ?''' '' ^'""^t't^t^d by the various tlie doacal septu^and tolack J^irnrr;?'"''" ' *" P''^^^'^^^^ o! apposition with this. "^""^ "^ *^^ "^^*"'" *" ^"me into tlu':.:J::l^raSof7^^^^^^^^^ "J^-^ -e^"' *« pass rapidly in review Two orde s of acqu ^ed ^iS;' °™ j*"^, P"-^'!'"" "^ the intestines. tivo; (2) paralytic' The J^rmt^shows Lelf af* " ™""'= ^'-^ °*"*^"^- str-Ktion whether by stenosis I.-nl^n it.elf above any repon of ob- "><.tter and. if orgenerlrde^ilc^;^"^ ^f ' • "'"'^ ^l" ''"'^'^*'"" ^^ ^^^^^^ tlu- latter is seen ^^erito;^t^ f ' '^^«^.""«t«^ ^^ith hypertrophy; ■""nia. etc.); it is evidSv the r!"i"7l' •"^'^.*'""^ ^*>Phoid, pneu^ "Pon the musculat.>re of the bo^eh "^ '"' "'"" '^ ^^^*^"«' *-'"« tl..' .Rifrhhorhood of the amo*!,^ ^7^""'". «"'• there particularly in i'nsn.t themselves at theTpJ ^*''"' '" *'^'" •'*"^«" '"testine hev -'«"-Iy. where the bllsS"l/T*^^* ""'^'^"*'^-^ "^ *'^^ ^^'j- t'"'. "innlar muscle :n:r;,,^:i„"Sdrtren;' '^"r'*"*; ^-''.""^'^ '•"-ircle thcKut. Thev thuscnn«tl^. u ' *V ^T"*^^^ *^'^'"Jes to t.ric attachment; the'" ma" be muU ni Z themselves at the mesen- "f tlu. colon. Thev ocTur n the wf I "'•'' '•""'''"' ^'^ diverticula tl'f longitudinal nnusc e and and mav r'""' "itermediate between "'■ tl"- nature of small hernias of T "'"^ numerous. They are , I,, fibres have HttL Z i^"? """""'^ ''*^tween the circular ^'f tl... sero :: ¥1 ev occu wheTlf '1 *''t 7'''' ^"* ^" -*" -^t •■"Hs of c-hronic crstinTn„ . f '"^'P' ''^ *'"' '""^^'e i« favored, in tlK' suhscrunat te * ?II 'k" "" ' ^"^^ "-^P"' disappearance of '"■'•'"•.(. the sea? ofr^r .-'"''T' ^'^^J^encl. Occasionally these -ll^linHilraJht "'«^""«*»«" (diverticulitis) with excessive smaT eitl°l^lc 1.;;;* sL^!7 '' --^ 'T "^ '"*^^*"- "P- -tself mav affect t" tn:,.;irp Teir^^^ •"*^^*"-- It '-''-^ naturallv -■^u: bvTsr^nL'r '"'J^'* ^''•""*' '-^-^^'^y —• -ther -"--ns a,u l™f„ he^e?..^^^^^^^^^^^^^ " hernial sac. or between ■'>" thrse rases the Z2erL^Z ''^'''^''' ''' ^> invagination. In '''•■■''-'•"rsaprogrrs fvelv nZr ^"'"P^^^^'^^ before the arteries and st.^f'r'l^.^^i'^J^*^^^^ is brought about bv irregular peri ' ^;. n,ore accurately, .ncoordinat.on between the contractions 5 in THE DIGESTIVE SYSTEM :ri . tii-...^.- of the longitudinal and circular muscles, whereby a part of the e above IS either projected into the segment immediately below or caught by that lower segment in its contraction. As k result on caught within, the peristaltic contraction propels it downward iu«t If It were a fecal mass within the lumen. In this way long segmer of the bowel may become invaginated within the portion of bow below and may indeed appear at and be projected through the ami It will be realized that the attached mesentery likewise becomes invagii ated, with compression of its vessels, congestion and liability to gan rene. Inflammatory adhesions are apt to form at tli. reactive upp; end of the invagination and thus the gangrenous intussusception mav n off without there being escape of feces at the line of junction In 'sue cases a zone of stenosis in the shortened bowel mav he the outcome ( the process. In other cases, unless operated upon, the obstruction an to.xemia may lead to death, or there may be peritonitis from perforatioi Ihese invaginations may involve the ileum done (ileal), or, at th valve, the ileum may become invaginated into die cecum (ileocecal) i which case the cecum and appendix may also be carried forward' t form part of the intussusception; may be colic, affecting the colon alont or colicorecta , the colon becoming invaginated within the rectum ^ Ihis irregular peristalsis occurs most often in young children, an( in them therefore invagination is most frenuentiv encountered As i curiosity we may encounter one invaginatioi, setting up a second invag mation below, and so presenting not three but five coats; or, again through reverse peristalsis the invagination may occur in an upwarr direction. ' Such reverse invagination is most frequently seen in the conditior of agonal invagination. Often at autopsies, more particularly upon children, small invaginations of the small intestine present themselves, evidently due to irregular peristalsis during the death agony or in the hour or two immediately succeeding death. They differ from the other cases 111 their tendency to be multiple (three or more), in their small size, in the absence of any signs of inflammation of the serosa, and in the ease with which they can be reduced. Circulatory Disturbances.— The great vascularity of the intestinal mucosa renders it apt to roact in a very pronounced manner to altered circulatory states; it shows extreme pallor in cases of general anemia, intense acute hyraremia in inflammatory states, and even more marked engorgement and purplish coloration in conditions of passive livpcr- emia, such as follow partial or complete obstruction of the p.irtal vein or its mesenteric l)ranclies, or obstructive cardiac disease. In this passive congestion the subserous veins stand out prominenth ; the muco.sa assumes a bluish-purple color, is swollen and succulent through cedematous transudi-tion, and, as already noted in connection witli the stomach, if the condition is of some duration there are evidenc.-^ of a secondary and accoi..panying low inflammatorv state. THE INTESTINES 547 "Irralion (typhoid. d3ier ™°f ™"'7. ">«lie"Mt growths, .»n„B to .lissoc-iation of the hemoXbin .^7 •■ bowel becomes tarry li<.lr.«..., of the feee,. ThereTav ti-f ."" ^' ^'Ph-WW tf ■» «Mher from the'tSch „t' S "." ICh b* °' """" iiiiKcale* hv the natural fnl,>r,,f+i, t ""*""^^' ^"icn becomes so >..v -lelicate Uo^.^'^^S'l^^^gt^^^^r *^ '^ — ^--ble. save ^^^ST:f^,^'^:^^ -tensive serial anastomosis of the tion where an important Cnch of S^ 1 'T <^o\\&teT^\ drcula- "" ''"'"'lus or otherv^se obliter« L"*'''i ^"^^'^ ^^^"•"^^ blocked by infant f,,rmation. Si ir^ou^^^^^^^^^ * '"^"'t' ^^^^'^ ^^y be than i„ the large gut tL rSfvS- inches and more according tf^K • ™' '" ^t*^"* f"""™ ""e to fortv •— bloS^r ex'S-d"^^^^^^^^^ *h%«^«^>- that his the intestine. It varies ?n«l ' *^^ "^'^tance of the lesion from oftin.thatelapt\TrelXnre? Tl^^ W"^' ^^^''^ ^^^^'th inijjth „f gut seen from without is of a hin.^i' ^f ^^ f tages the affected presents an intensely crgSed thtS ^'^'^T'^''''*'*"^ «"«P«"i"S I^ater tlu- superficial layers mav h^ t ?^ hemorrhagic mucosa '''-•'•'l-staine°»only Painfu . «"veral factors: (1) Hate of n««; "^ ' "^ *° ^''^ interaction of ^ '■''>: '-'^ to the suDerficLl n ^ f congestion of the rectal and ana ^;' ."- "'-eased rnSnTf1heT"*1 ""^'T '' *^^ -«' -'" «t^""nn« at stool and (4 b e,-,^„l T'' '."'^"'^ ^^ the act o ;:»'I'<^-tr of the distended vess?/^w!/^^^^ obstruction to the "" "-action of the spJinc ter anT Th "'*l "^T *^" ^'"bsequent '""^'' ■ " less complete circle of nrnLr '''"^* ''the prod ^.j^^^^^ I circle of projectmg varicose vessels at the anal 548 THE DIG EST I VK SYST f ring, external to the sphincter, whic-li are apt to In- irritated and chhI by the passage of hard feeal matter, which may undergo rupture and iiuhiee severe hemorrhage, or from which, again, there mav mere he oozmgof blood; or, lastly, the contained blood may undergo throi bosis, and some organization. Peptic and Necrotic Ulcers.- True peptic ulcers are now well reco nized by surgeons as by pathologists as occurring frequently in the fir part of the duodenum. Ulcers of similar nature, producetl by dige tion of small areas of necrosed mucosa are rare in the small intestiii although they may occur, at times due to infarction of the area suppli( by a terminal arteriole, or thrombosis of a small mesenteric vin. Via. 240 if; , r,i Section through a 8.„„ll simple neorotif ul. r of ilcim, involving only the mucosa; «, Ucl«r. kiihnian follicles; b, congested vessels of subniucosa. faflammation.— DiHcrent names are given to inflammatorv dis turbances accordmg to the region affected— duodenitis, enteritis (of tlit small bowel), appendicitis, typhlitis or cecitis (of the cecum), coUtis proctitis (of the rectum). Owing to post mortem digestion of the superficial layers it is bv nc means easy to gain satisfactory histological pictures'of the various forms of inflammation involving especially the mucosa. There may have been all the clinical evidences of an acute enteritis, but very little may manifest itself on microscopic examination that can siirclv be ascribed to acute inflammation. This is particularly irue of simple or catarrhal enteritis and colitis. If the mucosa be well retained It may show an excessive number of goblet cells. The subimicosa also may present pronounced congestion and extensive 'eukocytic infiltration, but the same hyperemia and leukocytosis are features of certain stages of digestion and some experience is needed to determine whether these exceed the normal limits. Petechial hemorrhages iuggcst an abnormal state, but superficial necroses accouipanying THE IXTESTIXES ^g ;1^^n.edifficu.tto.Hstin.uishfro.„reasof„.oreextensi.ep^ tiK' .ondition mkrhe onZ ' infiltration .,f phle^ml^ frnw h a"ln7""''l"'^' ^ «"P'>"r«tive --I large gut so inucTe.bg^lthatLfs "id ""."'" "^- ^"''j •^'"«» tins „f inflammatory origin or riis it m?J ""* Prominently. Is ti.e lymph Glides which is part an J Tr TJl 7 '^"'«^«^''n*^nt of Ph.sia common in childhoU? When th 5 Ir 'f ^^'' '•''""'""'^ ^^JP^'^- kv a zone of congestioH^^ind ne t„ **^"/'f ^'^^ «^^ surrounded each -iK-n, in addition, the Lniitlr '"««'»'"»t"'-y causation, and IS (iKountercd after adolescence ■iM.I there is evidence of erosion over these small nodes and actual ulcrratioM. the diagnosis becomes still more assured. It is more par- ticularly m the colon that we en- counter such folliculitis in the a'init, while in chil.lren in diph- tHTiaan.l other acute infections IH' solitary foliides in the small "•wel may be so promii-ent that tlH' („n,hti(m must be regarded iis (it inriammatory ty^ tliocarum and colon a. . t''''T"'>:/'"?r"**'^'^^' """^t "^'n in P^'t..i,..s over the ruLLndlr/nr • ?' '''""• '''^'' '"^^^^ "^ in WitI, .leeper extenS of L P^jectrng portions of the mucosa Fia. 241 — \tsr_ Lymphoid hyperplasia of ileum in a child ..,..,,.1 -->^vi.:,iuii VI me necrotic proc< ""^■""•-■...e, extensive ulceration mav ensue THp n~"";v '"^ •"' "'"" «''n m Miercurv and arsenic now!v • J • ^ condition is wdl »«n.iv.. ulceration o thT/a Th n^^r"'^ TT' ""'J' ^"'"^''^^^ ^^ith m-HM k-sicTTn tvn^ST^^^*°*?^**°^-~^yP^'~«» Fever.-Thecom- ^•'i^'- with no recognizable 2n*-'r 1 ™.^^'' ^"^^^^er, encounter '^tl..r. inwhich hesoltan foS^^ '^', '"^^'^^^ ^^'"Ph "odes, •^«v( ,,.„ onecaseiTwLht^ IV *^ ''''''" ^^^^^^ We »ltl-nd, before Heath trn ^ '''''*\'^' "'^"' ^"^ ^^ ^he appendix ^'tcr^h.thp reSu einf ^'"''u*'?", ^^"ber-VVidal reacK S pure cultures of typical typhoid badlli were gained from the 550 THE DIGESTIVE SYSTEM 1^ nor does the severitr^ the eaJ and thlf '" f "'"'^""eously affected, .lefinite relationship to the eitrntf.''' '*"*^ '^P'^" *° ^ave any and adjacent solita^ f«es\^ ot^g^^aSyi^^^^^^ well above the level of the rest of f^r,,,^ ^ swollen, standing' „ut congestion or distinctlv pale and anem.rT'J'!," ^^^''''''."'^ ?™« at the same time but commnnlv fK *," "'^ "'** involved affected and oth rs IrrTmot^exrhiT":;- '" l^' ""'-"^-"^ ^""- possible by the studv oronecTse to follow T '**^''' '* '' ** *'"'«« the earliest is seen to b^ an „tVf« u • ""*"?' '^*«^"«- ^ these of the Peyer's patches Section? l^^T ^''\^ "^°" ™t« «^«"ing rounded by a hCeSc zone a, d'^t''"' 'K '"I'T'^""' f«"'^'«« «"'' with large cellsTtheendot'h^?! * ^"^^^'''^ J^'^Ph spaces filled activelv phagocvtic and mav nnn. • T ("^^^ophages). These are andtheir^emLl^r'inS : Xl^^^^^^^^^^^^^^ \^ «'T'^'- of active proliferation of Ivmphocvtes At „ W * '.^^^^ toberendereclanemicTdpaTe '' ^''''"^ ^'^^ *'"'' ^^"^ ^^ day5:-t';ols''SL^tr ''""* *''^.*^•^'^*^ *« *h« "'-t-^h phSes" sh^ :y^o7"d^g: raTo^nrdt^^^ Z'i^if ^' "'"-- tTtrttr^fTnti^nr 4^^^^^^^ the stretche? oveSn^ Ic"?/^ Se'd ^"--«'\-hich i'nvolves with fecal Diement .rS K^ • J . u ^^^^"^ """^^s ^^come staine- - the lymph n«le but a J the 's,^„^„3^ "i^*^" "»' "<" ■»*" 'y .ff«e,, by ti,e nee Jra^&t P^:' °' """"""'" "- -" »om:whrral/'^"^',^!;"t.t'™i:5V'*''>--:'^^ floor, and n„„ the mSxHrmTmbr.?e "* ''°''" '»'* """""^ «° «l>« with a smooth shiny l"™" of erthX,; "«^r""."8' «»;?'» that floor tion tissue produced, aS Httr. r ,,' k '"" " ^"^ "«"' 8»a"la- death ooeu,? . few Intis ater 5| thattSr' contraction. Where small OV.I .re. where the wTis'l'hfa'ner'2n'"n„™* °'" " ' """"■ of The ofdret.'rf XSd Sr™"';*'^*''- "■« -»"*«»" that c«es are not LfZ^ent ^^«hS7h '" u' ^"'r «'' "^P<"" 'ourth week or later, Z^L'^^^^IT^'t^-^^J^t THE tSTBSTINES 653 Peyer's patches at the end of t first .veek. Progressive involvement of lymph nofles explains the long-continued cases; where successive crops of nodes are affectwl at intervals we obtain rcUpMt. Similar necroses are liable to occur in the mcsenter' lymph ncMles; the lymph mxle situated in the ileocecal angle is coni! jividual lymph nodes, there is not the same strong tendency to iinu, ite primarily the nodes immedi- ately above the ileocecal valve, and, what is more, in the subsequent st:'Kes the process spreads beyond the limits of the nodes and patcl :,, involving all the coats. The infection may be (1) of hematogenous itrigin (acute miliary tuber- culosis; this rarely sets up extensive lesions), or (2) of enterogenous origin, from the bowel contents, or (;i) peritoneal, by infection from the peritoneal fluid secondary to ovarian, tubal or other abdominal tuber- culosis. This last will be discussed later, it is the enterogenous that causes the most characteristic lesions. This may be primary, fmm the fotnl, and then most often set up by the bovine type of baci (milk), or secondary, due to swallowing of sputum where there ex. pulmonary or laryngeal tuberculosis (human type). Sayi ig this, a must be remembered that infection with the bovine type ^lows itself most often not in the intestinal wall b-it in the mesent' -i" nodes. It has been abundantly proved by experiment t • r tht- tube; J. bacilH may be carried through the bowel wall without ..ing up any lesion, only becoming arrested in the mesenteric nodes. The bacilli carried tlirough the mucosa may become arrested in the submucosa, and there most naturally in some lymph node or collection of lymphoid tissue along the course of a lymphatic. Thus there develops a submucous tubercle, and bacilli escaping or carried from this induce the formation of sec- ondary tubercles in the immediate neighborhood. These in their growth iuse and undergo central caseation, cut off the nutrition from, and even invade, the overlying mucosa, and necrosis and ulceration is the result. The subsequent stages are those of progressive extension of the lesion; new tubercles form especially along the course of the lym- phatics and as these lymphatics, like the blood vessels, hav^ a circular disposition, the tubercle formation and ulceration is peculiarly apt to r.c. 554 m\ I h: 1 THE DIGESTIVE SYSTEM be most marked in a trunsNerse .lirectio... often becominR completely annular Other yraphatics penetrate the mnscularis and tE S taneonsly tubercles become formed on the serous aspect of the 1 Thee groups ol subserous tubercles are tiie first indication of the con.lit.on upon uispectinj; the opened abdomen Fio. 1J44 TuberculDiia ulceration of the (McCjiII Pnlh Mu».) FlQ. 245 Syphilitic piTiproctitis. Portion -f thu lower i-n I „f fi,„ , . u K Jnlr 'r*^*'' ''"^ ^' >^'*'^ irregularly swollen bv the presence of under- irreoULir, tornied ot u layer of tubercles or of these THE INTESTIXES alternating with caseating areas. This caseation and ulceration may extend into the muscularis, which forms no natural boundarj*. Where this extension is marked, there also is well-defined subserous tubercu- losis, and, secondary to this, a notable tendency to the formation of local adhesions. Those explain why in intestinal tuberculosis per- foration and perforative peritonitis are comparatively rare, while the formation of fistulous communications between various segments of the bowel is comparatively frequent. We have encountered half a dozen of these in a single case. The disease is apt to be chronic and, what is more, to show healing, fibrosis, and contraction in one area, while in the immediate neighborhood new tubercles may be forming. The largest of these annular ulcers are to be met with in the caecum and colon. Tuberculous ulceration involving the mucosal pouches formed by the contraction of the sphincter ani, leads to one form of fistula in ano. Syphilis. — Save in connection with the rectum (and the character- istic lesions there are now coming, by some at least, to be regarded as doubtfully of syphilitic origin), acquired syphilis rarely affects the intestinal tract. A form of lesion is described as affecting more par- ticularly the jejunum, in the form of groups of small nodes arranged in a circular manner in the submucosa which, under the microscope, presents vessels with characteristic perivascular small-celled infiltra- tion. The mucosa over these is apt to ulcerate, leading to transversely (lis|)osed, somewhat shallow ulcers with uneven pale floors. What until recently was held to be a syphilitic proctitis and peri- I)roctitis is a remarkable condition of venereal origin, presenting a combination of ulceration and irregular hyperplasia of the rectal mucosa through the greater part of its course, with fistula formation and the production of periproctal abscesses. Sections show a pro- nounced plasma cell infiltration throughout, without the small-celled ptTi\ascular infiltration so common in syphilis being a leading feature. The intestines are more frequently found infected in congenital syphilis. The commonest form is a diffuse small-celled perivascular infiltration of the submucosa and muscular coats, but the development of scattered guniiuas has also been recorded and, more frequently, of multiple miliary gummas of the submucosa and muscularis, closely allied, we may suggest, to the first form. Appendicitis. — All the aspects of appendici*^'s are now-a-days treated in such full detail in the text-books of surgery, and the student is expected to have so thorough a knowledge of the subject thai we find ourselves in a dilemma. To fulfil his needs, to discuss the etiology, classification, histology, and sequels on the same scale as does the surgeon would consume many pages and be out of balance with the treatment here afforded to other important conditions ; to indicate briefly the main data may lay us open to a charge of neglect. Nevertheless as the student gains these data elsewhere the latter is the course we must select. r ;;i .■ih- ailmittinj;; that they are present in a small proportion of children exhii.'^'njr a milder form of catarrhal ai)pendicitis. Briefly all these factors signify imperfect drainage. By analo(;y with what we know regarding the earliest stages of infections involving the lymph nodes in the ileum, namely, typhoid iiiid tuberculosis, we are inclined to the view that bacteria are conveyed into the submucous lymph nodes without there being necessarily any Drcliininary destruction of the surface epithelium. Wherever there is irritation from within the lumen, a sin:,)le catarrh is the first disturbance, with increase in goblet cells, congestion of the sub- nuicosa, and increased passage outward of wandering cells, and tliese cells, we believe, convey the bacteria into the underlying lymph nodes. Thus while hesitating to oppose the masterly studies of Aschoff, we are accustomed to conceive the process as affecting essentially the 1,\ inj)li nodes. It is the active proliferation of the cells in these nodes, iiiid the consetpient swelling with accompanying small-celled infiltration of the siibmucosa and muscularis that in our experience is the dominant feature in acute appendicitis. Further, as a result of the swelling, rather than as a normal condition, sharp angles or pits of the mucosa beconu developed which clearly favor bacterial growth, necrosis, and ulceration t)f the mucosa. This we regard as a second, rather than ns a first stage. The condition apparently may proceed no farther than this and tlun become arrested, with little or no after-affects; or with the great swelling of one or more lymph nodes the overlying nuicosa undergoes nccrosi'- and removal, and with resolution a scar is i>roduced with some (onstriction of the lumen (simple catarrhal appendicitis.) Generally we observe more than this. It is a striking feature of the iipiM-ndix, due possibly to its small size, that once set up, inflammaticm li'iids rapidly to involve all the coats. The limits of the alfected lymph nodes become ill defined, small rouny the fretpiency with which we encounter its after-etlVcts, the so-called clironic appendicitis, seen where the appendix is removed after recurrent attacks, and characterized by diffuse fibrosis involving all the coats, and by the orgaiiizer a more diffuse collection of ',nl ion Hind with admixture of fecal matter The further effects .lepen.l largely upon the position of the ap,K«ndix- Nl.cther It pass down into the true pelvis, or be retroperitoneal «; appendix; iepend upon^he reactive power of the individual- denend also upon the nature of the infecting organism. Thus here m'v be a localized pen-appendical abscess well circumscribecl, a ™ii,^ retropentoneal inflammation, a rliffuse peritonitis, an in ense'tovllj atal before generalized peritonitis shows itself, a pvlephlebSextSTn.t a„ng the veins ot the appendix to the larger mesenttk ^ eins and o Jo Colitis-Colitis may be, as alrea.ly stated, of verv varied orders m.mely, simple catarrhal, follicular, membranou;.. ulcerative am othe ' Certain forms deserve additional notice. Mucous colitis iT^ remarkable condition ,n which from time to time, the indivi.lud pa ses casts o n . !!^{! T'*' "?^"'* ^"*'^^''^' "^ °^"^"«' ^vhich mav be mTnv inches n ength; the con.iition may extend over manv months "nd af"er a enod of quiescence, may recur. It is unaccompanieoweI with paj)iiiar> o\trgrouth oil the remaining mucosa. EntamcebH" are to THE n '-ESTINES 559 Epid:r^c bacillary colitis (dysentery) shows sorrif (iifference accorcling to the strair. oi badlhis that is the causative agent. The more severe type is that found in the tropics and in Japan, due to Shiga's bacillus; this is strongly epidemic. In North America a somewhat milder form is encountered, particularly in inmates of asylums and other institu- tions, and in infants, causing one form of sunmier diarrhiea; this is (hie to the strain isolated h\ Flexner, as well as toallied forms. In these ficcrative colitis, showing multiple, deep ulcers (a) mostly transverae. (McGill Path. Mus ) Fig. 247 Colma polyposii apparently secondary to old inflammation, showing at a an outstanding polyp. (McGill Path. Mus.) l)a(il!ary cases the rectum and .sigmoid are as apt to he involved as are tile upper reaches of the colon. There is intense congestion of the mucosa with .swelling and prominence of the rugse and superficial necrosis of the mucosa leading to the formation of a membrane, and leading also to erosion and ulceration. Tiiese ulcers in the earlj .stage are most apt to be along the ridges of the mucosa, while in severe cases, a purulent infiltration of the submucosa may ensue. The thickening of the submucosa is never so marked as in the amoebic form, nor is the ofiO THE DIGESTIVE SYSTEM bowd wall s«, niarkejily tliickene.l. Both f(,rms of colitis are character •ze. hy .iysentery which may he „f lo„« continuance. ^'^^''^^t"- Heference has already been nia.le to tuberctfous coUtis and to the ma^t charactenstjc form of proctitis, the so-calle,l syphilitic Progressive Changes.- As alrea.ly stated, hypertrophy of the bowel occurs above any region of chronic obstruction Tumors. _-It may he said of the small intestine that primary tumors of any order are .hstmctly infrequent, and of the large intes'tineZ benign tumors, suye napillary growths, are rarely met XeSe Is^ oases are on record of various forms of benign tumors of the intestines' fibroma, bpoma (either subser.>us or submucous), myoma (.litto), he;^- SThe blrtl '*""'• ^^ '"'•^ \^''' *"™°" ''"»J-t ^»to the lumTn ot the bo^^el they may cause either ob-truction or intussusceotion PapUloma.., whose epithelial porti<.n is o; the c.,h„nnar ™re'X ZZ^l ": "T "'•;•" *'"*''" i" *'"'.-^'"''^" '"^^^^t'"*^ «"'! "ft^^n are second y to previous ulceration ami continued inflammation (Fig 241) They trZun^'S w'r:r"T- /^"^ •^^"'" ^^'^^^^^^ immediately around the anipulla of \ater, the duodenum is singularly devoid of tumors. Ut malignant growths, we encounter carcinoma in the dumlenum the small mtest ne; it is more common in the colon, especially at the flexures, and still more common in the rectum. The next mos frtTnent c^me': tti T '"'Y *'; r"''- ^^ ^^""'^ '" «enerLT^he r?c urn comes litth m th;3 order of frequency of incidence. The forms that ?;X' rf S;"l •" ^ '"«•"' -/"-nar-ceHed ad^norinoma forms Lr.i,.^ ^' "t'^ ''■- ""r ^''" •'"^•""nter more infiltrati. , torin.s ies.> adenocarcinomatous in character, with scirrhous tendencies encircling and infiltrating broad areas of the bowel with accompanWng i^lithelioim, '""'"■ " ' "^''"' '" *^" ^"••'' ^^*^'""' ^q"'*™""^ of'^the d?ll"r'. 'T \'lf'''^^''^^ ""'"^■'•ous examples of carcinoma l,nW ; ' "" "^ *''*^ »I'I>e..dix; the form is usually of the smplex or the scirrhous type, and what is very remarkable is that w th a d no'rn^^ ttk'' "<• s.vmptoms. and what is more, little infiltration defined \C , . • "T*""' "/ ^'''''''^ ^'^''' ^'^^^ «™«» «»d well- defined. Wv have here, in short, the paradox of a "benign" carcinoma lllTreof tf ""''" * "'>'^ "" --■— "f the loteriofTle Ileum are ot the same benign type. maT*'n.!"ss on\o ^T'T "\'^' '"*''^'"'^' "^^ "^"«»>- "Iteration, which i fi tr 'ive vn ' •"™*r";/*|'* ""''"'' frequently the growth is of the 1 e.u r • ^ r; "^' ''"^'' '••■ '*' P'-"i*'^tion into the lumen ami bv the coiitract.on of the gut, to stenosis and obstruction. Hemorrhages ' efreauentin"tr"T' '" •; *^\-- ^^ S-t"c cancer. Metasta! s Se IherT' o k fr^'^'r*""™ 'J^^^P^ '™'^^ ^"^^ "" t^'^ perituneum; Ihe hvtr a.so is a frequent seat. Secondary carcinoma of the intestines' THE PERITONEUM 561 is not common; cases are on record in wliich a priniarj- cancer of the -tomacli has been followed by one or more solitary growths along the (durse of the intestine. There may further be infiltration by extension into the rectum of uterine carcinomr.. Primary sarcoma mav occur as a round-celled growth originating u'liuTiilly in the submucosa, and this most frequently in the lower part iif the ileum, though the rectum, cecum, and even the appendix furnish ciiscs. Spindle-celled sarcoma is distindy rare. Lymphosarcoma has the same regional distribution as has the round-celled sarcoma, and l)()ssibly they often fail to be distinguished one from the other. Second- ary sarcomas occur in cases of generalized sarcomatosis; melanotic sarcoma ■ particularly are apt to show themselves in the bowel wall. THE PERITONEUM Were it not for the necessity of peristalsis and motility of the stomach and intestines, the peritoneal cavity might be considered a superfluity. All those organs whose function demands a change of size and positi(m are surrounded by a lubricated cavity in which to work, and of these (•a\ities the peritoneal has by far the largest potential extent and actual surface. We must take it for granted that the student is lainiliar with the anatomy of the peritoneum, the disposition of the liarictal portion, the nature of the mesenteries whereby the viscera I'aiig relatively free within the cavity, and the relationship of these nicsfiiteries to the blood supply, whereby, while the bowel is allowed a large measure of freedom and of variation in calibre, each part is proventcd from escaping beyond a certain f^xed distance from tae origin nf the mesenteric vessels. We must expect that the student is familiar also with the anatomy of the great omentum and its relationship to the stomach and the transverse colon respectively. The great addition to the su])erficies of the lining membrane of the peritoneal cavity afforded by the great omentum has for long attracted notice and numerous hyp j- tlieses have been suggested to explain its action. It is eminently \ascular, its vessels being almost in contact with the contents of the peritoneum, so that if any portion of the omentum finds itself in an area of irritation, there is rapidly excited in it a secondary inflammatory l)n)(ess, and the ease with which it forms adhesions that are temporarily lirotcctive is very remarkable. W'ith so large a free surface as that atl'orded by the peritoneum, it seems necessary to have some such pro- tective organ to produce a rapid exudation of protective bodies; whether absorption occurs through it with the same freedom deserves further -tiuly. The general indications are that foreign particles present in I 111' i)eritoneal cavity make their way with greatest freedom into the I.Mnph spaces of the diaphragm. The peritoneum is constituted by a layer of endothelial cells, ,:.i. h, \\ liile thin, are by no means inert, and rapidly react to any inflammation, 5*12 rHK niCKSTIVE SYSTEM lis \l Iky utuIprKoing swflliiif; and often proliferation. These form a oontinnouf inemhrane honnding the cavity save at two points, viz., the opening' of the FaMoi)ian tul)es, tliroiijjh whieh there is a potential, thoii>;|i rarely actual, comnniiiication with the exterior. So. also, it must Ik reineinLered that o\»-r tlie ovaries the peritoneum becomes modifiid mto a more cubical layer of cells, the germinal epithelium, from which by downiirowths oripnate the ovarian follicles. Heiieath this endo- thelial layer is a subserous layer of loose connective tissue which in certain regions shows a pronounced tendency to undergo metaplasia into fat cells, as in the ap|)endices ej)ii)Ioicie. the mesenteries, and the omentum. Abnormalities.- Of abnormalities, jn-rhaps the one most frequently noticed is a \ ariation in the length of the great omentum, which may vary from a small irregular fringe an inch in length to a nuissive ai)ro"n otten loaded with fat, a foot or more long. Similar variations are at tunes to be noted in the mesenteries, most marked in the case of organs which normally are incompletely surrounded by peritf>neum. but may on occasion be fouii.l to possess mesenteries.' c. «/.. the cecum, anil ascending colon, and even the kidney ("floating kidnev"). We'havc already referrer\es note that +he presence of ov.vrian tumors is fre(]uently accompanied by a noticeable grade of ascites. The exact cause of this is somewhat obscure. On p. ;}(i(i we have already disc.isse.l ascites, and the related i)henoniena. How sensitive are the peritoiical vessels IS well shown when the perit(.neum is seen at operation even )ut a tew minutes after a i)erforation of the bowel; there may bo ittle obvious escape of bow<.| contents, yet the intestinal coils "mav be of the most angry, scarlet color. It will be understood from this tliat capillary subserous hemorrhagea are not uncommon, especiiillv where there has been soin.' toxemia with degeneration of the capillar^ eiuh.thelium. A favorit.- seat for these hemorrhages seems to be the lower anterior half of the parietal peritoneum. Thev are seen oar- ticularly in severely toxic conditions, as well as in the hemorrhagic dis- eases. Of gross hemorrhag.s into the peritoneal cavit\- the commonest and most oxiei.sive is that seen in ruptured tubal gestation, and in traumatic rupture of the liver, spleen, mesentery, and other organs. THE I'ERITHSELM 563 'I'lif ctfects of thrombosis and embolism iip<(n the visccTii are so >jrave that the acconii)ari\ iiij; chaiiKi's in the i«Titoncuni are rdativ«-|v of ininor importance, alth.niKh they are of a like nature, viz., stasis, iKinorrliane, ami neerosis. Inflamznation.- Peritonitis.— Without utternptinj; to make any full cliissifieation of the various aeute inHamm.itions of the peritdneum Irtim a surgical standpoint, it may l)e hiid (h)\vn in tlie first phiee that three t,\ pes are to he distinguished at autopsy: (1 ) local circumscribed, VI) locally diffuse, and Ci) universal. We may find, tliat is, that hy the nipid imxluetion of adhesions and the formation of fibrin an inflamma- tii.n is sharply eircumserihed to the rejjion of primary disturbance. \\V may, for example, find an api)endix bathed in pus which thus lorinsa i)eri-ai)pendical abscess, and through omental adhesions and the (ilirinous adhesions ' "tween surrounding coils of intestine, the rest of the peritoneal caviiy wholly closed off from, and showing no sij,'ns of, th<' iiiHamniatory process. N'ery often, however, we encoiuiter an acute lirritoniti.' of wider extent which fails to imi)licate some, it ma.\- be a <()nsiderable, part of the cavity, and this without the sharp line of dcniarcation l)y adhesions just noted. There may be, it is true, slight I'orniation of fibrin between the coils at the periphery of the area, lint so slijiht as to make it evident that M)nie other factor, such as ^Ta\ ity, is likewise efleetive. This we term a locally diffuse peritonitis. I'cr example, very frecjuently a pelvic i)eritonitis fails to extend into tiie middle area of the peritoneum, or a peritonitis involving the small intestines in general does not art'ect the area oi" the stomach and spleen. Ill the production of such a restricted inflammation, it is true that there iire certain j)hysical factors; thus, an inflammation may be largely restricted to the lesser peritoneal sac, or may be bounded by the meseii- t(T\ or by the great omentum. The universal form is in general of a Mippunitive type, the pus being as abundant immediately beneath the tlijiphragm and around the spleen as in the peK ic cavity. As regards the forms of peritonitis, it may be laid' down that what H true (»f one serous sac is true of another. We meet, that is, serous, serofibrinous, hemorrhagic, and purulent forms, though the purulent forms ;irc relatively more freciuent than in the other serous cavities. It is not safe to imagine that these stand in their order of gravity, for the most (|iii(kly fatal case we have seen, one fatal within twelve hours after iipparentlx- i)erfect health, gave a serous fluid containing a i)ure culture "f strei)tococci, while Bacillus coli infections may yield abundant foul pus and yet undergo complete recovery. What is' particularly notice- id)l«" Ml this relationship is that typhoidal peritonitis is characterized I'v it> .lilliise character, absence of adhesions, and lack of i)us cells; the 'hiiiger of such a diminished reaction as is seen in cases of this nature IK'S Ml the rai)id difl'usi n of the irritant, and generalization of the pruccss. Too few leukocytes exuded with defective fibrin formation on tljc one hand, and too abundant exudation of leukocytes on the other, with rapid digestion of fibrin as it is formed, equally favor a dittuse 564 THE DIGESTIVE SYSTEAf W i : I 4 as distinct from a localized peritonitis. A form of purulent peritoniti; that deserves mention is not infrequently seen followiiijj upon laparot omy, namely, that characterized l»y the presence (»f one or more isolatec pockets of pus between the viscera. This occurs chiefly where draina^t has been employed, the mere act of laparotomy having removed tlit greater part of the pus and thereby having improved the ability of tli« I)eritoneum to form adhesions; the very excellence of these adhesion: prevents certain remote infected areas or ixickets from obtaining frei drainage, and in such pockets multiplication of bacteria with progressive pus formation may go on. Fia. 248 Kxogenous per" lUou of thr lower cnil of the aRcendiQK rolon. The illustration, wiiicli ia natural size, whuvx- wr-ll the i-urious raised and perforatee wall. (Adami.) It is interesting to note how, in generalized peritonitis as in generalized pleurisy, the supi)urative i)rocess rarely extends into the walls of the viscera and induces perforation; it is only where we have these localized areas of su[)purative peritonitis that the presence of the pus upon a soft viscus arresting the nutrition of the walls of that viscus favors tlie production of what may be termed exogenous tilceration and perforation. Ktiolofiy (if Prritnniti.!. — As to the causes of i)eritonitis, these may l)e (1) traiunatlc, from without; (2) enterogenous; (o) from other viscera by extension or by escape of contents, p. g., \n\e and urine; (4) hema- togenous, and (.')) cryptogenous. Of these the commonest are those originating from some portion 77/ A' I'KRITOSFArSt 665 Fio 249 of t!u> howcl, oitluT through rupture or iwrforation or sec-oiidary to intlimimation of the saiiu- without actual rupture. It is u matter of i\ crx -('{|iuiit congestion of the viscera may itself (institute a cause of continuance of the pro- cess that cannot be designated otherwise than fisa chronic peritonitis. Other forms of chnmic peritonitis may be associated with long-con- timied passive congestion leading to a diffuse thickening of the peritoneum. A remarkable and extreme form of this chronic peritonitis is seen in the condition of hyaloserositis, or as it is termed, where it is local affecting par- ticularly the surface of the liver, icing liver. In tliis condition a dense, porcelain-like de- posit of hyaline tissue covers the surface of tlic liver and spleen and is accompanied by a thickciung and contraction of the great omen- tum, leading to the formation of a thick hyaline mass lying along the transverse colon. More rarely the same condition is seen in the ileo- cecal region. Its exact causation is still un- determined, but in a certain proportion of cases it is associated with a very chronic form of tuberculosis, and occasional caseous areas may be detected in the deposit. Coincidently, tlic pleune and pericardium are apt to present a similar condition. Aicouipanyiiig this lesion, there is ascites. Tuberculosis. — This is relatively common, and while at times it is 'Iry, it is generally accompanietl by a low form of serous peritonitis. Broadly two forms may be recognized: one in which the infection of Hyaloaeroaitia of spleen; sec- tion tbrough spleen showing at a sn area of hyal.>sero9itis of cap- sule; h, splenic tissue. (McOill Path. Mus.) :m Til!-: bUlESTlVK SYSTEM J. ,r„„,,,, ,.r „ ,,,,, , i,,„i,i I,, i,„„ , „ ,:.' 1 : t,', J I. I.:..,ll, „v,.r , „. s„rr„„. „r ,l„. |..,i„„„.,„„; ,1 „, i, „ „ , "™ ' ...«.> ,.r. „.s,,„l,l,„B „ |„„„|l,.| »,.,!,., „ I ,„ „„. ,,|,4t, ' ,", , ,"1 : '•t thr s..r..,is surfa(v of neiKl.l..M-in; ..oils of tin- how "',''•""",: '."'^ ChiU ;""" "" ",•''*•■" ''"'■ *" '"'rtal cirrhosis of tlu- liv" Actmomycods.- Actinomycosis is Iial,le to involve the noritonc- -n MVonWary to its presence in the appendix or other r -.i .„ ,. t e " w*. ' It nmy lea. to fistnhe thru„,.h the ah.h.n.inal wall '' iifimi oil ,111(1 iH' iree in tlie r'jivitx- -ic t^l..^- ..i .. T..o..^. rupture of the ^Nhh:!^;;' or ';• i^l.r^Kr t^lf'S Entire! M !?"•'""•■ ^'^'' "'^""•'■^ ^ "'">■ '•'•- the t^^ o c . ;r '■•V'"'">'^'^*"^'""- t'H- fa-tus inav esc.ipe into he h o^on tXs' • 'h '"'^*"7 ^■"''•'«"'^^-" -lithopedion); iJattemp!;; a.xrtion. needles or other instruments ii,a\ perforate the uterine w, II an. -..pe into the unity = while Hurin, laparotom v, Uges a n L^ "H-nts have been ina.Ivertentlv. an.l happily rarelV. ^lit.w^l io r;;„S;, in the cavitv. In perforation ..f the intestines., hesides the |„,u,.| . , , , • - ■-\--' """" "■■ '"'■ iniesiines.. riesides the nMni!,il i;:;;l.;r;::;i;:,;;::':!,'""" '-'> "'■"-••■"'"■> '■'• '■■■ -» i--. Twr '••■»»• TIIF. I'HUITnSErM 507 Fia. 2J0 Regressive Changes. --Uc>Krcssiv«> clumm-s in tlu> iMTitoiicuni are iii((iii>iiuilly \\v ciiciiiiiitt-r lu'crusis with licinorriiiiKt* (if III) iiKliviiiiiiil appniilix i'|)ij)|oi(ii tliri»ii);li torsion of its iHtliincle. Necrosis of the iicritont'Mm ami snhixritoni'al fat oiirhe(l. Progressive Changes. - What MiMie authorities term fibromas, seen nil the surface of the >ple«'n in elder- ly individuals in the form of one or more flattened, tal!o\v-like projec- tions, are not hlastoinatous hut are allied to hyaloserositis. Of the [KTitonenm proper, namely, theen- ijothelial memhrane, there is hut one new growth, the endothelioma, which at times closely resemhies liircinoma in the {inger-like pro- cesses that invaile the underlying ti>sues. From the suljperitoneal tis- -Mcs, a series of connective-tissue tumors may develop, lipoma, lipo- chondroma, lipoma myzomatodes, fibroma, angioma, and sarcoma. Thes<- ire particularly liahle to grow in the root of the mesentery and in the retro- lieritoneal fat; especially in the fat overlying the k'dneys are we liahle tn meet lipomatoid overgrowths and the pnuluction of massive tumors wliich may show tuyxomatons, chondn natous, osteomatous, and sarco- matous areas. Teratomas oirasionally envelop suhperitoneally. Secondary tumors are apt to involve the peritoneum hy extension; tliiis fie j^reat omentum may he the seat of extensive carcinomatous irrinvtl ~ "n cases of carcinoma of the stomach, pi,- reas, gall-bladder, 'ir (lu'is, and where there is colloid cancer of the rectum this sprea but through openings i,] t ^on e t ,n I'T' ""* *'";""«^ *''^ P^^^^tes peritoneal pockets.^ VVe t a, n .k •, I I' T-""7' "^ ^^''"^'«^^' "•• "'to the external, and the latter he i^temll •''''" '"V^^^™ *''« ^^'^^r, oocur in regions of «. "i/ital^^ fl™f ^ ^ Tf'' P'-^t'-"-^''^" •"«>' the inguinal or femora «. the 2 .r . 'I '>'"'"™i"«I wall, as at "l >"to that sar- tlicre coils of the small intt^th e v ^ \ "*""*'''" "* *''« ««^'' viz.. the or other portion .t.twg" , win ""'7'"""' ^"'""^ '''"'' ^PP-««-^ or portion of the stoma W ri^'^T; "'-^'/arely ovary, spleen. enlarges it is apt to expand-, in th ''"'.■'■'' '*'• '^^ *''^ ^»'^ narrow neck w th a more ,''"*'"' ;'"-\*r '^'"'""* ^ ''^''■'t'vclv patency of the sic nv^v n ''!"""""" V^*''"-''''"'""'"^' cavity. This the sac may oc^r ;^:'t;ir/'r^".'r'"''" "^ *'- -"tent o expans.on of the conlJn'; ' rUwelT^he^""*^- ^"^ >''^«"^'' be set up with resultant aclhesi^.n o t ' tr. k' TTl'"" '""•^■ Passmg „, may oppose return It is in tl '■ .•^""' ""^ *''^ t'''*^"^ imminent danirer with s - 1 ' , " " '" ^''^^^^ conditions that there is ofthenec.k:Sur ,eTree*?rrror. *'"' '^'^ ^'^"^*-^'«" mass becomes larger throne' this nl? ?• T' '''"'"'• The hernial more pronounced' L TLl ,Z'T l'""' *''' ^'"'.-triction. therefore, ending in stasis. I .ids to necrts s 'n I •"''"■«™''^^"/ !^ tbe result which and these, whem-ver a • por ^ l^'l '"'T "^ '^''- ''^''•"'«' ^""t"'^^' cerned, eventually bec.>n,c Wt 1 i ,"'' ^""taming feces is con- 1. External HerniaT V » 1 * """' gangrenous. inguinal H^^a rn-;n ttis ;;'';r'"^' '"'"-^ '"« *° ^e recognized: ?cen in woman. It s Z to u.i^^u 0^""'"''"''* ^r'' '"'^ '* ''' *»'- n the region of the ing h, d " ' ' 'Tin'.'"' • "" '''"''"^"' "^ *^^ *'=^«"- inguinal canal itself fobUque i^i^., J ''".\^ '^"T'" "'"•'' P''^^'' ''"^^n the HERKlA~rHE LIVER nm .leveloped what is known as direct inguinal hernia, ..riKinatinR internally o the inner side c.f the internal orifice of the canal hut present^n/hself through the external ring. Either of these forms mLv nw extern .l.nvn the scrotum to form a scrotal hernia. If the hernia \,es no in^Sl iZ' *'" "*^'"'"' ""^ ''^ '^'-^ "•^«* '^ ^"-" - ^-»Ple^ 2. Femoral Hemia.—This is more common in woman, the channel .nng formed along the course of the femoral vessels ^nd so be" w I -'P«rts ligament and along the tipper part of Hunter's canal .Mnl.iKwn; Hemia.-Abdominal contents may protrude through the ihcal ring. This may he congenital hut it is most often seen in the nu Itiparous female; the sac may attain great size. Somewhat smila^ heir* H"* ?^^r"^ ''''"^'•*^^ ""^^' '" '^' ""''"« 'in- i« the abdoSna the resul of a aparotomy in the me.lia„ line. Epigastric abdo^l hernia m the middle line ahove the navel is rare aoaominal 4. Other Forms.-Other forms are also rare, viz., obturator hernia Zal tLtirtri ^•"•r-'"l --««'' *»--«•> tl. s'acroscllulc no™; permeal thro igl the levator am; vaginal, through the giving wav of the uall of Douglas pouch. Diaphragmatic hernia ma v he .lue either t-! ;hCh';^umat!r ^Xr"'^^'"^ "^ *''"'™^= ^^^ -^ ^'->- ^^ ««»--' fiitemal Hernias.-Internai hernias show no protrusion through the ^> ..lonimal parietes; they are relatively infrequent. Through upture .;r imperfect formation of the mesentery oeeasionallv the abdom "J tt fntosn'"' '"''''^''"'Ti -f - J-.-, if not the greater, p7 ion 't the intestine may pass behind some part of the peritoneum- or Vn iowT;;^.^r'"''?^rr^ '^^ ^'"^^•"' through \he foZen S >N nisloH to the filling of the lesser omental sac. The fossa duodenalis .ay further give way ; similarly the subcecal and intersigmo 1 1 "1 ^ay iorm sacs containing hernial masses of the intestine. ^ THE LIVER Simple as is the structure of the liver, there is no organ in the bodv '^^ Inch more various metabolic activities have been j.^tlv attribute, y^reat importance is in.licated by its size (14()0 to ir,(K gram' ) n • I •• ^ ■'^^If.'-«t«>n "f the iron <.f the hemoglobin from the dis ; SSt^ri'n-'d r "r .?'^"7^= *•" ^"^^•''"^*''^ "^ '•- buerits nd i emr t Tv*" ?" "^ *'!" '"^^'•'"" ^"P^^''^' °*" ^^e blood and tissues e''ci culat^l fS •^^^'•r^'^"'^ "^'^ivities: the regulation similarlv, of ■ to .of n^ <■' ""^ f^'Y^^ the same and other lipoids: the for- •'•'t.on of urea. Sjtuai.d at the head of the portal system, which brings 570 THE DIGESTIVE SYSTEM i' to ittlu- various s..l,staiKrs;,l,s„rlH'.l from tin- walls of the intostine the CT acts as a protec-t.ve or^an. arresting an.l excrotin,. or S .^h^ t oxK- f,o- u.flamniatory and deK^nerativ^ processes ^lm•h, m tnue, uiterfere with its prime nu.tah,.lic purpo ^s Crthe ar-reac.lunguuport.„Ke of pathological change in itlstncture '^ 1 ^ rofoun.l general d,sturhau<-es to which .lisease of this vise urn gve S-h f "; 'f 't "'"' """^'"•"''' '"•'•^' ^'"*'''' i"t<' the minute aSomv ^^\wh should he known to every student of histologv \t m,^t L may nra 1 that it is ahun.lantly vascular, so vascular as m hf. lie n contau, the whole Mood supply of the body; that i a a 1 ouble 1„ upply, system.c and arterial through tlu- hepatic artev ta t enous through the portal v, in; that the entering '.ood rS' * he nd.vulua lobules from their periphery to be colk'te,! iutc a m tra mtralobular branch o the hepatic, vein, whic.h carries it to tlu- SS N.-na cava Toutranwise, the bile capillaries pass ou twanl o the periphery o the h.bule. there joining to form the' bile diSs and thus aspect, to a bloc^d capillary or sinusoid and, on another, to a bile canillarv 1 here is, uidee. , evidence that within the individual ive c^H t e e a e fine channels intimately connected with both s^•stems Abnormalities.-The abnormalities of the "liver, as comoared wiH, other organs of the body, are distinctiv few. It mav show consoler "nmcl of in t '''' '""• ■ ''7? «T^ '<">««. i» fjeneral small, or masse , snared ott in the course ot developme. \ mav lie in the neiirhb..r hood of the mam organ, .. g., i„ the suspensor;- ligament or !he m^t omentum. Liebermeister's grooves, cleprc^ssionsVun'rg n the anSro P|.ster,.. direction, while most often acquired, may b'e coi genS i i pc>rt ,.1 • of'ST'l- . '■ ''"''■'" "" '"^'^'"'"^ of the- diaphragmatic musculature, the grooves corre i-nti:";' ^[^I'lrtur ""*'^ "" "" ""'^•' •" ^^'"^'^ *»-- ^as bee,. a.;;^rL^&na.SJ X c St c h : 1 " ••^''•"'"•""'■'ts of the climate. In infective and mcnt of acTue congestion. In temperate zones, passive congestion THE LI V Eli 571 p niufl, more (•<.n.,n....ly .-noounterefl as a result ..f clironit- obstructive heart or hver . hsease. 'H.e orf;an is enlarged, tense, its eu..fJu.d; c. pigment from destroyed red blood corpua- f ?.h /TT'"' ''"'■" ''""' '*" ""' of the drawing lor the sake of clearness. Fia. 254 Later stage of the mmp- a, red blood cor- l>usr|„, which have escaped into the space previously occupied by the liver cells; h. greatly -shrunken and degenerateil liver cells. The :nus„i,i., Miu even more dilated than in the earlier stage. (After Mollory.) Still later stage of the same condition. Here the cells of the mid-.one of the lobule have completely dis«ppeare dyspepsia and anorexia, ascites more freciueiitly than jaundice, ITogressive emaciation anfl weakness, a slight grade "of anemia, a fair ' nliirgenient of the spleen, and death either from intercurrent tubercu- l">is or niflammation of the lungs, or sometimes (esophageal hemorrhage. ."6 THE DIGESTIVE SYSTEM ^2r^ ' '"."I'" "' *^t '"•'""''■ '"^ "'"'P-'i^^^-'l ^-arl V. the liver is foun, Kreatly enlarge.!. I.ut in the c„urse ,.f nu.nths it is at t t.. u Jem Z «ressu-e shnnkage until in a certain pn,,„rtic,n of ... es t is e7y n ud Fio, 257 Flo 2.JS 'mm^- Portal oirrhiisi» of the livpr- n rf' i...„i» j m The cli,ti„,,i„n ^etwee^the •;ffe?;mYb ,'1 rh''" T'" '"'"""'"' """"^^ '" '""*■ "—••"»- lost. (Green ) " ''""'" ""'' ""- ^'"'"""'^ »"»nge.„en,s of the ,eil» i» entirely smaller than normal. AcecrdinK to our experience, in general the liver t .^ e.,u.i,tu.n IS larger and heavier than normal. The main features <>» the or.an at autopsy are the notlular surfac-e (hobnail Uve^rth^ extreme firmness on section, due to the uicreased fibrosis, and usuallv the dis- tmctly yellow color t.f the cut\)rKan. It ras this last feature that primarilv save the luime (^v/uir, yellow) to the condition, althoujih by association we now api)ly this term to any condition of diffusV fibrosis. f)n inspectit.n t.f the cut sur- face the li\er [)arenc-h\nia is seen to be separated ofl' i„t„ small islands or irrcj;- ular lobules by bands of fibrous tissue. I nder the microscope in tvpical casts but irrcLnd-.r b-..,! ( . uf " •'.""•''^tiTi^tic is that the broa-l lese hnds t 'l ''"' ^'''■""' ''"^•'^' '•"'' '^^'^^y ^'^fi"*"^ '"'-..m fo med 2 les 7"';r''-^'"«' ""^ ••».'-^ these islan.ls seen to be wci!- tormtd lobules. On the contrary, individual islands appear to be llcjl)naile,l liver with small hob- nails, natural size. (MeGill Path Mus.) CIRRHOSIS OF THE LIVER 577 turino(l of clusters of several im|)erfect lobules (imperfe<-t because th.ir nuralobular veuis are not, in Kcnerai, central). It is this tortnation tliat gives the additional name of multUobular cinhosis t.. this particular type. Further, the bands present relatively few iiulu seen \n which many of the ncnlules are relativelv large (Figs 259 :'iKt), much larger than hobnails; a study of them shows that here we .l<>.il with a regenerative process. From this simple regeneration we may |)iiss on, particularly in adults, to cirrhosis with multiple adenomatous nodules and cirrhosis with accompanying diffuse carcinomatosis. The cause of thi.s hobnail appearance is obvious; it is the old story III eventual contraction of newly formed connective tissue with resultant lin.jection of the interinediate masses. Fio. 259 Fia. 200 Ilol.iiailiil liver with large huhnails du-; to rcgen- ■ I iiiun of the piironchyraa, naturni siie (.VIcGill l';ith. Mua.) Portion of the same seen on secliuD, As to the cause of "portal" cirrhosis, there has been great debate 1 !.<■ commonest type of alcoholic liver is that of advanced fattv infil- tration In such livers we notice often that the portal sheaths show a small-celled .nfiltration or slight fibrosis. It is presumed that some irritant agent, brought by the portal blood, sets up a low form of irritation around the branches generally, as also that the same irritant . a.ls to .legencration and atrophy of those liver cells which are exposed t- the mam brunt of the toxic agent, that thus there is a coincident I" np-rtal growth ot connective tissue and destruction of the peripheral I 'IN ot the lobules, the resultant irregular breadth of the bands of fibrous i-uc being dependent upon the irregular distribution of the portal ■ranches around the lobules. As to the nature of the irritant, it has ""■n louiKl that alcohol alone administered to the lower animals will not - r up cirrhosis, and that acute atrophy, pure and simple, of liver cells • 'I. as IS produced by chloroform, is followed not by cirrhosis but bv >' |:n.eration from the undestroyed liver cells. Hcktoen, Weaver, and • , jTs have occasional y noted that inoculation of laboratory animals ith certarn strains of B. coli will set up the condition, but this with no o7 f 578 77/A; lilCKSTIVE SYSTEM conPtaiK-y. Recently, Opie has shown tJmt if, after preliminary ncer...s ot the liver cells by means of rlilorof(.rm, the organ he snhjected I infeetion by a nuld strain (.f U. et.li or its toxins, then constantly cirrhotic process is .ley.loped. 'J'his, it is true, is not a i)' re porti cirrhosis, h<-cause chlon.form temls to produce a central rather than pcriplieral ncrosis. Inrh-ed from the similarity of the histoloijici, picture produced thus followinj; ui)on a centrilohular necrosis, to thii seen in the common human multilohular type, it mav he questione whether the loss of Iner parenchyma in the latter is primarily or esseii Fia. 261 ft .scion fro.,, a liver rnlnwd nnd showing .omWnod extreme f,,Uy im., ,.,iu>, :,ud .,KHlcr.,.e .■,rrho«,s. ap„r.,x.n,,.„n^ l„»,.,l„,ieany n.ure ,o Hanofs .l,«n to Lnennec'. type- „ fat Iv infi tn... hver eell., 6 and U. l.ile due,,. i„crea«.d in nun,bcr; c. rou„d-ccl,„l infiltration of fij^u, tialiy peripheral and whether we are ripht in speaking of this as portal cirrhosis. But these ol)ser\ati(.ns strongly support our contention that tliere are two factors at work in the production of cirrhosis, yiz., in the hrst place an agent acting through the stomach and intestines and there setting up condii. .is which fayor suhinfecfion (see p. 147) and in the second place, in consequence of the gastro-eiiteritis, the undue passiiL-e into the portal system of organisms of the B. coli type through the damaged mucosa. We have here described the typical form of portal cirrhosis; it must, bov>sver, be borne in mind that the typical case is the exception and riuiiiinsis OF the livkr .■)-9 iH.t the rill.'. In a larRe numlier of cjises this very growth of fihrous ti^>nr within the hver ha.ls to ^rnve disturbance of the hihnrv system :"". ^V t" ; '« •Mtercurrent .levelopn^ .f jaundice aiul c;.inci.h.nt irntation of the hde ducts. Farther. .,uiie a large proportion of cases .'""r w "^.'''''"'"*. " '"•'•w'lish piKmentation both of the liver cells i.nd of he fihrous tissue, the pigment being iron-containing. There is . vi.lently m these cases some hem..lytic agent at work with excessive h .cnvtion of hemoglobin. The most a.lvance.1 cases of this nature tl"/7"'''"J^r' I?'«r"^"*'"" «"•' «'"«titute the condition of hemo- chromat«5is. Often in thesj there is accompanying fibrosis „nhv |.f the lancreas (broiued diabetes). The ascites and enlarged spleen ... ported cirrhosis appear clearly t.) be associated with the «,ntraction ot the hbroiis tissue and accompanying compression of the intrahepatic portal vessels, leading to obstruction. ^ While making this statepy-nt, mention must be made of a remarkable condition known as Banti's disease, or, according to Banti himself hemolytic splenomegaly. Here, enlargement of the spleen i the S-st .hsturbanc,. not«l, and after the course of some years this is follows l^ .oral cirrhosis o the liver. Banti's observations on the resul .1 al, ation of the spleen indicate that the overgrown spleen f«,^- ."..atcs in excess, the anemia ceasing when the organ is removed- |"t!;i"!;l^i;i; " ' "'^ "^ ^^^^ hemolysis that act as th. BUiary Cirrhos«.-()f this we recognize two forms, C _ obstructive and "liat IS known as Hanot's or hypertrophic cirrhosis. We confess that ^w .have ,icv»r met with an example that we coul.l surelv say was ot th.s second kind, and the condition seems to be verv rar^ in North inlSi tat."""""" ^"" '^^'^ •^^'^■" ^^P"^*^"'' P-«-'>' The obstructive form of biliary cirrhosis is to be encountered where Ion one cause or another there is continue,! obstruction in, or complete >..;..osis ot, the common bile duct. It is to be seen, for example k, la..ts presenting congenital atresia or absence of the duct. o7xv5;e " HT. J,as been long-continucl impaction of gallstones, or pressure upon :'• . Im, fr,.,n without or where there is occ-lusion b- tumor grow " "'In., the duct. In all these cases the liver is enlarged and sh, w^ - mne jaundice, as do the other tissues of the bodv' AJlthe Ide ts hroughout It are markedly dilated and around 'each is a brS o n ■ ,t new connective tissue in which, in part through dilatation i ;;.;;"?'';:'"'- P-liJeration. a chaplet or circle'of terminal b ....„' \ .''^""""*'"t'y- "''re dearly is a cirrhosis around the 1 n^X' rr '"'-'' ^•" ^' ^"'"P'*^^^' ^-'t*' "-^^ fibrosis around ■ ^ ot esl*^' pancreatic duct following obstruction of the same. '......,''. 't^^ *';' T'''"'^ , ? °^ *'^" ^^-^^--^t^d fluid appears to be the -.'X o"S;E*c.ses '" '^'"'''''' ^^""'^ ^°"^^*"^ ^ considerable 580 TItK DIGESTIVE SYSTEM Hujot's Cirrhotli.- In this we have a train of svinptonis widtl •liffenMit from those of ordinary portal cirrhosis. There is not s«) niarke pistro-intestinal disturhance; there is httle tendency to ascites, bu what is most marked is a snccession of nKnieratelv acute attacks r janiKhce, and after each attack the liver is found liirRer. the jaundic takes a longer and longer time to pass ..tf. until it lu-comes continuou and the liver attains an enormous size. At autopsv. there is tota absence of hohnailiuK, the ornan is greatly jau.-.diced/cuts firmlv, an. under the microsco|M- the fibrosis is much more evenlv distributed Around individual lobules (monolobular cinhosis) the bands are no so sharply defined anil exhibit numerous bile ducts, or more accuratel' pseudo-bile ducts, little worm-like, conv(.lute-t atill containing fat. showing thus their liver^ell origin. no regular lumen and appearing lo rei)re.sent, many of them, collections ot shrunken liver cells snared off and compressed bv the connecti\e tissue as it advances into the lobule. Tins appearance is not entir.lv conhned to Hanot s cirrhosis, and is well .seen in Fig. 202. In other words, some cases of what appear to be ordinary cirrhosis show here and there similar appearances; as we have said, a large proportion of ca^rs of cirrhosis are apt to become secondarily of mi.xed type. The prominence of the icteric manifestations in Ilanot's cirrh„MS suggests strongly that here the irritation is of biliary origin. It has been suggested that it is due to an ascending chronic inflammati-.n of the finer bile ducts, and that it is of infective origin, but this has still to be surely determined. .19^»«^»K.^f3^- Wm^ ■■f<«J**£^ THE UVKR 581 Fiu. 2(13 Syp^tic tinhodi. 1,1 H syphilitic stilllM.rn infant ..ne of the most ^triKMiK f.'atnrrs is tho nhnn.hu.tr of spircMhett-s in the liver tissue- 1.1 infants sl.owniK syphilitic nmnif.'stations tlu- orjta-i is apt to Ir. «f r.h.hvely Kn-at s.z,.. „„,! f, pn-sent on n.icroscopi,- examination al.nn- .iHMt. sniall-,-,.||,..| n.hltration in the form of widely .liffustnl miliary iriir.unas. I his eon.htion may lea.l later on to a diffuse formation cif .ur.n.ttive tissue of what may l.eterme.l the iH-rieellular tvin-; not only ' .""■ l^/IPh^y /'f the h.l.ules but within the lobules themselves, separ- ...inKotl individual cells and eell .•olumns. there may he deveh.ijtl a 'l.li.ate but extensive connective tissue. Occasionally in acquired syphihs we meet, in the s.ncalled late secondary staRe, a similar enlaree- n..nt of the orRan with a like .liffuse pericellular cirrhosis; also (though Ins must not be consi.lered a true cirrhosis) in the neighb<.rhoo«l of lar^e Kimunas wc obserAe a similar pericellular fibrosis. French authorities lay stress upon a >i'iiu'what similar diffuse fibrosis stcii ill soineca.ses of tul)ercuh)sis, iin.i ascribe this to the action of tiilurcular toxins; although we lia\f sought for it. we have not seen this form. One of us (A.) lias seen and describefl an ex- treme condition of pericellular • irrliosis in cattle suffering from wiiat is known as Pictou cattle disease, now recognizinl as due to t!if tir,-.ts of ciitiiif; ragwort. Inflammation of Olisson's Capsule. This should strictly be consid- iTcd as a localized form of peri- tonitis; it may be acute or chronic. \\f niciition it here because one niiijirkable type of chronic pro- ^nssive iijflammation has often, from the accompanying extreme s and great shrinkage of the liver, been mistaken fcfr a portal >r Im.ms. 1 his IS hyaloserositis, or "cake-icing liver," in which there is j; -nsc. porcelain-white, fibrous ^^. cirrhosis of the liver tissues, but the cases we have seen have ii"t sliowr. any such process. The Specific Inflammations.-Miliary tuberculosis of the liver is not ;;;'on„non in cases of general disseminated hematogenous t'.W - ■ Of e„ the tubercles are so fine that they are noticeable only ^ ■.^Z^":'^rfT' rl *''''" "'^" •* •« characteristic that -ciural thej are isolated and show little caseation and appear as Section from a syphilitic liver showing diffuse pericellular cirrhosis: a, snmll detached cluster, of liver cells; ft. intralobular connective-tiaiue formation. 5S2 Till-: DIGESriVE SYSTEM tliough tl.cy .Ic-vdup v.iil, ,)iffi,„lty, sujrfrosting that the tiihercle hacilh do not rcachly multiply in this or>,'an. Ocrasioiialiv, lunvevcr as III the hraiii, we eriCDiinter solitary oongloinerate masses of case- atiiiK tiil)eral ,>rocesses ot fair size extemling for so- ..rr'.. distance hetvveen -!..■ lobules. The shrmka«e that this inHa.. .atorv Jih.^u- issue mav M.id.TKo IS very strikms. and tlie result is th .t t!.. .nerl.inr liver tis-ue 1^ pulled m and the surface of the liver slu, ,s v.li-maike distortion, nM..n!,hnf|, to eniploy a homely simile, a seat .,,1, .l-i < ,1 hv tb- button m.thod there bem^ deep unpressions with stellate furrows radiatini: Irn.n the bottom oi each. Where these cicatrices are abundant we ;|i.tau. the Kreatly .listorted, coarsely lobatc liver, the hepar lobatum. 1 Ins distortion appears t.. be permanent; we may. in old svphilitics .Meet with these dci)ressions which show at their base a small amount lit cwatricial tissue, running; into the liver tissue, but e.\- liii)itinjr no sij,'n of the typical :,nuiinia, the ^nminy matter liMviiijr l)een wholly 'al)sorbcd. A^ already noted, there may lie, tli()UKh rarely, a ditfusV -yi)liilitic cirrhosis, and sonie- uiiat more frequently than in tlic('on«;ciiital form we may -iinilarl.x i-ncounter hu>;e soli- 'ary syphilomatous inasscs, uliiih may easily be mistaken fur tumor growths, ^pcakinj; of errors of diaj;- iiiisis, it deserves mention that 'li<'\vphilitie cicatrices if situ- j't.d near the hilus of the liver may so compress or pull upon the l.iru.T portal veins as to cause obstruction an„■ rcmaimnj; as a whitish continuation of the liver tissue. Under li; •"•[•'■'-"•P'Nthe lobules, columns. an.l cells are small.and throughout, ulls may show small accumulations of brownish pigment (browii Surface of syphilitic liver to show the chanicteristic puckering (,i, ,,) over old fibroid gummata. 584 THE DIGEST IV K SYSTEM depression (p 572) or I-.^tN- .. • Ti ^^^^^ '^- •"'')- or i.s the cardiac Via. 266 Fia. 267 Teased cells from a fattily infiliralcl liver: „, nuclei being pushed to the peripherj-. Tensed cells from a liver showing the curlier stniic of fatly infiltration, with multiple fat droplets of varying size distributed in the cytoplasm. ami la th „ »: h?" "'T "'"? ''^ tuherculosis and ,.ther cachexias, cdt are ,; first vn' T -f" " P'-^'«"""c-y. While the peripVn.l may reS tit "j /' f •'••^;"'^' '"">• .?'" V»" ^''^ ''"-f-'^^^t store of fat. ^^o t^ oeH Udv i ?> • r]' r "'" *'"' "■" ""^'^"^^ ^till stains well. pI«riJ • 1 " clistended f,y one or more large fattv elobni.s tTcell bodv I ' ^f"' '•^'"''^'^' •"• ^"">' "«««'• throughmit S't^elltTHf """'">'• ^^"'^ "^ '-^ (^f^^-) ^ith Professor Mot. has called attention to (he frequency of this condition and has ■ •til, THE UVER-DEGEXEIfATlOXS -.s;, suggested that the irregular and angular form of the granules when stan.ed with Sudan II. indicates tlu, .ve .leal not with oJdi.urv ^eu ra tats but with some fatty compound or lipoid. This fattv degt-nen tio MHv u- either umversal. peripheral, or central in position in tl " obnle . n itT',:\"';r.f ?•' *° ""^'^^ *'^^ ™^"^"'"« «f p^'-t'^-'ar ininent ^m^ ' ^.. ^^ irt.ice. Microsopically. it ma\ be observe.l tint th.- rlnnnit HH ,h,r.^ .,f the lobule; later, the amyloi.l .leposit mav affect the - i^'Ie l..be. causing great atn.phy of the lix er .rlls .roper Pyental Inmtration.-TI,c pigment .ieposite,! n he liver mav be •' "'>«m-nt kin.ls. VI.., bile pigment (bilirubin), iron-frei der vad^es of '\ 5SG Ti:E DIGFST^VK SYSTEM blood pigment, and I.o.nosiderin. In icterus or jaundice the heaping up ot the i)iKinent is scti. nriuiarily within the liver cells and here at times It can be recogniz- 1 that it occupies a set of fine intracellular channels In more advanced cases the inspissated bile is f,„nid also m the bile capillaries between the liver cells an). With complete necrosis and disintegration of the cells there follows an adaptive dilatation of the capillaries with occasional hemorrl .:ges, so that now intensely congested areas alternate with or are interspersed among those still retaining the yellow color (acute red atrophy). In cases of red atrophy not rapidly fatal there is further an extensive small-celled infiltration with indications of active regeneration in the form of budding and worm-hke processes from the bile ducts. It seems probable that with recovery there may develop a cirrhotic condition. ProgresMve Changes.-Hypertrophy and regeneration of individual l..l)ules may be seen as above noted in non-fatal cases of necrosis, and also in cases of portal cirrhosis, where nodular areas of such regenerative liyi)erplasia are seen; as already stated these mav pass on to irregular mil ticentric adenomatous or even carcinomatous overgrowth. Loss ..t liver tissue is followed by no new formation of lobules but those in the neighborhood of the loss umlergo pronounced enlargement the cell columns actually proliferating. It is now fullv established that regeneration may occur by two processes, viz., by i>udding from pre- existing bile ducts or by proliferation of preexisting liver cells. Tumors.— Cavemoma.— A common abnormal condition found in the liver IS the presence of one or more, sharply defined, generallv small areas of deep red color (see Figs. 130 and 131). On microscopic'exami- nation these are seen to be composed of greatly dilated, communicating • a pillar, channels filled with blood or containing thrombus, with no intervening liver cells. We have discussed these on p. 279 and pointed "lit that strictly speaking, they are not tumors proper. 1 rue fibromas and other benign connective-tissue tumors are rare 'i> also primar>- sarcoma and hemangioendothelioma are infrequent. 'II the other hand, secondary sarcomas are not uncommon, and the ii\er IS notably a favorite seat for multiple metastatic melanotic sar- comas. A few cases are on record of included adrenal tissue, and of rnniors, hypernephromas or mesotheUomas, originating from the same 1 ^^(> lorms of adenoma are to be recognized, viz., the tubular adenoma, •Mdently originating from and to some extent reproducing the cubical [>r colnmnar epithelium of the bile ducts, and the true liver-cell adenoma, >n which the cells are arranged without lumina and reproduce irregularly t •-' structure of b-patic parenchyma. The multiple nodules of hvper- I'lasia already described partake of this tvpe. Solitary primary carcinoma of the liver is rare; a large solitary meta- tasis from some minute and obscure primary focus must not be mis- 'Ken for such a primary grow.b. In short, very careful search must rm THE DKIF.KTIVK SYSTEM »' s\ tht I, cr. A r„„s„kTal,l.. „,n„lHT „f rases „f .liffus,. .arci.u.inatosis sec.n.lary t., r.rrl.os.s an- r.-cnl.-.l. A s,nall-,rll...l form .,f carci,,, ma of srirrhous typo .s l,y so,.... l,.].! to oriKi,.at. fro,., tl.,- I.ile .lurts Z eons,.lm,.|r >u.y l,(-,.at,c ,ar'^- h nr """"t"'" «' 'I""Khter cysts takes place whoUv ..n tl..- inner asi>ect of the capsule, and in the .)tl.er. rarer form, ..„"the out- si.le so that ..umcrous ,„. h ing smaller cysts develop (multUocular) c';n;r Tl ""'' T'''^.""'"', "1 '"^r"' *''^" «PP--nce of a .•..lloi:i fin. 1 ' ^P^f^*?* ^'r '!>'«*"' >^ 'l""f^l'". consisting ..f an outer hi el-"''' I":T"*^'^''>' \'r' "•"t»t..l tissu.. of the liver, a,„l a., inn.r o okl s ,„ the hud, rec...gmzable by the micros.-., p., is the cbara.t.-r- ist^ .l.agnost,c t.-ature. 0.-cas,.,nalIy the parasites .lie, and the .■^•st contents underg., absor,,t,.,n, l„-ing ultimately re,)r..sente.l bv a fihn'.ns c.<-atr,x w,th a., irregular shrunk.-., .-avity in which l..,oklets mav still he toim.l Some thr.-e .,r four cas.-s .,f coccidiosis .,f the liver are on kZ ■ ,^.^'7 P'-f^f ^'^ "f t\n'\\y,T, n.,t .ansing .-yst formation, but duo.ienun,, are distomum (several species) an.l rarelv ascaris lumbricoides. K^M\ ■■«r^K^ GALL OLA DDK J{ A.\D DVCTS 501 . OALL BLADDER AND DUCTS AbnonnaUtifts.— Complete absence of the pill Madder lias been rirorded and ecasionally it may hang eompleteiv free from the liver its relation to the liv«T edjje is very variable. An important abnor- inality is congenital atresia or complete obUteration of the eommon bile diK't, leadmjr, with i)roj;ressive jaundiee, to inevitable death. Hemem- h.riii),' that the liver is a tubular outRrovvth from the duodenal region, a is obvious that such obliteration must occur after the definite differ- entiation of liver and duets. Circulatory Disturbances.— d with 'ii.se same gallstones, but may present itself in cases of severe infection ' .'/., i^ome cases of typhoid aiid pyemia. Ver>- frequenth- such suppu- I'lti"" IS seen to be secondary to complete or partial obstruction of iiif e,\stic duct from preceding non-purulent inflammation. As in the ■u>!><'n.lix, so here, stagnation appears to favor the proliferation and '"Teased virulence of bacteria, so that what was previouslv a simple "-'""ics now a suppurative process. Associatetl with this purulent .')n2 77/ A' l)l(!F.STI\ F. SYSTEM li.ll ron.litu.i. tlu-n- may l„. „,.,.r..sis of tlu- mucosa witl. ul• «li«ten,le the ^V.i.- .hie , or at its jum-tion. within the eomn.on ,h., t or ap,in at '"' ""•';"'" *:^^"'r'-- / an-inoma of the p.ll l,Ia.l.ler most frem.entlv ^ nus itseH e.ther ,„ the fnn.h.s or ut the neek; at the fundus eier tlirou^h the «rav.tat.onal presence of gallstones, or at the neek in asM- ci. ,o„ w.th the arrest ot the san.e in their passage to the ,iuot. We -.1. . here en.phas.ze that this is one of the frequent sites of eareinon.a uH.hly .. per .-ent, of eases of carc-inoma arising here. The tvpieal fo .' > .. M.lt. .■olunu,ar-ng mt« the gall himi.ler. an.l on the other to inHI- tr:...; ..xtens.vely the wal ami th.- liver tissue; hut variations are foun. At tmies there is al.un.lant stroma formation with alveoli filled with* roM.ul jells an,l the general characters of a sc-irrhous growth, ami sev 'r .^vm.ples are ,-ow on reeor.l in which through metaplasia, presun.ahlv 'ln.t.M.rm..n.gn.Hamn.at,..n.th..tum..rapproximatestothesquamous- ;. ■- .■I..tlu.ho„,atons type or shows a combination of epitheliomat. s M.I .len..carcn.omatousstructure(seeFig.l22,p.272). Theremavalso ;.. .."«h rar,.|y, cases ,,f coll.,. 1 cancer. Here, as in ch..lelithiasis t le - ht> o„ ,s m.^e .•..mn.oi, n. the female than in the n.ale. In a.l.lition I' . M. .hr..,.t ■nhltn.tion. there are apt to l,e large no,lular metastases -; "Pl. .....les at the h.lns an.l in the mesentery, an.l in the perit..neum u.M as ,s..Iate,l no. h.iar metastases in the m..re .li.stant p.rts .,f the ■..I i;h:i7'"';T " • '"'■^'■'" '"■'*' •'""^^ "'"" "f *'»' ^«"'-' t>I- »^ those . l.n .1 the latter, an.l as a consequen.-e are foun.l of smaller si/- ron. the.r regu.n ..f orign,, they necessarily lea.l to .,hliteration .,f -^ ............ „le .lu,.t, an. to fatal jaun.lice or through their ulcem i . I.' a. t.r to n h'ctu.n. ( arcmomas of the amj.ulla of Vater, it must • '■.■.nc,nl„.re,l. n.ay .,rig nate either fron, the ,nue.,us n,embra u . '!'• .rnnnal portu.n of the bile ,hu-t or from the .iucMlenal mZ "i"nl,rane covering the ampulla. 'HHMienai mucous THE PANCREAS -'liti.''fnncS.""!;"""^ i" a different way, the pancreas subserves "pi, Juncti. lis; as reganls its excreti,.n it affonls a tr^•psinoi:en 1 i^tiSr 7'\ ' r ^"*-"''^'"»- -Pplied by the mueoia "he ■' I .".t.Min,-. attor,ls the m,)st p,.werful proteolvtic ferment of the ; ;-n s „; .vheretore it f,>llows that arrest of this Excretion either t : i-iatuHi oi the .lu.-t or atn.phy .,r arre.ste,! activitv of the gland celk ... Wed by UK.,.T,p|,.te dissociation of the protei,is of th/S !„ j --im-nt la.k of assnmlat.on of the same, so that, as a matter o' 591 77//; DicKsTn t: system fmt. a ,;„n.l,ti..n nf tru.. starvati,,,. is l,r„„Kl.t al t a.i.l a „n.ur,.ssiv -nar.at,on ,|.-vrl.,,.,„« .....r.. rapi.ll.v than fr.„„ ...v ..th.T ./hm It al.M, ,.x,rrt..s a li|M.lvtic IVr....nt. strapsin. .^s.-i.tial to tlu-' ,liss, <|«t.o„ ami ,s„hs,.,„n,t al,s,.r,,ti.,n ..f tl..- fats; int.Tf.rr ., vih, a .S..K. o th. ,.x..reti.,„ is als., a „ot...., fa.,.. i„ tlu- ..nL i..: . ' nentione.!. In sm-h cialitions wo fi„,| that tlu- st.M.ls an- riav-colo from excess of .H.altemI fats. Other fernur.ts are pn^l , .. lot. an am.vlolytic or stareh-s:)littinjt ferment ' this orpan. we have .hseusse.! this on p. 104. l,„t we woul.l here re.Vl that there ,s n, the hoK the main ,hut of the m^e, w in 't';:,^- , '',' '^'\ T'"" "^ U,r llH- in..st i.np.,rtant .inulafry .li.turl.an.r is thi- sui>frv,.r.tion of acute hemorrhagic pwcre.titi.. Th,- series ..f events I..«dinK t. E -y- l.tum IS mm Kenerally H,knuwl..,lKe.l t,. I>e , 1) the .levei„prnen .. ocal areas of .se|,e,„,a ..f the Kia,..| sul.stan.-e !,v arterial ari.t o -liM-ase (J) the cells >„ these ar.N.s ,„„|erK.. necrosis with the lihera- ..... .nto the tHs..es„f the cellular f..r,n.-nts; C!) hK-alizecl ''if. iLes- t.on ..nsues w.th eros.on „f the .apillari.., a...l oth-r vessels, asscK-iated ".tl. w huh there .. ne.rosis of the fat ....||s in the ..eid.Lorho.Kl am] . .s^o,-,at.on of the . onta.ne.l fat thn.UKh the aKcncv of the liberate, stcapsn. (fat necrosis. The c.on.liti.,n is l,v „., ,neans ,.e! Jarik o .Mtect.ye or.j;.,,; arou.,.1 s„ch areas there may l,e, it is trne, evi.len.-e .. acute ...flammafon. I.nt this is secon.lary. Th.> effect of these l.hcrate. ferments are not confine.! to th. v.n.Teas hnt mav invol' s..m,umhn« t.ssnes; the c.m.liti,.„ n.ay he .api.lly fatal within a f. ,.. I.m.rs or. on the ..ther han.i, , .re are ..vi.len.rs that, if not extensi ■ re... very may ensue. Mmai , Inflammation Thc-e is a possil.ility that a .■o...iition si.nilar to .-■ above may b.llow a lo.alizc.l i„fla„.mati..n in the pancreas and tha? ..r,. .s thus a tr.,e acut.; .....Totic au.l heniorrha^ic pancreatitis, but I >o, bactenoloKical stmlu-s show that this is the exception a,i. not .he rule. Purulent pancreatitis is o,...a.io„alIy encounter. |ekher\4h m.hM.le s,nall pyennc al-s.-.-ss.. in .-as.-s of bacteriemia. or by ext ,. n ■ Thsr "■■■'• "*'"""7- ' • • P«'''-*"'"-»^"'" «f « ««^tric ..r ,luo.le„al ...<.r, .,r lasth, hs an ascending .nflammati..n of the pancreatic .lucts Chronic Pancreatit;is.-It has b.en experin.entallv 'shown bv OpTe i'".l oth.rs that by obstru.-tion or. airain. by r.tro^rra.lc How .,f bile into .e l.a„.Teat,c .iuct, there may .i.-velop a c.n.lition .,f fibrosis around I. ' -lu.t an.l Its bran..hes due to resorption of the secretion as well as '. h. .rnt...t,on of the ....•„„ fluid. Whether this be the essential ^au" or no. It is to be remembered that ... .-ases ..f cholelithiasis we frequently ;N.->.".ter a marke.l in.luration especially of the head of the parreH ins becoming so hrm that the surgeon is apt to mistake it f.,r new-g owth II.. organ also ,s apt t.. show extensive fibrosis in a.lvancing age asso^ <;ate.l with the chronic periarteritis of arterioscler.,sis.^ We £ .•roK..i/e more than one f.,rm of fibrotic change in the organ viz a ntnlobular, an.un.l the branches of the duct, a perUobularfsepamtbg "■ mdividua cllections of somewhat atrophic adni from elch other . ' LiSn"' T T'^' ^T'-^^"'"u'^^-^ *" f'^«-"- inflammation ..icr.,Ms of localize.} areas. It is to be noted that a chronic diffuse iMcreatitis or cirrhosis is n.,t infrequent as an accompaniment of • 'mosi.s ol the liver. .^JaUvof!^-""^!""*'-"^^'""'^'"" '^ '"''- ™^«- A« « '•^«">t of con- ^ nital .sjphihs, there may be encountered an extreme grade of diffuse 596 THE DiGESTn f: system ...t orstitial i,a.Rri-at.t.s with , nlargomn.; of the organ, an.l i.Hhiration an.l pro„ou„ml a rophy o a great part „f the panc-reatie tissue pro e save the ishi.uls ot Langerhans. We are indine.1 to regar.l the isla.uls ot Langerhans as the ...other tissue from whieh ..e^^^ci,.i mav be developed throughout hte, a,.d in this and other forms of fibrosis the pers.>tenee of the islands jn.lieates that this vegetative or mother sue IS the last to be destroyed. Others, however, it must be noted, rZd these as mdependent entities. '^gara Fio. 274 Ii;i :i - -.'^ •■' I.- i™,u, p-nj;:;,,::r';;;;r : m^:':::: r'.::;',::'': i'^j'™;""^" '^'^ ^'"^ '""""- ar.. ,i,„il„rl, ,,,,,,ratr,l by h cuirilohular fihro™, ""Lvdual anm U) in the lobul.-, J'Tr^u-u^T."- ''r T' '"■ *"'^''" *" '''■^^•"^•"^f' between nil. tin , -|> are i.i an active state, there is a marked tendenev for o ;^rm;,^s;"V" '''rr^' "■"' '•-"« aboit^rcSt^; L^mTv beLn '' °°- . .'" ""• •'"'■'•^' -^^''^''^ "f ^his proeess the tC^: nlS '/:'r\"?''?^ "'"' "" ^^'''tio" tl.e nuclei aS- i n ! .'';""• ^ '"^ •'""•"*'"" "'^*'™bles somewhat rS;' ion I .^^ •' '";■'" ^^^^-'^'..-''t^ii-K takes place with dis- rgan.zat.on. I„ , Iscussmg the so-calle^i^ "*>"nal stdning power, r ;. 2 Vh '"YT'"' ;'t "•-■•"tio,. or post mortem it is found that K- ..U.U foe. ot fat necrosis. This extensive necrosis mav S^Tot " m-lN the causes above mentioned, namely, stasis, vascular obliter- .t.<.„ ami ,nect.on, but may. as in the case of the late TrSent o;t';:s;;S:ir""' •'^' ''^^""' "'--'-^ -^^- -'^" ^'^^^^ KegartlinK the relationship of the pancreas to diabetes mellitus. while " l"Htt.ng that the matter is still unsettled, we are inclined as a mltte^ <' <'Iearness. to lay.lown the following: (1) i„ a co,,si.le ab ™^^ "t cases no change can be observed in this organ ; (2) in the raSv nr^ orru'rhTn t.r'-' "/"r'^" \^ M-pic deg^neLtion^^X la'nl langerhans followed by atrophy, with little accorapanving general hbros,. nt he organ, although there may be considerable Ttrophvo ab.S; <>;• ulZ'n? ' (Weich^lbaum); (8) the slowlf 3i^ noiu n iV':""'*^'' ¥' "^^y Ije characterised by marked fibrosis and : ph.N ot the organ m general, together with changes in the islands 1 l..•^e changes are most often of the nature of a hvaline deeeneSn M (n.itic acmi there are data favoring the view that they play a nart in till- sugar regulation of the economv. ^^ ^ tio'n ^7n'X *""".°^ '■^'K'-essive change in the pancreas is fatty infiltra- lon. „ adyancefl cases the greater part of the glan.l substance mav I'.-y^' atrophied without the organ being rduce,! in size a f.ct l ^h |> . ue to .ts replacement by fat cells; oft'en locali Ja^e"; of tch f v : on^^n • '"' '^T°"**'°" "^ '^'' ^''^"'' «'"« »'«« been „ot«l Amv 2 ,n I""r""'S- !"** necrosis has alrea.l>- been discussed Amyloid change is to be seen m general amvloidosis >mgle or multiple calculi may be encountered in the larger ducts- l-> are forme,l of calcium salts with a mucinous matrix amraedi; P ogressive Chai^es.-Tumors.-^ We rarely encounter benign growths ld.ll '""•''• /" ""■• '«»'oratory XichoHs has reconled locahm denomas ansmg from the islands of Langerhans, an n Htn '•'« -ther smnlar cases have been place.! on record ( thets have -nl.ed cystad^^^^^ representing m.Ire fully "! t'xtensive are recopiled. CHAPTKIi X THE URINARY SYSTEM THE URINARY FUNCTION General Considerations.-Einbryology.~The permanent kidnev ap- [.tars about the hfth week .,f f.etal hfe. and i.s made up of cells'from he U olffian duct, on the one hand, and the mesoblastic tissue, called the Lh^tema, on the other. The former gives ,>rigin to the ureter, pelvis, cahces, and collectmg tubules, the latter to the glomerular epi helium an. the rest of the tubule. This complex originlnd close relationship t.. t he prmitive myotomes suggest a partial explanation of the frequency with which mixed tumors (teratoblastomas) appear, and appear too ...early life The fact that the Wolffian body and the geS gland arise from the same primitive genital ridge, explains why developmental an.,i nahes of the kidney and the reproductive organs ar^ so apt fo occur tcftctiier. Anatomy.-The renal arteries are short and readily allow a trans- erence ot the aortic pressure to the kidneys; the kidneys are relativelv . I'. ...lantly supplied with blood, and theoretically all the blood in the "Hly may pass through them in a short space of time, ^he result being tli. brunt of It in full measure. When they are damaged, the other Mrretory systems, the skin, the intestines, and the lungs must assume tlu. responsibihty for the work which they can no longer'accompS sns vntnlll'T' ^Tr ""\* ^r.™"*"^ "^'•ves. and are therefore n .pt.ble to central . , pheral impressions; the effect of mental .■s upon the amou .nne is well known, as is also the reflex ;.!!;, ;,;;,™. "''" .mumcatd from the bladder, genitalia. nJllli.ll'r'''"'*' "^t''l^'^«'"r^• »« « plexus of unstriped m..-le fi'jres, M racf on and relaxat»»n to promote the circulation in the kidnev and .^^• mochty excretion. Their anatomical position in the My, 1 the peritoneum, protected as they are by abundant fat, ensur^^ 'IK kidneys some immunit>' from trauma, while, on the other hand ; -.nunica^jg ,n. L, in ,„,im„„. „,,„dS, " 1 hi. Ivmph. „,„, winch, „„„!„. the .lin-ctio,, „f «„„■ i, t,^^ the tub I » *..„« t„ ,„. „„t,i,h.; ,« „,„ e„tip..l.v so. We must rrnlZ ,h ^:tn:;;,:'c'^h;;erz,:':-i t^r: r^£^ " The VmcUu Suppl, of the Kidnej.-The arterial supply „f the cortex r o' K?!; ta't^l"":? ™'r*' "; "," *""™"- f '•e '""^ - - u.e Monitri luh in the afferent \essel, leaves t in the efferent vessel ; l^f"^,^^*^S1,'"r ' "T"^!^ 1 ^^'^'''^"- al^lS'lhV::!: m.T,I . V > ^ '""' '"''P'-'' "f t*'^ collecting tubules in the medulla is from capillaries of the arteri,e recta.. The bhlT sunnk of the cortical tubules, having been through one set of ca llarie Tl e '. tt 1 • 7u .?^ •• '""''■ ^ ••^''*'"-pt'<»» from the urine, which is not tn u '^1' ?: '""V*? *"''"'^« ^^•''"*' th« Woo'l pressure is hdu An in all probability this is what actuaUv occurs. *' I..0.1 pressure determines to some extent the .lischar^e of urine- rit srs irrr '" r:-"?' *" '' '"'"• "^' — '•>^ '^e a""":,- Z" is c? mo . 7 "■"'"*':"'''■ r™"' renditions, the rate of bho.l mc.ldtir..'^'' •'"■'■ *''"'; *''" P""^^^""' •" the glomeruli. U- ■e s, c "" '""'''' '"'*' ^""'^ *'"•"»'''' ^""P'^ ^•'""'t-'O «'"' gl menir., t. . ^^T-'r "*-'"'' "^■"""P'"'^ the water through th,. tear ^^■';'''' ^"'"'' "''^".•n'tion occurs in the coni)lut..,| . t tlu. .r *•"""■'"'" '""T' ■' '^' ^"'•t''^'- «-'«'tive excretion mto tlie urine ol urea, uric acid, and other "extractives " as well •!> s W^^^^^^^^ H ' "'•''"''"■ ""^ '^"tabolic, of which the result is al., ThrNe,lrSuni"'TT-^ 'ts way through the convoluted tubni,. to tlu L?? Supply.-^ -This IS of considerable complexitv; the ner^ ^ to the kidney form a plexus around the renal artery, ami are for the in,. I -M THE VRISARY FL\CT10\ (jqi I.an" !l.<' venou;;Lsll;:e";:"^£--^----^ --ase in -n.rease,! without increase in tL arterTaMes *' wlu"""-^ '^T"'' u' >!/<• of the arterial (•hai.i,».I« ;„ // 7 . , "'' '*^^^- , -^t t»i' same time the tl- urine is a onK v^h" "S" '""* ''\ ''^''■T' ««'"""* = n.ised. but even if vit .. t ■ ^ ^''"'''■"' '""*•''■'«' P"'s«i're is int.rh,buh.r:;:;^'L " ir^^^^^^^ ';'rl pressure, the interlobular and afferent «rt;r7 f ' ','" *''^ contrary if the '-.:^..era,pre::,^^;h:l:::::;;:^ ^-ation of -paratefrc.mitrblneesth„t«r ^ ^' ^™^""* "^ ^"^'•^- «»"'• «■«' *« « In'l. are br" iX Tf X i-n"* "f unnecessary or actually >^tL;-i '•''"?"' '" r'"P"«ition hut abnormal in qua 1 •""-1 in the ur n" Such a l.V -"''r*'"" "^ ^"bstanees not „o;-mairv :.. urate, becau tlu^i.nn/ • '"-'"'r' '^ '""••"•^' '' vsiologieallV ' the .n,ttT «>!,?" Its H^T'r '• ^^'''''^ ''>' '^^ ^""^-entratio;. ' i : u.av be bro„.,ht M HM^; M ^ '^''T'"'*^ *" '^'*'"*''-«' Princinles '''■•Hit renal chmle o n iinTJ"" T *'''' f "^''•"' «'-*^"«' P''^^^"^^ cnangt, or (-) dilatation of renal arterioles without, of 602 THE VRISARY SYSTEM V necessity, any rise in general l,l,.o.l pressure. (;}) T« tliese it is obvious that a third factor has to l.e added, namely, the effect of certain salts and other substances upon the secretory epithelium, stimulating it to greater activity. Diuretics may act in any of these three wavs, and some of them in different ways at different times, or even in more than one of these ways at the same time. Decreased Amount of Urine. OUguria.or Anuria.-Heduction of urinarx flow may be caused by (1) lowering of general blood pressure, (2) direct contraction of the afferent vessels, or (;i) increased venous press- ure; two of these may be included in the more general .statement that a red! • n in the difference between arterial and venous pressure leads .„ oliguria. To be adde.l to these is (4) any obstruction to the urinary outflow, i)rovided it affects both kidnevs. The oliguria that IS so marked a feature of acute nephritis is probably due to the amount of glomerulitis that is present, rather than to the effect of swelling of the epithelium and consequent diminution of the tubular lumen, although this IS often pronounced and cannot be whollv neglected The Solit ALBCMIMHIA 6a3 .... .nfrequent am unimportant compared with serum albumin and s.;n>m globuhn which are the bodies c-oncernod when we sZk "f ... n.nurm. They are the dominant proteins of the bio k1 Sasma k.K- ttat when thT;v^'^'•^?r«^**'^ «'«'"^"'"- •»•*■* '-^ «'- I -^ .^'it-n the tubular epithehum is disintegratinij the albumin sj. .lenved ,s added; further, when the tubular eF^theli.m s ^st T lu tubules Thus, m h severe acute nei)hritis, it is likelv that the tubules contribute a considerable am.mnt of albumin, while hf the miller .ases the glomeruli allow the albumin to escape. The .li^^inteJItT ' , ..Is IS not necessarily accompanied by the presence of albuS n le n,:.- K «bumm found m urine is usually serum albumin, bul ^ may be globulin alone, or with mere traces of serum albumin TZ^STi^-TZ^r^' '^'^^ f'-™* "' « -"sta't ratio to j,i..i)umi of .i to J and globulins are the more diffusible these facts s..™ to indu-ate that the glomeruli have a power of select .,, Physiological" Albui^urla.-This is the term used to designate H appearance of albumin in the urine in those whose suSuent ..count for It. It may appear after cold baths or violent exercise lo th^t:^'^^ '^ ''-'-"'-' ^^ ^^'- ^'^-^^^ frorjh:™:^ . Cyclical Albuminuria. — This is nr.twl ;„ +i ■ :;i; i:rSi:LfL"!r'""- '* •"'■'■ -«™ *- »■»''-- ilbuMMrt. ftom Olr(!iJ.tor, Dtatotanc-Wlmtever slows the rate . ri Tht" r".'! "'%''';I"'J» f"-»» the .ppearanee ,f albuiS^! un.i. ihus. contraction of the renal arteries n^ ;., l»o,i . • . "" -js obstructions, as in heart dil^^^^^^ ;^ '^ .^ST K ruMl xein. causes albumuuiria with lessening of the amount of Toxic Albuininuria.-Many mineral and bacterial poisons and the .known oxm of eclampsia, are capable of causing a buminuria Infectious Albuminurla.-This is exemplified bv scarlet fever and ; 't.K'..c.cus infections, and is especially' due to i;sion of the glomer' if abundant discharge of albumin, and sometimes even of bS "I "soles the parenchyma, too. is generallv damage.1 1^ 'Sr;7n ot"c!|;;"^^ '^'""J". *'" "^"^ ^^''^""^he intracellular '"sm of proteins is perverte ..r elsewhere in the tract; it may be evidenced by a Zk or bright ^1 H i 604 THE I HlX.un- .S'J-.sTA'U Hemoglobtauria II..,n,.Klnbi„ ,li.ss„lv.-,l i„ t\w nri,,,- mav a,,,,, «l.en lK-n.olys,s has ......urnHl. tlu- material bt-i.« a.f ,dh s c and ii„t filtere.! in a n»-Ivis ,.f the kidn ".1 lu- rrotcTs are merely an.plifie,! conchutors >f t e n .e T ;'r ' ""'V"';. -'t'' ^•"-•tio-al P.>-er ..f .liseharge The I nd .(.tnuH '■"'"'•'^•*"f "PJ'"'-»tus are. therefore, ehiefly ..bstructi .ind ..l,.tru( turn may arise in a variety „f wavs; it mav result f r. m I tn.m shar,) k nks m the tnhe; (2) thickeniiiK of the vails """"::;;"•""''' 'T'"'"''^ J.yper„Iasias: (.) pressure f,!" J i,, « .r 1 "'"7^- .'""'"*'''• '"■'-'""■'^ mi^plaee,!, traction or pressure , ft r ,us l.an.ls. |,«atures an.l so o„. Fim.Ily. the same ultimate resu r: ::;;:;" soiut.o„ of o.>ntinuity .,f ti.; tu... so that s;::s: whXr o e ; U. uf7 "^ ^'''^ ^'^"""'^ obstruetions .lepends upo wmtler one or both kidneys are concerned; mo.lerate obstrictio. Tc^S;" ^'th- '|^'-*-P'>>7''<- the point of obstruSn .M^.e « 1 i ,. ^ d;""""t.<>n of urine by the employment of mor ont. iJut this cannot k'o on indefinitely; the extreme of hvnertronh Magnation of the urine, an.l s..bse,,ueMt infection thus n-sults aTl "m an infectiou may j.roRress upwanl to the kidnev itself A^a fm iiaur. I the other kidney may compensate entirelv for the lack- but it bilateral, uremia and .leath may quicklv ensue. ' uri I'l'ti, n Wer,''.;''";';'"- ■ rrriT^ '" '•^«"''»^'"*'' tlu- functi,.,. of ^" .^ but i / '" ■■ "•' '•'"''''7' *''^' ""•»' ^^""'•' '^^' ^ontinuailv nusde wh ' ;i / '.""•^'"■"i'">- '* '"""^'^t^ "»■ t^^" ^•l'''n«»ts, a sphincter he .tiono»^ :''/'■ "'"' " '^''W "^"^'•'^' ^^•'"'•h -^x-ls the urine: ch 1, i ab . tn '^TT"\ " t'•^''''"^•'^''•• I^'-'tor. by education, tli. Se. cen ^o ".iitrol an, time the function. There is. therefore. :. cord ? a ^ 'f 1 '" *'" ^>"»irt''-t'^ -^vstem. not in the lun.h.r nmscle i..l ri """'?■ ^^"^ '^'^'"'''''''' '"'•K'^'y «♦■ voluntarv rrth;.i,mr T """''•' "'•' r'"'*'"-'^"""^ urethra to fill with uri,,;., an, he 1 np ilse becomes irresistible, the detrusor expelling the cent.- : ot the bla,lder. Factors which govern the reflex irritability are ti.e KIDSHY I.KSIOSS (iO.J •Mnonnt ,.f .listension, the state of the mucsa. anc Lu hueii innuences. Ihe vasomotor - n t'ZJ^ T^r\ '''^*=- ^."^^^"^ cleviation trX n- more important is the quality of the blood; it may be vitiated CifXi rilK VRISARY SYSTEM i^ b> the toxins ofhutona or l,v rhomiral poisons; hacteria mav » entrance to tl... k,.ln.v or n.a.v .lamaRo it l.y tlu-ir toxins prcKlumi d ^here m the ImkIv. Kven the pr-nlnets of putrefaction in th„ L mav 1h. potent eanses of damage. Substances that are norma excrete.1 l,v the sku.. th. hn.Ks, or the liver may In- thrown "^ ^t kidney u. states of nicomi)etency of those organs. Finally the kidne may Ik. damaKe" """"""t °^ ™«y even h- P~L r!- "'^Z'"::' «"d t^e «olids generally diminished. arc .!r.fm ""':"""'■ .'^.'^''■i^' """^'^^' ^^'t^'' epithelium, and ,.us the ?^in. If ir'"- = 'Y ^'°."*' "^ ** ^^^« hemorrhage may appear i„ the ur.ne; if there .s ulceration, shreds of tissue dso may bT^r.- llie causative bacteria may be demonstrated in the urine. The THE KlhSKY ,;j)- tl- l»-art had ti work hanU- o ".roMJ. l'"''.' ' "" "'*"." ^"^ ''""^''^ *''«* it is prohably more ' ^Jto ^uml^ ir h T"^-'' "« '^'■^'"*"-^"' '"'^ in part are the .n.'.st salLl:; o rj ^k^r^fw "'5^;.";:^^^^^^^^^^ MHi, can be excrete.! hv the skin'- a,.,! th ; .'.\!'^'»''V"'*' very httle tn,ti„K the toxic materials 1,1: b - ,n ^"',"'1 V T"'^'-^ "^ ^••"«''>- >'^ the ski,, so that ure.,Ji;^l^\n^,^,'"^: ;;"■"' ^-P^ 'f -ater I'nm.. to occur ••,- |„. ;„testin„"l fr-, .f i, • "''*''"»f«"'"^ that are •'■"",o„ia from the rJ^ eu- eti^ '"H-phr.t.s are probably ,h.e to i-t.Tial activity """ *-'^"*^"*' '"*" ^^e tract, assistt.l by increas.Hl ^^^'^t^^^^tS^ consists of hea.,- ^^>teIni,HhVate.lbvconv, on«'r •''^t'"-'>ance of the nervons t"xic eHect of all the 1,1 •• "'.^a^^*^ »« ""t yet kn.nvn; the -Hi;ient ^>ti:^fj;'r"iS^i' tfx^ r""'""' /^ • ^■'^^^^'^ ^" the toxic effects quickh- orrKlnc «« h' ' " •""""'at'^e, and |-""-i- IVrhaps. L, Z SS^ti u^XrrCi'l"* ^^'^*?^' ''^iN- certani toxins. The work of th ' J V.l i •'''*' P"'''^'*" "» '- "ot yet sufficientlv known ^'''' *^''' '" *''c«^' states )i'''ity, so that the s bj it o^^^^^^^^^ '"• ■ ti.ms of all sorts ^''"^'"" '"■^" ''"'''*' *" ^"«'"mb to «;as 77/ a; r/.VV.iA'K ,s) K\f THE KIDNEY wit?I!f*f *^ Abnomulities. Absence of h... |, ki.ln, Mtl. I tr. I,„t al,s..„,r ..f on,. I„,> |„ ,,, ,,,,, j,, „„,„„„ n^httm».s. It..s.sai,|.|.„„,.v,r.„,.,i„.„,,M.«sVc of tin- ki.liH.y has i„. iH-aririjj i,|h.ii tlio a I oftfti a<(„,„,,a„i,.,| |,v „|,s..„.,. „r anutiu,! I u' nret.T n,,.y l„. ahsont „r a l>li„.| im-Ur „ llw siirKical itiijx.rtaiuv of unilateral kidr.ev 1 r.-...ov,„K a ki,l,a.y tlu- prcs,-,.. .• ,.f tlu- r„ . r ,..,„. the wnttT n-ralls an c.,-,,,si„n on wl,i,.|, oL^, .„.,, „ the siir«..on from r.-in<.\ in^ th.- onlv ki,ln,v of i; ill- t: t nine I •ys is not <.«)n.sist«' autopsy (xjH^Ti*-!! ■art-ful fxainiiiarii y tissii.-. Ahst-n «• same M(|(., I.iit k'l'iiititl -triKtiin ' into the [)la(|(l, '■ '■ nil. that l.*'fo nnst !)»' vcriHiH Hi - mil 'ircNcnti m. Fio. 277 *^iinKiniiMl (•' >»ii' liiclnf\ S.',K muliipl,. ,.y„> „(T.-ciMiK I, .>l, i.MHiill I'lih Mu,., 'irlox :in,| in.. Anomalies of Shape. In ,„,ilatoral al,s"■ ^^^^^ rr ■ '^ ^ "'^'"* ' st«tr -affairs that . .nnot ea.lv , ,Hff;re, iat' ^'VKor ,t..r nephritis;. f«,,. ,.•«,. av. sTa^.f,",,. .>rn„ nml for such .liff-rentiation. ... o.rc^la, ,' Thrombosi8.-The arterie or ti *' , i„ .,f th --.I. most often as part o- ^^ n^^nif,- ,uZ 'l.nth does not ensue, an< ,..«,«.-, H ,' EraboUf n,.- En^ ,oh«n of the renal artVv r inlarete,!,,, ,t,,.ntiret>. Ex. in th' •ri.MH,Klohmn theurin.a.,,ltem,M>ra ';^il^ vuth the Himtion of a depress Inflan:?tiation. 'liiit .-rv sijfiiat file char *■« ar< ^nr>' to -eomp; III ulii,.!, iiechai,.- intccii Ik uinning^ '' "- U> said tha t'iitliulujji f is necessary ;f till pat Insists had ''- - er, -ified thTnrrWrJth" In .;" Th ' T "' '!"' ^-""'^''^"^ '"'^-'"Hvl made H inZth V ■!. ■■ The charge of incomplete- - 'i -phrit.s Xie ; could b^lf'^r!'"" "'"'"^ ^••"^•^•^- Jt '^"-^ "■"■"'••'•-'-"'US.,]' uZ i^«Sl '"*° "'■"*" '"^''^titial. acute 'Im- . ■ "^^^.*"^^"*rhtsf the largest infarcts, »■ 1' earance of I.Io«kI ' ten!. Hture; an infarct "ti t t' surface of the ''fer unri th th. Jiritis *h ;;■ ■ ^i^''* hfading the lesions - ner i.e, thai degenerative changes are ar ma. h dege. .ratp may have arisen from m. :i of the 4. ■i theunderst, 'ver l.issified' <)f the clinician and the f any disease; it seems as i'intis, just as the clinicians . 1 ill' 61 THE IRISAHY SYSTEM 11 Fi(i. 278 Anemic infani ni ciirlpi nf kiilnn i,. <,i i • side and Tt i;not nn 'W ; "' "'"' "lV'''^t'"^''«J ^"hanges are seen si.l.. l.v oui rne other. 1 hero are two extremes between which lie all the ,■■ ,.• first ™°*"""' """ "''■ ••"C.iti.llj non-infctivc will !«, deal, „ith 5ative factor, lal infection. i>f a kidney, pnchymatous ^generate by hritis by the cks of either >y the large, characters of i, one might r of cong'-^n-.n; one or tlie en side liy "xist wiili- the (■!.-<•<; ■)ronii: ^ lit of parcn- lealt with ACUTE PARENCHYMATOUS XEPIIRITIS 611 i.. the infectious disease. The ,r!Jl. ,,'•"'"*'''''• '''*'»'"' »ei,i„„. i„ fact it is Sate™! ^SS St^ e°„:^Ts:l„tt Fia. 279 Fia. 280 u.,h J5 , "'■""' P''«"«^''>™«tous nephritis. »ith marked cloudy .welling. Cell bodie, an 'loudy »,th beginning diswoiution. Note varia- '"-n m nuclear ,tain: a. pale staining nudei- 6 ■^"■Ply staming, c. J, interlubular capillary; , cell witli pule invisible nucleus. J'.'.ceii Acute parenchymatous nephriti., i ,„.r stage with more acute disinlegraUon ol the cell bodies into the lumen. Kia. 281 ^"■it lurcnohymatous nephritis, fully develotx^ A nK., . ■ • -.-.ng enlarged stellate Lint^, ^"^^l^'^^Z^Z^;^ '""-■ .' ' t.rin parenchymatous nephritis be iiseH TK^ ^ x . '^ • ''^'t i" which the kidnev tuhnles an^ n^ IX ^'''* ?*'*^"« ^""^^ ."-tion arresttHl all a tnl K ^T-'f^l' *1*^'^ ""F'« ^^H^^d '• - ""ution arresttH^^ an a "n-^ "ecToscd. tiieir nuclei killed, and " 'ii^ state, therrmav be no XL ^' "" overwhelming force of toxin; , mere may be no changes wrought in the outward shape of 012 77/ A' VlilXAIiY SYSTEM wi.h .he dnrker-ml mcliill, n,.l ™ f"™"-V P«le cortex contras sra- ;™i- !;S ^SP^^^. casts appear r- he ,„.r *-' V"'^"'''-"- «Pace, and bIcKxl an.l blocul nephritis! Clear sdV 1^1^ " "^J^! '^' '^™ hemoixhagic toxen,ia, nor is this q a «H bv . . I"": ^f t'^%"»t^«n>^ <'f « diffuse Chronic Parenchymatous Nephritis.- 'I'his ff.rm ..■M.A i u (liflnsc nephritis is elnri,.f,.r:Lj i i , • ^ '''"*^" ^^^^ chrome white," s,.L.tim; -W red • /•' '.^*'"' '^"''"•^■' ^""'''ti'"-'^ "l«,fe bo mereiv „ cc"^in„ano of t'l,.. 7" !"«« mottled kidney.- It max arise in;i.lio„s nV u ^ k-r P7'-''y'""tcn,s state, or it m.; varietv of <.han.e 'H e ,1 -.Ho V /.'^ the alcohohe exhibits this tant faetor i 1 1 e in t;. | ' of" . ' ''""'^-'/"I'ules is an impor- •listinKuish her n " rt .' ,. T • 'I'^V'' '" "^'''^i"" «hilo w-' notable t at t is „ii ,/'''?''"" ;"* ^''^ ^nt.rM[t\^ tissue, it i> tissue, and as fibroSas • ., ' "" "^ ^P'•'»^'■^*•^ation of eonneetix. of itsinereai.rsS H i^"nZs;:r 7 ''I"" ''"- '""-^'^ *''^ --" finally hy eontraetion if t le .• .1 '*, enlargement, to be followe.i tissue of the k , e ' l-.v ' T T '""^ ^■"""«''- '^''^^ conneetix. area in \^ZnZl^^Z^^i'7" "' ^•""^'-t ^"^ ti««"e of any otlur crease.l, and Z^Z^l ^, Y ' M"^"' V' ^^•''"•'' '*« ^-Ik is i„- .sin)s(c,iunti, to a sta^c m whieh its bulk is lessenetl by tl„ in a^pcrs.:":!;;;,,;:;;'';:;;:,:;:!;! .^^i^koM sug«est« that the w n,ottied ki,.,,,.. ^iimli i-.«b.,li ,„ the glomeruli and eSprn"l'wif''''^^.™''''?"^'''«' '»'''' «>"'":''• cireuliUiou. * '^"'- "*'"' elsewhere with resulting local disturbanc- ni Fio. 282 <«>ntraction of fibrosis Itfl.i.«««», *• :'^'>u« nephritis is but a. oaXr s ™T.rth""*''•'^^^''';"T■^'^«^ iMtcrstitial nephritis. *^' "'^ *'''' so-called .lifFuse chronic The enlargement of the ki.lnev si\es ' " Pli'rap look and if it be held with "- PHvis .n th.. pahn of the I a d t -•nvex surface looks broad, somewh t ^'1 "are, and there mav even b,' . L" ;'',.«;'tt-ingaIon, ti.e"co;. :xbod: "''-'••' reminds one of the h,,mtu Inl ;.rrowoverthespineofafath.,,!:;w '';•■ "ame "hog-back" ki.lnev . 'Hi, " ! "'-^nuadnWateral shape mav J ;;"";■ '"' 'y/'S^-'Htal. The bulkv kidnev ,s -"u-nmes soft, although if co "^i^t. t's firm, the c;apsule peels rea,lilv ^ '••='; t's a smooth surface on whic"h v'".s are .lilated an.1 prominent Tit ;;;;;;■•;;"« -lor m ■'l'1-arance .s due to the prten!; l.'t 1"^, '""""■'"■'' "Pilhelium lining the '■•^■.■onv,>luu.d„.bu,e.,. Asi„,,i™ted .ml™ ""'"'" ""■ '""•""matory l'n,.oss .8 Lore ,till .ominuing. '•' I'lvhitf r„) a ami „„al| granular. c.,ntn.,.,e.lki.ln..y, 8 ('.) (one-half natural ,i,e). to, ho w rHative siip. ■ ' ' -e or *„„, ,„,i„„ wS''t;,'T:;,r*,,X"'r: 614 TJIR VRISARY SYflTEM B ! that a gl«rnerJh>?„ V i „, to b/^'i;; ' t '^'•^^•/•''^'" '"''"'^*^'^- c isconnble, may be a definite, eas (listinj;ui.s|,e(J line „f perceptible thic ness tile first indication of interstiti proliferation. Chronic Interstitial Nephritip — Tl above form may ,,roKres,s into tlii or the interstitiai form may, on tl otluT hand. Kra.iually arise in a kidne t lat at no time has been much larg. than usual. Considering that there ai yanous Kra. es of invoK ement, a kidne ypic-al of the a.hanml condition wi be .lescnbe.1. For such there are man names such a.s granular ki.lnev, con tr- ed kidney, small white kidnev fi'To.d nrrhotic or .sclerotic kidnev or the kidney of indurative nephritis i iHTc seen, to be many different wav. at least by whicli a kidney arrives af tins; as a .swjuel to parenchvmatou.^ iicpliritis as a sequel to acute nephritis without the interposition of a stage in which the kidney is large, from arterio- poisons like lead, and •,. ., r.!'nu7''\ , ^""*' ^'^"""^ chemical hard, firmly elasti • ! i ^ ihe kil " V '^" ^^' '^'^"^>' ''' «'»""' small knobs of a few m linl l ■ 'i ' "' ""^^ '"'"^"^^ '^ '•o"k!' «"'' rcmo^■e the caj.sul V" " "f ^ •'""''''■• V'^^*^" ""« ««empts to of much pulling and Ih i? ! ?'■ '" '"•"'^' P'*"^^^ ^^'"^^ the exercis,- hreaking tl.,. itv fib o^V', I. , >^'"'K -^I^PPed one may see gradually itself niay be n,,,chth Sir ctso; •'"' *'^'1 '*• ^^^' ^^P^'' to be seen bv the naked e; .^'t *^ ''«"«"« «'^»'. ^roni those scaraiy jut from thesurface or be ml I^^V centimeter in diameter, m..^ them. The peK^ Ionics iT I * "' ''"*' ^ '*'*^«^ fl"'^ runs out -if lying in tl... CO .,; J -e ^iir? T"^ "'■''""' '? "■'*"'^"^^- ^-^n^Werable .at that the kidne", secti-r ''"'" '\''"'^ ^^' kWney sub.stane. . "H.. on .section may prove to be yet smaller than it seen., d. CUn.uiv in.e,Mi,i„| m.„l,ri,i.s u„,,,i| «r-,„. ular k.dn,-, ,. (MKii.i P,„i, Mus.) ina, the most suggest that >ts. Fats or ■h tend often >■ be seen in stitial tissue, isule, or the lobulattd, so more lobes, ace, and the ind scarcely Snite, easily 'tible thick- interstitial itip. — The into this: ly, on the n a kidney luch larger it there arc it, a kidney dition wiil • are many Iney, con- e kidney, c kidney, nephritis, rent ways arrives at hymatous nephritis I stage ill n arteriti chemical is small, >ugli with empts til ! exercisi ?raduall\ ! capsuli' ! scarcriy ter, niii,\ IS out ol' •able tut tanci'. ;> seenii il. CIIROXW IKTERSTITIAL XKHlRITIS ni 5 ...;sv exhibit a„,v wiilr *, t%i«^; '"rS''' ;■"'• r*''- ^ -''!•!•" more S^'m,2irffrh'V""""''''»'''''»"«««Pt^ ;- l«rRo,aml the ™XE,Jt «"'',';''» T °'l'" '"«'• """■"toes (>U\ THE rmxAHY system merely by a round hyaline mass in which a few flattened nuclei are seen; tiiese are evidently (jnite out of commission. On coordinating the Kross and microscopic a|)i)carance, it is found that the granular surface is due to the effect of fibrosis; where a bami of fibrous tissue has pulled it) the capsule, a depression exists on the surface, and the knobs are the i)rojection of masses of tissue not |)ulled in by the fibrosis (see Fig. L'N.'>). If such a kidney have suflicio " tubules left, it may show the marks of cloudy swelling, but too often there are no^ enough for this, and the cut etige remains flat and well-definwl, without any eversion of the edge. One is struck by the large amount of urine that can l)e secreted by such a damaged kidney. Fl(l. 286 Ficj, 287 .^ V>" ■^^ifgr.;%L Surface of an arterinsclerotic kidney to show the charartcristif depressioni* («), Seoliiin from a raac of acute scarlatinal nephri- tis: convoluted tubules showing acute parenchym- atous together with acute interstitial nephritis, evi- orv.;d for the coiuluctum of the infection being spared. Micro^ M.-pically. the abscess presents nothing that necl be here detailed- tl... surrounding tissue may show ce '^fo™ the general s> stemic toxemi^ as tn.n, the proximity of the abscess; by this is meant that if a tubule near an abscess be m a state of cloudy swelling it may have been rencS ■n I r "'"'/'i!'* '•'"', ^•'."»^o"gi"ally from this or another absct'ss and traversed the circulation before reaching the tubule Nuh a condition of the ki.lney tissue is usually called suppurative .hntis. in older phraseology "surgical kidney"; in the case in which I i> «ausergHn from a cage of tuberculous pyonephro- sis: the organ ia converted into a series of xica filled with brittle caseous matter. (MeGill Path. Mus.) k:.| (;2() THE rmsWHY SYSTEM i Ifj 1 imperfect. Pressure atropl.y (Mcurs i„ hyze. The Lest n.eth.Ml .,f .le.nonstratint clou.ly swellu.K pearinK as n.uiid masses, smaller han normal J he hyaline cast is probal,ly ,lue to the c-hange undergone b> epithelial c-ells after they are shtnl, although occasionally coagulated albumin may form a cast of like appearance. Vacuole Degeneration Vacuoles may be seen in the epithelium of severely damage, tubules in nephritis, usually occupving the part of the cell nearest the lumen; the discharge of such vacuoles is thought to increase the all)uinui in the urine. , Amyldd.-This apjH'ars in the ki.lney us a deposit occurring first in the glomeruli in cases of general amyloid de,«,sit. The condition has no hing to do with the appearance of the waxy, .so-called amvloi.l cast, which IS probably a m.Hlification of the more frequently seen hvaline cast In advanced cases not only the glomeruli are amvloid. but the capillaries and the l.a.semcnt membranes of the tubules show the change. Ihe ^-essel walls are thickened, transparent, and the lumina mav be almost <,r entirely obliterated. In an advanced case, the cortex is greyish, in plact-s translucent, and the glomeruli mav be recognizable as grey dots, which react to the tests referred to in the paragraphs dealing with amyhud in general. Pigments -Pigments found in the kidney are derived from the blood or bile. IJIood pigments may be laid down in any part of the kidnev appearing even in the .secreting cells. Bile pigments lead to a ditfuH. or circumscribed greenish or yellow color, the secreting cells again readily becoming af'ected. Uric Acid.— Ileferencc has been made elsewhere (p. 317) to the ill- understood deposit of urates s. m in the tips of the pyramids in infants at birth or shortly alter, the .s,,lts are de|)osited in the lumina of the discharging tubules. Progressive Tissue Changes.-Hypertrophy When one kidncN i^ removed the remaimng .mc gmws larger by :uercasc in the sizl- „f the glomeruli and th. tubules; it is not certain that in the very your- 77/ A- KH).\fCr~ri MORS 621 Iht.. is not an actual growth of new tul.ul.s. |,„t s..«l, is unlikclv. I Ik- vounKt-r the ,M-rson. tlu- Kmtt.T is the .•apacity for l.vrMTtrophv." Tumors.- t will hv nrall,.! tli.-.t ti.e mixnl t.in.ors of the ki.lnev arc nt .•onsi.lerahl.- important.' an to he (listinKUishe,l from the "hypernephromas." which also mav he very rich in fat. Most s,Hcall«l myxomas are .as., of mvx.>matous .l.«.nerati..n of some ..ther f..rm of tum..r. 'I'he so^-alletl Mriom* is pn.lmhly always more correctiv a telanfiectasis Adenomas.- These vary in size fr.)m a millimeter in diameter t.. >.v.ra centimeters, are single ..r multiple, soft and white. Hist.n "l^ncally. they are s..l.. or tubular, ma.ie of c.lumnar «.lls. an.l the 1.I..S may even be .lilate.1 into cysts. These aden.,mas arJ prone in I. .■ life to give rise t.. carcm..ma. an.l b.,th terms, considering th.- on«>n of the ki.lney. have t.. be ilschI in their hist.,I.,gi,.al sense ■ m tluTwisc; th.- . lagimsis iK-tween a.len.mm and the malignant ^muth may be .lifhcult to make. esiK-cially in those carcinomas arising n.n, the tubular ep.thel um, as .listinct from th.,se of pelvie origin . M.,rrh..us. simpe. an.l mclullary types are f.,un.l. th.' tum..r bdng N .. ,„.,s. I rone to degeneration, hemorrhage is a likelv .)ceur;ence . Huiulary carcinomas are more common in th.- kidnev than primarv Sarcomas.-Kndothelio.nas, peritheliomas, an.l sarcomas < f ,i ;l s .in. le eel s are foun.l in the ki.lney. b..th in youth ..nd in add • . the large tumors supposedly of this nature, in th. ^er^ voung "itn. pn.ve t.. be mixed (teratoid) tumors rather than pur, sircomas .l.™f^Tr ^-»f ^"r f-^-'^'^r ^'^ ^--' «' birth or sT-rtlv ' h-generat,on, and have l^n known by a great variety of name : "l"
  • i-is of ;i nu-sliwork of capillaries, \ rows of (rlls variously arratiKitl aioiig tlu-m; ti,e ci'lls are often those of the adrenal cortex, wliile in pla-^-: they are ..• anKwl masses auear in otherwise fairly healthy kidnevs of old people. !in THE URETERS Abnormalities. —The congenital anomalies of the ureters mi neces.sariiy of the ki.lney pelves) have been considered with those c the kidney; the circulatory disturbances are of no moment, apart iroii their occurrence as features of more serious changes. Foreign hody 77/ A- IRKT/tUs 623 « -state of affairs that s.H,n allows the suppur.. . .rspreac to th^ n<.. to r.n«I I- ^'''^ "'"^*" ^"^^"^ t'l^ bladder. This gives riM- to renal colic or more str ctiv nrataral .•aH^ „ . • ^ ">nii.hcation of nephrollthimid.fl ^ I' ^- '"'^' "»l>«rt«nt »s a foreien bodv in t),.> .., ♦ ' nn. ' "^ "'^ * *"'""'" ™ay act ■".)■ =r,« from the internal ,„se, tlS to aCe .;. ^^^^'T Impure fmm outside »hich „ ,v be exeS by . .ariet . ■ i ^^ -"'^'We to eianl anfr h ^"'*^- ^^'^ """^ '^•**^ i"*" it i. " V ^^rb l:'i£:„^7rrLw^it'r'if-'S'' ■"^■"■^ spn mliiii; bv contiViii-fv. «-Tk • * • ("**•"*"). the inflammatbn t ■'';^|<^f^"^sSS":™i;eS,'°sS . »el,t« and uretenfs occur bj- extension of a ber,oge„o;;^ (»24 TIIK llilSMiY SYSTEM infection .,f the ki.lney. The ,,y.,Kenie ccc-i. Baciili.s coll. a.ul «,„,,. infeet the ether by way of the ureters and hhi.lder nv V ' . the h„,„K membrane „f the pelvis, or the fluid exuded max be purulent, with or without the formation of a membrane; ..hen stone IS present, the irritant effect of the stone superad.led mav result m an ulcerative or even a Ranffrenous state of the wall. When the .nflamma ion is of long duration. pro papillate nature may be noticed. The ureter in its course caS rJpro^ luce any or all of these states, although the complications due to tll^ presence of a stone are infrequent, because the stone is not likelv to tZ"" Fi nl'll- ■ T- T*;'"'*'""*. Pr"'P'*"^'"« *'•*' ^.vmptoms of obstruc- tion I-i, alh, It IS to l>e noted that in states of chronic inflammation the pelvis and ureter formed masses of mucin may be thrown off \n the surfat-es, and their passage down to the bladder mav be the t)ccasion of attacks of ureteral colic. ^ Tuberculosis.- Miliary tubercles may Ik- found in the pehis or ureter ta of IfnT- "^ tuberculosis, but more often a localized caseous state of the pelvic xya 1 follows tuberculous infection of the kidnev Ihe wall becomes thickened, n.Klular, caseous tubercles coalesce, and' the H'lvic cavuy become, merely one compartment more of the multi- ocular caseous kidney (tuberculous pyelonephrosis) . Perforation of the wall IS provided against by the consi.lerable thickening that it undergoes. Parasites.- Parasites infesting the kidney, and. therefore, the pelvis and ureter, are not commonly found, but echinococcus, cysticercus. mana sanpmus, and eustrongylus figas may be mentioned among those tnat nave l)een found. Progressive Tissue Changes.- Tumors.-Tumors of the ^vis of the kidney and of the ureter are rare, \illous growths-papiUoma- are the most common, and are apt to give origin to serious hemorrhage, sarcoma, carcmoma, and teratoma are seen occasionally Cysts.- Following chronic inflammation, the wall of the pelvis or irre ter (,,r even that of the bladder and urethra) may exhibit liiimerous small pinhead c.vsts, containing watery, yellow, or even brown fluid, ihe trig<,,:e of the bladder shows the best examples. There is with these (.ysts some epithelial proliferation, ami the conditi..n is known i.s pyelius or ureteritis cjrstica. i THE BLADDER Congenital Anomalies.- The bla.l.ler may be absent, the uret.rs openmg into the urethra. <.r the bla.l.ler an.l rectum mav fail to '.<■ sei)arate.l ..rnimg a <'U„w„. Septa .)f the bla.l.ler may exist. Extrophy ". *•?'■ f;l«"l''r. the in.)st .inp..rtant anomaly, is seen when the two lialws ot the b.).ly have h.ile.1 to unite along the mclian line; the postci-.r THE BLADDER 62o wall of the bladder lies .,pen to the air, the pubie bones often Ivine M.pnrated by a considerable spaee. Freque, iy there is also wi h"f ■:';;\Tt;be w7*Tr"'^'^ ^a ^''^' ^"^"'^"•" "^ '"^^^ bladder th;ou;h fi,h;iV\.K ihe "rachus may remain patent (yeslco-umblUcal fisJJa). or hy .m,,erfe>et closure urachal cysts max be caused Circulatory Disturbances.-Hyperemia.-Active hvperc^n a occurs as . sta^c of mflammation, and may exist without developin/further in rases where the ur.ne is irritating, by reason of exccisive aciHtv i? tl.c presence of certam chemical substances. Passive congestir affec .n.' .specmlly the tngonal region, accompanies gcnerul svLS ~s. ...n; UHlema ,s a frequent accompaniment. Hen,orrhage in the form of ..•tech,a. ,s seen m cases of cystiiis. new growth, and those steteT Tn "Inch ,t IS found „, the serous an.l mucous membranes. Ilemorrhai^ ...winch .nuch bloo,| is effus^l is generally due to new grovv h^r'tonf .Vrtinr^r; '^^"*t "'^'^ -"- •»• -tension li inSmmaS Irom the ureter or urethra, or as a result of abnormalities in the .-...tents v.^., the presence of stone or decomposing uri, 1 areh ..■ .nfeCon is hematogenic-. Of all these, the most potent cause! f !..■ rc.tent.on ot unne, the distended blad.ler being less re istan thTn the .f mtate the wal ; n. th.s state, a .lirty catheter mav intro,luce - nrga,„s„,s, or waslnng n.ay wash ba<-k the urethral c-ontents or he I'l' '< '< I may carry the necessarv germs. Tl.c "rine is liable to un.lergo fermentation, alkalinity being produce.1 \ tl c action of the m,croaH-a,. urc^. It is bv no means necessar tl.at he unne n. cystitis be alkaline; indeed, numerous ca.- arr^,w M |.orted ot cystitis, with acid urine, due to the B coli Acute Cystitis. Catanhal cystitis is a comparatiA-ely mild attVctinn j- .t .s notable that the bladder wall at au'topsy mav shl ll;,^ " '•' ..ake,l eye, although the existence of the inflammatio be Ke 'I. -.tl. was undoubted. The mucosa may be faintly redden^? r wd tn S-naiy around the trigone. .\ suppurative staie, however, sSh' :i' "in." £™',t.i:'z;;: ' "- ""■'' -'""" »'• «- « '-- Chrome C^BS..-A sliRht act,, cvrtitis may ,„f,i„ i,„u.fi„it,.lv nn,l t 'ir,;,,;'''"'' ''.""■'"'"'• "'I'l »<>■"«""« ■«ntra,„,l and r , ..T™ 02C. THE VlilSAHY SYSTEM Tuberculosis.- 1 hv i,i„st fm|iioiit mumIc of infection of the bladder h tiilHTculosis IS l)y tile passi.jre of l)a(illi from the Ividnev ; this is evidence by the frtHiueiicy witli which a tiii)ercu!oMs ulceration of the hladdi wal at a .ireteral orifi.e is seen. Xotwithstandin^ this, tlie health bladder wall can resist the attack of the bacilli for a c.nsiderable tiin, but a preexistiuK cy>titis of any (krnr will lessen this power. Pro. tatic tulHTculosis IS also able to infect the bladder. The disease i seen as nnhary tubercles, each ^rey nodule surroundeci by » snia zone of hyperenna where tlu- bladder is infected as part of a generalize: tuberculosis, or occasionally where the bacteria from nearby sites hav been we I distributejl in the uriiu-. or by extension from a caseous foci. m the bladder wall; more frctiuent is the localized caseous lesion rapidly ulcerating. This arises by the coalescence of small tubercle^ ami tends to spread oyer the mucosa rather than deeply into the wall The caseous material, constantly waslici away by the urine, may no be eyident, and the ulceration may be mistaken for a simple one' Syphilis.- Gummas of the trigone haye be(n obscryed, but syi)hili of the bladder is Aery rare. ' Bacteria and Parasites. iJacteria are freq..entl\- fou.id in the urine the micrococcus urea seems to be a constant inhabitant of many healtin bladders. 1 athogcmc bact.-ria of all sorts are founrl, whether passe." through a healthy kidney or not is .lebatable. Yeasts are found i. the urim> o diabetics, and sometimes of healthy persons. AmoiiL parasites all thoM. referre.1 to as being found in the kidney, pelyi« of the kidney, or ureter are naturally also found in the bladder, added to which are the .gg.s of liilh„rJn hcimiohium escaping through the mucosa (if the orj;;in. Abnormal Contents. i{lo,„| corpn^.Ies .,r ,Hginents api)ear in the bladder urine in some ca,es of nephritis. i„ ulceration of the tract, 111 the hem<.rrhagic diseases and in cases when' there is a neoplasm Desquamated epithdinin from the bladder or any higher part of the tract IS seen, as vvell as casts of all kinds, an. I 'foreign boe.l •lown troll, tl... ki.lney, a...l may form the nucleus for phosphatic or other d.p..si!. I-oreign bo,li,.s or mass.s of cpiTheliun. may likewis,. lorrii a nucleus tor i)urc phospha.ic >toiies. Regressive Tissue Changes. Atrophy of the l.la.l.ler occurs in ..1.1 age. as well a. ... .some ca^.'s of a.lvanccd cacl...xia; the muscular tissi.e becomes git-atly l.-ssencl, ainl th,. wall may be of extreme tliinn<...s. !>istrn -on h.i.g .■o..fn.,.,..l, is ah!., t.. I.rinu about the conditi.m. The usual .rliular d..p-ncr ,r,ons ar<. f...,.,.i in the i.iucsi.l c.>Ils: widespread necrosis usuali. uct-urs from trauma as in i)arturiti«* ^-^^ '« als„ a "".i firm; the trabecnk- are e -^r i •*'''''''" ''"" '" thickened '"'wcen the trabecut i. h^ "/ '^'' '''"''''^''•i *''*' ^^-^l' ■"« thinner to >ac,.„iations c.r " t h r,e , S ^'X '""'"' ""*' «'^''"^ "«« ;" tl... fnndal half of the l>hMld t ' *" **"' "'"'* ^^^ *° "^^•"- i'lu 2'Jl Kpilh, l„.iiia "1 the blmlder infiltratinR tho tnu«-l.. ,.„„t : „ with comnifii.itiK invasion; l<. rnnciT ci'li»; , •■•inncftivc ii..»iio. muscle tilircs: ,/, >'« I.MSS Mtfa,.|,„| rr, " i . : T ""^'' " "■'< >'l„.,, „r 'I sr,„v,l,s ,; v„; ;„ ™ ' ,",' ""• "» ; '»"""> "••I i" <"i..r. "'■ ;■ »Hv. .lu..:;;,, '';,-" r i;;. »: "— . '-ii.v. <"iiiirrti\,. (issue .nr,. , I I irM-iike tuhior consist of a ^<"- "f thcS ,,2 ™ l' ^^^I'^T^ '"l''*'^'' o'- '■"'""-,. cell" ''-•l"-tl, seen Tn r J Iv, , n '*' . "I '^'" '^""""-^ ' Rbromas are Myo-nas, angiomas Ldenomll''" Vf "^'"." '«■<'>""■'»? '"^xoniatous. '^^'" -l.m,|. fUt • ,? ! l"-"j>ahly arisnijr from misplace.! pro.- "'■'^ U Hit ,,.»,• -*qnam.,us-c,.II,.l varL-f/; these ir.mths prtaent.s n„ marked naked eye .liHerenees, save that 628 THE IHISMiY SYSTEM perhaps the majority of cases of sarcoma show multiple growtl hecoiKlary carcmoma of the bladder is quite commc.n. in view of t liability of neighboriiiK organs to the growth. \iz.. the prostate t rectum, and the uterus. Displacements of the bladder occur frequentiv in the female as ■ accompaniment of displacement of the uterus and other organs- tl bladder has been found in hernial sacs, and we are acquainted with case m which a diverticulum of the bladder was removed as part the content of such a sac. THE URETHRA Congenital AnomuUes. The urethra nvax be absent in conjunctic with other grave anomalies. It may open on the lower aspect of tl penis (hypospadias) or on the upper side (epispadias); it mav have m..i than one oi)ening. or may open at the base ..f tiie scrotum or into H vagina. Obliteration or valvular obstruction of the urethra mav occu Inflammation -Urethritis. -This may arise by uncleanliness. froi toreign ImkIics, from trauma, from calculi, or from the injection of ant septic fluids, but of all cases of urethritis overwhehninglv the nw are ' """' "<■" " !""« Period, |.">tori(.;partof theure hra s"tZl T^ ^"'^ ^P*"" ** '«««* the »< ...iliarv or oai^u, f^r |„e , ' ,h. '''''° ", "f .""«"""■ '^'"e »«" l»rl,„ril„.trati 'P"'"'' °' '"'e'""" '"»" «het "< iirs as a iH.lviM.ifl mn« r«,-L i ^" "''"»"» occasiona v i^" I'i.iK th. li^. ,^ t\ ZIZT "•^.'^"l"' P''*"^-^»t« the instrument from "I' 'r, i, MM,. 1 ,, weaH-n '?• '"'' '''^P'^^^^V"?" P«'"* "^ 't latcrallv. -:: n::,;^;;:^:"ir^^'"'^^ dist«n.?:i:^^„S.t^\^^ rFFAPTER XI THE REPRODyCTIVE SYSTEM THE MALE SEXUAL ORGANS THE PENIS ni«2°**"l^, AnomaUes. -TJie penis may be absent, double, or hyp, Plastoc. ^yh.ch ast ,s found in cretins, m ptorchids.idiots^tc T^ 3rnnP»»«Pa.l.as have been considered with the urethrT nect^,^ ."^ ^^^'^^-^^^ valvular heart disease, the lax on nee t^^ e tissues of the penis are apt to be the seat of «dema, the corpoJ c-avernosa becoming enlarge.! ; the lax tissues of the prepuce m^-al' ;: t Tt'r^lr • '"'Vr^^ '^'-^^^ ^"••P^^^ ma^berme^Lkt M, that the corpora cannot be emptied, with the result that chroni, c-ongesion with erection (priapism) results. Bands, s rings or S Si':;')"'' *'' "^"? •'■■'^■•^ ^""^^ ^«"«-- by ;eason of the >^ r.ction and consequent great congestion. Hemorrhage may occn, hematoma. ""'" '^" '"'^"''^ '^""^ *''^"'"'^' ^'''^ thf formation ol Inflamnwtion -Inflammation may att-K-k the skin (dermatitis), the prepuce (balanitis , the glans (posthitis), or the corpora (cavTrn^tL) Lr^iLTl^""'' *''^ PrP"^'^ '"'' f^'^"^ ^'^ ^««^ked together Tb^^i: t^-ll^ • *''%P'-^'^"*'«' f^. being specially liable to inflammation from f the weliinrTT"''':™,*^^ ''"•^«™"' P"^' '"rt «"d urinary salts. fL 1 "r^ ''^^be parts be great, it may be impossible to draw esursle «"T^ (Paraphim<«is) Ulceration and even gangrene m v [he LZr? 'ir°"' ''"' subsequent adhesions of one laver of sequel? n ■:"'' °u "V'"^«tion and fibrosis are more frequent aSce s f,r,? T'""'-!!' *t' •"*'^"''°" being c.lo.se.1 in may lead to siderabl. :•' ^'.'tb^^b.sequent rupture into the urethra, or a co„- e s^,tr« r^ '" '*• *'""'•"*''• ^•'P*' Progenitalis, connected with vhi.h TrSr "'?■;"• ""'"'•'^^ ^ ^""""P "f •'^'""» vesicles on the glans which rupture and form erosions. i,nn!^^;~J'"lP"'""''''' '"'''•" "^ ■'•'■'^bilis. the hard chancre, is the most on^h n • "{'P^'«'"'« f'^ee weeks or more after infection. Til P"'''"''*^^' "^■"'- tbe raphe, on the corona, on the skin, or even ' r ; "'''*'"■"•„ l^eginning as a minute vesicle which mav rupture, thtrt IS generally a small ero.sion surrounde.l by a reddish i)orf the con- nay occur mation of ititis), the lavemitis). r (balano- ition from lary salts. e to draw jrene may ; layer of ' frequent r lead to or a con- cted with the giaiis the most infection. , or even rupture, >rdcr, the a s„peTO,„l iav" , f ,1. "' .'" '"/"""■ '"" '!»« M infect Fia. 292 ^^-^ '^%^, ^J.^^< --''uf;:;;S;h^;^*'''" ''^,^^'''""«- ««^«1 "fte„ by bacteria. . ourgrowth of the mucosal elements the condyloma, which is reat tendency to u ceriiti,,.,- «„oii, /»«"!», wmcn is ^'■•rr,,.- the formVt^n' J . " '" ''' ^''"'*'' '^^^'^'"'« ^''t'> much '" 'i'. site of Tr 'Tmfrv r^ ''"^ "" ^P«^^''«' '«'«tion --.itai^:.^=iors;;;lS:i^r ^^ "^^'^- *« ^""°^ - hard mre just described is the chancroid or soft chancre or soft (W: TIIK lih:i'liOhr(TIVK SYSTEM •K'y- sor^ a non.sypl,iliti,. soro that fr.-qnn.tlv arises on the iK'nis cans. »ase, on «lnc a nmnbrane. It is oftenest fniiiiH .,n . L n ■!: 1 I *- '™": ' ^'""^"'♦'••«J that many fomm..n pathoeeni, o7;' •• ''',"'\'":'' «'rta.nly present in nearlv all cases are caS of HKlucnp the les,on. A eha.KToi.i «,„y k-come infeeled whh sn ^ 1 om n It ^^"'**'"-*';;:' t''r ^•'•aneroid, but the systemic infect! „ III (K(ur all tlie san,e. The chancroid mav lead to severe balan t s ZnlT- ^"'*^/""' *•'«' Pt'">« "'ay even l)ecome phagedenic nhaire tutrek b.er.v like'"" flauS b?^?hl ;. f 'r.'"'' **" *'"' *^'^'"' "•■ P'-'-P"^^. sometimes Sze \ i.r, ^ n ' " "^ *"^''* P''^P"^*'' sometimes reaching a large vere.fl T'"' •■• '"• ' "^^ ^'^"'^'^t^ "*" « «»^'-o"« vascular a fe oven. I bj squamous epithelium, the core often branching so ahto easv The nLir t. / , " 'liagnosis from carcinoma is n<.t un ';s ulceration •. *' ^""'-V'"^"'^'^" "P"" ^^e subjacent tissue. pro ection sSr .r? ^'f**^'"' *''^ ""tgrowth of a hornv Et .?.,?« .. *'"'* '""'• "" *^^" •'^'^'"- '"«>• «'^^"'-. Elephantiasis, phaS: tt s nl'"''"^^^ *■?'"'= '* '"^>' ''« ^-ombined with ek- Sbe T In ""' '-'r' ".'•■''/ *•""'"• ^^■^'•^'""« 25 kilos has b..., o ten tie sent 7V"7'-'l,'' ''"''^•^' ''^ ^'"-"""^ *'««"« «"d is of course otttn the seat of marked inflammatory infiltration. THE !• HOST ATE 633 ""I»<'rta,K-e is c.n.si.loral.l... ' „ j v i7. t! ' ■?"•"''• '" *'"^ ''' «rmvtl,s just .iescribed ma rr r'"'" """ ^^'•'•^>- «"'' '^^'^atoid ".Tty growth bo«i„,s L, s^," s 7 ' r ! ''■"^•'"^:'*"^• ^''"^ « «•""" '-- that .n„y ennle thn. ^ tt .. , «•' M '"''• '"™"'^'' '"^""""t Miiiss contain a foul whitish T '''•'"'•''•.""' ""merons fol.l.s of tht --lily, the surface Cm nnSnT"'''',','' '""' "''■''™^'"'= «"-"r^ naturally the earliest sitTextentZ^^A^^ ""'""""' «'"'^<'-^ "^^ .-> well as endotheUomw ar . fo , -^^anofc a.ul other sarcomas, ^vl.ile of the iH-nignTr^Z fiZm.T'"'"''-' ^".'"'"-^ '"-^^ ""t common .S.|.am>us cysts of th'e "Ci. aX^nr? "'"' "^''^"'^ "^' ''^•«"''>^''' Injuries of Penis.-Iniuries of t J • ^'"■''"' t-ncount -re.!, luxation may occur b>- th^mai ifr' ^ '^r.""" " "'""^ '" d«-< Wpt.on; Tom the prepuce and c'^rTi 1„ ' '.f *'" "'■'^"" '»*"'■"« «Wt.ed tluskinofthitrunk theorTlLL, •' '".*''"* '* "'"""^ ^o lie beneath ^^in. P^acture. chtfly ru^ T thf cT'"*' "'" "" ""P^^' ^"-^- "ith some frecp,e,,cv when i was snnnfr T'''''"'''' "*^^»"«' <-.lee could becur;d by^Vlln^r-'irSg th-'coS/'^'''''"'" *'^^* '^ THE PROSTATE ".':Tar„f?:nvs:;lt '"?-"■ ^^ - -' •■■•"■ I'lrculatory Distorbaneoq — h„«- " • v.'^y oom^miy a J:^%^.S^^: :^:t;^ ^TTT'- '^ >.-.., and phlebolltbs are common *^" {"'"^t^t't' P'^xus -^^^^^mltsi^ti""""-'' ^*'""*'' '' ^-'-ho-al infec- '■" ""■ «lMui tubuL the nfced:: '"^"''•^ ^" ^''r "-tl.ra. He^inning ;'-!••• -"i -'tipieai,s:s"^s;n,ifs;;i '" *'- ^""""'"^"'^ " tl,.. almost entire destruction ITih .. """'♦'^"nt's coalesce "'"> '"'PPen into the b a 1 'r t •/ ^rT"" ^^""■'"'•^' ••^" ^" «»>«""-^'' !-^'"-itis is ."xc-eptional v";" i ;;r "^C!' rV"^'/"'""' ''"'' ^"--' """.^ 'T, unconmion. Chronic 't ids '""' "^r^^' '" ''"'■t'''"- '"- n.nlt inc.,,nsi,ierahlefibro^s an,n f;^^^^^ •j,'^"^^ «lestructive grade, Tuberculosis of the prostate tVarvfr" '''"'''''"" "^ ^he tubules, ""ultiple caseous nodulis vh ch ma o "^"'l!."' "'r""""« t'>^" '""" "f ■'-I' -lar.en.ent. The /ZlsTZgi^^^ '''^7' ^^^^ "';'.^ > I>i.rt of an extonsiv ■ nrotrenS .1 ' "'"''"' ^"•' ''^ "^'a"-'.^- Foreign Bodies - ^^r,ZJ ^ 11 f'^^'^ful'-sis. ^ 034 THE uh:i>H()i)itTi\h: sysTK\f or another, are f„un.l i„ the ,,rost«t..> ,.f a n.ajoritv of el.h-rlv u nirRt ami i ty hke grai. -se,-.|>. when th.v are i ,filtrat«l u.th « ='''K'r 1,"* """"■■ ""••"• '^'"■^'^"^z> " .ill: ::^S^:;^3:i;;;il';;-:."' "-" -■■ -«.-! fn.^*'^?"*^*' ^''?"* ^'**°«*»- Atrophy ,„rurs i„ aln^ut „„e out M-ase. or the r.rese.u-e of eoneretioos. I,. the last ..a,,.,' S; stn suffers most ..therw.se the ^latuhWur ,H,rtio„ fX . , h»» ofrr" '' ''" '"""'^' «''^- «"•' "^ '"^ n>ithehr'are"l'^S Ki(! 2!W middle lobe of pro.-ale; h «i. ,.|v l,v„ 7 " Tl , ',". "" ' "' "'" '"■•■*'""■ "■ ™l"««' "'"l"'^' mnse.is of , Z ; . ''^' ^'':'n'iy .hstiMguishe.! from the same. The oUn " con 1 f r'!-""'?'"""'"""t''» "f ♦»^'-' "r'^^thral part of (he S hu,ertro>h , ?^^ ''^''^^T'" '^^"^'""^ Ronorrhcea an.l pros- iimummation wi^ show itself in several wavs: •'l"'''*>■«" o^en n.;:..^' t :urp!;i:!;;ir:?';r "^ ^t ""'^•"-' •-^«*-. ^^i'l. o.v.stic dilatation ^"""^™*'"" "^ t''^ Rlan.lular epithelium, often "<■ ".ay fin.l a cwsiderab rdSuse^*^ ""* ''^, connective tissue. •"".''int.1 with that of the muscle ''•' ''^T''"^"' "^ '"""^tive tissue 't.n.i "TI from ailcnocarriunmo «f *u '» "t lumen formation. ''" """"""^ ™r,inoina.ou8 growth (r,, •troma (a), with mero ''-this „o.i„|e or ricfge p^^^^^^^^^^ '''-'•'♦r contracts, obstSTh^or^r t T' ^' * ^'^'^'^ ^'^^^^ the :'['";'/.on: this leads trhTpertXhv a^d K^' ""'"'^'^ ^"^ '"I^es '''"'•'•■r. and causes a bav or f ^ ^- 1 ?>«iuent dilatation of the "" '-'-H- wh,?h fail titsr • 'tw "V" '''' ^«^-* P"t of ''- 'table seat of bacterial jrrowt7 mm whTch "*'"?' ^"'^ bec^^nes an •"■' ''ntis, ,,yelitis. pvelonephrh s anrl nv k''*"'^'"^ inflammation, '"■'" -'I "rination calls "or thfemlvS. f^^T ""^^ ^«"'t- The Mini MICROCOPY RESOIUTION TEST CHART (ANSI ond ISO TEST CHART No 2) 1.0 1^ 1^ 140 2.2 2.0 1.8 ^ /^ppuEinjvHr E inc ^^ -655 tast Main Street —J Rochesler. New fofk U609 VSA ^Si ■ ^16) *82 - OJOO - Pt^nne 5SS : '16) 288 ' 5989 - Fa. (130 'tut: Jtt'PiiuDicriVE system It' for in the normal jjrostate of early life it is non-existent. Hy most it is regarded as an ontfrrowtli from one or other hiteral IoIm-. Tumors.--Of malifrn nt jjrowths, carcinoma is the most important, ocenrrinj; as a primary neoplasm, and not infre(|iiently in a gland previojisly enlarged. We have observed one ease in which urinary ohstruetion with enlarged jirostate existed for eleven years before tiie devel()j)ment of an adenoeareinoma. I'sually it is soft, nodular in one or both lobes, and spreading rapidly, it infiltrates the "eapsule" of the gland, the mucosa of the bladder and the prostatic urethra, or may go through to the rectum. Microscopically, it consists of cylindrical or polyhedral cells, arranged in an attempt at glandular formation or in solid masses. Metastases are not a markwl feature, and happen first in the retroperitoneal nodes, although in some cases there is a peculiar liability to form secondaries in the bones. Sarcoma is infre- quent in comparison with carcinoma, but occurs in childiiood, sometimes as one constituent of a mixed tumor. Secondary tumors rarely attack the prostate by metastasis, but may extend from the bladder or the rectum. COWPER'S GLANDS These small bodies, lying behind the bulb, are liable to inflammation by extension of processes that originate in the urethra, and rarely to cyst formation from blocking of the duct. THE TUNICA VAGINALIS TESTIS It will be remembered by the stmlent that the testis, primarily in the abdominal cavity, descends into the scrotum along the inguinal caiuil. In this descent it pushes before it a prolongation of the perito- neum behind which it comes to lie, and along with this there is pro- jected a p()rtion of the muscular wall to form the guhernaculum testis together with associated vessels and nerves. Folhiwing this descent, the j)rocess of the peritoneum becomes normally closed off from the IJcritoneal cavity proper. Xon-closure, with persistence of the inguinal canal, favors subsequent hernia. Tht' testis thus lies suspended behind a peritoneal sac, one wall of which, in juxtaposition to it, forms tiie visceral layer of the tunica vaginalis testis; the other, the parietal layer, is separated from the skin of the scrotum by loose tissue con- nective tissue, in which is the cremasteric muscle." The visceral and I)arietal layers enclose a .sero'is sac, and this serous sac may show all the conditions seen in the <»ther serosa.' of the body. Abnormalities.^In the preceding paragraphs we have already referred to these, viz., the patency of the neck of the sac. Inflammation. — There may be a certain amount of anasarca of the tunica; of greater importance, liowcver, are the collections of fluid resulting primarily from inflanunation, viz., the condition of hydrocele. rilF TESTES AXD EPIDIDYMIDES (W7 litre It IS held that the first stage is a serous periorchitis resulting in . isteiition of the sac by a clear serous fluid, and, once accumulated, the tendt-ncy to secrete fluid is maintained, so that tapping is often toi lowed by reaccumulation. In more acute inflammation the fluid may he blood-stauied and the exudate of a seroHbrinous tvpe with ^ "(curs occasionally after trauma, the testis being forciblv displaced ■/•■■m Its site, usually uj) the canal. Very rarely both testes have been '"I'i'l 111 the one-half of the scrotum. Aspermia. .\bsence of discharge of spermatozoa in the adult mav '' 'liH' to 0) lack of production in the testis, or (2.) to stenosis, obstruc- ().*?S THE HKPRODUCTIVE SYSTEM n- tion or destruction of the vasa deferentia as the result of trauma inflammation or new growth. Prolonged obstruction to discharge leads eventually to atrophy of the epithelium of the tubules of th( testis, and so in certain cases both causes mav be ()|)ei ive. Deficieiil production of si)ermatozoa, with consequent' sterilitv .m.\ be brouKliI about by many causes, some congenital, some acquirea. Thus aspermia IS encountered where :he testes are retained in the abdominal cavitv even although apparently fully formed; for a few vcars around the age of twenty it is stated that such cryptorchids may" present spermatozoa in the semen, but after the age of twenty-four they are uniformlv found sterile. Imperfect de'-lopment of the testes has also associated with It aspermia or oligospermia. Such hypoplasia is frequent in cretins accompanying defective development of the thvroid; in acromegalic giantism there is a similar aspermia and lack of sexual capacitv In the very obese, men and animals, aspermia shows itself, passing off with reduction of the olwsity. (Jeneral lowering of vitality as bv long-continued disease and after excesses of various kinds, including mental worry and overstrain, lead also to lack of development of the spermatozoa. To the contrasted condition of precocious sexual maturitv we havp already referred (p. 102). ' CircuUtory Disturbances.- The only serious circulator',- disturb ances are traumatic hemorrhage and the seer. as a .iiffuse fibrosis, 'the so^alTed white swelhng. Less frequently definite gummas develop. In the former ,o,Kht,on he testis beco„,es enlarge.!, hard, and insensitive to pressure hn.akdoll • " "'*'^ ^"'--ulosis, the skin may be involved and Regressive Chamres.-Simple atrophy of the organ with aspermia is . s. „le change and occurs in marasmus and wasting diseases aTak, as t u. resul of the influence of ;r-rays. Pressure atfophy 1" d n ...m^itions of hydrocele, hernia, and neoplastic growths Progressive Changes.-Hyperplasia.-Cases of precocious develon n.ent and .naturity of the testes have been noted partSaly in con! nect on with hypertrophy and tumor formation of the adrenal cortex In tlie adult there .s httle evidence of compensatory hypert^phy after "'vl^yjoung ""'"" "' '^"^ "' '•^^ ^^'' though^this mToc'cur in Tumore.-Tumors of the testis are not uncommon; thev are char- ajtenzed as a group, by rapid growth and malignancy. The varktv ot orms described is bewildering. Recent careful studies of several •rtions from various areas in such tumors are leading to the conclu .on that the maj(mty are of teratomatous nature Severafca es are now on record of chorioH^pitheUoma. \ery frequentlv we encounter m.xed tumors wrth glan.lular, cartilaginous sarcomatous, andothe tissues. In addition we may find tumors of simple type; it seems that pun sarcoma may originate from the interstitial cells of the test's and ha pure caicmoma occurring as it does in adult life, may or ginate tron. tl„. tubules ot the organ. Other cases of so-called ca/cSoma sarcomatodes are explicable, when it is remembered STat the tSS jpi iH unn IS of mesothelial origin, and that therefore, we wou Wexpect t" fiiKl transitional mesotheUomas. expect Cysts. We have already referred to the congenital cvsts and it •Mianu only to note the spermatocele, a relativeh large .'IfOrfdna . apparently from aberrant tubules of the epididvmis which under <■ .MHuonce of some ..bstruction, may become of rdativelv gr;at size .^n..ng into the cavn, of the tunica vaginalis testis and simulat Tng I'.v'irocde. Ihis on puncture affords a fluid containing spermatozoa THE SCROTUM i ..ic h. F "^ '^^ scrotum are, broadly speaking, those ^ ,.n md^f / .'" ^'T^h ^"*^ '''"^^•" modifications due to 1 t. o . .u„, th, ,,, ^,^.^ abundance of its con,stituents. Thus the ""*"= ^""^'""^ dislUictly contractile cremasteric muscle fibres It ()4(» TIIK RKPROmCTIVE SYSTEM juul there is a lack of siilKMitaneons fat; it is pe.uiiarlv liable to involved III elephantiasis, and then may attain a hii^e size Its v (Ularity favors hemorrhage in trauma and in obstnutive heart disea' in renal disease, oedema may be extreme. Vf tumors the most importa IS carcinoma (squamous epithelioma), apparently secondary to irrit tion. In the old days chimney sweeps were peculiarlv liable to tl forrn of cancer, and today workers in tar and paraffin^how a simil THE SPERMATIC CORD AND VESICULiE SEMINALES Especially in those haviiiR a long spermatic cord the accompanvir veins of the i)anipiiiif(,rm plexus are liable to varicositx-, and as the' are relatively abundant they may form a tumor-like mass, varicocel This IS found more frequently ,m the left side ir -onsequence, it held, of the course of the vein on that side, which ren.lers it more liabl to pressure and obstruction. Mammation of the yas deferens occurs, not as an isolated conditioi but in association with epididymitis and vesiculitis; as a result ther may be a reparative fibrosis leading to blockade of its lumen and consf quent sterility. Hepirdum the vesicu'a' seminal. .. there has been som debate as to whether these are to be repirde.i as reservoirs for th sperm or as aflordm- a special secretion for admixture with the same Apparently in man thev have the .louble function. Inflammation i. Its active state may lead to marked tumefaction, and subsequently t( hbrosis and contraction. As to its causation, th,. gonococcus is'th. most frequent intectinK ajrent, though pure strepiococcus infections also occur. Tuberculosis, both ascending and descending, may involvt these and the vas. '' THE FEMALE SEXUAL ORGANS THE EXTERNAL GENITALIA Abnormalities. Th'Te is a long list of abnormalities of the external genitalia, inv(.lving either indivi.lual parts or the whole tract. Of tlie entire tract there may be complete ai«ence as in certain monsters '>;R"I*."^."| "-^ '" cretinism aiul other forms (.f incomplete development. Ot induK ual parts the vulva may be abnormally small; the cUtoris may he absent or hyperplastic, us in some cases of false hermapl.ro- ditism, or double, . as the lowest grade of inferior duplication, or adherent o neighboring structures. The labia may be ahnonnalh small or abnormalI\- larr ; the labia min..ra, as a congenital condition or as an a,(iuireinent, may be of great siz.- ^Hottentot apron). The ImIm;. THE eXTEHSAL CE.MTALIA 841 til.' menstrual blood ^ '*^' ^'"''^ ''*^^^'"I^^ "-^t^nti"" of disturbances may show them el Xr"' AHrtit T'""' 'f"'*""' »i?'i.'<^'l>^^'' "' •l» kin, and, being general resilltn I '"'^ '"'' """"''>• "' "fllBuilvarOTifte ^ """^' '"•""'■ '" « l>K>gressive contraetion .iSSV„^rro-;i^i^r«r',» '-« there .nay be M2 THE ItEPIiOmCTlVE SYS V r 3 •' ,?'"'"""''^t *'""•"• *^»" tl'is r.gi„„. an,l . a-n then not v r.(,uent, is the squamous-ceUed carcinoma. Melanotic sarcomas hi c^u ^f 'II! ' ■ . "i"'*^ '■•'*''■ ^'*"""t'""S most common are retent cyste of the glands of Bartholin. A rare c>'st. corresponding to sere hydrocele, may originate from tlie canal of Xuck f THE VAGINA The vaginal walls are n<.rmally in contact, rugose, except in t j:c«nd after frcqncnt parturition, sparsely provided . J ,L ned hy squamous ep.thehum. Despite its sim,,licitv of .t„, tlie yagma partakes ni many diseased conditions arising in it nedii neighbors, the external genitalia and the uterus. Its .olatfon iZffT"''./'"' ;•'""•' '''"''••'^'^- -'•»""''«-' the viscera in Dough it T "'*^'^"f""r "'.P-r'ti'!" 'lue to pressure or traction exert, upon It. Ihe yagmal wall, havmg no inherent rigiditv, is liable become n.yerted, or even prolapsed through the vulvar Orifice, ip, m^v^desi;^ r*"" '""""' "T"'""' '•""•^' "''^""'^ themselves; the bladd. orw..r X , t'' """' "n*" '"''^'''''' (''y«*«"l«); the rectum mav pu> ^ZeiL^^T ""• ''"" ('««=*«««»«)• "■"! lo'>P« of the bowel or eve rJl t t"' '''■''"''■ ■"'"'■ '''"■'■•"''•'^ "P'^" the passage (enterocel ovanocele). In partunt.on, and otherwise, the wall mav be injured cZ;tl-- 'T ^:''-'^'" '-J'- i" fe-eat variety have C e CO ntercln, the yagn.a as, for example, forgotten tampons, pessarie: and objects mtroduced for purposes of masturbation. ( n one occasio M;^'imltVd*'r'"^V''" '"^^t '"'" "^ " ^^-^^-^"^^ «» >-'h ^^^^ hi^fnr . n '/* "' 'n ' '"" " '""^"^^'•"•'l*^ time. Such objects remain Ahnn™ ,!•""' "-^m''"- ■ ''''"'"^- ""^ted by phosphates and carbonat<. Abnonnabties-- Ihe xagu.a may be absent or duplicated. M..r, common than either of these states is a relative narrowing (atresil ctrTl' '""'t 't T '"■ "'••'■'■ P""'t^' '"• throughout the tube. co„- spread from the vulva; the discharge of acrid or infective material from the uterus is also a cause. Ihe wall IS rcd.iened, secretion is increase.l, and this, at first catarrhal, later becomes purulent. In young children vulvitis mav .spread to the %agina, in spite ol the j)rotcctive hymen, and it is worthv of note that accKlental infection of infants hy gonococcus may readily occur. In cmldreii s hospitals, a case of vunovaginitis is so liable to infect the enure ward, that it must be cared for by an attendant who does iM chondromas. leii not very rcomas have ire retention ig to scrotal oept in the lit* glands, t ' ' >?tiirc, nediate lolutions to in Douglas' tion exerted is liable to fiee. Tpon the bladder 1 may push vel or e\eii (enterocele, ; injured or J been en- !, pessaries, ne occasion n diameter urroundinjr cts remaiii- "arbonat's. ed. More ig (atresia) ibe. cy, passive traumatic, as vulvo- , as mi^lit ammatioti ulva; the ;o a cuu!;e. catarrhiil, ;ad to the note tli.it iccur. In infcit tlie does iu)t THE I TK/ifs 643 n:i:d^:';h::^i:a,£S£.:^- --- ^^^^^^ ^--^^ ^andim. i-.t''ttion in .lebiHtS suC ' '• T^' "•"«"'»*^ '^>' " '"^ form of .--bations ovir^bn^S leu^a) 'Vr'!?- 'l ^''"^' ^"«^* ut.rus are hert- also of importance h.T?!*^' • ^^'^ '''''^^"'•'^*'" ^^ ^^^ I'HHl result is hvpertrophTof the m. '""*'?V'^' *^" Tritation. The -r papillate. ev;n^tua l^t t mes TtSie I '•; ""*''' T^^" «^*""'" of inHammation in ne'k.v or^s Is w 'ri T"'''- /^' ^ '•^^"'t tk' \agina, flstula. mav be fonS «^« f ^ ^™""^ f''"'" ^''thin It is notewortliv tt.a/ !i '• ''*®^*«"**'' '"• vesicovaginal. or>,v,^.iHtln:fons ''' *'" ^'^'^'"'^ '•«^^'>- -^"^>ts either' tuberculous 'i '^'"c/^s^]iLir.:!;:e;^^^ f ^'^r -^'- *-^ *° Progressi-e Chafes -Tim.1 t ' T{^''^' ^'^^"™ng smooth. "iixvd tum;r. encoltered h, chn. ^*'' '' ^^^ t^ratoblastomatous -l™»-.ts along S 3 "cell t^J' T'""'"'' ^""'^'^^ sarcomatous sarcomas have%lso \Z ta,u^^J't htZ ,'"""''"^'' *'^^"^«- P"""- "-.V be the site of primarv qumo'Jceir^ /he vagina m- prone to infiltrate from carci^^ ITu carcinoma, and secondaries '.s well as from chorTo-'i^^^raTtfe^utr^^^ ''"''"' "^ '^«*"'"' THE UTERUS i'.■f!'^elmSa;d^itt'c^^..'' ' "'^;."' P^^'-^aped, but flattened from "f plain muscle fibres, ' '„o,^'.''™?""'V '"™^^''" t''^ «"«"'. "f its extent, and a muros ht enrS. f f'*™^"' ^pvermg over most 'Pitl-lium prolonged"m^tbe musdeTs """?.' 'T'^*^"^ '^^ ^°'"'""«'- S-'lan.lul.r acini. These dands Z^L «" abundant series of simple, 'l"m in the cervica Irelon Crr 'l'""^ ''^^°^«t« «nd abm.: '"" i'""K.diatelv underMng the enirr '^''^^y^^^^'^ submucosa, 'I'anKterized b^ a rSvelv abn.lnt "" '«,\ reticulated stroma i" Pa-ing «e would note must not J "??f"'«t.on of cells, which, ;i"''-tion. or for a d^tTalmlt^rusTotS' ^ V" .'"^^-atory f- >M.v,„„otrium is richly vascular anHYnVv. ^^ "'"^'' '"'''^'" ''^ tl'e^.• v.ssels show the evidences of i'nv I .• **^«^ '""'t'Parous woman i-m^lMTal hyaline change tcMvhich we h"*'"" T'^ '^^^^ ^"™«*'"" "'th -^; "'rther. abun.lant fvmp mt^f thie o7tT ''^ "" ^^ ^^^^ ''^''"^ "'"' '!'•' iJiac lymph nodes hose' of t.. K J TV"" ^""""^"ieating '•""I'ar .nd inguinS groups '^''' '"^ *^^ """^a" ^"^h the -.tS::^e?ndSt^^^^^ --- ->■ '>e n,ade If ^1 ;l If'pf' 644 77/ A' UKI'HOhlcriVK SYSTEM ti. the Miillerinn (hiots unite into a rommon cervix, the litems i> bic nuate; there may he two cavities enclosed in a common uterus (ute •optus). Coiisiderinp the juxtapositi 'H of uterus, hhuider, and reef ana('a, it is not remark".l)le tliat iK-casiona separation is imperfect with resultant uterovesical and uterorec fistula. There may he stenosis of the cav ity associated with imj)erf( development of the uterus along with that ol the other K('»>talia. Congenital Anomalies. — Two great classes of anomalies can recognized, tin- dystrophies, due to nutritive ilisorders, re.Miltiug ahnorniality of size; and the dysplasias, due to eccentricities of deveh inent. They may he associated. The uterus may he wanting (aplasia) or diminutive (hypoplasi and this may he symmetrical or asymmetrical according as the Miillcri duets, which form the organ, are equally or unequally involvetl. Ti ,, verse fission of the os uteri may he confouiided with that resulting fn childhirth. Ileal aplasia is rare, for nearly always some rudimei of uterine tissue are to he found. The external genitalia are genera intact, but the ovaries and tubes may occasionally be absent. Where one Miillerian duct fails almost entirel.v t'> develoj), 1 uterus unicornis is formed. If the ducts fail to fuse, uterus didelpl results, in which there are two separate uteri and vaginie, or two ut and one vagina. If the ducts fuse below, and not above, uterus bicoi results, and modifications of this are seen in uterus bicomis dupl where there arc two complete cavities; if these unite at the cervix have uterus bicomis unicollis, while if a septum divides the utcr cavity, the condition is called uterus septus or bilocularis, and there i names to distinguish the various degrees of completeness of the septii The cavity of the uterus may be absent, or there may be mniti rudimentary cavities; it may be narrower than normal or obstruct (stenosis uteri), or it may be in communication with the bladder l)> tube, or with the rectum (congenital uterorectal fistula; anus uterini The uterus may fail to develop beyond its foetal state (uterus foetal or beyond its infantile state (uterus infantilis). On the other hand, may develop precociously. Occasionally at birth the uterus is f fii retroflexed, in varying relation to the cervix, retroverted, or anteflex It has even been found in an inguinal or crural hernia (uterocele, h terocele). Acquired Abnormalities of the Uterus.— The pressure of tumors. Hi or organs misplaccil, or traction in unusual directions or its own wcij may misplace the uterus, and if it ' mobile may even impart an al)ii mal shape to it. As a whole tne uterus may be misplaced forwa backward, to the side, upward, downward (prolapse), or it may be turr inside out (inversion). Again, the same agents may bring about ^li pressure that there is an alteration in the direction of the axes ot 1 uterus; it may be rotated in its transverse axis (version), usually liac ward (retroversion). This may exist in all degrees from a slight tilt td tl in which the uterus lies with the fundus below the promontory of t THE UTERI- S 645 >a.r,im and the cervix fH-hind the symi)hysis p.il.is; these dishx-ations iM.nllv result from childbirth or alM)rti()n. when- the iiKrease«l weight ol thr uterus is not comiM'iisated hy the fixity of its supjjorts. Weaken- in;,' ..t the round iiRaments and, above all. the lack of iH-ririeal support Mlicr tears, are the most |)otent causes. A uterus so misplaced is prone tn impairment of circulation and may Ih'coii, • coiiKested and enlarged "I. I the pr.Mluction of emh.metritis. Abnormal anteversi,,,, is not so liiil.le to hapiM'u, and when it dws, is usually from the iraction of repaired ti»iit' in front. Inver8ion.-"In\ ersion or the uterus occurs in a large lax uterus, such a> may be seen after merge each of these in the more important ter/iio?! in the same liirciM,,,. Retroflexion is the most common, associated, as it usually »■ uii 1 retroversion, and if pregnancy occur the organ mav be incar- ^•■nit.cl in Its nev position, with abortion j. a result. The causes of n«Mn,„ are laxity of its tissue or its suppous and undue tractions or prosure n one or another part of it. armrfT^^"-' ^^'^ already referred to congenital stenosis: the aqni.d stenoses are usually due to contraction after curetting, or '""" Miatioi, or obstruction of the channel by tumors. It may tK-cur -Nancy as a result of gonorrhd'a. iiiHai in )n ^F^ 040 THE UKi'mnxi rivK system a ; DilkUtion. Anything that favors retention Iea«ls to distension of the uterine ;rowth of an intra-uterine fibroniyonia which encroaches upon the cavity. In such cases the hyijertrophy of the uterine wall may he remarkable. With im|)erforate hymen or cervical stenosis, there may he great distension from accumulation of menstrual fluid (hematometra). Retention occurring after the meno- pause or before puberty may result in the accumulation of clear fluid in the cavity (hydrometra). If the obstructed uterus become the seat of purulent inflammation, pyometra results. An infrcfiucnt condition is thf accuinulation of gas in the uterine cavity, .seen occasionally in the piierperium when putrefaction of the r.f,iiiied lochia or placenta is present. Rupture.- laceration of the cervi.x is a common event in delivery, particularly in the primipara. The severer condition of rupture of the body of the organ may l«e brought about by any condition which leads to continued, strong uterine contractions without progression of labor, such as occurs where there is a transverse presentation. Here one may expect a longitudinal tearing of the uterine wall, slight or complete, with passage of the foetus into the peritoneal cavity. Apart from the longitudinal, tears of all jiositioiis ai'.d degrees have been observed. Previous disease, with degeneration of the uterine wall, predisposes to these events. Bruising and Perforation.-These occur in attempts at mechanical abortion, or during operative measures (curetting) ; dilatation by force is always a crushing or bruising. I: must be remembered by the o\wt- ator every time he takes a curette in hand that the most skilful of operators have perforated the uterus by the use of a force that could not be called other than gentle. In these cases, the perforation is usually at the fundus. Apart from these operative perforations, there may be perforation resulting from cancerous and other deep ulcers, these often leading to the formation of utero-re'tal, utero-vaginal and utero-vesica! fistuljB. Circulatory Disturbances. — Hyperemia. ~ Active hyperemia occurs physiologically every month during the ]h liod of sexual maturity of the unimpregnated female. Each menstrual period is immediately preceded by a phase of active congestion of the organ culminating in multiple hemorrhages in the hypertrophied mucosa, and casting otf of the degenerated mu.osal cells. Under pathological conditions, active liMieremia is found both where there is a local acute inflammation and as an accompaniment of general infections. Hemorrhage. — Apart from menstrual hemorrhage of normal amount, there may be menorrhagia, an excessive loss of blood at the menstrual period. This may be brought ;;!>i)Ut as a result of chronic pa: jive HMX)MKrHITl!i fy\' ....Ktstion. pre|h»,«,He«l to hy tl.o existeiic' of ut.riiic tumors. Inith Im niK'ii and mnliKiiunt. as wvll as l,y tin- proMiic.. of iiiHarninati-.i, of till- uterus or its apjMTulaKrs. MstrorrbaKia is the esca|)e fn .1 the iit.rus of I.IchhI whicli is not menstrual. This assumes its gravest ihaKuostic imi)ort m women who have passed the menopause, in whom it> existence demands the suspieiou of the presence of carcinoma of the uterus. Apart from this, it may rl,T..tic changes in the vessels .,f : -, organs. ,- .., „,>t very uncommon tu have hemorrhage of a moder. gra.lc ii. 'c mucosa, with some • Mai.c of blood into and out of the uterine ca-.itv. Inflamm»tion. — Inaammatiou may affect the s.rous covering of thr uterus and the structures intimately connected with it (peri- metntis a local i)eritonitis), the surrounding j^dvic ..rgans, including the hroad ligaments (parametritis), the uterine muscle (metritis) or the "Hliiiiictriuin (endometritis). Endometritis. .Vccording to the region aft'ectcurc!y differentiated from those of iiiHammation. We recogniz^ tor example, acute catarrhal endometritis, showing hyj •■•■ nia With 'iiM hargc of an abundant viscid or in more advanced ca. a rauco- jMinil.Mt secretion; this latter constitutes leucorrhea, of which it mav !'«■ NH.i tiiat, in the majority of cases, it is the cervix which is involve from vaginal intection, not necessarily gonorrheal; more rarelv It H Ht dcscen.ling origin, and a degree of it may accompanv a variety '■t 'l^tiirl)ances of the adne.xa, or of the uterus itself, especially if these iirr .Krunipanied by a chronic congestion of the mucosa. Chronic Endometritis.-This results most often from a combined '•".'[Thai disturbance, and as in the stomach, for example, so here. 'jn lie one hand, there may be a distinctly productive or hyperplast .• t"iNliti,.n, sometimes even going on to the formation of nodular, polv- i" -. T iJapiilule osergrowths of the mucosa; or, on the other hand, (;48 TIIK liEl'UODVCTIVK SYSTEM -t;l if tho mucous nieinhrane becomes exhausted, to atrophy with thinnin; of the eiuiometrium. Here, agaiu, as in the stomatli, there may occa- sionally he iiiHammatory obstruction of the duets witii cystic dilatatioi of the same. On uiicroscoi)ic examination, if the glands seem to be the seat ol the most marked chanj;«', the state is called glandular endometritis in contradistinction to interstitial where th- morbid ciianges in tin interstitial tissue seem to i)rnlominate. Microscopic determination ij difficult because of the changes incident to menstruation. The gland tubules are generally lengthened, tortuous a.id irregularly dilated even to the extent of cyst formation; the epithelial cells have lost their cilia, are clear, swollen, and mucoid. Th<> lumina of the ducts are filled with mucus, leukocytes and desquamated cells, while the interstitial tissue is i)roliferated. The ])resence of the glands among the muscle bands nnist not be mistaken for malignancy, for it will be remembered that there is no submucosa. Late in the disease the mucosa i.iay become atrophic, smooth, thin, pigmented, and fibrous. The accompanying fibrosis is apt to compress some part of the tubules so that they dilate, .\nother result of irrita- tion is the conversion of the mucosa into squamous epithelium; this seems to bear upon the occurrence <(f scpiamous carcinoma in the body of the uterus, but it is likewise to be renu-mbered that islets of squamous epithelium have been discovered in the decidua, and even in the uteri of fo-tuses and infants. Like the other forms of inflammation, chronic endcmietritis arises from various causes, a recapitulation of which w»)uld be to repeat what has already l)ccn said when dealing with the acute form. In chronic cervical endometritis a freciuent result is the formation of small cysts, which may attain the size of a pea, the so-called ovula Nabothi. They ha\c usually clear, viscid contents. They are really retention cysts, due to erosion (wherein the proliferated epithelium "corks" the gland ducts), and are liable to infection, which may lead to abscess formation. Microscopically, the glands are seen to l)e enlarged, with many cells converted into goblet cells; such cases are readily mistaken for carcinrmia. As a rule in this form of endometritis there is abundant leucorrlia-a. As a result of injtiries in labor, and secondary also to such chronic catarrh, the cervix is api to show a series of disturbances. The external OS appears no longer round, but transverse, and the extremities of this transverse slit are so deep as to constitute actual fissures, whose edges are red, often tumefied, the tntire os sometimes appearing coated. The congested surfact- readily erodes and bleeds, and may show a variety of secondary changes, characteristic of progress or repair of the lesiim. Therefore, we may find ulcerations, scars, cysts, granulations of normal extent or so exuberant as to suggest new growth, which indeed may follow this nic inflammation. METRITIS fi49 Metritis.— Metritis is most frt'(|U(Mitly associated with the puerperal >tate, though it may be secoinhiry to acute iufectiou especially if asso- (iatetl with the trauuia of ojjcratiou. The uteriue muscle takes on a l)ale color and a soft, friahle consistence; aecompanyinp; it there may 111' acute hyperemia of the eniiiall-celled infiltration, not grouped into definite tubercles, may show liiTc and there an occasional giant cell, but only upon special staining fur liacilli is the nature of the condition surely recognized. Occasionally, lidwcver, large caseous tubercles are encountered, undergoing ulcera- tion, and the process extends slowly but definitely into the myometrium. Syphilis. — There has been much debate as to the extent to which tlic uterus is involved in syphilis. The jjriniary sore may at times li( ilctected either in the vagina or in the cervix or in its canal, but aiiparently infection may occur through the uterus without there being any recognizable primary sore. We refer particularly to those cases in wliii h tiie child is born syphilitic, and the mother j)resents no primary or < veil secondary lesions, and yet the prcsetice of the Wasserniann niirtion and the fact that the mother cannot be infected from the infant, as also the further fact that such a woman may give birth to a M rics of syphilitic infants, all indicate that she is infected. Parasites. Only rarely are echinococcus cysts foimd growing within till uterine wall. Foreign Bodies. -As in the \agina, so here, foreign bodies may lie found, necessarily less frequently. Attention must be called t») the 111' t that i)ortions of the placenta may remain attached, acting to all Mill iits and purposes as foreign bodies, setting up irritation, and even tiiiiiur growth. Regressive Tissue Changes. Atrophy. Just as the ovaries come til an cud of tiieir function at the climacteric, so the uterus, being tiiiH tidually useless, undergoes shrinkage after the menopause. It iHriiiies small, thin-walled, pale in color, and the cervical portion nun particularly becomes diminished. In very elderly women, there Is lUcn to be found an accomi)anying congestion with hemorrhages "I 'i'< fundal endometrium. This is not to be confounded with an ' >4 It ;i( Hilcction. ()■)() THE UKPRODVl'TIVK SYSTK.U : : Progressive Tissue Changes.— Hypertrophy.— Apart from the hyper- trophy of pregnancy, there occur other hypertrophies, sucli as that arising from infJamniation and from overwork; overwork hypertrophy, such as ib seen when a large fibroid Hes in the cavity, is hkely to involve the muscle most, whereas that from infianmiation need not do so. The formation of polyps, glandular hypertrophy, and even the formation of a decidua in extra-uterine pregnancy are all examples of localized hypertrophy. Tumors. — These are of great variety and of nmch i)ractical impor- tance. The chief benign tumors are the myoma and fibromyoma, lipoma, adenoma, and so-called adenomyoma. The most common tumor of the uterus is the fibromyoma, the so- called fibroid. Study of the smallest and earliest of these affords examples of pure myomas, of a reddish color, vascular ai'd moderately soft. Tumors of a larger size exhibit a combination of well-formed bands of uii- striated muscle fibres alternating with baiuis of connective tissue, although careful examinati(»n indicates that much of this apparent connective tissue is formed of atrophied muscle fil)res. The largest and oldest forms show great degeneratit)n of the muscle, and are com- posed in the main of firm connective tissue. These are very dense and of a whitish color. In all forms, on section, the surface is glistening and has a watered silk apiiearance owing to the d myometrium. This has been confirmed by finding changes in these glands at the menstrual period nientical with those seen in the uterine mucosa. These glands show no sign of active independent growth; we deal not with adenomyomas l.ut with a condition of myomatosis with jrlandular inclusion. The name a.linomyoma, however, has taken such hold that it is difficult to rt'pliicc it. These myomas may undergo conversion into more malignant sarco- ...atous growths. So, also, there are not a few cases on record in whS the mucosa over a submucous fibroid has taken on carcinomatous Rrowth, infiltrating the fibroid. rLinomatous Adenoma and Carcinoma.-Polypoid overgrowth of the mucous .mnibrane IS not very uncommon; so also there may be such a localized o\ .rgrowth of abundant uterine glands that it is difficult to say whether ^^e deal with an inflammatory or a neoplastic process. Nevertheless at tunes, this adenomatous infiltration of the muscular wall may be .^> (xcossive that there can be no hesitation in speaking of this as a mabgnant adenoma, more particularly as secondary growths of adeno- iiiatous type may appear in the pelvic lymph nodes. This is one tvpe o uterine carcinoma. Allied to this is the adenocarcinoma found in h.. cervical canal, and occasionally in the body. Here in place of .N pi.al there is atypical .levelopment of the glandular elements This .'nn appears to originate most frequently from the occluded glands muh« Nabothi. This, like the former, infiltrates extensivefy^ the I soIIh' """""^ r^T-*"/ ^'°''*''?' ^^ ^^'^t"'" *'>^ P"'-^ carcinoma, «itl sol d u ii masses. Colloid cancer is distinctly rare. I Ins forms one group of uterine cancers; the other, and smaller ^oup originate m connection with the squamous epithelium of the <'r\i.v, only a few cases having been recorded developing from the .■n .nd canal or the body of the uterus. This, the squaiouf carcLma 1 " ,! ^^*' "!'*'' "\'' somewhat superficial growth, at times tending K papillomatous, having a distinct tendency to ulceration and n.-ion with progressive invasion of the deeper tissues. It may extend ;. up the cervical canal into the body of the uterus, SsSy iiiii.i rate the neighboring oreans. ^ m the above description it will be seen that carcinoma involves all ' 'rt> o» the womb, but the cervix most frequently. Uterine cancer G.j2 rilE REI'RODVCTIVE SYSTEM is one of the commonest of all forms of malignunt jrrowth and of carci- noma in the female, one out of every three cases is uterine. In the nuUiparous, the condition is rare, and then most frecjuentiy affect- the corpus, whereas in the woman who has l)orne children, the cer\ix is the part most often involved. This leads us to see some relationship between trauma and scarring f the cervix, and subsequent cancerous de\elopment. Cancer develops most often after the menopause, and we can but rcj)cat the warning that a hemorrhage from the womb developing after the cessation of menstruation demands careful examina- tion for the presence of a carcinoma. Sarcoma. — Sarcoma is distinctly less frequent than carcinoma, is apt to arise at an eailicr life periotl, and most frequently affects the body of the organ. The gr{)wths are pale, nodular, often multiple with extensive infiltration of surrounding tissues. EndotheUomas are still less common. Cysts. — We have already referred to the ovula Xabothi and other retention cysts of the uterine glands, as well as to the necrotic and angiectatic cysts of uterine fibroids. Teratomatous cysts have been recorded. THE FALLOPIAN TUBES The Fallopian tubes may vary considerrbly in their position accord- ing to the relationship of uterus and ovakies. Their freedom of move- ment permits them to be included in any conglutination of pelvic surfaces and organs, and as a result they are distinctly apt to exhibit infiamniatory anither toward the distal end, or in the central region or somewhat rarely in the uttrine portion of the tube (interstitial). As a result, with the reaction on the part of the mucosa of the tube to form a decidua there is an extraordinary conges- tion of the blood vessels of the tu'oc and as the gestation sac increases in size the walls of the tube become so much thinned that rupture may occur with escape of the fa'tus into the peritoneal cavity or the broad ligament and associated profuse hemorrhage. In this new position the foetus may gain a new placental attachment, and rare cases are on record, in which the foetus has developed to full term. Much more frequently rut: FALI.OPIA . TUBES Cm:? t .«■ uiirontrollf*! lieinorrhaKe leads to a fatal issue, or where the hemor- rliajie is not so extreme, the foetus dies and heeomes a lithopedion. I liese eventuahties (K-eur, of eourse. in the ahsenee of surgical inter- vention. It is interesting to observe that a sympathetic decidual lormation or change in the mucosa may sIk.w itself in the op.K)site tiilie or m the uterus. Congenital Abnormalities. The commonest congenital abnormality, s(. common as to be practically normal, is the pi >sencc of the hydatid of Morgagni, a cystic dilatation and enlargement of the longest of the fiml)rue. This is present in more than 20 per cent, of autopsies upon tlic temale. I^ss commonly, variations are seen in the distal end Ihere may, for example, be a double orifice with a separate collection ..t tiinbria- around each, and very rarely the tube itself shows some (iui)iication. Diverticula are sometimes noted. There may be complete absence of one or both tubes, generally associat.d with al)sence or iniiltormaticm of the uterus. Circulatory Disturbances.— These call for no special remark, in inflammatory states, there is acite hyperemia, at times with associated hemorrhage. The condition of hematosalpinx or accumulation of blood 111 tlie tube IS occasionally encountered by regurgitation of retained menstrual blood, or, some hold, from actual hemorrhage in the tube (luring menstruation. Inflanunation.— The more accurately the bacteriolog\- of the inflamed till).- is studied, the more il is seen that gonorrhea is the commonest • Muse of acute or subacute salpingitis. There may, it is true, be infec- tioM by the strejrto- and staphylococcus, but these are not so frequent. I hi' results are a swelling of the mucosa with pronounced purulent M ( rction which in cases of obstruction of the tube pass on to its grc-.t (!i;t.nsi(,n with actual pus (pyosalpinx). A marked characteristic n -unorrheal salpingitis is that while the lumen of the tube mav be hll.MJ with ordinary pus cells, coincidently the greatly infiltratecrsub- niiHosa may show an extreme accumulation of plasma cells Recen'^ auilK.rities hold that this abundance of plasma cells is i-athognomonie "t L'Mn„rrhea! infection. With this infiltration of the submucosa, tlir Muicoiis membrane shows pronounced loss of epithelium and the riiUM' iire flattened, so that the mucosa becomes less iiifolde-i This v .lestruction of the mucosji favors the subsequent formation of iTH ires and bands of connective tissue with stenosis. It is characteristic "t "Ins acute inflammation of the tube, that the ends are apt to become Mill.,!; and even while at first this sealing be through swelling of the i"'j' osj, and the viscid nature of the secretion, it is apt to be ultimatelv l t'oinid reddened and congested: it may even i)e infected in general Imctcriemia; but by far the most frequent causes of inflammation lie in tlic spread of infection from connected structures, especially the tube, iind this notably from gonorrliceal virus. The inflammation so set up niiiy he diffuse or follicular, and as a result, the ovary mav be soft, •iiliirKcd, and cedematous, or suppuration in small or large areas be xrii. The entire organ may be converted into a sac of pus, which mav rupture: such a change is usually accompanied by fixation to the tube iiMil otiier nearby structures, so that a mass of inflammatorv mate-ial i> loiind in which it is recognized that both ov-ry and tube have par- ti( ipated. This is known clinically as a tubo-ovaiian abscess, and may iirbc ((pially from either constituent. A trc(|uent result of oophoritis is that j)elvic adhesions result, and the iiifiimicd ovary is often fotind in Douglas's pouch. In considering the f;< iirsi. of ovarian abscesses, it must not be forgotten that the verv ln(|ii.ntly seen follicular cysts of the ovary may become infected. Chronic Oophoritis.— In this the ovaries are found dense, of an ivorv <'|l"r. and while they may be smooth, the surface is usuallv corrugated, "ith ,,r without adhesions. Warning must be given that a similar < M'Timl aj)pearance is seen in the shrunken, atrophic ovaries of old "onu n. In the younger adult, this thickened condition of the outer l;i>< r of the ovary is due to an inflammatory fibrosis, and is important "' 'l.it. .)l)viousIy, it hinders the rupture of the follicle and the escape "' '!'< ovum. Such unruptured follicles undergo degeneration and I'" "in.' (oiivcrted into small cysts, which are a characteristic feature in "^:in. Y'f this order. The stroma in general shows an increased fibrous "M" rplasia. Chronic inflammation of the ovary usually results from ;"'"i;!nance of an acute infection or from recurrent attacks of a milii irrii iMt. Tuberculosis and syphilis are rare in the ovary. i\ry(\ Till-: ll>l('nVK SYSTEM Kicj. L'!l."i Regressive Tissue Changes. W'v liavo aln-ady rrforri'd to tlie atroii and fihrotic coiKlition si-coiidary to oiiphoritis. It was tluTe sta that a soiiH'wIiat similar appfaraiur is tiicoiintiTt'd after tin- niei pause. As a result of ineiistniatioii hyaline and elastoid elian^es s«'en in the arteries. Progressive Tissue Changes. Tumors. If a niorpholo^'ieal elas> cation he used, it is likely to i)e ineorreet enil)ryolo>;ieally, for etiology of many of the ovarian growths is yet in douht. It is possible to ilivide them ronjrhly into the eystie, the cystic ii solid mesotlielioniatous or carcinomatous tumors, the eonnective-tis: growths and the teratomas, a division which will serve to i)revent ci fusion. Cysts. 7 These are of ^'reat variety, and it may he stated hy wa\ preface that they can ori>;inate from the follicles, from the gerini epithelium, or from Wolffian "rests." 1. ('i/.itir Diiii'iiirntiitn of the Omry. — This is ciuiracterized hy i appearance of numerous small cysts throughout its substance, lined a single layer of ceils, in jjlaces ciliat( there is no follicular ei)ithelium of 1 usual type, and no ovum. They ni hv found in the newlxirn. The w is constituted l>y the thickened w of the follicle, and the fluid is cle It seems likely that an ill-timed rij)! ing of a follicle is responsible for th occurrence. '1. FdlliciildrCj/Kix.-'Vhvi^aKof t nature of true retention cysts. I'siia thtse cysts are multiple and sini but occasionally a single larger c; is f(,. lid. When small they are lin by cylindrical epithelium and at tin a persistent ovum is seen. When lar the epithelium, through pressure, flattened; they contain a limpid flu Quite analogous to these are the < y: originating in corpora lutea, usually l)e known by their thick, wavy, liyiili wall. In these the fluid is apt to colorcfl l)y modified blood pigment. 'A. Cjistiulcninnd.f {('iidDiiia.i, or (iUmduhtr P.ieiidounwinou.'i, Mul lanilar Ci/st.i). The alternative names, taken together, descril)e t'aii accurately these cysts, the most conunon neoplasm that is found the ovary. 'I'hex are unilateral or often bilateral. Xow-a-days tluy a iisually removed by operation before reaching a great size, but former cases have iseen ilescribed in which the weight of the cyst exi()ns between the cysts, the larger cyst being developed from the (i.iilhu-iice of smaller ones. The cyst wall is tough, thin, and trans- liK rut, hnt in some cases thick, its hlood supply being the large ves.sels tliiit nunify on the surface. The Huid is of varying consistence, thinnest ill the large>t cyst, having a specific gravity between 1010 and HYAO. It may be viscid, mucinous, clear, glassy, turbid, brownish, or at times I.IimmIv. B(Mlies related closely to nuicin (pseudomucin) and albumin arc I resent in the fluid. Multilocuiar ovarian cyst. I he (■> St wall IS composed of two layers, the outer dense and fibrous tlic iiiiMT cellular and vascular. A single layer of c^ lindrical, columnar ;ylU null basally placed nuclei lines it internally (see Fig. 143, p. 292). i'liH ' |)itliclium has a pronounced tendency to "form multiple papiHa'ry iiii;r(,utlis, and an equal tendency to give origin to downgrowths into tiii r\ .t wall, which, becoming snared off, ilevelop into secondary cysts. .Mi(n,M(.pically, the lining cells arc distinctly mucinous, but thev mav ^li"u \ ;iri()iis kmds and grades of degeneration. In addition to pseudJ- iiiii'in the Huid may contain fat gobules, leukocytes, degenerating cells, i'l'""l. aiul cholesterni. The i)osidon of the cyst in relation to the tube 1^ ' I .iia.tcnstic. The tube can be lifted off the cyst, except in those nin ,,,Ms Ml which the cyst develops between the lavers of the broad li^-Min^iit. \\i li the continued growth of the cyst, it lifts itself out of the true jii'ili, i dti't'.. it> li llt'(T( ■ Hid elongates the ovarian ligament, which, acting as a long In a relatively movabi, growth, is liable to be twisted, shutting ' irciilation. The cyst wall then becomes dark red in color, and -ii> max show all grades of hemorrhagic infarction, even to ■• A large cyst may break and discharge its contents into the II' \l ' i •I i 058 THK uEPRomrrivK system ]H>rit(tiictiin, \vlnT»' the mass t>f imicinoiis inatfrial may he walle burst forth; sometimes the pai)illi actually invade the cyst wall. In such a case the cystic quality (i the tumor has receded ami it approximates more than before to ])ai)illoma. The fluid is thin and watery, at times bloody in appearance. In tumor is an important one, because in time it Ix-comes malij;iiiiii (a quality foreshadowed by its infiltratini: its own wall), giviiij: ris to secon(iary nodnles on tlic |)eritonenin. The orijrin of cystadenoma has led to mudi discussion, and the question is still an open one. Lcav THE OVARIES— rUMOHS a-)9 111^' this questu.n nwrssurily imsettltfl. then- is h natural transition to tlu- carcincrnas, consi.lrrinjf tin- ^mit lial.ilit.v for the l)cniKn tinnors .-|..-'*t|i<'«'''<'"i"s. or even more fre.,uently, in the papillomatous .m.s. In the former, wliieh in p-ni-ral resemble their non-rnalitmant |.n.totyiH.s. the walls an. I,ut are h)und persisting in about 1(» per cent, of human ovaries III ' H I'.rm of spaces or cavities, lined by an epithelium which, according "' 111' iuriod and stage of development, is curiouslv variable in its ll^ir;,. t.Ts. An lutcrestmg feature about these persistent growths 1^ ili.t they show a marke.l liability to the formation of capillarv iu- ^rnuil,,, as again to the development of outgrowths at times solid •It tinirs glandular or cystic, into the surroumling ovarian tissue We 1|'--- here in short an organ or part capable of giving origin to "iiiI'M'l' cysts and to intracystic ingrowths. Connective-tissue Tumors.-Of the connectiN-e-tissue tumors, the most 'lip 'iMt are fibroma, adenofibroma, cystoflbroma, myofibroma, endo- tnelionia, pentheliomt, and sarcoma. Fibromas usualh- form difluse l-llllh Ti, 1 1 Mir; tlif\ „..i, .,, ., , "■■ "■^""■v ""111 uuiuse ;\tlis with unitorra enlargement ot the ovarv, but ma\- be cir- nlicd nodules, unilateral or bilateral. sarcomas are not nearly so common as are carcinomas of the I -Ike so many of the ovarian tumors, they tend to be bilateral • -|> be round-celled, spindle-celled, or giant-celled, and it has been -'I ('>('>() THE KKI'Kom criVh SYSTEM siiKKf-^tt'd tliat tlu' last (iriKiiiatc iM)s;*il>l\ fnirii tlic iiittTstitial «rlls wliic art- «)f lik«' orijjiii with tlif cells of t\\v (Jraatiaii folliclrs. Soiiu- cast are on rocunl of trm- e&rclnonui Bwcomatodu. Tlu'sf jHTliaps repn-sci transitional tvjM-s sirii in tumors of tncsotlu-liul origin. EndothellomM are ocrasioiuilly fncountcn-fl, but, lu-rr ajtaiu, tluTi- a HTViit lial)ility to classify eoniplicatctl and ilouhtful tumors of tl transition;!! type as cither endo- or iH-rithelioma. Much fuller >tu^arinn ns v vsts of any size u|) to fivi- or s inches in diameter, usually solitary, '.n\t sometimes multiple and li lateral, these are s|)ecially prone to api)ear after jtuhcrty. On openiii the cysts are seci. to contain tallow-like contents, mixed with liai sometimes the contents are thin fluid with tallowy masses. The hai are fixed to skin reseml)lin>; the scalp, which covers a knohhod i)art < the inner surface, the rest heing covered l>y what looks like mucoi memhrane. rnderlying the knob may l>e bone, and in it are oftt incisor teeth, sometimes in a row as in the jaw. Microscopic exaniiii tion through the knobbed porti«»n shows hair follicles, sebaceous ai sweat glands, portions of bone and cartilage, sometimes structures the eye; in fact, almost any structure found in the embryo may 1 seen, aiul even ath'mj)ts at limbs have been observed. Solid Teratomas.- The solid teratomas are less common. The tunn on secticm shows mnltii)lc small cysts with serous, mucinous, or U\\\o\ like contents, lined by ciliated, columnar or flat epithelium, in i solid parts muscle, cartilage, glial tissue, and so on; bat as a gener rule, the solid teratomas contain less develoi)etir neoplasm (ttmior in tumore). Almost every known combination i benign and malignant growths has been of)served. Teratomas are liable to complications of various sorts; twisting ' the pedicle may lead to anemia, hemorrhage, or necrosis; inflannniitic may result in adhesions oi supi)urati()n with rupture into surroinuiir organs, the peritoneum or to the outside. If the more serious r(>iil do not ensue, there is at least congestion, nav xive ris«' to cysts CircuUtoiy Disturbances. The veins in all these structures nmv U- .liliite.1 tortuous. tl.roml)os.-.l. or (especially those of the ovarian or lMin[muform plexus) the st-at of phlebolith formation. Hemorrhace mav :.n.e from many different causes connected with the iK-lvic organs, and the . nurse of the W.mkI vari-s. ucconliuK to whether it is intra- or extra- IMTitoneal If u.to the iwritoneum. it may gravitate into Douclas' •' ''.""•' •'•r" " Postuterine hematoma or hematocele; if in large enoudi •IM.M.tity or eircumscrilu-d, it may enlarge the space between the uterus '"'. , cX* "', «'\.»nt«-«t«'^« hematoma. If extraperitoneal, it mav iiihltrate, hffusely all the loose comiective tissue of the pelvis, or may l« .v'»-.i the layers of the broad ligament (intraUgamentous hematoma) In any case the bloo,| may be absorbed and leave traces as pigment; nr •..•lujr partly unabsorbwl may undergo organisation an.l be walled 1. the occurrence bemg marked finally by the presence of a mass of hl.n.ns adhesions; or while still fluid it may rupture the wall of some <'rp.i. and escape; or being infected, may become the basis of an abscess. 1 he hemorrhage of greatest importance is that due to a niptiir .! ect.)pic gestation sac, although bleeding mav also occur from ni|,turc of a Graafian follicle, from a cy.st. from th^ escape of blmKl rn„, the abdominal end of the tube, or accidentally after an opera- Inflamniation.-.\ccordii.g to situation, this mav Ik- parametritis- li.it IS, cellulitis or the i)elvic tissues, or perimetritis, a localized peri- t'liiiiis iittcctni), the uterine serosa. Parametritis. 'ilVetion of the pelvic connective tissue ...ises from M.i,M..n o* a goi.orrhccal or other infection of the passage, or from "Uiin.s in p..ifunti"n or from puerpei'dl sepsis. The exudate mav be >'rn,i., or th<; tissues diffusely infiltrated with pus, or there mav be ":iii/.d ah-crss formation, and even gangrene. Where pus is foi^med m: . I.nrrmv t.. the abdominal wall, the thigh, the floor of the pelvis, ,',''• It'" irf* ""'\'"™'' "^ ^^'"^ '■''^*'^'"^- ^^ '^™''"fJ ^^ ''ix'h « state tli.ii U r. abscf: s faci, 't Will be at the cost of much adhesion and fibrosis. 'he MiHamed tissues of a parametritis are dinicallv known bv "'.I descriiJtivc phrase, "the (inflammatory) pelvic m'ass." What- "a !s aHccted, Douglas' pouili is sure to ^uJler, sooner or later "II "t Its pos^ition, and abscess in this area is frequent (retro-uterine In all these inflammations, the adhesions are an important III I 1 , . ' "'■■■v.-.iwiia uic Hii important a low grade ot infection they may be the chief abnormal fact 002 THE REPRODVCTIVE SY'STEM :il (productiye pelvic peritonitis), and may leail to all sorts of distortio and occlusion; in an ordinary case, their position may detcrmiii the localization and ultiniate course of the fluid exudate. Progressive Tissue Changes. — The round lipuncnts may hypei trophy along with the uterus, and the broad lijjaments with ovaria or parovarian cysts. Tumors. — The tumors found in the hroad ligament are in the mai derived from the uterus, where they are not of ovarian origin. Th growths are mostly benign, myomas, fibromas, Upomas, and even adem myomas of the tyi)e already described as originating in the uterine wal Cysts. — Mention should liere be made c>f parovarian cysts, which ari;- from the i)arovarium. A parovarian cyst may grow as large as a man head. It lies at first between the abdominal end of the tube and th ovary, and as it develops the tube and ovary may be widely separate and greatly flattened. There is generally no {)edicle, and the wall i thin; internally the wall may show papillate ingrowths. The containe fluid is watery, and a low specific gravity. Teratomas (" dermoid cysts") have been found in the pelvic cor nective tissues, and sarcomas can arise from it; carcinoma is al\va\ secondarv. THE PUERPERAL UTERUS K;:i Apart from hemorrhages connected witli the injuries of labor, ani with imperfect involution, and hemorrhage due to accidental disturl ance of the placenta, diseases of the puerperal uterus centre arouii infection. As a result, endometritis, metritis, or "puerperal fever" jna supervt.ie. The otl'ending organisms arc most often the streptococcus pyogcnc and the stai)iiylococcus, and the i)redisposing causes are lack of cieai liness and meddling, nsuall\ in the way of examination, douches, aw improi)erly undertaken instrumentation of the lining of the uterus. Tli infection may be membranous: in general, the placental site is hkh affected, the surface is diy and gray or brown or even green ii color. In addition to this, there may be infection and decomposition d retained fu'tal products, blood, or lochia. The uterus of such a ens is enlarged, the wall (edematous, the endometrium dirty green o i)rownish-black in color, stinking and pulpy, the wall of the uterus sof and rotten. Micri>sco])ically. in either case, the tissues stain badly aiK areas of necrosis or of infiltration are seen according to the varyinj severity of the infection. Hacteria can usually be readily dcmonstratw on the surface and in the tissues. In slight cases of jjuerperal infection, there is no such serious state the ])lacental r"te, it is true, is ragged and unclean looking, but if drain age be efficient the affection subsides with no further onseqm ikcs For practical purjwses, it nuist i>e remembered that an intra-ntoriiK .::en the decidua>; hemorrhage and abortion are likely to ensue. Metritis.^ — It will he evident that any severe case of puerperal endo- iru'tritis is accompanied by a corresi)on(ling metritis, which need scarcely l>f considered by itself, further than to jxnnt out that the metrium limy be the seat of a diffuse serous or purulent infiltration or of multiple :ilisf(sses; on the other hand, the metritis may consist of little more tli;m an infection of the lymphatics or of the vessels with thrombosis. I'nmi such beginnings the lymphangitis may spread to the diaphragm, ilif tlirombophlebitis to the vena cava, the infection to the peri- and Iiiiranutrium, and an extensive ju'lvic cellulitis and ])eritonitis be the r(-tli(T names. It has been elsewhere explained (see p. 213) that this i> to lie cl.isscd as a teratogenous blastoma. When it appears in the uterus it is an evidence of previous conception, although this may have (Kciirrcd long before. I iiis tinnor tends to form ])olypoid or fungating growths projecting into the uterine cavity, but quickly invades the endometrium and the lit! nine vessels. It is of reddish color, often hemorrhagic, and soft, triiililc, and spongy. TIm' growth originates by proliferation of Langhans' layer of the iiMifioiiic villi; tliese cells, instead of undergoing syncytial change, niMMiii active and proliferative. After they have proliferated in ab- 'I'liiiiil situations, they may, it is true, undergo the usual transforma- iii'ii- into syncytium. The deeply infiltrating parts may show an alve- "Ih structure, but the spaces jjossess no special lining and the tumor 'i:i no struma and no i)lood vessels. The syncytial elements when I'i'-i lit are in the form of plasmodial giant cells. The cells of the '■ "Plans' layer tend to be spherical, and are grouped into masses of \ 'r nig size. In the secondaries, they possess all their original power III i TiKJon. Ml iitioii lias been made of the readiness with which this tumor 'III ' I !!isi/cs; tlie vagina is very often an early seat of extension. j'vS^iy ..1^^-i-'-' 'i.<:^^.. V.:%.^~.- 664 THE REPROnrcTIVE SYSTEXf THE PRODUCTS OF CONCEPTION The Placenta m The patliolojjy of tlie placenta is not very well un(!erstoo lie contaminated by ftetal excretions ^o ;i- to be dirty and foul, and may un- %v«iai;L.>^ >-,-«!^vj<^aB i-\^,frx&wvii 000 THE REPRODUCTIVE SYSTEM and various forms of acriti- or cliroiiic (iisease in the mother, i)ro(hi iuK toxemia, may suffice to kill it. Ectopic gestation may take phice in any part of tlie tube, but is mo common at the entrance of the tube to the uterus (interstitial gest tion) and in the mid part of the tube. It is not Hkely that abdomin gestation ever occurs, the foetus that is found in the' abdomen havii been extruded from the tube (tubal abortion). To this we have alreac referred on p. 052. The chief (langer in ectopic gestation hes in tiie liability to sevei hemorrhage at the time of rupture, and the necessity for operati\ delivery, for as will be easily imagined, there are but few cases th: admit of expulsion by the natural channels. The causes of ectop gestation are inflammatory, such as the existence of gonorrhoea, or son obstruction, either by bending or folding of the tube or by the present of a tumor or other obstacle to the passage of the ovum. THE MAMMART GLAND The diseases of the breast belong alike to both sexes, but by reaso of its function in lactation, the female breast becomes of prime import ance; in the male, a consideration of its diseases would be a very simpl and brief matter. The mammary gland is branched, and at the onse of pregnancy the single lobes become compound and many new acir are formed, while the vascularization and stroma advance equally i their development; at the time of delivery, the first expression bring from the gland colostrum, in which the "colostrum corpuscles" ar cells that have wandered into the acini and have engorged themsclve with the fat corpuscles that lie therein; after their dislodgement, th globules are, in the regular way, the product of the mammary cells When the function of lactation is finished, the breast, as a wliolt becomes smaller and once more simplified. Congenital Anomalies. — Amazia or amastia, absence of the breast often bilateral, is generally associated with lack of ovarian develop ment, and hypoplasia, the infantile breast, accompanies an infantile stat of the sexi ?! organs in general. Microthelia, an abnormal smallness o the nipple, may lead to difficulty in suckling. Abnormal developnien of the breast in the male (gynecomastia), reduplication of the nipi)l( (polythelia) or of the breast itself (polymastia) are observed. Accessor] breasts may be seen in such a situation as the axilla, from pinched of lobules (aberrant mamma), and such, as weil as the ordinary super numerary breasts, can produce milk. Circtilatory Disturbances.— Swelling of the breast sometimes charac terizes the premenstrual period, and occasionally vicarious menstru ation is exhibited by discharge of blood from the nipple. Hemorrhag* and the formation of hemorrhagic cysts may result from trauma citliei primarily or by bleeding into a preexistent cyst. ?^tat^.. m wim, TlIK MAMMARY GLASl) ti(j< Inflamm ation.— Inflammation may arise in the breast at any period of life, even in infaiiey, hut it is most often found durinj,' iuctation, where infection gains entrance throufjli the nipple canal, or more fre- (luently by way of small fissures or cracks in the nipple. Rarely the hreast suffers by extension of inflammation, as where the infection'from ii carious rib or a ruptured empyema reaches its tissues. Thelitis, iiiHammation of the nipple, and areolitis, of the areola, occur, with the formation of abscess, the so-called antemammary abscess. Inflamma- tion of the breast tissue itself (mastitis) is the most common form; the l)reast is enlarged, tender, and sometimes reddened; it may be possible to press pus from the nipple (galactophoritis purulenta), or there may iiiirely be evidence of a deep al)scess or of several such; more rarely, the entire breast is in a state of purulent infiltration ';mastitis phleg- monosa). However the infection may have reached the breast, the inter- stitial tissue is seen microscoi)ically to be infiltrated, while the glands contain a semipurulent material in which are abundant desquamated (Icgenerat. .' gland cells and leukocytes. If the disease be not relieved, the abscessMs may coalesce, and the entire breast be riddled, and the pus niiiy travel far for an oi.tlet, may break through the skin or even into the thorjix. An opening into the skin may establish a fistula through which milk, mixed with inflammatory products, may escape. A non- Mippurative mastitis may quickly resolve; abscesses' if evacuated mav 111 .il with scarring, and it not evacuated, the pus may inspissate, and nilcareous deposit occur; in a nuich scarred breast, the onset of a new pnijuancy may be attended by the development of retention cysts. I he so-called retention mastitis is nothing more than infection of a liniist in which there is already an irritation caused by the presence of -tiiiinant gland secretion. Tuberculosis.— Tuberculosis occurs with fair frequency in the breast, "" asionally as diffuse miliary tuberculosis, but oftener as caseous areas, ^nid as cavities, from which fistula^ may op<-n. The edges of the fistula arc covered by granulation tissue and the discharge is thin pus. The iiMlliiry lymph nodes also show caseation, and may even break down ;ni(l .lischarge. In the case of both these forms of tuberculosis the ml. ( tion is hematogenic. Syphilis may occur on the nipple as the primary lesion, and ditfuse and gummatous infiltrations mav arise in till' l.reast in the later stages, while the skin of the breast mav exhibit ^piiifu; changes, as the skin elsewhere. Regressive Tissue Changes.— Atrophy of the mammary r,land occurs iit \\\v menopause and sometimes after removal of the ovaries, although tiH loss may be compensated or overcompetisated in bulk b\ fat, without which the breast becomes small and flabl)v. Microscopically, t M. k.iinig and hyaline degeneration of the walls of the ducts occur, so 'hit tliiv appear as yell()wi-> -whi.e lines in the tissue. Progressive Tissue C"- ^ 'legeneration i destroyed tissue '""ir- only to a slight e> , . pensatory hy|;_. trophy of the rest "' 'l|' «land IS a more frequ. >t happening, and is not confined to preg- l ! ^n^syik^i^' ..^i^^^;^ 60S ruE nEPRonrcriv ';ro\vtli of the uterus and ovarie l{ar«' cases arc ohserved, usually in the young, of a kind of neoplast overgrowth (giantism of the breast) in which a hreast lias attained weight of sixty-four pounds. There is also diffuse overgrowth that soni times is of the nature of fibromatosis, at others of adenomatosis, or ( both together. The nipple does not share in the general enlargemeii Tumors. — These are of considerable c()mj)lexity and of great praetici impo'-tance because of the preponderance of malignant forms of growtl because they are readily iircessible to surgical removal, the patholi gist's opinion is frequently asked, and the decision is often very difficu to make. Because of the liability to error, and the frequency of malij nant tumors in this site, it has become a surgical rule to advise t\ Fibro-adcnoniii nf l>rraHt iifTnrdiTiK indiciitioiis of ovcrKrowth und ahorrant growth of the glatKiuI; clcnipnts: n, ciiniiirfswd acini; h, Kl>ri>u9 iiveriinmtli; r, a Biiniiwhat dilated durt, with epitbeli proIif<'rution. removal of any growth whose nature is at all doubtful. Although tli male breast is able t()siiowexanii)les of all the tumors to which the feniiil breast is liable, it docs so relati\ely infrequently; the latter is in a stat of physiological and anatomical instability throughout the years c sexual activity, and is liable now to progression, now to recession n vegetative activity, which is i)recisely the state of affairs in whidi w have indicated a "habit of growth" as likely to arise. Because of it cxj)()scd position, a history of trauma frequently precedes the develop ment of a tumor, and the association has been accorded, especially b; the laity, an importance that is probably uiidt-scrvcd. Among priniar growths, the epithelial are most in'i)ortant, and consist of fibroadeiioinas adenomas, cysts, and carcino'.ias. THE MAMMARY GLASD— TUMORS 009 Fibro-adenomas.— 'I'licse are growtlis from the size of a cherry stone to that of a wahiut, liard, soinetiriu's nodular on the surface, readily Fia. 300 P.riranalicular fibroma of the mammary gland. The Klandular acini and ducts are prominent aiul sl,o« some irregular overgrowths of the epiih.lium, Imt the main feature is the development of cuuneclive tissue both periacinous and interstitittl, the latter not sharply defined. (Ribberl.) Fui. 301 Intraranalicular fibroma or intracystic papilloma of breast. (Orth.) ,''.''.'' "V*^ ''"'"" "'^^ surroundnig tissue, which on section have a very 'I'S'iiitf fihrous structure; between the fibrous bands, the glandular "C3S 070 THE REI'ROnVCTIVE SYSTEM li tissue protrudes. It will he at once evident tiiat the term fibroadeiioii implies that not only is there ov«rgro\vth of the fibrous tissue, but al.- of the gland tissue, and it requires n)nsideral)le experience to be sin of this on microscopic examination. Pure fibroma of the l)reast rare; nearly every fibromatous growth includes in it some glanduh structures which necessarily becona- distorted, pressed, and lose soin( what of their orderly arrangement; there will be all grades seen betwee a very fibrous growth containing few acini and a slightly fibrous growt showing many acini, yet all alike may be classed as adenofibroniii It is customar\ to divide these growths into pericanalicular and intri canalicular adenoflbromas. In the pericinialicnlar form, single glan acini are snrroun.ltd by a thick hiy.r (.f ceiluhir fibrous tissue, whil in the intracaiialicular form tlieic arc papilloma-likc j)rojections ( proliferated stroma covered by proliferated gland epithelium e.xtendin into the lumen of the ducts. l)egenerati\e or other changes in the structure of the tissues formiii these tumors give origin to various modifications such as adenomyxe fibromas, adenolipofibromas, and adenofibrosarcomas. Pure Adenomas.— Tliese are comi)aratively rare, and are solid, o cystic. The solid forms approximate somewhat to the fibro-adenonia:- but arc distinguished by the extreme increase of glandular tissue The cystic form (cystadenoma papilliferum) is characterized by tin l)resence of cysts on the inner walls of which there are small pai)illo matous or jiolypoid j)rojcctions. Cysts.— If all sorts of cysts are here considered, it is needful to men tion milk cysts (galactocele) which arise by blocking of a duct durin« the time when secretion is acti\c. These arc true retention cysts Of another kind are the involution cysts found in achanced years; tliix appear as usually multiple, bilateral, hard small masses, riot capal>l( of i)eing shelled out and on section cystic, with variously colored Hui«i the state in which these cysts dcveloj) is called chronic cystic mastitis. Carcinomas. 1. Gland Carcinoma.- This arises most commonly in tin fourth and fifth decades as a firm, ill-defined mass in the breast not easily movable ixptirt from the rest of the gland. Frequently, tlun is a relatively early indrawing of the ni|)ple. The growth becomes more superficial, and as it does so, the skin until now freely movable over the tumor, becomes fixed to it, and carcinomatous masses ai)pear as knobs in the skin. Without complete removal by operation, the car- cinoma may spread ditinscly through the skin and subcutanecuis tissue forming a dense, ix.ard-likc mass (cancer "en cuirasse"). Sometimes the growth breaks through the skin in a fungous mass. Necrosis ami ulceration are [)ronc to occur. The lymph nodes nearby are early infil- tratcfl, not only the axillary but the supra- and infraclavicular groups, as well as the pleura, the other breast and the underlying muscle; the secondaries exhibit a tendency to attack the bones. Microscopically, om> may (h^tinguish a soft rapi<}ly growing (medul- lary) form and a hard, slowly growing (scinhous) form, between whicli THE MAMMARY CLASD 071 Viliriociiriinoiiia uf imimmary gland- a, b, cancer Fig. 303 acini with niuliiplc lumen funnaiion. f } i* \ - V .. --,^- /-.^. «9 ";::;s^'SS;::;r:;Si;;it^;;--i:-~;'-- ^ ' 4L'«Tsirc . vaK.jw.^:sKX-:r- ^^^^^SSSS^^SB (•.72 TIIK RKl'RomVTIVK SYSTEM arc ull (legn-es of variation. When lu'ithcr vt-ry H(»ft nor obvious fibrous, the growth is usually dt'iioininatotl carcinoma simplex. Tl soft tumors utv wliitisli, and exude milky juice, while the scirrhoi ones are fibrous, scar-like, and, if in the region of the larger ,in.. plasm or cement substance, and the sarcolemma. The fibre is I" ivnuciear the oval nuclei arranged in rows close to the inner surface «>l t he sarcolemma. 1 he size of muscle fibres differs enormousl v The muse e spindles are structures distinguished from the other fibres bv MiiiM size and a thick perimysium; innervated from the sympathetic sysi...,,. It IS thonglit that they may be the orgar of '"muscular sniM- After death as soon as a couple of hours in the young, the m>nall,nir,„s coagulate, so that in a short time, the muscles are firii. an< rigiu (ngor mortia), a condition which passes off after a day "r V,. 1 he muscle fibre is rigid and shortened. The muscles are much exposed to trauma and to infection, but they nr.. u.H protected by the tissue juices and the free circulation. The iuiimI,. whose innervation is interfered with is by no means so immune. Congenital Anomalies -These are so numerous as to forbid detailed '!< - ription. Absence of a whole muscle or a part, reduplication, abnor- mal onirin. insertion, or size include most of the modifications found- mn-' I's may appear in man which are normally found only in some '■tiH r spt-cies. 1 he one muscle whose importance entitles it'to special I- "ii.m ,s the diaphragm; defect of this muscle may vary from a small ' l-n,n,^ to a lack of almost an entire half, so that the thoracic and ab- ' '"' '"''.t'^ f f ff^'ly communicative. We have seen ai autopsy a < ongenital defect, with many abdominal organs in the thorax, in 'j'Hi ..t P^ore than fifty years who had some reputation as an athlete IN Numiger days; to so much can the body become accustomed Circulatoiy IMsturbances.-Anemia of the muscles of"~more"than ■i'jTary. juration rarely curs apart from generalized anemic states t ■ '■■ "■ ShI n^v '' '" f'^^'^'f-^ endarteritis of many vessels. ...,», supply may be continuou.siv restricted. Hyperemia occur., in and ;.bout are.s of inflammation, and in states "I I', -.ivc congestion. 4y iz^s^^m^: 674 rut: MOTOR AM) TEC.UMKSTAUY SYSTEMS HsmoRhage is usually of trauiiuttio origin; if a large amount of l>l( be extravasated, a hematoma results; this may Im> al>sorlH-<< II occasionally m the nniscles »-^"mot.x.cus are Regressive Tissue ChMges.- Atrophy.- Atn.phv of muscles „s a «Ii <• occurs u. old age. or in cases of inaniti.m. ixcVllentlv exemplified or n3*?1" "*"'"^''' ■'•' *^' '""" ^"'"S*'* «'"•"* »'>■ '«-«"'" "f the central ':';:::';.::.'?;;;h.mr^ii;;T.ir^^^^ l-'m^tlfli^^en.'r m """ ^--u^es there are certain fundan.ental .' iiri> t< l,t u'eii; the hl.res are shrunken hv loss of contractile si.h "-" i'- « ? simyl'?'"- ^^f f "'lemma and the nuclei' remain j:ran,,|..!: et. he S" a^opposedt,, degenerative atrophy, no such ^n'!°n> tr:t;^c"letl?HTn"'* "/ "'r'^^ ""^^ intoxications, there . I '" '"'"'''e '" «eet'f «i'"> ; such a state often progre-e« ann^r- -■■■ .. at y degeneration, in which the fat droplets may be" sSTn 676 THE MOTOR AND TEGVMENTARY SYSTEMS Waxy Degeneration (Zenker's Degeneration).— This is obscrveci espt- ally ill the rectus abdominis and adductors in typhoid fever, less oft in other infections and in trauma. The muscle is parboiled looking, pi and waxy in appearance. Microscoj)icaily, entire fibres or parts of fibi are seen to be ill-stained and of a uniformly waxy appearance, t contractile substance appearing to have undergone a coagulati^ necrosis. Transverse rupture of tiie fibrilhe appears to occur, althoUj some hold that this is an artefact. The occurrence of small hematomi however, is strongly against this supposition. Progressive Tissae Changes.~The regenerative processes of mus( have been discussed elsewhere (p. 197). Hypertrophy of a muscle fni increased work in the presence of adequate nutrition, consists in broadening and lengthening of the individual cell. Debate still exi^ as to whether or not a numerical increase of fibres occurs. Tumors. — Primary tumors of muscle are not very common, and t fibromas, myxomas, and angiomas that are observed, as well as the lipoini arise from the coiniective-tissue structures, the peri- and endomysiui etc. Rhabdomyomas originating from the muscle cells are singular rare. Sarcomas of various kinds may be found, and while we ha found rhabdomyosarcoma in the trout, its occurrence in man is litt known. Secondary sarcomas and carcinomas are not common, save I extension. THE TENDONS AND TENDON SHEATHS 'J'he tendons are relatively a\ascular bundles of strongly united pa allel fibres, held together by a small amount of connective tissue wliii carries the blood vessels, the interfascicular tissue, and which fori an external covering, the ju'rifascicular tissue. The tendon is encl()S( in a dense fibrous capsule, between which and the tendon is a space filii by synovial fluid which serves as a lubricant. The tendon slieai cavity is thus one of the synovial spaces, and as such is very like tl joint cavities and the bursa'. Hy reason of their little vascularii they are not prone to infections of a primary nature. Infla mm ation. — Tendinitis and Tenosynovitis (Tendovaginitis). Despite the name tendinitis the tissue of the tendon practically pla; no part in inflammatory processes, which concern chiefly the inte fascicular tissue and the sheath. Acute Tendinitis and Tenosynovitis. — This is an exudative inflammatii with fibrinous, serofibrinous, or purulent exudate. The less sexci forms may evidently arise as primary diseased states in rheinnatisn and from trauma, while the purulent forms are usually by extensioi or by infection from penetrating wounds, rarely hematogetiousi; With a fibrinous exudate, "dry tenosynovitis," the fibrin forms a thi layer between the moving surfaces, and motion gives rise to cr('i)iti tion. It is (|uite often seen in the extensors of the thumb and haiu The serofibrinous form, in which there is some fluid cxuilatc in the slieat! is oftenest seen in the flexor tendons of the hand; when absorption of th THE BURS^ 677 .natly limit mc,veinent, Zil n Sfh^ T"^ '^'jf"*''- These may ""■•'t they become length, ed thireH \' "'"^"'"«"ce of move- .'l-Ijear. ^^^rulsr^ ter^^X^ ^^/':; ^^''^ "^^y Anally dis- ="i«''"« "masses of degen- inflanunation. ^"^ ''^''* '""^ "^^•"'- «« " '•^^"It of a long-conti/ued ■-""J^SS'-^nlirS^^^^ can be prima.,, •■'m>i.st of a diffuse inflammatTon wifh^r •? "\"*'^'"^^'- ^^ ™ay ti-.u' which fills the cavitv"md co^^ s tl !'r T"*,^ ""-^ g'-anulation f»ue of the tendonmav i,ec IhJeL^^ *'"'.?' *''« interfascicular -■• The soft gra,„datio„ t^Z " ad^^'il^f ^7'°" -"ease in IToccss may ensue and finally bnUtfJ^l ^ . "^f ' ^'"'^ ** suppurative More rarely tubercul 1 ma ^1 ow Jti?^ ''^' '"P".';^^'^' structures. ■'• >'-v progression and TcL na iirhv': ^'7""^"^ overgrowths ■Ti- hodies," spoken of XvfZ be the" f'T^ ^'"""^■' ^^e pn„rss. *"' ™'^'^ ''^ t'l'' product of a tuberculous "I il"' ^liralli. inKctio.1, later, gumnias occur on the wall *■" ."„) I,e a prcJicrSZlorMiif, '■''''''*■'•''■?'"''• '■'''""■"''""■ "« " »M- ill size of the tejidoi, """"^*"' '"""e ""I a corresponding ^li> ill h. '^ ' " " '^c'l ; lipomas occasionally arise in the ^^'-'■•'1 fluid; it i; frequltly see on 'hri; i;"T ganglion, an,! consists of a her.S nouch uhn ""^ u^-' ""'"''' '"^^ •!'>'" 'If.! tendon sheath. ^ ''^""^ '''*•" '« "'"'^e "f the THE BURSA 078 THE MOTOR AND TEGUMENTARY SYSTEMS pressure, such as is caused by the phiy of a tendon on a bone. Th( l)ec()nie lined by a definite en(h)theliuni, and l)eing perfectly analogoi to the tendon sheaths, they are subject to much the same processes ( disease. Fibrinous, serofibrinous, and i)nrulent exudates occur inflammation of the bursa?, under conditions similar to those uwd which tenosynovitis occurs, with the difference that the bursae are moi exposed to trauma than are the tendon sheaths. Chronic bursitis characterized by much thickening of the walls and a considerable amoui of exudate, so that a large swelling may be produced at the site of tl bursa (hygroma). " Housemaid's knee," " miner'sdbow," and " weaver !)ottom" are all well-known forms of bursitis. Tuberculosis affec the bursa usually as a diffuse granulomatous affection of the linii mem}>rane. Sarcoma, endothelioma, fibroma, and myxoma of a bursa have ))et found, but none of these are common. THE BONES It is worth stating, that rigid as is its nature and apparently fixc( bone is throughout life undergoing a steady constant process of absorj tion and reformation according to the needs of the economy. Thei is, indeed, no more excellent exanii)le of the economical use of materii than is afforded by the normal structure of bon»- particularly the lor bones. Just as the engineer has determined tiiat the hollow ste cylinder is capable of standing greater weight and greater strain than solid column formed of the same amount of material, so the long boiK are formed not as solid masses of calcareous matter, but as cylinder and what is more, they expand at their extremities; instead of l)eii solid we find that the l)one is laid down as a lattice-work of "strut: whose arrangement is finely ailapted to bear stresses upon the bone particular directions. Now these stresses may vary with the changii weight of the individual and with the growth of the different parts, ai as a consequence we find that these "struts" undergo alteration i adapt them to the altered stress. On one aspect we may find reniov of the bony substance through the agency of osteoclasts; on the othi side of the same lamella there may be a simultaneous new formation ( layers of bone through the agency of ilio osteoblasts. In an exagge ated condition we may find these simultaneous prowsses of absorptic and new formation occurring in diverse pathological disturbances. Abnormalities.— In true dwarfism, as again in true giantism, tl bones share the giiieral abnormality of development of the tissue There are, however, other dwarfs in whom the bony development is w proportioned. One group, for exan Ae, exhibits a marked shorttiiir of the limbs; such dwarfs are examples of chondrodystrophia foetal (achondroplasia, mieromelia). There has been much deh-nte as \ the imderlyiiig process in this condition, but the disease may I J?^^ 'JT^ ^"p,«fcf *; '??>-. :-^*---fjai»»4»i-- Till': HOSES 679 ngiirded as a fcctal rachitis. It i toiuui that the periosteal formation lin\\ an abnormal liability to fracture. In a case in our collection, reported by Klotz, the body of the newly born infant showed over a Innidrcd such fractures. Associated with this there is marked deformity iind sliortening of individual bones and of the skeleton in general. Tills is, strictly speaking, more closely allied to rickets than is chondro- il.ystrophia; there is, namely, abundant preparation for the formation of lioiie, in the shape of well-developed cartilage formation, only there i- a failure both in the periosteal and chondriform metamorphosis iiitii true bony tissue. Even in the shafts, the periosteum may give ori-iii to fibrous tissue rather than bony lamellae. This defective liiriiiation may be so extreme that large areas of the calvarium may ri main purely membranous. Circulatory Disturbance.— The very rigidity of the channels within ilif lione substance prevents extreme alterations in the blood supply. I ill' iieriostcuni, however, is liable to exhibit more pronounced changes, active hyperemia, passive hyperemia, etc. More important, there may I'l ' Atcnsive periosteal hemorrhages, either traumatic or as a result of • liMaM.. Closely allied to the traumatic mu.st be mentioned a most ^inkiiij,' form of periosteal hemorrhage, viz., the cephalhematoma of lit' newborn. Here as a consequence of unduly prolonged presentation "I 'ill liead in the cervical portion of the uterus, and of the great com- |ir. ion exerted upon the body of the infant by the contracting uterus, tlir . xtrenie oo„gcstion of the vessels of the calvarium leads to rupture ■' same as they pass into the overlying pericranium, with hemor- t.i- \\v I3^- r-rfJ^JCK;\fcili 080 THE MOTOR AND TEGVMENTARY SYSTEMS W^ rhage between the tvo layers, and an accumulation of blood the ; of half an orange i>-ay result. This hematoma may undergo abs( tion, but if the process of removal is slow, a ring of bony growth n occur at the periphery. Infarct. — The predisposition shown by young children to osteom litis originating at the ends of the long bones is usually ascribed the active vascularity with new vessel formation presenting itself in neighborhood of the epiphyseal line, the new vessels here becom the seats of bacterial emboli. We have stated elsewhere that doubt whether such emboli are truly primary; rather we imag that individual bacteria arrested by the endothelial cells multi and set up a focus of inflammation with thrombosis. Whet actual infarcts occur is a matter of controversy. The appearance si in many cases of tubercult)sis of the ends of the long bones stron suggests infarct formation; wedge-like areas of necrotic bone may detected having their bases immediately beneath the cartilage, but h it may well be that there is not primary embolism but obliteration the nutrient artery in consequence of perivascu'ar tubercle format and the associated endarteritic changes. Extensive i ecrosis may oc where, either through trauma or through accumulatior. of inflammat( products, or of blood, the periosteum becomes separated from theund lying bone and the nutrition of the latter cut of!'. Tnflammation. — According as the inflammation involves the peri teum and the surfaces of the bone, or the substance of the bone and i medullary cavities, so do we distinguish between a periostitis, an ost myelitis or, inasmuch as one process, if severe, inevitably leads to i other, a general osteitis or panostitis. The study of these conditions is complicated by the fact that when an infective agent, acting intensely, leads ti, necrosis and absorpti of the bone substance, in the areas of surrounding hyperemia then set up coincidently a productive i)rocess leading in the deeper parts the bone to increased thickness of the lamellre and greater density the tissue, and on the surface to the formation of new bone layers of osteophytes, irregular processes of new bone. In extreme ca the intensity of the inflammatory j)rof'ess and the presence of tensi may lead to the necrosis of relatively large masses of bone, wlii undergo a \ery slow process of absorption while simultaneously t periosteum gives origin to new bony layers. As a result we oi)tair sequestrum surrounded by an involucrum, with associated thickeiii and deformity. Usually in these cases the purulent fluid surroundi the sequestrum makes its way along the line of least resistance, tliroii some area of weakened periosteum, into the subcutaneous tissues a so to the surface, giving rise to one or more sinuses. Periostitis.^ — Acute periostitis may be of two forms, simple and sii purative. The former shows itself in non-infective traumatic int< tiuns and in illfeetion^s of low virukmc, and is characterized by a ivM acute course with infiltration and subsequent thickening of tlu i)e •!^KElSJX^:•% =,'. . w^m OSTEOMyEUTIS 681 (i>rt>um, stimulation of the gonetic layer to active Ixme production ri lilting in a local increased jjroduction of hone in the form of osteo- pli.xtes or nodular thickening. Suppurative periostitis is much more .Kiite, and involves a larger area and shows itself as an accui..ulation lit' i)us cells within the periosteum and then between the periosteum and the hone. This accumulation of pus tends to extend around the shaft of the bone laterally in all directions, inasmuch as the density of both •MTiosteum and bone prevents extension either outward or inward. Thtre is thus great tendency for the nutrition of the bone through the periosteum to be cut off, as also for the process to extend to the joint setting uj) a suppurative arthritis. With the continuance of the dis- ease, the periosteum at t)iie or other point may undergo atrophy and erosion, the pus thus extending into the surrounding tissues and setting lip a i)eriosteal supi)urative process. So also in some cases the i)rocess extends along the vessels into the marrow, inducing a panosteitis. Such suppurative periostitis may be brought about in two ways, either as the result of an infective traumatism or, as happens not infrequently ill voinig children, as a hematogenous or cryptogenetic process. The or^;iiiiisnis associated with the process are most frequently the pyogenic (oeei, and such bacilli as B. coli and B. typhosus. The latter is espe- eially ai)t to set up a somewhat restricted and localized suppurative periostitis, sometimes showing itself long after the acute infection has passed. In the younp, there is a peculiar liability for this suppurative form ()f disease to extend along the epiphyseal lines and lead to separa- tum of the epiphysis from the shaft of the bone. Osteomyelitis.— In this condition the primary infection occurs in tlu marrow of the bones, and may be set up by the same organisms as iiuliur in other cases periostitis. Like periostitis, the condition is nin^t eonnnon in the young and during adolescence, while the long li'mes arc those most frequently affected. As already indicated, not iiilrecpiently the disease begins as an infective epiphysitis. The ordinary course of infection is modified in the case of the bony Mil.MaiKc by the unyielding nature of the framework; the congested \< -els cannot throw out much exudate or, more correctly, the exudate ami infiltration of leukocytes react upon the vessels themselves favoring tiiiuinl.osis and the rapid production of relatively large areas of necrosis. llm> caries or necrotic softening with absorption and more extensive iierroses of bony tissue is a common accompaniment. We have alreadv reterred to the results of these processes in the production of sequestra; ^". airaiii, the inflammation is very apt to extend to the periosteum in- 'lii- ing suppurative periostitis, periosteal iierforation and the formation "I h^tulre The process, if very ai ite, gives rise to a generalized bac- t' ' i. una or pyemia resulting in deati : if less acute, is followed by various siauxs of reactive development of new bone, although often f- -n the fii' o>ed nature ot the foci of suppuration the acute stage pa&^v. on to 1- nironic or latent form of osteomyelitis, with tendency toward acute e\;i ■ rl)atioiu from time to time, over, it may be, years. i a » a 1 r J I r iff I if :•**■/.??#!& '■•^^mpmKsrw'v 682 THE MOTOR AND TEGVMESTARY SYSTEMS M 1 Mn Chrome Periostitis.- Various forms are (lescrihed. As already ii cated, continued mild inflammation of the periosteum leads to b overgrowth, and the formation of osteophytes— periostitis ossiflc; 1 he periosteal overgrowth of hone after fractures is of this nati so, also, the bony overgrowths through irritation induced by neighf ing tumors or inflammation of overlying structures, as is well she 111 the nodular o\ergrowth of the tibia under a chronic ulcer To c()mmonest form of chronic periostitis, viz., the syphilitic, refere will be made later. A remarkable type of periosteal inflammati the penostitis albuminosa, has been described by Oilier in which a th serous fluid containing albumin, and a few pus corpuscles and so hbriii, collect:s between the periosteum and bone; it appears to be mildly infective origin, and differs merely in degree from the m^ acute suppurative periostitis. Chronic OsteomyeUtis.— According to the virulence or concentrati of the infective agents, so do we find two processes manifesting the selves in cases of long-continued inflammation of the bone substan VIZ., rarefaction, or osteoporosis and condensation, or sclerosis. Rarefyi osteitis is evidenced by the progressive absorption of the bony lamell Ihe marrow becomes increasingly vascular, and through increas osteoclastic activity the compact bony tissue undergoes reducti until It assumes a loose spongy appearance. According to Ribb« and others, m these inflammatory processes the i)resence of osteocla* IS not essential but ordinary leukocytes possess the capacity of causii absorption of the bone, as clearly happens when the bone has alrea( uiKlergone necrosis, as in a sequestrum. Condensing osteitis occurs, as already- st.jted, where the irritation is n so intense. One of two events may occur; either there is evidence increased osteoblastic activity so that the lamella; undergo progress!^ thickening and the marro.x sjiaces become correspondingly reduce, or the marrow first becomes less cellular, shows an increased fihrosi and the cells of this fibroid tissue undergo metaplasia, becoming boi corpuscles. In this way, save for a small space around the ceiitr vf>ssels, the whole of the marrow may become converted into deii: hone. If at the same time there is progressive periosteal new develo] ment the shaft may become thickened to twice its normal diametc aiHJ the central marrow may be completely replaced by solid boiK It IS this secondarily formed compact bone which, from its extreiu density and likeness to ivory, has been described as ebumated bone. We shall discuss the so-called osteitis deformans among the regressiv changes. Specific Inflammations.— The bone is peculiarly liable to be inftcte( in both tuberculosis and syphilis, and to present characteristic mo-lifi cations. Tuberculosis.— Tuberculosis may show it.self either as (1) of primarj periosteal origin, or as (2) ,i form ..f specific osteomyelitis, or (3) i generalized miliary tuberculosis. The last is relatively unimportant ■wmi^' BO\E TUBERCULOSIS 683 m..s„n,cl a-s death occurs before any ^-rave change has er.sued in the 1.O..0S. IV-nostitis, als:., .s apparently not of first importance- it s >rrn particularly u, the rihs. By far the most importa, ta tuberculous osteomyelitis Certain bones are particularly apt o be =iitK' «1, notably the en.ls of the long bones, the fen,ur and tl e t^b b >HMi the vertebrae. Less frequently the calvarium and the pl^^alants' .nay be nuolved. Tuberculosis of the spine and the ZgZZt l.-rp (xtent, to the function of the parts cent -ned. namely, that the wHght-beanng of the body is veste.1 in them; thus the tuberculous .hsease is assisted by pressure at all times during which the upSt i.v IR pressure, fh is osteoniyehtic process in the long bones originates «. I. great rarity in the sliaft, save in connection with the phalSes S I ..Idren spma ventosa) but almost always in the epiphyseal e S and tins ,n cnildren and adolescents. The process begi ,s by the forma- t...n of a conglomerate tuberculoma, with surrounding ... es while simultancusly new tubercles form in the surrouiiS " ■-Inllary spaces with, as a result, a progressive ami sprea.ling ^^ eou! .n Kc, and accompanying .lestruction and rarefaction of the Se y.. We have a ready pointed out how economically the normal bZ ^ul.>tance is laid ,lown in relation to the strain it is called unoio Ij-r, and. therefore, if there be any considerable area of rare acS "nd ■>tnu.t,on without correspomling overgrowth in the neigh borhr- the n otal.e result is that the bone gives way and becomes disto tl^ 1 IMPt un oh ed. At this process advances, it is apt to extend to the rnlaguHuis joint surface and with erosion of thJ cartilage thrmS rtiir,t.> ,s set up. A similar osteomyelitis involving the vertebre r;;;:;'?;" ^'^*\-'f -"--f the bodies, often as scattercUo ^^'l S^ 1 ■> /nlarge by formation of new tubercles at their peri, her t's I to tuse aiHl give origin to large areas of caseation and caHe he i i.m "w."' 'X "''" ''''^'' '^' IH-riosteum and interferes wih rm.rn. ^Vhen the process extends to the intervertebral disk it —^ a rapid destruction of the same with extension of the tuberculous li. t , n • I f''l '''™'"'' compressed under the weigh: to tIH^ are subjected and kyphosis or angular backward curvature ,n , Jr '''' ^ ''''"'* °* *'"' compressing force or from the ' 1-ratively thin periosteum covering the vertebral bodies L is P' Huunced tendency for th > softened caseous matter formed Sin tin ^.rtebral body to escape into the immediately overlying tfs u s" -M^^iSf 684 THE MOTOR AM) TKCVMKSTMiY SYSTEMS |. in wliicli it may travel ^reat distances by mifxiM'ctfd courses, indue wliat is called a cold abscess. The abundant contents of such are constituted of true \ms hut of diluted cheesy matter with a small |i portion of h'ukocytes an prosurc (though here also there is inHanmiatory absorpti(m of the ti-iic whose nutrition has been reduced). Halisteresis.- Such simple atrophy m r be distinguished from IwlMcresis in which the absorption of tin bone is preceded by solution jiiiil iii)sorption of the bone salts. This latter process is dominant 111 (t Ttain remarkable disorders, notably in osteomalacia and in many <:iM ^ (,r so-called osteitis deformans, between which disorders there are iii:ii!.\ points of relationship. Osteomalacia is a condition most frequently described in females and tlirii 111 association with pregnancy or lactatictn, but it may show itself iiiMi III adults either male or female. It is apt to affect the whole bonv triiin.uork and may show itself first in particular orders of bones. .\nt;iMy in tlic female, the pelvis is apt first to show disturbance, and, tlin i-li the loss of bone salts and softening, there may be developed ^triL iiir deformity, the acetabnla being pushed upward by the weight "' '1 ' body, the blades of the ilia pushed outward so as to become iii'T. Iiorizontal, and the pelvic outlet correspondingly diminished. *\ iiii this there may als(» be great softeninir of the bodi<-s of the vertebra' »itl, ii.r.losis, kyphosis, and scoliosis, and the h>ng bones may be found -" ncned that they can be easily cut with a knife. The process i 3" 5 ■ * ^ ii 1 1 08G THE MOTOR AM) TKdlMHSTAIiY SYSTEMS 'I';f niiiy jjo on until tlu-n- is practifally cniiijili-te abst-iKr of hoiw salt- imlividiial Ixnics, hut in frcncral, iiUn\ff with tlie aI)S()ri)tion, thtTo evitlcnces of attempted achiptatioii or reneneration so that, for exani] ill a Ion); hone which lias underKoiie the causation of this diseast* notiiing definite is known, hut the diffuse X\\w of the change, the known association hetweeii *he pituitary, the pitnithyroids, and the calcium metaholism of the hooy, lead us to tliB litTit'f that lu-re we deal with another of the disturbances associated witli want of balance l)etween the organs of internal secretion. A few (UMs have been recorded in which lesions of the i)ituitary and thyroid liavc been associatei>t through life. The process may involve the spinal column Itinliiig to curvature, and through the soft condition of the ribs tht-y > ii 1.1 to the forces acting up(>ii them, .so that the clu'st 1h'( omes flattened in till- anterolateral regions and the sternum forced forward, causing wliat is known as "pigeon-breast." The rachitic "rosary"' is a swelling nf -luccssive regitms of junction of ribs with sternal cartilages; while this can be felt from without during life, it is most j)ro!iounced on the inner aspect. The joints of the limbs ap{)ear enlarged relative to the shafts of the bones. The forehead may take on a curiously ><|M;irc appearance, due to what is known as cranio-tabes, with thiiming nf llic cranial bones, most markerc(lisposing factors, although of two children subjected alike -(• influences one may become rickety, the other not. Recently irtro, confirmed by other Italian patliologists, has isolated what inis as the si)ecific organism inducing the condition. The time t come to state with certainty that this is an infective disease. ciiiii: air ,i!!i stHiii to l!; Mo:; |i FRP ^V fiSK TIIH MOTOR WD TtJn MKSrARY SYSTEMS If Wf «'\aiiiiii«' tlu- «i)ii>liys«'al «'inl nf «>in' cf tin- luii); boiH's, tln> I of ciirtiliin"' iMtwt'CM I'pipliysis anil diaplivsis is found jtrtatly tjiickn anil fin>?«T-liki' priwcsM-s of nt-w cnrtilap- »'Xt«Miil iU'«'ply into marrow, nivinn an irrrjrnlar lint- of iliinanatioii. In tin- lU-eptr |i tioiis tlicM- .-olunuis of carlilaK*' «'ll^. instead of giving platr to t hony lanulhi'. pass into an arou of osteoid tissue, p«K)riy suiipiit"*! w hone salts. I lere and tlure masses of the eartilnge may herome isola and snrronndeil hy the osteoid tissue. This zone of osteoid tis passe.>i more de»'ply into the niedullated lione than normal, hut graihii givt's j)laee to l)one proper, although there may Ik- an intermeili zone ill wliieh the central areas of the lamella- contain bone salts \vl the i)eripheral i)ortions are devoid of thes*- salts. H»-t\veen the osteoid lamellie are relati\ely wide chamiels fillwl w a marrow, containing sparse marrow cells projKT, hut showing spin cells and fine fibrils, a more fibrous marrow than normal. This n unihrgo a direct metaplasia into osteoid tissue. AVith i)rogressing this osteoid tissue exhibits a more and more com|)lete dei)ositioii calcareous salts until the whole of the lamella' may take on the nori appearance, and the bones become of almost ivory hardness, with sii Haversian canals, rcriosteal bone is not laid down regularly, but wl its development is arrested in ccrtr.in areas it is aj)! to be excessivt others, osteophytes being i)rodnced. Infantile Scurvy ( linrlnw'n Dismsr). Tliis disease is on«' of rec observation, it having been unrecognized prior to the employni of pasteurized milk and various sterilized milk prei)arations. I( unknown in children fed upon the mother's milk, and presents it first as an exquisite tenderness of the limbs so that the child screi upon being movtfl. I'pon post mortem examination this tenden is found to have its cause in an acute congestion of the periosti with the development of subperiosteal hemorrhages; hemorrhage in medulla may also be present. The nutrition of the bones is gra\ aH'ccted: they are of lighter build than normal with a tendency fracture and curvature. Hemorrhage may occur in other organs ; recall those associated with scurvy. As in that disease, so lure, exhibition of fruit juices is found to arrest the progress of the comliti there is, on the other hand, a certain likeness to rickets, e. g., soften and curvature of the bones. Progressive Changes. — The important subject of the repair of b with callus formation has been touched upon by us on p. 192; as i we have dwelt to a considerable ext upon the diflferent order; primary tumors of bones in the sectioiis uixm myelomas (p. 236) i osteomas (p. 2:].")). Here we need only rei)eat that it is in very ni eases difficult to draw the line between local hyperplasias and tlic t tumors of bone, and that true i)rimary benign tumors are really in quent, most of tin- osteomas being hyj)erostoses. Tumors.— We thus recognize circumscribed hy|)erostoses- exosxo localized bony formations of periosteal origin projecting from thcsurl iki Tift: H0.\ KS~TUMORS 680 dl' till- Im)Ius and enostoses, originating from th«> siHingiosu. Of similar Milt lire- arc tliv ossifyinf ecchondroMS, niMlnlar ovt-r^'rowtlis projecting triiiii tlic iMine in tin- rc^cions where there liad U-en previous chondri- lonii developments, notahly in the r»-gion of the epiphyses. These liii\(- a superficial layer of cartiluRc and often a small hursu over their Iri'i- aspect (ezostMis bursata), and may he nniltiple. Oilier Itenign connective tissue overgrowths of tht- hone are rare, ii \\(- leave out those originating from the periosteum. If we include tlusc, fihromas of the hone are occasionally met ifibrons •polis), as also iiii-iipliaryngeal polyps of fihromatons nature, originating from the |Hri i-tciiin of the hase of the skull or the walls of the nasopharynx. I'lin- mjrxomu were very rare, mjrxo-chondromas :itid mjrxo-sarcomaa Minn- foinmon. 'rumors originating from the hone marrow tnay Iw of the relatively 111 iii^jii tyjH', so-called giuit-celled sarcoma, which we regard strictly as III! o^ti-iK-liistic fiant-celled myeloma. Myeloma multiplex may he regarded as a diffuse Mastoinatoid over- ^niwtii of the marrow, and may hecomp.i i of more than one tyin ^f iiiiirrow (I'll (see p. 2;{()). Sin !'• angiomas are rare, hut there are a ^ .- iHMsof a remarkal>!chemangio-endothelioma(m record, involving parti i i .rl\ till- hones of the calvarmm and showing channels filled with IiUmmI ainl lined hy an almost cuhical endothelium. Intermediate tumors of till- nature of osteosarcoma, osteoid sarcoma, chondro-osteo-sarcoma, and chondro-sarcoma arc to he found. The most frecjuent form of hone tumor i- iniiligiiant and sarcomatous. We distinguish sarcomas of periosteal ;iMil of endosteal origin. The former prtwluce large, o\al masses of new lirowtli surrounding or s[)rcading over the surface of the affected bone; tluy may he round or spindle-celled. What is more, a tumor arising litriii>teally may invade the shaft of the hone causing its absorption. Tlii'^i- lire more fre(iuent than tlie central sarcomas, which, again, cxduiliiii; the giant-celled myelomas, may be round, spindle, or mixed ii'll- 'I'liese central sarcomas are liable by progressive absorption of till -iirroimding bone to give origin to spontaneous fracture. 1 III -<• malignant sarcomatous tumors of bone show certain features ill ri'iiimuii, viz., they are apt to be extremely vascular and may present txit ii-i\(- hemorrhages, or later these hemorrhages may give place to '. t -. or, again, may be accompanied by extensive necrosis; the growths may vprtad into the surrounding soft parts, and the nearby lymphatic iiikIi . iiiid frequently att'ord metastases in the lungs. A- to secondary growths, many cases are on record in which thyroid ti-Mii has been found forming circumscribed tumors within the bones. Whiii jirimary epithelial growths do not exist, it is striking how certain 'iir ! iiiiis of particular organs show a predilection for extension into !i< s. This is notably the case with prostatic, and, to a less extent, mammary cancers. So, also, is it with the mesothelial hyper- •iiia wliicli may airt)rd metastases in bones eiilier b^v extension I distance. th. wit til i (ir 69() THE MOroU AM) TKGUMEXTARY SYSTEMS «i . A useful distinction iM-tween jH-riostfal aud endosteal saroomuj that the former, while they may have a framework of radiating Ix spicules, possess no covering layer of bone; the endosteal sarcoma, the contrary, as it expands and causes the absorption of the bony tis; in its neighborhood is apt for long to remain covered by a layer of p( osteum which layer, no matter how great the exi)ansion of the tuin contiiuies to give origin to bone and thus this form of sarcoma is ; to be covered by an imi)erfect tliin bony layer, so thin that on pressi it affords an "egg-shell crackle." Cysts. — Cysts may originate in bone either in connection with ii growths or with osteitis deformans as tlie result of localized necroi with or without hemorrhage, and subsequent autolytic absorpt; of the necrosed matter. Parasitic cysts are of great variety, connection with the jaw c\sts of another order may develop, v the dentigerous cysts, formed around accessory and imperfect toi germs; they may be either nni- or muitilocular, the latter being of 1 nature of cvstadcnoma. THE JOINTS \ Each joint consists «)f a cavity containing a s|)ecial fluid— the syi vial fluid — interi)osed between two or more bones which in this w become capable of ino\ ing oni' against the other. This cavity exti n somewhat beyond the apposed surfaces of the fntnes, and is linm an endothelium composed of one layer of cells, which ' ■ yond t apposed surfaces rests upon abundantly vascular tissue. Outside th again, is an outer fibrous layer, wiiicl. liere and there becomes nu condensed and reinforced to form the ligaments. Upon the apjjos surfaces the synovial endotlielium is more flattened and rests alni( immediately upon the dense thin laver of cartilage covering so niu of the heads of the bones as are liable to move one ujjon the otlu .\t the junction of the .synovial membrane covi ring the joint and t outer, saccular prolongation, the membrane is apt to be developed in a series of small papillate processes, the synovial fringes. The syiiov fluid is not a simi)le serous Huid, but contains mucin and albumin as to have a somewhat slimv character aoDropriate for a lubricjitii Huid Abnormalities. Iiu I ue la.xity of the joints, brought about by \i»>- iicss of the ligaments, and favoring easy disKx'ation, is occasionally im The condition is generally nuiltiple, affecting several joints. Mi> serious conditions arc those due to iiuperfect development of the Ikui entering into the formation of the joint. This is seen more especial in connection with the hii)-joint, where the head of the femur is iniiH fectly developed and coincidently the acetabulum does not beinri adequately hollov.ed out, so that there is no proper seizure of the In ; within the acetabular ca\ il\ , and in the upriglit posture, llic i.i . of the femur is forced upward over th'- wing of the ilium (congenit m THE JOINTS 691 dislocation of tiie hip). A similar loost'iuss and imperfect formation iiiiiy atVect the knee and other joints, in(luein<; subluxation. Circulatory Disturbances.— These are ineonsiderahle; thns anasarca i> not aeeonipanied hy any excessive accumuhition of fluid in the >,\ iio\ ial cavities. Through trauma there may be hemorrhage into the joint and the resultant coagulation may lead to the development of one form of false body therein, often subsequently absorbed. Inflammation. — A notable feature of inflammation of the joint la thritis) is the sympathetic inflammation, exudation and swelling of tli • soft tissues around it. Xor is the extent of this swelling by any iiiians a sure indication of the severity of an arthritis; an acute "strain" of till! ligaments may be rai)idly followed by intense surrounding swell- in^', iiltlujugh the actual injury to the joint is of simple nature, slight iiiiil localized. I'ollowing contusions there is in addition to this surrounding swelling a rapid increase in the serous contents of the joint cavity so that in tile knee, for example, the i)atella is "floated" or pressed away from the underlying bony surfaces. This serous arthritis is secondary to liMHiir.iia and is the simjjlest form of exudate, with few leukocytes. It tends to undergo absorjrtion but occasionally the inflammation !)•■( nines chronic with thickening of the synovial membrane, vasculari- zation and proliferation of its surface layer. The forms of trauma Mtting n|) serous arthritis may be various, either a contusion, a " strain," a loose cartilage or the sudden entrance of the same or other lo(»se body HI the joint between the joint surfaces. With more acute irritation till re develops the condition of serofibrinous arthritis; the fluid in these liiM > is no longer clear but turbid, and if the joint be oi)ened there is iiit.iiM' liyperemia of the synovial membrane with slight fibrinous ||<|>oMts in the recesses of the synovial sac. The turbidity is due to an uiireased migration of leukocytes into the fluid. More severe and il' -triK live inflammation, due to the jjresence of pyogenic organisms, rcMiiis ;n suppurative arthritis. With this the synovial membrane becomes •Toilcij and more particularly there is apt to be a degeneration and iToHiii ()f the joint cartilages, following upon which the jmurss may <'\ii 11(1 into the bone setting up an osteo-arthritis. Where these erosions taki iil.icc there is a process of healing if the joint be kept immobile: ■kIIh ions may occur between the apposed joint surfaces and with organ- izatinii and formation of dense connective tissue across the joint cavity til' iiovenicnt of the joint is almost entiicly arrested. Where the 'I' HiKtion has been very extensive there may indeed be developed 111 iMTsal adhesion between the two surfaces and in the process of '"ony ankylosis be set up, true bone rei)lacing the fibrous tissue, y be noted that where serous and serofibrinous inflannnations 111,' contiiuied, with voluntary immobilization of the joint by the r. altiiough the joint 'surfaces arc not invoh-ed, nevertheless the iiing, fibrosis, and shortening of the synovial membrane and the iits may also lead to rigixtension o{ the suppurat process either from the surrounding soft tissues or from the bone, again from traumatic entrance of infection, and, on the other ha is apt to extend beyond the limits of the joint cither, as above no into the bone itself or into the surrounding soft tissues, or both. There is a condition which it is usual to include among the cliro joint diseases, but which wc are convinced should be more prope regarded as an acute disease, as a recurrt^nt acute or subacute artlirii we refer to arthritis deformans. Here over long years the patient subjected to a succession of slightly febrile attacks with acconipanvi exacerbations of |)ain and swelling of the joints and the periartidi tissues. With this the joints show progressively increasing deform and progressive inflammatory thickening of the surrounding soft par The histories given indicate that there has been primarily a pure arthri hut with successive inflammations the process extends into the appn'^ ends of the bones leading to a rarefaction of apposed surfaces \\i flattening, compression even up to the stage of cburnation, ami d tortion, while simultaneously the process extending to the perio-tn in the neigliborhoiul induces there a proliferative overgrowth, often wi "guttering" and subsequent locking of the joint, the whole a''comi):ini by great deformity. We have seen such a joint after many mj showing purulent contents, though this is probably an unusual cmi Worthy of note is the involvement of the spine in this disease (spend litis deformans). Here the inflammation spreads to the ptrioMii and ligaments of the vertebne, and with the new bony growth :h results, there is developetl a complete sujK'rficial ankylosis Im ii TUBERCULOSIS OF THE JOINTS 693 invial form occasionally is of acute development inducing an al)un(iant serofi^ us exudation; more frequently this, like that has a chronic course, viz., with the formation "t tui)erclcs on ti - vial membrane and surrounding inflammation; thiii membrane e:. ,■ proliferation and fungoid overgrowth, becomes iK'iil.ly thickened, and not only is the outer layer involved but the surrnnnding soft tissues become infiltrated with the tubercular growth I -woilen. With caseation and breaking down of the infected tissue ' may be final fistula ft)rmation. Coincidently with these processes, I'oiu- if not i)rimarily the seat of infection, becomes secondarily Kc(i in a rarefying tuberculous osteitis with necrosis (caries). . as in arthritis deformans, there may be a coincident suiKrficial iituin of bone by the periosteum in the neighborhood of the inflamed in the form of osteophytes. philis. In the congenital disease an exudative form has been led with disintegration of the cartilages and fibrosis and thicken- tlu- capsule. In acquired syjjhilis, there may be an acute serous an th. tin (594 THE MOTOR AM) TEGUMESTARY SYSTEMS or serofibrinous arthritis in the eruptive stage, or later there may small-celled infiltration or gummatous formation in the synovial mt brrnes, either primary or secondEry to a syphilitic osteitis or periostei Regressive Changes. — Atrophy. — The most imiM)rtant degeneratii occur in connection with the joint cartilages. Here we may encouii either a fatty degeneration or a necrescent state of the cartilage c and with this a coincident dissolution of the matrix. This is «)ften v characteristic in old age; the matrix becomes more mucoid and fibrillation becomes prominent. The general result is that urn pressure the cartilage shows a tendency to ulceration with secondi sclerosis and eburnation of the exposed underlying bone. In ot areas the degeneration may be followed by some ])roliferation of remaining cartilage cells, and calcification with opacjue whitening these areas may eventuall\' show itself. The remarkable condition of ochronosis is characterized by a d( brown or blackish coloration of the cartilage. It is very rare si little definite is known about its causation. It must be rememl)e that cartilage has an affinity for iron aiu' also for blood pigment t that thus if there be hemorrhages in the leighborhood of the joint, cartilage may b--,ome the seat of a hen^atoidin pigmentation. Gout. — AnothfT infiltration that is very characteristic, is that s( in the gouty joint, especially the metatarso-phalangeal joint of great toe. Here the cartilages either generally or in patches may ti on a chalky white opacity, which is found, upon microscopic exami tion, to be due to a dense infiltration of the Mstrix with fine acicii crystals of sodium biurate (see p. 107). The same deposit may be si in the synovial membrane and its imderlying soft tissues and liganiei In the surrounding tissues, the: e deposits may occur as tophi or sn hualized ncMlules. In general, if the crystals be dissolved out, i1 found that the cartilage is necrosed, whether as a preceding oi sequent process is yet debated. Neuropathic Atrophy. — In the course of some cases of locomotor ata and syring(miyelia it may hapi)en that with complete absence of ]) an individual joint, such as tiie knee-joint, may : idergo a relativ rai)id, non-infianunatory eft'usion of fluid into the joint cavity w coineidt-nt atrophy of synovial membrane, cartilages and bone, whin in a very short period there is develojjcd a greatly disorganized jo cavity with a flail-like motion of the limb in all directions. Til!^ known as a "Charcot's joint." We arc still unable to ascribe any \morary dilatation of the superfii capillaries, the skin becoming pink or red; this may he the response different kinds of stimuli, such as heat, cold, emotion, e. g., hlushi friction, a chemical irritant or may be the early stage of inflammati Passive hyperemia is seen in conditions of general Aenous coi"'esti as in suffocative attacks or severe fits of coughing, in overfilling of heart, and impeded respiration from any cause. The skin then assui a dusky tint, and the mucous membranes may be bluish or lead colo ^anosis, lividity). In cases of severe long-continued passive hyj eniia, oedema or anasarca may supervene, with the result that the tis l)ecomes smooth, tense, and shiny, the skin and the underlying lo tissue being "waterlogge nated by the term purpura (see p. 35.')), and is due to a more or less ra] degeneration of capillary walls. Finally in circulatory disturban of the skin, it must be remembered that many states apj)earing throi the skin do not actually concern the skin at all, and are connected w underlying tissues. Inflammation. — There are numerous causes, direct and indirect, which the skin can become inflamed; of the former, woimds of all soi friction, chemical irritants, heat and cold, bacterial and other parasit are the most important; the latter comprise noxious agents carried the skin by the blood, as well as those disturbances of nutrition a of nerve connection which, while perhaps not effective of theniselv are yet strongly predisposing forces. While the main feature of inflammation of the skin is the exudatic this appears in a great variety of forms, the macule, the papule, t vesicle, the pustule, the bulla, the node, the wheal, all of which t aptly calle forms of hyperemia of the skin are grouped under the term erythema — often called erythema multiforme because iil" the impossibility of distinguishing these from one another in their mitrphology or etio'ogy. There is nothing distinctive about the red ureas of the skin, which fade under pressure; they may become changed liy hemorrhage, or by the formation of papules, vesicles, or other modi- fications. We have to recognize a large number of agents which can cause erythema, such as the local exhibition of heat, cold, chemicals or iiuciiimical irritants; the invasion of the IxMly by some toxin, as after the ingestion of certain drugs, quinine, turpentine, salicylates, mercury, (ir of certain focxls (this often an idiosyncrasy), shell fish, fish, straw- luTfies, etc.; as a result of certain infections, as seen in the "roseola" of typhoid fever, the bacterial agent being present in the lesion; as an accompaniment of sapremia in many different infections, and after surgical operations. Finally, many cases of erythema occur in which \w cause can be assigned, and, accompanied as these often are by gastro- iiilcstinal disturbance, we suppose that toxins elaborated in the aliment- ar.\- canal oi elsewhere possess the ; jwer of causing this manifestation. I'rythema of a diffuse type or localized and notlular (noflosum) may, of course, occur in specific infections, as in syphilis, rheumatism, and other states. In designating such, we are accustomed to lay more stress upon the disease that we know to be the cause than upon the I -distinctive erjthema — thus in sfwaking of erythema syphiliticum uc iiientally underline the latter rather than the former word. Urticaria.^ — I lere we deal with not only a hyperemia but also with an ilcni^' of the tissues, showing itself as slightly raised, pink or yellowish- rcil areas (wheals) of any size and shape, with a slight surrounding /'inc of hyperemia, which appear quickly and may as quickly disappear. 1 I miliar to most people as the homely "hives," they may be caused li> nettles or a like external irritant, by the injection of the various "I la, and by any of the drugs or foods or toxins mentioned above; they li.ivc some obscure relation to the nervous system, for they arise in si.iii(> persons as a result of a finger-nail drawn across the skin, and Hi iitlicrs without apparent irritation as the condition of angioneurotic |"l< Ilia. As a result of toxins from certain foo;e(l ( pitheliuni by t exudate -the bulla or blister. The eoverinj; of the Imlla may degent ate, or the eontei\ts beeouie infected the coriuin is almost eertai sutler in such a case, but unless severely infeete.\ ciuiicians for convenience in designating many forms of ilUlefined dermatitis. Impetigo. -This is an infective disease oftenest of the face and hands itrc(iuently by transferenc*') in which small i)ustules arise, with subse- (|iitiit crusts. The connnon form is designated Impetigo contagiosa, l.iit from the nature of the contents one would judge that under favor- iil.lc circumstances most of the cases, if not all, would prove communic- .;il)le \Ne recall that, during our college fiHitball team, the eruption appearing in som cases behind the • iir, where the skin frequently was broken by the auricle being pulled lorcibly forward in the pressure of the scrimmage; after a certain match iii.iiiiiers of the opposing team developed a similar condition, similarlv Inratcd, the result of head-and-head contact. I\ . Inflammation of the Skin Characterized by Pocks. Variola. As a result of hematogenous infection, a coagulation necrosis '" nirs m the cells of the rete Malpighii, with a cellular exudation from th.' \isscls of the papilla-; by the action of pyococci the contents of the niniiy-chambered pock l)ecome infected and, finally, a single-chambered pii tiilc results, which forms a crust and ultimatelv mav leave a scar Ol til,. sanH> general order are the pocks of varicella, and" of vaccinia. \ . Psoriasis, Lichen, etc.— Psoriasis is an inflammation of the skin in «l.iih an infiltration of the epidermis and corium occurs; there are I'Mu.tjitc heaps of broad plates of dry epidermis on a background of ^iyirply dehned reddened skin that bleeds easily. The epidermal cells 'j' 'li«' stratum corneum dry and are separated into large plates or '1;'''^ between which air finds its way, giving the characteristic ^il ' r\ apiM'arance to the scales. Lupus erythematosus, in no way connected with true lupus, is an 'j^ 'innation that shows itself as small round, raised spots with a '!■ " ssK.ii in the centre; these l)ecome covered by dry, yellow scales. ' dien IS a ciironic form of inflammation with papules which remain III jiii},'ed save for an increase in size; they may form scales, but not \' Its or pustules, although in lichen scrofulosum there may excep- t ^1 J: 1- s S I* ^ 700 THE MOTOR AND TEGUMENTARY SYSTEMS tioimlly l)e tiny piistult's on the summits of tlie papiilos. The moi of thf hair follicle is th«' part atfi'ct«>«l, a ]M>rifolliciilar inflammat and hyjK'rkt'ratosis resulting. \'I. Erysipelas and Other Inflammations of Known Bacterial Oricin. Erysipelas. — Tl>'s is an infection of the skin, sometimes by way of unrecojtnized iesicm, sometimes by increase of virulence of the ccktI hair follicles, which may be accompanied by great or by slif(ht systei disturbance; often the latter is out of proportion to the amount of s involvement. Formerly considered dangerou.sly infectious, the dise is now place«l on a par, in this regard, with other forms of sepsis, v danger exists chiefly in the presence of wounds or great bodily wcakni The lym[)h spaces of the connective tissue lodge the bacteria, usut streptococci, and there is marked hyperemia, cellular and serous e date, which pr()gresses with the existence externally of a welUiefii line of denuircation. The skin is swollen, shiny, and red. Vesi( and pustules may form and even severe necroses may follow. Abscess or Phlegmon. — Abscess or phlegmon does not differ grea from the above in its hkhIc »)f origin; fluid exudation and the distens of the tissues are more evident. The result of infection of the s may be aecomes sufficient to break through the s or before surgical intervention is securc«l. Acne.— This is a small inflammatory mass originally formed in vicinity of a hair follicle or a sebaceous gland, breaking down to fi a small quantity of pus. Acne rosacea has a different origin; hen found, in the simplest forms, a prominence of capillaries over the surf of the cheek or nose, while in severe forms there is a marked incre in the connective tissue and the glands, which latter become closed, f a great deformity — a kind of elephantiasis of the nose — results. Furuncle, Carbuncle, etc. — The furuncle is, pathologically speak! an acne pustule upon a larger scale; and a carbuncle upon a yet greu scale. In the last, by reason of the virulence of the organism, usui in all these cases the staphylococcus, there is apt to be a widespn necrosis of tissue and a marked systemic disturbance. When infection is not staphylococcic or streptococcic but due to the bacil of anthrax, the lesion is designated malignant pustule. In necrosis ii gangrene the skin is but one of the tissues involved; these have 1m (h-alt with elsewhere (p. 328). XTlcers. — Ulcers of the skin arise in many different ways, and n follow many causes; the essential condition is a loss of tissue broiij about in other than a sudden way. Normally the process of nj) comes at once into action, and according to the completeness of t reaction and its s})eed, coupled with the quality and amount of cx!'-'n the ulcer takes certain characters, indicated by names such as heali spreading, indolent, or phagedenic. The tendency of new growflis THE SKl\'-^LUPUS—SYI'niUS 701 the skin to uK-oration is very great, by reason of their F)o,)rlv-s ihe manifestations of syphilis in the form of efflorescences on tlif skin are very various; the simplest is the erythema syphiUtica or "'a' iihir syphihde, which is seen as red. ill-defined areas of varying ^1/' tending to apjiear on the trunk and t' >.xor surfaces They I'l.iv remain for a considerable time ami fack. leaving a temporarv '"'wnish pigmentation. The papular syphilide may show itself in the ""■l>t nf an area of the erythema as well-defined brownish-red papules "" Mif skin dry and on moist areas such as mucous surfaces, exuberant' j" ; t, and tending to ulceration. The mucous plaques of the mucos^ " ng to tins order, but the rapidity with wl ich they break .lown i< I- to thcr appearing as flattish ulcers covered by grey debris The I' nl.s muy hecome infected and give oritrin to pustules, which again " me scabbed. A combination of considerable proliferation with 'at i.)n and scabbing gives rise to the peculiar structure of concentric ' ^ called rapia. Actual gummas may occur in the skin, but more h 'I i! I I ro2 THK MOTOH rV/> TE(.i ^tESTAHY SYSTEMS i.i u. - often Im-Ioiik originally to the mikIitI; iiig tissue uiid involve the later. The true >;umnias of the sk ' show as Hat hani areas, liki hase of a ehancre, t»'ii«iiti>; t.. iileenui iii'l form ' |)iiiichee|)r<)sy)." This is seen in the skin as nodules of prolifer tissue <()ntaii)iiig the causative 1..' 'Mi, o<- .s yellowish-n"*! or bi sj)ots on the skin or mucosie, with i . rdaiuMatory iofiltration. A scarifiratioii yields a Huiil in wliic'' tin tuir cteristie bacilli are rei found. (Wyatt .lohnstoii.) Other Granulomas, Blastomyco''-, D«r-.ia'omycos«s, Etc. Glai oecurs in the skin as an acute inflai unati' u dii" to infeetion of u *■« or other solution of continuity and actinonyosis usui.'My us a se<;on prcK-ess, apjM'ariii}; as a clironic u'l ■ i itiun t.-. o* er^;rted gn is found. Heginiiiiig as a j)apule, the mass is distiii ly of inrianiiiui tyiM', and in the later, larger Itsions minute abM-esses oetnir in substance; in these abscesses, as elsewhere, the ycast-like organism be found. Favus is due to Arlicrion Srhd"li iiiii, which >uf skin. Ring worm nia caused by more than one mould, most comnHuily by the Trichnph and is known as tinea. It may affect the scalp (T. tonsurans), the i less skin (T. circinata), the l>card ^T. sycosis, often .icutc by rcaso eoc'.'ie infection), and the covered parts of the skin i"^. versicolor), latter is often -all' " pityriasis, and is relativelv nnirnpo mf. \'III. Inflamm&i..oas of the Skin Caused by Animal Parasites. The lc->ions caused by animal parasites arc often of themsihcs (| inconsideralilc but are nearly always coini)Iicatcd by the fact i the itching Mt up lea nmiM\ aiul tin- chigoi) arc also examples of piir.i ite> tliat hiirmw in ,< skic. BHnssiTe Chanfes Atroi^y .troj>' f t^ skin o<(urs in the old, a general pron^ of fii .nnig, t! Uf. |jt«<-^>niinj; narrower, tlji- epidermis dry, and the siilxii ,iw)Ur ai >ii L'reiitl; ■d)sorh f ai.ophy is noti. able in t'iif skin as the so-iailed Uaege albacantM, ^ iieli ure wliitish ilv«'ry liiii- tfi. result of ■' I'rev ions distt iis )t thi kin. Tht-v arc ren in»t niiinionly in tu. breu ' , tlie lome; ;ii lie ' and frc- umiith follow prc^' aiiey, t iough ' tehini; 'f tV irom any otiier eaii-*e v ill suffice t t! ir priHlucrHi. Necrosia,— \» Tosis ol tlu -kin oei ! i ae< i'l>i r tlssu«>s II. htnlsop . ai uUrrs if of . iiii;riiie and cirt u^ ttorx liistii; .luces su( ii - , Pigmentation. — ^ ariation- in 'le pigmeiitii.if wiii>i(lered in this i lass. '*^( <\m\>\ iiiTriial pigment of t •• n - -, i! «-oriui ;iiiil l)ile pigments, ii V.\) i\w^- M>»it of 'I'll ciiiigenital lack .igmi ,. 1 tat* I'cwlicrf. Vitiligo r Le>;^i(oderma i:- 1 1< ali:- < 1 1 liie normal p.. icnt, see mthi ai •' lecrosis of wi- -veil a in «»' ase. .»re Se ease i le ;H.arance of 1. ^| ngested pigments i.g reference lias l>een made iip|.(arin various J mrt-^i. ■el:>od> ii'.rnial pu'iuent k - en . rc-^ult 'il <'liilii!i(MMl, a- ilsi in pigment -da " i. '■^' X&ntiielasr . is an •'-' t' aU 'lit lid. trance or congenital alxnce )fti iier tliari the white races, by ieh the hair also is unpiiriuented, use is unknown. Increase of the etioii of suidight in the freckles m%^ uaN rts, in chloasma, obscurely in A .son's disease, in "bronse- linn < physical counterirritants, V. Most, if not all, of these have 'he general subject of pigmentaticm -iniderstood yellowish pigmentation ProfT .-.K;?e Cba,! ses. Ve have already touched upon certain con- ! ns . ;.!.riz«, 'v niarkwl n i)erplasia of the epidet i n . ; a local ixrplasia in;i ai i Ih' a< Irtil ;is the result of chronic irritation ■f he fami'iai •:al1 - ,)n the palm or sole, and the ihe result ol it slight irritati(»n there develops a 1 iiii reaseil d. unent of layers of keratinized epi- •h may be local, as in the abovc-mentione Ivmphaiigitis; while lastly, syphilitic and other chronic inflammati (if the skin bv causing a chronic n>dema, favor the setting-up of r orders of this condition. In all these states, it appears that we ( with a relative or actual lymph stasis, leading in the first plac« enlargement of the part, and secondarily to a diffuse connective ti: hyperplasia. Due to the distension, of nuxlerate grade, of underlving tissues, the epidermis tends to hypertrophy, forming i1 into f(ilds and sometimes more warty and ncKlular overgrowths. coiKlition most fretpiently presents itself in one or both of the ki extremities or in the scrotum, the latter being apt to attain a colo size, extending below the knees. A milder tvi)c of thickening of the skin with primary involveii (.f the dermis mav artect considerable areas of the limbs or trunk is H-en in the group of conditions known as scleroedema, sclerodei and sclerema. Of the - the first manifests itself in long-contin anasarca; it is allied to the condition seen in myxcedema, there hen brawnv hardness of the affected part, witli. however, little chang the overlving epidermis. In scleroderma a similar induration I continued", is followed by distinct hypertrophy iiuolving not only dermis but also the epikiii ,.t' the legs, evidently metaplastic. The skin is, however, a favorite -ini lor the development of lipomas, more espe.'ially in the ^liouider ri-ii)ii. These solitary lipomas have a lobulated structure and may attain considerable size. Several cases of multiple small myomas are 'III ncord, and '-ome of solitary myomas, of small size, originating evi- 'li iitly from the arrectores pilorum, and from the muscles of the sweat ulaiicls, I inlcr the heading of navi ('or birthmarks) anil moles are to be grouped a miinlxT of ditlVrent conditions. The hairy mole is a patch of normal ^kiii f;i\ing origin to large, coarse hairs in a region normally hairless, I n<|ii,.ntly associated with this there is marked pigmentation and ^ '■ hypcrtropliy of tive skin. A section through such a mole shows In .|neiitl,\- a more vascular condition than normal, with, in addition, i' I'i'iiii'iiiiced collection of chromatophores or pigment cells around the • 1^. The nevus is of larger size and comprises a variety of condi- t'n.ni the soft, warty masses, showing abundant cells, to states of ' "^ nnd widespread cavernous dilatation of the superficial 'Is whicli may involve the whole of one side of the face, or, as we ■ Mcii, tiic whole head, or, again, a large portion of the trunk. The i< I, eellular forms, like certain moles, show masses of somewhat ■ il i>r piilygonal cells surrounding somewhat enlarged vessels. '"• larger, the dilatwl vessels preilominate and cause a striking li "r reddish cajoratioii of the affected area ("strawberry mark"). ' 'Militiiin is most often what has been termed cavemoma, or cavern- 'ii^onia, but occasionally we meet with not merely this dilated \ I' tiu I'hi \i ll.l -|i| ml 111 ;r-" i !:S ' roG THE MOTOR AXD TKOUMESTARY SYSTEMS oondition liut a true blastomatons prolifcratiiif; angioma with jjroprvs: pniwth into tho surnniiidiiijr tissue. So, also, at tiiin-s wt- t'iu'(»\ij conditions of lymphangiectasis wliicii may wirp, and true cutanc lymphangiomas, or lymphangio-endotheliomas. Any of the aho\e i neetive-tissue tiniiors may ^ive rise to sarcoma or to sarcomat developments. \t the same time i)rimar,\- s^^eoma does occur, roui spindle-, or mixed-ceiled together with a remarkable form of difl sarcomatosis of the skin wliich may involve larne areas (mycosis (oides). The chara;iiizal)le: tlie one, the squamous epithelioma proper, sueli as is s.rn on the hp, serotum, or penis, is eharaeterized bv lar^e, mope of cell seen in this form with its ( .piirture from the typical prickle-celled type, led Krompecher to include this Miiiong the basal-celle''iih;,r tendency to spread along the cutaneous lvmi)hatics, giving FM' t,, til,, so-called cancer en cuirasse. Cysts. Retention cysts may show themselves in connection with the Miiar, .„w glands, (.tten secondary to a condition of seborrhoea or hvper- •■'■'•n tH,M. resuhuig in the pr .i.-ti„n of wen* .... the scalp or sebaceous cy s cMwhere. Uetentio- . -. may als,> attect the sud„rii,arous i : , "'"'" '." '"^^■!"K '>.yi " -tion, res„lti..g i.. miliaria, mi..ute, .i.,,r -..we vesicles immediau . under.ieath the upoer lavers of the cnln * !',V',"r""'"*''*" '''' '"">■ ""'"tion the allied condition of comedones ( b ackheads '), a c...,dition .lue to the bloekh.g of the ducts ' - oils gja.ids by plugs of sebum and .lesquamated cells. Thev ■" I- • .u.nnio.iiy seen upo.. the no.se a..d chin. Yet a.iother form ' 'leserves .nc.t.o.i, the implantation cyst, bro.ight about bv " - natic torcing of cells from the ' affect the i.i and the mycelial threads may actually penetrate and grow witHui nail substance. INDEX Abdominal epigastric hernia, 569 fissure, 72 Aberrant mammary gland, 666 proiitate, 633 Abiotrophy, 57, 299 of nerves, 478 AI>ii<>rniaHtie8, 61 of defect, 70 ill excess, 61, 62 inheritance of, 57 Abortion, tubal, 666 Abrin, immunity against, 154, 155 Ab,si;(>3H, 126 antemammary, 667 of brain, 488 cold, 684 of liver, 575 of orbit, 517 IK'rinephric, 617 peritonsillar, 437 pylephlebetic, 574 repair of, 126 rptropharyngeal, 438 retro-uterine, 661 of skin, 700 'stitch-hole," 89 of thymus, 472 I ubo-ovarian, 655 Abxihite immunity, 152 AiM|iiiia, 179 Aririliae monstrosities, 63 Aicioiie bodies, 109 A03 Albuminuric neuroretinitis, 513 Albumoses in urine, 25, 603 Albumosuria, autolysis and, 1(X) Alcoholic neuritis, .507, 508 Alcohols in cell, 33 AlepjK) button, 05 Alexm, 164 ; Alimentary leukocytosis, 364 i Alkaptonuria, lOH Allergy. 'S' Anaphylaxis. Alloxuric bfxlies, 107 Alopecia, areata, 708 Altmann's granules, 301, 365 ' Aluminosis, 325 I Amastia, t)66 j Amazia, titiO Ambocei>tor, 164 Amino-acids, 25 Amitosis, 3H Amitotic cell division, 38 Atnnion, 665 Amniotic fluid, 6t>5 Amccbic abscess of liver, 575 colitis, 558 I Amphimixis, 46 ' Amphoterisni of amino-acid, 25 Amputation neuroma, 108, 245, 500 Amygdalitis, 437 Amyloid, 34 I bodies of prostate, 321, 633 degeneration, 3tKi, 307 of adrenals, 422 I of lymph nwles, 413 I of mvocardium, 390 i of heart, "390 i inHltration of arteries, 401 ' of kidney, 620 of liver, 585 of pancreas, 597 reactions, 308 Aniyloidosis, 308 Amyotrophic lateral sclerosis, 499 Anadidvmus, 67 Anaerobt!s, 84 Aiiakatadidymus, 67 Anaphase of mitosis, 40 .Anaphylaxis, 117, 170 .\naplasia, 203 in tumors, 285 Anasarca, 336, 339, 366, 368, CM Anemia, 339 Addisonian, 300 of adrenals, 422 a|)lastic, 361, 419 of bone marrow, 419 of brain, 486 collateral, 339 of intestines, 546 of kidney, 608 of lurvnx. 441 ol liver, 570 of mouth, 523 ISDEX 711 Anoinia of musclos, O73 neurotonic, 3;jit of pericardium, ;{82 of peritoneum, 5t»2 |)erni('iouM, 3Wt of piu-arachnoid, .'i()4 of placenta, liM of retina, 510 secondary, 300 of tikin, 695 of spinal cord, 4!)5 splenic, 241, 415 of Ntomach, 533 Anemic infarct, 344 Aiiencephaly, 7'2, 4S5, 493 Aiic-itliesia, 479 Aneurysm, 27S, 298, 407 arteriovenous, 40S in hrain, 4S8 cirsoid, 278, 407 dilatation, 407 dissectinit, 407 false, 408 futiiform, 298, 407 miliary, 408 mycotic, 408 saccular, 298, 407 I Taction, 408 varicose, 408 Aiiciirysinal varix, 408 An(;icctas(>s, 278 Ahdiiia, 437 linlovici, 528 pectoris, 378 \iiicent's, 439 Aiiuiiima, 277 ndicitis, 548, 555 catarrhal, simple, 557 diffuse, 557 (jangrenous, 5,58 iwrforafive, 557 Appendix epiploica, 566 vermiforinis, function of, .541 Appo.siti metastasis and, 219 Aquela, carcinoma of, 672 i Areolitis, 667 Arjtyria, 325 Arrhincephaly, 522 Arrhythmia, 379 .Vrscnic c.-iters, 1.53 neuritis, 508 Arterial thrombus, 349 Arteries, 399 abnormalities of, 400 anastomosin);, 340 arterio-sclerosis of, 401 atrophy of. 4!K» degeneration of. 401 hypertrophy of, 409 hypopla.sia of, 400 infiltration of, 401 inflammation of, 400 occlusion of, 340 syphilis of, 400 terminal, 340 thrombo-sis of. 100 tumors of, 409 Arteritis, 4 r t If : ?,-* 712 INDEX Arteriosclerosis, 298, 402 nodose, 402 syphilitic, 403 Arteriovenous anfuirysm, 408 Arthritis, 091 deformans, 692 pauperuin, 093 purulent, 092 serofibrofibrinous, 091 serous, 091 suppurative, 091 Asearis luinbricoides in liver, 590 Ascites, 339, 360 chyliform, 370 chylous, 370 pseudochylous, 370 Aspergillus of lungs, 405 Aspermia, 637 Asphyxia, 109, 430 Aspiration pneumonia, 455 Aster, 40 Asthenic fever, 150 Asthma, 429 Atavism, 48, 50 Ataxia, Friedreich's, 498, 501 locomotor, 500 Atelectasis, 431, 449 impression, 450 Atheromatous embolus, 352 ulcer, 402 Atherosclerosis. See Arteriosclerosis. Atherosis. See Arteriosclerosis. Atmospheric pressure as cause of disease, 77 Atonic constipation, 542 Atresia ani, 74, 645 of gall duct, 591 of intestines, 544 of larynx, 440, 444 recti, 545 of vagina, 642 Atrophic gastritis, 536 pharyngitis, 439 rhinitis, 435 Atrophy, 297 of adrenals, 422 of arteries, 400 of bladder, 620 of bono, 685 of brwn, 4'M) brown, of heart, 388 of Uver, 580 of drum membrane of ear, 520 of joints, 694 of kidney, 619 of larynx, 443 of Uver, 574, 583 of lymph nodes, 413 of mammarj- gland, 067 from malnutrition, 297 of muscles, 075 of myocardium, 388 of nerves, 478 of ovary, 666 Atrophy from overwork, 297 of pericardium, 384 progressive muscular, 499, 675 of prostate, C>4 reversionary, J03 senile, 297 serous, 306 of fat, 298 of pericardium, 384 of skin, 703 of spleen, 418 of testes, 039 of thymus, 472 of thyroid gland, 424 of uterus, 649 of vulva, 641 Auditory meatus, external. iSee Kai external. Aural polyps in otitis media, 620 Auricle of ear. See Ear. of heart, 371 Auriculoventricular node, 377 I valves of heart, 373 Autochthonous blastomas, 223 i Auto-intoxication, 79 Autolysin, 103 ! Autolysis^ 105 I Autononuc nervous system, 475 ■ Autonomous tumors, 207 Autoplastic transplantation, 199 AuxeticB, 201 Axone. 473 aliiotrophy of, 478 degeneration of, 478 disuse atrophy of, 478 i pathological changes in, 477 regeneration of, 478 Bacillary colitis, epidemic, 558, 559 I Bacilli, 84 i Bacillus coli, constipation and, HI diphtherite, 86, 438 fuaiformis, 439 typhosus, 90, 121 "Hacoi ■ spleen, 308, 418 Bacteria, action of gastrin jaice on, of leukocytes on, 87 of surface washing on, 80 aSrobic, 84 in bladder, 626 as cause of disease, 84 damage of cells by, grades of, 121) development of ptomaines and, 1 H ectotoxic, 85 endotoxic, 85 entrance of, into body, 90 physical hindrance to, in resp ratory tract, 87 through genital passage.", '.'0 intestinal tract, 90 lymph nodes, 87, 91 ,86 INDEX 713 Bacteria, entrance of, through placenta, ao respiratorj- tract, 90 skin, 90 to tissues, 86 enzymes of, 84 exaltation of virulence of, 170 intestinal, 85 passage of, through body, 91 pathogenic, 85 phagocytosis and, 124 putrefactive, 85 saprophytic, 85 temperature limits of, 84 toxins of, 84, 85 transmission of, by air, 90 by direct contact, 90 by f:/mitC8, 90 by insects, 90 virulence of, 91 iiucterial embolus, 353 intoxication, 85 liuotericr.iiii, 145, 629 Hacterifii'lal power of blood, 88 of mucus, 86 H;ii;tcriolysins, 165, 166 li;ictrriolysi8, 165, 166 Hulnnitis, 630 halaiitidium coli, 97 HaLinoposthitis, 630 i^all thrombus, 348 li.iiiti's disease, 241, 579 Harlow's disease, 688 Basiil-celled carcinoma, 264, 270 li^ksiilow's disease. See Exophthalmic Koitre. Ikilsore, 76 HcmoJones' albumin, 603 H-o\ybutyric acid, 109 Ifircirnuate uterus, 644 Hile i-ysts of Uver, 590 ducts, 591 tuberculosis of, 682 «ravcl, 319 ill peritoneum, 566 Hilhurzia hematobium, 260, 620 liilliarziasis, 260 H'liary culcuH, 318 • irrliosis, 579 liiliniiiin, 318 Hilivi nlin, 318 liinnccrosis, 326 ■- 'plKTC, 24 ilioric molecule of cell, 24, 27 ■I htsja, 35 i litiiarks, 278 I' 'ii palsies, 61 l'ir!li>. multiple, 64 Hlill.-r, 024 iliiiormal contents in, 626 ■ Ispnceof, 624 vicnoma of, 627 ' iUKjiiia of, 627 iiiimaliesof, 624 Bladder, atrophy of, 626 bacteria in, 626 bilharzia hematobium in, 626 carcinoma of, 627 ectopia of, 625 extrophy of, 624 fibroma of, 627 hyperemia of, 625 hypertrophy of, 626 inflammation of, 625 myoma of, 627 papilloma of, 261, 627 parasites in, t)26 sarcoma of, 627 septa of, 624 syphilis of, 626 tuberculosis of, 626 tumors of, 6''7 Blastomas, 213 atypical, 237 autochthonous, 223 heterochthonous, 223 multicentric, 219 pleuricentric, 219 teratogenous, 211, 223 typical, 237 unicentric, 219 Blastomatoid, 228 Blastomatous papillomas, 260 Blastomycetes. See Yeasts. Blastomycosis of skin, 702 Blended character, 48 inheritance, 48 "Blighted ovum," 68 Blood, 334 bactericidal power of, 88 cells in inflammation, 128 coagulation of, 346, 347 corpuscleo, poisons acting on, 81 red. IkxlioH, NiiUil, 1!) tixroid, 1!) Bodily litate!) tw riiiises of diseaso. 1 1 1 Body cell, 44 incchuni»iii, disturbances of, auloly- aia tind, lIMi surfaci', iniiM'rfi'ct dosiirp of, 72 Bonia, t)7S ubnormalities of, 678 actinomycosis of, ('>85 angioma of, (>!S!) at rophy of, 685 caries of, 081, 084 cephalhematoma t ', 07!> chondrasarcoma of, (»M'i)ernephroma of, 492 inflammation of, 488 leprosy of, 490 malformations of, 485 myxoma of, 491 osteoma of, 491 porencephaly of, 492 sarcoma of, 492 soft(!ning of, 487 syphilis of, 489 svphiloma of, 489 thrombosis in, 487, 488 tuberculosis of, 489 tumors of, 491 Branchial clefts, imperfect closure of, 7 cysts, 289 Breast. See Mammary gland. Paget's disease of, 672 "pigeon," 687 Bridges, cell, 19, 20 Bright 's disease. See Nephritis. Bordet-Gengou phenomenon, 168 reaction, 167 Bronchi, 429, 444 adenoma of, 446 carcinoma of, 446 chondroma of, 446 foreign botlics in, 445 hemorrhages into, 444 inflammation of, 444 lipoma of, 446 lumen of, alteration in, 446 myxoma of, 446 occlusion of, 446 ost( oma ot, 446 pa.s.sive congestion of, 444 INDEX 715 Bronchi, porforaliMn of, 446 luirconin of, 44(1 tumors of, 44H HronohiertiiMiM, 433, 44(i cylindrical, 44() fusiiform, 44A snopulnr, 440 vuricow', 44»l Hninchitiii, 444 acute, 444 catarrhal, 444 chronic, 445 fibrinouH, 445 ganiirf noUH, 445 purulent, 444 putrid, 445 UroncholithH, 446 lironchopneumonia, 452 tuberculouM, 401 Uronzed diabetes, 579, 703 Hrown atrophy of liver, 5S.'{, 5S0 induration of lunRH, 44S, 458 Uubo, 412, 631, 032 liulhur paralysis, 499 KulloiLs emphysema, 456 "Bundle of His," 377 KiirninK of skin, 097 Itursip, 077 endothelioma of, t)7S fibroma of, 07S hydroma of, 678 inflammation of, 678 myxoma of, 678 sarcoma of, 678 tuberculosis of, t)78 tumors of, 678 Hursal cysts, 292 Miirsitis, 078 CwHKXIA, 216 t h yreopriva, 100 < 'iiissoti disease, 77, 353 < 'Mlcarcous deposits, 313 in stomach, 536 in tendon sheaths, 677 of thyroid Kland, 424 embolus, 3.52 incrustations, 315 (':ilciKration, 313 of auricle of ear, 520 of endocardium, 399 in infarction, 346 of liver, 586 of lymph nodes, 413 in myocardium, 391 of placenta, 664 of veins, 410 ( ilcium carbonate calculi, 310 "Vrtlate calculi, 31S (' Iculi, 315. See also Concrements. biliary, 318 • Calculi, calcium bi .rubin, 319 cholestcrin, 319 cysti", 318 Kuanin, 318 mulberry, 318 oxalate, 318 phosphatic, 318 prostatic, 321, 033 m ureters, 023 uric acid, 316 urinary, 310 xanthin, 318 Calculous pyonephrosis, 018 I Callus, formation of, 193, 703 I Calor, 125 ' Calories, 148 Cancer. 6'f< also Carcinoma. "bodies, 266 cells, irrcKular mitosis in, 222 "en cuirasse" of mammary sland, 070 of skin, 707 "parasites," 19 Canities, 708 Cajjillaries, 409 denencration of, 410 hemanKJo-endotheliomas of, 410 hemangiomas of, 410 hemorrhages of, 410 hyperemia, 338 inhltration of, 410 thrombus, 350 tumors of, 410 Capsular i;ataract, 515 Carlxjhydrates, 33 Carbon dioxid, asphyxia .and, 109 dy.spnu-a and, 109 Carbonic acid, muscular fatigue and, 114 Carbuncle of skin, 7U0 Carcinoma, 264 of adrenals, 423 basal-celled, 228 , 264, 270 of bladder, 627 of brain, 492 of bronchi, 446 "cancer bodies" md, 266 of conjunctiva, ."il") degeneration in. 'i>6, 272 of dura mater, 5< » J of ear, 521 of Fallopian tubes, 654 of gall-bladder, 592, .'593 -duct, 592, 593 gland-celled, 272 of intestines, 560 keratinization in, 270 of kidney, 621 of larynx, 443 of liver, 589 of lungs, 465 of mammary gland, 670 nietluliary, 200, 273, 670 of nose, 430 of cESophagus, 531 i ir 710 rSDEX Carcinoma of orbit, 517 of ovary, •»")!( of iianrrciw, 697 of p<"iis, ((33 of prohtatr, (536 RiWKcrB bodieii and, 267 stnr(:oinat40 «iiiiplex, 227, 266, 273, 672 site of, tiriKin of, 2tiT of skin, 7D6 of splifn. 4I!1 gquanidii -< I IIchI, 260, (572 of stomal h, M{i stroma of, 2t>"> of testes, 639 tumor ((ils of, 26.'> of urcti-rs, 624 of un'ltira, 620 of uterus, 651,663 of VHKina, 643 of vulva, ()42 Cardiac thrombus, 348 vegetation, 34!t, 351 Canliovascular syetem. 333 Caries of bone, 681, (iH4 of joints, 6!)3 of teeth, 526 Carnified lunKs, 450 Carotid fcland, tumors of, 285 Carrel's exp<-rinieii(s, 202 Cartilage, regeneration of, 102 Caruncles of urethra, 629 Ciists, cellular, 312 colloid, 312 epithelial, 312 granular, 312 hyaline, 312 waxy, 312 Catalysis, 28 Catai-act, 515 Catarrh, 435 Catarrhal, appendicitis, simple, 557 bronchits, 444 cholecystitis, 591 folitis, 558 cystitis, 625 enteritis, 548 inflammation, 133 jaundice, 323, 591 laryngitis, 441 Cavenitis, 630 Cavemoma, 278, 705 of pia-arachnoid, 506 of skin, 705 Cavernous lymphangiectasis, 281 Ceeitls. 548 Cell, aonormal states ol, 18 activities of, bioplastic. 35 (X)mp«^n8atory, 37 excessive, 38 functional, 38 katabiotic, 35 Cell, activities of. relation of growth 35 •ubnurm.'t!. 37 vegetative, 38 alcnliols of, 33 biophorii molecule of, 24 blo9, 20 carbohydrates in ;i3 centroHonie of, 19 chemistry of. 24 chromatin of, 18 connectiv^ns, 19 (■onnective-tissue, 126, 128 constituents of, 18 crystals of, 1!) cytoplasm of, 19 damage of, by bacteria, 126 differentiation, 41 division, unitotio, 38 aster in, 40 attraction sphere in, 40 diruct. 38 karyokinetic, 38 mantle fibers in, 40 mitotic, 38 -ndoth. iai, 127, 128, 138 epithelioid, i;j8 faU of, 33 germ, 44 giant, 139 histology of, 17 hyaline, 3(i3 hyperactivity of, within limit oi reserx-e force, 38 lining of, 18 lipoids of, 24 "mast," 133, 363 molecule, filirlich's conception of, 158 mononuclear hyaline, 132 multiplication. 38 non-protein constituents of, 31 nucleolus of, 18 olein in, 33 pabnitin in, 33 paraplasm of, 19 physiology of, 21 plasma, 132, 363 polymorphonuclear, 128 iwlyniiclear, 128 ''prexymogens" of, 23 proliferants, 201 proliferation, inflammation and, \\'.> proteins of, '>A regeneration of, 21 Kalto in, 32 '/^\ IN HEX 717 Cell, Nap, 10 Higiiificutiie of, 20 xiie of, 2U Moaps of, 33 Nomstic, 44 stearin in, 3.'i totipotent, 208 totipotential, 45 vacuoles of, is viiryioK X»twcn of re«i.-.tance of. 123 voKt'tative, 44, 216, 217 wanderinK, inflainniation and, 119 water in. 31 ( Vllular casts, 313 (''■llnlitis. 412 of orbit, 517 of skin, 4(X) (Vntral pneumonia, 455 (Vnlrilobulur pancreatitis, 595 ( cntmsomc, 19, .19 (Viihalheniatoma, 294, 502, 679 ( -ephalothc-racopaKUs disvninietros, 68 nicnosymmetros, 69 ("i robral ajwplexy, 354 hemorrhage, 498 throuibosw, 498 (Vrobrosides, 27 Orvical endometritis, 647 hydrocele, 281 (Vrvicitis, 647 ("hali«»si«, 325, 459 Chancre, 524, 630, 701 hard, 630 of mouth, 524 of Hkin, 701 soft, *>3l < liiincrojii. 631 < 'jiarcot-Uyden crysUls, 445 ( hun-ot'n joint," 694 Cliiiliris, 523 niiiloRnathopalatosrhisis, 5_'2 wieiloKnathoprosioix.-'chisiB, 522 < lieiloffnathoschif-is. ,22 (lieiloschisis, 522 Clieioid, 231 < liumical causes of disease, 75, 78 of inflammation, 122 J Kiniotaxia, inflammation and. 119 < liemosis, ;i66 ' Xi'.vne-Stokes' respiration, 431 * hickenfntclot, 346 ' liiKoe in skin, 703 < lulls, fever and, 149 ' liloasma, 703 < l.loroform poisoning, necrosis of iiver' III, oao < liioroma, 238 ' Morosis, "(SI • ;i"ku„ ;> , 22 system, disea-ses r. i.'» ;< m.' I Chromatin, 18 Chroniatophoroma, 28.'! ■. I Chromiilia, 22 j Chromophilic bojlies, 47.i Chromosomes, 39, 45 Chyliforiuascites, 370 j Chylous ascites, 370 hydrothorax, 370, 467 Chyluria, 370 CicatrJMtion in gangrene, 330 in infarction, 345 Ciliary body, inflammation of, .5:U Ciliatc infusoria. 97 Circulation, collateral, development of, coronary, 376 organs of, fxiisons acting on, 82 Cirrhosis, 141 of liveij 575 bihary, 579 Hanoi's, 579, ."JSO hypertrophic, 579 La?nnec's, 575 uHinolobuiar. r>80 iiiultilobiil(,r ")76 obslructivi .)79 ponal, 575 r 718 INDEX m il' i Cirrhosis of liver, svphilitir, .Wl Cirsoid iincurysni, 27S, 407 CliMlothrix of luiips, 405 Clasniatocvtps, 133 Cleft pahilV, 74, 437, 522 C'ilons, 040 absence of, 040 hyperplasia of, MO Cloaea, persistent, 74 Clonus, 4S2 Clot, 1)I(«m1-, 340 chickenfat, 340 Cloudy degeneration, 123 swellinfj, 123, 3(»1 of kidney, 01!) of liver, 5.S4 of muscles, 075 of myocardiuni, 3XH CoaRulation necrosis, 32S, 344 Coajtuline, 347 Coarctation of aorta, 387 Cocci, 84 CJoecidia of sporozoa, 07 Coccidiosis, 250, 5!K) Cold abscess of bone, 084 Colic, urete-al, o23 Colitis, 558 amo'bic, 558 baeillary, epidemic, 558, 550 catarrhal, 558 follicular, 558 membranous, 558 mucous, 558 ulcerative, 558 tuberculous, 500 Collapse, 178 of air sacs, 431 Collateral anemia, 330 circulation, development of, 343 hyperemia, 337 Colli(i'uative necrosis, 328 Colloid carcinoma of stomach, 540 ciist,312 defeneration, 3(K>, 307 in carcinoma, 272 deiiosit, 30<», 307 i)ropert ies of, 32 Coloboma, 509 Color blindness, 47 Colostrum, GtiO Coma, 4H0 Combined proteins, 25 sclerosis, subacute, 501 Conie09 of liver, 572 of luns;K, 448 of spleen, 4U> Culicjil all)uminuria, 603 (•■-. litis, 512 < Ml(pps, 70, 71 < '\liiiilrical bronchiectasis, 446 (■\lin.lr.)tna, 283, 311, 528 111' siihvary Khirids, .528 C\liriclr()inatous tivahnc degeneration, :;ii < v li:iuc-||(', .VJS <\ 1 fi)rination in infarction, 345 < \-i.iil(!ioma. •>'•}., 291 of I. vary, t).',(), 6.")9 "f pancreas, .597 |i ipiUifcruin of mammary gland, 670 I'f pcritoneiim, .567 < • ■ II- carcinor-in of ovary, 6.59 liV(jroma, 281 kidney, congenital, 291 '.MiipiiaiigiectaMls, 281 mastitis, chronic, 670 iinitoma of ovary, (MM) C' iiiTcus of brain, 99, 492 "i nuisclcs, ()75 'I pcricardiun;, 385 "I ureters, 624 *■ i'l, lOS iliuli, 318 *^ iiuria, 108 Cystitis, 625 catarrhal, 625 phlegmonous, 625 ; Cystocel", 642 Cystoma of ovary, 6.56, 658 Cysts, 287 of adrenals, 423 of antenatal origin, 289 of bones, 690 of brain, 487, 492 branchial, 289 of breast, 670 bursal, 292 of canal of Nuck, 291 composite, 293 congenital, 289 of Cow[)er'8 glands, 636 us epithelial, 292 of t tenia echinc-occus, 295 of teeth, .528 of testes, 639 of thyroid gland, 291, 424 thyrolingual, 289 of Trichina .spiralis, 295 of umbilical cord, t)65 urachal, 289, 625 of ureters, t)24 of uterine ligaments, 6«M, 662 of uterus, 6.52 i vitello-intestinal, 289 ij f^ 720 INDEX Cysts of vulva, 642 of \\ olffian body, 289 Cvtolysins, 163 Cytolysia, -iOO ninchanism of, 164 Cytoplasm, 18, 19 Cytotoxins, 163 DAruYOPa, 290 Deaf-mutism, o20 Death, ;{3() somatic, 331 Decifluoma malignum of puerperal uterus, 663 Defect of special repons, 70 Defences, normal, of organism, 86 Defervescence in infection, 144 Degenerates, .W Degenerations. 300 of adrenals, 422 albuminous. See Cloudy swelling. amyloid, 306, 307, 308 of iirteries, 401 of axone, 478 of capillaries, 460 in rari'inoma, 272 chondrcid, 309 cloudy 123 colloid. 272, .3I)«, 307 cvstic. "f ovarv, t),")6 fiastoid, 309 familial, 50 "fatty," 123,303 granular, 123 liematohvaloid, 31 1 hyaline, 123, 306, 309 liydropio, 306 of kidney, (520 lipoid, 30.T of liver, 584 of lymph nodes, 413 rimcoid, .30«), 307 of muscle, 676 of niyocariliuni. 389. 390 in neoplasms, 222 ,)f pancreas, 597 of placenta, 664 of irostate. 634 of retina. 514 of spinal ci.i-d, 496, 497 'if splwin, !iS of thyroid gl.'ind, 424 of tumors, acute red. 650 III umbdi'.-al cord, 365 vaciioliir, 306 Wallcrian, 198 waxy, 328, 676 Zenker's, 328, 676 Delhi boil, "."o Delirium, 480 cordis, 380 Delirium tremens, 480 Dementia paralytica, 4.''9, 490 Dendrites, pathological changes in, 4 477 Dental hyperostoses, 527 Dentigerous cysts, 293 of bones, 690 I Deposits, calcareous, 313 I Dermatitis, blafitoniycetic, 92 j of penis, ti30 ' Derm atomy cosis, 702 i Dermatomyositis, 704 Dermoid cysts of mediastinum, 471 of uterine ligaments, 662 inclusion of pia-arachnuid, 606 ovarian, 209 ; of skin, 707 Determinants, 42 Diabetes, bronzed, 579 predisposition toward, 115 D abetic coma, 109 ! Diacetic ac! ', 109 Diapedesis, 124 Di.aphragmatic hernia, 569 Diurrhoca, 543 I Diastatic enzymes of bacteria, 84 i Diastol.' of heart, 375 Diathesis, 56, ")7 1 Dichorial twins, 62 i Dichotomy, polar, 66 I Difluse parenchymatous goitre, 424 i Digestive system, 522 I fever and, 151 I po'sons acting on, 82 : Dilatation uncurysm, 407 of intestines, 545 of myocardium, 392 ! (.f uterus, t)46 I of veins, 410 ■ o\ ventricles o< heart, 375 DiiiK'thylamin, 110 Diphtheria, 138 of external ear, 518 of a-sophagus, 531 Diphtheritic membrane, 438 Diplogemsis, causes of, 64 iJirect cell division, 38 inguinal hernia, 569 Disease, acquired, 55 cau.ses of, 55 ! chemical, 75 ■ intra-uterine, 58 mechanical, 75 pprasitic, 75 j partvirient, .58, 61 j physical, 75 I predisposing, 55 ; functional, 58 j of nerves, 47*^ inherited, .55, M postnatal acquirement of, 74 Disintegrative intoxications, SO, w.< Disk, chok «', INDEX I )isl(K,'atioii of Icn.-i, .j<)it Dissecting aiiciirysiii, 4(17 Disyiiiiiii'trii'ul jaiiiccps, (is Distent ion, a caiiM- of disease, 7(1 Dislonittni in liver, ■'>!)() WestiTinanii of liiiiKs, 4(m Disuse as cause of disease, 11.") Diversion of coinpleinent, ititi Diverticula of Fallopian tliln's, (io;! of intestines, o4."; Meckel's, .-)44 of (I'sopliatjus, MO Ducrticniitis, ."15 Diilar, 12.') Diiiiiinant properties, 47 Dcirsal (jroove. imperfect closure of, 71 DdiiMe cleft palate, 74 monsters, (>4 penis, (>;}() Diiiiriiie, !•.") I 'r y uanurene, ,'<3() Dry" pleurisy, 4(>S tenosynovitis, (i7(> I >iiilus arteriosus, patent, ;{S('> Uolalli, pa!-ciit, ."{.Sti Duiiicluni fever, Leisliinan-Donovan liiiilies and, it,") I liiiiijenilis, .">4S Dii ll>i|ili. Ii'iuiin, .')41 icalioii, fiisional. (>S of rnyocardiuin, .'iS.l 111 (esophaKUs, .")2(( of organs, 70 of pancreas. .")!)4 I if v.mina, ()42 iiini Miater, lOl carci loiTia of. .")04 clioridrotna of, .")(i.) encjotlielioina of, .")0;i til>roina of, .")0;{ lieniorrliiuics of, .'lOl, inflaniniaticn ot, ."i02 osleoina of, .">IK! p>:tMjirioina (il. .')(KS sarconia of. .")0I s\ philis of, .")0;i I'lnmihosis of, .")0I tulierculosis of, 7i{y.\ luniors if, .")0;t >ii-i liiidies of hliiod, .'i(i(l ' ' nii^rii. 70. (i7s • -Tll..ry, .Mo, ."i,")'.! isiiiMiion of, from di.irrli i.i of utei'us, (>l I '■■la, IO!l, 4:i(l 'in.c ol' Irsiis, (i;j7 I illrril^, (11 1 iiiiiiiiiialilies of, lll.le (if, .■|I7 .•|(I2 \'< ■\'Va ,")4;i Ear, auricl1S jiypereniiti of, 517 inHaiinnatioii of, 51.S Eustacliiaii lube of, 517 e.vternal, ah.sence of, 517 ah.sence of, 517 angioma of .")21 carcinoma of, ,")21 diphtheria of, 51,S duplication of, 517 eczeniii of, 51N exosto.ses of, 520 inflanunation of, 51.S fihroina of. ."21 furuncle of. 51,s Kranulomas of, infective, 51» lipoma of, .521 myco.sis of, 51!S osteoma of. .">21 periostitis of, 5IX sarcoma of, 521 .sehaceous cyst of, 521 stenosis of, 517 syohilis of, 5I.S lllhen'ulosis of. 51S internal, alisence of, 517 hetiiorrhatje of, 51.S liynereiiiia of. 51X inflanimalion of. .")2() t iddle. adenoma of. .521 angioma of, 521 carcinoma of. 521 fibroma of, 521 liemorrhaije of. 51S hyperemia of. 51.S inllainmation of. 51S saricirii.-i of, .")2I lubinulosis of, ,j20 llburnat.'d bone, (W2 licchymoses, W'^'y I'^'hinococciis of br.iin, 11(2 c.vsts of pancreas. 5'.<.s of uterus, (5411 hvda' I, 2<14 of lun^s, 4()5 of muscles. 1175 of p"ric!irdium. W5 of ureters. (124 Iv'lampsia, 1 10 Ij'lopia of bladdir, (i2t cordis. 72 of myocardium. :fS5 vesi 'a-. 7.'i lOiopic gestation. (i(i(i Kctoplasm 10 I'lctosarc, ;i2 Kctoto.xie huiMeria. !S5 I i I v=l 722 IXDKX 5 IS 17 r:i Krtoldxilis, l.'iCi Kczcin.'i, WIS i>f auditory iiicaluw, niuiliiliiii.-i. til)!) papulosiiiii, titIS pustulosiiiii, tit)*.) vcsiciili)siiiii, ti!)!) lOITcri'iit iMTvim.s system KITiisioii, iiloural, V-iA K^lt alhiitnin, 2'> Klirlicli's orders of reeeplors, 17:5 side-('liaiii llieory, 172 theory of iinimitiitv, 1;")7 ItiO. 172 i:iastiii, :{"4 Klastoid chaiijres in ovary, ti")ti detjeneralio.', ;iO<), 401 Mlectricitv as eailse of disease, 7S Kleidin, ;n2 Klephantiasis. til, 2S1, 411, 71)4 iieiiroiiiatosa, .")()!) of penis, ti;{2 of scroluin, ti40 of vulvii, ti4I lOlevalion of uterus, t)4.") I'jnholie pneumonia, 4.")7 Kmliolism, ;«•), :i.'.l in lirain, 4S7 of kidiie.\, tiO!) of liver, .'u'-i in luntjs, 44!) of iymjih ikmIcs, 412 of peritoneum. ")ti;i of spleen. 41)) in retina, .'ill) stomaeli anil, 'M I'jnholiis, air. :{.")2 atheromatous. ;{.")2 haeterial. ;{.'>:{ ealrareous, U.52 eell. :!.VJ fat. :i.VJ liireidn hodv, •{■">•{ uas. :{.-.;( menaearyoeyte, .{.VJ parasitic. ',iXi pigment. :{5;i "richnK,' -i")! Mmhryomas. sporatlic, 20!) Mmtiryonie eell, US malitjnaliev of neoplasms .irid 2Iti tumors. 22ti Kin|.hys.Miia. 2!)S, 4,T_', 4.-)l), »l>!) lOmpvema, 4t>!) Kiieephaliti-. ISS, 4S!) Kneephalomal.'ieia, 4S7 Knehonilioma. 2.'i4 of larynx, 44:{ Kneysted hydroec Ir, 2s!) i'jidarleritis ot)liter;ins, 10.") Kndemie lnfe<'tion, 14;( Endoearditis, :{!).< aortic, S!)4 gonorrlueal urethritis and, 112.) EndocardiliH, inaliKnaiit, ;{!H) mitral iiieompetenee in, :!!)" NieiiosiH ill, 3!)7 simple, .'{!).') ulcerative, :i'M\ venetative, ;{!)4, MH> verrueose, :{i)4, :i!)"i Kndocardiuni, ;J!)3 abiiornialitips of, .'{1)3 atheroma of, 'A'M) cidcitieation of, :W!) clerfC'iierative changes in, ;5i)9 hematomas of, ;i!);{ heiiiofclohiii iinbiliitiun in, 393 hemorrhaKes into. 3!)3 inHaniniation of, 3!).'{ net rosis of, 3!)1) Kniloijenous intoxications, 7!), 100 pigment ut ion, 321 Kndomelritis, ti47 cervical, 647 (•oriM)real, ti47 neiirral, t)47 glandular, ()4S heinorrhadic. ti47 interstitial, tilS i'jidoplasin, 1!) Kn(losmoHi.s, 32 Kiidosteal osteoma, 23.') Kndothelial cell.s, 127, 13S cy.sts, 21)1 neoplasms. 22ti spleiioniecaly, 241 li.ssuis. 22»'> Kndr)tlielionia, 227, 274, 277 of hone marrow, 420 of brain. 4!)1 of bursa'. I)7S of iliira mater, .")()3 of luntjs, 4().") of lymph nodes. 414 of mammary ^lalid, Ii72 'if nose, 431) of ovary, ().">!), litM) of penis, ti33 of peritoneum, .507 of pia-aracimoid, "lOI) of pleura, 47t) of salivary (tlaml, ')2S of uterus, t).")2 luidolheliuiii. 22.") of l)loodvessels in inllaMinKilioii, regeneration of, l!)ti iCndotoxie bacteria, M Kndotoxins. l")l) F^nnorReineiit in pneuir.onia. I.j2 iMiostosis, 23ti, tiSi) l')ntamii'ba coli, !I3 hystolytica, !)3. 1)4 luileritis, .■)4S catarrhal. ■')4S follicular, .'vl!) membranous, .")4!) phlejjmonous, 540 B^ INDEX 723 Ktilororplc, (142 KntcrokinuBC, iictivutinn of trypMnoKon ')>', 174 lOniircsis, iiorturniil, ti()5 Knz(><>li(! inffctioti, 143 l'ti?;'inc action, 27 Kniwth und, 30 liydrolywis and, 32 k:.!.'i'i.si.s and, 2.S rovi rsibility of, ;jO anliiiiastatic, 1,56 antippplio, 1.56 of l)a('toria, S4 di.stitiction of, from formonts, 28 pxtracc'lluiar, 2S iniMiunity afcainHt, 15,5 inlraopllular, 28 of Iciikooytj'.s, 1(M5 rcscinblanpc of, to toxin.s. So l^iisiiiophiles, in influrnniation, 12S, I2it, :iti2 Kiisiiiophilia, !M», 3<)4 Klii'iidyfiial cysts, 2!»2, 492 l!|ii'iiilvinonia, 247, 4!)2 ICpibhisi, 223 I'^liild.'i-itic nooiiliisms, 22.5, 226 l.|iiil"'!nic bacillary colitis, 5.5N, ,5,50 iiifi'ction, 143 parrititis, 52S lliiilidvniis, 637 1 l>it.'ii:illn!s, 6.5, 2(H), 437, .525 Ipini'iilirin, 102 liiiphysis ccrobii. ^cc Pineal uland I pipliysitis, 6S1 I pi-|).'idias, 73, 628 Ijii-i.'ixis, 434 l.piil.rlial casts, 312 1 ysts, squamous, 2!t2 i rm'tapliisia, 204 pearls. 26-li(.i(l cells, I.3S 1 piil,(|i(,iri:i. 26!t. .S'cc also Carcinoma, s<|uaiiious-ccllcd. "I iiioulh. .525 iif ii'.-opliamis, .531 "f Nkiti. 7(Kj of stoniiiclp. .53(1 j of uterus, 651 I I'liiliurii, ri'Kcncration of. I'.)4 ' /iiiitir iiifcitidii 143 I ill-, J30, .52") lil.rous, 68!) ' "iMiiN, licmorrhattic, of stomach, .5.il * ipHas, 7(10 i ili.'riia, 6117 I . ilirocylcs, 35H liiiiioKlobiii contctil of, 3.5i» licinolysis of, ;i.5<.t ■''ir>plin(j" of, 3.5it I iTil.jci. in typhoid fever, .5.50 I'lriitylus Ki|{.is in lu'cters, 621 Hiheinala. pn>disj)(isition toward, 115 I •lions. P-orpiiou of, intoxications to, 105 Kxcnccplialy, 72, 485 Kxercisc, hypcrtropliy due to, IS7 E.xof;cnous intoxications, 71> pigmentation, 324 Exophthalmic ({oit re, 101, 424 Kxo.^mosis, 32 Exostosis, 2.36, 688 of bones, 088 bursiita of Ikjucs, tiSO of pxtprnal car, .520 Extrophy of bladder, 621 "Exuberant " granulations, 1.38 Exudate, 134 Exudative choroiditis, 513 plcuri.sy, 467 Eye, .5(K» anomulieH of, .5(K» inflammation of, .510 Eyestrain, 50i) FAn.\L clefts, imperfect closure of, 73 F'acultative anaerobes, 84 Fallopian tubes, 6.52 abnormalities of, 0.53 absence of, 6.53 carcinoma of, 6.54 diverticula of, 6.53 double orifici- of, 6.53 fibroma of, 654 Ronorrhn'al infection of, t)54 hemorrhage of, 6.53 hyperemia of, ().53 inflammation of, 6.53 lipoma of, 654 myoma of, 6.54 papilloma of, ().54 sypliilis of 6.54 tumiifs of, 654 tubereul<>us infection of, 654 False hermaphroditism, 74 neuroirias, .50it Familial charai'ters, 47 Fastiniuin in infection, 144 Fat in cell, .33, 302 embolism, 352 formation of, in fat cells, 23 necrosis, 32.S of panc,-eas. .5(15, .507 serous jitropliy of, 2(18 -forniinn ferment, 34 -splitting ferment, .33 FatiKue, 111 muscol.'ir, 113, 11 1 , of nerve I'cll, 1 14 Fatty deneneralion, 123, 303 of kidney, t)20 of liver. ,584 I ■I 1 724 IXDEX [V Fully ilruciioration of iiiusclfs, (17.") of inyocanliuin, :isy of paiHTCits, .V.»7 of prostate, (WW iiitiltrati7 tissue, reKeiierat ion of, Il'l Fauces of tonsils, 4;{(i Fa>us, 702, 7()s Febrile all)inniiniria, 1.'>I F'einoral hernia, ")•>!• Feiiestrati >ii i>f setiiiluiiar valves, ;{!>;{ Ferments, distiiiciioii of, ir )iu eiizyna-!*. •JS fat-fortuinu, 'M fat-splilliiiK, S.i lipolytic :i4 Fertilization. It Fervescence ill infection, 144 Fever, 14',t asthenic, loO chills ami, 140 continued, \W disturbances, associateil with, 14M in blood and, l-')(> in circulatory system and,_ lot) in dineslive system ami, l.")l in nervous system and, 14".), l.'O in resi)iration and, l.")l in urinary system and, ..'jI intermittent, 14',t relapsing, '.IS re of boni' marrow, 420 of brain, 4111 of bladder, (".27 of bursa', t>7.S of conjunctiva, of cornea, ."il.-) of ear. .")21 of l'"allopiali lubi of intestines, .■|l')0 of ki of inyoi'ardiuin, '.HKi of nose, 4;{(> of ovary, ().')!> of penis, (ilW of peritoneum, .j()7 of pia-antchnoid, ^I'M of placenta, ()(>4 of pU'ura, 470 of .skin, 705 of stomach, i>'-i\i of urethra, (12!) of uterine lit;aiiieiils, 062 of vulva, (141 Fibronmtoid growths, 'j;«) Fibromatosis, 247 of mammary gland, f)6S of optic nerve, .")I7 of perii)heral nerves, .tOO Fibroinyoma of placeiitu, 004 of uterus, ().")() Fibrosan'oma, 2.')0 Fibro.sis, 12,-), 141 in arteriosclerosis, 142 (lup to strain, 14H of heart valves, H!)H inflammatory, 142 of lung, interstitial, 405 of myocardium, liS7, 391 ncopla.stic, 143 non-inllaiinnatory, 143 l)ost-fibrinoiis, 143 liroliferative, 142 reph"'*'""''!*' 142 of veins, 410 Filaria nocturna, ".)'.) sanguinis in ureters, 024 Filariasis, 411 Fillnible viru.ses, i)2 Fission of o.s uteri, 044 Fissure, abitominal, 72 sternal, 72 vesico-vagiiial, 73 I'issured larynx, 440 I'istula in aiio, 555 of larynx, 440 re<'tovaginal, 043 uterorectal, 044 uterovesical, 044 vesico-umbilical, 025 vesico-vaginal, 043 Fixation of complement, 1(17 Fixed tissues in inflaminution, l.ii Flugellala, 04 Flat worms, OS Fleshv mole, 212, 004 Flexion of tlterus, 045 Focal change in nervou.s system. i»- necrosis, .32.S Fcvtal adenoma of thyroid gland. ' MJ: I .• --rV' r"j«fe;':- -.. -m ■ET9W? ^SiVrniU ■ 'Ain :W mmmmsam ISDEX Kd'tal inclusions, "JltS lobulution of kidney, r><)S I'ifliis, tMlo acanliiicus iinrops, (>:{ .•ii'i'i)h!ilu.s, (i2 acorniilK, Ki aiiiorphiis, (>2 ilciith of, tMir) flTcct of, u|M)n niaiiiiiiiiry Kiiiml, HY.i of plwrcnttil disease ii|hiii, (10 iiiuriiinificatioii of, (iti.j secrelions of, 1(K} syphilis of, (H).") I'ipllicular eolilis, 'i.'iS (•>sts of ovary, (i'ld enteritis, .'>4!l (lastritis, ").'{") tonsillitis, chronic, 440 liiinites, transmission of bacteria hy, i>0 lool-drop, .JOS I iiruiiien csecinn, 423 I iiree, reserve, 37 I'lireinii bodies in bronchi, 44."> embolus, 3').< in joints, ('>il4 in prostate, iVXi in un'ters, t(2;{ in urethra, t)20 in uterus, G4(t JTiictiires, healiuK "f, W^ of penis, Ki'.i I r:iijilitas ossium, ()7(l I lafiinentation of inyiicardiiun, ;{!)! I i:iriil)iesia, !S, 407 liroiichiectasis, 44t) o ■ M.\i iiKi-.i.K, 2!>(), 070 ■ iliihiplidritis purulenta, t)07 ■ ll-lihidder, .')!»! abnormalities of, ,")',11 absence of, .^ill rareinonia of, 'i!)2, .">fW irraiiulomas of, ■)()2 lieinorrhaKes of, .")i(l iiitlainmation of. r>!•;{ Gall-bladder, tumors of, .')!)2 duct, abnormalities of. .'i!)| atresia of, 'Ail carcinoma of. .")".I2, .V.t;{ grainilomas of, .'itl2 heinorrha(!os of, 5!tl intluniination of, ■'t'.H obliteration r)f, .")!)! (I'dema of. .">01 sarcoma of, .VXi tiunnrs of, ."i!t2 "Oallopinit consumption." 4(12. 403 ( iallstoncs, 31.S. Sn also Calculi, biliary. in peritoneum. .">00 (ian^lion of tendon sheaths. 077 (JanBrene, 32,S, 340 40 stomatitis, 024 Gartner's duct, cysts of, 2S!) ( las embolus, 3r)2 (iiustrie juice, action of bacteria on, SO (iastritis. .">3") a<-ute, .'>35 atrophic, ."»30 chronic, .53.5 follicular, 53.5 membranous, 535 phleKmonou.s, 'hi'i polvjxjsa, 5;{5 Gastro-mtcstinal intoxications. 111 Gaslrothoracopanus parasiticus, 70 Gelatin, 34 (ienital (jljvnfl'*. teratoma of, 209 I)a.s.sa(jes, entrance of bacteri.a through, !K) Genitalia, female, external, 040 (icoRraphical ton(£ue, 524 interstitial, (iOO tubal, 0.52 Giant cells, 13 CnwiMTs, ti;U) liyiHTIropliy of, (•oiiKcnital, JKi rcKcncnilion of, 1!H) M.ilivar.v, .")2,S (ilaiiilular <""ii(lotii('triti.s, (MM hyiMTlrophy, roiiKcniial, 2()! (•liotnatosis. 241). 4i)l (iliosareoina, 2')7, 4i»2 Gliosis, 24li, 4!tl (Jli.-won's capsule, inflammation of. rm (■lobular thrombus, ;{4i» (•lobulins, 23 .serum, 2") (ilo.ssiim inorsitans, !M> palpalis, !((i (ilossitis, .")2;{ (jlfittis, (rdema of, 441 (iluRe's corpuscles, 4s;t (ilycofienic activity of liver cells M (■lycoKeiious infiltration. MW, (■ ycolytic enzymes of b.acteria ,S4 (ilyroproteins, 2.5. .'{4 ' (jlycosuria. pancreas in. ."i!)4 (Joilre. (lifTiise parenchvmalous 4'>4 •'xophthalmic, 101 thyroid, 2!»1 Conorrh.ea |)re.lisposition toward. 11.5 (.onorrlueal nifection of Fallopian lubes o.j4 ' ophthalmia, (it urethritis. C2S (ioiit, 107, ()77, G94 f.-iully metabolism and, 107 predisposition toward. 11.5 'ophi in. ()i)4 (jraftinK, 1!H». -V'c also Transplantation (■ranular casts, .{12 degeneration, 12.'i kidney, small, (114, (ili5 r>'iarynKitis. 4.<<) (iranulution. "exuberant," l;{,s I'ssue. 12(1. 1. 5(1 (Jranules, Allmann's. of nucleus, 22 secretory, 22 (Iramilomas, infective of conjunctiva, of cornea, .5 12 of ear, .5 is ;{01 (Jranulomas, infective, of Kull.bla.ldei of duct, .5i>2 of iris, .512 of pancreas. ,V.)ii of (MTipheral nerves, .5 relation to cell activities. 3.5 (■uanase, 107 (iiianin, 27, 107 calculi, 31.S (iiiinea-wonn in skin, 703 (Jiimma, 13.S of bone, G.S4, 0,S.5 of brain, 4S!» of iris, .512 of lunRs, 46.5 of mouth, .525 of miLscles. 075 of myocardium, 3H,S of i)ia-arachnoid, ,50() of skin, 701 of spinal cord, 4 •'iiilocariliutii of, L'nijurunliiiin. fibrilliition of, ;{s(» intcraiiricular septum oriKJii of, ;j,v, intriivfiiiriLulur «eptuiii of, .Icfccis of, .'ISO "luscl.-. .ILseitso of, iilti-ration in ilistnhiition of bloru-ar,liurii of, 3,S(). See also rericardnini. poisons artinjt on, S2 rupture of, aoi seniilunur cusps of, rupfurc of, ;j{»<) valves of, .{7(1 septum of, arcessfiry im|KTfe( t, ;180 (leviatioi; of, .{so systole of, .{7") "thrush-breast," ,3!,() valves of, ubiioriimiities of, 39;j fibrosis of, ,3<),s veRetutions in, 34<» ventricles of, .iT.i flcat discharge, 148 priMluirtion, IIH rcKulation, 148 stroke, 78 Kc'iiiachroinatosis of liver, .57ft lletriannio-f'ndothejionia, 277 2S1 of bones, (J8<) of capilhiries, 410 of liver, 5.S!) of pia-anichnoid, .")(M') 'Ii'riianKioiniis, 278 bl;istoniut,ous, true, 281) "f capillaries, 410 of intestines, ."><>0 Heinanniosarcoma. 414 ll('m:-,feniesis, :i!rl lli'ti,.i(i,ir(,sis, .3.54 nciiiali!;, 2.'), 'M il'l|i;iloi)|;tstS, |<»4 II: n^.iMcele, ;{."i4, titil ll'iiialoKenic p:ie'im«nia, 4.51 iuberculosi:i, 4(;4 ll.irialoKenous hyaline cleKeneralion, :jll '■riialohyahne (IcKeneration, .{11 Miiriatoidin, '.i'M liiKnicntation due to, 322 i" iriatoma, 3.54 uFite-uter'ne, t>61 auris, i5I7 of endof-ardiuni. .JO.'j iii!raliKa;iientous, fitil of muscles, U7) 727 post-uterine, Oiil •>f vulva, (Ul '■•liatometra, tl4(i ^ii.itopi.ri.-ardium, 3.51, .382 ;i';-"o|.orphyrin. piKmentalion due lo, Heniato.sjiIpinx, (5.5.3 Meiiialos|M)ridia, (»7 llemalolhorax, 3.54, 4ti»i Hemalozoon inalaria-, !t7 Hematuria. .3.54, t>03 Hemiccphaly, 72 Hemochromatosis, 322, 4 IK, 579, 7ft3 Hemoclastics, HI Hemoeonia, 3()6 Hemofuchsin in liver, .322. .58() HenioKlobin, coHi|M)sitiiMi of 24 ''.5 imbibition, 322, .3.5(1 ' ~ in endocardium, 3i).3 pinnienlation due to, .321, 322 variations in, .3,5i» Hemonlobinuria. .322, (MM HemohepatoRenous jaundice, 324 Hemolymph nodes 1 1 I Hemolysis, KM, .3,51) Hemolytic splenomcKaly. 241 .57<» llemolytics, 81 Jlcmophilia, 47, 3.5(» Hemoptysis, 3,54 Hemorrfiage, 3.54 cerebral, 4<»8 etTects of, 3.5.5 in luHK, 448 [H'r diaiMHlesin, 33il, ,3")4 per rhexin, 339, 3.54 retinal, .510 in typhoid fever, .5.5.3 Hemorrhauic cysts. 287, 293, 3.50 of brain. 492 of mammarv uland, (507 enceiihalitis, 488 endometritis, ti47 erosions of stomach .5.34 infarct, 344 of intestines, .547 inflammation, 1.34 mo'e, 212 nephritis, (il2 otitis media, .518 pancreatitis, .59.5 IM-rittmitis, .5(5.3 I'lLiirisy, 469 retinitis. .514 sei.ticemia, 91 Hemorrhoid, 278, .547 Hemosiderin, .3.5t) in liver, .58(5 pigmentation due to, 32'.' Hepar lobatum, 583 Hepatiti.-;, .573 acut»', 573 suppurative, .574 Hepatization of limR, 4.52 Hepatolysin. 16.3 Heredit.y, 46 variation and, 47 Ifennaphroditi.sm, 74 lleriMa. .568 abdominal, .569 epiRn-stric, .5(50 i>^dt:<<). (Mi.". 72S lloniia li:iplir!i)tin;ilic, .'ti't ••M .ii.il, .'ids ft'inoriil. .Vi!) iiicarrcratiiin of, iiiKiiin.'tl, .'i(i.s iliri'ct, MM incoinpli'tr, <>hli(|iii', M)S iiitornal, .'rti.s, ."iti!! <>l>Mirator, .">ii!i IH'riiical. "iti!) n'(liiril>|c, Mis .xfiatic, ."i(ii( fiTotal. .">()!» iiinliilical. 72, vaKinal. .'i)i!) McriM's, (iO.H of corm-a, .">12 fai'iali.'*, ti!»,s lahialis, .V2;{ pn'imtialis, (i!l(» priiucnilalis. tl:!ll of >kin, (><>.s zi'.-^tcr, V22. ;f7(l, till.s MctcriK'htlionoiis blaslofiia.s. .'2;! Hftcrolvsiii, l(i;{ Hclcruly.si.s, |(M> H(>t(T()<)|)lial twins, ti2 Hctcropla.siii, 2(»:{ Hctcroplastif n.stcoiiia, 2.J,") lraii.-«plaiit:iti<.(.( flir-cli-piutiK's (li-ic;i.sc, .MJ. .-)li2 Hi.'siiiics. (i!».') Hi.s, hundlp of, 377 Histolvsi.s, normal, 2!(r. ri.l.r.Mlliv.T. .->7.-. .'iHl(jkiir-i (li.scasc. S.i'.K 11.; HdH-hack kiiliK'v, t)l;j Iloinophustic istcoiiiji, 2.'f.") MoMiotropisiii. 201 H()> Hott(.ntot apron, •)4() HoiirRla.'^s sloniai 'i. " Ffou-scniaiil' km. Hutch. lIMill'.S tcclli, M valine easts, ;}12 (•(lis, -.uy.] niononiielear. i:i2 clianRe in niyoe.irdinin, V.i] in ov.'iry, ().")t'i deiii'iM'r.'ion, I2:i, :W,. :■(()» ':!' .art cries, 401 of ciipill.-iries, 410 of kidtiey, (120 of IvMiph nodes, 413 "I >,.()slale, ("'! of i!i\roid kI.hkI 424 1).". ■ ti ■'7, rs r,->:i J.SDKX Hyaline deiMisii, 3iMi ("•inai. .'c'tioiis, .'{| 1 iii.'illralion of capillaries, tlO nioiio'iilelear eell, 131, l.!2 throi'ihiis, 317 Myalo-eiH'hundronia. 231 ilyalo.-'erosilis o( liver, jSl ill peritonitis. M;r> in pleurisy, -tti't Hydatid cysts*, 2!i.'. of liver, .llHI eeliinoco<'cus. 2!I4 of .MorKaniii, 2S!I. (i."),i mole, 212 Hydatirlifnrm mole ot pl.'.ceiila, (Kit Hydraniniii.-. (il, t>(i."> Hydiemia. 3;{.">, 3,'i7 of hliHid pli4sma, 3,".7 plelliora. .33.") Hylic ti.ssucs, 22.") HydnK-elc, .ititi, (WO cervical, 2.S1 cncystiil, 2X0 of fourth ventricle, 202 .scrotal, 2'Jl of tunica vaisinali.s testis, (13(1 Hydrocephalus, 01, 202, 3(1(1, 4.S0, 40,") Hydrolysis, enzyme action and, .32 Hydrometra, 201. 04() Hydroniyelia, 40.") Hydronei)hrosis, 77, 203 from kinks in ureters, (123 Hydropericardiiim iiiO, 3S1 Hydropic dr'ueneraiion, 3(Mi H.vdropncumothorax, 407 H\(lro|)s cvstidis fcllea', .".02 ex vacuo, 200, .304, 371 vesi.a' fcllea', 2!«) Hydrosalpinx, 2iH>, (l,"i4 Hydrothorax, .330, 300, 370, 1(1(1 chylous, 4(17 Hyuroina, 202 of burse, 07.^ colli, 202, 411 cystic, 2S1 of necl;, 307 of orbit, ,")17 of tendon sheath, (177 Hylic neoplusm.s, 22.1, 226 tumors, typical, of me.sotliclial oritjin, 213 Hylomas, 220 Hymen, (141 absent, 041 itTiperforate, 041 Hypamnio.s, 01 Hyphomyce^'s of hin({s, 10.') j)atlioKenic, 02 Hypisotonic solutions, o.smosis and, .l.f Hyperemia, 337 active, 337 of atir.i. ti7!» of liraiii, tsti ciipilliirv, X\S of ciioroiil, .'iltt no Hal I Til, :i;i7 of ciinjurirtiva. .'»()1l ^ rl. ,{;{7 t'allopiuii tiilH-M. ti.'k't of rris, ".III of kidiii s .Ml'* of iiilcsliiH's, .jKi of larviix, 441 of liver, oTO of luiiKN. 117 of lymph iio2:i of inusclox, ()7:{ ni'iiroparalylii . ncurutonic, ;i;i.s of iiosi', 4.{4 of paiicrcaH, oil.") of |M>riton(Miiii, .>(i2 of pharynx, 4;{7 of pia-iirachnoiil, ."> of prostate, i\'X\ of retina, ."illl •■r ■' 111, tilHJ Hi |.|een, 41."» of stomach, .VW of tpere.s|hesi;i, 47!l II'. periiiosis, ;{4.S, :{."i,S ll,\ perisotoiiic sdliilions, osmosis li\perkerato.»is, 'ioll, :\\2 llvpernephronias, 270, 277 of ailreii.'ils, 42;{ of hniin, 4!I2 of kidnev, 021 "f liv<'r, oSO l\|h lostoses, (l(;ntal, .527 !lypi|-pl;i.siu, ISO of adrenals, 422 of l)oiu' marrov, 41'.l uf holies, 'i^O, tiS.S »'• clit;OPS, 040 irrit:iti\(', 2t>;{ of lymph nodes, 4i;{ of parathyroids, 420 of sph'en, 41.S of testes, t>:{!l of thymus, 472 Ivpirthyroiilism, 424 1^ iicitomis, AK\ iM'crlrichosis, 02, 0!».">, 70S lv|iirlrophic eirrho.-is. ">70 iliiiiilis, 4.'!.") l\|"rlrophy. 3S, ISO acroi.iejj.'ily ,'ind, 1S20 of liver, ".").S!I of muscles, 070 of inyiM-ardiiim, ;t.S."i, :{'.)! nutritional, IS8 phy.siolofcical, 1H7 of prr>slate, 0.'{4 .simiilatol, IS!) sympathetic, IS'.I of uterine liKuments, ti02 of uterus, O.jO vicarious, !S,S Hypinosis, :{47, ;{">H llypobla-Ml, 22:i MyiKihlustic neoplasms, 22."(, 220 llypoKcncsis, polar, 70, 71 Hypophysis cerebri. Ni« I'iliiilarv hodv. Hy|K>plitsia, 70, 2!IS of adrenals, 42 1 of arteries, 400 of larynx, 440 of mamie-iry k'h'"!. •>'">•> of myocardium, :fs.") of ovaries, O.V1 of pancreas, .")94 of testis, 0;{7 of thyroid Kland, 424 of uterus, 04;{ Hypopliistie penis, i\M) unilateral, prostate, ftXi Hypopyon, .512 Hypospadias, (57, 02S HyiKistatie congestion of luncs, 147 pneumonia, 4.52. 4.57 Hypothyroidism, 421 iIy|M)xanthin, 27, 107 Hysterical paralysis, 4.S3 Hysterocele, 044 IcilTnvoai.'<, 312, 00.5 Icing liver, .5t).5, .5S1 Icterus. .Sec .(aundice. ldiosyncra.sy, 1 17 Imbibition, hemoKlobiii, ;{22 Immune boily, 104 serum, 11)4 Immunity, 1.52 ab.solnte, 1.52 acquirefl, U.5, 110 .ajjainst abrin, l.<4, 1.5.5 albuminoid venettible poi.sons, 1.54 enzynn's, li5.5 phytotoxin, 1.54 ■HB ma MICROCOPY RESOLUTION TEST CHART (ANSI and ISO TEST CHART No^ 2) 1.0 I.I 1.25 •flllM t 1^ 1.4 2.5 12.0 1.8 1.6 A APPL IED IIVMGE Inc =^ 16^! [051 Mo'" SUeet r«S 'Rochester. New lorh M609 'JSA JS ., '16) 48.^ - 0300 - Phone ^= me) 288 - ^989 - Fq« r.'U) IXDKX Immunity apainst riciii, 154, 1.") robin, 154, 155 Muhstanccs of known constitu- tion, 15l{ of unknown conslitution, 155. anapliylaxis an dermoids of pia-arachnoid, 5(Mi fci'tal, 20S Incompetence of lieart valves, ;}*17 Incomplete iufiuinal hernia, 5(>!( Incontinence of urine, (105 Incrustations, calcareous, ;{15 Incubation period of infection, 144 Individual inheritance, 4,S Indol, consti)ation and, HI Indolent bubo, ti^U ulcers, 700 Induration, "brown," of lunns, 44S in pneiunonia, 45S cyanotic, of kidney, tiO'.l of lungs, 44S mediastinopericardit i? , ;W4 Inchirative pnemnonia, secondary, 457 Inertia, physiological, ;{•> Infantile scurvv, tiSS Infarct, a2S, ;i41, M-i of ailrenals, 422 anemic, 344 of bones, ()7i' forn>:ition of, 'M'.i, ."UCi liemorrliagic, ;{44 of intestines, 547 of liver, 572 in lungs, 44S of muscles, (i74 necrosis and, ;V2S of phu'cnla, t)('i4 red, :i44 results of, il45 uric acid, 1117 white, ;{44 of liver, 572 Infarction, ;{1^! 141 4!! Si) ui, 141. Infe •tions. .! fastigium in, 144 febrile state in, 144 fcrvi'.scence in, 144, 14!) fevi r in, continui 1, 144 fulminating, 145 grades of, 1 15 incubation period of, 144 lat.nt, 121, 14t) localized, 145 lysis in, 140 meta.stas(w in, 145 m(Mles of, SS ])ersisting, 14t> premonitory symptoms in, 144 prodromal symptoms iti, 144 pyrogenetic, 14!) remittent, 146 se(|ueUe of, 144 of spinal cord, 4!)t) sporadic, 14:5 stages of, 14() terminal, 121, 147 wound, SO Infectious albuminuria, 60:i Infective granidomas, i;{S thrombosis of dura mater, .")0I Infiltrations, :{(M) of arteries, 401 of cai)illaries, 410 "fatty," ;J()2 glycogonous, ;}0*> lipoid, :>l)5 of liv(>r, 5S4 of lymph noriphpral nerves, 507 of peritoneum, ■")63 of pharynx, 437 phlegmonous, 134 of pia-arachnoid, 504 of placenta, 064 of pleune, 467 polynuclear leukocytes in, 128 purulent, 134 of retina, 513 serofibrinous, 134 seropurulent, 134 "f skin, 696 of spermatic cord, 640 Inflammation of spinal cord, 4!i5 of spleen, 417 Staphylococcus pyogenes and, 121 of stomach, 535 of teeth, 526, 527 of tendon sheaths, ♦)76 of tendons, t)70 of testes, 0;« of thyroid giand, 424 of ton.sils, 437 127 of tunica vaginalis testis, OJJO ulcerative, 134 of ureters, 623 of urethra, 628 of uterine ligaments, 661 of uterus, 047 of vagina, 642 of vas deferens, 640 j in vascular area, 123 I of vulva, 641 of veins, 410 wandering cells and, 1 19 Inflammatory fibrosis 142 a'dema, 370, 447 tumors, 207 Infusoria, ciliate, 97 Ingrowing toe-na :. 708 Inguinal hernia, .50.S Inhalation pn'>umonia. 4.")0 Iidiibitive poi.sons acting on muscular system, 81 Inheritance, 40. Sie also Heredity. of .abnormalities from previous gen- erations, 57 of acquired characters, .53 I "anti.specific" characters and, 57 atavistic, 48, 50 i blended, 48 I cumulative, .50 i familial, 47 i forms of, 47 of functional di.se!i.«es, 58 of hypospadias, 57 individtial, 48 I Mendel's law of, 48 j normal, 51 ; non-, 51 i " panuspecific " cpialities and, 57 1 parental, 48 ' particulate, 48 I of polydactylisni, 57 I progressive, 51 I racial, 17 retrogressive, 51 reversionary, .50, 51 theory of, 51 Inherited disease, 55 pathological states, .56 pre?» by, 97 m n! 7:?2 IXDKX Inspissalioti in H!iiij!i <'ni', -i'M uriitic, ill infiiiH'y, 1517 Intciilidii tremor, 4S4 Intcnmricular septum i>f liear* double oritiiu of. ■<><•) liilerciirreiit relapse, 14t) lliteriuediate body, HU Interniitteiit fever, 14'.l Iiiternid seeretious, KM), 2Hi Interstitial einpliysema, 4r)ll eiKlometritis, t)4S fibrosis of liin(js, 4(i") myocarditis, :}S7 n«M)hritis, tiOC), tU4, (iKi ledeina, :iti(i Intertrigo. (')!•!> Interventricular septum of Iieart. defects of, :{S(> Intestinal bacteria, .S."( tract, entrance of l)acteria tliroufjh, •H) secretions of. lO^i Intestines, al)norinalities of, .'>44 atresia of, .")44 anemia of. .">4() carcinoma of, .")(">() cysts of, r)44 dilatation of, •")I."> diseases related to secret iohs of, 1'):? diverticula of, .")4.") fibroma of, .")()0 liemaiittioma of, "itWt IiemoirhaRe of, .")47 occult, .")47 hemorrhanie infarcts of. '>i~ hyperemia of, .")4() hypertrophy of, ")(>(• iiitlammation of, .■)4S inttissuseeption of, .")4.") Ranurciious, r)4t) invagination of, .")4.") large, ■■j41 lipoma of, .">(>() lym))lian(jioma of, otlO lymjihosarcoma of, .")<>! myoma of, ."lOO papilloma of, ■")<>(• poisons ai'ting on. S2 .sarcoma of, atil small, .■)41 stenosis of, .")44 strangulation of, .")4.5 syphilis of, .">.").") tuberculosis of, ,j.")l{-.').')."i tumors of. .")()() typhoid fever and, •")4'.) idi<'r of. .")4S varices of, ,")47 volvulus of, .')4.") Intoxicatir)n. .">!<. 70. 14.") bacterial. S.") •distinction o'' from infection, S,") disintegrative, St), Id.') Intoxication due to non-eliminated iinxl- ucts of kalabolism, 104 to resorption of excretions, 1(1,') endogenous, 7i<. 1(H) exogenous, 7!<, .M ga.stro-intestinal. 111 internal .secretory, 7!) intra-uterine, us cause of disease, .")!! ni; tabolic, HO iion-para.sitie, 7!t, .SO parasitic, 79, .S4 sapremic, 145 saprophytic, 71) Ii.cracanalicular fibro-adenoniu of mam- mary gland, (>70 Intracellular enzymes, 2S fat aecunnilations, ;{()2 Intracystic jiapillomas, "ifil Intraligamentous hematoma, (iOl myoma of uterus, ().50 Intramural myoma of uterus, (')">() Intra-uterine cauf'< of disea.=e, .'J.S Intussusception, .")4.") Invagination of intestines, .")4.'), 'Aii Inversion of uterus, ()4"» Involucruni of bone, OM) Invt)lution cysts of niaiiniary gland, f)7() Ionization, water and, ;{2 lodothyrin, 100 Iridocv<'lilis, .512 Iris, a)).sence of, 509 gumma of, 512 hyperemia of, 510 infective granuloma of, 512 inHamniation of, 512 pigment of, absence of, 509 sarcoma of, 515 .syphilis of, 512 tubercle of, 512 tumors of, 515 Irritation, definition of, ll.S grades of, 122 local reaction to, 118 Irritative hypertroi)hy, 188 ])oisons acting on muscular sy^lciii, 81 Ischemia, ^{115 I.solvsin. !(>:{ Isoplastic transplantation, 199, 201 .Iacksoman convulsions, 482 .Iaiiice|)S, (18 ,Iaundice, :}4.3, 703 catarrhal, :VZ.i. .")'H hemolieputogeih is, 324 obstructive, lO-'i, '>'-.i skin in, 703 .lejuinmi, .541 ,Ioints, (190 .abnormalities of. (190 ankylosis of, 091 ISDEX 73.S .loiiits, atrophy of, 1>'.I4 ciiricts of, tiiCJ "Charcot's," »)!)4 corpora oryzo'uica of, 0'.(4 fon.'inii bodies in, W)4 heinorrhajffi of. •>'.•! inHatiirnatioii of, ti'.M H|>oina arborcscciis of, (>!(") nu'taplusia of, l>'.)') ochronosis of, ti04 ostco-arthritis of, O'.tl sarcoma of, tiit.'i subluxation of, G!>1 syphilis of, ()!)."{ tuberculosis of, (jtKJ tumors of, (>!)."> Kala azar, Le simian-Donovan ImmIIc.- and, !».5 Karyokinctic cell division, 13.S Karyolysis, 23 Karyorrhexis, 23 Kiitabiosis, 3.5 Katabiotic activities of cell, 3.5 Katabolism, elTects of pnxiucls of, 104 non-eliminated i)roducts of, intoxi- cations due to, 104 Katadidyinus, (>7 K;.talvt=is, action of eiizvnies bv, 2S Kat aplasia, 2!»9 Kailiions, 32 Keloid of skin, 705 Ke|)lialin, 27 Keratin, 312 Keralinization in carcinoma, 270 pathological, 312 Keratitis, 511 parenchymatous, diffuse, 511 piilyctenular, 512 suppurative, 512 Kcratohyaline, 312 Ki'ratosis of penis, 632 Ki Iney, (iOS abnormalities of, tills absence of, tiOS actinomycosis of, (il!) adenoma of, ()21 amyloid of, (V20 aiiemii' of, tiOS angioma of, ()21 anomalies in shape of, t>0,S atrophy of, til 7 bacteria in, .HS carcinoma of, (i21 cloudy swelliuK of, tl20 congenital cvstic, 2S'.( cysts of, Ii22 dcfjencration of, ()20 embolism of, tiO'.t (ibronias of, 1121 filial lobulation of, (iO.S Kiilney, ulatiilers f>f, (iPI granular, small, til 4, 1)15 hog-back, til 3 hors('-slioe, tiOS hyperemia, liO!) hypernephroma of, (i2l hypertrophy of, 020 ii ciuration of, cyanotic, t>it!) inflammation of, tiOO large mottled, Iil2 red, Iil2 white, til 2 leprosy of, til'.l lipomas of, liJl mobility of, tHlH myoniiis of, Ii21 myxomas of, t)21 nerve supi)ly of. ti(M) pelvis, disturbances of, ti22 pigments in, o of, 444 iiiicinia of, 441 at rcsia of, 440, 444 atrophy of, 443 carciiioiiia of, 443 cysts of, 443 enchondroma of, 443 Kbroina of, 443 fissuri'il, 440 fistula of, 440 ulanders of, 443 liy|M)pl:ueprous nodules of mouth, .525 Leptomeningitis, .504 Leucorrhea. 043, t>47 Leukemia, 304 lymphatic, 240. 305, 414 m>el<)gen Liquefaction of vitreous humor, 516 INDEX '.•55 l.ilhiiisis, iiriiiiiry, 'Mi\ Litliopadicjii, ;{l"4, 5G»>, (jtM I-ivcr, 5«!», 570 ubnorinulitips of, 570 acco.sMory lobes of, 570 iicfinoiiiycosis of, 5K;{ udciiotna of, 5S!I iiiiKi-bic abscesM of, 575 niiiyloid of, .5,S5 anemia of, 570 Asraris liimbricoidps in, .5i)0 atropliy of, 5h;{ brown, .5H;J, 5S(i red, arutr, 574, 5.Sij Vi'llow, acute, 571 autolysis of, 1(M» calcification of, ."jXti carcinoma of, ■5,'S!» cardiac depression in, 5.S4 cavernoma of, 5S<) cell embolus, ;{,")2 KlycoKPTiic :i.;livitv of, ;il cirrhosis of, .575 cloudy swelling of, ,5S4 coccidiosis, 5!K) congestion .if, passixe, 570 cyanotic induration of, 572 cysts of, 5!M) degenerations of, 5S4 distomum in, 590 emboli of, .573 fibroma of, .589 focal necrosis of, 573 giri-drinker's, .575 Gli^sson's capsule of, inflammation of, •)H1 liemangio-cndothelioma of, 589 hemofuchsin in, .586 hemorrhage of, .573 hemosiderin in, .586 hobnail, 575 hy.'i'oscrositis of, .581 hy, -eniia of, 570 liyiHi-ncphroma of, ,589 \\\ pcrtrophy of, .589 ic ng, .581 in icterus, .586 infarct of, 572 infiltrations of, .584 infianunation of, 57;!, 575 lacing-lobe in. .584 Liebernieister's grooxes of, 570, 584 in malaria, 586 mesothelioma of, 589 necrosis of, .586 nutmeg, .572 (edema of, 57.'} pigmental infiltr.ition of, ,585 poisi IIS acting on. «.'! pres.sure groo\es in, .584 regeneration of, 190. 1!!6, .589 s;i' unia of, .589 sii.ipe of. variations in. 570 syphilis of, 3a2 Liver, syphilis of, hepar lobatum in, 583 syphilomas of, ,582 thrombosis of, 573 tuberculomas of, .382 tuberculosis of, miliary, .581 tumors of, 589 Mvidity, (MM) I-obar pneumonia, 4.52, 4,53 Localized infection, 145 Locomotor ataxia, 500 Ixtoped imbilical cord, (565 Ludwig's angina, .528 Lungs, 447 abnormalities of, 447 actinomycosis of, 465 adenoma of, 465 apneumatosis of, 449 aspergillus of, 465 atelectasis of, 449 brown induration of, 448 carcinoma of, 465 carnified, 450 chondroma of, 465 chorio-epilhelioma of, 466 cladothrix of, 465 cyanotic induration of, 448 disea.se of, due to disturbance of respiratory function, 449 distomum Westermanii of, 465 echinococcus of, 465 embolism in, 449 emphysema of, 4.50 endothelioma of, 465 fibroma of, 465 fibrosis of, interstitial, 465 glanders of, 465 gummas of, 465 hemorrhage into, 448 hyperemia of, 447 hyphomycctes of, 465 hypostatic congestion of, 447 infarct in, 448 inflammation of, 4.50 infrequent infections of, 465 lipoma of, 465 lymphosarcoma of, 465 (edema of, 447 osteoma of, 465 sarcoma of, 465 streptothrix of, 465 strongylus of, 465 syphilis of, 464 teratoma of, 465 tuberculosis of, 4.59 tumors of, 465 Lupus, 699, 701 of vulva, t)4I I-uxation of penis, {i33 Lymph cysts, 292 of peritoneum, .568 nodes, 411 abnormalities of, 411 .tnthnicntic, 412 atrophy of, 413 ^^i-*i TM\ ISDEX 13 Lyiiipli rioilfs, calcilicMliiiii "i. \\.\ .liUctH'ialiiiii III'. ll:i ClillKllisIM lit, IIJ ('iiiliitlii'iioiiia lit. II I cMliaiirr (if li.arli-lia ami. ^7. !tl I)V|icr('tnia of, U'J infill lal ions of, li:! itillaiiiiiialioii of, 11'.' iicirosis of, li;{ irilcina of, 112 .svpliilis of. U'J lliliiiiiltosis of, II'J tuliiiriilosis of, II'J tumors of, 41 1 \ ariccs of, 41 '2 strcaiii, iM<'la>iasis and. 217 l.vniptiaili'iiitis, 412 I,yirililian(jit'<'l;isis, 2SII. 2M, Mu, 411 of ailrctials, 42:} of skin, "(Mi l-yinpiiantiio-i'iidotliclioiMa, 277, 2N2 of |)ia-.iracliiioiil, -VHi of skin, 7()() LynipliauKionia, 2S() cavcrnosuni, 2M of inti'stincs, .ICKI of larynx, 44:i of skin, 7(H) LvinphanKiosarcoiiia, 414 l.ynipli.itic li'iikcniia, 24(1. :i(i."), 41 I obstnirl'ion, n'llfnia from, iid'.l svsU'in, ;{()l'> vcssi'ls, :!71, 41(1 abnormalities of, 410 inllamiiiatioTi of, 41 1 tumors of, 41 1 l.ympliatisni, 472 I.vmpluM H's in iiifiammatioii, 12S, iiti^J Lymplioix tlii'mia, 240 Lymphocytosis, ;!(>4 I.vmpliojirnic imcumonia. 4.")t tuhcrculosis, 404 Lvmplioiil tissue, ri'tii'iiiratioii of, lOli l.ymplioma. 2:iS, 210 l,ymi)liomatoiii conditions alTcctiim the spleen, 241 Lyinphomatosis, 2oN Lymphorrhatria, 111 I,ymphorrh(ea. 2M l.ymphosarcoiTia, 240, 111 of intestines, .">()l of luntis, 4(>.') of >!iediastinuni, 472 of pericardiimi, ^JS") of mouth. o'JC) of thymus, 472 I.vmpliosarcomatosis, 211. 414 r.ysis, llCi, 14't M M.aeroi iphaly Macrocheilia, 4S.-) :i()7, 411 .Macrodactviv, 01 ,Macroi;lo,s..'ia. 01, 2M. :«i7, 411. .VJ:} .\lacropham s. ;io;5 M.idura foot. 702 .Mai lie C'aderas. '.Ci lie coil, 0."> Malacia, myeloplaslic, 07'.» M. liana, anOpheles ?• •)s(|uilo and, !)7 parasite of, '.t7 types of. 07 .Male sexual orjians. (WO Malformations, local, 71 rect.al, 74 .MaliuiiancN'. 2l"> NlaliciKint adenoma of uterus, ti.')l endocarditis, H'.Mi neopla; ms, 214 (Uislule, 700 absence of, 00<> accessory, <)00 adenolihrosarcoina of, 070 adenohj)olil)roma of, t)70 •ailenoma of, i)Ure, ()70 adenomalo.si.s of, 00^ adeuomyxo.sarconia of. (i70 anomalies of. 000 atrophy of, t)t)7 cancer "en cuir:i.s.se can iiioma of. ()7() chondroma of. 072 cystadeiioma papilliform of, cysts of. 000, 070 _ endothelioma of. 072 tibro-adcnonias of, 000, (>70 libroma of. 072 libromatosis of. Ot')N heinorrliatte into, 000 liypopiasia of, 000 _ inliammation of_. 007 melanoma of. t>72 o.'-teoma of, t>72 peril lieliona of, t)72 sarcoma of, 072 secretions of, KK} syphilis of, ()07 transiilanlalion "'•_-"" luberiulosis of, (>(>7 tumors of, OON vicarious menstruation in, d Marantic thrombosis of dura mater, ".Masked" iron, 27 ".Mast cells." i:«, :50:i Mastitis, 007 chronic cystic. 070 phlejjnionosa. 007 retention. 0(')7 Mastoiditis, .'dit of, 07(1 /.v/>a;.v fif (lisi'iisc, .V.I illiforni "*' Mf.i.sK's, iirKaiiisiii of, it.! skill in, t)!H), (i'.»7 Meckel's (li\erliciiliiiii, "i ' 1 .NIi'iliMi: i-left pMlale, 71 Mediasliiiiii-.. 170 Mediaslinopeiii'anlili-, imliirai ive. :!n4 ,\le(liastinuiTi. 17(1 deriiKiiil cvsls nf. 171 iiiflaiiiiiialioii of. 470 lyiiipliDsareoina of 472 sareoin.a of. 47'J teratomas of. 471 limuirs of, 471 Medullary eareiiioina, 2()(i. '27',i of Miaiiiiiiary kI.iikI, I>72 of sloinaeli, .">:{',• MeKiieoloii. .'i44, "itVi Mesalol)lasts, 3.")il Megaloeyles, ;{.")!( MeKiistoiiia, iM> Milaniii. :{4 Melaiioina, 2s;{ of niairitnary uland, (>72 of skill, 70t) Melanosis, H24 Melanotic piiiinentation, '.i'2i sarcoma of choroid, 51;") of liver, 5S*t of vulva, t)42 Melena, :C)4 Meinhrane, i:{4 diplitlierilic, 4;{S Meiiilir.'inous colitis, iiriS enteritis, ,'>4'.» (jastritis, .53.") larynjjitis, 441 pliarvnaitis, -i'.is Mc'ndel's'hiw, 4S M' 'linsies, cranial ami ■iKisinus, 4.*<.S icilis, .*)04 ..iidocele, I'M If inco-encephalilis, .")0,") li norrliaina. 3.")4, ()4t> filndid nf uterus and, 242 Mi'MNtrnation. vicarious, in liland. tititi Mcseii'liyinatous tissues, 22<'> ''li'seiicliyme. 22.") ilesaorlitis, syphilitic, 40S lesohlast, 22{ Mcsohlaslic metaplasia, 2!14 Uixnlidymiis, tiS >lt•^(lthelial neoplasms, 22."), 22(i li'sollielioin.as, 274. 277 of liver. .")S(1 of testes, (V^il iesothelium, 22.") I'taholie inloxi, atioiis, SO iitaholisin, faulty, t'out and, 107 impaired, as u cause of dise.aue, 107 part playeil hy nucleus in, 22 I'taholitci, l{;i '< laiiiorphosis, reveinioiiuiy, 2".l'.l 47 spinal, ")01 m.immavv .Metaplia.s<' of mitosis. 40 Nlelaiilusia, 202 (list inci ion of, from anaplasia, 20;{ epillielial, 204 of joints, ti'.t.") me.sohlastic, 204 o.s.-eous, 20,"). 2(!»'> .Metaplastic ossification. 2'Mi Metiislases of helMKii tiiiiiors. 220 liy lilooil slre.'iiii, 21N in hones, ti.V.I ill infection, H.") by lyiniih stream. 217 of neoplasms, 217 patency of, 221 retrourade, 21!> sarcoma and, 2.")0 tissue of predilection for, 221) hy transplantation, 21.S Mctitstasis, 21.") by apposition, 210 Metastatic abscess of brain, 4SS pneumonia, 4.")2, 4")7 Metazoa a.s cau.ses of disease, ilS excretion of toxins by, !•!> Meta/.oan parasites, !'.H Nlethemot'lohiniiria, 322 Methvlamin, 110 Metritis. t)47, t)4!», <)t)3 Metrorrhania, 3")4. (147 fibroid of uIi' |>r.)tfiii. 2t M.iUiis.^iiiii c.jiit.'iu "-I"". -•"''*• "*'•' lilii'.isiiiii, 247 M.iiickclxTji's .icl.TDfis, 4(14 M.)iiii.^hi)ri:il twins, <>2 Niiiliir I'irrliosis of Iimt, .JSO .\I.>iioini.^l.';ir liyiilini- .■.■Un, i:i2 Nloii.>.>t>li:il iwiiiH, t')2 Mori.)rflii.li>iii, ti;{7 M.diosyiiiiiictri.^al jiini.cps. <»S Monsters. .l.)iil)l<>, t>4 iil>ic.)p.)liir fusion in, tW, •>'•' pnrasitic, 'ilt M.mstriisitics, (H ^I.lrl>^ls cu'riilciis, .'isti Mortjauni, liv.iati.l of. 2X'.t Mortilication, ;{2S, :{4;{, :i4t> .Morula. 22:5 .Motility of kiilncy. ti"^ M.)tor sy.stcni, t)7;{ Mottlcrki.lncv. larn.', (112 MoiiMs, '.i2 .Moiitli, .522 abiiornialitii's of, .")22 actin.>inyc.)sis of, .")2") anemia of, 't2'-i an){i<»"!i <'f- •"'-'' chan.Te of, "»24 ^ (■lion.lr.nna .if, •")2('> epith.'lioma of, i>2.") filiroina of, .")2."), .")2(> mnninas of, .")2."> liyp.Teniia .)f, ")2;{ iiiflaniniation of. -t-'-i leprous n.xliil.^s of. .")2.") lip.)iiia of, .")2."). .j2t) _ lytnpho.sarconia of. ')2ii mucous pla.pK^s in, ")24 tnyel.ima of, )jiant-fpll.'.l, ")2.") myxoma .if, ")2.') poisons acting on, N2 syphilis of, .V24 teratoma of. .")2.'), ")2(> t uh.^rculosis of, .">2.") tumors nf. .j2.") Mucin, 2.'). :i4 formation. ;i(>7 Mucino(jen. ^54 .Nlucoid (l.'Uen.Tati.in, :{()(', •'507 ilep.>sils. :j()7 polyps in .r ■.>pha(jus. 'tM Mui'opuruli-ni iflammati.tn, i:{4 Mucous c.ilit . o.W cvsts, 2!)() mcmbr.an.', retii-nerali.)i. of, lit.) transplantation of, 201 Iila.pKW, ')'2\, 701 surfiicc, intlatnmation .)f, IIW Mucous, bactericidal iM)\ver of, S(> .Mulberry .'alculi. HIS Multilobular iiv.'r. .■>7(> Multil.HMilar cvsts .)f liver. .V.M) Multili" ulur cvsts of ovary, t>.')t» Mullipl.' births, «4 neurofibroma, 'M) s.'liTosis, 4 aiiemiii <>fi 073 ani^i.onii .if, 07*> atrophy .if, 07.") .•loii.h swelling of, (i7") contt .1 lions .if, 4S1 .•ysticcrcus of, t)7.") .lefect of, (i73 (leueneration of. 07.5 e.'hin.ic.iccus of. 07.") fibrillary twitchini; of. 4S4 tibromii of, 070_ (tlan.lers .if, ti7") guimiiii of, 07.5 _ hematoma ii. (i74 lietii.irrhane .if, 074 hyperemia of, ()73_ hy[i<"rtrophy of, 07(i infarct of, 074 inflammati.m of, 074 myxoma of, 070 |iara.site.s I'f, 075 pete.'hiir .>., 074 reiluplication .if, 073 r.'ti.-nerati.in of, I'.H), l'.'0_ rhab.l.imyosarc.ima of, 070 sarcoma .if, 070 spinill.-is, ()73 sypliilih "f. 075 t'oiULs of, 4S1 trichinia-sis of. 074 tubercul.isis <■> mechanism of respirati.jn, 42it system, poisons acfing on, SI Mutation, .50 Mvcosis of auditory m.'atu.s, olS funRoides of skiti, 700 Mvootic nneurvsm, 40S Myelitis, 405, 49S, MM) Nlvelocystocele, 494 Myolocytps, origin .if leukocytes tnni 194 Myelopenotis leukemia, 238, 365 .Myelomas, 2.30 giant -ccllwl, 237 of bones, 089 of mouth. 525 multiplex, 237, 239, 420 IShEX 7:}n Myt'lotims, multiplex, ol Imiif nuirrou, 12(1 of boiu's, (iS!) Myclonmtoid, ZiH MyeloinutoNis, '2'.i7, l'_'(t Mycloiiiciiitifiocolc, 4!ll Myolojiiiintic tiiuluciii, 07!) Mviaws, 702 Myocunlilis, ;iH8 u(;iit<>, liHH intcrHtitml, .'{S" Myocaniiuin, 3,S"> uhnnriniiiilicN of, 3.S."> lUrophy of, '.isa culcificut ion of, ;{<.U cloudy KwclliiiK of, '"IMS (k'Rrnoral ion of, 3M». .'{!)(' dilatation of, .VXi diMpluccnii'nts of, ;{,H,'> dupliration of, 3K.j ectopia of, ;W5 Hbrunia of, ',HY,i fibrosis ol, ;JS7, aiH fraKinentation of, 'Ml KUinnia of, 38X hyaline rlianne in, .'Wl hypertrophy of, liS'i, ;{!»! hy|M)plasia "of, 38.i infiltration of, 388 inflammation of, 388 lipoma of, 3S>3 malnutrition of, .■J87 myxoma of, 393 sarcoma of, 3!)3 segmentation of, 3i)l syi)hiloma of, 388 transposition of, 385 ti'berculosis of, 388 tumors of, 3'.»3 Myofibroma of ovary, (>.V.) Mvoma, 241 of bladrler, (>27 of Fallopian tubes, t)54 of intestines, .")C() of kidney, ti21 of U'sophagus, .")31 of orbit, .">I7 of skin, 7(),") of stomach, 53!) of uterine ligaments, H)>2 of uttTUs, 241-243, ti'M of vulva, 642 Myomalacia, 387 Myomatosis with "'anduhir inclusion in uterus, 651 Myopathy, 675 Myositis,"674 ossificans, 206, 674 j suppurative, 674 ! Myotomes, 225 Myringitis, 518 Myxochondroma of bones, 68i» ' '•lyxiLdeiuH, liK) hypertrophy and, 189 Myxa-dema, thyroid extract and Myxo-enchondroma, 235 Myxoli|Kima. 232 Myxoma, 232 of iHjnc marrow, 12(1 of Injnes, tiS!t of brain, I'.tl of bronchi, 4 !»'• of bursa', 67'> of lornea, 515 of kidney, (121 of larynx, 443 of mouth, 525 of muscles, 676 of myocardium, 3!t3 of skin, 705 of imibilical cord, <>(i5 Myxomyoma of uterus, 650 Myxosarcoma, 25C of bones, 689 of peripheral nerves, 509 N.nvi, 705 blue, 278 piismented, 7((3 of skin, 705 telaiiKiectatic, 278 of vulva, tm Xails, 708 abnormalities of, 708 favus of, 708 hemorrhuKcs of, 708 inflammation of, 708 ingrowing, 708 leukopathia of, 708 ririKworm of, 708 Nasal [Kilyps, 436 Nasopharynx, 428 Necrobiosis, 326 Necrosis, 32(). 328 of adrenals, 422 of bone, 681 coagulation, 328, 344 colliquative, 328 focal, ,328 of individual cells, 328 of liver, 573, 586 of lympii nodes, 413 of pancreas, 595, 597 of peritoneum, 567 putrefactive, 328 of skin, 7(H). 703 in typhoid fever, 5.50 Necrotic cysts, 287, 294 of brain, 492 inflammation, 134 ulcer of intestines, ." 18 Needles in peritoneum, ,")66 Nemathelminthes. 98 Neoplasia, 207 Neoplasms, 206 101 740 N( >|iliisiiirt of iiilrciiiilK. 27."), I-J aiiaplit'iiii ill, -^■> .'iiiciiiiii from, 2Hl of iirtcricH, 4(»'.t iitypiciil, -H uuioiioniou.f, '-07 Ix-nittii, 214 of bile «lu.ls, ■>7 blootl viLsculiir, ii^ of bone marrow, -Mli, 4-11 of hones, tiSS of l)rain, 4'.ll of brfiiHt, »M>S of hrotifhi. 44(V of bursa', t'wH of oapillarios, 410 of rarotiil uluml, '2s:t ci'Usof, ili'strui'tion (.1 J>>( imx'ulatioii ai.tU -^7 radium and, ■-X7 _ si'lonium and, '-K7_ tpilurium aIld,JJ^7 j-niys iind, 2S7 of choroid, TdS of conjunctiva, '.ii> of cord, .50} of cornea, ."tl.'i dcttcncralivc changes in, 222 distinction of, from cysts, JN< of doubtful relationship, 2M of dura ni:itcr, ."itW of car, .520 embrvonic, 22'> endothelial, 220 epiblaslic, 22.5, 22C. of eve, .51.5 of l'ai.,.iiian tubes, (j.>4 of trall-bla.ldc r, .5(12 -duct. r)<»2 healinu of. 223 of lieart, 'Mi livlic, 22.5, 220 atvpieal, 2.iO typical, 22S hvi>ol)laslie, 225,24(1 ii'iflamniatory, 207 internal secretion of, 200 of intestines, ■5(>0 of iris, r)I5 of joiiiis, ''15 of kidney, 27;5, 021 of larynx, 44:i lepidic, 220, 25< atypical, 2M typieal, 257 of liver, .5S<) of lunKs, 4t)5 of lvnii)h nodes, 414 of lymphatic vessels, 411 iiiaiiijnant, 214 ,,;■ ;,i,i,„iiiary ;r!and. '>•'>> of iiiediasi ilium. 171 inesenchymatous,l22t) IS 1)1-: X Xeoplusms, inesolhi'lial, 22.5, 220 metastasi's of, 215 mixed, 210 of mouth, .525 multicenlricjJl'.) of muscles, 070 of myocanliuni, IJICI of nerves, 5t''J of nose, 4:50 . , , , nuclear cnannes m. -'-'- of (isophauus, .>ll of orbit, 517 of ovary, 27.5, (mO of paiicreiis, .5(17 of iM'lvic structures, tm2 of iM'iiis, iVM of iK-ricardium, ;f>j.5 of jM-ritoneum, 507 of piu-arachnoicl, 5(M» of placenla.JHH of pleura, 470 of prostate, tWiO of puerperal uterus, IM)3 of retina, 515 ret roRression of, 223 of salivary (jlands, 52S secondary, 215 of spinal' rord, 4(10, 4'.>(S, 4!«>, .500 of siileen, 4\X of stomach, •53.S stroma in, 221 of teeth, .527 of tendons, t)77 terminology of, 207 of testis, 275, 030 theory of, 2N5 of thyroid itl'V'id, 42;) inin.sitional, 220 of tunica vaiiinuhs testis, t>i/ typical, 214 . undilTercntiation in, 2N> uniceiitric. 2 lit of ureters, 024 of urethra, ti2(t , urouenital ilucis, 2 Nephritis, fJ00,,tiOO , cryoscopy in. '>0<) hemorrhagic, 012 ^ interstitial, acute, 010 chronic, 60ti, 014-01t> parenchymatous, acute, 001), Oil i chronic, 612 ' scarlatinal, 616 _ suppurative, t)17 Nei)hrolithia.«is, 023 Nephrolysin, lt)3 Nerve-cell body, 473 patholottica! chaiiKCs in, 4. IXDKX 741 .NPrve-ri'll, falmucof 111 rfKi'Mcnitioii rif, lit.s NVrvf tiicclmni.Miii nI hear', .'<77 tixNiif, nulolysiN of, cliolin anil, UNI ri-KCMcr.'ttion of. 1!W Ncrvi'H, tiiDtcir, '(K'hI syinptoiiiM in, 4S2 ill I 'ii|ilitMiriM, 221 IHTiphonil, 'M7 n-Kcnoriition of, after .ffction, I'.Kt NfTvoiiH raiiNCH of inllaiiitiiutiun, 122 (liathcHiM, .").H iiirrhaniMiii of rt-apiration, 420 system, 473 afferent, 474 aiitonor.'iie, 475 efferent, 47.") foeal ehaiiKes in results of, 4S2 neneral ilistiirl>aiires of, 47') local I'lianKes in, results of, 482 |H>isoiis aclinic on, .SO pyrexia un«' 1 ")2 syinpathcl! , 7.'> tetanus tovi, ami, 1")7 N'eiirin, 1 1(» Neiiriiionia, 247, 24s of stonm<^h, .Vi'.) .\eiirinonmt(»sis, 247, riOll, 7i>1 Neuritis, .t()7 alcoholic, M)', ,")(I,S arsenic, M)S l«'a.l, .")()8 optic, .t07, .")17 toxic forms of, ,'>()S N'eiirobliwtomas, 244 Neuriicvtoma, 244, 24.'>, J22 Xeurofihronias, multiple, 'Mt N'eurotihroniatosis, 2.{() Neuroglia, reiteneratiiin of, I!IS Neuromas, 244 of adrenals, 422 amputation, lltK, 24.5, .'iOfl 'false." .■>()!» of optic nerve, .517 Neurone, 20, 473 connections between, 113, 11 i correlation of, 474 uroups of, 474 lesions of, 478 depressive manifestations of, 484 irritative manifestations of, 484 upper motor, diseases of, 408 Neuroparalytic hynereniia, 338 Neuropathic atrophy of joints, 694 of muscles, 675 (edema, 370 Neuroses, predispasition toward, 115 Xi'uroretinitis, albuminuric, 513 gravidic, 514 Xciirotonic anemia, 3.'?9 liypeiemia, 338 Neutrophile leukocytes, 362 New growths, 214 .N'ko'ih, '.15 Nipple, curcinonin of, l 7..' Nissl ImmHcs, lit, 473 xM'turnal enuresis, tM)5 NikIc, aiiriciiloventriciilar, .377 sino-auricular, 377 \(Ml(»se arterioHclerosis, 402 Nodule. 138 .Noma, .524 Non-parasitic intoxications, 7(1, 80 Non-protein constituents of cell, 31 .Non-s|M"'ific immunity, 1.52 Non-\ii ular area, ' inHummation of, 1.34 Norii, ii Iierilance, 51 y m, 164 .Nori. .(lasts, .3,59 Nose, 434 adenoma of, 436 anomalies of, 434 carcinoma of, 436 catarrh of, 435 endothelioma of, 436 fibroma of, 4.'«> glanders of, 436 hemorrhag*' "f. 4.34 hyperemiii . 434 infjammali.iii of, 435 leprosy of, 436 polviis of, 436 "saddle-back," 685 sarcoma of, 436 syphilis of, 436 tuberculosis of, 436 tumors of, 436 Nuck, Ci.nal of, cy.tts of, 2!)1 Nuclear changes in neoplasms. 222 fluid. 18 Nuclc-UM', lOH Nucleic acid, : Nuck In 25, 2'. bjses, -.5 ' ■nviition of purin buses from, 107 Nuc'i inic acid. 27 Nuv'W I ;: 18 NlK:le.^^ 18 alterations in, 23 chemisi ly of, 27 chromidia of, 22 composition of, 27 cytoplasm and, interaction between, 20, 21 interrelation bctveen, 21 liisintegration of, 23 dominance of, 20, 21 granules of, 22 histology of, 18 importance of, 20 karyolysis and karyorrliexis, 23 "inaskel)literati()n of nail ihiet, ")01 Ob.strucfion to air in nvpiration, 431 of ureters, (i23 Obstruetive cirriiosis of Hver, ."it eon.stipation, .">42 jaundiee, 10."), ;i2:{ telansieetasis, 2~.S Obturator iiernia, M'y'J Oe<'hisi()ii of arteries, 340 of bronelii, 440 of (esopliaftus, .")2!( Oeeuit heinorrhatje of intestines, ."(47 Oeiu'onosis of joi Is. 04 pulmotiary, 307 of scrotum. 040 of ski'i, OOO of tonsils, 4:{7 toxic, 370 types of. 30(» of vulva, 041 (Ks )ph;ij;itis, ."(31 (Ksophairus. .VJ!) carcinoma of, .")31 iliphtheri.a of, 531 diverticula of, ."(30 duplication of, ")2!( epithelioma of, .")31 hemorrhage into, ."(31 infljimmatioti <(f. .531 leuk((plakia of, ."(31 lip((inas of. ."(31 malf((rm.'itioiis of. .")2!l mucoid poly|>.- In, ."i.'il (KsophaRiis, iTiyonias ((f, ."(31 occlusion of, ."(2!( I)erforatioii of, .").30 rupture of, ,")30 stenosis of, .")2!> .syphilis <(f, ."(31 tuberculosis of, ,"(31 Old age, ."(.") Oleiii, .33 OliKemia, 3.3.') < )li)iolivdrainiii((, 00."( Oliuuria, 002 Onychia, 70,S ( )nyelioKryphosis, 70S ;)ocyfe, primary, 40 Oiipliorilis, ((."(."( Opacity of lens, .")()!», ."d" Ophthalmia, )!onorrh(e;ii. 01 sympathetic, ")12 Opsonic index, Itid Op.sonins, lOS phagocytosis and, KiS Optic disk, (tipped, ,"(lli nerve, ")17 neuritis, .")07, .")I7 Orbit, .")17 absces.s of, 517 angioma of, .")17 carcinoma ((f, "(17 eelluliti.s of, 517 hjcroma of, 517 inflammation of, 517 myoma of, 517 osteoma of, 517 sarcoma of, 517 teratoma of, 517 Orchitis, .".2S, 03.S ( )r(janisiii, normal defences of, ,S0 Orgaiis, defects in, 70 Osmosis, 32 hyperisotonic solutions and, 33 hypi.sotonic solutions and, 33 Osseous metaplasia, 2(15, 200 Ossification, metaplastic, 231) OssifviiiK ecchondroses of bones, 0,S!( Osteitis, 6.S0 eon72 of orbit, 517 IXDEX 743 Osteoma of pleura. 470 of skin, 70") Osteoiiiiilacia, 4 lit, t>S.'> O.steoniiitoid, 2;{(i Osteomyelitis, GSO, G,si chronie, (182 fibrosa, (iSti tufxTculosis ami, tlS.'{ Osteoporosis of hones, (iK2, (iS") < )ste()psathyrosis, 67!t Osttv)sarc()ma, 2.")t), CSO Otitis media, .jlX ,")20 acute, oIO hemorrhagic, 'AH suppurative, .jiit sclerosing, ,")2() Otosclerosis, .VJO "Ovarian dermoid, " 200 teratoma, 200 < )vario(!ele, 042 Ovary, t),")4 abnormalities of, ^t,"> a<'cessory, 0."),') adenofibronia of, (mO atrophy of, O.'iO carcinoma of, OoO cystadenoma of, (i.")(i cystom.a of, 0,jO (•ysts of, (i.")f) deReneration of, cystic, tJoti diseases relat(>d to secretion of. 1(>2 elastoid chaiiRes in, (•")() endothelioma of, (i.10, VM) fibroma of, C.")0 hyaline changes in, ((."lO hypoplasia of, 0.').") inflammation of, 0.").5 myofibroma of, <).")0 perithelioma of, tioO psammocarcinoma of. (\'i>.) regeneration of. 100 sjircoma of, (1.50 .secretions of, 102 syphilis of, O")") teratoma of, 000 fr.insplantation of, 2(K) I iherculosis of, 0.");") tumors of, 275, ().J0 connective tissue, 0.")0 Overgrowth, 1,S6. .SV. also Hypertrophy, conipen.satorv, IS.S irritative, l.S.H simulatinl, l.Sit vicarious, ISX Overnutrition, fatty infiltration ilue to ;«« Overstrain, 111 distinction of. from overstress, 1 12 muscular fatigue and. 1 13 Overstress, 112 a cause of disea.se. 112 Overwork, atrophy from, 207 Oviil.a N'abothi. 2<'«). (i4.S Ovum, "blighted," .")K Ovum. niaturati(m of. 40 polar bodies of, 41) Oxidiise, 107 <^>xidation, diminished, .UKi Ozen.H, 4;i.i I'.*<'J1VI)KI(MAT()CEI,K, .')00 P.acliy<|ermia, 312, 411 laryngis verrucosa, 442 I'achymeningitis, .^02 I'aget's di.seii.se of bone. O.Sli of nipple. 072 Pain. 179 collapse and, 17.S distribution of, segiricntal, 1.S2 localization of, I,s.'{, 1,S4 referred, IHI shock and, 17.S I'almitin, Xi Pal.sies, birth. 01 I'ancreas, .VXi abnormalities of. .'><.H absence of, ,")04 a<'ini of, accessory, .")!I4 adenomas of, ."i!(7 amyloid of, .")!)7 carcinoma of, .'i<)7 cystadenoma of, .")07 cysts of, .■.<».S duplication of, .504 fat necrosis of, oOo. ")07 fatty degeneration of, .")07 infiltration of. ."i07 glycosuria and. .")04 granulomas of. .50.5 hemorrhage of, .")0.i hyperemia of, .")0.5 hypoplasia of, .504 inflamrnation of, .50,5 internal secretion of, IO;i passive congestion of. 50.5 regeneration of. 100 sarcoma of, .50S -self-digestion of. .500 tuberculosis of, .50,5 tumors of. .507 I'ancreatic i'oncremcnts, ,jl.5 Pancreatitis, centrilobular, .505 chroi.i<-, ,505 hemorrhagic, acute. 505 perilobular. .505 purulent, .595 sporadic, 595 I'annus, 511 Panophthahnilis, 512 Panoslitis, tJ8<), (WI P.apillary cystom.a i>f ovary, (i5.S Papilloma, 257 of bladder, 201, Ii27 bla.stomatous, 2(i() of conjunctiva, 515 l^ll It' w ii i 111 f:l 7(!1 1711 744 Papilloma of coriira, .")l"i of Kallopiati lulic-i. Cm I of illlCslilH'-'. .")<>•) iiitracvstic, '2t)l of iriitalivf orisi". -•">" of laiviix, 4li{ soft, 2(i() of un'tcrs, 1)24 Papular svpliiliiU' of skin Paralvsis;47!) liiilhar, 4>.MI hysterical, 4S:{ lesions of neiiroiu's aiK Parametritis, (147, (Mil Parametrium. (Mil I'arapliimosis, t);i() I'arap'asm, lU I'araplejlia, coiiKeiiital spastir, 4!!S I'arasitcs in bladder, ti'Jti "cancer," I'.l of malaria. !>7 tnelazoan, as causes of disease of muscles, (17.") of pleura'. 47(' "sarcoma, ' 12."il of skin, 7i'2 of lueteis, 1)24 of uterus, t)4'.( I'arasilie causes of disc; cysts. 2SS. 2i).'i of ixuK's. ('('.k; of t)iain. 4". 12 of liver, .")'.(() of perilondim, embolus, ■ii)'.i intoxications, 7!> monsters, t)i( " Paraspecific" (pialitie.- l.XDEX •IS SI .".lis inlieritanee ;ind, PeptoiK Patent ductus Molalli. :{SIJ Pallio)jenie bacteria, s."i I'alholojjical slates, iidierited, ati Pcliculosis, 702 I'dlajira, .")1U I'elvic mass, inflammatory, lilU peritonitis, productive, (i()2 structures, (Mil Pemplii(£us, Oils Penis i).U) absent, (>;}(1 anomalit'.s of, liifll (■.•in'inoma of, ti-W chancroid of. O-il cy.sts of, (>l{3 dermatitis of, <»'{<• (hmble, (>:il) elephantiasis of, 0;i2 enilotlielioma of. (i^W (ibroma of, iY.i'.i fracture of, (i.'W hyi)opl;'stic, ti^iO intiammation of, iVM) injuries of, OIW keratosis Paiasyphilitic lesions. .")7 Paraluberculous lesions. .")7 Parathyroids, 42t> adenom.'i of, 420 diseases related to. 101 liypi'rplasia of. 420 se<'retion of. 11)1 Parenchymatous tioilre. iO in otitis medi;i. .")Mt of stomach. .V17 in typhoid fever. ">.>{ of uterus, ()40 I'crforative appendicitis, ')'>' Pernicious anemia. :iOO Periarteritis, chronic. 400 of luntj, 40.") PeribroiKhitis. 40.") Pericanalicular libro-adenoin.i mary gland. 070 I'ericarditis, 3S2 aS") (!cliino('(M'cus of, '.i:->' iiiHaniiiK tioii of, ;{>12 lyinphosan^oin.'i of, ;{S.') new n;ro\\ i lis of, ;W.") petechial .spots on, •'isl IVricliolwyslitis, punileiii. .")!t2 rcrichoiulritis, .")IS I'ericlionilriiiin, transplantation of, 2(11 Perilobular pancreatitis, .V.I") I'erilvinpliadunitis, 412 I'eriiiietri-.'s. ()47, ti4;}" Periosteal reneiieration of bone. ]'Xi Periostitis, (iS(» albuinino.sa, (M2 of ear, .")1.S ossificans, ()S2 suppurative, tiSl P<'riosteuin, traiis|)lantation of. 2ill Peripheral nerves, 5(17 defeneration of, .V'S fibromatosis of, .")()!( gliomas of, ."iO!t infective Kratmlomas of, ,")()s inflammation of, .')()7 lead poisoning and, oOs leprosy of, .")(IS lipomas of, .5()!( myxo.sarcomas of, ;"()!> neuroma of, oOil regeneration of, lO.S rhabdomyoma of, .'(Ht .syj)hilis of, .")().S tuberculosis of, otJ.S Perithelioma, 2S2 of manmiary gland, 072 of ovary, ().")!1 of salivary glands. .Vi.S Perilotieum, otil abnormal contents in, otMi abnormalities of, ")ti2 actinomycosis of. ,")(>(> anemia of, ")t)2 angioma of. ot)7 bile iti, ")(>() cystadenoma of, i"ti7 cysts of, ■")t)7 embolism of, odlJ endothelioma of. •'J<>7 fibroma of, .")()7 gallstones in, .")()(> hemorrhages of. .")('>2 hyperemia of, "i()2 inflammation of. .ViU lipochondroma of, .")(i7 lipoma of, .")()7 necrn^clN: (if, !\iu iiecdlcs in. ."itKi Peritoneum, i)a.ssive congestion of, .")(i7 sarcoma of, .")(>7 sponges in. 'Mi syphilis of, .5()0 teratoma of, .")tJ7 thrombosis of, .5(1;! tuberculosis of, ."id,") sicca of, ,")t)0 tumors of, o(J7 worms in, 500 Peritonitis, .")03 chronic, iili'i hemorrhagic, .">0:{ hyalo.serositis in, oOo local circutnscribed, ^AXi diffuse, .'503 productive i)elvic, 002 purulent, .")0;{ serofibrinous, 503 serous, 503 imivcrsal, .503 I'eriton.sillar ab.seess, 437 Pernicious anemia. 300 Persistent cloaca, 74 truncus arteriosus, 3,S0 Petechia-, 3.54, 074 I'feiffer's reaction. Kit) Phagedenic ulcers, 700 Phagocytosis, bacteria and, 124 opsoiiin.s and, lOS Pharyngitis, 437 acute catarrhal. 437 atrophic, chronic, 43'( chronic, 43it gramilar, 43!) membranous, 43S phlegmonous, 4.3!S Pharynx, 42S, 43t) abnormalities of, 437 hyperemia of, 437 inflanunation of, 437 anlema of, 437 Phimosis, 030 Plilebectasia Kirvnge.i. 441 Phlebecta.sis, 410 Phlebitis, 410 Phleboliths, 315, 351 of ))elvic veins, 001 of prM angioma of, 004 calcification of, OOi cell embolus, 352 chorio-ppithelioma malignum of, {')G-t cysts of, ()04 degeneration of, 664 disciise of effect of, upon f(rtus, 60 entrance of bacteria through, 90 fibroma of, 6t)4 tibromyonia of, 664 fleshy mole of. 211,604 hemorrhage of, (KVt hydatidifnnn mole, 211, 604 hyperemia of, 004 Placenta, infarct of, 664 inflammation of, (>64 (edema of, 6(J4 ! '/nevia, 664 i succenti .ata, (j(>4 I syphilis of, 6(j, (M54 tuberculosis of, 6(54 Plain muscle, regeneration of, IOC) I Plasma, blood, 357 i cells, 132, 3f)3 changes in, 357 Plasmorrhexis, 359 i Plasnioschisis, 359 Plastic cyclitis, 512 pleurisy, 407 Platelets, blood, 360 Platyhelminthes, 98 , Plethora, 335 i hydremi(!, 335 Pleura, 466 angioma of, 470 chondroma of, 470 contents in, -tOO endothelioma of, 470 fibroma of, 470 hemorrhage into, 466 hyperemia of, 466 inftanmiation of, 407 leprosy of, 470 lipoma of, 470 osteoma of, 470 parasites of, 470 sarcoma of, 470 syphilis of, 470 tuberculosis of, 470 tumors of, 470 Pleural cavities, 433 effusion, 434 ' Pleuricentiic blastoma, 219 ' Pleurisy, 407 1 "dry," 468 ! exudative, 467 I fibrinous, 468 hemorrhagic, 4()9 hyaloserositis in, 409 plastic, 407 ' productive, 467, 469 purulent. Sec Empyema. serofibrinous, 468 i with effusion, 4(58 Pleuritis. See Pleurisy Pleurogenetic pneinnonia, 457 Pleuiopneumonia of cattle, organism 93 Pneumonia, 450 aiirogenic, 451 apical, 455 aspiration, 45(5 brown induration in, 458 (central, 455 chronic, 457 congestion in, 452 ' (rrecpiiig, 455 embolic, 457 jBtm^v - 11!^^ INDEX 747 Pneumonia, engorgement in, 452 hematogenic, 451 hepatization in, gray, 454 hypostatic, 452, 457 indurative, secondary, 457 inhalation, 456 lobar, 452, 453 lobular, acute, 455 lymphogenic, 451 metastatic, 452, 457 miliary, 452 pleurogenetic, 457 resolution in, 454 septic, 452 splenization in, 4.')<) terminal, 452 tuberculous, 401 "unresolved," 457 "white," 465 Pneumonic phthisis, acute, 4t).{ Pneumonitis. See Pneuuionia. Pneumonokoniosis, 325, 457, 45h Pneumothorax, 434, 467 Poikilocytes, 359 Poikilothtrmic animals, 148 Poison, 76 acting on blood corpuscles, 81 on digestive .system, 82 on heart, 82 on intestine, 82 on kidneys, 84 on liver, 83 on mouth, ,•52 on muscular system, 81 on nervous system, 80 on organs of circulation, 82 on stomach, 82 on vessels, 82 endogenous, 79 exogenous, 79 Polar bodies, 46 dichotomy, 66 hypogenesis, 70, 71 Poliomyelitis, 495, 499 Polyblast, 133, 191 Polychromatophilia, 359 Polvcythemiu, 358 Polydactyly, 70 Polydactylism, inheritance and, 57 Polyhydramnios, 665 Polymastia, 70, 666 Polymorphonuclear cells, 128 leukocytes, 362 Polymyositis, 674 Polynuclear cells, 128 leukocytes, 362 Polyorchidism, 637 Polyp, aural, 520 I'olypeptids, 26 I'olypi, destructive placental, 212 Polyps of nose, 436 I polythelia, 666 i'lilyuria, 601 Porencephaly, 486, 492, 498 Portal cirrhosis of liv(!r, 575 Post-fibrinous fibrosis, 143 Posthitis, 630 . Post-natal ucquLi-ement of disease, 74 I disca.-":, 55 ! Post-uterine hematoma, 661 Preeipi jns, 161 ; Precipitoids, 162 ; Predilection, tissue of, in metastasis. 220 I Predisposition, 1 ' '> I age and, ll(j habit of life and, 1 16 inherited, 115 malnutrition and, 116 previous infection and, 116 sex and, 1 16 Premature labor, causes of, 60 Preputial concrements, 315 Pressure, atmospheric, as cause of disease, diverticula of u'sopnagus, 5.i(» grooves of liver, 584 "Prezymogens" of cell, 23 Priaiiism, 630 Processus pyramidalis, 423 Procidentia of uterus, 645 Proctitis, 548 Productive pelvic peritonitis, 662 pleurisy, 467, 469 Progressive cataract, 515 muscular atrophy, 499, 675 inheritance, 51 tissue changes, 185 Prolapse of uterus, 645 Pinliferants, cell, 201 Proliferative fibrosis, 142 Prophase of mitosis, 39 Prostate, 633 aberrant, f "3 absence of, 633 amyloid bodies of, 321, 633 anomalies of, 633 atropl.y of, 634 carcmoma of, 636 concret'">s in, 633 corpora amylacia, 633 cysts of, 6.33 degeneration of, 634 foreign bodies in, 633 hyperemia of, 633 hypertrophy of, 634 multiple caseous nodules of, 033 phleboliths in, «»33 sarcoma of, dSQ tuberculosis of, 633 tumors of, 636 unilateral hypoplastic, 033 Prostatic calculi, 321, 633 sand, 321, 633 Prostatitis, 633 Protagon, 27 Proteins, 24 combined, 25 ifi k HI 74S i.\i)i':x f.f [ii. ri- IVntcins, conslitulion of, 24 fiizyiiu's of biictcriii, Kl free, 2") tni)li'('ul<" of, 21 of iiiirlcus, 27 Protozoa as cause of (liscjisc, !W (I'.'vciopiiiftil of toxins in, !W "I'roud flcsii," I2(i Psaiiiinocaicinotiia of ovary, 0.')9 Psaiuinoiiia, 2,S2 bodies, .')(»;{ I'seudoeliylous ascites. ;{"() i'seiulolienuapliroilisinus iiiusciilinils, 74 i'setuioliyiM^rtropliy, isti I'seudoinelaiiosis, 1522 I'seudoniyxoitiM peritoii' •''•">M I'soriasis, ti'.Ht I'terytjiuiii, .")11 I'loiiiaines as cause of disease, I If) development of, bacteria anil, 11(1 Puerperal uterus, (i()2 l»ulinonary (edema, ;i(>7 Pulp tissues, primitive, 220 Pulpitis, .")2() Pulse, veiions. 372 Puncture, 70 Puriii ba.ses, 27, lOS bodies, 107 I'urulent arthritis, 0'.»2 bronciiitis, 444 choroiditis, ,">!;< cvclitis, .")12 encephalitis. Sir i'rain, abscess of. inHammation, i;54 paiicre:itius, .")'.l.") pericanlitis, '.iS'.i pericholecystitis, .")!t2 periorchitis, 0.'17 peritonitis, ;")();{ pleinisy. .See Empyema. teno.synovitis, 070 Purpura, 3.5.5, OiMi Pus, 125 ••lau40 I'yonephrosis. til 7 calculous, 01 S tulx'rculous, t)H' _ Pyopneumothorax, 407 Pvorrluea alveolaris, 301. .527 P\iw;i!piii\, <>53. 054 Pyrexia, 147, 1 4'.t causes of, 151 (Ji iNsv, 437 1{ai'Hi.sciiisis, 4it3 "Huchitic rosary," 0S7 llucliitis, 087 Kar'ial characters, 47 diathesis, ,5N •nheritance, 47 inherited preilisiK)sition, 115 Radiant energy as cause of iii.sea.se, 77 iiadiinn a.s cau.se of di.sease, 'S cells of tumors and, 2S7 "Railway spine," 495 Ramila, ii'JO, 525 Rarefaction of bone.s, 0.S2 Rarefying osteitis, 082 Raynauil's disease, 320, 339 Receptors, 158, 10.5 orders of, Khrlich's, 173 Recessive properties, 4.S Rectocele, 042 Rectovaginal fistula, 043 Recurrent fever, 149 pericarditis, 3S3 splenitis, 417 I{ed atrophy, acute, of liver, -574 bl ot jwripliiTuI iicrvoN, lilS of HobaciHuis glands, IKo of spleen, ISMi of sweat glands, lit") of testis, 1!M> of thynml, liHi Regions, special, defects in, 70 Iteiapse, 146 {{(■lapsing fever, OS Relative innnunily, 1")2 Remittent fever. 149 •nfection, 14b Repair, 122 "Replacement dropisy." ;{71 fibrosis, 142 Reproductive system, (530 Reserve force, .'{7 Resistance, lowered, oO Resolution, complete, in infarction, ;{4") of lung, 4'A Respiration, Cheyne-Slokes, 431 disturbances of, 42'J asphyxia, 430 coughing, 4:iO dyspncra, 430 sneezing, 42!) ipochanism of, 420 Resi)irafory system, 427 tract, entrance of bacteria through, 90 physical hindrance in, to en- trance of bacteria, 87 Retention cysts, 2S7, 288 of liver, 590 of pancreas, .598 of skin, 707 mastitis, 667 of urine, (50.5 Reticulated cnchondronia, 234 Retina, .510 anemia of, olO choked disk in, 510 degeneration of, .514 embolism in, 510 glioma of, 515 hemorrhages in, 510 hy-ijeremia of, 510 inflammation of, 513 thrombosis in, 510 tumors of, 515 Itetinal glioma, 246 Uetinitis, 513 hemorrhagic, 514 pigmentosa, 514 IJetroHexion of uterus, 645 IJetrogrtide metasta.sis. 219 lictrogression of neoplasms, 223 Hi'trogressive inheritance, 51 !!i'!niph:iryngn:il abscess, I3H Uetro-uterine abscess, 661 Ueversibility of enzyme action, 30 1.54, \: 253, 254 537 Reversion, .50 Reversionary jitrophy, 203 inheritance, .50, 51 metamorphosis, 299 Rhabdomyoma, 243 of perii)heral nerves, 509 Rhabdomyo.sarcoma, 257, 676 Rheumatic fever, 692 Rheumatism, 692, 693 Rhinitis, 435 Rhinoliths, 315 Rhinoscleroma of larynx, 443 Rice bodies, 677, (>94 Ricin, imniunitv against, 1.54. 155 Rickets, 687 "Riders' bone," 20t), 236 "Riding" embolus, 351 Rigor mortis, 331, t>73 Ring-worm, 702, 708 Robin, inmnmity again. Rodent ulcer, 264, 707 Itosarv, rachitic, (>87 Roseola, 697 Round-celled sarcoma, ulcer of stomach, .536, worms, 98 Rubor. 125 Rupia of skin, 701 Rupture of heart, 391 of heart valves, 399 of lymphat ic vessels, 4 1 1 of (i'so|)hagus, .530 of urethra, <)29 of uterus, 646 " Rus-sel's bodies, " 267, 312 SArcri.AH aneurysm. 298, 407 bronchiectasis, 446 Sacral teratoma, congenilal, ()5 "Saddle-back" ro.se, 68.", "Sago" spleen, 308, 41S Salivarv concrements, .315 cvsts, 29t) glands, 528 cylindrcmuis of, .528 endotheliomas of, .528 ; infiammatiiin of, 528 I peritheliomas of, 528 I tubcrculf>sis of, 528 tumors of, .528 ' Salpingitis, 653 Salts, simple, of cell, .32 Salvar.san, spirochetes and, 98 i Sand, prost.ntic, 321, 633 Sap, cell, 19 Sapremia. 145 Sapremic intoxication, 145 Saprophyfi ' ^teria, 85 intoxications, 79 Sarcoblitsts, 244, 299 Sarcodiniu!, 93 :»() l.\l)KX SiircDiMa. '2'.i7. 2.">(l iif aiiri'iials, yj'.i of l)lii(l of liroiiclii, I to of hiirsi', ()7.S of coiijuiicliva. 'il.'i of dura iiiattT, "idl of car, .VJl of (jiill-hladcItT, .VC of nall-.liicl. .V.fi (jiant-cclli'il, 2:{7 iiiirriiii'ili.-ilc, 2.')2 of iiilcsiinc.-i, ■)()! of iris, T)!.") of joillls, tilt,') of kidney. -.'lO, (HM of larynx, lit of livi'r, .".sil of luiins, Ki.j of iiiaiiiiiiary filalid, ()72 of iiicdiastiiiiini, 172 of inilsclcs, ()7() of iiiyocariiiuin, .'!'.»:{ of nose, 4:>(') oat-sliapc I'clli'd, 2.") I of orhil, .")17 osteoid, 2.')(i, ()S!t of o\ ary, (')")!• of pancreas. .V.IS "parasites," 2.')l of penis, tili:{ of peritoneum, "itw of pia-araclinoid, .")(KJ of pleura, 470 of prostate, (>.'{•> lounii-ccllpd, 2.')li, 2.')l of skin, 7(H) spindle-celled, 2.")2, 2.">.j of spleen, US of stomach, iSM) of tendons, (>77 of testes, 0;{!» of ureters. (524 of urethra, (t29 of uterine li(£anients, ()(>2 of uterus, (i.")2 of vajiinu, (143 f^arcomatosis of skin, 71K) Scahii's, 702 Scar, 12(> Scarlatinal nephritis, (lit) Scarlet f<'Ver, orttanism of, 'Xi skin in, (')i)7 Schizomycetes. ■SVf liacteria. Sciatic hernia, .">0!) Scirrhous carcinoma, 2(')(>. 27o of mammary ttland, 072 of stomach, 5;}!> Sclerema, 7(14, 70.") Scleroderma, 704 Scleni'dema, 704 SclerosiiiK otitis media, .V20 ScliTosis, 4!I0 of hones, t)S2 comhined, suhacute, .">01 lateral, amvotropliic, 4(t!) family' type of, 4it<.) MiinckeherK's, 4((4 imiltiple, 4',t.S, 4!»0, ^(H), r)01 in spinal cord, 4!Mt Scrofuloderma, 701 Scrotal hernia, oO'.) hydrocele, 2!>1 Scrotum, KM carcinoma of, 040 (■lei)hantiasis of, ()4(( hemorrhaKc "f. MO (I'deina of, 040 Scurvy, infantile, OSS Sehaceous cyst of ( ar, ")21 of skin, 707 (tlaiids, regeneration of, IH.J Sehorrlura, 707 Secretin, 10;{ Secretion.s, internal, as causes of discii 1(N) Secretory cysts, 2SS Kranules, 22 Section, a cuu.se of di.sea.se, 70 Self-ditjestion of ])ancrea.s, ')'.)r> Semilunar valves, accessory, Hita fenestration of, 'A'Xi Senile atrophy, 297 .Sensorv and motor neurones, di.sea "alTect iiifs, .")(K) neurones, disea.ses atTectiiiR, r)(K) Septa, iini)erfect, of heart, ;',S0 Septic infection of umbilical cord, 00' pneumonia. 4r)2 Se(Hiestration cysts, 2!W Se(|uestrum of hone, tiXO Serofibrinous arthritis, tiitl inflammation, 134 jM'ricarditis, ;W2, liSH l)eritonitis, 'iKi pleuri.sy, 40S Seropurulent inflammation, 1IJ4 Serous arthritis, Odl atrophy, 29S. :}(«>, 41!) cavities, accumulation in, ,'507 leptomeninpitis, .")04 membrane, transi)laiitatioii of, 2( pericardit is, :5S;{ l)eritonitis, .503 Serpiginous ulcer of cornea, 512 Serum albtimiii, 2.5 ■•death," 170 globulin, 2.5 I inunune, 1(>4 inactivated, 104 "sickness," 117, 170 Sessile hydatid, 2S<1 Su.Kual orean.s, i-.ialc, 030 fenudo, 040 Shock, 17S LSDKX 751 jnt'8, ilisea.-'cs Siiilolillis, .V.»S "Siaiiicw twiii.t, " (is Siclc-cliiiiii tliciirv of iiiiiiiuiiity, I.")7 ItH) Sidcrosi.s, l{2."i, t.V.I Silicosis, A'J.'t Sirio-auriciiliir iiodc, ;{"" Sinus i)f Imiiic, (iso SirctiDiiirlus, 71 Skaliil, (•(iiisli|iiili<)ii artil, 1 1 1 Skin. <>il."> alinorrnaliMcs of, i><,)5 absrcss I if, 7(M> acne of, 7 anasarca of, (>!»(> anemia of, i)!(.") aliKioni.'i of, 7()ti atrophy of, 7().'{ l)lasloni\rosis of, 70- hurninii of, r>!)7 callus of, 7();i I'aticcr "en cuirassc" of, 707 carbunilc of, 700 c.'ircinoina of, 700 cavcrnonia of, 70"i cellulitis of, 7(HI chancre of, 701 cliiKoe in, 70'{ chroniatoplioronia of, 70<) coniciloncs of, 707 corn of, 70l{ cyanosis <>(, OiHi cysts of, 707 dcnnaloniycosis of, 702 dermoid of, 707 ec/,em;i of, tiilH ch'pliaiitiasis of, 701 entrance of hacleria lhroU({h, ilO epithelioma of. 700 erysipelas of, 7tH> erythema of. t)!t7 favus of, 7(:2 fihr.ima of, 70."> freckles of, 7();{ freezing of, tilts furuncle of, 700 gangrene of, 700 ({landers of, 702 (traftinti, 2(K» tjranuloinas of, 702 Kuinea-worm in, 70;} (tummas of, 701 hairiness of. W)'i liardenind of. 704 hemorrhage of, lillti herfies of. (i'tS hyperemia of, titMi ill etigo of, tilHI intlammation of. tilMi intertriRo of, (i!Kt ko!()i hipus of, 701 erythcmatosu.s of, ti'.M* iyiiiphaniiiecta.sis of, 70(i lymphaiiKio-cndothelioma of, 7(M> lymphanKioma of, 70<) iiutliKuant pustule of, 70(1 melanoinu of, 7(Hi miliaria of. ()<)S moles of, 70.5 molliiscimi <-on(a)ciosinn of, 7().'{ mucou.s |>la(|ues of, 701 mycosis fun^oides of, 702 inyiusis of, 7(M) myoma of, 70.5 myxoma of, 70") na-vi of, 70") necrosis of, 700, 7((U neiirinoniatosix of, 70.") o'denia of, (i'.Hi osteoma of, 70.5 papular syphilide of, 701 parasites of, 702 pediculosis of, 702 pemphiKUs of, (iOH phlegmon of, 7(K) pigmentation of, 70;{ psoriasis of, 01)9 I)urpura of, (ilKj ringworm of, 702 rodent ulcer of, 7(,'7 roseola of, ()1)7 riipia of, 701 sarcoma of, 7(M) sarcomatosis of, 7(Mi scabies of, 702 scrofuloderma of, 701 "strawberry mark" of, 705 .syphilis of, 701 ihickeninK of, 704 tinea of, 702 tuberculosis of, 701 tumors of, 70.5 ulcers of, 7(M) urticaria of, (ilt7 variola of. (iltl( verruca- of, 704 vitiligo of, 703 warts of, 7(t;5, 704 xanlhela.sina of, 70.'{ xantiioma of, 70") Snee/.inu, 420 "Snuffles, " 4;}() Soaps, Xi Soft chancre of penis, 681 .sore of penis, ():{2 Softening of brain, 4S7 Somatic cell, 44 S)riics, ,52.3 Sore, soft, of penis, 032 Spasm, 4S0, 483 IXDKX S|i:i.-tir |)Mr:i|ili'Ki:i. riiliKi'liit.'il. I'.•^ Spci'ilir iiilii'iili 'I |)li'ili>|i(i>iliiili, 11." S|M'ClIill l:ij> ;i» 1 :iM.-r iil i|i>fii>i', 7>» S|HTiri;tlir ciiril. tilO v.iricdci'lr (if, liKl iliHiiiiiliiatiiiii III', till) lillM'rriilii!*i> iif, tiKI S|M'riri;ilipcclc of IcnIcs, (>:{!( S|>i'riii,'ttcicvli's, 4."> SiiiTiiialiiui'iiiiii". ••"'■ "• S|M'riiiiil(i/.ii:i. iiialiiialiiiii ol, l"i SpluKcliis, MHi S|iliiiiK .iiu'iiiia III'. VX> aiHinialii'^ "1. I'-'-' I'unnrsliiin "I, l''"> I'orpiira .iinylarca in, I'.Mi (li'KoiuTaliiiii of. uliimiHS of. .'itU (jlaiiilliiiiias of. I!»'.l UHrnnias of. I'.Mi. .VHI liitiiorrliaKi' into, Iil." infection of, tiMi inllainniatioii of, ttl,') scli'io-'is in. 4'.Mi tranina of. 4ftt> ttihcrrulosisof. tiMi. ."ilK) tiiinois of, I'M), 4',tS, 41t! nicninuc.i. .'rfU .".') teratoma, '.'tHt Sporozoa, iM) life-cycles in, !•() spore formation in, (Ml transmission of, ',(7 Siiuamous-celliil carcin a, 2ti!l of niainniary ^lanil, t)7°J of skin, 7IM) of stomach, ."):{'.• of vulva, M'2 epithelial cvsts, 'J'.f-' Stalkeil hyilatiil, -'Sit Staphvlococcus pvojrenes, ami", l-Jl •Stasis of hlooil, XW Status lyniphaticus, 411, 472 Steapsin, ■i'i Stearin, ;{.'{ Steatolilhs, 'MS Sleatopyny, 2:{:{ Stenosis, conijeiiital pulmonary, atresia, ;iS(') of heart valves. ;{!t7 of intestines, .")44 of (esoph.iBU-. •''2'.t pyloric, o^W of ureters. ()2:, of uterus. t)44. t)4.') Slerilitv of I)1imm1, >S of healthy tissue, ss Sternal fissure, 72 Sthenic fever, 1")() Stilll)irtli, causes of, 11(1 Stimuli, iileoijenous, 4S2 •'Stipplintj" of erythrocytes, :i."i!t "Stitch-hole," abscess. Sit St()kes-.\ilams symlrome, ;{7!l Stonuich, ");5I{ abnormalities of, .").'i:i iibsonce of, "):{;{ actinomycosis of, ."):{() ailenocareinoma of, "liSlt ailenoma of, .JiJlt anemia of, .>i.5 intlainini iililiiiii" alTi'cl- ISDEX rw . 211 la, 2l')'.t iil,t)7i ', intlaiiiMiatiiin 172 iliiKiiiai'v. with , ;57it 5 r> Sliitiiai'li, (•alran'^ll■^ in, ."hill carcitioina ol, ">i'» I'lnlioliMiii aiiil, 'hit <'|iilli)'li.{!• ({laiiili r* cf, .'i.{ti hfriiorrliaKi-M iif, ■V{.'< h.'{.'{ Iiyix'i'i'iiiia of, ."ill.'S intiainiiiatioii of, .'i.'(.'> lipoiiia of, '>•<<,) niyoiiia of, .W.t iii'iiriiioiiiH of, .Vi'.t poi.soii.s arliiiK on, S'2 .sarcoma of, .VIO svpliilis of. •'>■(•> lliroinl)osifi and, .">.'{4 lubfrciilosiw of, .");{<) lunior.s of, it'AS illciT of, it'M Stomal it is, •I'SA, .T24 aplitlioiis, .")2t ItunKrciious, ">24 suppurative, .VJt ulcerative, .">21 StraiiKulaliou of intestines ."1.") ■'.Strawberry mark" of skin, 7'!.") ton(iue, .")2U Streplotlirix of lunijs, 4(i."> Strialiil muscle, retietieralion of, 1!I7 Slri<'lure of urelhni, t)2S Stridor, 42'.t Stroma in neoplasms, 221 Stronjjylus of Iuiiks, M\ii Struma vasculosa, I2."> Subinfection, 147, Iti2 Siil)lu?;ation of joints, llitl Submucous liemorrliac' of stomaeli, 'M myoma of uterus, r>.">l> -Subnormal cell activity, ;i7 Subserous mvoma of uterus, li.'iO Siil)sultus tendimun. 4S0 Sunuillalions, :j"i.") -^unburn, skin in, 7(i;> Sunstroke, 7S, I")2 Siip<'rf(et:.ti()n, l>2 >llppur:lti^•e arthritis, li'.M cholecystitis. .")iH hepalilis, .')74 keratitis, ."il2 leplomenin(jitis, ."lO.") myositis, 1)71 lieplu'ilis, 1)17 otitis media, .")!!• periostitis, liSl splenitis, 417 stomatitis, '124 Surgical" kidney, Iil7 ^'wra, 9.") ^ isccpiibilily, 11.5 ■.ve,ii irlands. reueueration of, I'.l.') -uellmtj, cloudy, I2;{, Ml \Mipathetic hypertrophy, ISO 48 Sympiillietic nervous svhi em, I'.'i ophthalmia, .*>t2 .■^ympus apus, 71 .Synapse, I lit, 474 .Synco|M', 177 Sviievlial carcinoma of puerperal uterus ' IHk") Sviidai'lviv, 71 .Synechia. ;<.s;t, .■>12 .Synorchidism, i\'.i~ .sVphilis, !>K of adrenals. 422 of arteries, 4(HI of bladder, (>2I> of bone, l).S4 of brain, 4S!t of conjunctiva, .'>1 1 of cornea. .")12 of dura mater, .")0:f of ear, .".18 of Fallopian lubes, l).")4 of fielus, IK).") of intesline-, .")">.') of iris, .")12 of joints, W.y.i of kidney, I) 10 of liviT, .")82 of lungs, 41)4 of lymph nodes, 412 of manmiary (jlaiid. 111)7 of month. .")24 of muscles, 07,') of nose, 4;{ll of (esoi)huKiis. ."):n of ovary, 11.")") of p<'iiis. I>:{0 of peripheral nerves, .")I)S of peritoneum, 'M\ of pia-ara<'hnoiil. i")IKl of placenta, im, 0114 of pleure, 470 of skin, 701 of spleen, 418 of stomai'h, .i3ti of tendon shealhs, 1177 of testes. liUS, Ki'.i of ihvnnis, 472 of tonsils, 440 of tiniica vagifalis testis, 1137 of umbilical coni, liH.") of urethra, 1120 of uteru.s, 1)40 of vulva, 1141 \Va.ssermann reaction in, 1117, Ills (Syphilitic arterio.sderosis, 403 cirrhosis of liver, 581 liirvngitis, 443 .nesoarteritis, 408 |)ericardilis. 3.S4 Svphiloma of brain, 480 of liver, .J82 of myocardiun;, 38S SyriiiKoniyeloceie, 202, 40.") Svstole of heart. 37.T 7:>\ ISDKX I- i ■\\A»> i|cii>,ili>. '.(HI •rii'li\.:iii|i;i. :i;»' I'MMiiii rrlilliiMnc-.n-, '.l<.l._-_".l.> TMil.ir 111' liTlh. :>l"i, .V-'T 'r;iltlHlill|t. ii-t •r.fiii, .v.'ii liiiii's (pf, .VJ(> cvsis i)f. "r.'s (IclVil^ I if. •■>--., lliilcliiiiM'ii -■ '''■ ■''-•' ihllaiiiiiiuliiin "f, jjti, .'i^T liirl.'ir n!'. :(!.■>. .")J7 trail.-" ' ,'iim iif. 201 llllliol" • . '>-' 'rrliiiiMlifi'laM-. .-TS ..f kiilii.'V.f.Jl •I'riliiriuiii. •■•■lis of nir > aiul. '.S/ 'I'llHiiliaM' . t'>7t'> ■rciiiloii slii'atlis. t>7t'> calrurcoiis cli'|)o>its in. In i "(laiittllon" of^t'>77 liVL'foiiia of. 1)77 iiidainiiialioii of. Ii7(> li|)oina of. 1177 •lice lioilirs" ill. t'>77 s.-irroiiiM of. t'>77 svjiliilis of, ti77 IMi)(irlllo>i> of, (177 I iiiiiois of, t'>77 'riiiiloiis, t)7i> iiitlaiiiiiiatioii of, l>7(> - iiroin.i ol, t(77 tumors of, t'>77 'rciiilova(iiiiitis. tyi 'I'liiosviiovilis, t>7l'> ■[•••lata, 3>7 '|"cratol>la-t.iiiia-. -Mil of l^illll.■,v. (I'-'l 'r»'ratoni'liotl> lila>tollia-, 211. -'-■• 'rciatoids, •>'••_ 'rcratoiii;i. '-'(•7 ronpMiital -a.-rai. t).i. ^.i^ -<«• rvslii-, -.'It'.' o'f Kciiil:.! iilaii(l>, -'<«• of lllll(.'>. l'''"> of iii('(tia>liiiuiii. 471 of moiitli. 'V-'p. •''-'' of orliit, .'117 „f,,var.v. -'Il'.l, f.liO_ of iiciitoiKiiin, .">t>7 sDora.lic, -'(Mt of t.'sti-. -'(f.t of iircti'is, (VJt of I- lii.f li^aii iMt.-. •■'••- 'rrratoiiialoiis vy^" of unnis. ti.VJ rcriniiial iiiftilioii. lil, I 17 l(iikocv;oMs, :{tU |iiii'iliiioiiia. t.VJ IC^iis, i>;i7 aliiioriiialiiii's of, (i:;7 alropliy of. ti;{".| ramiioiiia of, t'fci'' rliori(M'liilli il\>lo|iia of, I'fcl7 hviicrplasia in, •>:('.» liV|Mrtro|ili> of, nmipt'iisator.v li\ |io|ilasia of, <>;t7 iiilVclivc Kranuloiiias of. ^V^>> iiillaiiitiiatioii of, ihiS iiicsotliclioiiia of, <'•!"•• ii'tjriicratioii of, \'M\ sarcoma of, tiit'.t secretions of, HVJ •(iicrmatocclc of, (i;>'.t svphilis of, v,:is. c.:;'.! ,■ teratoma of, 'JO".' tiitierciilosis of, fiH.s tumors of, •_'7.'., <'':4".i Tctaiiie contractions ol muscle, ISI 'I'd anus to\iii, I."i7 I'elanv, 101, I'.'O 'I'lielitis, f.ti7 'riicrinoiieliesis, 1 t7 'I'lii'oinhiii, Hit) 'riii-omhoaiitjeitis ol.literaiis, UMl rinoml)oncn, ;5U'i I'liroinliokinase, :!lli 'riiroinl)o|ililel>itis, ;i.')l. 410 'riiromliosis, lilt) of arteries. 400 lilooil plalelets ill. .'17 ill liraiii. |n7^4SS causes of :i47 cere!.,,il, 41IS of ilura inaler. .'lOl forms of, ',V\S liemolvsis mil, ''.i^ of kiiliiey, (MHt of liver, .'')7:{ of iympli iioiles, U'J of peritoiieiini. ."iti:') results of. jl.-)0 ill f.iina. ."jlO of spleen. 41t) stomach ami. 'M of veins. \W 'i'liromliiis. Ii4t>. ;!47 _ absorption of, ^foO arterial. :{4'.> ball, ;i4>i capillarv, il.'iO I'ar.liac. MS nlolmlar. :W livaline. ;<47 !ii.el:'.t<-l 'I'linisli, .V.'t ••'riirii^li-hrra.-t" lii>;irt, :i!HI 'riiyinii*. i''. .f, »:■_' Mtrii|iliy of. 1"'- liv|M'r|>l:i>iii of. •' lowirriiina f. »T Ih Iviiipl xyliliilix "f. •"'- lillM'iculosis of. i''2 ,ri>iiii aiiil tOI IIIV \(i'ili'-iia ami, 1(11 Klaiitl. CM aliiiiirinr.lilifs of. l'j:{ iiliM'ii'M' of, ^^2^ ncci-ssory, V2'-i ili'tiocarriiioMia o f, 1-J ■ ll'Ilolll l.f, fj itropliy of, 4JI cilraii mis < lc|>osits of. I'Jt cuniiioina, Narroiii cotitjfslioti of. 421 cvsts of. 421 f. 421 (li'dcncralloii ol liyiMTplasia of. 421 |iyj)oplasia of, 121 iiiflaiMtiiatioii of, 124 f. \'M\ rcijcncralioii ol transplant at ion of, 2(K( tumors ol f, 42.-I l£"itrc, ri'.'ictii 2 Itil'OK I Lodics, lit, 47;{ Tini-a, 702 rircinata, i (12 sycosis, I lipiisiiraiis (12 702 olor, 702 I'll cniliolus, :)."i2 >s, l.S.'>, 1M> c'lianu( (li'vclopincnt of, 22:{ .■n.lotlK'lial, 22t> <'iilran<-i' of badcria to, S(> .•pil)laslic, 22.1, 22(1 lii-aliln , stcrilitv of. .S,S hvlic, 22."), 22ti hypoblast ic, 22.'), 22t> ic'piilic. nii'sot rlivniatoiis hclial. 22.-). 22C. f priHlilcclion, 220 22(» pr< pulp, priniitivi Tor-nail, iiujrowinK, 70S I'oi.i ' contractions ol f inusclc, 4S1 )ii)ju('. defects of. .■)23 ccoirraphical. .">24 stiawherrv. :)2;4 tic. r)22, rv>:i Toiisilljir concrcinci :ii: 'ronsilliijs. chroiiii' ' Hinilar, 110 ioiisils. IHtl aliiioriiialitii's ol, 1;17 vudalitis of. l;{7 aiiiyK' fauces of. l.lCi ivtH'ieinla o f. i:»7 iiillainiiialioii of, lit" ii'ilcnia o f, l;!7 svpliilisof. 110 tUlM Tculosis of, 1 10 Tonus of iniisi'lc, \s\ Toplii in ijout, (iOl Toplius, .■)20 ■roti|Mitcntial cell. I.'i, 20S 'I'oxciiiia. I 1-) I'oxic .allxiininuria. (lO^I (rdcina, 1170 Toxins. S.'i, l.'iti ai'tion < if, s:, ititoxins ami, l")(> of Macillus diplitlicria', N.'> of I lactcria, M. S.-1 liialodes of. I2."i Ictiriition of. l.'iti devclopinent of. in protozoa, 'Xi excretion of, l>y nieta/.oa, O'.l resenililancc of. to enzymes, ,S.'i tetanus. l.">7 T IXoplK d. I.- Ik !.■ 1.' Trachea, 420, 140 'I'rachonia, .")! 1 raction aneurysm, l(;s livertiellhi of (isophauus. ao Transitional lepide neoplasms, 220 Transplantation, lOO autoplastic, 100 of hone, 201 heteroplast 100 r4 isoplast 201 f mammary ulaii'l. 2(M) i(f mucous tiK'Hi t.raiies, 201 l.f. 2(HI f pericliondriuni. 201 periosteum, serous tiieiii 201 hiaiii 201 of teeth, 201 of thyroid, 2(K1 of vfssels, 202 Traum.atic causes of inflammation. 122 liironibosis of dura mater. .'lOl Tremor, 4M4 Treiionema i)alliiluiii. ^M. OK Trichina spiralis, cysts of, 20.") Trichina'. 00 Trichiniasis of muscles. (174 Trichocephalas di'struction 00 Trichotnonas, 00 Trimcthvl.inr 1, 110 of tissue bv. Triplets, (14 Tropical ab.si esS of livrr. .")7.") Truncus arteriosus, persistent. :!S(1 750 rxnEx TryiHinosoiim briicci, d") cviiii.ii, '.>'t Kaiiihiciis(>, ((."> 'rry|)iiii(is()ni('s, (t4, it") Tn lisiii()(jcii, jictivation of. In- cntcro- kiiiusc, 174 T.st'-I.so Hy disease, !).") Tubal al)<)rti(ni, (Miti Keslation, tJ.W Tube, Fall()i>ian. <)">;{ TulxTcle, l.SK of iris, .^12 TulxTculoirias of liver, .")S2 Tut)ereiil<>sis of adrenals. 122 ai'ronenic, 4(')() of bile duet, :>S2 of bladder. t)2() of bone, (),S.{ of brain, 4,S!> of bursa-, iuS , of eonjunetiva, .'d I of <'ornea, .")12 of dura mater. .")(K{ of ear. r.IS. .■)2() of Fallopian tubes. ()."4 heniat overlie, 4(14 of intestines, .Vil? - .").") of joints. W.i of kidneys. (ilK of liver, .").S1 of lunifs, 4.ji) of lymph nodes, 412 lymplio)renie. 4t')4 of tnammary Kl.and. <>li7 miliary, 4(>4 of mouth. i')2.") of luu.setes. t'>74 of myocardium, .'iss ! of no.se. 4;!t) , of (r.sopha^us. ,");{1 of ovary, tio") j of pai'ereas, iiii't of penis, (i;j2 I of peripheral nerves, MS of periloneuiri, ">().') I of pia-araehiioiil, ."lO'i of p'aeenta, t)ti4 i of jjieura", 470 of prostate, iVSA of salivary tjlands, ")2S | of skin, 701 | of spermatic cord. (IJO j of spinal cord. 4!Mi. .'itM) of spleen, 41.S of stomach, 't'M> of tendon sheaths, (177 of testes, ();{S of thvnnis, 472 I of toii.sils, 44(1 r nf tunica vatriiialis testis. t(;i7 of uri'lers. (124 of urethra. ()2!l of uterus, tl4!t of vulva, (141 ' Tuberculou> bronclio])neimioni;i, 4'>9, 4til colitis, .')tlO ' laryngitis, 442 pneumonia, 4(11 pyelonephrosis, (124 pyonephrosis, (11!) Tubo-ovarian abscess, tl.^.') Tumefaction in typhoid fever. .")0 Tumors, 20(1. Sic also Neoplasms, nomenclature of, 22(1 ordinary. Sic Ulastomas. in tumore, 20!(, (KM) Timica vaginalis testis, (iUti abnormalities of. (1;{(1 inflammation of, V\',U'> hydrocele of, tll{(l i syphilis of, (137 i tuhei Twins, (12 dichorial, (12 heteriMiphal, (12 monochorial, (I'J moTioophal, (12 une3 intestines in, .")4il necro.sis in, .").">() perforation in, 'tri'.i predisposition towan relap.ses in, .")").'{ skin in, (l!t7 stomach in, ii'M tumefaction in, "),")() ulcer in, .j.')2 i.rKR, 7(K) Htherom.'itous. 402 of cornea, oil, .512 healiii)!, 7(M) indolent, 700 of intestine, ,")4.S I)h.a(!;e in typhoid fever, .5.52 leeration of peritoneum, .504 Icerative colitis, .5.5S ("tidocarditis. .3i((l itiHammalion. i:{4 stomatitis, .524 tuberc\ilosis, 4(12 'tramicroscopic tnicrocrganisms, 93 IXDEX 757 Cltniviolot 7.S I'tiihilic: rays as cause of disease, il lord, ()0."> aiigiomit of, ()('),'> cysts of, (i(i,5 defeneration of, tltio liernirt of, 7'2, IMio looped, tit)") myxoma of, (H'tit septic infection of. (Mm syphilis of, titii') twisted, tMJo hernia, .jtiit I'nconscioiisness, 4K0 "I'nditTerentiation," 2im rnequal twins, t)2 I'nicentric blastotna, 217 ITnilateral kidney, tHW Universal |)eritonitis, hKi "rnresolved" pneumonia, 4.")7 I'rachal cysts, 2.S<», 2i«», (>2r) Cratic calculi, ;{l(i inspissation in infancy, :{17 I'rea in iirine, ()t)2 rreniia, t)()7 causes of, lOo Ureteral colic, 023 Ureteritis, ((23 Ureters, 622 abnormalities of, t>22 calculi in, 023 carcinoiiia of, 024 eysticercus of, ()24 cysts of, 024 echinococcus of, 024 eustrongylus (jitJus of. 024 filaria sanguinis of, 024 foreign bodies in, 023 ({ravel in, 023 kinks in, 023 inflammation of, 023 obstruction of, 023 papilloma of, 024 parasites of, 024 sarcoma of, 024 stenosis of, 023 teratoma of, 024 tuberculosis of, 024 t lunors of, t)24 Urethra, 02,S absence of, 02S anomalies of, ti2S carcinoma of, ti2!) caruncles of, 02!) condylomas of, 02!l fibroma of, 02!) foreign bodies in, 02!) inflammation of, 02S sarcoma of, 02!) stricture of, t)2!) syi)liilis of, 02!) tut)ercul()sis of, 02!) tumors of. 021) Urethritis, 028 Urethritis, Konorrh Urtii'a, hvbrids of, showing Mendel's law, 4!) Urticaria, 007 Uterine fibroid, 241 Uterocele, (i44 Uterorectal fistula, ()44 Uterovesical fistula, 044 Uterus, t>43 abnormalities of, 043 absence of, 043 adenocarcinoma of, t»,")l adenoma of, 051 adenomyoma of, 243, 0.")0 anomalies of, 044 anteflexion of, (544, 04o atrophy of, 040 bicornis, ()44 bicornuate, (544 bruising of, 04() carcinoma of, 051 cysts of, 049, (552 didelphys, 043 dilatation of, 040 dysplasias of. 044 dystrophies of, 044 elevation of, (')45 (mdothelioma of, ()52 epithelioma of, 051 fibroid of, 241, 050 fibromyoma of, 0.50 fission of o,s of, 044 flexion of, 045 f liKttiiifnts of, ()!, (»t)2 fibroiiia of, (it)2 licniorrliaKc in. ''><">1 liypcrlrophy of, <)<>2 iiiHainniation of, ti()I lipoma of, &V2 inyoina of, (><)2 plili-holith in, (i(il sarcoma of, t)(>2 Icratoiiia of, t)()2 tumors of, <)02 lipoma of, («() myoma of, 241-2415, lioO myxomyoma of, tl.'id parasites of, ()4!l pcrfonilion of. ti4('> |in«'i(lcntia of, (i4."> prolapse of. t>4."i puerperal, (Mi2 ehoriiwpithelioma of, tl'i;? (ieciiluoma malijinuin of. <>)>:{ syncytial carcinoma of, (\iV-i tumors of. (Ml:} retroflexion of. (>44. t)4.") retroverled. (144 ruiilure of, ()4(> sarcoma of, t'>ri2 septus, 044 stenosis of, (>44, tt4.5 sy|)liilis of, (i4!l tuoerculosis of. ('>4!t tumors of. <>.")() unicornis, "14 I'vulitis, 4:57 . VAcnxiA, organism of, !W \acuolar (Icfseneration, •W>, (i2l> Vacuoles, IS \agat)on(l's disea.se. 702 Vagina, 042 abnormalities of, 042 absence of. ()42 atresia of, 042 carcinoma of, squamous-celled, 04:{ chorio-epithelioma of, (')4;5 (lui>lication of, 042 hemorrhage of, f>42 inflammation of. ti42 h'iomyoma of, 04:i l)ji.ssive congestion of, 042 sarcoma of, M'.i tiunors of, 04;j Vaginal hernia, 509 Vaginitis, 042 Valves, auriculoventrioular, 373 semilunar, 376 Valvular piieumot) ivux, 4(>7 Valvulitis. :iit3 \;iriation, here() N'arices of intestines. .")97 of lymph nodes. 412 \'ari('ocele of spermatic cord. 041) X'aricose aneurysm, 4I).S bronchiectasis. 440 veins, 27S, 410 Variola, O'.Mt Xa'rix, aneurysm.-d. 4()S \'as deferens. 1)40 inflanniiation of, f)4() Vas<'ular area, inflammation in, 123 Vascularization of new formed connectivi tis.sue, 130 Vegetable forms, pathogenic, other thai bacteria, !)2 \'egelations, 13."), 3'.)4 cardiac, 34!». 3.')I fibrinous, i:,'") Vegetative cell. 44 ai'tivity. 3S endocarditis, 3!tt) Veins, 411) calcification of, 410 dihitation of, 410 hbrosisof, 410 Inflammations of, 410 thrombosis of, 410 varicose, 411) Venereal wart, 2.").S, 0.">2 Venoms, animal, lOS Venous hyp<"remia, .33.S pul.se. 372 t lirombus, 3.")() Ventri<'le, fourth, hydrocele of, 292 hydrocephalus of, 4S0 of heart, 373 dilatation of, pathological, 37") distention of, 374 Vernal conjunctivitis, .")I1 \'erruca', 704 N'errucose endocarditis, 3!14, 3!>.") Version of uterus, (')44 Vesieo-umbilical fistula, 02") \'esicovaginal fissure, 73, (i43 Vesicuhe seminales, 040 \'essels, poisons acting on, S2 transplantation of, 202 Vicariovis cell activity, 37 hypertrophy, ISM nienstruation in mammary 000 Vincent's angina, 439 Vinilent bubo, 032 Virus, filterable, 92 Vitellins, 2.') \itello-inteslinal cyst.s, 289, 507 Vitiligo, ;03 i Vitreous degeneration of myocartliur I 390 ' humor, 516 glan( INDEX 759 Volvulus of intestines, ")4.") Weaver's lM>tlom, 07S \on HeektiuKliuusen's disease, 2.H), 1 M7 Wens, 2!M), 707 Vulva, WO White infarct of liver, ."544, 072 abtiormalilies of, 640 kidney, large, 012 iiriKioiiiu of, 04 1 I)neunionia, 4().") atrophy of, (141 soft en. ig of brain, 4H7 )40 eareiiioiiia of, s(iuainoiis-<'eileii, 042 swelling of knee, 0S4, 0!):{ ehondroina of, 1)42 Widal reaction, 102. PUtaiuKuis (listurbanees of, (141 WolHiun body, cysts of, 2S<» eysts of, f)42 elephantiasis of, 041 Worms in peritoneum, 566 Wrist-*lrop, 508 fibroma of, ti4 1 lienuitonia of, ()41 lieniorrliaRC of, 641 X n 1 *>X infective granulomas of, t>41 11, 1 >.f 1 <*oniuH'tiv*' inflammation of, (141 lipoma of, M2 Xantiiin, 27, 107 calcuH, :iis other tliiiii lupus of, I>41 Xanthelasma, 70.'{ \'iii\ 1 iiit^ii myoma of, ()42 Xanthoma, 2;{;{, 705 luevi of, ()41 X-rays as cause of disease, 7S (edema of, ()41 cells of tumors and, 2S7 passive eongeslion of, 4I Yaws, (tS X'ulvitis, acute, 041 Yeasts, <»2 N'ulvovaginitis, 042 Yellow atrophy of liver, acute, .574 fever, organism of, 92, !•:{ prc
  • d initrition. ;}. Aiiasarca.-"Rememberinj? what has been said regarding the want of relationship between the tissue spaces and the lymph channels it will be seen that two main factors determine the accumulation of fluid in the tissue spaces: (1) the rate of escape of fluid out of the blood vessels into the tissue spaces; (2) the rate of escape of fluid from the tissue spaces into the lyni])hatic chaiuicls. If fluid can be carrici. off by the lymi)halics as rapidly as it passes t)Ut from the bhwHl, no aecunudation can occur. In other words, an (i-dematous state may he brougiit about by an excessive discharge from the blood, or, on the contrary, by defective draii:.ige away through the lymj)hatic channels. There has been controversy extending over long years as to the relative importance of the difi'erent factors found associated with the production of tiie (edcjnatous state. On the one hand, there are those who would reduce the problem to its very simplest physical factors, who regard the lining wall of the vessels as nothing more than a filtration membrane, who thus ascribe oedema in the main to pressure difl'erenees. to increased discharge from thinned and dilated c{\i)illary and other vessels. On the other hand, an important body of investigators holds that the endothelial cells lining the blood vcs.sels are not merely mem- branes, but possess a selective capacity, and thus regard the frdema fluid, not as a filtrate, but as determined by the state of mitrition of the vessel wall. Neither of these schools seems to have paid sufficient attention to the problem of how, once in the tissue spaces, the fluid gets into the lymphatic chaimels. A compromise may be reached. We must admit that when the smaller vessels become dilated their walls become thinned and the intercellular spaces of their endothelium become enlarged, so that if there be any iufTease the \ itreous, is so great that the eyeball is liable to undergo rup- ture. If, again, a frog's limb be ligatured or cut oH' and now be placed 111 the water in which previously the frog had been swimming, there iKviirs iiii intense imbibition (.f fluid, with development of post mortem •iMiisin fi. .\s we know, when muscle and other tissues die the\- become iiH n ii.iiigly acid. It is to this acidity that Prof. Fischer ascribes the I'lilMhition 111 this last case, and he is inclined therefore to ascribe many i.i^i^ (it (i-dema and anasarca not to mechanical changes in the blood lin-iirc or, again, to changes in the blood itself, but to alterations in the \<'\\"u\-a\ tissue elements, whereby these need and attract to themselves ji" i-M>iiig fluid. The idea is suggestive; we cannot, however, see that It rovrr. tile whole ground; rather we woiihl say that we continue to rti ii-iii/(. tJic tollowing types: /.v/"^' "l""l't.dly, tlirrr IS U') increased capillary pressure, (b) dilatation of q'lllaries. witii tlniining of the walls, (r) slowing of the blood '■ iiid iiKTcasnl wnosity of the blood, (r/) lowered nutrition and "t the . ..piilary wall. Possibly here, secoiidarilv, the nutrition ' MMies and the changes occurring in those tissues form a factor M^atiirc „t the main vein of a limb in a healthv animiJ is not 'I I'v (edema, though such (edema will occur if the animal be ■ I pii\(Tislied state of health. CEdetna from Lymphatic Obstruction.- It has alreaih Ix-en noted pliiitic obstruction, while leading to dilatation of the Ivmpliatie I'xp not necessardy cause tedema, in fact experimeiitallv the ;"Pliiitics ot a part may be ligatured and vet no cedema mav .' li'' '>l<'..d capdlanes are capable of taking up fluid from the ' ^'^ they permit fluid to pass into them. Hut sometimes iilts, and here again the condition of the tissues appears to be \\ <• may find, for example, oedema of the arm occurring in the thr . \itw|i 111' l\: Tim tnll,, ill .1'! ■> tli;il niiii (i(( , ti-i (i'tl( 370 THE CARDIOVASCULAR SYSTEM later stiifjos of rancor of the hreast, when all the axillary lymphatics have befome involved; hut in the earlier staj^e all those lymjjliatics may he excised, in order to arrest the extension of the disease, and no a'dema shows itself. In this eoiuiection we may note three varieties of ascites, viz., chylous, chyllfonn, and pseudochylous ascites. The first of these is due to rupture of tlic abdominal lymjjhatics, or of the reeeptaculum chyli, whereby the milky chyle escapes into the peritoneal cavity. Of similar orif^in is chylous hydrothorax from rupture of the thoracic duct, and chyluria, from rui)turc of the lymphatics of the pelvis of the kidney or of the bladder. Chyliform ascites is found in cases of abdominal car- einoma or tuberculosis, the emulsion of fat giving the milky appearance, and is due to breaking down of leukocytes and other cells that have undergone fatty degeneration. The percentage of fat in these cases may be much higher than in the former. In pseudochylous ascites the milky appearance is associated with absence of fat, and is brought about either by mucoid substances or suspended proteins. '.i. Inflammatory (Edema.— All acute inflammation is accompanied by a local increased i)assage of fluid out of the vessels. The fluid in these cases approaches more nearly in its composition to the blood plasma than does that of congestive a-dema. As will be remembered, the capillary endothelium shows a striking series of changes in acute inflammitinn, and to this changed condition we must largely ascribe the increased exudate, although here also we must recognize that the tissue cells in the involved area exhibit marked disintegrative changes which may undoubtedly attract more fluid. 4. Toxic CEdema. — We know, experimentally, that there are sub- stances which act as lymphag have been preeminently ;iilv;iii(e(l by the study of normal and perverted function. For such a -tii.ly, It is true, a knowledge of the anatomy and histologv, and, iiiilcnl, .)f the embryology of the organ has been a prerecpasi'te, but iiii'i":il.teM(.l();;y of the heart is of profound importance to the medical man. liiu> ut necessity a chapter must be devoted to cardiac function ami It- iii-tiirl)ances. I'unrti.mally the heart is nothing more nor less than a pump— a 'l"ii ,1c pump and double-actioned-the indications being that the filling "t the \ciitncles IS not a passive process, but in part at least active, 'liif tn suction exerted by the expanding ventricles; it is a suction Piiiiip. cN ,11 if, to a greater extent, it is a propulsive organ. With this It I- ixtraonhnarily responsive to variations in the work it is called iip'"i "> accomplish, altering its rate or rhythm and the force of indi- y'ln.il iMats^according to the amount of blood supplied, the resistance ii- t;H I I III, iiit! ililF. Iii;i. ; 1. ■ th.-v Illnl ,! t winch the blood is propelled, and the stimuli received from the I- rriitres. We must, even if rapidly, mention in order the varying \\ nch modify its activity, taking for granted a km)wledge of the 'itiiiiis of its anatomy and cmbryogeny. •I iMjitter of difficulty to determine tfie order in which to treat 'iMiis sections of our subject, and this because there is such an ' interaction between the work and the disturbances of the ' pnrtions of tile heart, that it is impossible to discuss one phase ■ H'lun without referring to the other. The following, however ■ id helpful: ' Auricles. -We must regard the auricles as distensible pouches ' i\ clx weak muscular walls. Their very structure indicates that riMTvoirs to accumulate blood during ventricular systole r It freely into the ventricles during their diastole. It is true 372 THE CARDIOVASCULAR SYSTEM m li that these walls are muscular, true further, as has been abundantiv demonstrated .hiring the last few years, that the heart beat commences at tlie sino-auricular rin>;, where the veiue cavie open into he auricle, and from there the contraction spreads through the auricle, and so later to the ventricle^; but in the auricles the contraction is relatively feeble. I'nder normal conditions there is indeed verv little need for vigorous contract' )n. The very size of the auriculoventricular orifice, as we shall jwint out. and the active dilatation of the ventricles together afford an easy How of blood into the ventricular chambers— a flow so easy that no proper valves are present at the orifices of the vensE cayje and the pulmonary veins respecti\cly. At most, with the contraction of the circular musculature around each orifice, there is a dimiiuition in their lumen. It thus becomes a matter still under debate as to whether witii each auricular systole some small amount of blood IS not driven backward into the veins. As already noted, the flow forward into the ventricles is so easy that if normally such legurgi- tation is present, it is not propagated, and does not, for example, show Itself in the neck veins. 2. Venous Pulse.— If, however, there be obstruction to the onflow of blood and dilatation of the auricle, such regurgitation easily manifests Itself. There have been luinierous conflicting studies upon "this matter durmg the last century. We owe, more especially, to Dr. -James i.Iackenzie and his em^)l()yment o' Jie i)<)lygraph (/. e.] of an instrument pernntting simultaneous records of venous pulse, apex beat, arterial pulse, etc.) that today we recognize the different forms of venous pulse and are able to translate the significance of the same. Mackenzie has shown very clearly tliat according to their position relative to the phases of the carotid pulse, we may recognize three separate waves in the venous pulse (r. (/., in that seen in the jugular vein). I. If the auricle l)e distended and its contraction be powerful, there may be pro|)agated along the vein a wave corresponding with the auricular systole. II. If the auriculoventricular valve be incompetent there mny be propagaied backward a regurgitant wave corresponding in time with the ventricular systole, and III. Owing to the .-hjse proximity of the carotid and jugular witiiin the same shcatli, an active impulse propagated along the carotid iirtery may be transmitted to the column of blood in the vein showing itself a little later than the regurgitant ventricular wave. Sometimes all three of these waves are present together. Where there is little or no regur;itation through the tricuspid, the aiirii iilar systolic wave alone may be present, as in the rare condition of tri< uspid stenosis. Where the tricuspid is markedly incompetent, and thnmgh regurgitation the right auricle is overdistended and enfeebleay regarding regurgitation and auricular function in connection with our next section. :: The Auriculoventricular Valves. As already noted, the most striking feature of these valves is their relativelv large size, so that their <.rit..rs permit an easy filling of the ventricles in diastole, and this w thuiit resistance. The very size of the orifices demands a special nurhamsm. so that during systole the pressure on the under surfaces ot tlic large valve flaps does not make them give wav and allow escape int.. the auricular chaml)er. This mechanism is afforded bv the i)apil- lary muscles and the chorda" tendineie. The chord* are attached in r..«. to the under aspect of each valve, and originate from the papillarv niiixl.s n, such a w-ay that each muscle gives origin to chords passing to .a.l. valve flap. 1 hey are further so attached, some to the verv edge ot th,. va ve, others to the under surface, that when the valve flaps are I'jill'H.ii.'d up by the pressure of blood in the ventricle, the flaps are not al.s.,hit(ly flat, but have a marked convexity upward in such a wav tliat the distal or terminal border of the main flaps does not meet th"e Hi;.' ot Its fellow, but there is apposition of the auricular aspects of the t.Timnal portions of these valves, and i;. this wav the greater the pnsMirc withm the ventricle the more firm is the closiirc of the valve As to the action of the papillary muscles, there is this to be noted that II, systole it is the breadth and not the length of the \entricles that iiiui.Tgoes serious alteration. Were the papillarv muscus to <"iitni. t simultaneously with the ventricular wall while the ventricle is ^" :"". til. last portion of the ventricular wall to und-rgo eontract:r)n It woiiM thus seem that these muscles come into action after the increasing pr.;"ur, within the ventricle in systole has led alreadv to the appo- ptjoi, ..I iIh. Haps, and that by their contraction thev pn-vent excessive : '"'-"' t'«' valve into the auricular chamber. Thev and other "!'-> , r. have shown that the papillary contraction mavbe irregular "r "II I..- wanting, and have associated these irregularities with other |li nirl.u,,,. ,„ the heart action. The main cause, however, of regurgi- tnti. I , is .listension from an overfilling of the ventricle. This we shall •Jixii- 111 iiur next section. The Ventricles. These are essentially the pumping apparatus of ' ' ■ '■t. and their structure in tliis relationship shows certain inter- ■itiires. Each ventricle does not contract as a sphere and "lie narrowed in every direction. The lavers of muscle are ;-v.l tliat with contraction the length is practicallv unaltered, '1 systole singularly little internal pressure is exerted upon the th. •■still: thii- s" an ••■O tllll 374 THE CARDIOVASCULAR SYSTEM h < IK' i IS'- I apex, whicli, iiulecd, is sinpularly thin. Tli- arrangement i»f the fibres and their mode of contraction are such that the walls of the apical portion of cither ventricle, and particularly of the stronger left ventricle, are brought together and compressed. Above the apices of the papillary muscles there is left a small chamber around each auricuh)ventricu]ar valve, which even in the completcst contraction is never entirely emptied. The more recent studies of the electric reactions of the heart show that the contraction begins at the base and travels down toward the apex, and, as already noted, it affects the i)apillrrv muscles at a comparatively late period. But, also, with Krehl, we are led to recog- nize a third section of the muscle the ring nuisculature, controlling the )rifice of the ventricles. This i> held to play an important part in preventmg regurgitation. Where its tonus is reduced and becomes enfeebled the eidargenient of the auriculoventrieular orifice leads to incompetence. In the right heart also we have to distinguish a coiuis or jKissage leading uj) to the pulmonary artery. Embrvologicallv this originates as a separate jiorlion of the \ entricular cavity! Lasth.'it has to be recalled that the weaker right ventricle is ai)plic«"l in a soiiuwliat cresceiitic manner upon the side of the more conical left ventricle, atid that the musculature of the two ventricles is not absolutelv distinct. A considerabie number of the more superficial fibres pass from the one ventricle to the other. Some clinical obser\ers have reconled an independent rate of contraction of the two hearts. From anatomical considerations it is difficult to see how this can occur. While the cardiac muscle presents certain distinctive features in its mode of contraction, we must regard it in most respects as possessing the same general properties as other striated muscle. If we attach a weight to a resting band of muscle, such as that of the frog's leg, we find that the b-ind undergoes progressive elongation. So, similarly, if under pressure increasing volumes of blood enter the ventricles, tlie ventricle expands antl undergoes distension. It is very probable that, as with skeletal muscle, there is a certain optimum load under which the maximum amount of work is accomplished, and that thus a moder- ate grade of distension of the vf utricles is most favorable for the iicart work. Without entering into the physics of the matter we would lure point out that with increased exercise up to a certain point the ventricles of the heart undergo a physiological distension, which seems to i)i- to their advantage, inasmuch as in thi; state a smaller range of contrac- tion of the individual muscle fibres drives out a relatively much larger amount of blood into the arteries. Saying this, it must be remeinlMTcd that the normal heart possesses a very large reserve of force. It is found, for example, that with the internal pressure raised to four times the normal, the organ still continues to pump out regularly into the aorta. Thus it can stand temporary increase of work with comparative ease. Nevertheless, this reserve of force can be used up either by nial- nutritio!! or by continued work up to the limit of the capacity of the organ. Where this is the case we find that the organ undergoes what THE HEART: GENERAL CONSIDERATIONS 375 iiuw we may term "pathological dilatation." Even in this dilatation, jiwItriiiK from the continued stre:ij;th of the pulse and the arterial Mi.(m1 pressure, the organ may continue to function adequately, and i!ri\<' forward the amount of blood necessary for the organism at large, liiit this only so long as the individual is at rest. J{elatively slight (Mrtion, or increased demand upon .ne organ brings about 'cardiac l.iiliire and acute distress, or otherwise we recognize three grades— lihysiological distension, pathological dilatation with partial incom- pctciici', and cardiac failure. It ;<^ l)robable that in all cases of what we have termed "pathological ililiitution" there is incompetence to the extent that regurgitation shows itH'lt. .\s already pointed out, such regurgitation through the dilated :iiiri(iil()ventricular orifices is of the nature of a safety valve action, \vlK'r(l)y the strain is removed from the ventricular muscle at the IMwsil.ly lesser expense of congestion of the lungs and abdominal and (itlitr organs. S.) long as the heart is working within the limits of its reserve force we fni.I, m accordance with the principle laid down on i)age 142, that imnasfd w.)rk leads to hypertrophy. When, therefore, we encounter tiu' <'on(iition of marked increase in the volume of the ventricular MINX Ic, we must not regard this in itself as a pathological condition. It b iiilaptive, but, at the same time, is an indication of the existence "t x.ine condition, either in the heart itself, as from «lisease of the \iil\.js and obstruction to the onflow of the bloocess, it is only comi)aratively recentlv that Stefani has ■III"" •'! absolute demonstration of the active elongation of the heart ||||| H, Ho has demonstrated that blood enters the ventricles, and 1^ K .|" llcl into the auricles when the pericardial pressure (the pressure "M tile heart walls) is 2') cm. of water higher than that in the iiva-. Only by the suction action of the ventricles, bv their 'il'itation, can there be continuance of the circulation under "iKiitions. ' iibservations throw light upon the hypertrophy of the Ief+ ven- •A infrequently present in cases of mitral stenosis; thev suggest - \ securely, owing to the relativelv large extent of the peripheral i...rtioi,s of .-ach of them which comes into a,,position with Its neighbor, anl DKRATIOSS .{77 ..II tW inm-Hsnl work .-annot he met hy ,lilatuti„n arnl incmis,.,! nutrmo,, „f IH. Iu.art ,m„saratc.l strips .)f mammalian \-..ntricnlar nuiscle Inrt.T). ,1 .l..hl.nnato.l l.l„...| |„. perfns...! through th. attadu'l \ZX o tin. ...ronary artery sp.,ntaneons .-..ntra.-tions .,r heats will, nn.ler t.. o ah e <"n.ht>..ns. show themselves. It is c-lear. theref.,re, that the o n.,,„.ns o» „,.|,v,.lnal fihres may oeenr in tlu- al.sen.r ..f anv stimni trnin o,alize.l pinKli.,.ne .-entres. situate.! in the heart ...It ,s st.ll a n.atter ..f .lehate as to whether this last ..r.ler of eon- tr.,rt,n,us „|,.,museular, an.l this lurause it seems i.npossihie to isolate anv part ..t the heart mus..ulature whi.-h .l..es not show' fine nerve fiS. a-o(iate.l with whu h are scattered ner\e eelN 1 riH.se wh..h..l.l t.. the i.li..museular hypothesis p.,int out that " t .,.. ...Kk an.l ..ther embry.,s the heart is .lev..|ope.l an.l aetivelv U-.Ujj„r .„n,r dm,, brjore uu„ uenr fibre, ami "->on Sj,str,».-Our knowlclge of this sNstem is base.1 upon tlHoi)M nations of (Jaskdl (l,S,s;{), Kent (l,S<)->) Hi; Ir l^c- To ;- nsbynK)rerece„tw.,rkers. Atthejnnctionof thesuperiorvena '■' ■' - ' lu- ngh auru e is an accnmulati..n of peculiar small muscle Illrlit SIIJIC' X'Culii of t! . then 'llir ■ lllll: ■ , . • . - — — • •"^-......,,i,„ii (,i pecunar small muscle .. e nbed(le.l in a densely packe.l .-onnective ti.ssue. Strands r ,rlls pass from this s.,-calle.l sino-auricular node ..ver the inner ^ the auricular .all and appear t., be .lirectly connecte.1 with a r ;,';!'' *'"'"wf°*?''^" °^*' ^'*""**''' i" the neighb..rhoo.l ■■n.n. rx sinus at the ba.se .,f the auricular septum. From this frl ^ ) ^'"^heathed ,n a fibn.us canal, which at the y>«r* """ •■'epU of the ventnde divides, the one branch becoming 378 THE CAHDKn WSCVLAR SYSTEM .•..Mtrihuh;,! t.) tl... U-ft, tl... otluT t., tlu. ri^l.t vH.tri.l... Ka,I, hn.n.l, K v.s oil tn-.,n..nt .|>v,>,o,.-, ru,.,m,« „„,|,.r ,|u. rn.l....anlin.n. tl,.- ,„...i ar ...n..af n„s U„,^ .■..ntnlM.t,.! t., tl... papillary ,nuM.|..s ..f ..i,|,..r vn" tr„l... a.ul InrtluT lK.,.,„„,nj; ,iir..,.t|y <„,.ti.um„s wi,|, tlu- s.,lH.M.I..,.a . ; "I "<'tw..rk ..I Purkinj. ceUs, whi.l, li,... th.- int.Tior ,.r l..,tl. vontri.i: . I luM. c-lls hav,. l„...„ known lor lon«, an.l l.a.l Intlu-rto l.mi r.-Kanlr.j as nn.naturo ..r on.l.rvo.n.. nu.s..|,. fil,r..s. It is tl.ro„«h tlu-s. that J network ..onus n.to .l,r.-.t .■...nnnnueation with the ventrieular nn.s,'!!. <1. It shonl.l Ik, a.l.l..,l that associate.! with this system is an al.nn.lant plexus .,f f,„e nerve fil.ri s with .nrasional Kan.^li.in ,rlls. an.l t I .! snu,-anrKular no. le rea-ives hran.-lu.. l,.,th Cr.wn the Jagus a syinpatlu'tic (aeeelerat.)rj nerves. The Kr..at imp..rtanee of this system lies in this, that pra.ti.'allv all reec.nt w.,rk .lenu.nstrates that tlu- r..,M,lar e..ntraetions of th ..r are mtnnate y as.s.„-,at..l with its pres....,.- an.l lnn,ti.,nal inte^ritv Ihe r.-,,;nt stn.hc-s w,th the el..,tr.Kanlio«raph show that the wave of .■..ntra.t.on Ik-k.,,s at the sino-anri.nlar n...l,.. ,1) |}.,„<,ve the n.nle a", the .•ontra.tions .ras... ,2) iVstr-.y th,- a.,rir centres of the bulb. wh,tlui .lirect through the ,nflu.-n,r of .ir.-ulatiuK Mo,.,! upon tho.se centr.>, or rell.-N. ,■, her from stimuli reacliiuK thos,- ..ontrt-s fron: other orjjans ..r parts ol the bo.ly, .,r fr.m, the heart itself. Hut. in a.l.lition, we nrof;- mze that by .lire.t stinuilus fr.,m within the heart itself, an.! whollv .-ipart r,m. this con.lu.-t.ve systeni, tliere niay arise a series ,,f in.lepen,l.-nt n,M- tra,ti„ns, wheth,-r of the auricular or .>f the ventricular muscle. Tlu- out,„me of these investigations has resulted in a mass of observ.ti,.ns more particularly upon the various phases and forms .,f canliac irn u- larity observations .so recent that much has still to be clarifi,.!, hut luvertlieless, tcrtaiii points stand out ch-arly. Heart Block. .Just as experimentally it is possible, bv injurv t,. tlif aunculoventricular n,.,!ean,! its branches, to bring ab,.ut inconiii.a.ion l.etwe,-ii auri.-l.'s an.l ventricl.-s, so a like incoordination is fouf.l bv elinicai an.l aut..j)sy stiulies to result from .lestructive disease aflVrting UK ART BLOCK 370 iIm M...K' mill hiindle. Tlu- cnnditioii Ims Ihm-ii known for some vcnrs \uiiuToiis casrs liavr l.trn .lrs hill] tallni from the normal 70 or NO f. :;() or less, tht; fall" l)i-iii(,' ^(""iiipaiiu'il l.y syinptoMis »,f an i-pilcptic tMu- (Stokes-Adams svn- 'Iroin.i. It IS iii«..nion>lysn;;geste;raphs, with record nt tlic venous pulse, has shown that in these cases, while the ventricles ,irt' -Jowcd tlu. auricles retain their normal rate. The various grades of tlii> heart block may show themselves either as ( 1 ) u leiiftheninK in the interval I.etwceii the onset (.f anriiiilar and ventricular svstolcs. (l>) an nrr;iM(.nal veiitricular dropped heat. Ct) peri.Mlic dropi)e'd heats, every Fio. ISO >.".iilt.,n..Hu, IrminK, of the jUKulo.aroti,l ami radial pulso waves. The .liiiKram. oonstruete,! fro.,, .• . V. I.:, re,-.,r,l.-.l ,i, the traeings. shows that no »timulu« pa«8..» aloUK the n-p fihres to the veii- I'l' I's, l.iit that (here is eorntilete ilissneintinn of ihp. vot.tr;....,.... r,..-., i- t- \ *___ .. . . " •••"•"e.'^' o..v/nn luuv UU eillllUIUF* paaSCS aiOlig ui that (hen- is eornplete liissoeiation of the veHtrieular rhvtl,m ( idil'.nn ami Kiiehie.) r. S.) fro,,, the aurieular i'tli urniiifl, pulse, etc.. hein^' wanting, until there may he devdoped ' "'"litiun known as two-one rliytlim. or three-one rhvtlim, the auricles ini.- twice „r three times the rate of the vtMitricles, or, lastlv, com- 'f'^ liciirt hiock, so that there is no relationship hetweeu the two :• iiiMis. Here, with entire failure of transmission, the ventricles may It tor years with an inherent or idioventricular rhvthni. Other Forms of Anhythmia. The time is not yet rij)e for a complete - ifu atiui, „t tile arrhythmias. Some of these are clearly of external ' r> "II- »rv^\u. Thus, in those recovering from acute ilines.ses, there marked cliansres of pulse rate which clearly are associated with ii:;., i ' i'lrMtory act. These appear to he of vagns orifrin. Experimcnt- ■I ' ail 1..; sl,.,uu that vas^'iis stimulation either mav hrlng the heart itii'Istili, may slow the heart rate, or may so act upon the con- in ai)i)aratus as to arrest the passage of auricular impulses to the .ISO riiK <\\unin\ \srn..\u sysTf-:.\f Vfiitrule Hut otlu-rs an- .iss,«ia;oil uith to|i,- pluis,-. \\V thus ,nav <«.n..- a.r..ss n-Kularly „r irnrularly int.ri.ose.i hrats ui.rrlate.1 t.. th".. nuuiar rliyth.n. 1 h.-st- hn.ts may be int.T|,„sf.l in tlu- n .ntricl.- alon.- cii Ml tin- auriclf aioni-, or in Imtli. WbriUation. What may hv r»Kar.h-.l as th.> .-xtren... conrliticn .,f irn-jrular y uit.r|.ns,..l luats is th«- cou.litiun of fihrillation or delirium '." V'a ■ ""^""'' "*' " '"'"' »""*'''"« '•••uolarly through tht- h.art 'nusd... ,hthT.i.t arras of thr .uumI,. arr s.m to hv .•ontractinK in.l.- pru.l.utly. so that th.n- is •■ .•ontraction of the h,-«rt as a wholf hut tlir or^an pa>s,.s into a n... ..ion of proKn-ssivily incn'asin« (lihitatiou with an cxtraonhnary fil.rili.ry niovfiiu-nt ..f the wliolf surfarr ' appvaraiKTs surj, as iniKJit h,- ^'ivi. In a mass of snail worms, ,it.ns..|v pa.k...|. wnwlin>r a.tivriy in a thin-walhMl !„,«. Where this .on.lition a e,ts the v,.ntri.l.s, unless it l,e imnie.liateiy arrested l,v v«lmis „r :•*'"■.'■ »/•/ *'»• .f'-^V'^ ■' •'*""^''- "•"' ^'"'^ '"•••""■^'' tl»' '•irnihitioM u M.evital.ly arreste. . It seems pr..l,al.le that this ventrinilar fil.rillafion is a cause of su.l.lni death in some sentiai. hut simply s.-rve as reservoirs.' THE PERICARDIUM From this point on we shall in due order pass in review the main features of the morl.id anatomy and histology of the different organs. It woul. I..- well to say here a word or tw<, reKardiiiR the svstem employed A .lefinite order will he preserved in eonneetion v itli each section, the treatment heinji as follows: (\) AbnormalUlr., (2) Clrruhtun, i)is1urh„ncp,, (;i) 1,,/lamwntnm, (4) l(c,/n:s.i>er I),d„rh,i,„rx (deKencration>, infiltrations, necruses, traumatic disturbances), (.-» !'ro!,rc.s.ve,' Disturbances, including new growtlis, (h) . /,,/ run(liti„„.s tint combui inuirr the ah<,vc headiiujs. It will be understoo.1 that where any one of these headings is passed ov.t, th,'. Tll!."!;''i;,' ^'•'■''1 "'",'" "': -■•i ' H"" 'i'^^BTS"* TIIK PKlili'MHtU'M .JSl nn .list.ir».,u.c,. ni this parti.iilar ..nLr is .I,ti:»-.I nntrxv..rtl.v in o.n,,,. - tn.ii witli till' nrpiii iumKt coiisidrnitiDii. ir. the seconcj phur. lu.t in.T.-ly for .■conomv „f spa not . .ouKht necessary t.. enter into a .letaih..! j,-ct is to pass in n-view these con- .lith.ns with which the or.linary. as .listinct fr.,ni the advance.!, student 'Miylit to lie tanuliar. With these prefatory n-marks we now pass on to the pathological !i'l liisto|o>;ical anatomy of the pericanlium. AbnonnaUties.-There is only ,„». noteworthy ahnormalitv of the l>« ri.„ni.uni. and this is rare, namely, the con.lition of defe<-t. either l'..rtial or complete, of the parietal lay.r. resulting in eith.-r a passace 'T .•nmnmmcat.on between the peri<-ardial and left pleural sacs, or in iNe h.art lyint'. as it were, naked, in apposition t.. the left Imiu Circulatory Disttubaiices. -All serous surfaces, from the similaritv Imt strncture. show « similar succession of changes associatcl with 'I liTcnt grades of circulatory aial iiiHammat<.rv .lisorders The i' "JM. ant network <.f capillaries situated immcdiatdy umlerneath the ;• M.;.l n er renders them all pc-iiliarly liable to present profound irl- I '". ' I*"'* '''"*■*'' "* '"''^ '""'^''•" '''• »>«''l''"'tl.v encounter r. .niial pctcchue duo apparently to irregular and .spasnuKlic lu . t ""N ." he agonal perio,l, with consc(,«ent .listension an.l rupture I ..„, o the poorly suj.ported uperficial capillaries. Tin- hin.ler v< . t of t'le heart is a not infreque.t seat of these pctechiie. ( Vrtain X . M.hstances. phosphorus, and the like, are peculiarly apt to lead " 'I'-, multiple small hemorrhages, secondary it would appear t - - -n. -on o the capillary endothelium. - .y may apji'ir! that • ■''i'a;;;t';;.irtu; r"'' '"' "'^" '"""^ ^'-^ ^""^^^ ^^ -"^^^ ' n.muhtfr'?""-^"!, '•';'•" T''^*^^'""''^ '-^ i'..vdroperi,.ardium. with I „ ,;""/'" ;:^'17^.'" t''«^ ""••mally there is present a small accumu- •';' > n,us f,;:id (Iron, 10 to 20 c.c). In obstructive heart .lisease "-..It becomes greatly mcrease.l (frcm. 100 to . nmch as 1(K)0 ■u mtercstmg point ,s that, despite this large amount of Huid, pressure It brings to bear upon the licar. there mav be ^',is . . .rmnulat.on ot fluid without arrest of the heart acti*;... \, ith .r,Hl , I pounng-out of the fluid there is expansion of the parietal ^ ;;,■";■'"*■• ^V yiat the pressure does not rise sufficientiv high to : - tut auricles, and so arrest the onflow of blood. This con- I'^zjr^vKimsisn- 382 THE CARDIOVASCULAR SYSTKM llij Mn,in,^ often . SX So '' L f l]',"'"" f^'^'^-^' ""'» villous, I" <•" quicklv puIIH apart F^hrin " '•'' ?'''" *'"''^' '"^'^''^ ^'^^^e tl:- -uter cases of' tZre^ o ^of h"errSL"Te ""^' ? ^'^" '" e congestion is so infl.m.nuition. ^'' '"'"'"' "-""^^^^ *here is a hemorrhagic -'•■'.I with infection and btter'Jad;;: to " '"'•""*'"?: «^^ *''"* ^^ or a-ain it irnv h^ ,J 1 V • I ™ '• '*^ *" organisms of low virulence son.;;7:it'lr ormt oclTerS^^^^^ tn tlu ,.ericardium ^''''"'**^^ ^ '^^ t'^^ extension of malignant growth mi.ro.;p„ i rjlaite i^c .1°'°''";^ "'t''""^'/ occasionally odier '-'.';'' rin are separ- ^'•'-rl> ,i 3;i s th P'""^*'^%'^ ''^^""S the excessive fluid becomes V.I ruiar ,M,I thon ^ .^ -^ organization continues there is first ^^''i'l""av be either r«nocri;;«1 V *''*' ''"■.^ 'developed «r/^r../o«,, "P-..n,.rth,.u „ he fo rn^^o'fibro;.rF . ''""!?'' '" '^' ''^'"'^ "^ t'^^ ^'"'n. !<■. or W nnK ™ ?." ''''.'"''' "' (''^ Keneralized o^er both •"^■"1 i^ simprSc perie"d?tir « ^'"^ continuation of an acute "•"" '""^ are lot n,T ,**"""'*'*"• «"* ""ce formed these organized ''""'■ '" ZS-. but Pf™? '•^"*;.«t «"toP^v we encounter «of a r^ i"'i.l. i np.: rthUenTm^ " '""^¥°" "^ "^"^^ Pericarditis ^""■^ '^ilanimaion Th? "' P^Tuar.hum. the results of pre- "mation. This recurrent pericarditis may be met with in 384 THE CARDIOVASCULAR SYSTEM i I m recurrent acute rheumatism; not infrequently, however careful e cam ination will show that we deal with a tuberculous affection. While wi may encounter the more acute form of tuberculosis of the pericardium with abundant recojinizable tul)ercles throughout the thickened peri cardium, it is fretjuent, in cases of tuberculosis, to find few tubercles oi caseous areas proper, but, in the main, a difl'use extensive connective tissue formation, the fibrous tissue being laid down in regular layers which, toward the free surface, give j)lace to a recent fibrinous peri- carditis (see Kig. 1S7). SjiphilHiv Periranliflti.-^ This form is not frequent. It appears generally as a continuation or extension of syphilis of the heart musclt with formation of adlicsions. Actinomycosis is as rare or rarer. Uvtv may be noted the condition of indurative mediastinopericarditis, a con- dition in which the inflammation of chronic type with adhesions extends into the surrounding mediastinal tissue aT'.d'pleura, and, with the con- traction of the ti^Mie, is apt to pull upoi, and distort the heart, giving rise to aberrant nuirmurs and paradoxical pulse. "MillcSiJots/'—Tn this category also belong milk spots. These are localizetl patches of thickening of the epicardium seen most fre- quently upon the front of the right ventricle; they may be present also at the back of the ventricles, and less commonly over the auricles. They are slight overgrowths from hypertrophy of the epicardial connective tissue, and appear to be induce*! by the rubbing of the heart wall against the parietal pericardium in cases of do not grow easily upon the ordinary media, is a matter which has still to be determined. Regressive Disturbances, - Of these only one conditioi? de-erves note, namely, that of serous atrophy of the pericardial fat. In -eiiile conditions, as also following exhausting diseases, the fat of the fiit ( ells may become replaced by serous fluid, so that without much shriiilvage, MYOCARDIUM 385 growths verycon..„o„. th:>uKh tli:!:' ^a! '^^ h^•^xL::J,^'"''T;: .xan.,.le, -n cases „f mediastinal lymphosarcoma. .>r M n ct" '^is ' ( ases ot cysucercus an.l echinococcus l.v.lati.is have been'escribed. MYOCARDIUM • K ,hv^e t em .„t.. four main groups: (,) thosraCng the trunks, duet,.: arteri:;::^ eu '" '""" ^""""^ «"^' ™«'" «^t^"al ^•■p'liiii i /, I tl„. ;.,♦„-, 4. ■ 1 ' • ^"^^^ («) the interauricu ar 386 THE CARDIOVASCULAR SYSTEM is the commonest of all ahiiorniaiities of any organ. In Montreal we have fonnd it thus patent in 14.5 per cent, of our autopsies, and believe this to be an understatement, as frequently the oblique channel is so small as only to admit a fine probe. At other times it is large anu conspicuous, there being various grades up to complete al)sence of septal development, up to the condition of cor biventriculare triloculare, with a single auricular cavity. Often this condition is accompanied by no physical signs or symptoms, but aberrant murmurs have been recorded, together with the ^ihi*iiii^>?«*' '^^aae^^Bann?- « MYOCARDIUM gg^ of the pulinonan'. or tifn,;,, „( *i ti.-"sps, the result of postn;u;;iXI;;;;l-;r"'^'^^*^ ^^"'" ^"-" ^^ '-rt.r hypoplasia of the aorta am 1m ""''TT'' ''"^''-tation of the •oronary arteries, of the s "temic n^,'''",f '?, ""^^j^- -'•'•' of the lMmn.f,Hailifetheductus\.r e^iosns oi'ni/^fh ^ P"''"^"^^- veins. ■mrta is a short, thick trunk foZ nn '^ ''• ^"''""""'•.v «rtery and t'- '.i'"reatior, of the p2onl;v a^e rt'o T'"'/'''V^'' '•^•«'"" "^ ;■ the aorta, below the origh i t t L> , k ' '"' '"' ''^ "'' "''' ''l-ntri<.Ie reache tl t k ^ ^^' " ''''•''"'* t''^ '>l"o''^^»^^^^^^ ■'-ti.' ^ah,.. Walized^J^b^ri the J'"'"'"'-'"^' P''^'^^* "^ th« ""<" -"..dary to chronnmhrt^ritis^or. •'"' ?'"'?''" •^^■^"*' "^^^t r' ^-'"'-l*'; (1) if the brand rsmL^MiS?"*^^^ V'' '"'^^'^ '"-Hlf,Vi,„t collateral drculati n A TfV ™ 'f ""'• ^here may ";"-l^' Iron, either — ^,,1 .,e obiitlr^t;' , ^^«'"»t"tion of the heart t'H' r-runarv art.- ' "^'teration of a branch or branches of :'''*iiHa,;i|,pearsto „ '* '"'"'"^^'"r ' the same and relative (ir 388 THF CARDIOVASCULAR SYSTEM Bejresshe CllM«es.-The heart musele is verv suseeDlible t„ Sa r,., i '■ ™'f'" " l"-'*"-'«"e wasting disease, the ndaXe'''Lrlh'V:ri:::''e^^^^ ™ ™, em 1*1 ,"';■,"'""" " ■■' "" '•""""'■ distnrbanos t„ I,. Cloud, swelUn, (,,. ail) is ,„.„, |,„„ieul,.rlv hi eases „f hvnennre.i. ftt; ;.;':.':;;?■ "■"' '"'""-"r '"""i-'^- The^entS. ' * . «tln tl ,'r"|l'"'*'''" ""■ """""I "'■I' ""^O- "I". I»'< ><"■ i;"ili"g ^aier " " «l>l-«ra.ue „f ,„e„t that has been di,,,.,l i. is fonn.l'"^!!;'!?? 'r ""•"""'""""" "' '!«• "I"« '"<> »e>« heart musele. This iond,ti„n appears to l>e a free.irance and j.-Hhui,... ee" c, t^elVT "" ^^"l'""*" /'--t. This cn.litiou is 1 " stu c„ ti.e naU-d-oye exan.u.atu.n of the interior ,.f the left ventricle otsh,.w„,K Itself well in the papillary .nuscles. The heart .mi .l^r '"«'' " '''"".''^?' "':•' ''''> ■""'''^'- "^^ that np„n pre.ssnre I ' ^Neen the hngers and thnn.l. the tissne ea.silv l.reaks up sonu-tinas ".deed .t has almost a l.nttery eonsistenee. * In onr exp'crie . c ttuse form n. ^vhi..h the whole of the nu,s,.le has a pa er .wi a MH-arance. IS found as a result of c->tre«.e toxie eonditio'ns. the tl . .. cases of penncions anenna. In the latter forn. the small are„s of .legeneratum are tlu- parts farthest away from the Mood sm, tl .nusele ,mme.hately around the tern.inalarterioles no he ng .volv Fia. 191 lid. 192 S2j- *?:-:*iK5-- ^.i^-i. A- YOCARDIUM 391 Fill 10.) 1 1... are f<, .nd sw..!!.,, a.ul l.yalir.e. with I.m „f .mcl.ar stain an.I of rlZni ■'"; '■""""•• ^:*"«^'^ "*■ ^n>'»«''""'t »»y fibrous tissue Fra«mentation.-I„ examum.K sections of the heart muscle it is not umonal to come across ahun.lant fractures, as it mav l>e temu'i h tl:.' .-..urse o the hhres. Aromul these r.o reacti^•e d.auKe ' " ' I n. c,! and here has been much .iiscussion as to whether tn-se J. -tdacts or the result o agonal rupture of the fibres, due. f< r exampi t" a t.rnunul state of irregular fil.rillarv iMirnpu. • oiitraction of the ventricles. That it is not a mere artefact we are iiiclinwi to tliiiik from the fact that the condition is ln(|iicnt in certain particular conditions ;rc ( .r less fatty degeneration. Ilektoen ;lMinjriMsl.es between true fragmentation in wliicli there is rupture along the course " ii lihrc. and segmentation, occurring along tlK' lilies (.f demarcation between the separ- iiif fibres. Fibrosis^ We shall refer to this more piirtKularly under the heading of Inter- >titiul .Myocarditis, noting here that it !> n trecpient result, not only of acute '""•""•"atK.n, but also of degeneration iin.l necrosis of areas of muscle tissue ■\-o, lated with it we frequently get hya- line .liange (p. 309), more rarelv we en- "'iiiit«T calcification (p. .313). "'■re, as an outcome of degeneration ^''"1 '"'rnsis. may be noted the occurrence '.rupture of the heart. This may follow '■'".V degeneration or infiltration, but ";;;•■ re,,„ently is the outcome of coroJ ■'r.^ - isci.se, with loealizwl necrosis. The ;;-' n.,,uo„t. site is the lowest third of :!:" ;:S^ - ^'^"*- ^^-^ --^ition may also follow upon abscess W„llof left vcntri,!,- out into ob- li'iucly, or roughly parallel to the ■i't'rnal aspoet, to show extensive areaa of fil.ro.si.; „, „rea elosc under theemioennliu,,,; 6. areas in depth o myoeanliu.n. (MoGill Pathologieal Museum.) m^-M'^^.^mi^F'^«^M?s!¥s^mmi n92 THE rAnnfftVASrULAR SYSTKM hi,"): "■"" '"'• "' "■""■'l">'iKt. of „l,„„„.,i„,; to the onflow „r a...':,!:;,!!;;: isS:';™''" ' "■ - ^' '"™" "' »«-i-wi,, -'. \NitliiM tlu> lu'iirt its«-lf. tr. p n ,„ tlu. ,.l,uml,..r ,,r c-hatulK-rs iH-inn.! the ohstnu-tio,.' •" W I .n.UK'l, val\ nlar i.K„„,,„.t(.n(r iiri.l reK'iirKitati..i,, the rmimtanf n . IiK-rmsed activity ..f the h.-art, .hie f, central nervous stin.uh- iea-^ir?"" ^;"«^^'V^*' V"'''^-^''"-'"'^ "^ exophthahnic goit heart has been toun.I (h.tn.ctly hypertrophied. If the cause ..f he hroexhJt'^' ";''•'•■ 'f "''' '•' ^'''' J^'"^'^' fi--^* t<, .lihitation an.! 1 ' I fnl nn!. T 7*^'f^'''/'.""^-'-<-«>Pi«tlly the individual fil.res e uH^id; T; 7T'' ""'' 'l'^ P^-'-fopfm-d. Without taking up i*ere Vl ^ t?''"' ''-VPertrophy of particuhir chamhers we n.av unt of 2 ; ' ^""7"' '" ' '^* '^ '^ ^''^- ^'"""f'^'- ^^''i^''' bears the e he I r"*""^ T";'' "'"^"'■^* '^'"'^^-^ hypertrophy. Th„s. \M.re there IS stenosis of the aortic valve if ^s the left ventricle in pdrn...u.ry ohstruction the right ventricle. , is firsttir^i.^ d 1 d r I FT '""'^T"* *•* ^''•^ """^'" "f Wood from one leld 7. 1 ''''"""^•'»'":''^' "P?» the chamber in.mcHliately behind. ,n,.l eft a. .1 .''^^f f"P''y- Thus, where there is aortic stenosis, the emntt [?n "> "r "'"'^8^ '^^P^'-t^^Phy because it atte.npts to hiToi^r A "/^''k"' '"'■"'"''r """''^"^ ^"^"tricle, and this is follow...! in courst- of tune by hypertrophy of the right ventricle. .....uHH,*. r '*'-^"'" '' ""' " progressive but rather a regr.ssive Ik I".Pa««">K. we would recall our contention that two h ^ l' '"'' ^" '•'' reognized, a physiol.,gicaI distension fnllMll r-r '"■^■•""P;"'"^^'^ increased work thrown upon the h.art, followed by hypertrophy an.l a pathological .lilatati..n, an indication that the heart cannot fully res,)..n.l to the w..rk thrown upon it, a condition in which niicr..sc<,,,ically we fin.j that the fibres which had ndergone a true simple hypertrophy n.>w show regressive cIkh:.,^^, with s.)ine shrinkage. THE KSDOCARDIUM 303 New Oroirth«.^-I'rir..ary t„m..p.s ol tlu- rnvo,ar.lium are .listinctlv I,- ..rally ,, „„,|„p.o „„„„r, f„„,„l i„ ^.|,i|,|„,, J^ ,,r,,\.™ZS THE ENDOCAROIDM K-Mlocanlitis is s„ ..ftm confiiu-.l h. tlu- valves tliat wIh>m we use li.s t.r,„ we are apt to pic-ture to o„rselv,.s a 'valvulitis" an I hv a .,< i -^ '• ».;rget that the e„.loeanliu,n i,u.|,..les the whol f ih i , i-litt;:;!:;^::::: """ "" -^ ^ "^"- ^''"■' ^"^' ^•'^'- --^ Abnormalities. -These are rare a.ul co„fi„e,l to the valves. There "!..> ..accessory semilunar valves or onlv two; vers- rarelx has I ».» -;-... I a d.uble orifice ..f the ,„itrai; Abenations o u wn ," "•,";l"'<'a-. ur..l cords ,,ass,„g from o„e papillarv mus.l.. to the th.r ;mli..„t to,u.h,„g the mitral eusp are „ot\.!ry .,K..mL .. \ st II n e ;;i'';;. .al.n,,r„ml.ty is fenestration of the semilunar val '^ T "se I'n-M .tu.ns are situate.) .mme.liately hen 1, the free e.ise in tin- .T.^M.t appos.t^^.,. and cause no functional disturl.ance ^ n^^^^ Disturbances. -The c-in-ulatory .listurhanc-es are of slight 1 •.rt.u.e. llu- healthy valves are non-vascular, hut, just as in J,, 'HI.., alter mHa.nmat.on, there is nrbances. seen m connection with the endocardium, are ; m ed under the heading "endocarditis/' whether acute or Ac ute endocanhtis most frequently affects the valves, although ' "»;'»''';;-l that the mural endocardium ma.; also be •Hctt Ji i, t ' 'T'"'''"'" '^^ '-•h'^'iKes seen more particularlv ■i vniror tw;:;:!^"' "^^ "'^" '^^ ^"^-""^--^ ^^^^^'"^ *»- '-phSlcvH''"'"' '""T *'"^* *he emlothelium lining the I^haRocvtic power and can take up bacteria from the blood. liH|;i| •■lir. ■! ir ti:i iii\..l ill (•.,; Wjill. i'ix lu'iin .lot THE CARDIOVASCVLAH SYSTEM 1 *^ )^"^»''«"irn, w,. may in.HKi.... that „t iM.i.Us of .mrnmin Otic Hct.„„ .s ,„.,st liM.v t.. ,Kr„r, «,ul sn tUv »..ri.-, I h 't tt ... ru.,.|ovn>tru.,.lur valve an.l the vn.tru...lar asin't 7t e • .. . valvfs are favoral.lr amis t<. this procNs H,,t at tl ...... r >tr.n ,1, thr l.u.tma ,„ thnr nu,lti|,lir..teolvtic, the fil.rin of the ve,,.ta- ten a r Ire f r • " ^'^^^'V?*'"^ ^^'t'' ^^eir containe.1 bacUria ic ve „. ^1! U •;.""; •• '"!:""' '•''' ^''^ '''""^^ ^t^'^'^'"' give origin to Ilmc er i.. ^ ^' "''^■'■"^"' ^"^f^^*" ''^-V" •'« expose,!, and . uKt ve'r r^^^ '"*" *''^' ^'^'^-^ ^"'^^tance gL ri>e to K .^i h V„r ; ' f ^•^'".'"P"">ving which, with thinning of the ma DO, tt i "'"T "'fi^'-^" ^"?'^ ^^•'^>' »'"' 'levelopment of a„eur^s- r nSor t , ' r ^^f V^'^' '"• ^^'t^'""* «"^h aneurysm there niuv anZ^^ ,1 ^ ^'•"•"^•"'••I'tis an.l various observer, have Hifferf.! .mkH aniong theii.selves as to the classification of these various grades. -^mm9mmsaBiE^si^z:'if^mm^'^'w^^s^^& THE tSDOCARDIUM ■ -i^rfs 305 h is usiml to make ii hmuel distinction lM.fu-....n (\\ .i».-u Fiu. 100 •it'MMtiv.- •■n,i„™rf!iti:! „t mitral vi;vr- vf. «ilKli„n or. n.uioul»r surface .u «. tMK.ill Path. Mu«.) Fia, 107 ■^'■"''■(L.lr:,! cndoci urait« «itU rupturo of ol.ord* tendinc: „, papillary mu«le; 6. rup.u, rupturad chorda 396 TIIK CMiDIOVASClLAR SYSTEM 1(5 i I i ami iuconsidtTiiMi' and also tlie fil)riii forniatioii over the affected areas is very slight in amount. (2) Vegetative endocarditis, in which the niaiii feature is the extensive formation of thrombotic vegetations, and (.'}) ulcerative or malignant endocarditis, in which the dominant feature is the extension of the bacteria into the valve substance, with necrosis and ulceration and their sequ«'ls. But while making this distinction it must be remembered that an ulcerative endocarditis may also be vegetative, that there may be areas of ulceration, and surrounding these abundant formation of vegetations. Here once again we have to recognize that we deal with a succession of grades of the inHainiritory process, and not with distinct forms of infiannna- tion. Ki(i. 198 U I Iccrativo cndocarditia witli aneurjsiiial pouchinx and perforation (n) of mitral valve. The same in reverae (k). Of the different valves the mitral is most frequently involved in the acute jjrocess. Next to this is seen a combination of aortic and mitral, and in third place the aortic alone. The tricuspid is least frecjuently involved. Chronic Endocarditis. — What we said regarding the pericardium is true with regard to the endocardium, namely, that we can recognize widely dilferent conditions which familiarly, but often fauhily, are included under ihe heading of "Chronic Inflammation," namely, the organizing healing stage of aii acute inflammation, the effects of a recurrent acute inflammation, the effects of granulomatous inflamma- tion, and what is not inflammation at all. the persistent remnins or outcome of previous inflammation. The result of an acute inflaniuia- ^v:M^ mf^'^tm^Ms:. wsmm. THE ENDOCARDIUM 397 Fio. 19U tioii is in the first place a liability for the affectetaKes ()f healing, with cell proliferation and cicatrization in the area lit' i)revious acute infiamnia- tiuii. Thirdly, the vegetations may undergo complete reso- lution or absorption, or, on the other hand, the organiz- iiig process in the underlying valve tissue may extend into tlitni and they may thus hccoine replaced by new con- nective-tissue formation and may become represented l)y ciHitracted fibroid nodules l)roji(ting from the surface (if tlie cusp. 'i'lic condition that we most fr((|iu'ntly refer to as chronic ciidocarditis is, however, one (if ditf'iise thickening, with con- traction of the cusps, leading titlipr to stenosis of the valve, with great narrowing of the orifice, iir to incompetence, with incapacity of the cusps to meet and close tlic orifice, or often a combination of the two conditions. As regards the mitral valve, which is most commonly affected, it must be Mitral incompetrnce Been from b<-low, to show short- ening and tliieltcninK of chorda- tcndinoip and largu orifice a, papillary muscle with attached chordte «o shortened that the muscle impinges upon the valve; fr, patent orifice of valve surrounded by greatly thickened iibr -sed cusps. FiQ. 2(X) liiiil Ml .-i«: bniiiin-hole seen from auricular aspect: ■'■ '' ■ -lit-like opening hidden by fibrous fold (6). Aortic strnosin swn froni aliove, with fusion of cusps, leaving but a small cen- tral orifice. kfiii !)iit I'liai; Ml mind that this valve is not composetl of two distinct cusps a \eil of irregular depth hanging down into the ventricular r. If we study a series of hearts, we find not a little variation 398 THE CARDIOVASCULAR SYf!TE^f in the coiiformiition of tliis veil, and, as a result, when this becomes diffusely thickened hy new fihrous-tissue formation, in some cases the result is a funnel-shaped narrowinj;, in others with contraction of the fibrous tissue there develops a slit-like, or button-hole orifice. As regards the semilunar valves we find that the fibrosis affects more particularly the distal portion of each cusp, with contraction, the cusps become much shortened, so that the corpora Arantii, in the act of closure, cannot possibly meet, incompetence and regurgitation being set up. Or, on the other hand, the separate cusps undergo fusion. Where all three become fused marked stenosis is the result (see Fig. 201). It has already been noted that there may be congenital fusion of the cusps, but it must be recognized that such fusion can also occur as the result of inflammation. If the inflammatory agent attack two neighboring vahes in the angle of origin, where there is little movement of the cusps, adhesion and subsequent organization Fio. 202 Fusion of aortic cusps. The two cusps at a have become united in consequence of progressive slow inflammation oricinalinu at the angle of junction. may take place, and thus immobility of the cusps, with progressive inflammation involving the angle of apposition, may continue until the neighboring cusps become bound together along the greater part of the area of apposition. While it is true that fibrosis of the valves is a resultant of acute inflammation, we are of opinion t to encounter a series of degenerative changes— fatty degeneratioii and necrosis with atheroma and calcification. THE ARTERIES '1 "he arteries may be divided into the two broad groups of those »( the clastic type and those o'" the muscular. The aorta and its main l.raiiclics l)cl()iig to the first. In these large vessels receiving the first iMiiiuIsc of the blood wave, and thus liable to sudden expansion, some- ilnnj; is evidently needed beyond muscle fibres, both to prevent undue (lHtcii>ioii and to bring the vessels passively back to the normal when the (listciidiiig force is removed. We find in the media of these vessels iimltii)lc sheaths of elastic tissue alternating with layers of muscle fil)rcs 111 the media proper these muscle fibres have a circular arrange- iiuiit. Iniinediately within the media, in what is known as the musculo- cla>tic lay(>r of .lores, there is to be found a small zone of fibres having ;i l"iii:itiidiiial direction. Smaller arteries are of the muscular type, III whicii tlic elastica is often reduced to a single prominent layer] '"'•iiiiii.U the iioundary between intima and media; there is often to be iHitrd a„ external elastic layer between Jie media and adventitia. t 1- these smaller arteries, with their relatively abundant muscle l^ivr nid capacity to undergo relatively great dilatation or contrac- ti'Mi that are the great factor in determining the blood pressure. As t" !h. extent to which the contraction and dilatatitm of the arteries i~ '111' er the control of the central nervous system, the evidence before II- iiidicatcs that the same conditions obtain as in connection with the ""' namely, wc have central influences acting through the vaso- L'Hi-Mietors and vasodilators; there exists also a rich system of nerve 4on rut: < \i{i)iov.\scrr..\R systkm cells with prr ccssi's, fdrmiii^' ii pU^xus in tlu- arterial wall, aiul, thirdly, the iiuisclc < I the media is toiiiid to l»e capable of direct stimulation The larger arteries may exhibit strong contraction many hours utter deatii and many hours after the vasoconstrictor nerves are no loiij;er irritable. Leonard Hill, more particularly, has called attention to the fact that, under heijfhtened internal pressure, arteries tend, not to expand, but to contract, and this so immediately as to indicate a local and not a reflex reaction. With regard to the nowrishment of the arteries the vasa vasorum penetrate only into the outer half of the media, )■• the internal elastic lamina is seen to oppose a considerable hindr to much nutritive intcrchanfie between intima and media. We must conclude that the intima is nourished from the blood stream, at least the outer two-thirds of the media by the vasa vasorum, while the inner third of the media may i)ossibly receive nourishment from both sources. Abnormalities.— We have already referred to abnormalities of the larger trunks {p. :>S('»). We may here note in addition that a general hypoplasia has been described, with smrU size of the aorta and main trunks. Some would regard this as truly c( igenital, and as a condi- tion predisposing to chlorosis, general malnutrition, tuberculosis, etc. Others regard it as secondary to impoverished state of the blood, with weak heart action. Inflammation.— The arteries ma\- be involved in the inflammatory atiections of tissues, their walls often being erodeil. That severe hemor- rhage does not happen more frequently than it does is due to the fact that the inflammation causes a thrombosis. Inflammatory states primary in the arterial wall, especially those due to syphilis, will be discussed in connection with arteriosclerosis, by which means that imi)ortant process, belonging largely to the regressive changes, will be discussed without being divided. Biirger, of New York, has of late called attention to the frequency of an obliterative arteritis (thrombo- angiitis obliterans) among Polish and Russian .Jews, leading to presenile gangrene of the limbs. Beginning as a migratory localised inflamma- tion with thrombosis of certain veins, eventually both arteries ami veins of a limb become I'Xtensively thrombosed. The smallest arteries are free, and there is accompanying periarteritis. The cause is unknown. Regfressive Changes. — The observations of Aschoflf, Klotz, and Foster show that the thickness of the larger arteries undergoes pro- gressive increase until about the age of thirty-five, then remains sta- tionary until about fifty years of age, after which, in the majority of individuals, a reduction is to be noted. It is the media that in the main shows these changes, and here, after fifty, both the muscle fibres are at)t to show l)cgiiuiing atrophic disturbances, leading to shrinkage and fiisappearance of some elements, and also the elastic sheaths show greater irregularity in contour and with the disa.jpcarance ot inter- vening muscle fibres, are apt to run together, forming coarser Uranus. Hut beyond this simi)le atrophy, in elderly people ve frequently THE ARTERIES 401 (•iiii.iiiitcr iiulicatioiis of Ixttli fatty and calcamms (k'Keiicratioii of the iiiiimIc. often assc.ciated witli a failure on the part of in(li\ ichial ehistie ImimI^ to take the ehistie tissue stain, which may he mistaken for rn|)ti!re nt the fihre-. All these a|)|)earanees indieate that ith advaneinj; iii;.' tile wall of arteries of the elastic- type becomes weaker. In the :irt. Holes and smaller arteries hyaline degeneration is not infn-cpient. I'.nih in the media and in the adventitia there is to be noted a deposit or inliltration of a homoj^eneous hyaline material. Somewhat similar 1(1 this, involving not the ordinary connective tissues but the elastic ti-iics, is the elastoid degeneration of the uterine, ovarian, splenic, and nili.r arteries already described (p. 809). Amyloid infiltration has a Iinihlection for the muscular coats of smaller arteries as well as the iiiitcr surface of the capillaries. 203 Fig. 204 •ill - I :ik^ nf a.irt.T. (McGill Piitho- loRioal Muw'um.) N'odosp .irtorinsclcroHis. Showing fibroid dvprgrowths of intimu anmnil thn orifircs of the intercostal urierics. (McGill I'atholr.niral Muwum.) Arteriosclerosis.— This condition, or as recent (Jerman authorities t'lin It • atherosclerosis" or "atherosis," is the most common cause 'it 'i- ilh, direct or indirect, in those who attain to middle life or, we iiiii' .ly, after thirty years of age. "A man is as old as his arteries," ' i> incapacity on the part of the diseased arteries to respond to I ' < d- of one or other organ that leads to malnutrition and atrophy " ' organs, even where graver and more immediate disturbances i 1 produced by distension of the diseased artery (aneurysm), ' 'uptiire of the same (hemorrhage and apoplexy). It is thus all ' r!;iiit to have some general ideas regarding the nature of arterio- ■■ ■'- .iiid the conditiot ; leading thereto. Ill of (legeneration, frequently observabh' in those dying from • ii-< ISC is the i)resence of "fatty streaks" of the aortic iiitima, i'i'iir streaks, (lisposed longitudinally, jKirticul in the dorsal ■ 'lie aorta. Examination here shows fatty changes which mav '■' M' to the intima, but xery frequently involve the cells of the nil. I til, nf I 11 Pi or i imp Mi. I A ilru; wiii; I ml! t'\t( 102 THE c.\nninvMii' n ,,. ,i„, tormer is found along the whole length of the aorta, and ■"'!•! most inarketl ni the abdominal section, this secoTid form involves ■'|""i"iii.v tlie ascending aorta and transverse aorta. Here we 'T patches ihat are of a somewhat translucent appearance, liii (.■III-, I'- •; i 1 If : I I wm 401 TIIK CAKDIOVASClLAIi SYSTEyf that Iwiir III) special reliitioiisliip to ciiuTjieiit vcsmIs, that often have their lonj; axis transverse, ami very often have a puckered ap|)ear- anee. Sclerotic chanp-s of this nature are secondary to syj)hilitic inesaortitis. It is now ahnndantly reco^Mii/ed that syphilis finds what nii);ht he descrihed as a "point of eh-ction " in the vasa \asorinn of more particularly the first part of the aorta. There occurs a sinall- celled infiltration around tiie hranches of tliese small arteries in the adveiititia and media, and tliis is followed hy what mijjht almost he descrihed as a "meltiuj; away" of the media in the afi'ecteil areas (see Fiji. 2(t.")). One of two results may follow, either (and this when the I)rocess a|)parently is not very acute or very extensive) the wiaken- inji of the media is followed hy an overgrowth of the connective-tissue elements of hoth iutima and adventitia, or (where the process is more extensive and more acute) in ])lace of such compensatory overgrowth the arterial wall fiivcs way, with rtsultant aneurysiu formation. Scrlion fnmi !torI;i of s\pliiliric mcsnnrtitis tn show rxtri'inc (IruciHTjituin (A nii-iiia iitid iili'iirplii'ii tit I'liistir ti-^sti*': /. thiikinctl intitiut: .1/. liicdiii. thr (inrk«\'^t parts twiutz the I'histir tissiir. At -V, this has (Ijsapprarcfi ; -'t Y. r(tun;eneration occurs in transverse patches, so that at aiitupsy there are to he seen a succession of ring-like or transverse de])rt --!<>ns which are very characteristic (see Fij;. 2()S). The important pnint regarding; this form is that a similar calcareous infiltration of tiic iniiiut is ajH to involve the smaller arteries; if a series of the well-kiiown "pipe-stem radials" he examined, it is found that their hanlm - <>r E*i'i'^0^ .^rC^'^A-S'l Ain'i:hi(ts(Li:i{(ts/s M)n Fiii -MH ri)sis is not at, freciuently to be made out in the branches of the rv (>r apparently following upo,; this !in pcrtrophy, there '"I there exhaustion and degeneration of the muscle; there is '-IS and, in addition, where the muscle has given wav, an '\trgrowth or sclerosis of the intima, or with difluse d'ilata- toi> THE CMiDlOV ASVri.Mi SYSTEM in tidii of tlicsc smaller iirtt-rics tlicn- is ,' fjeiierally thiekeiie«l (chronic periarteritis;. A very reinarkahh' I'onii of sclerosis i^ seen i>i tlie uterine arteries and in the hrandies of the ovarian arteries of niultiparie, clearly in relationship to menstruation. We have already described this, show- ing how large masses of elastoid material become formed, together with the regeneration of a new artery within the old one (p. 'M)). I fere again \vc deal with no infective process, but with a functional stimulus, leading to active new growth of intimal, medial, and adventi- tial elements. The process is clearly adaptive. The observations of Klotz and others show that experimentally, after the intravenous inoculation of certain bacteria or their toxins, there may be developed localized areas t)f intimal proliferation. More than one ol)server has called attention to the supervention of arteriosclerotic changes in young adults following upon typhoid fever. Were the organisms of the exanthems and of the commoner infectious diseases the cause of arteriosclerosis, we would expect to find this condition common at or following the period during which these infections are most rife, namely, in childhood and youth. On the contrary, arterio- sclerosis- is commonest in and after middle age, at a period, that is, wlieii the individual shows a strikin, -"lativc immunity to infectious diseases. Etiology. — We thus supp rt view that arteriosclerosis as such is not in general of infective origm and. indeed, is not an inflammatory process. We hold that it is the expression of a disordered relation- ship between the internal pressure to which the artery is subjected and the strength of the arterial wall, that strength depending, in the main, upon the condition of the media. The same results ensue when there is increased internal pressure, the wall being of normal strength, and when there is only normal internal pressure, with weakening of the med'ii. Whether this weakening be due to inflammatory infiltra- tion, as in syphilis, or to degeneration, as in old age, is a seeoiidary matter. The tendency will be in any of these conditions for the wall to gi%e way at the point of least strength; if it give way suddenly an aneurysm is formed, and, what is more, the intima is overstretched and overstrained and shows little tendency to take on excessive growth. If the strain, on the other hand, be not excessive, it is followed by active proliferation of the intimal connective tissue and this pro- liferation continues with the laying down of layer upon layer until the new development is so thick and firm that it is no longer subjected to strain. With this the sclerosing process becomes arrested. In favor of this conception two series of experiments may be quoted: (1) that of Klotz, in which holding up a healthy buck for a few minutes daily by the hind legs, over a period of four months, the increased l)ressure brought to bear upon the thoracic and cervical region led to marke"l'i.-. ■■! 11,,- ;nl,i,,.. vM,h in. III,-. I , , i. i , .. ,~.. ,,. -ii'- li I'll I- {-t..i 11.-. I lil.'i, U ■ I| 1 fi ASKIIiVS.M 1(17 ill.' r..nr>c nf till' lanitid artery of the rulihit «.r cat. of ropliuiiij;, timt i . .1 iM.rtiuii of the iirtiTV hy ii like length of ii \Vm. IVrforinetl pro|MTly ihf o|)enitioii Ifiuls to no tliroiiilM)sis or arri-st of I)1 fibrosis can onlv lie regarded as fur)ctional or reactive, as a resjwnse tti the increase*! strain thrown upon the vein. Thns. to conclmle, we recognize (1) a .-ue itiManmnitory endarteritis, i\w to l.actcria aiul their toxins, mainly involving the arterioles, wca- -ioriiiliy, and to a slight ext.rit. affecting the aorta; (2) an inflammatory |M riarttritis and mesaortitis, of which -yphilis affords a most striking t Aiiinpir; ('.i) an intimal sclerosis, non-infiamtnutiry in nature, secondary Id actual or relative weakening of the middh- coat (and there may be an adventitial sclerosis of the same nature) ; (4) aminlial sclerosis (Moncke- Inrg's sclerosis) of degenerative nature, tlie hardening being due to the deposit of calcareous salts in the middle coat; (5) a functional M Icr.isis, as seen in the arteri. > 'f the uterus and ovary "n which the nucii.rati(.n and i u formation of the arterial coats v' the dis- ttiidcl lumen of - r older artery is accompanied by a hj. 1^ »r more iuxiirately, (lasi.iid deposit outside the newly formed artery, but il- lived from the internal elastic lamina of the original artery. Aneurysm. An aneurysm is an abnormal and circumscribed dilata- ij'n "I tile lumen of an artery. From old time we distinguish between 'lie true aneurysm, in which there is i)ersistence of one or more of the eoats of the artery to form the boundary of the dilatation, and the false aiieurysin. in which the wall of the art-ry in the dilatation has become a iM.rl.i,! iind the surrounding tissues form a secondary wall enclosing the lolIowingOslcr. we may still further classify the forms as follows: l.ln.,.1 '.'-■I True Aneurysm. {(t) Dilatation aneurysm: (l) fusiform, limited to an area of one of the larger \essels; (2) cirsoid, invoKing an artery of the second order with its branches, the whole series thus l)ecoming greatly distended and tortuous. [0) Saccular aneurysm: this is the commonest form, in which there is a localized and lateral giving way of the aorta or of a smaller artery. Dissecting aneurysm: here with rupture of the inner coat tlie blood makes a passage, dissecting between the layers of the degenerated middle coat, and either makes its way eventually into the pericardial sac or to the exterior f-f the aorta (leading thus to sudden death from hemor- rhage), or back again into the artery at, it may be, some oonsiderahie distnticc from the original site. In this case the new channel gains an endothelium, and the condition may persist for years, the individual possessing apparently a double aorta, and even double iliacs, etc. 408 THK CAimioVASCVLAR SYSTEM [I ■ ■Vj i I II. False Aneurysm as altove desorihed ; strictly the coiulition here is one of heiiiatoina. III. Arteriovenous Aneurysm oecurs, in whieh, from traumatic or other causes, there is established a coniinunication between an artery and a vein, either direct (aneurysmal varix), ii condition in which there is marked dilatation and tortuosity of the vein anil its branches receiv- ing; the arterial blood, or indirect, a siic orifjinally of the nature of a false aneurysm intervening between the artery and the vein (varicose aneurysm . 1\'. Other Forms. There are other forms (rare), such as the parasitic aneurysm seen in horses (in which stronjcyloid worms, present m tiie blood stream become arrested in oiu' of the smaller abdominal arteries and, ftrowinf; and setting; up irritation in the arterial wall, come thus to fill a sac which is in direct conununication with the blood stream); traction aneurysms, erosion aneurysms, etc. As stated in the above table, the conunonest form that we have to deal with is the saccular aneurysm; next to this the fusiform aneurysm of the aorta. Hy far the commonest site of the.-e dilatation.; is the aorta, and in this the ascending and transverse |)ortions. Aneurysms of the abdominal aorta occur, but are not so frequent; of the main branches of the aorta the i)opIiteal arteries deserve .special notice, although the splenic, renal, and other abdominal arteries are occii ioii- ally involved. Another site, of no small importance, is the 'in ie of Willis and its branches, while carefii! examination of the sei.nr brain, particularly in those who iiave been syphilitic, reveals the not infre(iuent i)resen not inicommon to find saccular ancurvsms of hranches of the l.iiliri.mary artery projecting into the cavities; hut senile, or presenile (li'LTciuration. trauma or erosion do not compare in frequency with ~,\|)liilis, as causative agents. Results of Aneurysm.- The aneurysm heing due primarily to a weaken- ing: in the wall, the greater the s(Is ol those structures, instead of the formation of such capsule, tlicre is a process of necrosis and absorption; the aneurysmal wall Im' <>in,.s so thiiined as to undergo rupture, either with extensive hemor- rli.i-e and sudden death or with the formation of a localized hematoma a'id false aneurysm. Thus, for example, a saccular aneurysm of the aMcrHlmg arch ma\- completely perforate the .sternum, and" then form a titlse aneurysm, pulsating and forming a protrusion in front of the Hi.>t, with eventual atn)phy of the skin that covers it, and final <\t.rnal rupture. Kveii in a true aneurysm, sudden increase of pressure ^1^ l.,\ exertion, may lead t.) rupture at some point where the external ' q'sulc IS thinnest, with resultant sudden death. On the other hand, where the circulatory conditions are favorable w I. re. tor examph. the aneurysm is so situated that the contained 'l"<« IS relatively stagnant, a process of obliteration may show itself '> the laying d„wii of layer after layer of fibrin unti'l the cavity i'"">iHs hlled up. This complete obliteration of an aneurv.smal cavit'y I, li..\vever, rare. Xiimerous attempts have been made' clinically t'o "■I'atc or induce this natural process, as by temporary ocdusio'n of t M Mptcry above an aneurysm, by the a they deser\ e. Regressive changes are common and. notably .*»" ■!&«•• 410 THE CAHDlOVASCULAR SYSTE.\f 1i p i under the aj;ency of hactcrial toxins, passive congestion, protein poi- sons, varions mineral antl other drugs, the en(h)theliuni is apt to mani- fest a condition of fatty degeneration, wliich in its turn favors capillary hemorrhages. Hyaline degeneration or infiltration is not uncommon. In our chapter on Inflammation we have called attention to the pro- found changes that may atlect this endothelium as the result of local irritation. Congenital dilatation of the capillaries (capillary telangiectasis) is seen in certain nsevi, and similar 'Uatation may be acquired as a result of active or passive congestion. The tomors that may originate from the capillaries, hemangiomas and hemangio-endotbeliomas have been discussed on p. 277. Veins. — Regarding the veins the following may be noted: as with the capillaries there may be congenital or acquired dilatation. Such dilatation nuiy be rosis of the connective tissue, or, again, of the nerve sheaths, and a cutaneous hypertrophy (pachydermia). As a result of obstruction, tliere may also be rupture of the lymphatics, which, when the pelvis of the kidney is involved leads to chyluria, when the mest leric lymphatics are involved causes chylous ascites, and when the super- ficial cutaneous lymphatics undergo rupture brings about the condition ot lymphorrhagia. \\c liave already discussed the tumors of the lymphatics, namely, the tal>c tumors (lymphangiomas), p. 280, aiifl the true tumors (lymphangio- endotheliomas), together with the rarer true lymphangiomas. In this 'onnection we may recall that both carcinomas, and, to a loss extent, sarcomas, are apt to extend along the lymphatics, and, doing this, may '"niplttojy obliterate thorn. THE BLOOD FOBMING ORGANS THE LYMPH NODES nut iii;.'ll s.i,'. th. ■ \ < ■ . * i i' ; :i AV St.fiJ ai.t-, I'M' ;.^„M nations of lymph tissue are found liiroughout the bo.ly, "il,v III the large groups anatomically described as cervical, axillary, 'iial, or other nodes, not only as the tonsils, and mixed with various ^ir,\ true glands in the region of the mouth, but also as unexpected ■ ariahle aggregations on the course of lymph channels and around 'HIS „i any part of the body. The amount of this tissue varies in ";'nt ages and some structures rich in it in youth, as the appendix ' ' '"I'l^ lose it to a great extent in old age. Its protective function "ii|«'rtaiit one. normalities.- A condition still not understood is the so-called lymphaticus ..f infancy and childhood. In this, accompanying '■ iitiN a proper development of the other tissues, there is found 412 THE cardiovascclah system m 1: I a gentTiil hyperplasia of tlu- lymph tissues throughout the ho;einent of the thymus. The causa- tiou of this state is most ohscure, and some hold it to be congenital. Circulatory Disturbances. — Active hyperemia of nodes occurs in the early sta>;es of infections, and is not so much a step in disease as a preparation for function; the presence of toxins causes a congestion of the lymph node which results in a i)rolifcration of the lymph cells and an increase in their iiumhcr which is defensive against the near-by infection. (Edema of lymph nodes is seen in the case of nodes that are inflamed. Thrombosis and embolism are of no importance, because the node has a perfect collateral circulation made not only of vessels, but of lymph sinuses, so that its initrition can scarcely be interrupted by anything short of a complete cessation of circulation to the part or member concerned. There is one means whereby the circulation through the node can be interrupted, viz., by excessive accumulation of leukocytes and lymphocytes in the sinuses and the proliferation of endothelial cells. This is a factor in producing the central necrosis seen in the bubo and in necrosis of m 'senteric and submucous nodes in typhoid fever. Varices are 'lilatations and tortuosit.es brought about in the sinuses of lymph iKKjcs, with the final f«»rniation of cysts, due to blocking of the efferent 'liimncls. Inflammation. — Lymphadenitis. — If bacteria be introduced into a limb or into a serous cavity tliey are found in the adjacent lymph noiies within a few minutes. At first they nmy pass readily through these and be found in tiie blood; rapidly, however, the node is found to become impervious, to become swollen and congested, to have its sinuses filled with leukocytes, and soon there occurs active prolifera- tion of the lymphocytes of its tissue. Later the endothelial cells lining its sinuses become greatly ;'.wollen and enlarged. All these are condi- tions found in simple lymphadenitis, but where the pyogenic microbes have gained entrance in great numbers, the further phase of suppiuative lymphadenitis is apt to sujjcrvene, the nodes becoming still furtlier swollen, soft, and pinkish on sectici!, yieldiuf on scraping a th'n, purulent Htiid. Central necrosis may occur with the formation of tliick pus. These acutelv enlarged nodes are known as buboes. Frequently the inflammation affects also the immediately surrounding tissue, wliich becomes congested and (edematous (perilymphadenitis or cellulitisl. Chronic lymphadenitis is represented by the enlarged fibrous nixlts which are kept in a constant mild state of inflammation by some irritiitit of moderate virulence, such as is seen in the submaxillary nodes wUvu the teeth are badly preserved; e(iually well-known examples are seen in tuberculosis and syphilis, as again in the anthracotic nodes at tii< rnot of the lung in coal miners, etc. The affected ncMJes are enlarged, firm, and, according to the nature of tlu- offending material, more •'■'• \'y^ pigmented. In the earlier stages there is simple cellular hypcrplii>ia, but eventually the capsule and the stroma undergo fibroid thick* ning THE LYMPH NODES 41 :} which may be so extreme as to cause atrophy of the lymphoid elements |)r()pcr, the node becoming represented by a dense "ncapsuled mass of fibrous tissue. In addition to this in tuberculosis, the nodes may !)<■ the seat of tubercle formati«)n, with a^Klomeration and caseation. Regressive Changes.— Atrophy,— Physiological atroph>- of lymph tissue appears to be pro>;ressive through life, the lymph' nodes being at their maximum in early childhood and diminishing i)n.gressivelv, until in old age the ence of lymph tissue is most marked. Degenerations and Infiltrations.— Hyaline thickening of the capillary walls and of the stroma is not uncommon in coimection with chronic iiiHammation, especially in tuberculosis. Amyloid affection of the (•ajjillary walls is met in general amyloidosis, and more particularly ill local amyloidosis such as may be found in the head region. The disease may ilso affect the fibrous interstitial tissue. Calcification is III it Tuicommon in connection with old caseous tuberculosis, while pig- mental deposits, whether of dust particles or of modified hemoglobin, arc very frecpient, t!ie former in the bronchial nodes, the latter not infrequently in the deeper mesenteric and retroperitoneal nodes in lascs of chronic intestinal disturbances or where hemoperitoneum has ixriirrcd. Tattooing leads to the presence in the near<"st lymph ucmIcs iif the ])igment or pigments employed. Necrosis is met most frequently in tlie mesenteric nodes at the ileocecal angle in cases of typhoid fever, lint may be encountered in various cases of acute infection, bacteriemia,' (lipiitluTia, and bubonic plague. Progressive Changes.— Hyperplasia.— Hyperplasia, as already indi- I itcil, is a not uncommon condition wherever a group of lymph nodes I- -nhjected to a mild grade of irritation; it is peculiarlv difficult to 'Ir.iw the line between this functional hyperplasia and iiiflammation, il. in.leed, it exists. The particular function of these nodes is to respond I" irritants by increased activity which shows itself in lymphocytic pri.iit.ratioii. A compensatory hyperplasia has been noted by .several in v( -tji^ators as following excisitm of the spleen. Hodgkin's Disease.— In this usually there is first noted a progres- H\r tiilargement of the cervical niules which may become extreme, '"■"inig huge conglomerate masses; progressively the other lymph II"!'; of the body exhibit enlargement, group after group, ^iacro- >' irally, the condition differs from tumor formation in that, in early < !■' . tlure is a multiplication of different orders of cells, some of them I" - liraiiiilar and eosinophilic, while accompanying this proliferation tl' I;- a coincident fibrous hyperplasia suggesting strongiv that we ^Mtll a clironic inflammatory process. Indeed, chere is one type 'iTciiimis hyperplasia of the lymph .^les which histoh.gickllv Its cl-isely the picture seen in Ilodgkii. .. disease proper. Much HUTS have demonstrated the existence in a certain number r.f i lloiigkui s disease of a number of curious fine granules taking • ■' tcnstic stain and have suggested that these are derived from I'iicilii; the granules, however, are not acid-fast nor does inocu- iii r( .'II. ai(l that it is a "killing ground" for red corpuscles, that it is in fatal hie and for a short time subsequently a place of manufacture for the saiiie, and that in case of necessity this function may be reassumed. It IS \ery vascular, and its arteries open somewhat freely into its sinuses, at areas, the IMalpighian corpuscles, where the active prolifera- tion of lynipliocytes is favored by this abundant supply of fresh arterial hl.M.(l. The spleen pulp consists of sinuses lined by endothelium, in whuli can be seen disintegrating red corpuscles. The splenic veins form part of the portal system, and apparently the amount of relatively arterial blood that can be temporarily contained in the organ is very large. Its capsule is provided with plain muscular tissue, and, as shown l>,y Roy, the organ exhibits a slow periodic contraction and expansion wli.Tehy the contents of the sinuses are driven out and renewed. Tile spleen resembles the lymph nodes not onlv in its structure and it^ tiinctioii, m short, is physiologically part of the same system, but like the nodes, it has few diseases of its own. Like the nodes, it suffers III general infections, and appears to be to a great extent protective AbnormaUties.— The spleen is rarely absent, but may be very vari- 'l'l<' 111 sriape and size, and accessory spleens sre very common. They arc iHiuilly of .small size, and are to be distinguished from hemolymph 'i;"liiiiis(s arc ciilart^ftl an«l cn^rMrpd with hlooil. tiuTt' is iiim-asril deposit of Mood |)ij;iiM'iit :md tli< coii- neotivf tissue of tin- traltrcula- tfiids to In- iiicnasfd; wiuii the .oiuh- tiou of stasis hists for a loiij; time, tlie fil)^o>i^ is fairly well marked, and '.lie cut surface of the orjrai. is perfectly smooth. >;listeiu,iK. dark red >r hluish red, and the orpin is dense and firm- cyanotic indtiration. Fui 2\i Scrtion frcim an onliirRpd niriijcsti'il !'f,\rvn i)f i-hronic (.liMlniriivc 1 i ili.tcnsp, shoninK thf siuws gri'aily ili.-ti'iiclcil: u. diluted splinif sinus filli-d with n-il r(,ii -. li-s: h. splenic- corpiisili-s Embolism, with the formation of infarct, is frecpient in the s])l(en, hy reason of the larf;e amount of i)luod that reaches it. although it is an orj;an of relatively small size; the embolus is derived usuall.\ from the heart vaK'es, and the resultant infarct is often wedjje-shajjed, with the hase outward, of yellowish-white or white color, showing upon the surface of the uncut spleen a raised area (Fig. 214); single or iiuiltiplt', large fractions of the total splenic hulk may he occupied hy infarcts. The infarcted area undergoes coagulation-necrosis, the nuclei heci)lorii is itself fill«' renderiim the capsule tense, so that on section the capsule ri|i- and the contents seem to hulg" .is if freed from restraint. The c 111 surface is seen to have lost its distinctness, ami the chocolate- (iilored si)leen tissue is seen to Ik' moist and \n\\\>\ in its consistence, UP at times diffluent. The enlargenu-iit may at times hv very great, and .such i\ spleen has lieeii known ,..„. ._,,^ to rupture, either without, or with ^ ' only slight, violence. I'lider the microscope, the changes seen are l)y no means distinctive. Defi- nite necrosis, es|)ecially confined to localized areas, is sometimes seen. Suppurative splenitis may occur in Fio 215 I I >-'tiMli iMiiii utiili' tnfiirf-t of splrcii. It, • ' »ri 1 : /i. -iirrountliim ^plt-fui- ti^^Mir wilh iM .-! 1 iimr^tiun surrcmlHiiiitf iiit'urct. Tul,f'rrnlf»sisnf >plcrn wiltl prcHlurtivc IuImtcuIous pcrispU'nitis iiiiii c-iMOduM tubcrcU'ri, iMc(iill Patho- IttKical Mu>t-iilll. i! I -t.itf jnst described, l)ut ofteiier is merely the direct result of I ' iiiiiiojiciioiis infection in hacteriemia, or of the breaking down of ■i iiiticted infarct. \\\ abscess may burst through the capsule and i'lMiitc a i)eritonitis, or if small, may be absorl)ed, leaving a scar, or ' I'll- may remain and become inspissated and ultimately calcified. Recurrent si)lenitis is exemplified by the state of the spleen in malaria. I , as a result of often repeated attacks upon the organ by the n.i I organisms, many of which undoubtedly ultimately find their way M ^'^a(lnal enlargement takes j)lace. In this, as well as in other • lironic aifections, there is hyperplasia of the splenic tissues I a> 'Veil as of the interstitial tis:me, with nmch increase in size, iiiinness of the tissue (induration), and increased deposit of i)ig- -iicli enlargetnent constitutes splenomegaly. Such changes may oj^KiK-Pl* •»*'ik«"«gKBaW«ftSti-Vt«'«"=' aatliifaaaBRv itnAtUgawr "-, mm.. 418 THE CMiDIOVASCULAH SYSTKAf J A. mi m Ii1 1 occur in the spleen in a nnniher of differont diseases, malaria, cirrhosis of the liver, syphilis, kala-azar, and especially in Banti's disease. Although there arc yet other forms of disease in which the spleen is enlarged, the histological examination of the spit iiic tissue is not very illuminating, nor does it differentiate one form clearly from another. None of these forms of disease apjM'ar to he, pro|H>rly speaking, diseases of the spleen, although the spleen is always involved. The franulomu arc found to affect the spleen. Tuberculosis appears in miliary form in generalized miliary tuberculosis, and at times one finds agglomerativc and caseous lesiims (Fig. 21.")). While the syphilitic Cnmxna is found, the disease is manifested oftenost as a general diffuse splenitis, with fibrosis. Leprosy, Kl&nders, and actinomycosis are found. Begressive Cluiiges. — Atrophy of the spleen is familiar, as it is seen in the old. The organ is small and soft, the capsule opaque and wrinkled, on section the prevailing color is a pale red, and the trahcculffi appear to be abundant, not from actual increase, but because relative loss of the parenchyma of the organ brings the trabecuk' close to one another. The weight of the spleen is greatly Icssencfl. Degenerations and Infiltrations.- The spleen is a favorite site for the deposit of amyloid in general amyloidosis. The amyloid material ap- pears as translucent small areas of dark brown color, separated by normal splenic tissue; the appearance of these amyloid areas has been likened to that of grains of sago, and the name "sago spleen" has been given to the organ thus affected. Where more advanced and dlHiise the walls of the sin>ises also are involved — "baconv" spleen (see also p. 39S). Pigment infiltration is frecjuent in the sjjleen, as will be gathered from what has already been said about its functions in the matter of blood destruction. Apart from already mentioned states, such as malaria, in which it is well marked, is hemochromatosis in which there is a markcil deposit of pigment in various parts of the body. Progressive Changes. — Hyperplasia. — We have considered in a brief general way the hyperplastic states and have also mentioned, when discussing leukemia and Ilodgkin's disease, certain conditions in wliiih there is an extraordinary development of splenic tissue. In some cases the hyperplasia affects the lymphoid elements, as in lymphatic leukemia; in others, as in Gaucher 's type of splenomegaly, the overgrowth in- volves particularly the endothelial cells lining the splenic sinuses.' Tumord. — Primary new growths are rare in this organ, altlioiiKh various connective-tissue tumors have been reported. Occasionally is found a diffuse lymphosarcomatous change, more rarely a nodular sarcomatous growth. Secondary' sarcoma is not common, though it lias ' For the reason that there is diffuse si)Ienic eiilargenient in many general >iatcs it may be serviceable here to tabulate nomc of the various diseases in which splenic enlargement, occurs; we give Ihrni roughly in the order of the degree of enlaruenient that may, as an average, be expectetl: myelogenou.s leukemia, malaria (ague ciikei, splenomegaly (Banti's), splenomegaly (Gaucher's), lymphosarcomatosis. Hodgkin s disease (late stage), acute infections, clu-onic congestion, amyloid, syphilis. - . ^ 55= ^^mm^:ff'j^. THE liOSK MARROW 419 1.. scfoiidary carcinoma; i)rinmry carcinoma is (naturally) unknown. THE BONE MARROW It is difficult to descrihe the hone marrow as a distinct tissue; there I. Ill It an intimate admixture of cells of various orders. In man-- re- ixrls it is intimately allied to lymphoid tissue, not merelv in the e.xist- • 11. (• III Its meshes of ahundiint lymphocytes. Imt also in jreneral structure. N.v.rtlicless, the existence of abundant leukohlasts nivinft origin to ^'niMiiiar leukocytes (jwlymorphs and eosinoi)hiles) l.riiiKs it int<» a ilitl.n lit category, as do also the ahundant osteoblasts and meKacaryo- • vtcs. Pathologically it is as a bl(.o,|.forming organ that it possess«s interest. Circulatory Disturbances.— Anemia in the body generalh is, for once. a-ociated not with anemia, but with hyperemia of this particular struc- tiirr. This IS most marked in sudden hemorrhage and in pernicious jiiKinia, the color of the tissue being i>accs. The marrow in these cases is markedlv reddVried Inflammation. It is difficult to separate inflammatorv disturbances 111 t ir I,,,,,,, marrow from inflammation in the bone as\ whole, such <>tal .iistiirbance being part and parcel of osteomvelitic changes (see J)iMas(s of l|one). The suppurative and graimlomatous forms will Miinl:ir. he discussed m the section upon bone Regressive Chan«es.-With advancing life the amount of red marrow "ii'l(r normal conditions .shows progressive diminution, the active MMiTovv n.IIs of the shafts, and elsewhere, becoming more and mor<- r.|.la.r.l by (at cells, until only at the extremities (.f long bones is anv n.l marrow to be detecte.l, and with yet farther advance in age, the jit Hing absorbed, its place within the fat cells is taken bv a serous 'iMi.l >.. that It becomes translucent (serous atrophy). In 'conditions y osteitis deformans along with marked absorption of the trabeculie I" si'ty inarroxy may become replaced by a fibrillar connective tissue ""I' " lis |y,„K in a somewhat thick mucoid or hyaline matrix. Asso- l^lji'-l with tins there is a diminuti(m • 'le number of osteoblasts. 11 < SUM,, .iiniinution is seen also in osteoiudlacia. ami in both of these "■iinnons active red marrow is characteristically defective Aplastic anemia .iiffers from ordinary pernicious anemia in that >•' Mm. there is an absence of red marrow and of signs of active '•.ituiii ot the erythrocvtes (p ,301) Progressive Chan«es.-What at nrst "si.Tht seems clearlv a hyper- i '.i ■ I the bone marrow, viz., the increased extent of red marrow lltTi n plaFi: tr^', a . ■ ■'• r>ioo(l regciicraticn as after hemorrhage, is scarcelv a .P'rplasia in the sense in which that term is ordinarily used - no uuTcase in the marrow as a whole; there is, nevertheless IToduction of red corpuscles and coincidently of leukocytes 420 TiiH cMi-nnn \<( > i..\i< sysTK\f anil also an awakt iiin;; into activity .f (.Hs liitlu-rto inactive, ,(> tlinf wlicrc prcvitin^lv then- liail >"'ii t.niy marrow \vc now encounter red marrow. In certain <'ases ■•! in\' 'o^reriotis leukemia tliere may Ik- » pyoid marrow ilne to th< cxct'SM priMlnction of myelohlasts hikI leukocytes. Tumors. 'Plic commonest form ■ *' prinu'ry tumor the so-cailcil fiant-celled svcoma (p. .':?7), a form «»f myeloma in •vliicli the nmltiiniileiited cells o' • 'eoih- ic type are prex-nt in >;rcat ahimilance alonjt with other, mi <'nU<. cdls which ;tre polynoiiai, irregular in si/e. tending to he M'.i \ ; inille-sluipetl. As we have jMiintcd nut, this ditlVrs from ili" 'liC r<-(mia in Ix-inj; relatively henif;n, so that >imple excision n a in »l. ratelx early stajtc i> rarely followed hy recurrence Fibroin i' choudro.nM, and myxoin;3 of the marrow have heen described, th^.n^h rh'V me n-fc. .\n interesting form of alveolar urowtii often \v r ■ ■:: cnditioii. ilure is the appeaiancc in -f\rral hones simultaii.uu>ly of diffuse, ili ■icfiiicd frrowths of ^arcon; ifns appearnnce; the cells fomiinir tlu-se ^.towt'iis ^how Mime ariifH ii in different cases, perhajis the commonest form heinj; ma tp ot m isses of cells not unlike plasma cells. Tresumably these are .' myeloi i .stic nature, rncoinplicateil <'ases now no metastases, bi an indi\ iduai nias> may i.ike «»ri m.iii^iiiuit ii;fi!trat:vt- when this is the case, se<'ondary LT'.wths of saicomato' found in other organs. Occasiona i li mile- and roun-!-celk*' -^sn-inas il.v j-rti' THE JfiRE' \LS 421 iiiiiv Im- eiK-oiuiti'f «I, iiriiiiiiatiiiL' in tin- iruirr. w, ft i,.rm( dcrntd iicit fn 111 marrow <•( !|s irniH-r but ir.ini tlu- ■ lOiMitivi ^ssu. franicwork. Wv iiiiiNt lioiihi rh existj-inf of priuiii-y ran ikhhh i>f tin- hone aiit . mv tl=.' m 't of -.".»idar> cjiiicitous irn»\vtli T'uii- <'ureful oumiii itii.n of t!i. mul I hv \. in-r.is Am.wh iiifiltru- li'in l>y ••arciMoiiia ii«ii\»'(l ir !ii he i ,ii m m a \nrfiv |>n>[M)rtioti ol ni-is(it l)rt'u.-,t caiurr. (Vri.nn ni('tt>{iia!it tinman show a jH-culiar l!:il iht.\ to form motustns«-s in {he Im>ii. marrow, notahl.N 'arnnomas 1.1 i' thyroid aiui pn tati-, ar»rtex 'f the iiniially we can find m; vl i^ derived fro;-; the ^^ ijk. iippareiitly dep.i 'ed '\ priiiMTty with wl ■ h foinicctioii with Miten ■ tVatrn- a rrii.ari '■■■ e iiif' ha r .Ictert 4iu'd .-onsi-rri Til idn ' 'I is a di-ctl -ss < It' tl V adrcilii idney a ■ relatiui, ! •tie -xst'iii, ryoffetii tieally m, 1» fune- It^ >m I ■ • an rrtioi u ■ all didia have • t i ve t.s ill rikin^ CI.I' ti„ til. Cfi i> • r|„ t;U' '!., |)oi.' , ',,. iii,i ,.y^ almiul \ and a nj«"«hi!l I The foriii< iiiteniiost coiisi of uia--t ^on* jlomeniUjM, ,' w'uh 'ntaiunj; hiindant file eoiiiiiiii>. of cell- ie 11]" 'f irre^rtdar iii na reticularis The li.rii, ..u. ■;t':iii ii, 'Ui ecli tli< ■en i t- . the V I! l)etwe<' le I 'IS fiK he on ^H' ii It IS endow . tl IS a^ its most :<• arterial tonus; wherefore we ith the vascular system. , ,' in clo.se juxtaposition to the tly vaseulii'-, and coiisistinj; of a divided into three zojh's of wliich cells with relatively large nuclei, consists of coluniiis of polygonal jioi the cajnllarics running be- ona L iculata; the innermost layer i I'olyi (Iral cells, often i)igmente«l, o! cut rely diH'erent structure, con- with 1 imerous nerve fibrils, being, in fact, iglia . the sympathetic system. iiserve, obscurely, it is true, a certain inter- fiinctioi a! activity of the adreii'd the thyroid, Abnormalities '■' ' la\C( Herat e system. Further, th r ■ ;s evidently le a.innal glanils and the pigments of the Hypopi the adrenals is found at times in iiliires ot iopment of brain tissue, and in some sexual dexelopment. Horseshoe adrenals have been accessory adrenals are common; these appear as tiny 'dies oi: the surface of the otherwise normal adrenal; at ory adreiiai ii,-,Mie niay be found underneath the kidney embedded in the liver substance, or again in the neighbor- <• testis and in the broa ! ligament. 422 THE CARDIOVASCULAR SYSTEM m '' lit u 1 Circulatory Disturbances. — Anemia is unimportant; hyperemia of the active sort occurs in infective diseases, and passive hyperemia in general states of blood stasis; with hyperemia, hemonhage is prone to occur, usually punctate, hut sometimes of large size (venous infarct). Fairly frequently in our autopsies on infants, we have found hemor- rhage in one or other adrenal without having any clinical details to correlate with the condition, and in quite a proportion of cases in young children hemorrhage or infarct of one or both adrenals has been the only serious lesion seen to explain sudden death. It seems as if there were at times symptoms referable to suddenly occurring hemor- rhage of the adrenal, viz., a sudden onset of abdominal pain, vomiting, diarrhoea, and collapse. Inflammation. — Acute inflammation of the adrenal occurs in some cases of pyemia and by extension of inflammation from nearby struc- tures. It seems likely that cavitation of the adrenal is often due to roughness in removal of the organ. Softening may, however, occur. Abscesses may appear at times, and sometimes a considerable degree of fibroras is found. Infective Qranuloma.^ — Tuberculosis is important by reason of its relation to Addison's disease. The adrenal may be affected by miliary tubercles, but more often by massive tuberculosis with caseation, affecting one or both organs; here a marked degree of fibrosis is at times to be seen. Syphilis has been noted in a few instances, usually as gumma, though there are enormous numbers of spirochetes in the adrenals of the premature congenital syphilitic. Begressive Changes.— Atrophy occurs in the old, but the alterations in size appear to be usually connected with differences in the amount of fats and lipoids. It may be said that no organ in the body varies so little in size from earliest to latest life. Degeneration of cloudy and of fatty nature is seen in states of general toxemia. Amyloid disease is found in generalized amyloidosis and necrosis is seen in intoxication and locally in infarcts from thrombosis. Progressive Changes. — Hyperplasia of one organ may occur in cases of insufficiency of the other, and it has been noted that in destructive disease of the adrenals there may occur a multiplication of chromaffin tissue outside the adrenal, especially in the solar plexus. There is still some debate as to whether in chronic Brigiit's there be not a distinct hypertrophy, more particularly of the cortex of the adrenals. Tumors.— Two wholly different orders of tumors originate from the medulla and cortex respectively. Several cases are on record of pritiiary new growths of the medulla which, carefully studied, are seen to be true neuromas or neurocjrtomas, resembling in cell arrangement and in the size and appearance of cells the developing sympathetic ganglion (p. 245). In the cortex we obtain tumors of a wholly different order. The simplest and most benign present themselves as nodules from the size of a pea or less upward, originating within the cortex and in struc- ture, formed of columns or cell collections recalling the arrangement of the zona fasciculata. These may be spoken of as adrenal adenomas. THE THYROID GLASD 423 Several cases are now on record of an intermediate type presenting transition from the above arrangement to a sarcomatous, diffuse, and infiltrating distribution of the tumor cells. In other tumors, asain, the capillaries or sinusoids of the new growth become a striking feature and the general arrangement is difficult to distinguish from that of the hemangio-endothelioma. Lastly, there may be what seem to he pure oval- or round-celled sarcomas. As we have pointed out elsewhere, we believe that these are all stages or states of development (if one common form of tumor, • j mesothelioma or, if the term be I)ret'erred, the hypernephroma proper. Great confusion has hitherto reijiiietl regarding the nomenclature of these tumors. They have been •,|)tikeu of as carcinoma, as carcinoma sarcomatodes, as endothe- liomas, etc. Secondary carcinoma is l)y no means uncommon, particularly in cases of cancer of tiie pancreas and stomach. More rarely do we en- eouiiter secondary sarcomatous growths in the adrenals. Blood cysts ha\c heen reported after hemorrhage, and lymphangiectases occasionally (iirnr in the organ. THE Tir."^OID GLAND The thyroids are developments from the loor of the embryonic iiKiiitli. .\t a very early period the connection between the alimentary I iiiial and these offshoots from the same becomes broken and the gland «le\(lo[)s through further growths of side processes which in time hcconie dissociated into a collection of ductless vesicles. Even late 111 htV we occasionally encounter in the stroma of the organ small nill(( tions of cells tending to develop into new vesicles. Each vesicle prcHiits normally a single lining layer of cubical epithelium and is Mirrontided by a connective-tissue stroma rich in bloodvessels and lym- [Hiat us. .\i)parently under normal conditions there may be considerable variiition in the contents of the vesicles, which show all degrees of ">!lH^teIl(■y up to a dense, inspissated, gluey or colloid material. Upon < Mr.njtioii this colloid material affords iodothyrin, which appears to be til' ^iMcihe i)roduct of the activity of this gland. AbnormaUties.— There may be marketi variation in the size and r.l.tioij.hip of the middle lobe, and in a considerable proportion of '1-'- tins shows a remnant of the original median duct in the form "I I process of thyroid tissue passing upward toward the middle of t !'• h.void iKHie, the processus pyraviidalis, sometimes adherent to this ]'} ■• •aiid-like contmuation of connective tissue. In rarer cases there 'iireet extension of this co the foramen rcecum of the tongue, or !'r« M lice of a fistula leading down from the foramen ctecum in the ' '■ line toward the gland. Again, at puberty or even later, cvsts '"nil u! tlie substance of the tongue or between this and the middle i|<>se are lined by glands'lar epithelium and are evidently rem- "I the original thyroglossal duct which have now taken on active """. Accessory lobes or isolated masses of thyroid tissue are not t!i. III!. II' Inl,, .Sic: 424 THE CARDlOVASCiLAR SYSTEM uiicoinmoii. When these occur between the trsophagus suul trachea they may cause grave dyspiuea tlirough further eiihirgemeut and con- gestion. A remarkable feature is that occasionally collections of typical thyroid tissue have been found included in one or other part of the bony skeleton, and this without any obvious tumor of the thyroid. They appear to be fcetal inclusions. Cases of congenital hypoplasia or even of complete absence are on record as well as others of congenital hyper- plasia. These conditions of imperfect function result in delayed growth of the individual and the state of cretinism. Circulatory Disturbances.— It has been observed that with menstrua- tion and pregnancy, the thyroid shows a sympathetic congestion in the female and the great vascularity of the organ makes it susceptible to hypereniic states, so that in passive congestion it may be found markedly enlarged. Cysts of hemorrhagic origin are common in the organ, but this apparently always in association with the formation of local "adenomatous" growths. Inflainination. — It is somewhat striking that in so vascular and so exposed an organ acute inflammatory changes are rarely noticeal)!e. Abscesses occasionally occur in cases of pyemia, and have cxen been known in pneumonia and typhoid fever. Regressive Changes. — The thyroid (,." elderly indiviiluals not infre- quently shows extensive atrophy of the parenchymatous elements accompanied with generalized fibrosis, with hyaline degeneration, and at times with calcareous deposits. In long-continued cases of exophtliiilniic goitre we obtain cvideiice that the parenchymatous cells undergo degeneration, possibly from overwork. There .ire cases on record in which the synptoms of hypersecretion have been followed by tlitise of inadecjuate secretion or hypothyroidism, this being correlated with a form of atrophic flattening of the cells. Progressiye Changes. -The progressive changes of the thyroid are difficult to classify, but the work of recent years appears to be throwing increased light upo the relationship between the different forms. There may be, in the first place, a condition of active hyperplasia of the gland associatetl with increased fimction and coincident increased formation of the specific internal secret- )n. This is notable in the enlarged s(»ft gland of early acute cases of Graves' disease. In these cases, the alveolar epithelium is j)rominent, the cells of good size, and there is evidence of active i)roliferation of the same in the form of ridges and papilhe projecting into the vesicles. There may even l)e more than one layer of epithelial cells, and many mitotic figures. Xv- companying this, the organ is distinctly vascular and the alveoli are moderately distended by a thin secretion. The picture is identiutl with that seen in active regeneration of the gland following experi- mental removal of part of it. An<»ther group of cases exhibits a ditiise enlargement of the vesicles (diffuse parenchjrmatous goitre) but now tlie epithelium is of a flatter type and the vesicles are distended with