CIHM Microfiche Series ({Monographs) ICIMH Collection de microfiches (monographies) Canadian Institute for Historical Microredroductions/lnstitut canadien de :.i!?;roreproduction£ historiq ues ©2000 Technical and Bibliographic Notes / Notes techniques et bibliographiques The Institute has attempted to obtain the best original copy available for filming. Features of this copy which may be bibliographically unique, which may alter any of the images in the reproduction, or which may significantly change the usual method of filming are checked below. D Coloured covers / Couverture de couleur □ Covers damaged / Couverture endommag^ □ Covers restored and/or laminated / Couverture restaur^ et/ou pellicul^e I I Cover title missing / Le titre de couverture manque I I Coloured maps / Carles g6ographiques en couleur □ Coloured ink (i.e. other than blue or black) / Encre de couleur (i.e. autre que bleue ou noir r~7f Coloured plates and/or illustrations / que bleue ou noire) Planches et/ou illustrations en couleur □ n □ D Bound with other material / Reli^ avec d'autres documents Only edition available / Seule Edition disponible Tight binding may cause shadows or distortion along interior margin / La reiiure serr6e peut causer de I'ombre ou de la distorsion le long de la marge int^riejre. Blank leaves added during restorations may appear within the text. Whenever possible, these have been omitted from filming / II se peut que certaines pages blanches ajout6es lors d'une restauration apparaissent dans le texte, mais, lorsque cela 6tait possible, ces pages n'ont pas 6t6 fiim6es. Additional comments / Commentaires suppiementaires: This item is filmed at the reduction ratio checked below / Ce document est film^ au taux de reduction indiqui ci>de«sous L'Institut a microfilm6 le meilleur exemplaire qu'il lui a 6\6 possible de se procurer. Les details de cet exem- plaire qui sont peut-6tre uniques du point de vue bibli- ographique, qui peuvent modifier une image reproduite, ou qui peuvent exiger une modification dans la m6tho- de normale de filmage sont indiqu6s ci-dessous. I I Coloured pages / Pages de couleur I I Pages damaged / Pages endommag6es n Pages restored and/or laminated / Pages restaur^es et/ou pellicul^es Pages discoloured, stained or foxed / Pages dteolor^es, tachet^es ou piqu^es I I Pages detached / Pages d6tach6es [j/j Showthrough / Transparence I I Quality of print varies / D D □ Quality in^gale de I'impression Includes supplementary material / Comprend du materiel suppl^mentaire Pages wholly or partially obscured by errata slips, tissues, etc., have been refilmed to ensure the best possible image / Les pages totalement ou partiellement obscurcies par un feuillet d'errata, une pelure, etc., ont 6t6 film6es k nouveau de fafon k obtenir la meilleure image possible. Opposing pages with varying colouration or '^iscolou rations are filmed twice to ensure the best possible image / Les pages s'opposant ayant des colorations variables ou des decolorations sont film6es deux fois afin d'obtenir la meilleure image possible. lOx 14x 18x 22x 26x 3nx 12x 16x 20x 24x 28x 32x The copy filmed here has been reproduced thanks to the generosity of: McLennan Library McGill University Montreal The images appearing here are the best quality possible considering the condition and legibility of the original copy and in keeping with the filming contract specifications. Original copies in printed paper covers are filmed beginning with the front cover and ending on the last page with a printed or illustrated impres- sion, or the back cover when appropriate. All other original copies are filmed beginning on the first page with a printed or illustrated impres- sion, and ending on the last page with a printed or illustrated impression. The last recorded frame on each microfiche shall contain the symbol —^- (meaning "CON- TINUED"), or the symbol V (meaning "END"), whichever applies. L'exemplaira film* fut reproduit grAce i la gin^rositi de: McLennan Library McGill University Montreal Les images suivantes on: itt reproduites avec le plus grand soin, compte tenu de la condition et de la nettet* de I'exemplaire filn.4, et en conformiti avec les conditions ij iontrat de fllmage. Les exemplaires orlginaux dont la couverture en papier est imprim^ sont filmis en commen^ant par la premier plat et en terminant soit par la derniire page qui comporte une empreinte d'impression ou d'illustration, soit par le second plat, salon le cas. Tous les autres exemplaires orlginaux sont filmte en sommen^ant par la premiere page qui comporte une empreinte d'impression ou d'illustration et en terminant par la derniire page qui comporte une telle empreinte. Un des symboles suivants apparaitra sur la derniire image de cheque microfiche, selon le cas: le symbols — ^ signifie "A SUIVRE", le symbola V signifie "FIN". Maps, plates, charts, etc., may be filmed at different reduction ratios. Those too large to be entirely included in one exposure are filmed beginning in the upper left hand corner, left to right and top to bottom, as many frames as required. The following diagrams illustrate the method: Les cartes, planches, tableaux, etc., peuvent Atre filmte i des taux de reduction diffirents. Lorsque le document est trop grand pour itre reproduit en un seul clichi. 11 est film* A partir de Tangle supirieur gauche, de gauche A droite, et de haut en bes. en prenant le nombre d'images nicessaire. Les diagrammes suivants illustrent la mithode. 1 2 3 1 2 3 4 5 6 MICROCOfY KSOIUTION TEST CHART ANSI ond ISO lESI CHART No 2 1.0 I.I 1^ 140 ;fi^ Ilia ■1^1^ 12.2 2.0 1.8 ■•25 III 1.4 i 1.6 -^ -APPL IE D INA^GE Inc J—-. tfei3 £asl Man S\ri-^\ ^S !""6) 492 - 030C - Phone ^S (71b) 288 - 5)989 - Fq. IT IS TOI^OW / \ GXCIBRIS /pi WvA^^i^ ^ j5l ^ McGill n V >' 1/ PLATE I. STBrtTIKFJ^ ; f>. ilistal eonvohileil tvilmle; 7, irreguhir iKjrtion of distal eonvohiled tubule; S, eml iiortiim of distal convoluteil tuhule; >», rollecl injr tuhule; 10, aseendini; loop of Ilenle: II, arteria reeta: 12, vena recta; i:{, liK)p of llenle; 14, pyramid; l,"), papilla; Ui, papillary vascular plexus: 17, main collecting tubule; IS, calix; 1!), boundary zone; 20, larger brancli of renal vein; 21. larger brancli of renal artery; 22, ilescemling limp of Henle; 2:i, interlobular vein, collecting from the stellate (dexus; 24, narrow portion of aso<'nding loop of Henle; 25, interlobular vein; ■-'(■>, interlobular artery; 27, gloiiienilar capillary network; 28, stellate plexus of caj)il- laries; 2!l, efTerenI vessel; 30, alTerent vessel. THE ANATOMIC HISTOLOGICAL PROCESSES OF BRIGHT'S DISEASE AM) THF.IR RKLATION lO THE Fl'NC'ION \l, CHANGKS LECnRKS DKLIVKRtD IN THK RISSKI.I, SA(iK INSirri TK OF HATH()LO(]Y CllY HOSPITAL, NKW YORK Oi HIM. iH» WiNim ti* I90y BY HORST OERTEL l'lll»> Ion lit |H» KI^^H.|. s»i,, IWIITITK "► KA IHiil iir.V, \».» Vi)«« //, /, LS r R J IF I) PMII.ADKI.I-IIIA AM) t.DSDON W. B. SAUNDERS COMPANY 1910 < iii'vidi.iii , I'.iKt. in \\ . M, Smmikio (iimi'vs^ rKIVTKl) IN AMKHII V KDWAUIXi. .lAM.WAV M'HIK.M IMK ^< IKSIIHl I'll \. I I. f; 1 It MKllll INK I \ ^\IKCI•^ "'H^.^. \ m:\\\ nuiii. wdwiiiimk \ikiimiiis. wikik I IIMI' l>.ll«t.\l» KWK, \l \l.l. lIMKf III KN KWMI'I.I. Mil. Wll ISKI-lllt. n<>\. i\ i.\si iM, i.KMiii iif: PREFACE Tmksk loclun-s wMc «l«'livcn'(l at tin- mjiu'st (»f tln' Ui-sulciit Staff (tf the New York City Hospital in tlir HtKsrll Saji*' In- stitute of Patlii»|o;ry. during the wintrr scimstcr MMIN to 11MM> Iw'forc an audience of recent v:ra(luat<'s and some advained nndcr- ^T-'duates in medicine. My liearers wished to olttain in syste- matic and coimected form tli«' almost daily ex'iM'rience in hospital and |)atholo my cxiMM-iciicc, is not apt to develop ill him a plastic, hviii<; and ficxihic conception in any sul)ject, in other words, no independent thoujiht. Forceaves him no academic freedom, in- divicUial responsiliility and time for thoroiijihness, he memorizes, mostly from text l»ooicitations. and discon- nected demonstrations and clinics many statements and some facts. His coticeptions are those of a certain text-hook, of a certain pii-ic. or, similarly, of notes of a certain instriictor. They are, if the term is permissible, fossilized and immovable. The ability derived from personal, well directed experience under an in.stnictor, the ability to form plastic pictures of occurrences which enable one to comi)ine visual and live, true itleas of patho- lojiical proce.sses without becomin^^ unreliable and ,*.iantastic. are foreiun to most of our |)resent medical .ireneration. Thus, our present methods of teaching resemble the dead inflexible formalism of the scholastic period tau>>;ht in the F.ni'.pean uni- versities durinji the middle aj^es. The medical irraduate of to-day enters a hospital, faces life and meets the keene.st disappointment. His hard and fast text-book lines and schoolboy classifications, memorized care- fully for recitation and writteji examinations, are broken and shattered. Hut wor.se, havinii no other foundation, no critic-il judf-nient of relative values, which is derived from historical knowl(>(lii(' of a science, he is unable to utilize his new experi- ence. He holds new parts of a chain, but cannot unite them, nnich less link them to the old. It takes a stron<>- mind, much stron^icr than the average medical jiraduate has, to evolve successfully out of thes(> complicated circumstances. The others are si?nply c(,ntent to airain memorize actual experience in the Hospital, and apply it as well as they can. They remain un- cultured. PKEFACE Vll Horpiii lip.s a dpfifipiicv of our system of instruction. " Die Welt (les Sehenden," I liave heard Winu't impressively say in one of his lectures, when I was a student in lieipzijr, " ist die der (Jesichtsvorstellun^ren." This view of the jrreat psycholofjist is amply followed in all l';uro{)ean universities. .Medical teach- injr is prijnarily directed toward developing; the power of ol)- jective oh.servation and a scientific method of thinkinj?. In- .struction is <-iven not outside of the hospital, but in the hos- pitals and iti the autop.sy rooms where things can he seen, with much personal freedom in work and study. .Xothinji is more important in the education of a physician than the development of clear visual, anatomical ideas of diseased processes and ability to con.struct their po.ssii)!e relations. The importance of this "anatomical idea" in the education of the i)hysician was con- stantly empha.sized l>y Charcot and X'irchow. It is to he rej-retted, therefore, that unfortunate circum- stances still make it impo.s.sil)le to conduct most of our lar<>e hospitals as academic institutions. Hut I also view with some fear for our future in medical educa- tion the present tendency in some of our medical collejies to introduce s|)ecialized branches of patholof-y, medicine and surj-ery into their underjrraduate courses at the expense of the morpholo-ical discipline, instead of a -reater effort to properly develop the opportunities of the latter in its relation to clinical medicine. I would not deny their value. Indeed experimental patholof-y, medicine and surjiery are very neces.sary supplements or better complements of morphology for the elucidation of sjK'cial proi,lems and in the hands of experienced patholo-ical anatomists; they are suited particularly for advanced students. But thex- can never replace that knowledf^o which is obtained from tlie study of a disea.se. The latter is an experiment of nature which develops out of ever-varyinji, complicated, external Vlll PHKKACK :iii(l ititcriiiil coiKlitioiis wliich we ciimiot exactly artificially duplicate in causes, nuniher, time and expressions.* NO less a inilliaiit experimental investiirator and leader in experim(>ntal pat hole tiiy than Colinlieim significantly delivered his own inauiiural address in assuminu; the chair in jieneral patholojiv in the I'niversity of I^>ij)zi.!i. " I'eher die Auf(l and more spectacular spi'cialization in patholoiiical research without soimd anatomical foundation. Those who douht my words should read the warninzeichnun,u- der IWisartijien epithelialen Xeuhilduniicn." Zentrallilatt f. allii. I'ath. u. path, anat., 11, MXIS. and v. Ilansemann in Zeitschrift f. Krel)sforschun<>\ Vol. \II. 1 !)(»<». .\ spirit of anatomical renaissance, therefore, permeates these lectiu-es. Hut I h.ive .ilso endeavored to emphasize what Cohnheim in his inaujrural address s;iid of patholojiical anatomy as contrasted with normal anatomy: "Die p;itholo<:ische Ana- tomic ist ,u;u- nicht eine deskriptive W'isen.schaft in dem Sinne wie es die normale ist ." Pat holouical anatomy is an explanatory discipline. Its (>ducational v.ilue is therefore twofold: It pre- sents the visual picture of a process and it discloses the irenesis * ( 'i)in|>Mic llic idni'liuliiin remarks of Marcli;iiiil in llic ilcscriptiim of the nrw pallidliUjiial inslinitc at I.i-ipzitf in llic IVst.sclirift fur the .")0()tli aniiivrrsrir.v of tlic riii\crf.ily III Austria a very ilcsiralilc si-paralioii of patliolouy into two cliairs, patlio- ioiiii-al aiiatoiiiy ami cxpcriiiiciilal pallio!o(jy. li.as alrraily taken plaee; in (ierinany the latter is now taimlit by eliniciaiis. 'I'lie siliiation is very similar to the state of pliy-iolo(jv anil anatomy lifty vears a(jo. PHEFACE IX of the process, at least, prepares the proper way for its uiider- staiuUnji. These iM)iiits I had constantly before my eyes in the delivery of these lectures. Some may find, perhaps, a more extensive review of ele- mentarv and jreneral patholoj-ical questions than may seem warranted to them hy the nature of the subject in a jiraduate course, .\fter deliberation, I have (-)ncluded, however, not to eliminate them in the publication of these lectures, for the activ- Uy of invest ijiators has been so productive that such reviews mi«iht possibly be welcome to tho.se who have been unable to completely follow the.se subjects. Some of them have had important contributions since these lectures were ready for publication. Particularly in the doctrine of fat dejieneration and fat infiltration, the views still underj-o a kaleidoscopic cliaii.iic Many of the ideas expres.sed in the following; pajres are ba.sed on data collected by me and former and present assistants dur- inji a period of six years at the City Ho.spital. My f-reate.st indebtedness is to Dr. I.indsay .Milne, who has .sacrificed nuich of his own time and thouj-ht, and to whom I owe the selec- tion of typicjil pictures for the acccmpanyinji plates. They wer(> execut(>d by Mr. Martin, the artist of the Hu.ssell Sajje In- stitute, '{"he -renerosity of the Trustees of the Hu.s.sell Sa publication possible. To the publishers I owe very hearty cooperation and valuable sufr-iestions. I may fittinjrly introduce these lectures after the manner of Morfrajrni in his j-reat " De sedibus et cau.sis morlwrum per anatomem inda,iiatis:" ("ra.s.sus in Cicero, ' De oratore," II, 0. 2'), quotes Lucilius as follows: " C. Lucilius, homo et doetu.s et |XM-urbamis dicere .solebat najiw .sr ah itulortissitnis ncque a (loctittsiniis k(fi vcllc, quod nlteri nihil intclhqercnt, alkri plus /o//rt.s.sr quniu i/isc." •' C. Lucilius, a lejirned and ver>- polished X PKEFACE man was in tho habit of sayinji that he did nol irish to hr rend cither bjf the vcrtf learned nor hi/ the very iinediieated: for the latter would not nnossibly knoir more than he himself did." IIoHST Okutki,. HvKsKi.i. Sauk Instititk ok I'ATiiDi.iiiiV. Cirv IIiisi'itai,, Nkw Vokk City, Vd/v «((«)•, IHIo. CONTENTS FIRST LECTURE ,.„,y, UlSTOKK Al, InTKODICTION AND C'lASSIKICATION 1 SECOND LECTURE Tin; Stui fTiiiK of thk Normal Kidney and thk Diffehknt Views OS Its P\ncti(>ns in Tiieik Relation to the Patiiol()(;i(al \'ahiatio.vs 27 THIRD LECTURE The De«!Eneuati\ e and Exioative Featikes of Nephhitis 4.") FOURTH LECTURE The Rksilts and Tekminations of Degenerative and Exidative NeI'IIHITIS. i'ltODlCTIVE CllAN(iES IN THE KiDNEY IK) FIFTH LECTURE FUODK TIVE XEl'ilHITIS. CllANOES IN OtHEK ViscEHA. (EdEMA 1()1 Notes and References .7jjj AlM'ENDIX .,. , Classification of Nephritis 014 Non-inrtaniniatory Lesions of the Kidney, Oecasionally, l)ut Wrongly, Grouped as Nepliritis '^14 Index of Names ,-,,- iu Index ok Sl'h.iectis 291 THE ANATOMIC HISTOLOGICAL PROCESSES OF BRIGHT'S DISEASE FIRST LIXTUHE* HlSTOHICAL I.NTKODrCTIOX AND ClassificATIOX (lenthmoi: , It is with -reat pleasure that I have followed ^•our invitation to speak to you about the diseases of the kidnev ordinarily grouped as Brijrht's disease. But I appreciate, and'l think vou probably will before I finish these lectures, the ^^eat difficulties which prese,it themselves in a study of renal lesions, and more particularly ui that -roup which we intend to discuss. The diseases of the kidney differ in a peculiar wav from the diseases of other or-ans. Three points enter into this. First, there exists an exceptional, intimate correlation of the diseases of the kidney with concomitant or associated conditions which we cannot dismiss from our consideration as we do in the study of other orjians. To illustrate this concretelv I mav sav that one can investij^ate the inflammations of the lu.iji, of the heart of the liver, or of the spleen, more or less independently of other organs. We can abstract them from the rest of the ^ody, so to speak, and observe them independentlv. This is I'ardly po.ssible, however, in the diseases of the kidnev, more especially in Brij^ht's disease. I need only to remind you that *Deliverpuiiiiii- uria, etc.. arc so iiitiiualcly coimcctcd with tlic cliaiiKcs in the kithicys that it hccoincs (>vi(lcnt at once that licrcin iics a con- sidcralily coinplicatinii factor. Socondly. tiicrc exists irreat difhculty, and at the same time a much greater necessity here than in ahnost any other orjjan. in estahlishinfi a pntper relationship Ix'tween structural and func- tional changes. \U\t not only are we almost entirely ijinorant, or at least uncertain, of many of the physiolojiical conditions of the secretion and of the part played therein by the various com- ponents of the kidney, l)Ut in the patholoj^ical variations we are constantly confronted l)y obstacles which consequently are hard or e\en impossible to overcome. Finally, a third factor which conflicts, and a rather personal one, is the multitude of views held with rejrard to the normal and patholojiical functions and the anatcmiical and histolofjical chanjics in the kidney, which, on account of their number and of the peculiar subjective tendency here displayed, make it almost impossible to present them .satisfactorily and entirely. It is by reason of these conflict inn- opinions that the presenta- tion of the subject is diflicult, and it will undoul)tedly plainly appear when I review for you in a necessarily short and circum- scribed way the evolution of tiie various conceptions of the character of Brii-ht's disea.sc. To a ^reat extent this is respon- sible for the uncertainty which exists even to-day. This leads me to (pialify the necessity of such a historical review. It is, no doubt, interestinj;; and instructive to follow the historical development of the various views held al)out any disea.se; but I consider it imperative in the diseases of the kidney, because it is im{)ossil)le to have an appreciation of the relative value of the present ideas, unles.s we are fully acquainted with HISTOHICAI, INTHODl CTION AM) (I.ASSincATIO.V 3 tho ori«i„ „f thos.. ideas a,.,l tho (lrvelopmo„t,s thr.„.jih which they have passed. It apiM'ars (hat there are es«.,.tially three interwoven dis- I""«'<1 IxMiits. and. as you will see. fundamental ones. Th.- first IS. What u.Han,nmtions of the kidney are to be in<-luded under ♦'"' J»"'din^r of Brijihfs diseas«.? The seeond. What are th.. ••hara<-t(.ristic features (,f this inflammation? Ihe third Are there any non-inflaumuitory proee.s.ses which form es.s^ntial parts of this disease? Of them. I consider the second the most imixirtant. It is oa.sy for you to appreciate that whatever conception mav l,e held of an inflammaton- con.lition of the kidney is necesslirilv dependent ur,on the view o,>e has of inflammation in ^^eneraj- and the various views which have \>een advanced from time to Ume center around the evolution of this ^eneral pathological conception. One nristake. too frequently made as the result of histolo.dcal stu.l.es. IS to re,.ird pathological pro,.e.s.ses as stationar^; in- flex.hle. of .reat m.iformity in appearan.-e. or at least froin« on with mathematical precision in temporary arranjjement. One oujrht to appre,.i.,e from the start that, as the name implies i.it u,loo;H-d pro..esses are processes; that is. foivver .-hantin. H..stolo,.cal!y weol,.servesta,esof a process, but we cannot ime^ pret them m the sense of a simple introduction of certain abnor- "•ahties „,to an oroan. where they lie more or less like foreign -hes .Neces.sarily. they c-ontinually vary, constantly influ- ced by conditions which a.ain depend upon a lar,e number of outside factors and an equally lar^e numlx^r of ever-chansin. •ndivKlual reactions on the part of the organism. Stricth- «peak.n,. one mi.ht say that there are as many di.seases as thei. are disea.sed individuals. While this is to be taken into con SKleration m the study of any disease, it can much less be dt 4 HHKJIIT S niSKASK n'.i;:inl('(l iti nephritis. Diseases must Im' >rr<)U|H'(l, therefore, with a tliornii<;li appreciation of tliese |H)ssil)le variations, and the strict(>r and more circumscrilx'd a chissifieation, the more faulty it will always he. For a definition, to Ik- exact and <'xhaustive, must consi.st in a rejM'tition of all component parts of a sub- stance or a process. These it sets out to systematize. Thus, as Taine lias put it. '•un systeme est une explication de I'ensem- hle et indicjue ime oeuvre faite." l)isea.s«'s live, however, con- stantly chanjie, and develoj). Influenced l>y iiuuimerahle outside and in.side conditions, they defy strict codification in nuich the same mamier that any form of life does. C'.uided l)y such considerations. I shall not follow the plan frecjuently employed hy lecturers in a too dogmatic and coniplete pre.sentation of the sul)ject. It will Ik' my endeavor to pmsent ess<>ntially the certain anatomical and histolojiical kaowled; time; even the Hii)le mentions as imi)ortant "to test a man's heart and kidneys," which nniy indicate a possible knowledjie of the rela- tion.ship between heart and kidneys; but reliable data do not appear vmtil more thorough knowledjie, gained by autopsies of human l)einj:s, drew attention to certain anatomical chan<>;es which the kidney may under-io. -lltius. between ;i()()-4()(» \. 1).. came to the conclusion that certain cases of (edema and ana- sarca were associated with hardened kidneys. This knowledjje was extended on the clinical side by an equally fiood observer, HISTOHICAI, INTHODrcTloN AM) (I.ASSIKICATION Avimiiiii, !il»rvation8 which he made in order to determine the caus<> of dropsies ho fouiKl healthy kidneys hut distinctly diseased livers. Dropsies, which were then regarded as morbid entities, were therefore clas- sified as with and without kidney disease. A fireat step toward better knowledge of the diseases of the kidney was made by ("o- tu-ino in 1770,' who demonstrated for the first time the occur- rence of serum-albumin in the urine of dropsical patients. He brouudit that fact into proper relation with ease.s of u'dema and anasarca. i'Ut erroneously held that it represented an efTort on the part of tlie orjranism to <;et rid of the (inlcMiatous fluid. Cruikshank' ehiborated Cotufino's fin , and found that certain cases of (wlema showed no albumin i the urine; finally Wells' demonstrated the presence of blood and albumin in the urine of scarlet fever. (Iradually, then, positive anatomical and clinical evidence accumulated, which pointed more or less closely to the connection of dropsy, all)umin in the urine, and kidney dis- ease. Early in the last centur>' the examination of urine had lieen well elaborated, particularly by Brande and Scudamore,* who already knew that idbuminous urine contained less urea than tlid normal urine. Brifiht's work was ushered in by that preliminarv knowledjie. Like his predecessors, he commenced his observations with an investijiation into the causes of dropsy, and it was his purpose to determine the underlying anatomical condition. He collected and frrouped, ver>' excellently indeed, a certain number of cases m "I i >1 ilKKillT s DISK \^K (if u'llriiia :issii«-i:it(>(l with chaiiucs in the kiiliicv, mixI in a similar fashion certain ras»'s of ascites, anasarca, or tnlcina with diseases of the liver. .mikI it is mainly lki>:hf's credit to have pointed ont more clearly than an> one hefore him that certain easi's of dropsy are constantly associated with cerlidn changes in the kidneys, and others (Mpially w'lh certain diseases of the liver. Thes<' fir>-t ol>s«'rvations apjM'ared in IS27 - a classical pul>lication illustrating: the;ire:it value of thorou;:h. painstaking:, ohjective observations and deductions therefrom." It may Im' said that almost everythin;: which Hrijrht advanced, as far as pure oliservation j:o<'s. has stood the test of time until to-day. The clinical pictures which he presented, particularly later, in the first vohnne of the (iuy's Hospital report on chronic renal dise.'ise. have never Ix'en l»ett<'r drawn hy any later author, and to-day we have no lietter description than that he jiave us." Kven on the anatomical side his ol)servations stand to a jrreat extent to-day. He properly correlated the hypertrophy of the left ventricle of the heart with .some diseases of the kidney, and he advanced the same views with rejrard to this relation which are held to-day. ( Particular attention oujiht to he paid to the exe- cution of the plates accompanying: his first report of melish(>d a number of very important observations, extendinii his oriiiinal views on the subject. He divi(h'd the disease into three y is traiisforiiHMl into a jjraiiulatiKl H'xtun'. as if tine fjraiiis of ^'••u^l had Ihm'II spriuklod over it. ami wMiu'titncs innmiH'ral.l.' s|MM-ks, of no clrfinito form, an' eciually sln-wn over llx' surface. I-itrr, tlu" kidiu'V assunu-H a tuln'roiw ;i|)|M'araiic«'. as in stajic one. • In tlif tliinl. tho kidney is (luito roujih. witli numerous |)in- point projections, yellow re»l and purplish. It is hard, lolnilated, idinost cart ilajiinou.s. and contracted." In these lesions just «piote- rela- tion to each other. He rejiarded the chan>:es " as due to altera- tions in the circulations of the kidney, brought about by in- fluences of the skin and stomach, or [noiiucimi a (hridally in- Ihmitintonf romlilioti of the kidnvif."* Hrijiht did not think that the lesions here presented were the only ones which were found in the kidney, for he described in his orijiinal article .several others, which, however, were rejiarded a.s of minor importance. The ideas of Brijjht necessarily attracted attention, primarily in Kn^dand, and were taken up particularly by Christison, Osborne and Crejjory.'' Christison separated the disease itito acute and chronic forms, althoujih he held that it was e.ssentially chronic. He doubted that all the various lesions were stages of one morbid process, but left the exact nature of it undetermined. He described the following seven different chaufjes in the kidneys: • 1 particilarlv i:(Mi(M';ili(>n of ('orti(';il or tiilmlar stnic- turc. I'M Finely .;:r:iiiiil:ir, (/'I hotrvoidah o. Dciiciicratioii l>v a smooth, lioinoiicnrous, ycllowish-iiray mass, iiit(M-mt'(liat(' in consistence between tliat of the liver and the lirain. 4. Disseminated tuliercles. ."). Induration of semi-cart ilaiiinous hardness. (>. Atrophy with disapjx'a ranee of proper renal structure and with or without one of the previous morbid states. 7. Simpl(> ana'mia. lie recognized these in the followiuir stajies: Incipient sta<:e of coiiiiestion. or reaction. .Middle stau;e with a nearly destroyed cortex. .Vdvanced staiic. where the tubular masses were (le- stroved. Christison knew that the di.s(>ase tends to suppress the solids in tlie urine, that it is fre(|uently associated with serous inflam- mations and severe .-iiwemia. and emphasized the imprejination of the body-fluids with urea. On the other hand, some oj)position arose on the part of (ira\es, lOlliotson,'" and Copland." (iraves.'-' particuhirlv, re- ;arded as the secret- iiifi structures of the ki(hiey. But because of a very insufficient and somewhat hypothetical conception of the finer structures of the ki(hie>, they proved of little conseciuence. (lhis. contracts, and produces a cirrliosis of the kichiey. He employed the term cirrhosis in the modern sense of coni'ective- t issue formation with contraction. Based on his own observa- tions ;ind those of others, he differentiated between these tyi)es: I. Steatosis (tf the kidney ((iluue and Johnson). '2. Subacute inflanunation with cyst forn-iation. '.i. Cirrhosis of the kidney. 4. Swelling- of the kidney due to (edematous infiltration and first sta.iic of cirrhosis. ."). Acute descpiamative nephritis followinu, exanthemata (Johnson i. The lilomeruli. in his opinion, were not chanjied. Ho should l)e particularly reniemhered as heinsi the first to jiive a careful .lescription of tube casts, later studied thoroujihly l>y Xasse. Simon. Scherer. and Hovida. He held that they were composed of tii>rinousex\!date. and similar views were entertained by \ ojiel. On the other hand, Canstatt.'' who with Siebold had studi(>d two cases of the disease, reii;irded the lesions as either a non- inflammatory det)osit of albununous fibrinous uranules. or of fat in the /ortcx: a "steatosis renum.~' In llntilaiid there appeared about this lime Bowman's jiveat work on the finer structures of the kiilney. which .uave a new impetus to the study of Brijiiit's di.sease. Of these works, tho.se of Johnson,-" Toynliee.-' Simon.-'^ and Busk"' are of es- petial importance. In these investigations there appears for IIISTOKICAI- INTHOOrCTION AND CI-ASSIKICATION 11 tho first time an eiuloavor tohold difforeiit procossos rosponsiblo for the syiiiptom-coinplex and charactoristic features of Brijiht's disease. Toyiil)ee was tlie first to describe the thickeninjr of the arter- ies, and interstitial celhilar proliferation, 'v'lile Johnson paid particular attention to the fatty infiltration of the tubular epitheliutn. leadinji to what he called a chronic des(|uaniative nephritis. He held that th's may develop independently without previous acute chan^'es, and therefore was one of the first to discard the uniform view of Brijiht's disease. He reeo}>;- nized. further, amyloid and fatty kidney, iiusk's idea was that the contracted kidney resulted from a capillar>- phlebitis, as granular liver results from a portal thr(mibo-phlel)itis. Important coiitril)Utions appeared in works of Reinhardt '" and Frerichs." Keinhardt reeculiar hick of organization on the part of the fibrin, and leadinji to a destruction of the epitheliimi. Krerichs. extendinji these views, distinjjuished between the fol- lowiiifi al)S()lutely correlated stajies: First, hyperiemia and l)ephritis. We come now to a very important turning-point in the history of Bright's disease, as well as in the whole history- oi pathology. In lSo2 Virchow" published a celebrated article in the fourth volume of his " Archives," on " Parenchymatous Inflammation." 12 UHKillT S DISKASi; lie WMs the first to use lliis term, which since then h;is hccomc coinnum property. In it he hiid the corner-stone for ;ill future idens ;il)out parencliyiuiitous inn.MUUUMtion. ;ihhouiih you will |)resently see th;it N'irchow's ideas of parenchymatous inflamma- tion are entirely dilTeicnl from what was later reuarded as such. It may therefore he necessary to detail some of his views in that relation. Before the time of N'irchow. the ideas of inflammation may he uained from N'oirers definition : " Inflammation capillary hyper- M'lni;! : hydrops tihrinosus." \'irc'!ow's ohservatior.s led him to the conclusion that it was (>rroiieous to reuard the exudate as the essential features of any inflanmi.ation. hut that the constant char.icteristic of inflammation w.is parenchymatous tlejiener- ation. This resulted from an excessive imhihition of e" "ded fluid, which lie rejiarded as exaiiiicrated nutritive materia! It led him to the idea that the inflammatory process was really a nutritive disturhance of parenchyma cells, and he ajiplied this view particularly to the kidneys. .\s the re.sult of this excessive nutriment the cells heconie larjje and .swollen, and the alhuminotis molecular contents are increa.sed. Thus, he as.s(nned, the pro- toplasm (>f the cell disinteiirates and hecomes fatty and jirauular. In some cases the whole of the exudate is thus consumed hv the epithelial cell, so that the fil)rin does not appear, and the only evidence of the presetice of the exudate is fotmd in the alhumin which is carried ofi" in the urine. Virchow, then, rejiardod the parenchymatous chanjie as the essential feature of every in- flammation, and this disturhance of mitrition, as he termed it, differs from simple dejieneration only in dejiree. He concludes with the.se words: "I vindicate ahove all the dejrenerative character of inflammation, and althoumia renum oritur, in renum super- ficie astra venosa conspiciuntur, (piia sanguis venosus refluere n(>(iuit. -Turn celluhe ilhe metamorphosin adiposam .subeunt, emollivmtur, deniipie massam formant pultiformem, (pue urinie admisceri potest, (pio urina fit adiposa. ilmv quidem admixto raio fit. plerum(iue massa iUa resorbetur. Processu progrediente canaliculi uriniferi collal)untur. (piai in renum superficia loca tlepressiora formautur et renes speciem granulosam pne se • llalii's iniiu'. 14 HIJKiHT S DISKASK fcruiit. Loca data in rciuim snpcrficia coloro intense flavo |)()rt(>s sunt. (|iue nietainnrpliosin adiposani non suhierant." lie. theretore. classities the lesion in tli(> three previously detailed stages.* It is interest inir to recall here that Virchow sharply dilTerentiated the cicatrieial formation as the result and not as part of the inflanunalory process. Wv will learn that such a stand has only receiuly been taken ajiain by .XscholT. Ill IS.")!* Arnold Heer. a |)upil of Virchow. stinnilated by Hownian's and (ioodsir's work. |)ul)lished a inonojiraph on the eoiuiective tissue of the human kidney in health and disease." In this he paid |)articular attention to the inter.stitial hyperpla- sias in various forms of nephritis, which he carefully described, alone and iti connection with the accompanyinif vascular and parenchymatous ehan<:es. It is interesting!; lo note, in view of Weiiicrt's later work and ideas, that he inclines to the belief that atrophy of tul)ules and jih)meruli prec-edes the connective-tissue hyperplasia, and that the process is more or less of a peculiar complementary character, i Pp. 110 and 122.) Interestinji is. further, that he, as the first, attaches considerable sijinificanco to the proliferation of the epithelium in nephritis (p. 12")). which explains, in his opinion, that kidneys may show microscopically .small atrophic glomeruli and appear by Klebs,'" and which was later rejiarded by Hibbert'''as the universal incipient lesion of all forms of Brijiht's disease, broujiht equal support to the prominence of the vascular and interstitial chanjies. However, it remains Traube's fjreat merit to have conclu- sively separated the cyanotic and amyloid kidneys, as non- inflannnatory, from nephritis. These views of the pureh' vascular, interstitial inflammator>- nature of nephritis did not entirely succeed in replacin<>; Virchow's conceptions. As in other scientific discussions where both sides of an ari^ument contain truth, both were accepted, but un- fortunately as distinct and different types of nephritis, and it became prevalent to speak of parenchymatous and interstitial i\ephritis in a contrast iny the curlier writers and also by Cohn- heiin ami Nircluiw. Whereas these <-()iisi(lere(l an inflammation only as an exudation, and Virchow essentially as a dephritis. This, of course, included the non- iiiflannnatory amyloid in the cate^'ory of Hri^rht's disea.se. while a contracted kidn(\v without cedema and albumin was to he ex- cluded. A perfectly untenable position! In I'.n^land. further studies gradually led away from the orijLiinal id< as of Hrij-ht. After ("hristison and Johnson had doul)ted the intim.ite relationship of all forms of nephritis, voices in that direction became stronjrer. Particularly Sanmel Wilks^' renarded the lariic whit(> kidney and small «iranular kidney as independent .-itYections. followed by (Irainjier Stewart,'"' .'"id in ISTlMiuU and Sutton " went so far as to declare that artoriiil and capillary fibrosis was the cause of ccntracted kidneys. In (lermany. liart(>ls" was the first to introduce the idea of the independent chanicter of the so-called chronic interstitial nephritis which he attrilmted to a primary jirowth of interstitial tissue, lie distlii,miished it from the so-called parenchymatous form. Senator.'' however, ajiain drew attention to the point that a sharp division bef.. occasion to nie'ition immediately, the present fjeneration does not attach any more patho^eiietic sijinificance to these terms. Weijiert distinuuished l):'tween four intimately correlated forms: Acute nephritis, characterized mainly by cellular exu- date; the (subchronic nephiitis. characterized by bejiinninft coimective-t issue s<'(I. iiimiiiIv l)v Zif'dcr," .\;iu\V(Mck.'^ Miiilcls." :iii w ('1"<'II III so far :;s ln> also takes a uniform view of all lia-matojii'iious forms of nephritis, helieviiij; only in a •iiaded and no essential dilTereiice. That it is jiossihle to difTer- entiate strictly lietwein deucnerations and inflammations is denied l»y Zienler. In opposition to Wei-icrt. following Hartj'ls. he descrilies a primary interstitial nephritis, the result of a pri- ma ry connective-tissue hyperplasia, leading to induration. 'I'liese views, opposing Weijicrt's conclusions, found furtlier support in certain observations on the so-called acute interstitial nejihritis, as first descrilKHl by liiermer. '' Mrnst Warner.'- Klehs,"'' and lately, with particular c:ire, by Councilman.'' Tlie latter re- •rards this lesion as a foail infiltration by plasma cells, derived from emigrated lymphocytes; but this cannot find its explana- tion in a primary epithelial dejreneration, which is always tlilJusc. When tlie latter, however, becotnes intense, polynuclear leuko- cytes are attnicted, and not plasma cells. He arjiues. therefore, that the interstitial exudate is primary and accompanied by, but not dependent upon, epithelial destruction. With this battle of opj)osinN A\l> X 19 IMtthiuji iirtif niaininif. In this iilrtt the hinitst niutil»r oj jxilholo- illsts ittitl rliiiirinns at jiirscnl conntr. As ;i sitlxlivisioti and iiitcniu'diary form ln' rrjianlM jflo- mcniloncpliritis. \lv .states:'" "It has \m>u attctnptcd from varu)iis sourros to ('stal>lisli a uniform view for all the uon- piinil.'iil nephrites, iiiasmueh as some h(tl(l that the parenchyma cells are always primjrily involved, others that all commence with a jilomerulonephritis. I caimot ajiree with one or the other opinion; in fact, with no exclusive view at all. .\s far as I can see. a uniformity exists only in so far as any inflanunatory irri- t.inl chanjies vessels as well as tis.sues, hut I hold it justifiahle to speak of various forms of kidney inflanunation, because the dif- ferent constituents of the kidney are concerned in a most unecpial manner. Followinv de^icneratioii on part of tln' paren- eh\ II result either from a previous acute condition or may develop inde|)eii(iently. Chronic nephritis may also result from arterial chaiiucs in the kidne> . leadinj: to atrophy of ^ilomeriili and liilmles. I'inally, any of these chronic types may at any time under^io acute exacerl tat ions, producinji new. very variable, anatomical and clinical pictures. .Vt a recent discussion of the (lerinaii Patholojrical Society. Midler ^iirain has revived the discussion about the impos.sil)ility, even clinically, of ditTerentiatinjr between acute and chronic nephritis, and the erroneous conce|)tion implied in .s|H'akinv; of parenchymatous nephritis, because the lesion is always diffuse a^'d the interstitial tissue as much invohed in the process as the parenchyma, even showinj; de>i('n«'rative ciianjies in the form of fatty infiltration Lolileim. .\uain. in the so-called interstitial forms, it would be erroneous to believe that the parenchyma was noi much involved and lesions prodiircd liv cholera, syiianclH'. |K»isoninns, pn'^nancy, etc., there exists MO real iiifiaounation. Itiit a (iejieneration, which has a ^reat tendency to Iwal. and prolialtly almost always heals eoni|)let(>ly. 'l"he true nephritis is infianiinatory and has its prntotyix' in the ;rloiiierulon(>phritis. The |)arenchyinatouH ehan>ies thej-e de- |M-nd mainly n|M)n the glomerular ones in their intensity and duration. Acute interstitial nepliritis must, howev<'r, 1k' con- sidered in(le|M>ndent. Chronic nephritis with hydrops n'sidts fn»m all cases of jtlomerular nephritis which do not heal, or may commence insidiously without acute manifestation; in reality they reprt»s<'nt the results of an acute nephritis. Lastly, the secondary' contracted kidney always presents anatomical evidences of a ^tlomerular nephritis, which may he traced to piwious acute lesions. It is certainly more frtHjuent than sup|K>sed. In some of these cases the featun's an* so characteri.stic that, without knowledjie of the previous history of the individual, the diajinosis of nephritis can l)e made. In this connection L(>hlein emphasizes a ty|)e of case which, havin UKKillT S DISKASK fiirllicr Minyloid and fatty iiiiiltratioiis. and. as will appear lator, the senile at ropliy of the kidney. Specific inflaniiualory lesions of known etioloiiy or riiori)liolo.uy have also, hy virtue of their characteristic etiology and niorpholoiiy, lie(>n elinnnatod. as well as ascendiiiii inflammations from the bladder. 1 say that this opinion is uradually jiettinj: the upper hand; some seem to think that parenchymatous dejienerative lesions should enjov an independent recounition amonji' inHanimat(.ry changes. To these invest iiiators the term Hrijilit's disease appears still indispensable as a more jiCMieral one than nephritis. I caimot aiiree to that. for. whatever theoretical considerations mav form the foundation of that idea, and 1 consider them very sliiiht indeeil. |)ractically we not only iiain nothinu; hy this fine line of ilemarcation. l)Ut it forms the source of endless confusion. I shall ipialify my position in this matter more fully later. Tlu' term nephritis will therefore l)e used in the followinjr discussions as synonymous with and instead of Brijiht's di.«ea.se, liecause it has a ceilain definite meaninji and caimot lie misunder- stood. We caimot ajiree as easily, and will pnthahly meet mui'li ,i:r(>ater opposition, in dehiiini; our position on the second and most important point: namely. What are the characteristic features of this inflammation? and, sulKsetpiently, how the vaiious inilammatory processes in the kidney may he ade- (piately classified. Here you must well reniemher what we reviewed ;i .short while a^o. The terms parenchym.itous, interstitial, diffu.se, persist like threads, hut of ev(>r-chaniiin.ii: colors throuiihout the historic de- velopment of infiannnation in general, and nephritis in particu- lar. I hold that the sooner we iireak with their use, the hetter for the progress of kiiowledjic hut particularly for our under- standinji of inflanunatory phenoiiema and that of nephritis. We have seen how the views of \'i'"cliow. Beer, Cohnheim, UISTOKICAI. INTUODICTION' AM) Cl.ASSIKICATlON Zi Wciircrt.aiul others, iiftor whom the words parcncliyiiiatous and interstitial iiiflaininatioiis were employed in a strictly patho- jiciietically contrast inji sense, have not been upheld hy future invest i;rat ions. It is undeniable and clear that certain inflamma- tot v initaiit! atl'ect extensively and perhaps primarily the ep helium in (lc':,('neration a'ld j)roliferation, and that there an itliers wliicii similarly involve the interstitial and vascular system in exudation and production. Both are, however, always comhined. correlated, and, at least after a short time, ecjually afl'ected, so that in ;iny established inflammation in other words, in any nephritis a differeiitiation between par- enchymatous and interstitial inflammation becomes practically impossible. Hut with the pathojienetic meaninji of these terms lost, tlieir em{)loyment is no more justihable, for I cannot even aiiree that these terms may be u.sed in a purely descriptive sense. Aside from th(> fact that it does not seem wise to me to con- tinue terms in an arbitrary other .sense, which is bound to pro- duce return to coiifiisiou instead of an advance to jireater clear- ness, this nomenclature has not even exactness in its favor. We have learned, you remember, that many changes which some have predominantly related to the parenchyma, are eijually well and -severely represented in the interstitial tissue (fatty dejieneration and inflannnatory o'demai. Ajiain, in the .so-called typically interstitial lesions, <;lomeruli and epithelium of the tubules are exten.sively affected antl destroyed, ^^'ho could state, therefore, which were more affected in one case than in the other? Such an opinion can be based only on very su- perficial examination of disea.sed kidneys. iMpially objectionable, finally, are the two terms acute and chronic, for they not only do not describe with any des of so-called acute character. Xothinu at all is, therefore, ;>ained for the understandinji of the })athoiojiical process l)y th(> terms acute, subacute, and chronic: they may even actually mislead. For all these reasons, and to further progress in our knowledj^e of the inflannnatory lesions of the kidney, I propo.se to di.scard all these terms, which, on account of the many ways in which they may he intended to apply, have and always will he the ureatest source of confusion, and a drawhack to ;i hetter under- standinu of pathol- uical conditions. 1. The term nejjhritis. which in itself means inflammation of the kid nev, nd which therefore comprises a 11 th processes which are held to lie comj ')n(>nt parts of an inflanunation, should hav(> added to it, when necessary. (lescrii»tive terms, not definiiiff particularly the location of the infl.anunation or its patho or of minor importance, no such tlescriptive terms are reijuired. These I jiioup as nephritis simplex. This type is represented mainly hy varyinji comhinalions of parenchymatous deo-onerations and ii.flammatorv (edem;i. HISTOHK AI. INTKODl CTION AM) (I.ASSIFICATIO.N 3. Whon cortain iiiflaiiunatoiy attril)Ut('s predominate, thcv are added as (lualifications to the term nephritis. In this sens(> I speak of nephritis defienerativa. exiuhitiva, luemorrha<;ica, and proHfera. It may he one or more that are mark»'d in this way. To sijinify any particularly i)roniinent location, one can adil tuhularis or jilonieruhiris. 4. When in certain kidneys fatty chaiiftes occur which assume cm objectionaWo to some. a.s thpformiition of nrw tissue concerns largely the supporting .structure, hut it i.s perliaps admi!lo wlicn it is considered that far-reuchiiig inoditicatiua of cells occurs in the essential parenchyma. 1 , 'm 26 HHKiHTS DISKASK iioimMicl.'itiirc aims at. will 1 tetter knowledjie iie diseases of tlie kidiiev he made |)<>ssil)le. not only for tli uiids of the in- vest iiiators. wlio larucl.v do not understand each other now and l)attle with words, l)Ut particularly for those diaftnosing and treatin" them. Sl-X'OXI) LIXTIHi:* Thk STurcrrHK ok thk Xohaiai, Kidnky and thk Difkkkkxt \'lK\VS ON ITS Fl NCTIONS IN THKIK HkI.ATION TO THK Pathoi.<)(;i('ai. \'ahiatio\s (icntlcincn: H(>f()r(' \\v cutor uj)()n our suhjoct, I tliink it wise to recall to your niiud cortain histolo<>ical and physiolojiical facts and theories. Unfortunately, they are not as complete as we would like to have; particularly on the physiolo<>ical side testimony is scant. The role played in the .secretion of the urine hv the vari- ous component parts of the kidney is not definitely .settled; and if this knowledfic is deficient on the physiolof^ical side, we are in a jM'rfect chaos of conflictin<>: testimony on the patholo-. We may admit from the start that there is really not one theory of urinaiy .secretion which directly conforms with all the patholofiical evidence, and allows us to form clear conceptions of the patholojiical variations. The reason for this will appear later. Let us examine what evidence there is.' Commencinff with histological considerations, I believe I may disregard in these lectures the emhrvolofiv, and immediately invite your attention, with the aid of this diagram, to the structures of the normal adult kidney ( Plate 1 ). You know that it is composed of two easily recognizable and separable parts; The outer, or corte.x, and the inner, or medulla, which stands in direct communication with the pelvis. Both of these enter, however, upon the field of the other, for, as you see, the medulla, • Delivered on Janiuiry 21, 1909. ■js HUKillT S DISKASK l)y cliMnictciislic r;i(li;itiiiir lines, sciuls ot'fspriiiiis into the cortex, known .is in(>(hill;irv r;iys: while in.isses of cortex se|);ir;ite parts of tile niednila. tlie pyramids, liy tlie so-called colunuisof Hertini. The inedull.iry r.iys .are produced hy a rejiular inierclianjie (»f ves.sels with the collectinu and str.iiiiht tuhiiles. the .ascending and desceiidini: loops of Henle. 'I'he cortex proper, on the other h.and, contains the iiloinenili and the proximal .and dist.al ends of the convoluted tul)iil(>s. |{eferrinctly. without passinji throuiih many divertinji channel: The reii.d artery is a rather short, thick brancli.iiiven off directly from the aorta. It proceeds to the hilus of tlie kidney, where it immediately divides into .several branches which ascend to the point of junction between the cortex atid the medulla. The first liranch of the renal art cry is s|)oken of as tli interlobar artery, while its branches, which you see represtMited, are spoken of as the interlobular arteries. They proceed up throu-ih the cortex and down throu-ih the medulla. In the cortex they pass directly to the domerulus. The formation of a jilomerulu s is intere.stiii<;. It i.s a lobular structure, c(>mi)osed of a vascular network, kn own as capillary STUrcTlUK AM) FIXCTIONS OK THK NOIf.MAI. KIDXKY 29 tuft, ami enclosed in what is ternicd Howinan's capsulf. It is, luoicovcr. peculiar and characteristic that the afferent vessel of the jilonieriilus is very much lar<;er than the efferent or centri- fuj-al vessel. In other words, the hlood is hrouj-ht under hiiih, almost direct, aortic pressure to the reaks up into a capillary network, and this network follows the convoluted tubules. Hefore the hlood reaches the convoluted tuhules at all. it must rulus and, as will ;il)pear later, must have a jireater concentration. The veins which correspond to the.se arteries are es.sentially the .same, with the only exception that they do not enter the jilomer- ulus. The lymphatic vos.sels of the kidney are not very well known. It is supposed that tliey accompany the vessels. It is douhtful if there ;ire any in the filomerulus. With regard to nerves, there exists a complex derived from the renal plexus and le.sser .splanchnic. They accompany the ves.sels and :dso extet.u to mltles somewhat (he secretory epithelium. .\t the point of entrance of the first convoluted tiiimle the epithelium ch.an^ics <:radually. so that tr.-insitioii cannot lie definitely estalilisheiiiiil. The epithelium of the convoluted tuliules is hijili. well difTerenti.ited. The iiiich us is situated near the tunica propria. 'Ihe protoplasm is extremely jiianular. These ^taiiulations are arranged in definite order of streaks or rods. Their extremities are delicately liruslied with non-motile cilia. 'ihe epithelium of the descendinji limh of Henle is low and Hat. it is rather poorly defined, so that the line of demarcation between the different cells is not clear, and it looks more like a .syncyti.il formation or the e|)itlielium of the cai)sule of the •glomerulus. The epithelium of the a.scendinji- limh of Henle, as well as of the distal end of the convoluted tuhules. is hiain he- eomes distinctly <>;ranular. somewhat re.semhliiifj the epithelium found in the proximal limb of the convoluted tubules. This is s(.lut(' proof exists ;is rcjr.-iids their spccinlizcd duties. I'ossil.le excepti(»ns :ire only tlie ;ilom(>niliis mikI the proxi- il eoiivoluted Hil)ule, ;il)oiit whose (hities we are somewhiit Ix'tter iiiforined th:in al»out the rest of the stnieture. So iiiiich. then, for anatomical considerations. Tl ic arrantre- nient ditTiTs from that (tf other glands mainly in tlu' hlood- supply and in the peculiar course and structure of the secret in;;' surface. I must now review the various conceptions which are held with re^Mrd to the .secretion of urine.' The (»ld idea had heen that the kidiiev wa? es.sentially a filter, that is, a structure lU'inarv constituents throu;ih which water and the characteri.stic were pas.sed hy a simple process of filtration. That idea gained ground particularly after Bowman's classical description of the ^domerulus. Hut, on account of the length and the es.sential structural variations of the tuhules, it soon appeared that a specific, secr(>tory function on their parts was also prohahh'. Thus Bowman (1S42) ' himself l«>lieved that the ^domenilus filtered water, i)Ut that the tul)es were a secretorv structure, and he based his ideas entirely on the previously detailed anatomical considerations. Ludwi^S who in 1S44 puhli.shed his cla.ssical observations, at the time of strongest conflict between vitalists and mechanists, wa- I he first to offer a purely physical theory.' In substance, this theorv- assumes that all urinar>' constituents transude throu^di the ^domerulus, uiuler the force of its hi^h pressure and in v(My dilute .solution. Passing' through the tubules a re-sorj)- ti(m of this water to the more concentrated lymph occurs; the fluid, therefore, assumes its urinous character. Ludwi^- based his ideas of filtration on the fact that the amount of urine depends mainly on the arterial pressure and on the rapidity of flow in the kidneys. If the arterial pressure is i m I 32 HIIKIMT s l>lsi;\sK iiiciVMSfd. Mini if llic rMl«> <>f flow of the M 1 lliroiiy is also iiK ivasrd, tlicii. of coins.', llif aiiioimt of uriiif iiicivascs. If. on the oIIht liaiiil. wc li.ivr .1 diiniimlioii of llir aiit-rial lucs- siiiv ill the kidiK'v. .iiid a diiniinilioii of llir rate of flow <>f the l.lood tliroiiiili llir kiiliK-y. tlioii the amount of urine decreases. Tliis is a perfecllyol'vioiis fact.. and is also suppoited liy patho- logical e\idence>. We know that in eases of inccmiplete coin- pensatisison that side and the urine is increased. Stimulation of the spinal cord and the splaiichnics raises the Mood-pressure, and h:is. therefore, the same result. Further corrol>oration is found in the dose relation of the amount of fluid taken to that excreted, so that the (juantity of urine de|)ends laijidy upon the pro|)ortion of water i)resent in the lilood. If a person drinks laiiic amounts, there is an i.lino.st immediate response on the part of the kidneys. The effects of cert.iin driiiis. like cafTein and diuretin. have also been looked upon as favorable to this idea, in.ismucli as ;heir action is con- sidered to depend upon .an increas(> of blood-current due to a vascular dil.at.ation. .althoiiiih this has been disputed. Now. in order to explain certain properties of urine, which caimot be accounted for by the fTect tl K'en fi^iured out h lis concentration, if would re- <|uire, under circumstances, a force .six t imesjtreater than that of human muscle (,S(MK) jjm. per .s(|uare centimeter), die deprived a cat of water for three days, :ind then drew olT the urine, which had a freezin«t-point of 4.72° (*. The hlood at tl le .san>e time Had ().()()° C. Now von fHofT ha.s shown, if is the dei)re.ssion of the frcezinji-point, and T the ah.solute freezin s«'|.:il!itc llic volumr tlv of |)un' \v:i trr:isi.Tfr..m 1 |mt of water. I •_*•_'. 7 in or We li.ive. tlierefore, to uiiilliplv l> ,1,.,. ,„ ,,l.t:iiii the osmotic pressure in metefs of water in Miiv solution. In tl le ciise o f the c:il just mentioned. thes<> differences in the freezin^-jMiinl denote an «»sino tic (HtTerence of JUS meters water. f l*.».S(M» i:m. iH'r s(|uare centimeter /. ( .. a pressure o Dreser has eiideavoret "ilomeruli. to demon: the liniiiy: epillielial cell^ I'rom our standpoint there are, a^ pointed out, son >f I 11(1 win. 1 to silow the same with rejrard 1o the itratj- in tliem al.so active work on l)art of MiiUer"' has only lately Itjections to accept the |»ure filtration idea We all know that in chronic venous con^jestion the le o iiinoi ml of urine is niK h diminished, while tin* secretion of mtroiienoi IS material is kept up to Ilea in extreme ca ses of oliiruria. Mow can rly normal limits, except i.udwiji then account for this? One would li.ive to suppose an almost normal transuda- tion from the ;rlomeruli with an inrmis,le from phy.siolojiical and tele- olofii.-al considerations, for an injured kidney would Ik> called \ipon to do more W( irk, to the iiijur>- of the patient. For similar reasons, Midler holds an explaiiatum of the hirtedly others, like the formation of the urinary chromoj-cns. <'tc. There can lie no quest ion that the epithelium of the tulmles of course, we do iKtt know which imist lie actively concerned in this formation, and that these substances are, in all pndtahility, di.s- chaified directly into the tuhules. It certainly ap|M'ars that, if a, all. a resorption of water camiot Ih- the sole duty of the tiihules. 'I'hese ideas of Ludwiji h;ive, therefore. I leen actively and Imt- manentlv op|)osed, primarily l)y lleidenhain and his followers. Ileidenh.ain " took the extreme other view, attrihutinjr the whole process to ;in active secretion, and denyiiifi any iiltratioi\. His ideas were essentially based on three i)oints: If one ties the renal vein, the intrafrlomerular pressure is increased. In spite of that, the urine is not increa.s<'d. hut diminished. If one ties the renal Uately II lese arterv and then relea.ses it. the flow of urine is not iiiime( recstal)lishe(l. imt only .after a consideral)le time, phenomena, he arirues. speak ajiainst a simple transud;;tive character of urine water. Hut the fact to which most im|K)rtanee is attacheil is the result of experiments after the injection of indijio caniiin. He found that, if indijio caiinin was injected into the renal artery and the animal was killed after ten minutes, the indiiro carniin was always precipitated in the epithelium of the convoluted tuhules. It was never found anywhere else. I'rom nuKiin's nisKASK that he coiicludod :i siM'cific select ivc ;n ■tivitv oil the part of that portion of th(> reiia Icpitlicliinii. Now. all <)f these three arjiimiei Its of Heideiihain have not stoot 1 the test of time uiKlispiited.'" 'I'he resi ilts of tviiiii the r(M\ ,1 vein and tliiis iiicreasiii-j mav eas without increase ot iiniu stasis. .\ diminution in to purely mechanical causes, nanu the intra-jilomerular pressure ilv he attributed to venous the amount of urine may there he (hie ■ly. pressure of the prrts fjiainst another, a resu lit of the venous enjiorfi( meiit . Similarly, the secoiK 1 ariiument. tvinii the renal artery, with out. o II its release, ohtainin-: an unmet Hate How of urine, appoan of (loul)tful va kidnev. it would take consii and rapidity of flow ar(> rei Kinallv. the most impcu hie. because, in a comi)li("ite«l strueturf like th the results o denied its value by many mvestiji lerable time before normal pressure ■stablished in the -ilomeruli. ■tant arjiument which he advanced. iniin. has been ;ti"ators who claim that, if the )btaincd from injection of indi'io c:i no solution of indiiro carmin b Heidenhain employed, and if the kidnr t of the exact concentration •v is examined earlv after injection, thi bstance is a Iso found in the liiomeruli. so that 111 rea ,litv sele.-tive activity docs not occur. It has further becMi pointed out that on its wa> a has also been brou-ht forward a>!;ai!ist the sweepin^i secret orv ideas o if Heidenhain bv Senator. i*i STIUCTIKK AM) KINCTIONS OK THK NOKMAI. KIDNKY 37 \V(> know a nunilxM- of kidney lesions tissociated with extensive. Mlthoujrh slowly projiressinji. destruction of the epithelium. Accept iiifi nei.ienhain's views of a purely secretory function of the epithelium, one should reastmably expect a jrradual diminu- tion in the amou.it of urine in these lesions. But the facts speak differently. Path()l()jrists and clinicians have known for a lonji time that in certain types of productive nephritis, and in the amyloid kidnev, the amount of urine, instead of heinji diminished, is a.-tuailv markedly increased. The gradual loss of epithelium of jrlonieruli and tubules does not seem to have the slightest relation U) the urine output . How. asks Senator, can this \w rejiarded as the active product of the e[)ithelium? S(Miator, in conjunction with Munk, bejjan, therefore, ♦o in- vest i^^ate that [)oint further." They were aided by a discoverj-, made shortly before by Hoy and others, namely, that it is possible to have kidneys functiotiate after they have l)een removed from the body. Takinj: advantafje of this method, they transfused defil)rinate(l blood through kidneys, and were able to observe closely the results of chan' little va- riation from the normal. That latter point is interesting; and important to remember. Then they did the opposite, diminishinj: the quantity and the pressure throu«:h the kidney, with these results, that the amount of vnitie decreased decidedly, that the amount of nitrofjenous material also decreased decidedly, while the amount of sodium chlorid showed no difference from the normal. Incidentally, I i :{s HKKIIIT S DISKASK should mention tli:it tlic :iniount of ;ill)iiinin wliid' ucli an artiticial urine al\va\ s shows diniinished with arterial hypera-niia, am en 1 increased with passive hypera tnia. Interestinji is the ex- ■tion of sodium chlorid. which remained practically imaffected l)y active hypera-mia or stasis. It arsiues for an at least partly traiisudative character of the urine, for pressure and rapidity of a transudiiiii fluid determine the (plant ity of a transudate, hut not its amount of dis.-^olved cry.-^talline substances. Based on these considerations, they concluded that the lu-ine must he regarded jjartly as a transudation and partly as a secretion. The transu(lativ(> part is furnished hy the jilomeruli, the arraiiitement of which is also very nuich in favor of its l)eins a secr(>tion of the epithelium, which is also in watery .■solution. The combined fluid is taken up by the collectinii tubules and discharired into the pelvis of the kidney as urine. These ideas also have underjione revision by other investi- •rators. It has been urjred that it really has not been demon- strated beyond doubt that the jilomeruli filter only water and sodium chlorid, and as a contradictory fact is mentioned that in arjivria the silver imprejiiiates the loops of the jilomerular tuft. It is, therefore, argued that these tufts ar(> probably permeable for other, normal, urinary substances. Aiiain, it has l)een claimed that, if the jilomeruli truly filtered, sujiar as well as albu- min ouiiht to be found in normal urine." .\11 of these oltjections, howev<'r. carry very little weijrht. That a foreign subst.iiice like silver is arrested in the hner believes, therefore, that the filonieruli Hlter all the sul)stances which are contained in the blood in cr>s{alline form, while the convoluted tubules secrete such substances as are in colloid state (urea. uric a.-id. phosphoric acidi. He and other investigators have revived for this latter i)rocess Ludwi-'s idea of water and Na("l resorption. Hans Nh'ver. Cushny. and Hausmann found, as previously mentioned.'"' after extirpation of the medulla, an increase of from th-e to four times in urine quantity with a proportionate de- crease in concentration. Meyer states that •' the excretion of ("1 and X after such operation corresponded to the contents of the l)lood. so that the fluid eijualed an albumin-free l)lood Hltrate.'" Hans Meyer. I/.wi.'" (lottlieb. Mafimis.'^ ancretio"n of a verv thin urine. But this latter mifjht easily be attri!»uted, as Mrich Meyer-"' remarks, to a kidney injur>- which interferes with its secretion. A-ainst the idea of filtration of dissolved crystalline sub- stances bv Glomeruli and secretion of coUoiil compounds by the tubular cells, ajrain are Asher and his pupils.^' who fovmd no regularity in the excretion of urine uater and XaCl, and conclude, therefore. s<>cretion of even these substances. Asher furthermore points out that even si,ecific jrlands. like the salivary, show a proportionate relation -f dissolved blood 4(» HUKillT S DISKASK const it lUMits Mild water. Hut it must ho nMiiniihorod that no other i)ur(> inland res|)oiids so instantly to chaniLK's in the con- centration of tlie lilood. Finally. IJich >h'yer.-'-' who has studied very carefully the elimination of urine in (lial)etes insipidus and other polyurias, is of oi)inion that this urin(> caiuiot he rejiarded as a filtrate of hlood-seruin. inasmuch as it is too dilute as reuards its total concentration, hut as reirards urea. al)out ten times as concen- trated. For instance, in a case with a total urine amount of SdOlt c.c. and a nitrojieii excretion of 1 1 fim. pro die. the percent- ajic of ur(>a contents would l)e ahout OM. while, according to (iottliel). the hlood only has a concentration of ().((3 to O.Oo. On the other hand, tlie ("1 content of this urine was on some days almost ten times less than th;it of the hlood. He further foiuid that the diuretic thef)cin. j)roduced in diahetes insipidus an increase of concentration without increase in (piantity. hut this could not l)e explained l)v a disturl)anee of resorption. Similar to the modernized conception of Ludwijr are the ideas of Koranyi.-' whose view- I will mention in detail, hecause they acipiired considerahle practical importance. He helieves that the nUmieruli filter only water and sodium chlorid. hut that in the tuhules occurs an eciuimolecular exchangee with metaltolic products: a purely phy.sical process. The so- dium chlorid of the urine is, therefore, inversely pro|K)rtional to the amount of nitrojien. Based upon this fact, which is actually found in a numher of conditions, he e.stal>lished the so-called urinary (|Uotient. This is ohtained hy dividin<>; the freezinjj- point of the urine hv tlie amount of sodium chlorid, ., ,., = .\a( 1 urinary (juotient. This (juotient, in Koratiyi's opinion, depends upon the rapidity of flow of hlood throujih the kidneys: With diminished STIU (Tl HK AM) KINCTIONS OK THK XOKMAI. KIDXKY 41 flow the (Hiotient is low. This litis 1)(>(mi found correct in cases of heart disease with faihire of compensation and (rdenia. It is interestinj: to know that in ciises of orthostatic or physio- lofiical allnnninnria the (piotient has been found hijih. very much as in circulatory disturliances. while in true nephritis with all)U- minuria it was aliout jiormal, provided no chanjie in heart compensation occurred. It has, therefore. Iieen urvidence indicates that the production of urine can not be resartled as one uniform process. This complexity un- doubtedly accounts for the many in parts conflicting observa- tions and ojMnions. In the production of urine there appear to be concerned two processes: The first is transudation, and the second secretion. The structure of the <:lomerulus, as well as what we know of its function, supports the contention that we have here a proc-ssof transudation. (Recently Brodie has further emphasized the fact that the glomerulus acts a good deal like a piunp; by virtue of the elastic capsular fibers the filtered water may be put under high pressure, in which it is aided, of course, by the abrupt narrowing of the tul)e below. Thus it flushes away the secretion of the epithelial cells. ^ That the glomerular epithelium is secre- ll 4J HUnilir's DISKASK tory sccius iinpn)l»:il)lc. for the reason tliiit it only partly covers the -loinenilws. tliat it has not the morphotic character of secre- tory cells, and that, under pathological conditions, water dis- charu-e continues after its loss, unless there is a mechanical obstruction to its outflow, or the tuft l)econies diseased. This is |)articularly well illustrated in cases of contracted kidney, and in some cases of stasis, when the epithelium has been lost, hut the tuft itself remains an>ulate the concentration of the blood. Xow. we must remember that this water, which is furnished by the proce.ss of transudation from the <:lonierulus, is modified on its way. That modification cannot. I believe, be explained, at least at present, on a jihysical basis. We must as.sume that the ei)ithelium of the convoluted tubules, as well as that of the other tulniles, plays an active part in the modification of that Huid to urine. The reasons for it are these: The osmotic pres- sure of the uriie is nnich hiiiher than that of the blood, and it contains specific .substances, and in such varying: amounts, that an active part of these epithelial jrlandular cells is made most proi)able. It is undoulttedly for this reason that the blood is furnished to the epithelial cells of the tubules in a much more concentrated form. The chan<:e from alkaline blood plasma to acid urine, however, can be explained on physical basis. The anatomical arran-rement of the tubules indicates that there must be stajination of the transuded water in the con- voluted tul)ules. This may be for the sake of water re.sorption, but to me it is rather more for the purpose of complete solution of nitrofienous elements disciiarjied by the epithelium of ihest- STKIC TIHK AM) KlNi TIONS OK THK NOltMAI. KIDNKY 43 tul)ul(>s. This is ill harmony with the ()l)scrvati()ns made in «'y- anosis of th(> ki(hn\v, wlioro thourino water is diminished, but the nitrogenous <-ontents ahout normal. On account of the venous stasis less water transudes through the jilomeruli, hut the func- tions of the epithelial cells are carried on profHTly. until they 1,,-in to sutTer from nutritive disturbances. The urine is. there- foiv. concentrat(>d. -V theory of exclu.sive water resorption would hardly account for this phenomenon. It is also possible that water resorption occurs only when the am(.vmt of transuded water exceeds certain limits. We must ,.„nfess i-norance of the specialized functions of the various parts, and types of epithelial cells. comiK)sinji the tubules, ami of the details of the secretory act. A f(.w words about the discharge of the urine from the pelvis of the kidnev into the ureter and bladder. The physiolo-ical text-books leave us in the dark about the mechanism of this process, althoujih we are informed that the urine is propelled by active contraction of the ureters into the bladder, and that a return flow from the i)elvis into the tubules is made impossible bv compression of the tubular orifices by any increase in pelvic pressur(>. Both pelvis of kidney and ureter have essentially the same structure; they are stronji, elastic, muscular orjians, lined bv nuicous membrane, and it api)ears probable that the activ(> waves proi)ellinj: the urine throujih the ureter into the bladder take their orijrin in the pelvis and similarly force the urine into the ureter. This has for us considerable interest. In manv lonji-cotitinued diseases, but notably in the senile kidnev. there occurs marked weakening of the elastic muscular layer of the iM>lvis, with the result that this gradually dilates to a c(indition of hvdronephrosis. although no mechanical obstruction outside of the kidney exists, and the ureters ami bladder are not dilated. In these cases the jK'lvis evidently loses its power of active tli.schar>ie into the ureter. ;} 44 UHltiin's DISKASK I hclicvc lliiit this covers as much as \\v arc justified to assume at i)resent almul the secretion of urine. Much is still uncertain and contradictory. We confess its d(>ticiency and uncertainty, and there exists ;:reat ditficulty in the ap|)ncation of the experi- mental physiolojiical knowledge for the explanation of diseased fimcti<»ns. In this connection. I would like, however, to empha- size '-ertain points, which may. at least to some dejiree, account for these discre|)ancies. It appears that we are vmahlo to tran.s- pos(> directly physiolos. in exajijieration. diminvition. or aliolition of certain fvmctions which depend on similar or' (edema; that is, serous exudate with diminished resoq^tive :,l,ility. This type of kidney lesion is now variously classified as :.cute nephritis, or acute parenchymatous nephritis, or acute parenchvmatous defeneration of the kidney. The impropriety „f the first two terms I have already covered, hut i am ohlijred t„ pav some attention here to the last, the acute parenchyma- tous ile-enerationof the kidney, inasmuch as stronjr attempts irive l)een made, onlv - but essential de-enerat ions. and Marchand.and L()hlein and Heineke." with some others, look more or less favoral)ly upoji such classifi- cation. The evidence for it is that there exist some diseases, cholera foremost, and some intoxications, like those of phos- phorus, chromium, and corrosive sublimate, in which extensive parenchymatous dejreneration occurs primarily and i)rominently. which mav or may not become associated later with inflamma- tory henu)rrha-es and cellular exudate, and finally with pro- ductive interstitial chanjjes. • Dclivrml on l'cl)ru!iry 4, HKK). 45 HHMiins KISKASI M;iirli:iiiil.' s|M';ikiiin <»f the kuliH-y chriiim's ill (•(•rnwivo siihliiM.itc iMtisr, to a iion-indammatorv. increased capillary jM-rinea ibilit^ an( li )()S- sible h'ssened resorption, a nalojrous to the amvloid kidnev. and )ases this view on the absence of hy|M'ra'mia and hemor- rhaues. It is ditliciilt to follow this attempt of a finer chi.ssificatides the cellular exudate as non- inflanunatory. and ^genetically unrelated to it? The absence of general hypera'mia and hemorrhafies cannot be taken as proof ajrainst the inflammatory character of the I)Kre, it apjM'ars from Heineke's description that in early cases • the cortical capillaries, the ;:lomerular tufts, and the medullary- capillaries showed frecpieiit ai)undant l»l(»od injecti- of nephroses or parenchy- matous dejrenerat ions inde|X'ndent of inflammations, as .MuUer would have it. Indeed, even Marchand is quite con- scious of the additional difficulty thus introduced, for it would still become necessar>- to afiain apply (lualifyinfj adjec- tives. How nmch, for instance, wo»ild l)e - nephrosis? The latter, particularly, would soon lead back to a confusion from which we are oidy t(K) anxious to e.scaix'. We will therefore not recognize in our study a non-inflam- matory, parenchymatous defeneration. \ow. to return to the discu.ssion of simple nephritis: It is the form which is mo.st frequently found in connection with all t.\ pes of fevers, such as typhoid fever, the early stages of scarlet fever, synanche infections, cholera, septica'mia. and others. It also (»ccurs in toxic and cachectic states and in .some ixiisonings. Such a kidney, firo-ssly. varies little, if any. from the normal 4S iii(i(inr°>^ hisKASK n'v/.v. Itiit :i|)|H'!ir!< swollen riic fiipsiilr i> stivtihnl lluii, l»tH „'lH^ strilMM-il otT will. .-MS.- riu- suifa.T l.uk,.>, m.uI this ran fivtiiinitlv Ik- srni im UsumUv :i SOI 1 of iliiskv-^'niy. pinkish color. lliMl. howcv.'r. is o|MMi I.. ">in.- v.ni.-itions; < )cc.isioii;ill\ . IIk' surf: ic«' in; ,v show .lislincl Miras (.f vas.ul.n iiijc-tion, l.iit <.u iccol lilt of the iHTSsiin' ( fwial •nfhvina, lln' siipci ,1 tlir swollen aixl (j-^lcin.ilous par- veins aiv iisiiallv not at all .roinineiit , and soinctiincs ca nnot lie tnatlc out iit al ap|M>ai of uiu'(|U: coinpcnsatoiy • .\::ain. th«'V in:iy •ount moir prominent in itla.rs an.l l..st in ..th.'-. .-n a(( I (list ril.ut ion of inllaininatury ••hjinyes and r(,ns4-(|uciit •liaii>;< in the Mood-sticimi. < 'ti m'cIioii. th kidiH'v shows roiiditions siin ilar to tlios<' oliserx-ii on uross ex- am illation. The cortex :i I liromineiit. ir rows, ins he markinu? Iwavs liuliies and ap|)eaiv rehitively show irreuulnnties and tlie -lomeiii- tead of presenting; a v( •rv dehnite arraiiiieineiit .are distorted. The -lomeruli apiK'ar in s,M.ts very prominent on ,t of a very marked vascular injection, and in others they n he recojiiiized in accoui inav have disa|)i)eared alto-n'ther. or they ca en ;h. slisihtly elevated points. They se<>m Ik. rais(.d ov.-r the" surface of the cortex. Such rows of jilom- ,li are .separated l.v tlii.-k. j;ray. swollen, tulmlar masses. the form of fine, irrayi to Occasionallv. one can .s.,ueeze from the kirous exu( Similar conditions preva (I il in the medulla. The me«lulla, ijr dear and dehnitely striated, is rather dull, The medullary rays are prominent, pale, and di'inatous, while the interp<)lat<>d vessels are for this rea.son instead of appearin uravish, swo .lie obscured or, for compensatory re esse isons. apjM'ar in places much more prominent than they on linarilv do iVvA- l>- Pressing: I is: 1 .\i|iliriii> -iinplrx, frnin pntTjiI sent ioirmia fi)llii«in); niiildlc-c.ar .lis. asc. ( l..u.lv"-u.lliiiL' aiiil MToiis iMi.lal.'. Si.iiic iif tlic (rlimiiTuhir rows with iiillamnial.iry .ni'nri.'iiiuiit, tint grmmllv llic cortieul ii\:irkiii(rs l.>sl i.r .lislurlx.l Uy cli.mly sw. Iliu); uiul -mills cMi.lali.m into ilir parts. Similar -late in tlic m.'.liilla. Mu ri>»r.ii.i< allv, tins ki.lii. y showi.l IK) (illiilar or liliriiiiius !>sii.latiiiii, li\it iIdii.Iv ^«illiiitf "I nils. v«, Ihiiir of irl.."!. lular I'li.lotli.liiiin an.l cintlicliuin, ami .sii|»ulo aii.l iiilirstitial tlHsiii'. Wciulil, 2.')0 Kius. ■In! I)K(iKXKUATIVK AND KXIDATIVK FKATIKKS OK NKI'HKITIS 49 ifli I Mi. I'in. 2. Ncplirilis siinplcx: Iiifltinmiiitorv <'i)|i()r({cnn'nt iif glonH-nilar capiUarifs, with nciicr.il .•iilaiKrmtMl of the tuft, ilouilv swi'lliuK of its i-iidotliclimii and cpil helium; the liilUr parllv ioiial nuto'rtji'miMit of iiili'ituliular rn'at extent, of des- (juaniated tubular epithelium. This leads us to the mieroscopic aj)|K>a ranees. We observe, here, certain variations from the normal, which are more or le.ss evenly distributed throujih'>ut the whole kidney substance. In the sinii)lest :ind earliest f(..' .s, the more promi- nent features are turbidity of the jjlomerular tuft, .serous exuda- tion into the jrlomeruli, and a parenchymatous ded by it, and thus its circulation necessarily nuich interfered with. If this process a.ssumes any dimensions, tlie capsule Inn-omes dilated, while the tuft itself is further pres.sed ajrainst one part of the capsule, usually at the entrance of the vessels; such jilomeruli ap|M>ar then as the fine, slifihtly elevated, pale, iil. swollen IIK 1 the cMpillMiy Wiills thick, piilc. :itnl pluiiip Tlic I'h.iii-cs 111 tl lie ( i)itlicli:il fdis of the convoluted tiiitiile re more evitlcn t at lirst si-iht tliiin the ch;in,i:es tountl m tl Malliiuhiaii coipusi Thev consist of varvinii' deiifees ot pai eiich\ nialous i niatoiw (leLl no you tile present l,.oviieratioii Fi-. \k The nature of pnivnchy- tself a very important and fundainen- lolo-v. I take it that you are familiar iciieral patl sint'ial '■•alures of it from your previous sttidies. t l)e amiss if I shortly summarize once more for knowled-:*' reiiardin.!: it. itl otiieif ■rh(> kidney from the time o the favored ori:aii for inve f \ircho\v ' has lieeii, above paieiu nature express U( structures ^ranuk ■itijiations into the character of ■hymalou.-. d.-uciieration. Virchow. whose ideas (m its 1 h.ive already presented, introdiK-ed the appi'opiiate f 'cloudy .swellinii": and these two words ^uch cells lose their definite normal iiul outline. The delicate, rod-like striation. com- lar arranuement of line .■iiamiles i.Xltmann's u rnnemher. forms a feature of the jho- descriptive term o llit^ nneaiaiice (sed of a fciiu WlllCll. as vo ,lasiii of the cells of the convoluted tuhules. becomes ll as a whole appears ( brushe(l extremity may succulent, swolh larker. nd more finelv (hist be lost. The cell enlariics. appeals n. turliid. and plump- :""• occasionally as if (Ml with -raiiules. This has ,i:iv(Mi rise to the term - irranular de>reneration.'" These lifanules are iiiso luble in chlorofoiin. ether, 1 alcohol, but soluble in acetic acK 1 and weak alkalis, and have therefore been rer. hyaline. ;rlol>ular bodies. Thev aiv rejrarded by some as the product of a i)ath olojiica 1 secretion. I shall say more a bout these in the discu.s- )K(iK.\KI{.\TIVK AM) KXri)ATI\ K KKATIUKS OK NKIMIUITIS ii'.i KitJ. :t. — Ncpliritis -implrx: ( ilmnciuhir capsiili' ilistciidiMl liy sitiiiis cxui lair. Th. lufl iDiiipirsscil .mil ailliiicnl to i):irt of the capsular wall, wIium- cpilliclii ■ III IS ri'lalivrly well prcMivcil; ildiidy swclliiiK ; I (i-iliiiia (if siirroiiiiiliiin struct arcs. X "JIO. l.'i^. 4. — (iranular illsiiilc(£ratiim iif coiivolutcil lulmli's. A better prcscrviil loiiii of Hcnlc. II |)K(iK\KU.\TIVK AM) KXl DATIVK KKATIHKS OK NKI'HHITIS ")') sioM of tube-casts. Tlic imclous is |)rimarily imaffoctotl. ami is involved only in progressive and severe lesions. Its chaiifies are those of chroniatolysis. /. r., a centrifufial lo.ss of ehromatic sub- stance, and. as Benario" holds, are similar to those ol)serve;rates into a «rramilar detritus and dissolves. When such severe chanfies are absent, but the parenchymatous destruction continues, the apjM'arance of fatty siib-stances l)e- comes pronovmced. 1 shall leave the discus.sion of this subject to a later date, when we are dealinjj with the fatty type of nephritis. Opinions about the nature of parenchymatous defjeneration differ widely. It involves two main que.stions: What is the derivation and sifinificanee of the jiranules, and what the orijrin and sifinificance of the swelling of the afTected cells? Both were easily explained by Virchow's conception of over- nutrition of the cells. Only shortly l)efore his death Virchovv declared : The swellin^t, as well as the cloudiness, depend uiK)n a IM'rmanent assimilation of soluble substances, which are pre- cipitated within the cell and underjjo further ehanjjes. The swelling' is, therefore, not caused by the usual nutritive, but by changed material." An entire chanjje in the.se ideas went necessarily with those of the character of inflammation, for inasmuch as the parenehy- nuitous degeneration was no lonfjer considered a nutritive dis- turbance, but the direct result of an injury, it l)ecame necessarv' to explain the cloudy swellinji in some other way. It has, therefore. l)een variously considered either as a granular precipitation of normally dissolved proteid (Rind- it! r>(> UHKiMTS DISKASK Hcisch.' ("t.liiilicim"'. <>r as a coaiirulation i Klohs "*), or. inoro ■rciuMally, as a (lisornaiiizatioii of protoplasm with resorption of fluid iZiculcr " i. or as a rcfrrcssivc iiictainorpliosis due to uiulcr- iiutritioii Tlioma'-i. Soiiio, like Bircli-Hirschfcld " and von Hcckliniiliauscn." retain partly the views of Virehow. The former Itelieves that it represents an accumulation of undis- solved or precipitated i)roteids as the result of increased proteid destrviction with an increased supply of proteid; the latter rejiards it as an increased functional activity similar to the increased productioji of mucus in the catarrhal inflamnuitions of mucous meml)ranes. ('onsideral)le experimental work on the subject has l)oen done. Schilliiifi ' ' obtained cloudy swellin^i of one kidney forty-eifjht hours after tyinj: the renal vein of the other. He concludes, therefore, that this nnist he the result of com|)ensator>' action on part of that kidney, caused by the increased amount of urinary constituents in the blood, a forerunner of hyjK'rtrophy. Land- stcMner,'" however, has pointed out that these result.s are not identical with those of infections or intoxications. The cells of the first convoluted tubules were left entirely free, and the lesion remained strictly localized to the cells of the proximal convo- luted tubules. This is the very oppo.site from what is usually ol)served in disea.se. Such experiments are entirely unconvincinji for exi)lana- tions of either hyi)ertrophy or parenchymatous de<>;eneration, for the reason that such an interference suddenly produces marked complications in the lanctions of the other kidney, and to such an extent that one is not justified in drawing: any con- clusions from it. One mijiht interpret these results as moderate injury to a particular jrroup of cells of the kidney, caused by the .sudden ( aanjies in circulator}- conditions and th(> increased amount of urine constituents. There is no evidence, as far as I l>K(iK\KKATIVK AM) KXIDATIVK KKATIKKS OK XKI'HHITIS .)< know, which could corrolwrnitr the view that parciichynmtous (IcjroiM'ratioii hears a fienetic relation to hyiMTtrophy. There is i»o uiiiforinity of opinion about the derivation of the jrrainiles. While some l(M)k upon them as an increase of the normal tyiM'. (ialeotti'" holds that they represent a ditTerent a^'v:i'<'>i:>te condition of the cytoplasm, while the normal nded in the other (tropfifje llntmischunji). Based on his own studies, Landsteiner '** concludes that the process is essentially a destruction of the filamentous structure of the protoplasm with dumpinf: into jrranules. The swellinji is to l)e attributed to the destruction of the protoplasm. He is inclined to attril)ute the whole to autolytic processes. Similar are the views of Orjrler and others, who, having!; foiuid substances of the myelin jrroup in such cells, look upon it mer(>ly as a myelinic (lerocause they play so imiK)rtant a role in the correct and I'lear conceptions of nephritis, and we will have to refer to them fre»iuently in our subsefjuent study. To return to the subject of simple nephritis. I shall only have to add that the tissue U'tween the tubules shows the same in- flanunatory cedema which I have already mentioned in connec- tion with the |H'ri«ilomerular tissue. It is stretched, hazy, se|)arated by (edematous fluid. The intertubular capillaries are in parts enjiorjred or may 1h> compres.sed. The result of simple nephritis is restitution to integrity in the majority of ca.s<'s. The inflammator>- (rdema subsides and, after clearinji of the lymphatics, is re.sorl)ed; the filomeruli and the vascular apparatus, not havinji underjione jjermanont injury. DMiKNKUATIVK W KXIDATIVK KKATI HKS OK NKniHITIS .W MssuiiM' their fornu'i comlitiMn. Tho cpitlioliuin also rcjU'iiiTati's ra|)i(lly. iiiasinucli as (.nly littl«- of it has undcruono actual necro- sis, and the kiay. therpioro. !)<■ said to recover coinph'tely, iniless conditions su|)ervene which, prolon^'ing the interference, liradually lead to tlie more severe tyj)os of kidney infianunations wiiich I am now ahout to descril)e. licfore that, howt ver. a few words alM)ut the functional clianjjes in these casi's of simple nephritis. The structural clian}.>es in the vas«ular apparatus, as well as the mechanical conditions in the swelling of the parts, result necessarily in a much din.iiiished aniount of urine, of relatively hijih ccmcentra- lion and .--H^cific jxravity. hijih colored- the typical .so-called fever urine. Sennn-all)umin is usually present, and. deiiending upon the amount of inflannnator>- (vdema into jilonieruli and tuliuh's. never more than in traces. In morphotic elements this urine is |M)or. as the proi-ess never leads to extensive loss of cellular elements, and the exudate, as we .saw. is purely serous. The first indication of recoverv' is rapid in -rease ii the amount of urine, which indicates clearing of lymphatics and cupillar\- enjrorfrement ; with return to physiological fu-ictions. alhumin (lisap|)ears and the urine loses its increase in concentration. Closely allied to nephritis simplex is a ty|)e which is characterized not only hy parenchymatous degeneration and iiitlanunator>- (edema, hut hy a marked de.scjuamation of ei)ithelium and excessive proliferation of the same. To this subdivision the term nephritis prolifera mifiht proi)eriy l)e fiiven as distinfiui-shinji: it from the simple form. It was called by \ircho\v the catarriial form of nephritis; later it was much nefilected. Imt recofrnized by Orih-' and Kaufnvui- as desqua- mative and proliferative papillar>- catarrh on account of its predominatinji appearance in the medulla t)f t he kidney. In this form we may squeeze out, at autopsy, an alnuidance of turbid i*i: \-«K fliliil trniM llic iiinlulla. inii~i>liiii; <'t ciiitlicli.il ct'lls iiinl ilctillus. It i«. lidWi'Nrr. I)\ llu liM'.-llls colltilH'il to IIh'sc Ilililllo. Iilll ucfU's «litlii>c. :i> icct'iil iiivcsliLL.ilioiis ••!' ntlicrs .irid iii\ own li;tvc .slidWii; it is x'cii |i.iHiciil;iil\ in cases wlit'ii tin- pan'iirlis iiialuiis ilt'ucticratitui of llic fiiitlicliiiiii is tiiarl\f(l. ami imicii of il (Icstroxctl ami lost. Il iiia\. tiicrcl'on'. Imtoiiic assurialcil willi all tillicr tvpcs nf ncpliiitis. and |ila>s, as 1 pifsc iitl\ li(»iic t(» show, iiiucli inorc nf a nilc in tlic inilaininainn |ini((s> tlian is nsualiv supposed I'iir. 't . Wiiile \inliM\v liad ol)serve<| the desiiuaination of tiie epithelium, it was shown l>\ Heer in 1S')1» th.it tliese <'ells rapidly and excessively pfolifeiated. that the tubules dilate and are fre(|ueiitly filled with these cell masses.-' lie rejiardcii this h'sion as an inllaminatory phenomenon. Later ohservers, like Weiiiert,-' (iol^ii,-' and others,-" studied these cell types more carefully and descrihed the fortnalion of epithelial uiaiit -cells in neiihritis il"i^. ()'. Hut the idea ul>limate poisoiiinu: have hroujiht corrohoration of this contention, for he too oh.served the satiie llKtiKVKII All \y. \\l> lAI l»\TIVr. KKMIUKS t'K NUrillllTIS (il I 111 "i Nipliriti- |iri>lifir.i il piii.|iiiliv:i pMrtr (.r lli'iili'- liMip- tillr.| :in, :i -iiiMllcr niH' ,\f. 'I'lic lllliTM IlillK liliroll- li»Mi- lliirkrIHil ■ illMI. riu. (>. f.ii'iiMliMr. ..f iiiuiiimii-h-ir j; i;tt:i-fcti til •*>nvr,!iiH-t iuS-uli' I)K< !;\KI«.\TI\ K AM) KXIDATIV K KKATl HKS OK NKPHIUTIS 03 (lilTii- 'xcossivo opitlu'lial proliferation. Theso cells, nion'over. were . tinctly phiifiocytic to the necrotic cell mask's. In this way s<'veral jienerations of epithelial cells were produced, dis- iiitejirated. and eliniinaternianent rejieneration commenced. The epith( appreciated as an iiniM)rtant factor in the pathofienesis of the inflanunation. Functionally the lesion lH>comes evident hy the fnt' discharjue of the newly forme:enesis anstions which are involveme attention he paid at least to the more important details of the discussion. Vou will n'lnenjher from Miy first lecture, and from what I s.iid in the iM'jiinniiifi to-day, that modern pathologists are divided into .si'veral <-amps as it'jiards the conception and definition of intl.-unni ition. One jrroup adheres to the old term (»f parenehymatous in- 11! CI MKKillTS DISKASK fl;iiimi:itiun. AscliotT, for instance, in liis new hook on patlio- loiiical anatomy, states: " As lonv; as cloudy swellinir of the tu- Imlar epitlieliuni controls llie picture of tlie inilaiinnatory reac- tion witliout particular cliaiiiic in tlie vascular coiuiective tissue and the irloinerular l)odies, one is justilied to speak of a tulmlar nei)hritis." The parenchymatous deiicneration is taken as the i-esult s processes are looked upon either as an accoinpaiiitnent or of the ei)ithelial irritation. This view has. as you .see, a relation to the old. previously dis'ussed ide.is of Virchow on parenchymatous de<:eneration and inflau'.mation. Hut it ditTers from them essentially in rejiardinf;; the parenchym.itous dejreneration ;is an (irlirr pro<'e.ss. the direct result of an injury which is followed, and not caused, as Virchow would hav(> it, Wy exudation. I'an'nchyinatous infl.Mtnmrtioii is. therefore, the prototyp<' of .an iiiHainmation : only when the epithelium is killed the itiflammation U'comes modified. A se<'ond irroup restricts the inflanun.itorv conception solely to the v.iscular and exudative reactive ehany:es, anil divorces the deiicnerative features alisohitely from them, 'i'hese latter may, in the minds of .some, eitlwr precede and excite tlie inflammatory chanjres (.Marchand. /. r. i. or they may initiate .and cause a deirenerative parenchymatous involvcjuent . Nauwerck " has come out p;irticul;.rly strong: for the Latter view in ne|ihritis in an attempt to disprove \Vei;rert's conceptions, hut von Kahlden '■ properly reinarks th.at in an extensive study he has never met such cases. .\ thinl jrrou|). finally, holds, to (piote wi.h l.uharsch. that only the comhination of, and intimate correlation of, alterative. exu lK';>innin}i of this lecture, a non-inflanunatory |)arenchymatous den as an e.s.sential, l)ul no* a nephritic, lesion. (hie c.iii recojrnize, therefore, various ;itt<'mpts of classifica- tion on the part of invest ijiators: I. Degenerative chan<:es in the parenchyma form the <'s.sential feature of nephritis; and they may or may not l)e .iccompamed or tollowed hy va.scular exudation. 2. N'a.scular exudation is the characteristic phenomenon of a nephritis: i^n This may or may not become associated with dey:enerative chaiifics in the parenchyma. (/*) It de|M'nds uj on the parenchymatous destnK'tion. id It may involve the whole v.iscular apparatus of the kidney or only parts of it ifjlomerulo- nephritis). ;{. .\11 estahlishelute de|M>ndence of one change upon the ss m;iy a|)|H'ar more prominent, and in a numlwr of ca.s<'s may contimie so. This latter standjxtuit ap|H'ars to me the most acceptable one, with the followiti^; (jualitications: m MKK.IITS DlSKASi; 1.1 • The term iiifl;imm;ili<»ii (•(•inprisfs tlicsimi toljil of lliosc onclMlcd I'lil iKii ;il)S(iliil('ly (Icih'ikIciiI dciicm-nilivc. piolifci- Mlivi'. Mild «'\iid:ilivt' ( Iwiniics which ;irc llir (hrcit rrsiih \ Mt IcMst Mil inflMmiiiMtory (I'detiiM of the parts, do not exist. Mild it is .in MitificiMJ stretchinu of idcMs to keep them distinct from the conceptions of the iiitlMmiiiMlory process. This conception of inflMmm.ition is, therefore, not tlwit of ;i sin«rle either purely jKissive (\'ircliowi or purely iCMctive i moder III process, hut Mil expression of the sum totiil of s, which are excited li V irritants. '(' |.:iri ZhkI'i. I •I"' 'I' II U('jirliW;ir(lKrri Stiiiid ilir I.1I1 III ilir KiitzuMiliiiiii, DfiiiMlir Kliiiik, \i l)K(iK\KU.\TIVK AM) KXIDATU K KKATIKKS OK .NKi'llKITIS (i7 Other coiici'ptioiis suffer, in my ((pitiion. from the inherent weakness and artificiality of too strict classification. Following the ori;rinal description hy F\lel)s of glomerulo- nephritis, it has l)e<'n the effort of many to estaldi.sh this as a ((articular characteristic ty|M' of nephritis, and si<'nili alone are atTected. aixl in a characteristic inflammatory thrombosis of the capill.ary tuft. On tile other hand. IJiMiert " regards glomerulonephritis as the start in;r-point of any nephritis, and he therefore cla.ssifies any further chanjies as suhdivisions of this uniformly |)rimary • inatomical lesion. While he strictly adheres to a division of pai-enchymatous ;ind interstitial nephritis, lie interprets them as sulxlivisions of the jilomerular afTection. These represj-nt rather extreme views, and in my opinion suffer from the endeavor to create ty|H's of nephritis either out of st.ijies of a lesicni. or from an undue imj)re.s.sion witli pniminent I'e.itures of the inflammatory [irocess in certain cases. Dejretierat ive and exudative nephrites are always tiie result of inten.se >:eneial and characteristic intoxications and infec- tions; al)ove all, the acute exanthemata, particularly durin;: the Lite stajres of xarlet fever, hut other infectious di.sea.ses as well, furnish a larjre numU'r of the ca.s<>s the .severe s<'ptic condi- tion of the usu.al or s|H'cific tyjM's. .se|)tica'mia, pya'mia. pneu- monia itlie latter not at all infnMjuently i, syphilis, erysijK'las, and others. Sometimes the primary focus of infection may he dillicult to detect, or may ap[H>ar insijrnificant, as in an^rina pharynjiis. tonsillitis, or purulent otitis. But there can l)o no doubt that .stnere nepliritis may Ih' either asso('iate ins|M'cted durinji life and at autopsy. II i la III ('»S HKKillT S DISIASi; (Irosslv the kidiifv shows llic ciiiulitioiis of simple iicpliritis intt'ii silicd. It is l:ii-; :cr than iiorinal. firm, Iml-riiiy;. and tin- surface |)idmiiH'litl\ roiivt \V!tl leaves >moolli \. The capsule stretched, remove*! surface, with an opaijue. dusky. ie( Idish-while iirouml-coliM. and lumierous irre^iular. small. |M.inl-like or streaky hemorrhaues. These may occasionally (lit ume such (luueiisioiis as to ^.ive to the whole kidney a pre- (hwninaliniily liemorrh.i^ic apiH'anmce. Sometimes small areas of yellow fatty color .are irre-rularly distriliuted il'itr. T'. On section the kidney is juicy, and discharj:es readily a turhid. leiienialous lluid. The cortex is enormously swollen, pale, and contains irrejiular lu-morrhai:i<- streaks and dots. The normal ^lom-rular rows have apparently, to yireat extent. disapjH'ared. lent in the form of .iilistenin<:. white. es. '11 le mterveinnji hut the i:lomeruli are evi< sliditly elevated |M)ints or mimite -irami! tuliular suhstance appears thick and cloudy. The line of de- marcation Letween cortex and m< dulla is uiuisually well marked. I.v a mo re prominent hut ditTuse piiikish-}:ray cyaiiotici ap- |M'arani'e of the melished forms; and n.iturally th(> variations lu.-iv lesion; secon* U'jrreat. These de|K'nd. first, on the stajic of tin' llv. on the (|ualitative features, dejicnerative or vascular cliaiii:es predominating. In tl le ea rlv st.ijies the evi- dences of inflammatory hypenemia are much more prominent thanlater.wheiide'ienerativeand part icularlye\udativ<< chan«:('s. by mechanical c(»iiipression. a;r;;re<:ation of necrotic material, and hv the general (edematous iml>il)ition of the part.s. chanjie )r vellowish J)ale. and make the the picture from red to ^ray mar kin ":s trra* luallv UK listinct. and cause finally entire olilitera- tion lie 7 Xi'pliriiis ili'^mirraliva rxiiilativii li:rm(irrlijmicii, frmii lii-i' (if iiulniarilitis ~' f'lr.i A hiT>:<\ Imlt'ilii;, uiiil'ormly --wnlliii kuliiiy. All iKiriiial iiiiirklii/is li>M llrni;.r i:i!i>ii Uiw.i II iiii'iliilhi uiiil n)rt<'\ olililiTUtid. Smaller innl liirci i liiiii,irrlijM;i!. iiiicvihly liii uiiifcirmly ilislrilmliMl iivir tin- hIihIc kiiliirv iiirt<\. liil(T|Kila!. i| iiir sinirluri'lt ^^ yi l|ii\>i^li-w!iiti' Mnviks ami iialdus wliirli , ViHnU iiijcctcil \\(i>;hl, tlMt mil-. l»Killai'ii'>, Irtiil- 1 111; Id fusiiiii ami liyalinr >\H'lliii(j<'f tlir liilmlo: miiiic imrt'asr in iiiiiiilx'r ami «izi' of cmli*- llnlial nurlri Scrims fvililalr ililci caiisular -paiT, IcacliiiK t<> ililataliiin ami In liyillim- -wrIliiiK of tiji' i'a|>-'iilar i'|>illirliiiMi. wliiili is icraililally liftnl olT llii- liasciiit'iit iiiriiiliriuiir 111 I pil-liril lowar.l llic lili'l. I'i'W Irukoryti-s in tlii' rapiular spare. X -•><). lii!. '^- Tiifl of jslomcriiliis with ilisliiiil scparalioii iiiio lolmli's; inlraiapsiilai I'xmla- liirti more inarki'il • '-'•>•(. It ill 111 lid 10 V.iriiiil« itUiMii'ruliir. iMriiiloiiifnihir. tiiliiiliir. :iiiiil:ir ih.iliK"* >» iii|iliiilj- i\i|i|:itiMi il iliitiiKrMliv.i. |«irtlv niiri-^i'iili',! in I'in'. s :iiiil '■> In iiilditiiin. ulniiitriili »iili iiiurkcij itiini- anriii« "f iMiirinliyiii.iliiiH ilcui-iii'nilinii iinil miTiisi!. In llir ii|)|mi |i;lll 111 I 111' llirtliri' tllhlllr- llmv Ic »ll'll In rii|lt;iill li llki"Mf« ■ tj."i I'iu II III till' iipiwT piirl iif till- ficlil a dlomrriiliis slio«> M'piinitiiin inln iiiii iif caiiilliiry liMips. willi lucalizi'l alliicli nl loraiisulc. A (jIohhtiiIus li.li.tt ilii- allows niiiipioMiiii l>y fXiiilalr anil liyaliiic Iraiisfiiri.ialiiiii of llir liifl. JHiirkrii- iiiK (if niniiiTlivc ll.-wiir. ( "yslir liilalaliiin of fiilmir in lower part of lirlil. ■ I7"i. 71 MICROCOPY DESOIUTION TEST CHART ANSI and ISO TEST CHART No 2| ^ '^PPUEDJM^IGEJ ^^1 'f-^-^ f'^S) M-J.n St'Mt S'-S "ri^rf^'f; '^'* ""'''' '*^09 USA rjse , ' 1 6) ♦8J - 0300 - P»ione DE(;i;\KHATIVK AM) KXIDATIVK FF.ATIHKS OK NKI'HIMTIS 73 I'in \2 I'lisioii of (jlonicnilar tuft liy ((iinprcssion of ('xiidittc, wliicli leads to its iio- (■ii>sis, and also ilihiti's the capsule. Beloxs it, hyaline (colloid) cast in a tubuh'. I'cri- nloniiTular airl pular cellular infiltration. ' JIH). Kin. IM. - l{ielily cellular (leukocytic) exudate into (cloineriihir capsule, with ilisintL>Kr»- tion of the glomerulus. Similar exudation in surroundin)? ti.ssue and into the tubules, which show parenchymatous swelling. X 210. DKU i:\KKATIVK AM) KXIDATIVK FKATIKKS OF .NKPHKITIS 75 FiK, 14- — Typical capsular ppitlidial proliferation in Klomcruli. becoming unulually flattcncil and fibrillar, willi markoil fusion of capillaries, leailinn to separation of Blotiierular lobu^w anil final ilisintegration. X 1S5. I I)K(iK.\KHATI\ K AM) KXIDATIVK KKATl l{KS (»K NKl'IIHITIS 77 Kilt l"i. MMikil punilciil inlilinilioii ami sliiptiylococcal i'iiil)oli in the (jldincnihir loopx, whii-li has cxli'iiclcd to tlic pcritfloiiicnilar lissiic, Icailintj to necrosis of tlic «)iolr glomerulus. The sinrriuiiiliiiu luliulis sliow typical paiciicliviuatoiis ilcdcnrration. X 1">(). 1 I'iK 10. — ("oiiiplctc piirtilciit necrosis of glomeruli. Capsular space and tulmle free. X 2(K). relatively DKdK.NKIiATIVK AM) KM DATIVK KKATIUKS (»K NKI'IIUITIS 71) liK. Hi.r lii|)injr:i|)lii(:il piiliirc (if nephritis rxM(l.iliv;i ili'({ciicr;itiv;i li:iiii()trliii|jl(M. In the ii|i|.(r piiii of field seviTal (jloineriili ill stall- of necrosis. Cellular inlilliation of interstitial tissue, I'areticliyniatoiis ileiieiic'ialioti ami nernisis of epithelial cells of eoii- voliiled tiiliules. with iiiarkel lieniorrliaKic exudate into them; (itie hvalitie cast. X Iti'J i Tits. 17.— lleniorrhaKie necrosis of a gloinenilus. N'porolie infliimmatorv cells siirroiind the Kloinoruliis. IlenioiTliaKic exudate into tiilmles. x I2">. DKCKNKUATIVK AM) KXl DATIVK KKATIHKS oK XKI'HHITIS SI I'ilJ. IS.— Inflaiiiniatorv cxinlalioii, fusion, and necrosis of gloiiiiTiilar tuft, with u'dpiimtou.s swi-lliuK of <'apsular cpitlicliuni. l>KliK\i;U\TIVK AM) KXIDATIVK KKVTIHHs oK VKI'MUITIs ,S;t I'itJ l!l. lltiiKiriliaKic' fiisiim aii'l ii.'crosis of liifl. Tlir siirfiKT still shows f.-w dropsiciil, swolliii. iMiilotlu'lul or cpilliclial (clIs, (Kilrtiiatoiis swclliiiK "f capsular cpitlicliiiin. iiMi DECENERATIVE AND EXUDATIVE FEATURES OF NEPHRITIS 85 In certain cases hemorrhajies occur early and persistently, and therefore jiive to the whole lesion a characteristic appearance. For the sake of study, we may divide the manifold microscopic processes under the following? headings : chanjjes in the glomeruli, changes in the tubular substances, changes in the intertubular substance. First, the changes in the glomeruli have been well studied and are of the greatest importance, for, as we will see later, the ultimate fate of the kidney depends largely upon them. The first changes 'w the glomeruli are degenerative in char- acter and affect the endothelium of the capillaries and the lining epithelium of the tuft. Coincident is inflammatory' hypera'mia of the capillaries, rapidly followed by serous imbibition of all the structures of the tuft. In severe cases all of these are well accentuated from the start. In milder cases, von Kahlden-*' found degenerative features the very first phenomenon, con- sisting mainly of fatty degeneration of the capsular epithelium and capillarA' endothelium. Even in these milder cases, how- ever, infiammator>' a'dema into the tuft and into the space be- tween it and the capsule follows so rapidly that it cannot well be separated from the degenerative changes. As the result of lx)th of these degeneration and serous exudate — the capsular epi- thelium is lifted off the basement membrane and pushed forward, the epithelial cells of the tuft loosen and desquamate, hyaline swelling, leading to thickening and turbidity of the capillarj' walls, occurs. As a result of this, fusion of the lobules follows with the characteristic inflammatory' accumulation of leu- kocytes, and their emigration into the tuft and capsule. The appearance of free red cells is frequent. The exudate lies partly in and between the convoluted loops and lobules of the capillaries, but later fills the capsule, gradually compressing the convoluted tuft toward a peripheral portion of the capsule. As :=-.= * S() HHKillT S DISKASK a coiisccnuMicc'. the tiifl. thus affected, appears primarily larj^e, plump, pale, filliuji the capsule (•()m|)letely: hut later the capsule distends, as the result (if pressure from coajiulated exuded masses and cell detritus, .and leaves the capillaries retracted and less conspicuous I Fins. S to V2k Much discussion has arisen over the (|uestion as to whether here proliferation of the epithelium lininj; the tuft occurs. On account of th(>complicated pictures in the tuft, it offers particu- lar difliculty. I do not share the view that this takes j)lace to any extent, llvidently. the initi.tl dejr(>nerative chanires and the other inflam- matory conditions make this impossible. The hulk of the nuclear increase within the tuft appears to me of leukocytic and en- dothelial derivation iFiii. \'Ak On the other hand, proliferation of (he epithelium of the capsule is a freipient. rather constant |)heiiomenon. It is seen particularly heautifully in scarlet fever, and .sometimes in the other exanthemata, .spvei'e septic condi- tions, al.-io in syphilis. Whether it is a very oiirW phenomenon is (loul>tful, \'on Kahlden was never ahle to observe it in very recent cases. It is certain that it occurs only in well establishe(l nephrite-;. One can oh.s(>rv(> th.at jiradually rows of l.ariic epithelial or epithelioid cells, followinii the inner circular wall of the capsule, concentrically advance from the periphery toward the lumen. This proliferation usually commences in those lilomeruli which have become widely stretched and dilated by free exudate, .and in which the tuft h:is been pushed tow.ard one pole > !• iii. 14 1. From the opposite diicction, this epithelium advances into the capsule, inclosinii the exu(l(>(l masses within it. and fifadually assumes a characteristic i)rominent crescent shape, which the (lerman patholojiists have lontt descrilu'd under the name of " Halhmond" icrescenti pictures. In some cases it becomes DKCKMilJATIVK AM) KXIDATIVK KKATfHKS OK NKI'HHITIS 87 Via. 21). — ('i)inpl('t(' Kraniilar niMTDsis of (jloiiicrular tuft, surrimiulcil l>y (•"adulated serous exudate. I'cw swollen epitlielial or eiidottielial eells still visible. X 4(H). I''i»!. '21. — Destruetivi' pareneliymatous deneueratioti of fibular epithelium. Fusion of granular rellular detritus into easts within dilated tubules. X H'M. DE(}K.\KRATIVE AM) KXl UATIVK KKATIKKS OF NEPHRITIS 89 £.^" rifi 22. — IIIkIi iiiii|{>>>i><"»><>>> of :' ttlhulc, with K>°anular ('ytoplusiiiic (lisinlcfcnition uiid iiiK'Iciir Idss. ' ii DKiJKNKKATIVK AM) K.M HATIVK FKATl HKS OK NKI'HUITIS 91 ^■^ ;T£";ci5» 'iQm • "Til 1 Mi if k ^-1 1 IV ^ ^0 i-^v" I'iK- 2:i. ( Iniimliir cfUiilar llKl^s<•^^. leukocytes, iiiid epillielial cells in tuli\iles, willi extensive neiTosis of these iles(|ii:iinateil cells, infliininialiiry cMKorRenient ,'a>'J liemorrliages of inlcrtulmlar tissue, x 22.">. I'lK- -l- — One tutnilo with leukocytic exudate, another with epithelial necrotic iniisses, two others with hvaline formation in tubules. DKOKNKRATIVK AXI) EXtDATlVK KKATIRES OK NEPHRITIS 93 rxcpHsivp, replaces the whole of the tuft, and underjtoes hyaline defeneration. This epithelial proliferation ap|)earH to l)e an inflanmiator>' phenomenon, excited here, as in the tubules, by the accunmlation of necrotic and exuded masses, and fulfils primarily phanocytic-dearinji duty, inaujiuratinjj; fibrous and hyaline replacement. These we will consider later. Of rarer occurrence are the formation of inflammator>- hyaline thrombi in the capillaries, descril)ed by Friedlander; and Hibl)ert observed flattening of the thickened lining epithelium, thereby adding to a compression and impermeal)ility of the vessels already established by exudate and desquamated en- dothelial cells. Diapedesis of red blood-cells may become very marked, with severe hemorrhages, complicating exudation into the tuft or capsule. In these, rapid necrosis is the termination. When the exudate becomes purulent, the glomerulus meets the .same fate (Figs. 15 to 20). Secondly, as regards changes in the tubules. These are un- evenly distributed, usually more intense in the first convoluted portion, and relatively less in the limbs of Henle and the collecting tubules. Senator '■''' has pointed out that this is probably the re- sult of the greater concentration of the blood-current, after leav- ing the glomerulus, which necessarily exposes the epithelium of the convoluted tubules to direct and greater injur}-. On the other hand, the experimental investigations of Lyon ^" have dem- onstrated that in certain acute intoxications the ascending limb of Henle suffers most severely. They are the least resistant parts, and show disintegrative and necrotic changes more commonly than elsewhere. The cells, in thus affected parts, show intense parenchymatous degeneration, leading to fatty degeneration and necrosis. Unlike simple nephritis, the tendency is here to de- struction and loss of cells. Swelling and turbidity, with loss of cellular outline, are here marked from the lieginning, cell masses 5>4 MHKillT s DISKXSK fuse, the prdlopl.isiii disiiili'jrratcs «'iilin'ly, mikI fatty siilistaiiccs tend tDMpiM-ar in the foriiiof fiiH- dniplcts; vaniolcs appear; the laiuc mamilcs of the cfll, l>y (•(iiifiiicnrc. form iiccnttic massrs, and after lireakiiiii of the cell inemliraiie, the iletritiis is dis- eharued into the hiinen of the tuli\iles i I'ius. L'l to 124'. In severe cases tlie lining nieinlirane may lie eoinpletely des(|iia- maled I"ii;. JS . It is interest inn to note, and was first |)oiiited out liy nililtert. tliat tlie ap|M'aranee of fatly substances commences early and primarily in the cells of the loops of llenle, aiid if we look at such a specimen, one cannot help lieinj; astonished at this ap|»arent selective location. Later, however, all tlie cells under- -id the s.ime f:ite. ( h.-iiijics in the nuclei appear later, hut .ire here of e(|ual .severity, leadiiiii to their entire lo.ss. They are destroyed either \>y rapid chromatolysis, with some persistence of the achromatic siihstance. or the chromatin ix'comes clum|M'd. solid, and homoiiciieous. .so that the orii|ii:iMl:lll.Mi iil' ipil liclilllli iil rilliiilcs, willl |£l\ilml:il ((illliul.s III lllllK'll ol lillilll(«. . t(N) Ki(t. '-<•• — Mjirknl dilatation and distention of tul)iilw. X 12'). UMiKNKKATIVK AM. KXI I.ATIVK KKATI UKs OK \KI-H«ITIS 97 K'lrut ihtiil Nimcof Ihcrp hrliiliii piK iilr soli.l ,„ll„i,| ,.,,ms i„ mhuU-s. Tlmsr .(.MlaininK th,- ,asts will. i)K(;k.\ki{ativk and kxidativk fkatires ok xkphritis 99 (Fijis. 2;i and 24). This important fact appears plain from the ol)sorvati()ns of Lyon. Hoineko, and my own. The cells thus de- rived from the linino; epithelium of ti.e tulniles differ entirely from the normal in appearance and function. In the lower portion of the tubule they are r()wth. As I said before, their function must be brou<-ht into relation to the inflammatory defenses of the tissue. This is indicated, not only by their distinct morpholo<:y and abundance of production, but also by the phajjocytic power of these cells. Rejieneration of typical permanent epithelium does not occur until all inflammatory irritants and products have thus l)een removed, but then with fireat activity. The process here outlined cannot but arouse one's «ireat interest and astonish- ment from a «>;eneral patholojjical standpoi»it. Consider for a moment that hijrhly differentiated epithelial cells, under the necessity of foreif-n invasion, so to speak, throw aside their hi^dier attributes, and produce an offsprinules contains more than tliis material: leukocytes, red cells, coaiiulated .alhuminous exudat(> enter |)artlv throuiih their own injured walls, and to some extent are washetldown from the iilomenili. Asa coiise(|uence. tiietuliules enlariic so that their lumen is fre(|uently double the size of a normal one l'"iii. -<>'. Ciradually the contents are moved to- ward the pelvis of the kidney, and finally are wasiied out with the urine, or pressed and fus(>d into casts. To t'le latter we must now pay ;ittention. Casts are either cellular or they are homogeneous, p.ile, transj)arent hyaline, or. if thicker and more solid in appearance, waxy: finally irranuiar. Not infrequently they may he mixed hy the adiiesion ol cells to a hy.iline or waxy en the oriiiin of the hvaline aixl waxy type: (•as A numl)er of investiiiators beli(>ve that tliev oriLiinate from fusion of des'|uamated epithelial pro- toplasmic renmants. Others, however, believe that they are the product of an alltuminous exudiite into the tubules. The formation from fibrin has also ix'cn advocated, and finally it is held that thev are the product of a s])ecific secretion of hyaline •ilobules of the epitheliai cells. The literature on the formation of casts is very extensive, so that it will brieflv review ;ill of it . nnpossible to even Doubtless you recall that it was the lireat anatomist Ileiile'" whofiist discovered this rela.tionship.-md importance in comiection with the iuHammatioiis of the kidney. Me interpreted them a.s fibrin coauula. Uovida '' later thorouirhlv analvzed them cliemi- DMiKNKUATIVK AM) KXIDATIVK FKATtKKS OF NKI'HHITIS 101 (•ally and dcnioiist rated thorn as albuminoid hodies. Sin<'e then very numerous anatomical and exjx'rimental invest ijiat ions have endeavored to demonstrate their exact derivation and chemical constitution. Physically t'.icse hyaline casts are us" illy under 1 mm. lonji. and the thickness is between 0.01 and 0.05 mm. Their shape necessaril\' varies accordina, to the tubes they come from; and on their downward way they are freijuently broken or bent. In the kidneys they may be found in all parts of the tu- bules. l)ut with particular frecjuency in the loops, undoubtedly on account of the mechanical difficulty of propulsion there. \ relat' )n.shi|) between albuminuria and cast formation does not seem to exi.st ; and one may be abundant without the other. This fact, as well as their aj)parent different chemical constitution, has been particularly emphasized by those who do not recoj-iiize their derivation from exuded serum-albumin. On the other hand. \Veiss; the process of parenchymatous defieneration, may be discharjjed and fuse, with the formation of casts. He calls these "secretion casts." Similar are tlie views of Landsteiner.^' who hokis that hyaline bodies develop in the epithelial cells as a result of patholofjical stimuli. They are discharjied and fuse to casts. Hibl)ert, on the other hand, claims that such hyaline bodies may be observed in healthy kidneys, and that any relation to the formation of casts does not exist. Pfister" observed the occur- 102 HKKiHT S DISKASi: ivncc of jii-aiuilcs within the (Ic^ctHTatinjr cells, which rospoiidod to the Hhiiii stain of Wciiiort, ami also in other staiiiiiiarded them as fihrin, particu- larly as they answ(>red to Weijrert's fibrin stain. This has l)een contradicted l)y Lul)arsch.'" who holds that other substances directly demonstrated in all stajies. That a DK(JKNKKATIVK AND KXIDATIVK KKATIKKS OK XKl'HKITIS 103 colloid secretion is fiirinslieil l)v the epitiiplium is not probable, but, more likely, that a colloid dejieneration or transformation of the cells as Lyon expresses it contributes toward them. Finally, it appears that both of these substances may fuse with inflammatory ali)uminous exudate. We can recojinize, there- fore, these three factors that enter into cast orifjin, and as one or the other predomiintes or may be absent, the character of the cast varies physically and chemically. These views are further supported by the observations of Litten."^ who demon- strated not only the participation of coajiuhited epithelial matter, but also the addition of trajisuded serum-all )umin; and Lanfjhans,'" who saw not only epithelium, luit also chanjted leukocytes and red blood-cells enteriufi into their com])ination. That in the presence of much disintesirated cell material, fer- ment action may play a role"'" to further change the constitu- tion of these substances, and cause coajriilation, seems likely. Hibbert contends that the acid reaction of the urint may be a factor in the coajjulation of albuminous matter to casts. A few words about cvlitidroids. These, as you know, are pale, lonji. tortuous, narrow, usually distinctly striated bands or ribbon-like formations. One end is usually rounded, while the other extremity frequently presents a torn, fibrillated appearance. Some hold them closely allied to hyaline casts; others, however, — and I .share the view, — believe that they are mucoid threads, which owe their orijiin either to prostatic secretion or secre- tions from Cowix^r's and Lit t re's jilands. They occur, some- times in otherwise normal urine, in jireat abundance, but particu- larly with other nuicoid and slimy matter. On the other hand, they do not seem to have any relation to the inflammations of the kidney, and I have never seen anything in kidney sections which resembled them. This makes it probable that they owe their orijrin to other parts of the fjenito-urinary tract. 104 HI{l(;HT S DISKASi: Thirdly, the cli.iiijrcs iti the iiitcrtuhular interstitial tissue. This is not only the support in-: connect iv('-tissu(> frame of the parenchyma, but tin- carrier of liloctd-vessels. lymphatics, and the nerves, '{'he chanires occurrinj: in it are partly . But, further, while the.se chaiiiies.-dTect the tuhules, their disturbances, by nece.ssary interchanire, cau.se subsecjuent patholo<;ic;d alterations in the in- terstitial tissue. It will liive you ••m idea how intimately all these various structures are related, and that much of the c(miplex picture of the disease is not nece.ssarily the result of direct injury or in v.ision, but a .subseipient development , the result of disturbed anatomical relations. This accoimts, in no small de<:ree, for the jireat individual variations which we daily meet in all diseases. The flrst chans.sel-walls, and lack of resorption on the part of the lymphatics. This inflanmiatory irdema leads to imbibition of the coimective-t issue structures and, as we .saw be- fore, the epithelium of the surroundinji tubules. The comieetive- ti.ssue fibers .separate, become stretched, jrla.ssy, pale, inflexible; and stafjnation of blocxl-and lymph-streams follo\ ^. Then occurs, i)k<;k.\ki{.vtivk and k.mdativk kkatikes ok nki'iihitis Kt") I"i(f. •_'!». r(ii(jlieneratin- of the vessel- walls. The blood is discharjjed into the tissue spaces and tubules. In these more severe cases fibrin is also present. Under these circumstances the kidney l)ecomes succulejit. softer, and an abundant turbid fluid may l)e squeezed out on section. However, these are not the only chaufres wiiich are promi- nent in the interstitial tissue. Connective-tissue and endothelial cells underjio cloudy swelling' and fatty chanjies. The latter may become vory marked, and lead toaccun)ulation of abundant fat- drops in the interstitial tissue and within tissue and lymphatic spaces. Lohlein"'- repirds this as an indication of resorption. The fatty sul)stances are partly ordinaiy fat, partly doubly refractin-stalline protafjon- like l)ody. I will discuss these matters in detail in connection with fatty degenerative nephritis. It remains to sketch the functional disturbances thus induced. t I OS HUKiMT S DISKASi; Tlic scvric tliimjics in the ^tlomcnili nrul tuNiiU's ncci'ssarily lend In ;i innrkcd diniiiiutioii in the iiiiiouiit of urine, .soinetinies to alinosl Mil ;iiiiui;i. 'riic urine llius U'conies ne<'essarily liiyli colored. :ind fimdu.illy. as e\uer of desijuaniated and iiewiy formed epithelial cells. Necrotic cell mass(>s are also present. Ca.sts are very numerous hlood. leukocytic, epithelial. f>raiiular. fatty, hya- line, and waxy, with the cellular type predominatiii"!. .Many of the hlood-cells underii(» Iwemolysis. .settinjr tli(> pijimeiit free, which adds to the characteristic smoky color of the urine. These evidences vary necessarily with the predominance^ or ahsence of tlie.se patiiolo;.ncal chaiifies. and this leads me to say a few words ahout these variations and their prohahle cause. \() douht you appreciate that what I have presented to you here is a composite picture, suhject to many individual modifica- tions. Out of the.se we can recoiMiize two larger jrroups: one in which the proce.ss is related more particularly and ener«>:etically to the vascular apparatus, and one in which the process is pre- d()minatin;rly dejrenerative and proliferative amonji the fixed cells of the kidney. .\s one or the other pnvlominates and in- fluences the later manifestations of the disease, we c;in recofjiiize that exudative or dejienerative and proliferative features pre- dominate, and therefore jrive t(; the whole lesion a characteristic DMiKXKHATIVK AM) KXIDATIVK KKATfUKS OK NKPHKITIS 109 stump. The caiisf for this lies iiii(loul>t('(lly not only in the (|iU'stion of <|U;inlitativ(' irritation, hut in the iwculiar affinity which cc'rtaiii invasions have for «»n(' or tlu' otlx-r tissue. It has iwi'ii found hy Mauni<;art(>n. for instance, that the intro(lu<'tion of tulxTcle liacilli leads ni.iinly to the fo'ination of y exudative processes. The .s;inie fact .applies to other intoxications and poisons. Snake venoms, f(»r instance, have a fireater destructive and. therefore, reactive effect on the vascular apparatus. In .scarlet fever this has Ion;; In'en reco^inized. On the other hand, certain dis<*ases and |M)i.sons exert the greatest destructive inffuence on the fixed cells, and their lesions, and results therefrom, .-ire more evident and dominating in such cases. Certainly it would lie a mistake to endeavor to draw lines of mathematical distinction l)Otween these various manifestations. In the end, we are dealing with one or another accentuation of fctitiirt's of a nephritis, not with independent distinct disea.ses. It is only for th<' jnirpose of study that we can divorce, or abstract them from the others, thus lifting them above concomitant, correlated, and dependent changes. lOriMH LKCTlHi:* I'm; IJksi i.Ts wd 'I'kumin atiun^ (ik l)i;iiK\Kii \ti\ k and \'.\\- datim; NKi'iimris, I'iiudi iti\ k ('iiwiiKs i\ thk KlIlNKV (it n III nil II : We liMVf followed the iicpliritic process to the lieijilit of its (U'veiopinetit. \Vli;it .•lie its teniiiiiiitiolis? 'I'liey ;iie tliree: first, f.'ital; secoixi, MtteDiiatioii, with eertaiii tiXMliticatioiis in theinfi.'iiiiiiiatioii. which allows progress in a less l)rus(|iie iiiaiuier, ami therefore extends over a prolon^^ed jM'riod of time; tliird, latency, with (onstant daiijrerof exacerbation, and ultimate fatal tenninati')!!. I have not included recctvery in this list, liec;iuse I consider it extremely doul>tful wlx'ther actual restitwtictii to intejirity ever occurs in severe nephritis, and wh<'ther it can (>ver he rejiarded as healed or cured, in the sense in which these terms are ordinarily employed. If you recall for a moiiicnt • . <> seveu destructive chancres which we observed in the glomeruli, and the anaton)ical arranj;ement of the lioratioi) of tin* inflanunation will niak<' |M»s.sil»l<' at Irast soinr functional activity in houh' mon- than in otlu'ix; howevrr, the |)atholo};ical chanj^cs in thcni hav«' at least jXTniancntly affected the normal structures, and, while not com|)letely ainiihiiatin^ them, leave them in an injure vulneral)le and hasten the ultimate fate of final destruction. In the tuhules, as we will learn pres<'ntly, a very simihtr state of affairs exists. Indeed, strong evidence has gradually accunuilated which points to tlie fact that many of the .s()-calle they furnish an objective anatomical basis for these ideas. I hjive already touched ufK)n them in the first lecture, but yoi vll 112 nUKillT S DISKASK n'c;ill tliMt he found lliat tlicsc s()-c;illc(l s('c()iul;irv (•oiitnictcd kuliu'vs arc iniicli more frcMjiiciit lliaii supposed, and iiiav he fracod to previous stages of dejiciierative and exudative uephfitis. lie also. you recall, drew attention to a type of cases which, haviuji' pa.ssed thfouirli a so-called acute attack, enjoyed felative iiealth. .iTid then suddenly died witii all the syiriptoms of nephritis. In them he found typical pfoductive jiloincfulonephritis with marked contraction of theoriran: the process nuist have jrone on insidiously, hut no less perniciously, for years. Similar are the views of .\ufreclit. My own observations in the matter fully corrohorate the.se contentions, and I am of the opinion that at least the majoritv of (•.•i.ses of late nephritis have been ushered in hy previous deirenerative exudative lesions, which, havinii become latent, have been disre;iarded clinically until their proufess has led to a point where the orfranisin is unable to adapt it.self. Then it pro- duces manifestations which ap|)ear n(>w .and stidden. but mijiht h.ave been .anticipated lonu' ai^o. riKpiestionably. this has much pnictii-al be.arini; in the matter of pro;rii<»sis and in the matter of treatment also. ( >ne should l)e very cautious in niviiii: an opti- mistic ultimate projrnosis in any deucnerativeexud.ative nephritis, .and no doubt many mon' cases of nephritis i-ould be benefited bv treatment if they were more carefully watched for.a lon^ tim(> after the evidences of the i>ru.s(iue initial lesions had subsided, and later at intervals. Mut here, as in other diseases, ale to alt.iin with our hasty, purely objective methods. .Much u.sed to enter into the lejiitiniate practice of medicine which now has passed away for lack of time, or has been consumed by the charlatanism of schools, and exafijrerated l)y uneducated, unrefined followers. Dilettantism and notoriety to-day march under the flaji of l)road scientific knowledjie and busine.ss methods. I\H)ple forater variety of pictures. This depends probably upon complex (jualitative as well as (juantitative chanfies within the kidnev and the irritant. It wouhl lead me I ^1 If •■(: 114 UliKillT S DISKASK here too far to enter into a detailed discussion of tliis (luestioii, hut I will oiilv indicate to vou that this nuist i)e attril)Uted. first. to tlie chaimes which the iiiflaimiiati( )ii as proc luced HI tl)( th tissues of the kidney and in their anatomical airanfreinent . Into this natuially enter the (|ualitative clian,ii(>s within the cells and niech; inical factors due to the reai ranirenien tofti le parts. Secoiu owini;; to the chaniics in the irritant hrou^ht ahout i)y the in- flammatory condition of the orjran. much of it has been directly destroyed, or .-it least altered. Moth thes(> points are complex and intricate, and involve many other problems, and I therefore can- not fully discuss them within the scop(> of these lectures. Suffice it, therefore, if you api)reciate that tiie inflanunatory alterations in the structure of the kidney and the concomitant chanii'ed rela- tionshipto the inflammatory irritant havedrifted toa jjoint where the oriiiinal response of the tissues to the invasion iiecessarilv ceases .and undermu-s < asily, the surface bulfics very prominently, as .so, on section, does the cortex. The normal markinirs appear lost or nnich distorted. The jilomeruli ;ire pale !iiid <:lisieniim-. the medulla dull pale yellow in color, and the line of demarcation between it and the cortex poorly accentuatermed it at the bejiinninii of the.se lectures, the de.!i(>nerative fatty nephritis. Inasnmch as these fatty sub.-;tances play such a role, we nnist have a clear picture in our mind what they are. and what is their derivation and siunificanc( Here we enter another very nuich di.sputed and much foujihl over liround of jieneral patholofiy. Vou nuist, therefore, be content with a .short .summary of the situation. Vou are aware that X'irchow ' orijrinally distinjiui.shed between two ty|>es of fatty chanjies: de(). and. in phosphorus-poisoninji. even 75 j)er cent. These l.irjie percentafies ap{)eare(l to Hosenfeld as only ascril)able to infiltration, and he found the proof in the followinji in;:('nious exjH'riments: If an animal is made practically fat-free by starvation, and then fed with a foreiost -mortem softeninj;. This is especially well illustrated in certain inflamed oriians, [)articularly the lunjis, whii'h are ri<'h in exudate. This s(»ftenin!H', or autolysis.'-' is accompanied liy the ap|)earance in the cells and tissues of an abundance of iiranules. somewhat similar in mori)holo^ical aj)- pearance to the chauiics we ol».ser\-e in the process still called fat deucneration and in late parenchymatous (lejicneration. These small fat-appeariuu e of the chemistry of the.sp substances is still very uncertain, which is larjicly due to the fact that it has l)een extremely difficult to i.sohite them in the pure state. The entity and constitution of .some of them, at least, are, therefore, .still doubtful and uncertain. DKCiKNKHATIVK AM) KXfDATIVK NKI'UKITIS 1!) Acconliiiu to the invcstifiMtions of Tliiulichum and Haii^r. wo may classify tliciii first : As pliosphatidcs, /. < .. lipoids containiiifi iiiti()y;(>M and |»li(»splionis. 'I'o this jiroup holonji the lecithins and the related bodies, kephalin in the brain, myelin and para- mvelm an( 1 spl lyiijromyehn, o( '11 currinji also in the brain, in e^^ ri) yellow, in red blood-cells, and m the snprarenals. Ihese repre- sent niono-ami(lo-mon()-i)hosi)hatides. mono-amido-diphospha- tides, (li-amido-mono-phosi)hatides, and tri-amido-j)hosphatide, the latter a substance occnrrinji in the kidney. Their chemical constitution is perhaps best illu.strated in the lecithins In order to trace this structmc we have to synthetize the decomposition products. ( oinmencinji with amm(»nia. with which you are all familiar, H N H Ainmimiiim and its livdroxiil H N H HO Aiiimoiiiiim livilroxid we may obtain by simple substitution a compound known chemically as trimethyl-oxy-ethyl anmionium. or more fre- (juently as cholin. an anunonium l)ase. as follows: ,('H.-C'H,(OH) N -(('H:0;. OH Tills ba.se may combine with jilycerin phosphoric acid: ("H,(()H) ('H,(OH) CH — O \ OH PO, OH in'which two of the hydrofjens have been replaced by two fatty acid radicles, say of the stearj-l f>;roup : 12() HUItiHT s DISK ASi; •H.. (> (',JI,,() CU. O N IK) I'O ( HH () N (CH,). OH Jiiid wo thou ()l)t;iiii the (listcarvl-Iccitliin. It will Ix- plain from this foniiula and dovclopniont that there is nioro than ono kind of lecithin, dependinj; upon the kind of fatty acid radicle in the -ilycenii-phosphoric-acid j-roup of the compound. We. therefore, have also palmityl and oleyl-lecithins. and Thudichuin rofiards it as pos.sil,le that two difTereiit fatty acid radicles may enter into the combination. therei)y increasinjr the numher of possible lecithins. All of th.M' substances occur in ;inimal cells in abundance, and their decomposition products are found normally in traces in the urine." but under abnormal conditions, particularly in certain metabolic and nervous disturbances with toxic .symptcmis. cholin and -lycerin ior.i-ani(M pho.sphori.- acid have been foun.l much increa.sed in tho urine.' ' The second -roup is made up of nitrogenous but phosphoru.-- free lipoids, the so-called cereimKsides. and related to the jjlyco- sides. which form constituents of the .so-called prota^on. The third ;ind very important j^roup is represented by the Mon-nitro-.'iiousand iion-plu.sphorized cholestcrins. which belon- to th.' terpenes. T|„,s,. ,,,-,. „f very -reat interest, not .,nlv on .'•ec(.unt of their wide occurrence in the animal and vegetable kinfrdoni. as the so-called phytosterin. but Ix-cause they par- ticularly have acrjuire.l a very -.vat nMe in the pr()i)lems of fat defeneration .and fat infiltration. The elch-r Beneke drew atten- tion to the abundant (•ccurrences of cholesterin nianv vears airo. DKiiKNKHATIVK AM) KXIDATIVK NKI'HKITIS 121 hut not until rocoutly has this iniportaiicc liccii proiK'rly valued. Chcinically, it has the formula (VHu.O. and is a nionovalont. simple, unsaturated, secondary- alcohol, containinfi four saturated hydrated miclei. The chemical constitution of cholesterin stamps it evidently as c()mi)licate of investijiiition into this problem .some very interestinu jioints developed. i{osenfeld as the first drew at- tention to the fact that the inicroscopi<- ap|M'ar;inces and valua- tion of fat contents of an oru:in .are umcliable, and that, there- fore, chemic.d .and morpholo^iical results do not cover each other in fat determination. I!(>.ilth\ and fatty kidneys m.ay not .show their fit contents at all, even if this amounts to '2'.i |H*r cent. .\|(»re curious, however, is the fact that kidneys of the same fat contents ( I7.*.> to IS. -J per cent, i may apjw'arat one time healthy, at another extremely fatty. Kidneys with even a diminished amoimt of fat, say, 10 percent., may .seem to us at times extremelv fatty. That this is not peculiar to the kidney was .shown l)y Bo.-rable .amounts of soap and cholesterin. Ivlotz,-" from Adami'.s laboratory, has only recently pointed out that at least part of the myelins in the kidney «>xist as soaps of oleic acid, and that su;'h fatty compounds are not readily demon.st rated l)y the ordinary' stainin;; with sudan III. but can l)o obtained by extraction with ah'ohol. It is. therefore, evident that the pre.sence of fat and fat-like substances may not always be visible; on the other hand, may l)ecome visible, with relatively .small quantities, not expeedin<>; the normal. From the forejioinj; it follows that the morpholofiical ap{)earance of fat in the orfian.s means not neces- l)K«iK\KUAII\ K AM) K.M DATIVK NKI'IIIMTIs 12:{ sirily iiici«';i.s<' in f;it, l>ul :i tiiolcciil.-ir pliysicil (Iccoiistitutiori of the cell, \vli('tcl)y f.it <»iiv:iii:illy coiilaincd :iii«l coiiccalcil in the stnictuiT <»f flic protoplasm :ip|M'!iis fret' to lis. Kraiis, ' and particularly Alhrcclit.-'-' whose ideas I have already presented in coiincclioii with parencliyniatous dejieneration, assiiinc for its explanation that proto|)lasni exists iiornially as a fluid pulp, an emulsion, which contains fatty siihstances so finely divided that they are invisilile. !\ rails draws at tent ion to the fact that neutral lluid fat does not reailily emulsify. Imt does so as soon as some f.itty acid is added. i'liis is expliiinal)Ie liy the supposition that fluid fat is a solution of f.itty ;icid. whose molecules ;ire e<|ually distrilmtcd. :is in all solutions, hetwicn those of the neutral fat. If this mixture is hroiijrht into contact with an alkali. the.s<' nioleculesdiffu.se into it and form soaps, which unite as a honeycomh (Biit.schlii. inclosing within it the fluid fat in the form of drops. .Mhrecht's "troptijic llntmischun^." or myel- inic deconstitution, wiiich we have reviewed, would Ik' of a similar nature, althoujrh it also includes important chanjies in the protein constituents of the protoplasm. 'i'he old conception of Virchow, who spoke of a direct tran.s- formation of protein into fat. has l)een discarded, therefore, and Kraus has reintroduced the term fatty metamorphosis, by which is understood a physical deconstitution of the cell protoplasm, with the lil)eration of fat-similar substances. A different view, however, is entertained by A.schoff.'' who still rejiards the vital fat proces-ses as infiltrative in character. In favor of this, he puts forward the coexistence of i.sotropous and anLsotropous drops in the same cells, the oceurr'^'nce of anisotropous substances in cells which show no evidence of dejieneration, and particularly the re.sorption of anisotropous drops by the endothelial lymph-cells of the fjall-bladder in lonji- continued bile stasis; he holds, further, that in abscess formation I- h |i :! , it { ^^ IE :r r' I Il»l HHKMIT S I)1SK\SK :iii»l (liiriiifi «l(M;«-iicr;tliv»' itifl:itnin!il(trv lesions. :is in loii^-con- limicd lu'phtili.s. clKtli-stcriii is s<'t free, .iiid citlicr rcphiccs the v:lv(( rill with the forni.'ition of li|M>i(|s, or is t.-ikcii up l>v cells :is eoiiipleted cliolesteriii ester with other iieutml fat. lie therefore sjM'.iks of two irroiips of fat infiltrations: one, the jrly<<'iin-<'ster- fat infiltration, .md the other the cholesterin-ester-fat infiltration. .\scholTditrerenti;ites these chan-ies definitely from the .so-<'alled po.stinorteni or .•iiitolytically orijiin.atinv: myelins. The latter, he st.'ites. .almost always lack .arii.sotropism in contradistinction to the intravit.il forms. They .ire not f.-ttty in reaction, and then^- foH' lack the chanicteristic stains of these suKstafices with sudaii III. Sch.arl.ich. Nilehhie. and osmic .icid. Hut he admits that durinji autolysis fatty .sul)stances of the ;rlycerin and cholesterin tyjM'. which were stored in the cells durin;: vital proc«'s.ses. may apjM'.ir. There .are one or two other points which deserve considera- tion. Uuhow-' showed that the percent.'i^-c increase of f.at in the fattily de^renerated he.trt was relatively very low i.ti per cent, of the moist. N per cent, of the dry. mu.scle sul)stance. amountinj: to only ;d)out .i |H'r cent, of the fn sh mu.scle, not more than ') to S) fim. for the whole heart. Many times it is |<>ss. These fiviures. HuIm)W holds, cm he explained |H'rfe<-tly on the strenerv(>rt(>t:ilH>listii. pnxliK'cs more iicid :iii(l |»n>h:ilily discliMivcs less. As ;i result . tioii. Oswald"' has |M)iiite(l out that the ideas of Huliow are really not o|>|M»sed to thos<' nfeld, inasiiuich as it may Im* su|)|>os<>d that the Idood leaves its fat in the dej;eneratin;; organs to later carry more fat to it from the distant fat de|Mits of the Inxly. Now, to sum up: I'roiu the fore^oiny: it ap|H'ars that the oc<"urrence of fat in the orjiaiis is not of uniform character, and also not of uniform derivation. It may occur first as a tnmspor- tation of material to cells for the purp<»s<' of supplyinrial l«>comes im|M)ssilile, fat is sulhstituted. This accumulation is aided, undouhtedly. in many ca.ses. hy in- ahilify to burn fat pro|H"rly. The nature of this fat is largely neutral, isotropous fat ^rlycerin esters. But win ii this proces.s liecomes a.s.sociated with, and takes pla- and dis- orjianizinji cells. The conii)licate(l nature of nutritive disturb- ances in orjians makes a conihination of both of these at times probable, and tlu dimini.shed alkalinity of the blood may well be an infhiencinj; factor. Under normal conditions a moderate dejrree of fat infiltration in th(> kidney has Ikhmi noted by von Haii.seniann, and we can easily conceive of this. Hut. on the other hand, the myelinic disintejiratioii of cells, and the occurrence of jM-otajion. choles- teriii. and related bodies in considerable amount, must always l)e of j)atholoiiical orijiin. Jieariiiii in mind the experiences of this excursion, and to return to our morpholonicai considerations, you will be in a position to appreciate the j-reat individual variations wliich the kidney under consideration may present. The fat may either be recojinizable in patches, streaks, or cover lar<;er areas; it may be confined to certain parts of the tubules, jiarticularly the loops and proximal end. or it may l)e diffuse, involvin<> the whole tubule, althouiih in varyin;- dejiree. In the be-iiiiiiini!; of the process, fat appears in the peripheral portion of the cell near the tunica propria. While these chanjies are more prominent in the epithelium of the tubules, they may sometimes reach a hifrh dejiree in the iilomerulus. I turn now. secondly, to the further events which take place in the lilomenr' and tubules subseciuent to the infiatnmatory chaniics with which we have already become actpiainted. In the jilomerulus we had. you renietnber, dejicneration of the linin«i epithelium and endothelium of the tuft, with proliferation of the latter, exutlation within it and into the capsule, and at times i)roliferation of the epithelial cells advaiicinji from the periphery toward the center. The whole tuft l)ecomes thus DEliENKUATIVE AND EXUDATIVE NEPHKITIS 127 riH- ;fO. lliiih iii;i)inific,iti(ifi (if (jlniiuriilus, r-liovvinu l"'''!"!! inh allied lo lliiit observed in serous inenihraiics. A<:ain in protracted, less l)rus(jne cases, the ;rlonierular loU's are transformed liy hyahne swellin<>: (»f the loojis and eiidothelial and possiljly epithelial proliferation into a compact, i)lump. first cellular, then hyaline, body. Amyloid material is deposited in the capillar) loops, particularly in constitutional di.sea.ses. a.ssociated with hyaline infiltration of other orjraiis and vessels. According! to Wicliman and Martland. amyloid material infil- trates the parts, wnile the cells are not transformed into amy- loid, and Hueter finds the amyloid dejK»site(l within the lumen of the capillary vessels.'' Other j)rocess<^s may als , as the res\ilt either of lack of pr()|)er Mood- supply of the glomerular tuft or, as l»onfi<-k Itelieves. as the result of stajiuation within .and ohliteration of the convoluted tuhules. In such events the epithelium and endothelium of the tuft heconie p;ile. turhid. swell, and fuse to a structureh .ss. hyaline IxkIv. This is occasionally initiated 1)V (edematous iml)i)>ition of the parts, so that the }il<»"i<'"ilii^ 'iUs the distended c;ip- sule. A common event is connect ive-tis.s\ie invasion from the capsular tunic, which pushes before it ;i «i'"a(lually atro})hyin^ capsul.ir epithelium ( Fiji. HSk Accordinj; to some of Dr. .Milne's observations, this seems to be the cast* in •ilomeruli wliere oriiiinallv the exudate lifts the epithelial cells off tlu' ba.sement membrane and pu.shes them bef(»re it toward the tuft. I^ater, this exudate is repl.-iced by gradually thickeninji e;ipsular con- nective tissue, which occasionally still shows toward the tuft :i very thin, :ilniost endothelial-like, cellular lining; ( Fijj. S and riiis. :il) and 4(h. Similar is the fate of the ulomerulus in ca.ses when, as we saw iK'fore, only a portion of the tuft has In'en firmly attached by DEOKNKKATIVK AM) KXIDATIVK XKPHKITIS i:i." li(£. ;!:i, -In one uloincriiliis, iiiflainnmliiry nttaclunrnt lo rapsulc, with localiztHl pcri- illoiiicriilar tliickcninR; incrcii.se of emiollirliiil nurlei in l)<)lli (jloineruli. Diliitalion of lapsulc. X 1S5. DEiiKNEKATIVK AND EXIDATIVE NEPHKITIS 137 Km. 34. -Various Htaffioti of hyalint' nlomonilur rcplacpment. X 200. Hyaline rmtts in tubules J E KiR. IC).— One glomerulus with complete hyaline atrophy. Hyaline elianne in u glomerulus eommeneing in the part attached to capsule. X "220. DKtiKNKK.MIVK AM> KXIDATIVK SKI'IIKITIS i;jiilar ihickcniiiK vvitli <'xt(•n^i(ln of lining cells bcfori" it iind fibrous rc|>lacciii<'nt frmii an attacliril jioinl of tlii- liasc of llic tuft. CompU'ti' hyaline transforma- tion of a Kl<". Some of the tuhiiles till<"ni- eruli. The best pre.serv(>d met iH'forc. /. <■., iiiflaiiiinaton- and rojtpnorativp. Iiifiammatorv hyiH-rphisia of (>|)ith(>Huiii occurs most ahuiulaiitly iii tlic loops, imut accordinjc to my oi»servations l)y far most frecjuently l)V amitotic division, and I would put this latter down as the rule for the multiplica- tion of renal epithelium. In clear, or at least relatively clear, tultules the epithelium rent themselves. That filandu- lar cells, when their environment chanjies, also chanjje their type, is not a new or isolated occurrence hei-e, but it is well known that in the sclerotic lunI)s«tv«' diirinjr the inflammatory hyiH'rplasia. ritimatcly. when conditions ••••••oiiic mon- s<.|tlc(|, a -cncrally uniform, althouj-h morpholojr- ically .litTcrciii. regenerated epithelium forms as the result of more iwrniaiient. Iiut clianiicd. environmeni . <>f -reat practical interest is. <.f coiu'se. the ;issoci;ited func- tional chaiifie that imist -o iiand in hand with such ;, morplu.h.^r. ical transformation. .\l.out this we know very little. Ixit it seems :is if c(>rt:iin complic;it«'d .-uid ohscure functional chan-re.s. which .ire .always ol.served l.ite in these nephrites, mijrhf possihiy l.e traced, not only to the intlanunatc.ry involvement and ana- tomical rearran;:,.,,,,.,,, of the parts. i>ut also to the loss of nor- m;d and the production of entirely new. secretin-; cell ty|M's.* 1 shall refer to these matters ajiain in the discussion of the so-called coiitractnl. or interstitial, hetter termed, productive, nei'lnitis. where these morphological and functional chanties are m(.st prominent .and ch.iracteristic. Consider.ahle variations in size of the tul.ules (,ecur. Some are very nuich hi r<;er and di- lated, either .as the result of functional hy|M'rtrophy. or as the re- sult of stoppa;re of cellular mas.ses with stajrnation of fluid ahove. Others ajiain apjH'ar collap.sed, and atrophy for reasons which we will presently discuss. This leads directly to the cpiestion of the result of such chaiifres in -lomeruli and tubules upon the kidney sul.stance. Glomerulus and tulnile are, as you appre- ciated, a unit fn.ni the .anatomical and physiolojiical .standpoints. A iH'nnanent injury to one will nece.ssarily involve the other. So it hapjK>ns that the tuhule who.se filomerulus has iM'en lost in either of the ways just de.scrilx'd will collapse, atrophy, and ulti- n / l"''" \T '"•'■'' ''••""'"■^"•••'"•-I i" llii;^ inslilut,. for «,„»• tin..-, aii.l rocntly V. UiMvr Iro 8^0;^ rulo. "' «'""'-"''--'"-' »"t it ... n-ully „o, h. alUnfnM,„,. „,' I>Krtioii of it. and ;)arti(iilarly fn'tjuciit in th<' region of \\iv l(M>ps, citluT hy cHlular masses, dotritus, and ph- IH'cially hy finiily attached casts, will s(M)n load all the slru<'tun' alM»ve the point of occlusion to tin* sanio fate. While this has loiifl l)een reco^rnized as ;i factor in the loss of kidney structure in the.>*<» lesions, it Ins n ntly In-en particularly emphasized Ity I'onfick-"* as tin important cau.s<' for the w.iste of parenchyma. Indeed. Ponfick ji'X'x ?<«> fi»r :»^ <«> i»>lss must 1k' attrihutrd to a Mocking of tlie tu- l)ules at a considerahle di.stance Ih'Iow their orijrin. Then' can Ik' no (pie.stion that lK)th of these mechanical factors are lar. projjres- sively sliffhtly irre;j;ular, puckered, and this ap|M'ars primarily and more prominently in the cortex. At this jH)int the cai)sule still jH'els rather easily. However, this loss leads now to certain other chanjjes, which alter still more the ap|K»arance and anatomy of the orjian. They take their orifjin and pur- sue their development particularly in the intertubuhir tissue, and spread in a streaky and later diffuse fa.shion throufihout the whole or^an. We nnist, therefore, proceed ii"W to l>l>K\^K. Mo.krd Willi fiitty .iiiil cclliiLir iiimsscs. while the infl:iiimi!i»(»ry u'dcniM cnnliiiiH's. N-.ids very soon to Idss of these celhiljir el«'- meiits, followed l>y :i |trolifei;ili(.ii of etidotheli;d cells within tlu'se iliMliliels ;md the ;ip|H'ar!iliee of lymphocytic i poly I. hist ic, h'ukocytoid :iiid lil.iol.l:istic i-ells without The cells thus pro- duced .lie pMitly |th;iuocytic :iiid partly reconstructive: licit is. ;i ceii.iin nuinlM«r ;iid in clejirinu the p;ith for the development of lii>rolil;istic cells. While this is primarily confined to the inter- tuhular sul».st;mce. and local, it soon assumes ^trealer iliinensicms in all areas where adjoininii tuhules and ;rlonieruli are wasting and atrophied. It stands to rea.son that this thickeiiiiii: and ((Iditeration of the diaimels of nutrition and n-ahsorption must also interfere with the tulmles and j-htmeruli. .so that, in my opinion, thes<' two chaiijies interact and <:o hand in h.md. .Now. as the HIiroMastic cells matun-, the intertuhular con- nective tis.sue hecomes less cellul:ir. hut thicker, and. by rephice- ment of atntphied parenchyma, hands of comiective ti.ssue (h'velop leadin;: to more (»r less firmly contracting, scars. Hy jrrowth on the surface, the capsule U'comes now irrejiularly .id herent. so tiiat it can he removed only with ^^reat difhculty. and usually takes ,som<. ,,f the parenchyma with it. As tiiese chaiijies :ire most pronounced in the cortex, this .suffers the mo.st. It becomes very irrej-ular, jinmular. cicatrices divi(h' Iwtter pre- served areas, .md the normal markin;:s have almost entirely disapiM'ared. ni(M.th, althoujih the kiihiey shrinks. Both types are now reco^inized under the name of secondary contracted kidnev. I)Kay l)e influenced in two ways: first and directly, hy inflaninuitory chanftes; second and indirectly. I)v chanties in the general circulation, whii'h result from the effects of the nephritic lesions on the individual. We have s(H'n In'fore how in certain inflammatory lesions the affinity of the toxic excitant is particularly found and accentuated in the 1 )Iood-vessels : al)undant dia|)edesis of red Mood-cells occur, hcmorrhafjies and even extensive hemorrhajric extravasations. .\s a con.seijuence. the kidney irddens. either diffusely or shows hemorrhagic dots and streaks. corres|K)ndinf!: to hemorrhajric extravasations into the jjlomeruli and tuhules. In others, ajjain, the dejtenerative lesions, fatty metamorphosis, seem to empha- size that there the irritant effects a primary and jjreater injurv of tlie fixed tissue-cells. In thes(> cases the orjran appears pale and yellow. Fmally an onlematous iminhition in some forms, particularly those associated with general (edema, may fiive to the kidney an almost colorless, hut moist, ap|)earance. The kidney, therefon\ shows here, as in other nephrites, the evidences which |H»int toward one or the other inflannnator>- attributes, or i»oth may l)ecome comhined to alx)Ut an etjual dejrree. In addition, the vascularity must Ik* influenced by the infiammator}- :inatomic:d changes in the architecture* of the kidney. Wei^ert w( lit .so far as to hold that the (luaiuitative differences in the Mood-supply and infliinunatory enfiorsrement of the ves.sels accounted fully for the diffei-ent ap|K\arances of these various forms of nephrites, aniitial difference M'tween thes«' ir)4 HUKiHTs r)isi Asi; vmHoiis fyiK's u.-.s illusti-MtcMl vciv f(ucil.ly to ..,(> oi.lv n-cci.tly, when I fouii,! .•. typic;,l hn-c licnioiTliMjric kidney „i, the loft si.l'c! .'11(1 :. siiuilMily typi,:,! l.-.r-r pnlc kidney «.n the ri-ht side, of a yonn- -rirl wl... died „f ... .^h.wjy projrivssin- nephritis. It ap- IH'.-ired to the unknowin- as if these two p,.rfeet examples ean.e from diHerent ind;-. idiials. It has U'cn claimed In some: K.ieJK.hls and his tV.ihmers. who .•idvis<. derapsulalion of the kidney in nephritis, that with the attaehment of the .-apsnle to the parenchyma collateral circula- linn with the snrroundin- sirnctures may thns l«> estahlished, i'Ut extensive experimental ohs<>rvations of Theleniami. von '■•'><■ •"'«l Ilcrxheimer ami Hall,-"' and others, have shown eart .and vessels, which iK'k.njr to the last chapt..r ..f these |ectur<-s, l>ut it is particularly to the com- pliunfs for the fact that the st.asis appears first and is Inst m.irke.l at the I)K(;k\kh.\tivk and KXIDATIVK NKIMIHITIS l.j.j junction of nicdiilla and cortex. Therefore the lino of doniarcii- lion iK'tvvccn lioth U'conics more pronnn(>nt. Later, the inedulhi shows accentuation of its vess<>!s, which liave usually l)een much better prcM^rved tlian those of the cortex, and, finally, the re- niaininiir chaiuiels in the cortex also l)ecome more prominent. Hut as these, as well as the {ilonieruli, have larjiely l«'en lost in the intlainniatory process, this is relatively less conspicuous. \\ hile, then, the kidney as a whoh* feels fuller, is en of the cortex, Ix'iiiii :it ihe same time most prominent in the medulla. After venous stasis has exi.sted for some time, it leads to (edema atid hemorrha^(>s into tuhules. In the projrre.ss of the lesion, if the individual (htes not suc- luml). which is usual, it is difhcult to separate the effects of the stasis from those of the nephritis. :is tluMpiantitative and (|Ualita- tive conditions iH'coine well .-ind completely interwoven. Where the Mood .sta;;nation is marked and |)atchy extra vasiitions occur, ha-molysis withsettiiifi free of lilood coloring-matter and precip- itation of jiranular pie iinjMKssible to solve.* In hospitals which, like ours • rriifcsNor .S'li.ihir liii.« (old iir llmt 'rriiiilM' uscil to |)ii\ [liirliruliir iitti'tiliiin to tho ciilcir ipf till' iiriiii' ill such citscs. In vt-tKu- siiLsis I'liinpIicHliiiK » iii'pliritis tin- color rc- Mmill> pull' ill ipitr of ll-s.«'llnl '|imillilv m 14 i.v; uKUiin's insK\sK 'City Hospit.-.l. \,.\v V,.ik'. receive M br-e lum.her cf I l.esi' .•.veii definite diajriiosis, I helieve that such ••liiii.al dia-iioses. althoii-h praetieally eonf.ssiiijr ifrtiotaiice. are '•"tter. for the sake of relial.le stati.sties. than an elahorat- aiitemortem anatomical dia,i.iio.sis. which cannot he controlled l)y autopsy. Now. (.n the other Inn.l. venous sta.sis may not occur until late in the .lise;..s... and after .secon.h.ry c(.ntraeti()n has well adv.-.ncfMl. While it follows, then, the -eneral c<.urse I indi- cated, it necessarily ap|H'ars much m<.re irre-ular. particularly in the cortex, where many of the vascul.ar paths have l,e(Mi either entirely lost or ol.literated. and distorted. The kidney in all thes<. c;,s«>s loses much of its pale or yellowi.sl, coh.r. and a.ssumes a dark<>r. cy.motic ap|)<.ar.mce. The su|M'rficial veins ap|K>ar I)roininent. Mere, as in ordinary stasis, cyaiio.sis is accentuated in the medulla, and nnist not Ih' conf(.unded with hemorrhajric inflammation or inflamm.itory .•xa<-erl.ation: thes<' are alw.-ns "lore pn.minent in the cortex. .ukI never lea: functioti.il corrolarij's will jro with them. .\s Ion- ;.s the proce.s.s,>s of exud:ition anr cent., hut only rarely more, and the hi^rlu'r |K*rcenta<:es rejKjrted refer to those of volume. The urine is ver>- rich in morphotic elements, and as the fatty dejieneralive feature U'comes now marked, its evidences are ahundant in the microscopic examination of the scnliment. Katty cells, fatty casts, free fat. and detritus, altove all others, ^ive the le.sion a characteristic stamp as fatty nephritis. Where, in ad- ditioti. liemorrha^res (x-cur. the blood apjK'ars in the urin<'. hut not with the same con.stancy or ahvmdance as in the more active lesions |)reviously con.sidered. As the process proceeds and the exudative featun's n'}>n*ss jrradually to the hackjiroimd. which .illows the field to l)e somewhat cleared aJid su|)ers(Mle(l hy the .(trophy and loss(»f the tissue with productive cicatrizinji chanjres, the functions .show correspondinjr changes. The amount of urine rises; it iK'comes paler and clearer. The .sj)ecific ecific jrravity. This increa.se in amovmt of urine is usually coincident with a decided diminution in the jii'iieral (rdema. which, as you know. l.-)S u;ti(;iiT's i)isi:.\>;k IS most alw.-.ys very innrkcl .luriiij: tho .v.rlv stM^os of this "•'Pl'ntis. ...mI whirl, w,. will tnorc fully .lisniss in the iioxt l<'<>""<'. All..m.i.i Mixl inorplmtir ..|,.nu.|.ts .lin.inish rmw- s|...n.hi,;rly. (),H.„.ust Ik> .•...rrfnl to ,.ot r.-.-,n| this fn.,,,u.„tlv ••'l"«l|.l .m,! |M.r,,|,.xim .I.T,.iff„| rh;,t.-... sotMHinu-s .•.ssoriafil with :. t..,.|M.j.^ of rHiof ovidciH-cs i„ pro,H.r n-L.tioi. to '''••H.orplH.|,,jri,,,|H,ai.ji('si.H-iations. On lh<> other han.l. when venous stasis iK'coines manifest, this ,sres|H.nsil,le for oth.-rsuiHTaddedfunetional derangements! Ih-n- als<. the urine diminishes ajr.-iin, hut. eontrarv t(. the '""••'""natory exaeerhations. does n<.t l.-a,! toa-reater all.umi.,- "na than fortnerly exisfd or to an in.-tvase in morplu.ti.- ele- ments, l-at.-r a relatively small acon)es extremely rich in Idood, ans\ilt of the mechanical pressure and interference with nutrition, serum will transude into the intertultuhir tissue. The kidney apjH'ars, then'fore. in later .stajies. (edematous, and the interstitial ti.ssue stretched, homojjeneous, :»nd fihrillated, es- pecially in the medulla, whih' the tultules are relatively eom- pres.sed. Later, I»I(mmI extravasationsoccur into tubules, and sj'c- ondary luemolytic chan«r«'s, with .settinji free of l)l(MHl-pi^ment. The latter is particularly well shown in the };lomeruli. Now, as the result of these larjiely, and primarily (piantitative. chanjjcs. atrophy of ;;h)meruli and tubular {M)itions occurs, followed by collapse of kidney sul).stance. In such areas cellular lympho- cytic ami fibroblastic ma.ss<>s may accumulate, leading to mon* or less prominent fibrous tis.sue jirowth. As a result, the kid- ney .shrinks and contracts in places, and the surface apjx'ars necessarily mon' co.arsely jrranular. When tubules have Ijecome cut off, cy.st formation may take place under such conditions, particularly in the ni(>dulla. This kidney has Ikhmi deseril>ed as cyanotic induratioti, or cyanotic contracted kidney, and is, .strictly .s|M'akin>i. not of an inflanmiatory ty|H>. It di(Tei-s from the inflatiunatory lesions in the evidences of its extreme cyanosis, associated with ;:eneral (edematous imbibition and ma.s.sive prominence of the larger va.scular channels. This state of affairs never reaches e(|ual uniformity of distributi(»n or the .same di- men.sions in a .stasis which is engrafted \\\xm a previous nephritic lesi(»n. The contracti(»n of the or«ian in the cyanotic induration, on the other hand, d(M's not ever ac(|uire the pro|)ortions often f I m '*'** HHKiin's DISKASK si'vu in tin- iiifl;imiii:it(.rv |min'.ss«.s, hut \h(> kidney. :iltli()Uj:li ••o;irs<'ly -:ninular. ivrn:iins hrm^. ;,iul the innlnlL-iry jHirtiori particularly pri.miuciit. Inilliitiv:. aiitl the cortex never excessively scarred. Microscopically characteristic an- ahserici- (»f marked • leycneralions. or <"vidences of old o,- recent cellular exudation. This is particularly well shown in the jilonieruli. The.se, althou^rh iinnien.s,.|y <.nvM,iir,.,| with hloromiiient .1 feature of the inflanunatory conditions. IVn.s*. jH'ri- ulonierularcelhil.ir infiltrations .md fihrous ti.ssue growth are al al).sent. Iiiit whenever this forms, it ^mows less.iliundantly. c;irriei many eno(,r}ieoiiited out th.-it all ves,s(.|s, .arteries. :itid veins are here enormously thickenes (,f nephritis, to which we will next devote our attention. .so s FIITM IJKTrHi:* l'Uo|)t(TIVK NkI'IIHITIS. (HWCiKS |\ OtIIKI ViSIKHA. (Ki )K.MA (i< nllinicii: I turn t«)-<|jiy t<» the last cliMplcr of nephritis, to the considora- tion of that ty|M' I j:roii|M'- .small: the smallest kidneys on record arv of that tyjK'. The surface is extremely irre«rular in the uncomplicated |)ure cases, liiiely jrramilar. with delicate cicatricial c«)ntractions. It is cither reddish in color or pale, sometimes yellowish pale. On section it is jM'rfectly evident that there is a marked diminution and loss of kidney substance, particularly in the cortex most of it may have completely disap|H'ared. In ca.ses complicated with arterio-sclerotic infarctions deep cicatrices form and interchanjje with the finer v:ranulations. The normal markinjjs are U-sually cntin'ly ol)literated. (Jlomeruli and jilomerular rows cannot often Ik' made out at all. The jtlomeruli apjM'ar mort> frequently on the cut surface, in the form of small. |K)int-like. pale hyaline elevations. On the other hand, in places, umisually dilated, irrcfiuhir v.-iscular channels run through the cortex. That, a.s .\(iu will appreciate in a monient, is pnnluce*! I»y the j)eculiar pale or pinkish. Siii.illcr aiitl larger cysts, sniiiciiiiifs ;u(|iiiniiy coiisitlcralilc iliiiicrisiitiis, nrv also conmioiily ilistriluUrtl throiiirli (lie corlcx. (MTasionally at the junction of nicilulla and cortrx, ran'ly (l('«'|H'r in the pyianiids. As a rule, lliis linr of dcinaication U'twccn cortrx and incdiilla is poorly defined, except in cases wlien- stasis li.as complicated, wlien the vess«'|s of the pyramids are nniisnally prominent, :ind nuliale well into the cortical remn.ants. Sometimes cilcium or urate de|Misits m.iv lu're \h> s(>en. When inflammatory exacer- li.ili«>ns li;iv«" su|»ervened. or hastened the final termination, ihe whole kidney a|)|K"ars more difTnsely rddened or mottled. In c;:ses of f.ir .advanced contraction the pelvis is rel;itiv«'ly very l.irnc and very fatly. The fat extends well upward U'tween the atrojihied pyriimids. \ery prominent .are the thickened arteries. This thickenin<: may involve only the smaller ones, which, on section. stanres previously discu.s.s«>d, particailarly tlie s<»-calle«l .s<.cons«'(|U«'nl in\esti;:ators. nolal»l.\ iienle. Heinhardl. i'rerichs. and especially Wei;ierl. '•ii tl llici" hand. Christ ison. while acknowl«'dy:in;i this to some extent, was the first to doiilit th.at .dl these v.arioiis lesions were st.iv:es of one inorliid process. This ir.-iined much support in Kiiyland in the works of .Johnson. TovnlMe. Simon, and Husk. Hk 1-|. Ncpliniis iir.i .maliir.' filin.iis tisKii... intcriiiunjrc will, r.il.li>l, va^.iijar L-i:nHiIan..n li-Mi.) ..r y.jl.m i-l, i.,l |K-,rli<. All vi>,s I'KODlCTn K XKI'HHITIS. VISCKKAI. ( MANCiKS. (KI)KMA KV.i with which wo iK'came fainihar in the first lecture, until finally Sanniel Wilks and (Irainjrer Stewart rerience in the matter has led me to believe that there is no essential anatomical difference in anv of the chansres -•a ■'I I I H)4 UUKiHT S DISKASK which (tccur in this ty[U' of product ivc nephritis from those which we observed in the other forms and which we have discussed in detail. On the other hand, it cannot l)e denied that there exists a nephritis the developm<>nt of which differs in certain points from those we have considered: Inflammator>- features are neither so intense nor so fjeneral and diffusely distributed from the start as in the ty|)es of nephritis previously discussed. The process pre.sents itself as a jiradually advancinji, patchy inflam- mation, leadinfi to a proj^re.ssive loss of circumscribed area>s of kidney substance, while other parts are preserved and their functions continued and c(mi{)ensated. (Iradually, by chanjred anatomical conditions, an unusually complicated orjjan is thus formed, whose functions show marked abnormali- ties. On account of this slow projrress and a fjradual adapta- tion of the or«ranisni to the.se conditions, it is compatible with a lonjrer jM'riod of life. Such a kidney, however, is easily vulner- able, and may experience at any time an active and diffuse in- flammatory exacerbation, placinji it in the catefj;or\- of the types previously studied. I am. therefore, of the opinion that anatomically no particular feature differentiates any of the contracted kidneys one from the other, but ix'lieve that the mode of orijrin and development may differ. It may result, first, from a diffvi.se inflannnation (the so-called secondary contracted kidney), or, .secondly, very insidiously. ;is the con.secjuence of .slowly pro' slowly, and, therefore, normal functionatinfore, and had l)etter l)e drop{x>d altojrether. Anatomically, we should speak of productive nephritis, then, when the exudative and dejienerative attributes are less prominent and, on the other hand, the formation of connective tissue ver>- abundant. It is evident, therefore, that the causes of productive nephritis are ver>' numerous. It may either result from a previous diffuse exudative degenerative nephritis which has underj^one remission and cleared in certain areas, so that conditions for a patchy projjress of the disease are thus created; or it develops ver\- insidiously, usually quite unknown to the individual, until it reaches an advanced degree, and. as the consequence of lonjr-continued intoxications— lead- poisoning, etc., gout, and probably metabolic autointoxications. These may lead directly to patchy, irregular injurj- and corre- sponding inflammator\' foci, with eventual loss of kidney sub- stance. In the description of this productive nephritis we may safely disregard all the various changes which presented themselves to us before, and devote our tittention mainly to those characteristic features which appear especially accentuated in it. From these considerations it Ix'comes intelligible that the kidney of a productive nephritis offers the greatest variety of pictures. It represents really a combination of all the inflamma- tory- features which we previously discussed. P'ar-advanced fibrous areas with hyaline, contracted glomeruli, lost or dis- torted tubules, may change abruptly to Ix-tter preserved and ill 2 i(;() HKHillT s DISKASK t i even licnltliy kidney parenchyma in tlie state of conipensatory iiyjM'rtropliy. I'liis. ajiain, adjoins patches of kidney substance which are the seat of recent intiaininatory dejienerative and exu- dative foci. The latter are particularly prominent in the intor- tuhular tissue, and consist of lym))hocytic and polyhlastic cells, which, accompanied hy fihrohlastic proliferation, soon lead to considerai)le stretchin.ir and thickeniii}: of the intertuhular tissue, and the formation of waxy, mature, fibrous conjiective tissue. Similar lesions prevail around and within the jjlomeruli, and as we h.ive become fully a(r state than in the cases of brusipie and jiCMieral ii(>phritis. where inflanunatorv de- tritus and iiener.'il inflanunatory swellini: seriously i)lock the mi- tritive charuiels. As a conse(|uence the production of new cells ;.nd til)rous tissue occurs here with nuich ureater abundance ;.nd [)erfection than would be possible under these conditions. These ^ ery slow developnuMits are also responsible for a complete and permanent new arranucment of the components of the kidney. I consider this of the sireatest imi)ortance. as it .iccounts in no small decree for some of the perplexing functional (h'viations which ar(> very characteristic and constant. These anatomical chanji<'s manifest themselves in the paren<'hyma and in the vascularity of the kidney. Hoth are intimately comiected. In the tubules two chanjies occur: First, a ccmiplete rejienera- tion f)f epithelium, of the type which we met before low, smooth and .syncytial, endothelial-like. On the other hand, it is not unconmion to ob.serve the formation of hiiih, cylindrical epithe- lium within old tubiiles. One or the other chancre is so jieneral that we may .safely .say that the kidney r h.-md, in places wlH>re complete loss of cortical substance has taken place, compensatory dilated channels form in the cortex: finally, when this becomes impossible by destruc- tion of whole cortical capillary systems, medullary vessels are pressed into service. Under such conditions, the blood reaches the medulla directly, avoiding the cortex altoficther. This is lirossly well illustratean has been altered. No blood circulates tliroujih filomeruli. and nuich avoids the cortex altoj^ether. to proceed directly to the medulla. .\s the consetpience of these essential interferences with the structure of the kidney, far- reachinji fvmctional modifications nece.ssarily develop, va.stly different from anythinical con- ditions. You readily understand how difficult it will be to d II I I : f H I(»S MKKillT S DISKASK explain the functions of such a radically clianjicd or>ran on the hand of siniph' physiolo^iical experience. Hut iM'fore sketchinji these patholojiical functions for you. we must '-onsidersonieothj'rniorpholojiical features of this nephritis. Of v.rf':it fre(|uency are cysts. 'Ihese occur, sometimes few. at other times in jireat tunnher, so that tlie name (»f actpiired cy.stic kidney has been nt parts of isolated uriniferous tubules, which, havin^^ been cut off l)y the sclerosing; inflanmiati(m, underjjo cystic dila- tation. It is, therefore, held by some that the cyst fluid repre- sents retained urine. But the different nature of the lining epithelium of such cysts, as well as the phy.sical and chemical character of the fluid, makes a modified .ecretion probable. On the other hand. I observed a jjood many years ajio in 1895, while workinj!; in VViirzhurfi that some of these cysts are dis- tinctly of jilomerular orij-in. This can l)e directly oiwerved in certain smaller ones, where location, size, and arrangement of the wall and lininr, arteriosclerosis as results of a nephritis plays only a very subordinate role. I"'ahr l)elieves, therefore, with Marchand, that the arteriosclero.sis I'HuniCTlN K NKPHHITIS. VISCKHAI. ssion of the - indiviciuiil is jnon> or less ex|X)se(i. (Ie|)eii(linn u|M»n occiipation, tein|H'ra- inent, and mode of living. In other words, a wear and tear process. I iM'lieve. however, that it cannot Ih' denied that lonp-eon- tinued increa.sed n>sistaiice in the kichiey as the ivsult of ob- literation of normal vascuhir paths may l)e a factor in producing ehistic thirkeniiifi of renal vessels. This view was particularly advocated by llindfleisch. A combination may. therefore, occur with the third vascular chanpe, which may l)e observed in these kidneys, which con.sists in a hy|)ertrophy of all the coats, partic- ularly (»f the nudta. This has Ix'en emphasized by Friede- nuin.'* who separated this lesion distinctly from the arterio- sclerotic process, although, as you ai)preciate, it may lead to or combine with it, so that a shaq) line of distinction cannot always l)e drawn. This process is characterized mainly by a hyper- plasia of the nui8cle-fil)ers of the media, which distinjjuishes it from ftranulomatous arteritis, endarteritis, and arteriosclerosis. In them, you rememl)er. there occurs essential lo.ss of muscle tissue, with fibrous or elastic tissue n>placement . Indeed, Adami looks uix)n this as the es.srmeability of the vascular paths in the pwfiress of a nepnritis may also play a role. Finally, the capillaries show inflammator>- endothelial pro- liferation. This neces-sjirily leatls to thickeninji of their walls, and frequently they under^jo hyaline transformation. Hi 174 HliKJHT S DISKASK \\v SCO. therefore, th.-it the thickeiiiiifi- of the vessels whieh is observed (hiriiii; the pro^jress of ;i iiejjhritis orijriiiates either from coiKUtioiis arisiiiii within or outside of the ki(hiey, and that, as in tiie hypertrophy of tlie elastic tissue and the media, hoth factors ma\- lie active. Hut whatever may lie their orijiin. they, in turn, are ;ipt to very materially influence the proj-ress of the lesion. 'I'his occurs particularly in the arteriosclerotic and the inflammatory end.-irterial chanjics. 'I'hese are naturally fol- lowed l)y marked diminution in the caliher of the ve.s.sel, and. in time, lead to thrombosis ;ind complete obliteration of the thus affected va.scular channel (Fiji. 44 1. '{"lie n'sult of such an occlusion, however, has, particularly in larjier vessels, a decidedly l>ad elTect, as it is necessarily followed by infarction of the area supplied by that vessel. That part underji(!(%s, therefore, ne- crosis, is entirely lost, and heals only with the formation of a deep, thick scar ( i'ii;. 42i. .\linost all advanced cases of pro- ductive nephritis show these evidences of previous infarctions. This leads directly to the consideration of the so-called ar- teriosclerotic and s(>nil<> kidney, which is usually cla.ssified as the arteriosclerotic type of productive nephritis. I speak of it as sclerosis or atrophia renum, iK'cau.se its inflanmiatory nature appears very doubtful. It is the typical senile kidney, and on account of some .similarity to the productive types of nephritis, has fre(|uently Ixen considered as identical with it. There are. nevertheless, certain features which justify its separation from the inflannnatory productive nephrites. As the nam(> implies, this kidney appears durinji later life. .\o definite i ime for its development and occurrence c.-mi be miven, ;iny more th;in an exact answer to the (luestion. When do people aiic? Indeed, the senile kidney is dependent upon the jieneral process of ajiinjiof the whole individual, and more particularly upon the conditions of its circulatory ap[)aratus. It is, therefore, il Kit:. I">.- Atnipliiii senilis arloriosclorotica. Wripht 5() Kms. F'roni a woman, stncnty- four years old, who died of friiiijrreiie of )jiit due to arterioselerot ie thrombosis of arteria meseraiea su|)orior. Kxtreme loss of whole kidney sulistanee. and thickeninR of renal arterj-. Idiopathic hydronephrosis extending to cystic dilatation of the medullary pyramids. II 'Koni I'TIVK NKI'MHITIS. \ ISCKKAI. (•HA\(;KS. (KDKMA 175 eminently a nutritive (li.sturl)an('e, into the prfxiuction of which three factors enter: First, and paramount, the condition of the blood-vessels of the kidney; second, the condition of the jieneral circulation; third, certain orjtanic cellular chanfjes incident to advanced life. In our previous discussion about the arterial changes we learned that the vessels of the kidney are particularly exposed in an unusual de^'ree to the wear and tear of life. Outside of the spleen, there is perhaps no other orjian which is so constantly imder marked variations of pressure, tension, and rapidity of blood-current. All the arteries in advanced life show evidences of strain in the form of the various processes collectively jrrouped under the term of arteriosclerosis or atherosclerosis, but for reasons just mentioned it reaches in the kidney more jjeneral and much ftreater dimensions. With Fahr and Marchand we may look upon renal arteriosclerosis as physiolojjical for advanced life; so it hapi)ens that a characteristic, rather constant feature of the senile kidney, recojjnizable almost at first sijiht, is pro- nounced thickennijr and narrowinj: of its vessels. The results of these, and {K)ssibly still other, interferences with the nutrition of the parts show themselves in parenchymatous atrophy of circumscril)ed areas of the kidney substance. The glo- meruli and the connected tubules shrink, become hyaline, and thus the involved portion collapses. This loss of substance gives rise to the formation of slowly maturing granulation tissue, rich in engorged blood-vessels, usually taking origin around vessels; comiMMisatory and sometimes consideral)le enlargement of the neighboring structures follows, unless they also have become in- volved in a similar fat(>. The process, which commences in small patches, may finally affect a considerable portion of the whole kidney substance. Henmants of tubules have Ix^come buried within the increased fibrous tissue as adenomatous loo[)s or as f:% I7(i HHKiHT S DISKASK cystic papillary IxmHcs. Small hyaline "ilohulps may Ih' the only evidences of previous jilomenili. The kidney, as a whole, dimin- ishes therefore in size and ap|K>ars irre<;ularly jiraimlar, and, de- {)endinji upon its vascularity and the presence or al)sen('e of serous inil)il)ition. which I will discuss in a moment, is either red or pale. This state of affairs has almost always added to it stasis. The latter dejH>nds partly u|)on lunv circulatory conditions within the kidney, partly upon the j-nulual weakening- of the jieneral systemic senile circulation. The re.sults of .such a Ioiiecomes (edematous. Its fjeneral ap{x>arance is hazy; the markinjis iKH-ome disturl)ed and less distinct. It is for these reasons that kidneys in such a stajie are frecpiently. l)Ut wronjiiy, sj)oken of as nephrites, and not in- fretpiently such kidneys are rejiarded as an inflanmiaton,' exacerbation of contracted kidneys. Hut, as you see from the short description of its j)athoical diajiiiosis may here not always he easy, ;ind must l)e made with thoroujrh appreciation of the factors which we have studied. But the decision of this point, ptrticularly in relation to certain cases of hypertrophy of the heart. n>ay become of the e ofTered in cases when such kidneys as you can readily imajiine become the .seat of su|M>radded exudative and dejienerative inflammatory conditions. J.et us return to the siihject of productive nephritis. We have arrived at the second (piestion which presented itself at the start of this chapter: What is the rehition of the extreme parenchymatous loss to the abundant filu-ous ti.ssue prolifera- tion? Here we step once more on very disputed jiroinid. You will recall from the first lecture that there are two entirely opjiosed views on that subject. It had l)een Weif^ert's idea ajul in this he was essentially supported by Cohnheim and many otliers - that it was necessary to presuppose a parenchymatous injury in order to account tor the fibrous tissue growth. He rejrarded this latter, therefore, as strictly c:)mpensatory. .\n entirely different view, however, w.is enter!., ined by Hartels. who rejiarded the hyjMM-plasia of interstitial tissue as the primary feature of the contractc.! kidney, and thus created the conception of the pri- mary interstitial nephritis. In this he was actively supported by Xauwerck, who held that epithelial dejieneration by no me:ins always preceded the interstitial inflannnatorA- chanjies. Some, like .V.schofT. .separate entirely the connect ive-ti.ssue formation from the inflammatory proce.ss, and, extending; the ■-iy ■■'i'-- PRODICTIVK NKI'HRITIS. VISCKRAI. CHAXOKS. (KI)KMA 179 . 1 views of Wt'i^ert . look upt)n it as a process of repair. Tliat fjroup of invest ijrators is therefore uinvillinfi to speak of productive nephritis at all. l)iit rejiards all the various lesions of proliferation and production of new tissue, nuich as \'ircli()w did, as consi- f/ucnns of the inflainniatorv (le an increase of fibrous tissue at the ex|)ense of parenchyma, are not inflammatory at all. What is, for instance, freijuently referred to as chronic interstitial myocarditis is jjenerally scar formation as the result of infarc- tions. Similar illustrations may he found in other orjians, and I have already itisisted l)efore you that in the cyanotic induration, and in the senile and arteriosclerotic kidney, we are dealinji; with nutritive disturbances which are absolutely unrelated to. and therefore to l)e separated from, the inflammatory conditions of that orjjan. However, it is very doubtful whether the proliferation of cells and formation of new tis.sue, which is characteristic of certain inflammations and with which we are dealinji in the (juestion of productive inflammations, can pro|M»rly ])e rejtarded (mly as evidences of repair, or as a pure healinjj process. There are some points which difl"erentiate them from the previously mentioned fibrous irrowth which results from nutritive disturbances: if 1 1 II I! '^ ISO hhkjut's KISKASK rirst : Tlif cliaiifrrs in the interstitial tissue in iiiHainniatoiy processes are characterized l)y ati active participation of compo- nent parts of this (issue in tlie (h'fense ajiainst th«> inflanmiatorv irritant. The clianjies thus j)ro(iuce(l difTer, therefore, (piantita- tively and (luaHtatively from those whidi occur (hiring the process of repair. Wliile. therefore, .some of the features of repair are evidv ii< in th<' inflanunatory interstitial chanjies, they liave others .so clo.sdy allied and acting with and modifyinji them, that one cannot well l)e separated from the other, l-'iuther, the close interchanjre between interstitial tissue, parenchyma, blood- vessels, and lymphatics lends, as we have learned, certain (jualitative features to the inflammatory coimective-t issue changes which jro far beyond those found in reparative processes. Second: The inflanunatory iiiterstitial i)roliferation always lirows beyond the limits of n'pair. This important i)oint had become evident even to Wein pure n^i^arative •RODICTIVK NKPHHITJS. VISCKHAI. ('JIA\(J»:S. 0';nKMA ISl Pt and iiiflaiiunatorv tissiw growth, and one which justifies us in upholding the conception of pnxhictive inflammation as distinct from processes of repair. Now, an investipition into the problem of the rehition of parenchymatous loss to the fibrous tissue formation is made extren«>ly difTicult l)y the complex nature of these changes, and by the fact that it is rare to obtain kidneys in such stages of incipient nephritis as will allow definite conclusions on that point . It seems, however, as if somewhat intermediary antl more flexible views would come nearer the truth than any one-sided and ri;;id idea: Certain forms of nephritis are associated from the start with progressive parenchymatous destruction. It ap- jM>ars that in these we cannot attribute the lo.ss of parenchyma to primary- proliferation of interstitial tissue, but that it is at least concomitant, ami by its loss does not opjmse an vmre.st rained connective-tissue hyix^rplasia. These cases would conform with Weifjert's views. On the other hand, there exist types of nejjh- ritis which originate as primarily localized ix^rivascular infiltra- tions. These localized areas, howev; r, are rapidly followed, pos- sibly by virtue of their existence, possibly by extension of the inflanunator>' irritant, or both, by nutritive disturbances of the involved parts. Pareiictiymatous destruction, therefore, ensues, and inaufiurates the possibility of furtlier extension of the in- flammator>' infiltrations and connective-tissue growth. With the stM'ond view we take, as you may see, a .somewhat reconcil- ing stand l)etween extreme ideas. Ijet me now touch upon some of the important functional characteristics of productive nephritis. One of the most inter- esting: is the strange fact that throufjhout the course of this disease the urine (|uantity is verA* much increased. This in- crease, althoufih not reachinj: such high figures as in diabetes, is nevortheles.'* considerable, aiid, curiously enough, persi.sts toward 1 i- i I I ^ I I ■ 1S_» HUKiHTS niSKAsK llwriul. 'riial is its most [HTplcxiuji phniomcnoii. No matter wlu'tlicr we (iiid at autopsy almost all tlw normal kidney sul)- staiicc ilcstroyed. the (piaiititativc excretion of the waters elements has remained hi}:h to exitus. unless circulatory dis- turbances or exacerbations complicate the terminal pictun'. We have no really satisfactory explanation for this phencmienon. It may. of cours<'. Ik' supposed that, particularly at the l«';iinnin;i of the disease, conjiH'nsatorj- hyixrf unction on the part of the preserved kidney portions occurs; but how does it keep up as the kidney substance wastes and is replaced by con- nective tissue? It is here pariicularly that we must look for other than purely physiolojiical n^asons. The kidney of an advanced productive nephritis is really not comparable to the normal orjian." Not only, as you rememln'r, has there taken place far-reachinji chan-tes in the vascular supply and secretin}! chamiels, l)Ut the epithelium has, as you also recall, chanjied its type entirely. From a hifihly differentiated, six>cialize(l form, it has either k'come cylindrical or more fretiuently descended further to an endothelial, syncytial-like formation. These atypical forms of epithelimn receive their blood, by elimination of most <:lomeruli, in uimiodified, unccmcent rated form. It is evident that this complete reorachinf productive nephritis nuist l»e |M)or in niorphotic elements and seruni- all»uniin. I)<'st ruction of kidney suhstance is ver>- slow, cer- tainly never intense, and wide-spread, rapid desquamation of epithelium, and the formation of nuich inflannnatory detritus and active diffusi' exudation heinjr lacking. A moderate num- U'r of hyaliiH". occasional firanular and fatty casts, often found only after consideralde centrifufjinn, and occasional leukocytes, an' therefore the only elements found. Serum-alhumin exists only in traces, except where the lesion is complicated l)v amyloid defieneration. Herewith we have fini.shed our pro|)osed work the considera- tion of the pathological an.itomy and histolojiy of Bri^ht's disease as far as the kidneys themselves nrv concerned. From the mass of evidence and known facts, it has l)een my endeti to select the most important, not presentiiiii them as inde|)ende. or incoherent de.scriptions and statements, but moldinj: them into a plastic form which will allow you to form visual pictures and relations of the nephritic proces.ses. In conclusion, however, I must touch upon some featui-es of nephritis which, although lyinji outside of the kidney, are really part of the jjeneral mori)holo{rical consideration of the subject. First . chaiifies in some other viscera; and. .secondly, the ques- tion of cedema. These are so inijiortant and characteristic that we cannot well omit them. Of the chanjies in the viscera we immediately re<' )>inize those of the heart as the best known and very important. That any nephritis which extends over a lonfier jx^riod may In^come associated with a hyf)ertrophy of the heart was known to Brifrht, and so overwhelminji has l)een the evidence .since his first observations, that this is one of the best accepted complications of nephritis. While the carefully tabu- !i I I n IS I UIIKiriT S DISKVSK latcd oliMTViitioiis of MiiiiilH'i-jjrr and TriiuU' and ji«'U<'ral v\- |H'ri('iic»' <>iii|)|)asiz«'*l the |)n>|M)ii(lcraii*'(> of tlir' hy|N>rlr()|>hy of the left ventricle, it is really only very recently that indisputable evidence lias iK'en furnished alntut the niaiUHT under which the heart hy|H'rtrophies in nephritis. By can'ful weifrhiii);. aci'ord- iii^ to W. Miiller's method, l{oinlN>rv;. llasiMifeld. and llirsch have denionst rated that in .S2 jht cent, of their ca.s<>s all cavities of the heart, auricles and ventricles, show hy|)ertr(>phy of their walls. The left ventricle, howevj'r. pre.s<'iits this most markedly. In 14 |H'r cent only the left ventricle was hy|n*rtrophied.'"' Hirsch demonstrated that tin* hyixTtrophy of auricles and the ri variations. In the first place, it is well settled that hyj)ertrophy of the heart occurs only in thos*^ ca.ses which are as-sociated with an appreciable rise in l)lood-pres.sure. It is, therefore, not abso- lutely dejM'ndent upon or associated with any particular kind of nephritis. While it is most constant in the bruscpie exudative ty|M's, particularly tho.se with marked vascular injury, as in scarlet fever, and in the productive forms, it may, nevertheless, l)e al)sent in all of them for the followinjj rea.sons: The factors leadinj: to increased blood-pre.ssure may Ix' lackinj;; or the or- jianism may 1k' unal)le to resjK)nd to the.se factors; lastly, a once estal)lished hyjK'rtrophy may .^ive way to later atrophy. The latter two features are imiM)rtant to rememU'r, and have been fully tlemonstrated by our own ecords. The hyper- trophy then occurs and jK'rsists only when the nutrition of the orjiun is kept up to the r!?cess;ir\- stantlard. j? PHODICTIVK NKI'HHITIs. VISCKHAI. «ll %\(iM. (KDKMA IH') Sj'niitor,'" Honio yourH a^'". |H)inli*(l out that ntw coul*! diffor- f'litiato iH'twrcn two foriiis of hyixTtntpliy : oin' with dilatation of thr ventricle, the so-(alle- jjood till toward the end. Here concentric hy|)ertrophy is then'fore moiv freipiently foimd. An absolute de|x^ndence of any form u{)on a particular kidney lesion does therefoH' not seem to exist.'" Now. how is this hyi)ertrophy to lye interpreted? Bri<;ht held to two jM)ssil)ilities: luther the heart is directly irritated hy an abnormal composition of the bl(K)d, or this affects the finer and capillary vessels, thereby aujimentin<>; the work of the heart in order to drive blood throu^jh thus affected vascular districts. The immediate successors of Bright in the study of renal disease did not further our knowledjje refjardin^ this matter, until the work of Traulx*"* gave a new stimulus to it. Traube showed during; life that within a few weeks after the occurrence of a severe nephritis symptoms appeared which pointed toward increased tension in the aortic system. These are abnormal resistance of the radials and the apex-l)oat, and j'n accentuated, i 1 1S(> HHICHT S niSKASK liijlh-souiuliiij:, diastolic aortii- and carotid tone. To thorn is addod soon an increase in the heart vohnne, and Tranl)e (h>mon- strated in some cases hypertrophy of the heart in as short a 'inie as four weeks after the l»e,iiiiniinfi of a nej)hritis. In this way he conchided a causal relation between nephritis and hypertrophy of the heart, and assumed for its explanation the followinjr: First : Infianunatory lesions of the kidney cause, hy presence of an exudate or l)y loss of kidney substance, a diminution in the amount of fluid al)stracted from the aortic system for the pro- duction of urine water. Second: They diminish the quality of blood which in a jriven time flows from the aortic to the venous system. This purely mechanical liypothesis was soon attacked for physiolo<:ical and j)atholojiical reasons. It was demonstrated by Cohnheim and Lichtheim '' that a hydremic plethora has al).solutely no influence on the blood-pressure, and by Ludwij; and his pupils that even tyin<; of both renal arteries had no appreciable etTect on it. Furthermore, it is well known that, particularly in the productive nej)hrites, tlie amount of urine vvater is not only not dimini.shed, but actually increa.sed. Never- theless, this mechanical theory was championerl l)y Cohnheim in modified form, l.ariiely for the rea.son that exjH'rnnentally and clinically left-sided hyjwrtropliy follows total extirpation of one or jrradual elimination of both kidneys, notably exemplified in cases of uncomplicated hydronephrosis. Lack of occurrence of hypertr(>phy under (he.se conditions, and in amyloid kidney, was attributed l)y ("ohnheim to purely nutritive disturbances. In order to meet the previously mentioned ol)jections to Traube'.s theories, Cohnheim supi)o.se 1 that the rise in pressure was due, first, to entrance of an unchanired amount of blood into the kid- neys, where it meets increased resistance, and, s(^cond, an PKODrCTIVK XKPHUITIS. VISCKHAI. CHANCKS. ms unreasonable. For Krehl -' and others it is im{)ossil)le to understand how elimination of a relatively small area of circulation should be followed by such a jwrmanent rise in sieneral blood-pressure, and not by compen- satory dilatation in other districts, a fact which is t!ie rule in other conditions, finally there is no direct relation between the ext(>nt of hypcTtrophy and the defjrec' of kidney contraction. Schmidt,--' who ditTerentiates l)etween two kinds of nephritis, fllomerulonephritis and pure parenchymatous tyi)es. in which I am unable to follow him. lH>lieves that the affection of the jilomer- uli is of jireatest importance in the rise in tension and ultimate hypertrophy, althoujih intensity and jrenerality of tlie ;lomeruli have larjiely di.sappeared ; and why nuidi lower in the fatty dejienerative type, where glom- eruli are still {wrsistent and jienerally diseased. i INS HHKillT S DISKASK By far tho larjiost jiuiiiIkt of invest ijiators look for tl 11' cause of hijrli tension and hyjHTtrophy of tiie heart outside of tiie kid- ney. One uroup of ideas finds the exphmation in chanjies of the arterial system. To them, rise in l)loor- trophy of the heart is not dependent upoji. hut associated with, the nephritis. The ideas of Cull and Sutton, and others, on ••arterioeapillary tihrosis." form the foundation for these views. \\v have previously studied the arterial changes in the kidney, and those of th(> other arteries outside of the kidney are verA- similar. .Many, as we saw. are not the cau.se of, init actually dejK'udent on. the rise of hlood-jH-es.-;;,' and the heart hyix>r- troj)hy. Furthermore, the occurrence of arteriosclerosis in nephritis varies .so nnich. and frecjuently in .severe cases with much hypertrophy in the youn-i is .so conspicuously ah.sent, that we cannot l)rin^ it in any essential relation to the hypertrophy. Some time a-io the question of splanchnic arteriosclerosis as cause for hijih hlood-pre.ssure was much discussed. It was tlK.ujiht that, althctujrh the larjier alxloininal vessels mijiht not show marked lesions, .smaller arteries o*" the abdominal orjtans in spleen, liver. i)ancreas. or the other chemical or toxic explanation of ri.s(> of blood-pre.ssure with hyjK'rtrophy of the heart. We owe to Senator-"' an exceedinjily well-formulated expression of this view, and the ideas of other investigators alonjr these lines may I'KODICTIVK NKPHHITIS. VISCKH \L CHANtiKS. (KI)KMA 1S9 well \ic rpfianled as modifications of Senator's ori^jinal coiiocp- tion. In tlie first place, he holds that somewhat different factors are potent in produciiif;; hypertrophy of the heart in various forms of nephritis. In what he terms " parenchymatous, nephritis," and whfit we call degenerative exudative nephritis, the kidney and the whole orjianism are exposed to an irritant, which therefore acts on heart and blood-vessels as well as on kidneys, and produces primarily mlema. The latter process HMnoves some of the toxic irritants from the circulation. If the lesion thus ameliorates, a neces.sarily somewhat weaker but per- sistent irr tant continues a vasocontraction. followed by thicken- inji of ttie vessels. Simultaneously, this irritant acts on the heart rnusde. The heart muscle hypertrophies, therefore, for two reasons: First, as the result of an increased resistance; and, secondly, as the direct result of an irritant. These are the responsible factors, accordinjr to Senator, in what he terms the chronic parenchymatous and secondar>- contracted kidneys- conditions which we called dej-enerative exudative and dejiener- ative productive nephrites. In the primary- productive neph- ritis, on the other hand, the irritant, althoujih constant, is never stronjr enoufih to lead to hydrops or anlema. but produces here also contraction of smaller arteries, which is necessarily followed i)y hyi)ertrophy, particularly of the left ventricle. Under both conditions, then, a .similiir resultinj>; nicreased pn^ssure in the aortic system occurs: These ideas were actually supported l..- experimetital oi)servations which showed a transient rise in blood-pressure after injection of urea, althoujrh Senator himst^lf is inclined to attribute an even j:reater influence to the other nitrofienous waste-products. This theory is very in-jenious. i)articularly as it accounts not only for the rise in blood-pressure and hypertrophy of the heart, but brinjts these at once in a relation with the (edema of nephritis. 1«>U HHKJHT S niSKASK As I told you. the main principles of this toxic thcon- have now Ik'cii iiciicrally accepted. Krehl's idea, which is somewhat simpler, is that the contracti(»n of the smaller arteries is tiie most important factor, and that this is not to he rejiarded as a spasm of these vessels. i>ut rather as an increased tonicity of the normal vascular tone, which is probably under th(> influence of definite nervous vascular centers. A discu.ssion of these clinical features of hi^h blood-pressure will be found in T. ('. Janewav's niono- liraph on the subject.''' A secret i(»n of solids and urine water is not oidy not diminished, but actively increased, the arterial tension is very hijih and the circulatory evidences appear freipiently before any of the renal lesions becoin<' manifest. The ret(>ntion of urinary pro- ducts, to which Senator attributed the toxic vascular con- traction, nnist. accordinu to Cohnheim. be therefore out of (pies- tion. I. too. am of the opinion that in dilTerent forms of nei)hrites different factors enter into the production of rise in blood- pressure hypertrophy of the heart, and some of these are to l)e found outside of. .Mud some within, the kidney. In the first place, it appears i.rol)able that in the early sta-ics of productive nephritis a toxic factor must be(»f nce indicates, camiot be a retained normal urinar\- product, or products, for circulatory cliaiiiics occur at an early date when retention of urine and solids is not only not diminished, but increased. It is. therefore, more prob;d)Ie to rej>;u-d it as an abnormal either infective or metabolic poison, which increases, as Krehl su-r'iests. the tonicity of all l)lood-ves.sels within and I'HODICTIVK NKl'HKITIS. VISCKKAI, CHANCKS. (EI)EMA 191 outside of tho kidney in |)enn:uient fashion, k'a(Un. thinjjs difTered when the resistance was introduceri- menlal evidence points to the fact that resistance within the renal circulation may have an effect on jreneral blood-pressure, and, therefore, if not the origin of hi^h bloo(l-pres.>mic manifestations, with sudden, some- times tremendous, rises in blood-pre.ssure. would indicate here also the jwrsistence of the toxic influence, which, after consid- erable accumulation, suddenlv rises to exert an overwhelmin a-rents must Anally !«> added, in some cas(>s at least, a jrradually increasini: rigidity of all blood-vess<>ls. which is attril)ut;!ble to the loiiii-coiitinued increase in their tonicity and their jrradu;il thickenin.i,^ In this connection a few words ;ii)out th(> relati(mship of the suprarenal irlaiids to blood-pivssure and hypertrophy of the heart: Heceiitly some observers.-"' particularly anK)njj; the l"rench. have claimed that in lonjr-contiiiued nephrites with hijih *riH(|iicslioM wliillicr tlii- i> .liic t,) .1 ri'lIcK i,r i •Ii;,iiir;i| art is still misi-ttlcil 1 rc.frssnr >,;t:,\„r |„|,| i,,,. I:ili-I.v lliut iii rci-cMl .■xpcniiicnts ti,. ;im,1 othns >vcr.> iiiiiiMc to iil)t;ilii tins rise i!i l>l(««l-|)rissiiii' if ;iiimmls were ilfi-piv iiaridtizccl. This \ .iM uricuc of course, anaiiist a iiiiTliaiiical faclor. I'UonrCTIVK NKl'HHITIS. VISCKKAI. CHANCKS. (KDKMA 19Ii hlood-prpssurc a hyjKTplasia of the suprarenal inedulla occurs, while the "ortex also shows nodular, adenomatous hypertrophy. This is l)rouns that such patients aic oix^r- ated upon, l)ecause duriiifi; life an appendicitis or other localized peritoneal infection is suspected. This conunon involvement of the serous membranes was, as you will recall, known even to Bright and Christison It is usually considered that the cause 14 MM HliKillT S DISKASK for such tciiiiiii;il iiifcctious lies in flic Icssciictl resistance of tlie intliviroductive lymphauiritis. The thickened, partlv ohliterafed lymphatic vessels stand out very prominently in the form of |)ale, milky-white streaks, formin;; an irreiiular network, and, in places, accompanied l»y a perilvmphaiiiiitis, hecome confluent to form smaller and l.arjicr patch(>s. ihese latter lesions are usually well ai-centuated and easily observed in the reflected visceral jMMitoneum, hut can also 1m> seen in pericardium, meninjics, and pleura. From this exjM'H- eiK-e it may Im' concluded that the productive inflannnations of all serous memhranes. which often iK>come a.s.s()('iated with serous, fibrinous, and (>ven purulent exudations, are the result and ex- pression of a jicneral irritant to the lymphatic .system in nephritis. It leads us directly lo the causes of (edema and hydrops, a field which has for years heen one of the most fruitful forex[)enmental patholouy. For a full discu.ssion of the early works and thoujihts in the matter I refer you t<» the masterly presentation and criticisms of Cohnheim in the first volume of his lectures on jiencral Path- olofiv, S.') 'I'lic oldest (•()ii('<'i)li()iis. now disrardcd as (>ssd. the (edema readily followed. For in.stance, if the femoral vein of a healthy doj: was tied, no oedema occurred, yet if now a considerable amount of a sodium chlorid solution was infus(Ml, anasarca resulttn'. If. further, one of the hind paws of a doji was irritatcnl .so as to Un'ome inflamed, and cannuhe were in.serted in the lymph-ve.ssels of i th lejis, it was olKserved. after injection of a sufficient quantity of a solution of XaCl into the jufjular vein, that decidedly more lymph dropjx'd from the inflam(>d extremity, while the healthy .side showed no appreciable chanjre. The .same occurred after the hydremia was continued for several days. Cohnheim's conclusion was, I1H-. HKinirr DISKASK llit'icfnic. ilirit iiiiaci vessels through wliirli a normal 1)Ixten(led the e.arly observations of Cohnheim and Lichtheim, and showed the snsce|)til)ility of the l)lo(«l-ve.s,s'ls to a numlu rof .substances, anioiii; them the retained normal urinary products. Of ecaus(> evidence is here so .stronji tliat we accept it : but the (juestion remains whether it is the all-important and only factor in this matter. This possibility must 1k' denied. For, as we know, increased transudation is by no means identical with u'dema. In order to obtain the latter there must 1k> added an interference with the lymph-flow. This, however. deiH'nd.s, as you recall from your physiolojiical studies, tipon the pressure diffe'-ence in the capillary and lymphatic systems. The pre.ssure PUODl (TIVK NKI'HItlTlS. VrS(KH.\l.< HAXdKt*. (KDKMA Wl ill tho IvinphaticH is partly (U'lM-mlcnt ti|K)n thr l.l(M)(l-pro«Hure an(J, as l^iiulonT '-' luus shewn, the tissuo tension (.f tlio surround- ing' structures. Magnus and Krohl " have |x.intcd out that thes<> may vcr>- well Ik- involved in nephrites. Biit . unfortunately, we have as yet no reUahle data alK)Ut the tissue tension in nephritis. It seems, nevertlieless. very jKissihle that the sam.' tc.xi.- sul.- stanees which injure vessels, injure tissue elasticity, either di- rectly or l)y hijrh osmotic pressure with water n'tention. V«>u recall tlu'se views as familiar. But it seems that the chaiifies which take place in the lym- phatic apparatus, and with which I made you accjuainted a few moments a-o. have not received adcjuate attention in their relation to the production of mlema. These indicate that there must also Ix' a decided interference with lymph resori)tion and lymph motion, for it can certainly not U" conceived how lym- phatics which display so prominently the effect of irritative influence .)n the form of productive and ol.literative lymphanjri- tis and jMMilvmphanjjitis can contimie their normal functions: and. as a matter of fact, they would he called uiM.n. under the previouslv outlined conditi(ms, to do increa.sed (hity. I am inclim'd. indeed, to regard the chanjies in lymphatics, for which vv(> have anatomical foundations, as very essential for the production of any patholofiical transudate, as not even ("ohnheiin could produce (edema after injuiy to the vessel-wall unless the blood was hy.lruMnic. In nephritis, however, it fre(iuentlv oc<-urs l)ef(,:e hydra-mia has develoi^ed. The lym- phatics have usually been jiiven a very subordinate position in the relation to (edema, mainly on the ground of certain evidence which has demonstrated extensive anastomosis amonj; them. Obstruction of even lai-e lymphatic vess(^ls is. therefore, usually not followed bv anv accumulation of lymph and production of (iMlema. But "tlu^se facts are hardly applicable to the question \m HKKiin's IHSKASK of (i-i(:iI. lyiiiplint ic iiilly the surroundinji tissues. |,ater in the di.s,.i,.s« metaliolic .md mechanical circulatory distuihances as well as retention may alter the comi)osition of the hiccd .-ind the vo.sel- walls to favor further the pa.s.saiic of watery «-lements thihiili<- process is all inde|H'ii.leiit li'si..n of the kiihiey. For it d<-p«'iids. in an essential dejin'*'- >MM.n concomitant and corre- lated chan-es outside of the kidney. Ihis is so much the case that tiiese ac(|;iire here an iinp<.rtan<-e alm..st unparalleled in the .liseases of other oi-aiis. We saw in the study of the anatom- i,-al features that we must sharply separate the results of the i„il:,ininatory .hanjies in the kidney from thos.' which occur as the results introduced l.y disturl.aiices from outside. Similarly. i„ (he sympK.matolojiy of nephritis you will find that the com- plex clinical lectures of the various ty|M-s may he separated into two^M-eat ^roui)s of symptoms the renal and extrarenal. The i„,por1an<-e of those in iii.lividual <-ascs, as you -an iradily see. varies .-onstaiitly. In the early staples of slowly projire.s.sinji pr(. ne|)hrites. for instance, the extrarenal symptoms are of much fireater value and im|M>rtance tliaii the renal, for the kidney is still sufficient, and. if anythinjr, hyiM-rfunctionates. N„t until much later occur the suiM-radded eviden.-es of the serious renal involvement. Vi<-e versa in some of the rapidly tlevelopiiifi exudative de-eneralive ty|H's. the symptoms of the renal afTection may dominate from the start, and later l)ecome modified hy the extrarenal chanjies. Herein liesa jjreat difficulty in the studv of renal infiammations. And if this offers, as I pointed out at the hejiinninji of these lectures, fireat ohstaeles on the anatomical side, they are necessarily nuich L»(M) liUMillTS DISKAsi: '^vvMvv on the .lini.al. \\V may fin.l in this aLsf> tho cause for tlic <.<-casionai c.nflict l.(«lw,-oii (ho views of the patholofrica] .•"iMK.inist aii.l th(« cliiiiciaii. The hitter ehissifies neeessarily hiruely a sum '••tal nf the interfereiiees pnuhiced l.y a (Msease in t lie relation of all \ is.rra to ,.ach other. Thr former classifies the chanjics ill «'Me or-an acconlin- to their pathojicnesis. and endeavors"., •iiiMlyze them m more or less ahstract independence. Wehavearrive.lat the end. I'erhaps my presentation of the ■ ii'.ie<'t has scrmed v<'ry ..Id-fashioned t<. yon. It p.-rhaps has i'een .li.MMisse.l t.i.. mu.-h for y..nr tastes i,, wcll-t,,,,!,!,,, path.s. or it h.-is n..' ac.|U.aiiile sa ciidiiiious, and of latr years so inii.h, i)arti<-iilarly .■xt)crinicnt ', • <„k has ace Miiuilatcd, that it has Ixrn p-rf.'ctlv itiipossil)lc to cvi'ii nii ..iioii :ill th^' imix.rtant coiitrilmtions to the various i)lias('s of the suhj.Tt. Omissions will, therefore. I.e foun.l freit>li sive . vii. Morfrasjni, De sedihiis et causis morliorum per anatomem indapitis. 17()1. Kpist. xxxviii. xl, and xlii. In the l.eKinninsj of the I2d episth' the history of the knight. (|uoted fn.m Valsalva, will he found i)articularly interest- iiifl, not only fn.m the ])atholo(jieal standi)oint. hut as a contribution to the social conditions of the times. :{. C„tunii; De ischiatle nervosa coimn. ntarius. Vienna-. 1770. p. 24. •t. In Hollo: Diahetes mellitus. Chaiiter vi. London. 171IS. -y. Observations on Dn.psy. which Succeeds Scarlet F.-ver. Transactions of Society for the Impn.vement of Medical and Chirurni.'al Kn(jwl- ed({e. vol. iii. JOI •_'( L' MHK.irr S DISKASK ti. Kiaii.lc: All Accmiil ol S.iiiic CIimms.s finm l)i>rMsc in the Cniiiix.i-itimi ■ ii lliiMKiii riiiii', I.diiildii. 1S07. SciiihiiMoic: A Tic.-iiisi' un tlic \:itllir uT ( Jiiiil. I.oiiilim. 1S2:>. |):ii;c ;{1.!. 7. r.rialii : l!c'|)i)ii~ (.r M.(lii';il Casi-^. i. ls_>7: ii. |s;j|. N. Cav-Mii,! (II.MTVMli..iis llliistraliv.Mil- HcmmI Disease, A.-cuiiipanicd with thr Scnvlidii ..I All.iiiniiioii> I'liiic. l.y Dr. Hrifilit. Cuv's Muspital l{ipnlt>. v,,l. i. MDCCCWWI. I npr.Hllln. I,,.,-,, his rxivncit 'loriipiimi ni I hr chiiical history .if th.' ilis,.as,> for those who arr imaMc lo fon-ull the oriiiinal on pp. o.S'.l. :U(t. and :!t! : ■ ^ ''"I'l- "I' ;iii :"1"1'. i-' al'tVctcd with scarhitiiia. or soi ihrr ariiir chscasc: or liauniiii. Mis pulse i- fiiii and hard, his skin dr\ . he lias often liead;i<'lie. and soiiietiines a sen.se ,,f ''■' ' ""'iiili' across the loins. I'nder Ireatinent more or less active, or sometimes without .-iiiy treatment, the more ohviousand ilistressinn of these symptoms disappear: the sweliin-. whether casual or constant, 1- 111. loii-ier oliserved: the urine ceases t,. evince any adini.\ture of red particles: and. accordinii to tiie dejjr f importance wiiicji h;is heeii att.ached to these symptoin>. they are "jradually lost sijjht of. or are ahsnliitely loi-fiolten. NeNcrtheless. from time t-> tiliu' the couilte- ii:iiic(. hecomev liloated: the skin is dry: headaches occur wilii unusual ''■'■'|iiiii'> : or the calls to micturition distiirh the night's repo.se. .Mter a time, the healthy color of the I'ouiltenallce fades: a sense of weakness or pain in the loins increases: headaches, often ace paiiied l>.y vomitiny:, add iireatl> to the sieneral want of c^omfort ; and a s,.n,s(. of Lassitude, of weariness, and of depression, uradualiy steal over the I'odily and mental traiiie. .\iiain the assislan.'c ..f medicin.^ is sought. If the n.almv of the disease is sus| ted, the urine is carefully tested; and h.und, in almost every trial, to contain alhiiiiiin, while the (|iiaii- tity of urea is gradually diniinishin),'. If, in the attempt to fjive relief to the oppression .,f the system, hi 1 is drawn, it is often hulTed.or the serum is milky and opa(|Uc; ami nice analysis will frcfiuenlly detect, a iiivat delicieiicy of all.umiii. and sometimes manifest indica- tions uf the presi'lice of urea. If the disease is not suspected, the liver, the stomach into the urave jjlottis c solution ir a sudden elTusioii of serum into the if the air. and iirins;s on a more sudden dis- rs the passaj; Should he. however, have resumed the avocations of lie I.- auaiii. ilsiiallv suli,i«'ct to coiistan t lecunences of his s\liil)toiiis: or almost dismissiii'; t he recollection of his ailment, he is s- ( ddelih sei/eil Wl th an acute attack of iiericarditis. or with a still more acute thout aiiv renewed waniiiiK. deprives ittack of |)erilonitis. which, wi tiini. in eight and forty hoiir-^. o lanni'r likewis iliserved to liecome mo e. other perils await limi; •e iie(i f hi> lite. Should he escape this lies have been di'raiiKed: his us lieal. 10. London Medical C.a/.ette, vii, 1S:U. IL Dictionary of Tract ica' Medicine: under Dropsy. 12. Duhliii .journal of Medical Sciences. IS;W. U\. IS. I'rimiry Di.seases and Their Treatment. London, 18:}8. IL Uayer: Traite (h's maladies des reins. Paris, 1S40. 1,-). Ti.ssot: De riiydroi)sie causee par I'affeeti.m granuleuse (hs reins, Paris, It). Suhatier: ( onsiderations <"t oh.servations sur lliydropsies .symptomatuiui' d'une lesion speciahMh's reins, .\rehive MK'ix'Tiil*' de ineih-cine. See. JIM Hl{|t;in s DlSKASK 17. IV-ir: I),, a \>rvsrnrr ,|,. rMll,u,„i,i,. dans luriiic, cmsid.wc .•oinmc |)li('n(>iii.".|r It coinriif -imic ilaiis Ics iiialailit >. Paris. iSIC). 1>. c. ( la/. riKMl. ,\v |>aris. |,s;{ti. p. 1 1!». 1!». M. Solo,,: I),. r,.,||,„n ,r i Imln.psi.. caus.V par uii.' riahulic .1, . niii<. I'ari<. IS.is. ■21). I<,.,-,,u,,,l: .S-..n.-.ioti,|„r ,1.- uriiio. ,„. Trait.', .l.s alt.'r.-.ti.ms ,],. r„ri„,. ilaii- l.> iiiala.lii >. I'ti'. Paris, isll. 1.>1. In Ca-p-rV \V,M|,..M>,.|,rilt. lis. :>,'.,. Id. IMi-t. .\n.l. .\„al.Mtii>,.li.. immI rmlrl.., Ilriuliiii .l..v:.'ii,.ratis. Di.ss.Tt. inane. Hero!. |,s;{'( 121. Z.ii>,|,nri lVirrati,,n,H,.M,.,li/in, Isil , i. p. ,i7; ii. p. .'20. a,„| Ha.ulhuHi 'III- i-aliiin.'ll.'n l';itlii.l.i;;i.'. ii. |S17, p. ;i(i:j |V. 2.'>. 1)( niorlx. Hriiilitii. lalaiiiial. IMI. ■2*<. .I.,|ins,m: M..li.-.,-Clinuriri,al 'I'laiisaiM i.ms. xxix. xxx. xxxii. .\l.s,,. Til.. Dis.asi > ..f til,- Kidney, anil L.tIuivs .m Uriiilits Disease. 27. M.'.lii-.>-('liirmv;i.';d ■i"ran-.i.ii.in«. xxix p .i\s •2S. 1 1, id.. XXX. -'!». Iliid.. xxx. :ill. Cliarii.' .\nnal. n, i, |n.".(I. ••51. |-reri.l,s: |)i,. Mri«l,t's,l,.. Nienn Krankh.it. ..ti-. Mrai.n.M.hwei^r, |s,-,i ■^2. H.i.kitaiisky: l...|,rliu.li .l.r patli.)!oKisel„.ti Anal.iinie. ii. :!;!. I .■i..r paniiil,yinat..se Knl/iindiinn. iv, p. 2(11. (Cla.-si.. .^^iMml.l I..- r.a.l liy .'Xi-ryliDdx . ' :!t. r)i.. Hin.lesul.stan/ d.r Nier.. in, ii,-mu,Uu un.l krank.^n Zu-Ian.l.. Mi'riin, |,s.-,.». :r.. ('.)liiih..irns w..rk ..n intla.n.natii.n i^ to I,,, .•.msult..! in Ids \ orl.suiiK.n til-r all^i.ni.in.. I'ath.,l.,fri.'; ..n the ki.ln.ys li.. f„ll„„,.,i niaiidv W.'iticrt's vi.u-. iliid. ;!li. Traul..-s vi..ws ar.^ pr. ,s,nt..l in: IVI.er .len Zusainin.nlianf; \nn ILtz nn.l Ni.r.iikratdvh.il.ii. I'.erlin. jS.-.c,; Deutsche Klinik. IS,",!!, .{j :{2: .MIsiiineine ined. Cenir.d/iituns. IN")H. i,:,: Deutsihe Klinik. l,S(i:{.' :!-. Kli-lis: l.i'lirliui-h il.r paili.il.iirisih.. Aiiat.ind... lS7(i. i, |i|. oS. Nephrili- ini.j .Ml.utninuri.. M.inn. iSSl. Mil. Di.. l'atli..l..trie und Therapi.. .Nt Ni.Tcnkrankh. it.^n. lMi:{ an.) Isdl. 10. \.Thaii.llun-,ii .les (uiurr.-s.s fiir innere Me.jizin. Krster ( oiicrcss 1SS2. ' ' 11. (lily's ll.i.-piial Hip.irts. viii. 1S.".2. 2.1 series. NOTKS AND KKKKI{KN(KS 205 l-J. A I'raclirul Tniitisc on Hrinlifs Disease. K and 1S77. l.V Nircliow's Arehiv, Ixxiii. 1S7S. Berliner kiinisclie Woeliensclirift. 1880, No. 2'.t. It). Dielirinlit'selie Nierenkrunkheit voni i)atliolo(iiseli-anatoniisclien Staiid- jmnkt. Volkinann's Saniinluni; kliniseher Vortrafje, IS7!I, Nos. 102 and Hi:}. (An exeeedinnlv important work.) 47. TelxT die I'rsaelien der Nierenschunipfun}!;. Deiitselies .\nliiv f. klinisehe Medizin. xxv. ls7'.t, p. ')Sti. IS. Meitra-ie /ur Keiintniss des Morbus Hrinlitii, Ziejrler's Meitra^ie, Jena, lSS(i. i. t'.». I.oc. eit. .-,(). Die Erkrankunjieti der Nieren. In Notlmagel's series, W len. A. Holder. .')!. Virehow's .\rehiv, xix, IStJO. .VJ. .\rchiv fiir Ileiiknnde, 1S(')7. .■>:;. llandliiieli der patliolofjisehen Anatornie, vol. i. 1S7I). .VI. .lournal of I-Aperiinental Meilieine. ISDM. iii. .".."). I.elirl)Ueli der .speeiellen patlu)lot?iselien Anatoniie. 18(»:i li. .")ti. Loe. eit., \mm' 47. .")7. Loe. eit., page I'.H) IT. .-)S. Verhandiiint?enderdeutscli(>n patholosiseln'ii (leseliseliaft, .lahrsjanR lOOa, p. t)4. .V.t. TelxT die entziindlielien Veranderunpen der (Jlonieruii. Arheiten aus dem patholonisehen Institut zu Leipzig, 1007, monofirapli. CO. Studies in I'atholoKieal Anatomy, Acute and Chronic Hrisilifs Disease. SIX'OND LKCTIRK 1 Consult: Schafer's Histology. Rolim and Davidoff's Text-book of His- toh.tjv, and St.ihr's T.-xt-t.ook of Histology. Also Lundois and Ster- ling's IMivsiology. where hiatologieal and jihysiftlrgical problems are discuss.'d'. Als(i KnTich's Die Mrighfs.'he Xierenkrankheit. ISol: Krehl, Pathologische IMiysioloKie; and Oswald, Lehrbuch der cheiii- ischen Patliologie (Harnab.sonderuiig). 2. The Devei<.i)ment of the Malpigliiaii Hodies of the Ki.lney. etc.. .lournal of PatholoRV and Bacteriology. 1000. vi. p. 4.')'.». :i Consult here particularly Starling on the secretion of urine in Schiifer s Text-book on Physiology, vol. i. an.l Hermann's Lehrbuch der I'hysiologie. The former, particularly, gives a readable presenta- tion of the whole subject. 4. Philosophical Transactions. London, 1S42. •JOfi HKKIIIT S DISKVSK .'). Ill llic Wirlifl- Aklldrliliscln' Sit /uilJIslicl-irlitr. M.illi. nat. Klussc, llciiimiiii ill hil. :iii ( is.Vt . p. :)l".t; IM. I.'. ( l.^iil i, p. :ii7. f. I.iiduiii. iliid.. l{,|. IS, ij ( is,s:{i. c. l.inlwi;;. Wamici's llaiiilucitcrliiiili. jj. (i:!7. »;. Rilihcit: \inlimv'> vichiv. |{,|. xciii. Hill. After iviiioval <>i the iciial iiii'iIiiIIm ill lal.liils IMiImii oIiscivimI a very aluiiulaiil Hcivtii.ii of thill iiiiiic. Tlirs- i\|HTiiii<.|its aic npcii to ulijiM'tioii. as Miink ami Senator point out. I.oc. ,ii.. p. j:;. foot-note: and. further, Uoyd, .hiiirnal of I'hysio|oy,y, vol, wviii. l".tlL>. The later evidence: Mans Meyer, leliir Dilirese. Sit zuiinslieriehte d. ( Hsellsehaft >.lir Mefor- deriinfi der jiesanmiten NatiirwisMiisihafleii. .\I;irliiiru. IlKfJ. p. !f_> i\'. < iishny. .journal of I'liysiolotry. I!ML>, vol. wvii. 7. Cited .ift-r Starlinn. .Mecliani>iii of the .Secretion of Irine, in Scliafer's 'l"e\I-lM,okof j>liy>ioloiiy. vol. i. I'lVlfer, < )siiiot Isclie riiter~i|c|ninKell, Leipziii. |s77, Dreser, .\irhiv fin- e\pcri ntelle i'atholoijie iind Piiarinakolonie, l.sit:.', \\i\, ;{()7. S. \'erhaiidlini!;eii der Deiitschen patholoiiisi'licn ( lesellscli;ift. .I.ahrttanj; I'.IO.-.. .Morliiis Mrinhtii. p. (14 tT. '.I ".r:-lauer ar/tliche Zeitsclirift, lS7!t. 22. and extensive discussion in ller- nianiis Haildlpuch der IMiysioloyiie. v. i. pp. ;{(!<». 1(1. Oertel: 'I'heories of Iriiiaiy .Secretion from the Patholos-icaj Standpoint. New ^■ork I'niversity Mlllletin of the .Medical Sciences, vol, ii. No •> April. I'.HL', 11. Soliieranski: Archiv fiir exp. Path. ii. I'liarm.. xxxv. 111. 12. Senator: Die .Mlmmimirie. IS,S2. uives a full discussion of this subject ami further references. .VIso. X.Tliaiidluniieii der Herliner Physiol. Cesellschaft. Dec, IC. |S,SI. i,, Dll Mois lieyinomrs .\rcliiv. l.SSl. and Mcrliiier klin. Wochenschrift. ISN,'). 1:5. Munk anid.. vol. 4.">. IS. Hofineister's licit riisre. ii. l!t()2. lit. Iliid.. ii. 1!I(I2, 2(1. Teller Diahetes insipidus und andere I'olyurien. Deiitsches Archiv fiir kliiiische .Medizin. IlKC). vol. S:{. p. (17 IT. ((Quotes the other literature) 21. .Vshcr. Tropp and .Michaiid: Zeitsclirift fiir Hiolojiie, Md. }.-, n. 4(j. 22. 1,0c. cii. 2:{. Zeitsi'hrift fiir klinisdie .Medizin. :j:{, i, 1S!»7; :{4, i. ISK.S. NoTKs AM) hi;ki:i{i;\(i;s •2(1 Tinm) iKcnHK •ilirili" mill iillini .yiil'irvls (!i iicrnl ri )( I'l nil ifirl:.'* mi iiif), Senator: Die Krkrankiiniiiii ilrr Nicrcii. Wicii. V.Wl. AlfnMl Huldcr. ((iiioirs literature extensively. Very \x.uin\ liistorieal inlrodiietion.) Kaut'iiianii; Lehrliucli der specielleii patlioloniselien Ariatoinie, Berlin. I".M)7. (ieiru Keinier. (Kxci'Uent tor rel'erenee ami literature.) Ziejiler: .Mlsenieine i'.itlioiotjie und patliolosiische AnaloiTiie, Hand "_'. Jena. l, Hiistav Kischer. (Literature.) Cohidieiiu; Vorlesunfieii iii.er all}ienieine I'atlioioKie, Merlin, |SS(». Antiust Hirseliwald, Zweiter Hand. Krelii: ratliolottische I'liysiolojiie. I.ei|t/.i(j. Iit(l7. ."itli Aullasie. 1". < '. \V. Vomel. irartieularly for llie functional eliantje>. ) Ortli; Kelirhueli der speciellen patliolojjisclien Anatoniii', U. Hand. I. Ahtei- lunti. Merlin. IS!«. A. Hirseliwald. (Literature.) Freriehs: Die Mri({lit'silie Nieren Kranklii'it. Hraunscliwein. Vieweu, 1S,")L I With review of early literature. ) AseliotT: Lelirl>ueli der i)atiiol()M;isclien Anatoniie, IL Md. Jena, Fiselier, 1 <)(•!). Iloelie et Hri(iuel: Les Lesions dn Hein, Paris, 1904. (With tjood atlas.') S. !t. 10. 11 12 i:{ 14 IT) li°) 17 Morl.us Mritihtii. VerliantllunKfn der deutsclien patliolofjisehen tJesell- s<'liaft. Jalirnang I'.tO."). p. ti."). Naturforselier VersaininlunK in Meraii, 100."). Die VerandenintJfn der inenselilielien Niere nacli Sul.liniat versiftimn. etc,, Zienltr's Heitrase, vol. xlv, p. U«. ll.id., p. 241. Il.id., p. 2(M). Cellular l'atliolo)j;ie, lierlin, 4. AwH.. 1K71. Die Lelire von der triihen Seliwellunfj. Preis.selirifi, \inzl.iM-K, ISOl. Virehow's .Vifliiv, .'xlix, p. 4t)l. Kleniente der PatlioloK"'. '■'>■ AuH.. 1S0(). VorlesuiiKen iiher allneini'ine Patliolosji''. 1^><-- Allnenieine I'atlioloRie, ISSO. Lelirl)ueli cler allfjenieinen PatlioloRie. Lelirhueli der alltjenieinen patholoniselien .\natoinie. Lehrbucli tier iiatholotjisclien Anatoniie. Haiulliueh der allnfineineii Pathologie. Virehow's Archiv, cxxxv, p. 470. Teller triilie Seliwellunn, Zienh-r's HeitriiRe, xxxiii, VM\. Internationale Zeitsehrift fi'ir Anatoniie und Phy-^iolonie, 189.'). •JOS HliKIMT > Disi: \si-; IS. \ itIimIIiIIiIIIUcii iIiT iIiIIImIkii |);illliil(icis(lii'n ( Icsi'llschuft. l".l(l((. lit. 1,(.,-. .11, •JO. The l'liiui|>liM.r l':illi. hcrr; l.iir, cil. 21, l)ii' I'liiiilii '.s<'lic' Nitn'iiUiMiikhi'il. NdlkiiiMim's Siimiiiliiii^ kliiiiscticr \(irli:iiit'. lt.2 H.;!, isTs 7!i. pp. Ill, 2."). .\r('lu\io pir li' .s/ituzc incilichc, |SS;{. vi. :{. Sulla hypcrlrdtia coinpcn.-ia liiria ili'i iriii: and Nriilpib.lir uii.l I's.'U.ldr.'HctnTatioii Kci Nicrciiiiifarktcii. \ ii. h.iw's .\r.iiiv, 1 IC), IMMi, H.is,-,!.': Siiinmn.'ii .l.T K.ijcii.Tatiiiii v.in N'icnti.'pitlii'Iicn. \ ir- .■h.iw's .\nliiv. I7(t, l'.K)2, .latia: Sulla n«iii.'i;uii)iic ilcircpilcliii .l.'l r.iii'. .\rcliiviii per s.'U'iizc nicliili.'. wiii. p. U2o. I'.ia: I'llicr Nitiiiiirilaik!.'. Zicjil.i's Mcitraijc, ISSH, v. 2". K.'itiau;.' zur .Xnatoiiiic .1. s niiliari'ii Tulicrki'ls. II, r.'hcr Nicrciituhcr- kulisc, \ir.li.iws .\rchiv. ISSI.SH. 2S. li'li.i- TuImt' .■! uii.l TulxTkulosc. Zcits.'lirift fiir kliiiischc Mcdizin, ix-x. •2!t. Ocrt.i. II.ir>i. On i^pitli.'lial rnilifi'iati.ni and tln' l".)rinati()n of Kpitlic- lial ( iiant-.-.lls in Ni'pliri1i>. I'ulili.'ations of the l{u:;s('ll Sape In- stitute .il' ratli.i|.iy:.\ . (il.v ll.ispital, New York, i. (I-itrratun'. ) :i(l, I..).', .it. :{|. Mcitiaj;.' zur K.imtnis.s .Ics Morhus Bri){litii. Zicslt'r'.s Hcitrajif, i, 18S0. o2. |)i.' .\(tiiiliini.' uud ( Icncsf ilcr akutcn Nephritis. Zie(jler's Heitriigr, n1. IS! 12. :{;{. Teller Nepliritis siariatitiosa. Fortsehritt .ler Me.lizin, i, 1SS3. .•54. Nephritis uini ,\lliuniiinirie, Honn. ISSl. O.I. l,ii.'. fit . ;!(i, l,.ic, cit. :!7. IntlaTnniatiirv Chaniies in the Kidney, etc. .lournal of I'atholoKy and Ha.teriolody. .luly. I'.ttll, ;{S, Zeit.sihril't fiir rationelle Medi/in, Heft i. p. (12. .Mso dcscrihed l)y Niusse in Schmidt's .lahrhiiclier. ISlIi, )). ;<•")('). Further, early contrilmtions iiy Simon. Meitrajie fiir phy.iiol. uiid pathol. Chemie, i, p. 1();{, and Scherer. ( 'hemische und mikroskopi.sclie I'litersuchuiinen, Heidel- li.'rc. INJ;?. :19. Hovi.la. in Mole.sehott's rnt(T.-U(hunn<'ii zur Naturlehre. 1872, xl, 1. 40. .\rchiv fiir experimentelle Pathologie und l'hariiiakoloj;ie, vi, p. 113. 11. 1,0c. cit. and Die nonnale und patlutlopische Anatomic und Fhysiologio NOTKS ANO HKKKKKNTKS 2()9 42. u. 4,"). 4{i. 47. 4S, 4!t. 51 .l.-r Nior... Hit.li.,tlu..a .nr.li.u C H. un.l Hil.iunK later investigators. 2. Loc. cit., p. !••.». 4: Zur' Entwicklungsgeschichte des Krel.ses nehst Henu-rkunRen iiher Fettl.iUlunR in, thierisehen Korper und patholoRische Resorption. Virehow's An v, i, p. 94, 1847. 5. I'ettenkof..r anlu HUK.in > nisKASK '.». I(l..i |Vtl.ni~:il/ nil l'liirrkoi|H r. M.il. /,. nli;ill'l:ill . s. IW-'. Ali.l, IMIiimi- Aivlnv. :!l. II, l>vi. III. I!,i\. M:m D.iiiioll :iiiil l.il-k. Aiiiilir;iri .lipiirn;il nl l'li\ -iuluuy , IS'.I'.I. ill. I.ii-k .iiiil MMiiiltl. i.Milic .\t\i\ in lnlriinti|i:ii\ M(t:ilH.liMn. il>l>l.. I'.HMi, \vi. I.ii-k. M(i;il»ili»Mi in IMiu-.pliiiin«-|'"i-'">'i'^i '''"'•• I'.MIT. \i\. I.ii-k. riic i;irniinl- ill III'' >rnni<' nl' Niiiiiliiin, I'.MM'i. SmuihIi r-. II. I rlicr iA|»riininlrll n/riliili' |Vll-\ mlii-r. 111-., \ iiiliiiw- .\ii'liiv. 171. I ".mi:;. r_'. {.ill Tiinirc «in :iiiiip|.\-i-i: Cinlur, Dii' l\lini>i;li-|i:'*liiiliim-rlii' Mcdnituint iliT \iiliil.\~r. Mnlinir klini-ilif U uclii n-ciirili , I'.Hi:!. \i, IV"). Ojiic, .IuiiiiimI 111' 1a|i. .Mill.. I'.Mi'i. vii. p. :!lli. T.Vt. IIimhi'. Nntc mi Aii- liii>>i> in l.uli.ir Mini I nn-ihiil l'niiiniiini;i. 'ri;ni-Miliiins of As- >(iri:ilinii 111 Ainiiii;in l'li\ -iriMii-. mdo. wiii. W>"i'i. \V:ililvii«i'l, .\nliii\-r iHiii Irltiiii' Diiiini'ialiiiii. Nnrlmw'- .\iiliiv. I'.lltl, I".'), i. l'liii~pliiir\iTiiilliiim nil. I Aiiiul\-r, DmNi-ln- .Vnliiv I', klin. .Mnli/.in. I'.iii.'.. vj. t:i7. I'. .Miillir. I':iiliiilii!iir ili- Sintlwiili-iU. Lcvrni', I*. .\.: .\nliily-i-. IImimv l.niiins, N. V., llHI.'i llMMi. I.ippinnitl Co. |:{. .\n iMilliiii l)i-iMi-.>.iiin in .Viliinii"- :iililiv~- luroif the Niw \i.rk lliirvoy Soiiii> nil M,vilin~. ill.. pulili>linl in till' Ihiivi'V l.ii'liiir> lor IllOtl to I'.III?. Niw \iiik. I.ippiniiitl (n. For iIh' ■liiini-lry -ir ll;tnmirr- -Ii'ii. I'liy>ii>li>i;i-rlii' ('lirinir. Ii:in-l:iliil into I'.nuJi-li Ky .1. Maiiiicl. .Vi-o. lloppi-Srylrr'- l'li\ -ii ili ini-i'll lllnl p;il lioloni-rh i-jicniisclic .Vnaly-r. A~holV. Ziiiilrr- Hiilriii;i\ IM. 17. i. p. 7. iiWf< tiic most rri-fiit Mii'l i\li'n-i\r ili-i-u~-ioii. II. Orrii'l; JJiiir.iijr /ur l\iniilni--~ ihr .Xiis^rliiiiluiiiJ il's or«;aniscli«t'liuinl- iii'ii I'lio-piiDi- iiii llani. Ziiisi-lirilt I'. pliy>iol. ( limiii'. xwl. Keller. iliiij.. \\i\. M.illliiMiii. jiioiiiiinii'ai .loiinial. iv. '>. li. ami 7. Maiiiiel .mil Oirlri. N. \'. r iivrr~ii\ Uiilliiiii of Meiiial Siiiini-^. i. p. 111.'). I '.Mil. l.-|. S\ 11-: .loiinial of I'alliolouy ami Uarltriolocy . vol. \. I'.HI'). p. I.'i< T. anil p. 127 If. III. Sit ll.'innnerNlrii, i.ihll>iiili ilrr pliy-ioloiji-rlien ( 'llilllir. I'.itl7. |>. '.VAX. 17. rii.ir l'"eninllliraiioii. .ii-.. Ninliow- Anliiv. IMI. I'.ill.'.. .\l-o. Order, leliir ila- .\iifl iiiiii \ on .Myrlin in Zellen. ete.. \ iirlmu- Anliiv, 1117, I'.iilJ. IS. See Sloerik. lilier I'rolaiion Uml illierilie i;io>se wei--i Niere. Sitzmifis- lieriilile ilir I\. Akaileiiiie iler Wissenseliaflen. \Iatli.-n;il. Klas.se, Willi. II,". IVlil. isaufniaii. Sperielle pal liolotii>rhe .\na1omie, I'.in7. |>|>. 7s7 7^^. !'.». S,- Kraiis. I'lii r I'lliilei; inralioii mi I Kelliiitill r.ition. \erlianillun«i'n NUTK.S AM) IIIKKIIKVI KS !ll ,lrr IVutsclnn |.atholnt:isrl,.n ( irsrllsrhaft , ^r.'listr TaKUim. I'.HU. p. •_>(». On tt.r l.art!c Wl.it.' or Soapy Ki.ln.y. .I.mn.al «{ Mr.li.al K.s.-arrli. Hn-iiiii, XX. p 27. 21. I.'"'. Ill- 22. I.«"'. 'it. . 2;{. I'.'lHr .1( u L.Mill.iiiiJ.'lialt .l.s ll.rz.i.s ii. .Irr Ni.t.m. n.-., .\r.t.. i. rx|.. I'allKilc.uic iiikI I'haniiak.ili.uir. .V2. ITS. P.Mt.'). 21. l.rl,il.il.l. .1. .•lu'inisrhr l'alliol..«ir. I'.KtT. lias a r.vi.w of tl.r s.ll. jicl (.1' lal ili'Kfiirratioii aiul lal iiitiltratioii. •>:, Wi.lni.an: Di.- .\invl..i.lcrkrai.kimn. H.itrau.' vui, Zi-^l.T. xin. lWt:i; aii.l Maillanil. in M.'ili.'al an.l Suiunal Hrpnils uf NfW N -rk ( ity Hospital lor Utos. ||.i.t..r. ( '.•ntralMalt iTir I'atl.oloKir. M. xix. 2:i. p. IM'I- 2(1. ll.rxh.iinrr; Hyalinr Dr^rnrralion .1. r ( linn.rnili .l.r Ni.'tv. /h^uLt s H,.itra«c.. IM. 1.-.. llMl-.t. , „ . , I 27. llistolojjy of l.ivr Tissur Hrpii.rati.ui. .loi.rnal ol lalliolony and Uarlcriolotiv. xiii. p. 127. 2S. V.rlian.llunurn .Irr .l.Mitsria'l. patliolouis.lan ( l.s.ils.hait. I'.MI... I HMr Morliiis Mrinlitii. •'., I|,.rxlaini.r an.l Hall: ICl-r .li.' Knlkai.s.lunn .l.r Ni.tv. \ inlu.w s \r.liiv I7!». I'.Hl.V .li.s.uss this inall.T iully an.l also nivc \\\>- litrratiitv. :«). r,.|,..r.l.n .V.is^anu .l.r .•yan..tis.li.n lii.lnralion .I.t Ni.'ir m Cranulai- atro|)lii''- \Vi<'sl)a.li'n. \>^'M- I'llTH l-KcrrHK 1. Vr. .Mull.r: I.o.-. cil.. p. '•«»• •' Kaufmann: I-.'lirl)ii.'li .l.T patliolosis.li.n .Viiatoini.'. "{. Z.ir K.^nntniss .I.t Cir.'ulati.mstorimK.'n in .l.^n Ni.'ivn !>.■. (•Iir..nis.ii.r int.Tsliti.'ii.T N.'pl.ritis, Vircl..)wV .\rcliiv. H.l. 71. |). 12. 4. r.-l.rr .li.' pui.ktfonuiurn Kalkk..rp.nh..i.. .•!.•., \if.hoWs .Vivlnv, M.l. n ■ri...'lii.'rat,'nr on arfrioschrosis is vry ..xt.-nsivc. Tlu' rolL-winn will 1,., ,„un.l us,fMl for n.f.n.n..-. .lor.'s, Wrscn t.n.l Ki.twa-klunK .I.t \rt..ri..skl,.r.,s... Wi.sha.K'... UKU: Maivl.an.l. r.'h.T Art.Tioskl.Tos... K..nKr..ss fur inn.^tv M.^-lizi... I..'ip/i«. 1!'<»1. -^ soin..what .lill.-tvnt .tan.l is lak.M. l.v -V-laini; s.r his pai-.'r in th.' ( ).'tol..r nunilxT ..i th.. AnuTi.an .l..urnal of th.^ M.MJi.'al S,.i...K..s. V.WX "Th.. Natntv ot th.- \rt('ri<)scl.'r..ti.' Trocss," which also covers Kh.tz's w..rk. ,i loc .-it an.l r.-lMT -lie Art.TioskhTosc .I.t kl.'in.-n ( )r«anart.TM.>i. nn.l ' ihn- H.'zichun«.-n /.ur N.'l.hritis. Vin-how-s .\r.'hiv. 17S. Hyp.Ttrophu- nn.l .Vit.Tioskl.Tosc .Ut NiiTcnart.Ticn. il.i.l.. ISl. HHHillT S |)|SK\SK .? 1 7. I'ryiii; l.lxr An- \ .•ruii.l.nmK.'i. .l.r arl.ri.ll.i. ( irfiissr l.ri iiiliT^tili.'ll.T Ntpliritis, MnliowV Ar.-liiv, M<1. 177. s. IrlMT .l.n.nisclir NrphritiH iiikI ilirr IW/.iclninK zur Arliri.mkliToso. Vjn liiiw- Ariliiv. M Ar.liiv. l.V.I, l'.HK». An.l. rrpiy t(. .Ions, Vircli-'W s Arcliiv, M isd. 1_'. r.l..r Siliniiiipl'ni.Tr cliiic Artcri.»kl«Tnsc. \irclinwV Arcli., IHO. i:{. !."«■. lit. 11. Km/ ilrhcr l.tlMTrirrlKisr. Wi.iiir kliiiisrlif \V.Hli<'iisi'liritt. 2. I'.MH).) .>iiinlarl\. has >li<>\v!i an .•iilinlv cliaiinnl rcunicraliv.' r. nstruftiim ill till' aii'liiit'tiirr of the liver in cirrlio.scs. l.V Consult h.r.' thr presentation of Krehl, l'atliolo(jisclie I'livsiolojjie. !,eip/i«. 11MI7. pp. M IT. (Literature. An here sironner and more eonrliisive than the anatomical. l,s. Teller .hn /iisammenhaiin v..ii Ilerz mid Niereiikrankheiten. iierlin, 1S.-.C.. .\nd. Naehtraiiliche I5einerkuii«en da/u ill i)euls<'lie Klinik. 1S.V.>. M and :VJ. An excellent modern presentation of the whole suhject of l.iood-pressiire ill T. < '. .lanewav's monodniph. "The Clinical Study of hlood-pn -sure." 111. Cohnheim; Alltiemeine Tatliolonie. vol. ii. •-Me Anfl.. pp. 2.-)S and M)] . •2(1. Loc. cit.. ntOJ. p. 122. 21. Patholouische i'hysiolonie. p. :{S. etc. 22. \'erhan. (In the general discussion on Hrinht's disease.) 2:5 l)u Hois l{eviiiond"s Archiv. 1S77. 24. llirsch and' Heck; Archiv f. kliiiisch.' .\le(li/in. C.'.t, .".(W. and 72. o()0. Archiv fur experimentell<- Pathol., etc.. .-)4. (.Cited l.y Krehl.) 2.'). I-. 28. Consult IVarce. in the .Journal of Kxpcriinental Mcdicint'. x, l'.K)9, p. T.ih ff. NOTKH AND HKKKHKNfKS 2i:{ •21.. Meltz.r: IxTturr. .... (K.i.n.u. A....ria... M.ai.i.... l!HI-». 12. », .....I :.. SturlmK: I.-tuns. U..c-.-t, I'.Hm, May '.M- M. S-,- ..U: Ada...., I'ri.nipU'H of I'litliolonv, ii, p. !»•:* 'T. ^. i..,K,r,u... i..'tiu. an. ti ..rv...io..s „....!.. ... -.-;;";;; ...phritis i„.l.......l with ..hr.....i...n u...l ..m...u". .Halts. •"•:"" Jl ,.ru,.iu... l...tl. pn,.l...... a ....pLriti.. whi.-h. h..w..v..r. ... t .. ...u. r is u..a......n.pa..U..l l.y ....l..."a. wl.il.. th.' latfr .. .«.s.,.-... .-.l «.tl. .x- tonsiv.. ....l.....a. ll..i..ok.., ,..or....v..r. ha.s f.......l that h.; s.t..... .^ ani.,.als ,...is.„....l wit I. ..ra..i..... has th.. pr..iH.rty ..( P5'"'"P '^''^ " in .„h..r a,.i,..als. Si„.ilarly, it has n sh..w.. l.y K.u^t "•"' > ''-^T th..t tlu- l.hH..l-s..r..... ..f .|..l.....at.mH ...phriti.'s ..a.is... ....Tcise. l>».ph- ;,;.w i." ani,..als. S... als.., IVarc.-. Ar.hiv.. ..f hm-rnal Mod.c.ne. iii, I'.HMt, p. 42._'. 32. Oi.' (liw..».t.spa.inu..K. Kciii/in. 1^>*4. Xi. Kn-hl. 1..C. .it., p. 12;*, with further lit.Tutur... APPKNDIX Cl.ASSIKIt ATION OK NkI'IIKIIIS I. .\i iihnlis .-///////(X. Cliiinly swelling, infla!iim:iti)ry (i'«lcm:i. ami serous (Mil late. .V< /ular tissue. Inflammatory proliferation of epitlieliuin. ( ast forniatioii. Frequently licmorrlianes and i)roliferation (»f fi.\ed ceil>. III. \ii>liiilis iliiji iiiniliiit it j>n>ilit<-tii(i: The exudativ<' features in the liack«rouiid. The de;r,.n,Tative (particularly fatty) changes pronii- neril ; ca-t formation: proliferation of epithelium ami formation of epitiielial jiiant-cells; gradual <'ollap.se and loss of kidney suh- stance, appcarani-e of leukocytoid and til)rol)lastic cells in the in- terstitial tissue, with the gradual formation of matiu'c fibrous tissue, first patchy, then more ilitliise, Ilemiyrrhaijes occasionally ))resent. (iradiial thickcninnof lilood-vi'ssels. with occasional infarcts. IV. .\i iilirilis i>n>(liii-lini: Cradual, first patchy, then more dilTuse, in- tlannnatory oliiiteration of renal parenchyma, leadiiitJ to general, particularly cortical. lo«is of kidney suhstance. Aliundant over- jiniwth of fibrous connective tissue. (Iradual change in the ty))e.s of secretory epilhehum. Marked thickening of hlood-ves.sels. with eventual narrowinj: of lumen and oliiiteration. As the result of these, infarct formation with healing I'.v ^'"ir tissue. NilN-IM l.\MMAlo[{V F.KSIONS oK TMK KinNKV. ()( ( ASH )\ AI.I.V, HI r \Vui)N(iLY. ( iuui I'Kn AS NKi'iiurns 1. Iii(liin:liii fijiiiiiiUcii riiiinii: The <'yaiiotic induration of the kidneys re- sulting from mitritive disturlpanc<>s as the result of ioiifi-continued venous -tasis. Connotioii of all vascular districts, taking origin and remaining markeil particularly in the medulla; accentuation of •-'It AIM'KNDIX 21.') 11. .,11 MKirkii.K> I„11ow(m1 I.v .riiciiKitoiis ini!.il.iti..n of the parts; hwal- \,,.,\ atn.pl.v an.l .•..llu|.sr nf ki.ln.'V suLstanc.' witl. .■•lually U>vM fil.n.us tissue tjn.wtl.. Sr,-..n.la.y .•luinti-'s in l.lc.a-pinincnt, lysis aiKl scttiiisi Ire.' al pan.n.'hyn.a. will. n>ark..,l artHioscU-rosis. ..Miteration of vcss.is. an.l infar.tions. Dilatation oi renal pc'lvis with n.ark...! iMvakinj: ui. ..r loss of its .lastir n.uscular layer. Hv- ,,n..„llv a.l.liti.M.al stasis with 7, 1J.J, i7:i .l-'.tius, 4 AUwcht, .")7, .IS, l'2:i Altmunn, 52 Arnold. tM) Awlu.ff, 14, ti4, 1J:{, 124, ITS, 17',t Ashor, :«• Aut r Councilman, is, 107 Cruikstiunk, .'> Ciwhny, ;<:«. :«• Dblakiklu, 24 Desir, S Dnwr, :j:{, :{4 Bam»k.iu;ek, 1st Hang, ll'.> Hartrls, Ki, IS, U)3. 17S, 105 Baupr, UtJ Bauni, 14S, 16S Baumuarten, 60, 100 Book, ISS Bocqiiorol, Boor, 14, 22, t)0 Benario, .w Bonoko. 1-20 Bortini, 2S BiorniiT. is Biroh-llirsohfoUl, .'>•') Bossard, 122 Bowman, 10, 14, 20, :U Boy.l, ;« Brando, ,"> Bright, .1. .■.. 7, 10. ltV2. lo:{, is:i, 1S.V iss, io:i Brodio. 41 BiiHk, 10, 11. HV.2 Biitsohli. 12:i KUKHOIILS, l.")4 Khrlioh, ISO Elliot son, S Kngol, i:« Km-st, 1(V2 KwuUl. 170, 1S8 Fahk, ItHt, 170, 17."> Fisohlor, 117 Krorichs. 7, 11, lt>2 Frio:», 170, IHS Casstatt, 10 ChriHtison, 7, S, l.i, 102, lOiJ CV,hnhoim,14, 1.-., 10,22,.V.. 1.S.1S„._1M,. 187. liH), 101, 102, 104, 19,"), I'.Hi, 10. Coplaml, S Hai,i.. 154 Hiwonfold, 1S4 Hausmann, 30 217 ^!r 21S 1M)K\ llx'lll. >. \r,\ ilcllllllCl. Ill llirvcli. IM. iss l|i>l'iii:iii. III! Iliirn, Hill llili'trr. |:il .M.iivl, .111,1. ■-Ml. I.".. Hi. 17. lit. Hi:!. 1711. 17.". Miiriliiiiil. i:il Mc'lizir. I'.ll .M.y.r Kriilii. :«•. to M.v.r .Il;iii-i. ;{:i, :i'.i Milii.'. i:u. I l>i Miii'uiii'iii. ."i Miillii-. Jii. -'1. :!l. 11. l."i. 17. III. l.'iO. Hi:!. ;si .Miiiik. :i7 't, \i l-IHKI. IIIJ. \\<\ .)\NKw \\. mil .liiliiixiii. Id. I I. Hi. Ili'J .Ions, Ki'.l. 1711 l\ MVI Nsll IN. I'll Kaiifniaii. .">li Kicl.s. I.-.. Is, .-,•;. (i7, IIL' Klitziiiski, I IS Kldtz. IJ-.' Kiinui.vi. to Kraus. I-.':! Kr.>hl, isl, ls7. I'.lll. I!ir. l.WDKHKH. MMl l.aiiil>lriii(l'. ."ili. •■|7, nil l.aiiiiliaiis. Ili:> l.rl..'(lrlT. llr, l.ryrlill. 7. Hi I.i.li'liiiiii. Isii. HI.".. I'.Ki l.i.l.r.i.li. IJI l.itl.'ti. UK! l.<.lil.iii, -Ml. -'1. 1.".. 1117. 111. IJI. i:::!. Hi:i Liivvi. :i!l l.iil.ar-.li. 111. IIIJ l.ii.lwin. :il. :iJ. :il. :i.".. :!ii. ■',''. m. II. isii. I'.ll l.ii>k. I Hi, 117 l.vi.ii. '.i:!, '.I'.i. inj. lo:i Mai, MS. :!<», HMi Matiti. Ill \ i:i.i I I. .".7 N,-.>M-. Ill Nauwirik. Is. (il. 1.7, 17s \i. ■111:11.11. Hi (llll.l.KK. .')" Ill-ill. is. ."I'.l. llll I Ishiiriir. 7 Oswal.l. IJ.". , Hi. H>J IfililMTt, I.".. Xi. 07. '.i:i, '.It. llll, lo:{ Hiii,||l,i-,li. .".li. 170. 17:! |{,„kii:iii-k.v. 1 1 H,iiiil..iii. |s| li,,~,nl,l,l. llll. 117. UJ. IJ.". |{..Ml.>lrill. I.".. HI l{,,-,iillial. UJ lii.tli. 170 li,.M,la. III. llHi li.iv. :17 |{ui...». IJt. IJ.". Itilliipf. iir. INDKX 219 Sahatikh, '^ SilirrcT, 10 SiliilliiiK. •'"•' Silimails, ItMl Schinidl. l'^" Schiiioll, 122 ScuiiaiiiDrr, •"> Si'iiiitiir. Iti, In, is.j. 1S7, ISS Si<'l»>l'- ."Nilmi, '• Sl.irlinii, I'M Strwiirl, Iti, Ki'l Sicvrcr, i!'.' Siiiion, If., ll>:i, 170, Iss 10. JO, ;i.'>, ;!T, o;i, i,v>, n>;!, IVI, I'.Ml, lO.'i, l!Mi, 107 Vm.kntin, (I Villi C'cill. l-'il Villi ill.ilT, ;!:i Vtnvorii, -'i^^ Vinhim, 11, r.', l:f. It, 1.-., 10, \-.22.rvl, .->.->, .V), •■>!•. 00, Ot, <>•■>. II.-., 117, UN, V2.i, 170 V(.)£(l, 10, IJ Villi llilllSCIllilllll, IJti vmi Kiililili'ii, ti4. S.^i. Mi villi Kcckliniiliiiii^^i'ii, ■'>'i vi.ii \iiil, 1 Hi WAIiNKIi, IS \Vri)£.Tl, 14, 17, IN, iO, KiJ, 17S. 170, ISO. ISl \V, ItiU Willis, s >:i. 1.0. 04, liv-', l->i, Taisk. 1 Tlirlrinunii- l-'.l Tliiiniii. ■>»>. ">". !""• ''•" ■niuilirJii .1, 110 'rifsoi , s , Trf::'iri:^.'.s" is., ,.>, is7, .oi. .o. Z.kuuk„, is, .o, m, i:«. .0:1 INDEX AriTK intcnilitittt nephritis, vu-w« on, IH piinnchymiilous ai-Rvncriilion, 4.i usi" i)f woril, '2;t AlbriM'lit's views on pnitoplusni, .')" Albuminuria, first demonstration, .') in fatty stage. \-t~ in productive nri>hritis. l^^i in simple nephritis, ."ii» nephritie, urinary (juolient in. 41 orthostatie. urinary (luotieni in, 41 phy.siolofiie. urinary ciuotient in. M Solon's views. '.I r ii Alkalinity of plasma, diminution of, l-», IJ.-) , Altmami's tiranules in par.iul.ymatous d.- neneralion. •"'- Amyloid deposits. i:U Anasarca. VM. l'" Arsenic, adema from, 1!M> Arteries in proiluelive nephritis. lliV, !•>'.• \rteriocapillarv fibrosis. Itv?. 1*^*> Arteriosel.Tosis in pro.luctive nephritis, UW splanc'hnic. Mood-pressure an.l, ISSs Arteriosclerotic kidney. 174 \*her's theorv of urine secretion, -V.) Atherosclerosis in pro.luctive nephritis. Ul'J Atrophia, '-•'' rciiuni. 1"4 vel sclerosis rcinmi. '.il'' Atrophv of nlomcruli. i:!;i, l.">l Autolysis, (iranular deceneration and, .>. Aulolytie processes, til, !!><, 1-'^ Hkiitim. <'olumns of. '2S Hil.lionraphy of fifth lecture. Jit of tirsi lecture ■.'1)1 of fourth lecture. JOit water in. urine secretion anil, :i- HliMMl-pressure, ISH suprarenal (rlands and, I'.l'i urine secretion and, •!! »lo■ in exudative nephritis, 6S in simple nephritis, 4S of kidney, epithelitim of, 30 Casts in i.roduetive nephritis, 1S;1 Catarriial inflammation, detinilion, 13 Cellular casts. UK) Cerebrosides. chemistry of. 120 C^'Srtalion of symptoms. 113 Chara<'t eristics of inflammation, i! Chemical causes of (edi-ma, 19S theory of blood-pressure, 1S4 Cholera, kidney in, 4.") Cholesterin. IIS chemistry of, 120 Cholesterin-ester-fat infiltration, V2i Choliii, Hit Chromatin masses, (14 Chromium p«)is.mini£, kidney m, »■'' Chronic, use of wonl, '23 221 •>•)•) INDKX ('l:i>-itir,iii.iii. I. :;. I. ji. >;:,. .'i i ( liiiiily >\M lliiiu, .'r.' "riiiiii. .Vi ('..lli>hi ImuIk'-.. II I ('iiliirnii^ 111 Uiriiiii. J> CcplTiTlillir i:ll'i||;li' lix |irrl nipllV III IM nil-, Is.'i ('Mlllliili\i'-tl"llr cli:iln;i-, |H7 ill iMiiy i|ir'tiii;iiiiiii, |:!( ('(iiilr:ii'li'l. Hi'.' -rcm.l.irv, 111, I IJ. |,"iJ, ,<.(■ S,,;inil'ini finlr.uhil l:i:lin ,/. CorniMM- ,-iil>liiii:iir |Mii>iinim' kiilm v 1"., Hi. no CiirtiA ill ■lii;(iii-i:iii\i> iii'|i|ii'ili~. Us ill r\iiii:iti\ f iii'itlirili*. (is ill »illl|llc' Mi'|illlili~, Is .if kiilnrv. ■-•7 CrcMTiil piciiiri's. s(i ('rilll|«il|» illl1:illllll:lllnll. ■Iilillilinti. 1 1! ('rviisrii|iy iif iiriiii'. ■>■> ( 'viiiiiiiir iinliirMiiiiii ill iMplniii-, I.Vt ('ylin.lnii.l.. Ill:; ("y-t- III pniiiiirnM' Mi'pliriil>, Itis Dkc \r--i I, viiiiN, l.")l I>i't;i'iii'i','iiiiiii, L'niiiiiliir, -VJ, .Vi iiriuiii, ,'i."i, ."i7 >ii;iiilir:iMri', ,'i,'i, ,')7 p:iri'lirliyiii;itntl-, lit :irllli', l,'i in "iiiiplc iiipliiili-, .">■_' !nii*rti--ciipir ;lppr;ir,-|lli'i'*, .'I'J without llitl;ilnll);l1 lull, l.") Di'lIc'iiiTulivr i\ii l:iti\c iH'pliiili-. li:! ri>>-:ili(iii iif >yiiiptiiiii'-. II:! r:ilty chaii!;!-. 1 1 1 I'lllli'tidll.'ll C'li;illl£l'S. Ills Hill" ;ippi:il;lllii<, lis lii«liii;riic-i-. li:; lllirlo-i-..pic :tppi;ir:tlli-'-, S."i iiiiiniiiiii:il ili.iiinis. 1 1 ! iriJi'Ml.l ill, |S',I p'llllii(;rlii-i~, (i:l pliMll|fti\r rlhirini- III. I HI pni|iiiii-i>. 1 10 li'l:iti'.| kiiliiry ili:iiiur-, I ,"iS tv,,i|i~, 1 10 pll- Drp'llrnitlVi' i'\llilMli\i' lli'plllili,^. trrillill:f tiiiiix. 110 uriiii' ill. Ills I III I y iicphrili-. 1 1.'> lV,iiiin>, !•") II' plii'iii-, li:! i;iii-i«, Ii7 lifn-* ,ippi',tr;lIli-|->, tis hi*tni;('iii'-i", ti:» piitlmm'tiois. Ii;l l)i:llirti'- ill-ipilllls. lirilli- iif. 111 I )i:iuiMi-i~, c'.'irly. 1 12 ill Villnll> »t;isi-, I.V'i I )i-Miiiiilii-iiiiiiiii-plici>pli,itiil( -, iliiiiii>iiy i)f, ll',i l)i>cnM>. rliMiiuiiii: cliiirarlrr III'. :! iiii'lilili'ii. JI l)i-t(ar\l-liritliiii, IJIl |)iiip,-iy, kiiliii'y clitiiiiic-i .itiil. ."), 1) livrr rlialllli'- :llli|. li l)riiu~, ui|i'iii:i liiiiii. l!Hi !■!( iKMiiir ciriiiiir liypcrlidpliy in iicpli- lili>. Is.', I'lii(l:irl(iiti> liliiii^M ill priuiiii'iivi' iK'pliritis, 170 rjliliilhrli.'il I'i'lls. I'li.'iliKrs ill. 107 I'liiiliitlii'liiliii. i:ipill:iry. prnlil'iT.'iliiiii nf. Mi li!il:ir^riiiriil ol kiiliiiy. Il."i l'.pillii'li:il ui:iiit-ri'll- ill ii<'plirili>. liO l')pillirliiiiii ill f:i1ly ilriii'iiiiatliiii, H'.l ill siiiipli' iK'pliriti-. .■>! Ill' i-ap-iilc III' kiiliirv. :{0 priilircnliDii. S(i III uliillli'I'llli, '.".I III' limp- of Iji'lili', :iO of tlll)llll>. •_".» rills ,|rri\c I flMIll. '.Ml iiiwly foil I, I l'( proliferation. !ll of iiift. prolifcr.iiioii of, S(i ICxlraniLiI >vnipiiiiii~, I'.MI l!\llil:ilr. {•ollslitlli'Ill- of. 107 ill sinipli' niplirili-, ."il oiiciii. 107 l!\uil:ilivi' Iratun-. I."i nrpliritis. .'si'i' Ih III III ml in i.rinliiliir iiilihrilis. INDKX 22;i K*i'-i>ii"i'-. I'lT l'';ilty (l(iiiiiir:iliiiii. II t. I I"' ilisinliiiliiiii I'f fill- l'-*> fiiiHtiiiiiiil rli:iinji-. I'lll. I">''> llliiiiiiTilli ill. 1-'' nlvioKill iiillllllt .Mill. 1 1" lillrllcil)lll;ir \\yi-nv ill. 1'>1 of liral-t. I'.lt IPiTil'lllMtC 1-1 lulllllr~ ill. I 1*> v:iMiil:ir apiKiriilil- in. I''' iiilillrnlioii. 1 1 1. II'' I'liiili-tcriii-i-iir. \2i (li>iiiliiiti(iii 111' ImI. r.''i |'miilii>iiiil ili:iiii:i'-. I''". '•''' tlomcnili ill. I'-'li ({|\( riiii-r>li'r. I'-l intcrlolmlar ti>>iii' in. I-''I mlmlfs ill. 1 IS vjisculiir ;ipii;il;ilii> i". I"''* iiict:iiiiiirpliii-^i>. 1-! Mi|)liiitis, ili'Ki'iirnilivi-, ll.'> ictciirnilion. 1 1" >iil>s(;ilin'>. (Icmnii^lnili'iii "I- 1-- iii acKi'iK'nilivc iMi.hilivr iir^plirirH. '.H. 107 irhtjin. 1 1'> -iliiiitii'Miiii'. 1 1.' IVvir iliilir ill >imp'i' n'plnili^. "'■' l'il)nisi>. :irtiTiiii:ipiU;iiv. l"''-i. 1^"^ Kihroiis tissiir priilifcniiioii :i"'l p;ircn- iliyiii:ili>ii> liiss. KiJ. ITS Kiflli liMliirr. nil l)il>li(iiinipliy 111'. Jl 1 rill nil i'lii llii'ory of iiriiii' ^icnlioii. M (il)jiclioii~ lo, :!l I'irsl Irilurr, 1 liil)lio)jr;ipliy. -'Ill I'InicI f-it. ciimlsiticMiioii of. IJ:'. I'liniis of Hiiulil'^ in iiiplirili^. •><• ( lloiinriili -S iiltiralioii ill -'"'• I '"* ..ITiTlsoii. nil. Ill ( pithi-lial liniiii! of, ■_".» fiiriiialioi'. Js ill iji.urmr.iiivi' nipliiii'>. <''S. s."i ill fitly ili'irmriiiiion. I'Jii in priKJiirlivr nrplirili-. HH'. Hi" ill l«, HKI ili'lirniialioii. .'ij. '<'-\ origin. •'>•''. ''I r-inniliraiHi'. ."i."). •''" iMiilativr II M liMiiMi piitiiii'^. sr> ll.ail. rally ilrp'i.nalr.l. fat pm-rnlaur Ml, I-' liypiiiiopliy of. ill iic|)linii^. ls« in nrplirili-. ls:i llciiliMiliainV lliiiiiA l laliiin. •"' ll.nioirliau;"- in ilitfini'raliv iii'pliriti-. s."i. !i;! ll.iiiorrlianii- ncplniti-. l'>-> llciilc. loop- of. -'S cpitlirluiiii of, :V) virws. Ill llippiirir aiiil froni sLv''"'-" ^•"'' '"■•"'"" acid in kiilniy. •!•"> Ilistoloitiial invrslinalion-. '.» llisloloay III kiilni y. -~ llisloriral riviiw. 1. -I. *1 llvaliiiili'i'lii- II' Va-.l>. ItNl I'oiislitiili'in. IIHl. HH tliroiiilii. ".I^i inin-forinalion. i:i:i. l^i^- 1 *" llvilrainia. 1'.'7 llviliaaiii.' pli'tlioia. udiina ami, lll.^ llyilroiH'pliroMs in sniili- kiiliu'V, 1T7 Hy.lrops. 19:! irritations. IIMI, li>7 224 INDKX llvpcniniia. ai live, iiitmiliii imtiiIoii hi, a; siMliiiiu rliliiriil rxiTrlicin in. -i'. ^^ iiritir sccrrliiiti in, '^7 III il((£ciiiT;ilivc cxiiilalivc iirplirilis. HM ii'clciiia :iii llyprrriiiniii'iisatiiiii, IMt lly|Mrtr<>|iliy. r;niMs, "Hi of iiKils (if :irtirii> in |irciilii(;livr iicpli- rilis, I7:t of Klniiirnili, 1 1^ (if li(':irl ill iicplirilis, 1*>4 (if tiilmli-, ITiO |\i 1 .Miniiii iiijiitiimn intii ri'iml iirlcry, wlicrc fiiiiiiil iifliT, ;i."i, M lniliir;iii(i iy:iiioti(;i rcnuin, 'Jl t Infiircts. ITii Inllaniiiiiitiiin. (■li:ira(l(Ti.':i views on, In tissue, chaiujes in. IIU Use of leriii, '2J iMieholesterin, I'Jl KM-HiisrKltlN. I'Jl Kephalin, ll<) Kidney, imatoinical changes. - anatomy of. -"^ arteriosrlerotie. 171 as lilter, ;{1 liliMid-siipply of. -*» capsule of, epithelium of, :iO Kidney clialldes, H colli ra('te(l, Hil, D'l'J cyanotic. IVI red, H>:t .s, iidary. Ill, II-'. ••'•■J pnHliictive neplirilin and, rchilions, 1(V2 cortex (if, 'J7 disease, ditiiculties of sllldyuiK, I historical review, 1 incliiiled under Urinht's diseiinc, Jl structural and functional cliaiidcx, re- lationship, 2 enlargement of, 1 M functions of, - patholoBi'al variations and, 27 vii - on, 27 (llotii 'ili "f, 2S eiHthelial linitiK of, 2!l foriiialioii, 2'> hippiiric acid formation in, :<•'> histological chann'i', 2 liiHtoloKy, 27 ill cholera, 4."i ill chroniiuiii poisintiiiK. ■♦■"> in corrosive sulilinmte poisoiiinu, •!.">, Ul, m in phosphiirus-poisoniiiK, 4."i, lit) in simple iiephriliH, 47, 4S inner part, 27 larise white, 1 l.'i, M^ lymphalics of. 2i> inedulla of, 27 extirpation of, urine secretion after, ,'iO medullary ray.s of, 'Ifi nerves of, 2!t outer part, 27 liatholottic, dilTerent from normal, 44 pelviw of, diMchar(£e of urine from \'.i in senile kidney, 177 structure, 4i< productive chaimes in, 110 pyramiils of, 2S senile, 174 struct lire, 27 synthetic processes in, :<"> lutiercles in. formation, tKl tubules of, 2H epithelial liniiiK "f. '-^< •"' l.udwijs's theory of function of, '.Vi, 3S INDEX 225 Kidnoy, iirinury clirDiMOKi'iit i". :*•'» vnMi'iiltir iipimrnliis "f, in f"lty "'nH''. \Xi Koniiiyi'fi tlicury n{ uriiir Mccrt'lioii, »•' iiriimry (|iioli(iil, H> I.AioiK wliilc kidney, ll.'i, l.VI I^..illiin, US, 11(1 l,i|Mmls US, ll'.t l,i>lil('in'~ vicwM, '.tl l,:J Meyer's views on urine secretion, W Mono-ainidi»-ili-ph<>«phatides, chemistry of, 1 lit Mono-ami(lo-mono-p'""'P''"''''''''' '••»■""»- try of, lilt Muller's views, 2(1 MiinK iiid Senator's theory of urine doore- tion, H7 Myehns, US, U'.t Nki'HKITIS depenerativa, 'i'> adiposa, -'> et exililaliva. !>:< exudativa, -'i ha'tnorrhaitiea. 2."> prolifi-ra, 2it, .V», til tin- mphrilix. et prodiictiva, .">'.), til. See also I'ro- lifemtiiv luiihritix. simplex, 24 lU Nephropatliia chronica inflammiitoria., 170 Nephroses, J.'i Nerves of kidney, 20 Nitrogen excretion in hyperu'mia, :{' in stasis, 117 Non-inflammatory proceiwes, i wroiiKl.v uroiiped a.s nephritis, 21 1 Nutritional channi's, 114 (I'.liKMA, Itil, IKl, 1S1», HCi in (h-Kcnerative extlilative nephritis, KM, is'.t irritation, l'.t7 Oleyl-li'cithin, 120 (trth's views, IS ()smoti<' prensiire of urine, Xi See also I'rnlifera- I'Al.MITVI.-l.KriTllIN, 120 I'aramyelin, chetnislry of, 11!) rarenehymutoiis and interstitial forms, (li>t- ciission, 14 deKcneration, <>4 acute, 4."i in simple nephritis, .")2 micn)Scopic appearance»i, r>2 inHammation, definition, 1^ Virchow's views, 12 nephritis, (edema in, 1S9 u.se of term, 22 ratholottical processes, channinK character of, :{ I'elvis of kiilney, discharRe of urine from, 4:{ in senile kiilney, 177 structure, 4;{ Peric;>rdiuin in nephritis, \SV.i l'eril..-mphaiiKitis in nephritis, 107, 194 reritoneuni in nephritis, 19:5 I'fister. 101 I'hosphatides. ehemi.stry of, U9 l>hospl»)ric acid, ijlyccrin, in urine, 120 rhosphonis-|M)isoninK, kidney in, 45, 116 Phrenosin, 121 l'hyto.sterin, chemistry of, 120 l'la.sina, alkalinity of, diminished, 124, 12.-> Pleura in nephritis, 191$ Productive cliandps in kidney, UO nephritis, 2.5, Itil 22(> INDKX rriHlii.iivr ll(■|l|lnll^. :ill>iiiiiiimii:i in, IV! artrriri" III. ll>7. HiM iiriirin^c lrrip»i- in. H'>'', IT I Mtlii ni-ilirii'-i- 111. It'i'.t i;i|iill:irM- in. \~i ( iinliiir li.\|MTUii|iliv ill. I VI lu^ls III. Wt r:iu«r«. I*i''» rirciilatiiiii 111. Ii>7. Iii'.t ry«l.- ill. Il'''» ciiilirtiTiii^ tilirii-:! I'l. 170 hliroii- li>-iii' prclifirtimii in. liiJ. 17>> |iiiiilic.n:il ili;ini£r-. Iti7. I>«1 llliiiiirrilli III, \*'*': l'''7 l[rll^^• :i|i|M';ir;ilii>>, Mil liviMrlriipliv cif rii:il> nf arlrrii > m. 17:! nilcnixcipir ;llipi;ir;lllir>. I''>"> piirriiclivliKitipii- lll•'^ ill. !•>■-'. 17N .Si Mii.vriN VI nrpliriii-. \'.»< .SiliTll^H. 171 riiiiiin. -'< .Si unci Irrliiri'. ■J7 liililixitrapliy <>l. .'H.'i Si-niliiliirv niiilriHii'il kii|l"\. III. II.'. I.VJ :iliatiiiiiii':il rviilrnn-. JI priHliiitivi' iii)iliriii» ;iimI. ril:iii'iii-. Hi J Srrrctlim iii»l». I'll .Siiiiliir's vicwi. \'.> llirury iif cariliin li> |.. in.pliy. IVI S.'imliir :iiiil Muiik'- lli.nrv of iiriiii' -.cr. - Hull. :I7 .Snilr kiilnry. 171 pi'lvi> in. 177 Srrnll- nirlnlirillicj' III 111 |illflll>. I'.''t Siriliii-:ill(iiiniii in iirinr. -mt MliHmiiiiinn .nnii.l.iry rMiilr:.rlr.l ki.lii.y Mii.l. H- Siinpl.' ii.lilirili-.. »•">. 4 l;ltillll>. III-.' llllllllr« ill. Itili Ul'ilir in. I'^l viiMiil:ir ili;iiii:i -. I'i7. Hill l'riii£iiii>i-. 1 1" rri«lifiT:itiiin ill I'atly ili«i'ii.r;iti(iii. I IM iif (•piihcliiiin, Mi (ll lllllllliv. l»l rnilifrniiivc ii.plinii>. -•">. '>'■>. •'>! fiincticinal cliiiiiKi-, '>:> urine ill. ti:! I'n.laBMii. 11^. U". I-I I'mluphiMii, viiws (111. ."i7 l•ykllll.-i^. '.tl I'vraiiii.l-ol' kiilmy. Jn Uavk.h's vicwf. '.I Kcnivcry. IHI, 111 Ui'cl kiiliiiy, Miiall, Hi! Krilrx llictiry of rarili:i>' liyprrtnip'iy, IsT Ucuciicraliiiii, fatty. 117 Ui'inliart > view.-. II Ki^nal arlcry. .'s iiijntions (if iiiiligci c ariiiiii iiilu, whin' fciiind after. :t.'i. :f(> .liarrliea. :«• ^^ylllptl.lll:<. \W liepair ill inllainiiiatory priiees>ef.'ls<» Hdckitaiiskv's view^., 11 alhiiininiiria in, .'>!> epitlieliiiin in, ,'>l eMiilate ill, .'ll fever urine in, ,'>1» fillietiiinal ellallKe^, *■'> ([Icinienili in, 1^, '>\ MiiiTiweiipic up|M'araliee« "f kiilney, :,\ pareneliymatiiii.* ili'Heneralimi in. -VJ pallmliiuie tii^tiiloitv. 17. J>> ti'riiiinatiiiii. -"iS lisKlle liitwei'll tllliule^ in. ."iS nilmles ill, .VJ urine in, .Ml ."icMlium eliliiriil ami water resorptiun, :iJ, :«• I'Xi-retioii in liyiieriiiiiia. :t7. :tS uileiiia ami. 1!I7 Solon's views, 11 .Sphyiinoiiiyelin, clieinislry ■ i. l I'.i Splanelinie arterioselerosis. M l-pressuri- and. IHS Stanesofilisea.se, Uri(!ht's views, li, 7 SlainiiiH aflinitiesof tiilie-ia.sts, lO'i .Sta.sis. nitroijeii exiretion in. :17 urine .secretion in, ;{7 Siilpliiiti' iiijei-tions into Mood, urine after, M Suprarenal «lan.ls, l)loi>d-pres.sure and, 11>'J .Syinptoins. I!t1* .•^yiillietie prlllf». . |mll«l- II' I'M ni f:ill\ -laK"'. I'll !i «imt>li- tit|ilirlli-, .'iS Tom, 'lic» TnynlMT- Mrtt-, 1 1 Trni-uiliili' •lyX". I"l uw i>f Irriii. I!'" ■rriiiii"!!' iiii'i'-"*'"'"'""'^ tliiiirv of mini' >>"•- IT'lil'll. '"^ 'I ii-.iiiiiilii-|«li'"'lili!i'i'i' I'" Trniilini' iiiliiiiM liiiiiK. i". ">^. '-•' liilir-iii^l- KKI r<'lliil:ii. UN) 111||1|H1-1I111I1. 1"" (traiiular. Km tiviiliiii'. M"' I'linslitiiliiiii, MNI, I'll scirotiuii. Il>l "tiiiiiiiilt iitliiiitir!". UC- transuiliili I'll waxy, m) rlitiltii>n. HI*!. 1"'- TiilM-rrlcs in kiiltu'V, fiirniiilioii. tut Tiilml" >. -!>*. ililatatioii iif. HI' (■tTr(l> nil, 111 (•iiliirncmt'iit of, \M rl.illii-liiim.if. St, :«1 nils iliTivi-(l from. <•>.• newly f(iriin- pnilifcration, !M in ilfgrnrralivr cxuilativi- ncplirilis. >X\ in fatly ili'Hi'nrralion. 14s inpnHitictivciiciilirilis, UMi in simplo iicphrili.'*, .VJ l.iKlwiu".-' ilii'ory of funiiion of, :!-', :t:{ 'I'lifl. apiM-arancfs of. Ml I rinr • xannnatii.ii. rarly. I fiMT, in -iiiipli' niplini)-, .V.» fni/inii-pi'iiil >'f. -t'l uly.rrih pdo^pliorir anil m l',ill in ili'urncraliM' ixu.laliM n.phriii- KIH in f.i'lv -laili- IVi in iirixImliM' mpliri'i". 1^1 in prolifiraiiM' mpliritif., •■>;( in -iinpii- iiiplinli!', 'I't III villous -ta«i», I'i'i. I"'» iif ihaliili" iii-ipiil'i-. !'• ii.MlotIr |»rrn»liri- ol, -l-l ^IMTI'IlMll. •" afirr ixiirpation of iiiiiinlla, :i'.i afliT iiijcrlioii- iiilo IiIoimI of siMliiiin -iilphali'. •!"• Xsliir's theory, -i'* liliHMl-prissiire ami, M Hownian'.-i theory, M filter theory, :U lleiileliliain's theory. :!."> in hypera'inia, ■!" in .stasis, it" Koninyi'.s theory, 40 laiilwiuV theory, M, 'H Meyer's views, 40 Senator ami Miink's ihi-ory, HT suininary of views, II Iriiimuihition-seiTelory llii-ory, :i.H views on, it! water in lilooil ami. :V_' V.\!< efferells. Jit Va.seiilar apparatus in fatly staiie, I.IH in priHluitive nephritis, lt>7, ItlH Venous stasis, 1,')4, 11»7 Virehow on paretiehyinatous iiiftammation, \2 Viseeral changes, llil, ISil Watkh anil soiliiini ehloriil resorption, :VJ, :«i luKTKH, iliseharije of urine into, 4:i St met lire of, 4:5 Iriniirv ehmmoftcns, formation in kiilney, "■';'"''""'"•/-,„, .,., by tubules. .12, -t-t ' '.■ . ,,\ Waxv ca-sts. UK) niiotient. 40 ■ , ,,, ,,^, Irinr, rrvoseopy of, lU . constitution, 1(X), UYI .liseharge from l«.lvis, Vi ^^ '-'K'-f' >< ^"•"■^' ' '