THE LIBRARY OF THE UNIVERSITY OF CALIFORNIA LOS ANGELES GIFT OF SAN FRANCISCO COUNTY MEDICAL SOCIETY THE NEW SYDENHAM SOCIETY. INSTITUTED MDCCCLVIII. VOLUME LIV. A MANUAL PATHOLOGICAL HISTOLOGY TO SERVE AS AN IXTEODUCTION TO THE STUDY OF MORBID ANATOMY. DR. EDUARD RINDFLEISCH, PEOFESSOB OF PATHOLOGICAL AXATOMY IN THE UXIVEESITy OF BOlflT. VOLUME I. TEAXSLATED BY E. BUCHANAN BAXTER, M.D., Lond., MEMBEE or THE EOTAL COLLEGE OF PHYSICIANS; HONOEAEY FELLOW OP KIITG's COLLEGE, LONDON ; IIEDICAL TUTOB IN KING'S COLLEGE ; AND PHYSICIAN TO OCT-PATIEKTS AT THE EVELINA HOSPITAL FOE SICK CHILDEBN. THE NEW SYDENHAM SOCIETY, LONDON. MDCCCLXXII. 577 Lo>-DO>' : Printei by W. Clixksk-el, at Eastcheap Printing Works. ^1 XOTICE TO THE EEADEE Tke following translation has been executed from the second V German edition ; those who may compare it with the original will ^ notice that the latter half of § 24 is entirely altered, while an important addition has been made to § 481. These changes >^ were introduced by the author's desire. The second volume ' •"•^ "^ is in the hands of the printer. ,V ^ The translator has to thank Mr. Nettleship for readnig ^ fhv Q PQ through the first twenty sheets as they were passing through the press. King's College, London, ^0 Juhj, 1872. 3 ^ ^ 593153 r>l„C-c-.Ve AUTHOE'S PEEFACE TO THE FIEST EDITION, In offering a new text-book to the student -youth of Germany, 1 feel obHged to say a few words about its contents, and the main principles by which I have been guided in its composition. Pathological Anatomy is one of the youngest branches of Medicine. It was founded by Morgagm in his great work : De sedihus et caussis morhorum 'per anatomen indagatis (Veiiet. 1761). It was elaborated by its founder and his immediate successors [represented in Germany by Johann. Fr. Mechel {Handhuch der Patliolog. Anatamie^ Halle, 1804-5), Otto, and others], in entire accordance with the methods of normal descriptive anatomy. During the first thirty years of the present century, it came to comprise a summary of the general alterations to which the various organs of the body are liable in disease ; alterations in form, size, number, consistency, continuity, position, relations, colour, and contents. Micro- scopical investigation, which supplemented the anatomy of Vesalius by normal histology, had necessarily to confer a like benefit on pathological anatomy. RoJdtanshi and Virchow have rendered undying services to our science as the founders of pathological histology. It soon appeared, however, that j^atho- logical histology was destined to stand in a relation to morbid anatomy, very different from that of normal histolog}- in re- ference to normal anatomy. Pathological histology shows us how the coarser alterations in the size, consistency, colour, &c., of organs, are based upon certain definite changes in their structural elements; it explains the former by means of the latter. As time wore on, it took its place, not merely as an authoe's preface to the first edition, vii integral constituent, but as the true centre of the entire domain of pathological morphology. The following treatise was under- taken from this point of view ; attention has accordingly been directed to the pathological histology in the first place, while the coarser data of morbid anatomy are relegated to the second. For the benefit of my colleagues, I may add that this book was written in the laboratory rather than in the study. The number of original investigations which it embodies, must serve to atone for the absence of an exhaustive and uniform treat- ment of individual topics. AUTHOE'S DEDICATION TO THEODOR BILLROTH {Standing In lieu of Treface to the Second Edition). My dear Friend, I very much regret that I was away from home a few weeks ago, when you paid me the visit to which I had long been looking forward. I should have keenly enjoyed discuss- in o- with vou the frreat events of this most memorable time, and talking over the little difficulties which beset the author of a hand-book of Pathological Histology, when he desires to keep pace with current discovery. It is a hard thing to play the part of architect to a building, the materials for which exist only as a heap of stones, more or less roughly hewn ; but for which no general plan has been laid down. One has to build in continual peril of having to pnll down remorselessly to-day, what seemed ]3nt yesterday to be solid and enduring. Compare the section dealing with Morbid Growth in this second edition, with the same section in the first ; not one stone has been left upon another. For this we have to thank Billroth, Cohilteim, Thiersch j Walde^/er, Strieker, Koster, and many others. And how long may we expect the present edifice to last ? As you know, I am the last man to complain of this. But I should have good reason for complaint, were any one, in looking over this book some years hence, to forget that the views laid down in it were the views of the author in October, 1870. This has been done by some critics of my first edition. On more than one occasion, I have been pained to find myself regarded as '^ older" than I really was, by a vigorous and energetic youth. I own that author's dedicatio:n^. ix T have myself to thank for some part of this annoyance, inasmuch as I have published but little beyond the present hanl-book, daring the last few years ; I found it more con- venient to incorporate the results of my work — so far as they were worthy of such incorporation — into the new edition of the hand-book, than to print them separately. I would therefore ask you to bear this bad habit of your friend in mind, while reading this new edition which belongs to you, and to judge what I have written, with indulgence. EINDFLEISCH. Bonn, 1st Novemher, 1870. CONTENTS OP VOL. I. Page Inteodtjctio>' 1 GENERAL PART. I. THE EETROaEADE METAMOEPHOSIS AIsD DEGENEEA- TION OF TISSUES 3 1. Neceosis ... 3 2. CoNDiTio>'s OF Intolutio^- 19 a. Fatty Degeneration 19 b. Cloudy Swelling ... ... ... ... ... ••• 29 c. Mucous Softening 30 d. Colloid Degeneration 39 3. Conditions of Infilteation 41 a. Amyloid Infiltration 43 b. Calcification 48 c. Pigmentation 56 d. Fatty Infiltration 64 IT. MOEBID GEOWTH (INCLUDING INFLAMMATION) ... 68 1. Geneeal Consideeations 68 2. On Noemal as a type of Moebid Geowth .., 87 3. PEODrcTS OF Moebid Geowth deeited exclusively rEO^i THE INTEEMEDIATE ApPAEATUS OF NlTTEITinN 110 1. Interstitial Inflammation 110 a. Eesolution 114 CONTENTS. xi b. Organisation 115 c. Suppuration 118 d. Organisation after Suppuration 122 2. Non-inflammatory overgrowth of the Connective Tissue ... 129 3. Specific Inflammations (Syphilis, Leprosy, Glanders, Typhus, Tubercle, &c.) 130 4. Hi stioid Tumours 142 a. Sarcomata 146 The Granulation-like Eound-Cell Sarcoma 148 The Lymphadenoid Round-Cell Sarcoma (including varieties) 149 The Alveolar or Medullary Eound-Cell Sarcoma (in- cluding Melanotic Cancer) 152 The Small-Celled Spindle-Cell Sarcoma 154 The Large-Celled Spindle-Cell Sarcoma 15G The Pigmentary or Melanotic Sarcoma 157 The Fibroid 160 The Cavernous Tumour 162 b. Lipomata ... ... ... ... ... ... 168 c. Enchondromata ... ... ... ... ... ... 170 d. Myxomata 175 e. Osteomata 177 f. Myomata 177 g. Neuromata 178 h. Compound Histioid Tumours 179 4. MoEBiD Geowths due to AbjS'oemalities of Epithelial Development, whether intolying the Conjoint Blood- Vasculae and Connectite-Tissue System, oe not ... 179 1. Glandular Carcinomata .., 183 Soft Cancer 185 Telangiectatic Cancer... ... ... ... ... ... 188 Sarcomatous Cancer 190 Hard Cancer 191 Colloid Cancer ... 195 2. Epithelial Carcinomata... ... ... ... ... ... 195 Squamous Epithelioma 198 Columnar Epithelioma ... ... ... ... ... 206 Appendix. Cylindroma 209 511 CONTENTS. SPECIAL PAET. I. ilOEBID STATES OF THE BLOOD AND THE ORGAXS CONCERNED IN ITS RENEWAL, PARTICULARLY THE SPLEEN AND LYlilPHATIC GLANDS a. DjscrasicD (Chlorosis, Leukhsemia, Melancemi:}) b. Coagulation of Blood in the Vessels c. Inflammation and Tumours Pace 211 211 221 II. MORBID ANATOMY OF THE CIRCULATORY APPARATUS 214 1. Diseases OF Aeteeie3 A^'D Teln'S ... 244 a. Inflammation ... ... ... ... ... ... ... 24S a. Acute 248 fS. Chronic 250 b. Dilatation of the Vessels ... ... ... ... ... 258 a. Of the Arteries — Aneurism ... ... ... ... 258 y5. Of the Veins— Phlebectasy 2G3 y. Of the Capillaries — Telangiectasis ... ... ... 260 2. Diseases or THE Heaet 267 a. Myocardium ... 2G0 a. Hypertrophy 269 (3. Atrophy 272 y. Inflammation ... ... ... ... ... ... 275 8. Abscess of the Heart 276 e. Heteroplastic Tumours of the Heart .. ... ... 278 b. Endocardium 279 a. Acute Endocarditis ... ... ... ... ... 279 /?. Valvular Aneurism ... ... ... ... ... 2S2 y. Perforation of Valves 2S3 S. Chronic Endocarditis ... ... ... ... ... 286 e. Valvular Defects 2S7 C Fibroid Patch and Partial Aneurism of the Heart ... 292 7], Thrombosis of the Heart — Polypi ... ... ... 294 3. C0^'GE^'ITAL MALE0EMATI0^'5 OF THE ClECULATOEY APPAEATUS 296 in. MORBID ANATOMY OF THE SEROUS MEMBRANES ... 302 a. Inflammation ... ... ... ... ... ... ... St'S b. Non-inflammatory Formations ... ... ... ... 327 CONTENTS. xiii Page lY. MOEBID ANATOMY OF THE SEIN 33i 1. Diseases op the Epideemis akd the Papillaet Eodt ... 334> a. Inflammation 234< 1. The Erythematous Exanthem 2. The Papular Exanthem 3. The Wheal ^^^ 4. The Yesicular or Bullous Exanthem 342 5. The Pustular Exanthem 344 6. The Squamous Exanthem b. Hypertrophy c. Heteroplastic Grrowihs 2. Diseases of the CoEiuii and Subcutaneous Aeeolae Tissue a. Inflammation b. Hypertrophy c. Heteroplastic Growths 3. Diseases or the Haie -Follicles akd Sebaceous Glands ... 387 1. Eetention of Secretions 337 2. Inflammation ^^^ 3. Hypertrophy ^^^ 4. Heteroplastic Tumours 5. Atrox^hy Y. MOEBID ANATOMY OF MUCOUS MEMBEANES a. Inflam^iation 1. Catarrhal Inflammation c. Specieic Inflammation 1. Typhus 2. Tuberculosis d. TUMOUES 1. Papillomata 2. Carcinomata 339 340 355 35G 3G9 37G 3S2 398 402 403 405 405 2. Croupous Inflammation ^-^ 3. Diphtheriticlnflammation 5. H^:^0EEnAGE 431 433 438 43S 445 453 453 455 INTEODIJCTION. § 1. Everything that lives is subject to perpetual destruction and renewal of its constituent elements. These changes are inferred from observation; we mark the continual adoption of certain substances into the organism, and the excretion of others in proportionate quantity ; these others being demonstrably pro- duced by the metamorphosis of the living substance. § 2. The human eye, even when armed with the highest magnifying powers, cannot detect this molecular activity of matter. It becomes apparent to our senses only when it is dis- turbed, whether in a plus or minus direction. Who can see the nutritive processes taking place in the fibres of striped muscle in the tail of a living tadpole, or note the silent coming and going of matter in a neighbouring connective tissue corpuscle ? So long as these structures continue to exhibit, even to the smallest dot and line, a certain definite and familiar aspect, we hold this "morphological permanence" to be a proof that the metamor2:»hoses associated with nutrition are progressing undis- turbed. It is only when we discover some qualitative change in the cells or other elementary parts of the organism, that we are made aware of some past or present change in their constitution, and incline with reason to the belief that such chanoje is due to some alteration in the nutritive process. § 3. Changes of this kind occur even in the normal course of life. The age of the body, its gradual growth and decay, are to some extent reflected in the condition of the tissues. We must distinguish vi limine between two leading tendencies, under which all tissue changes may be grouped ; these are, development and retrograde metamorphosis. The former teaches us to trace the origin and growth of the entire organism from the repeated multiplication and manifold differentiation of the cell ; the latter shows us that the infirmities and the frailty of the body as it 1 2 INTRODUCTION. grows old are associated with a more or less striking decom- position of its tissue elements. § 4. Those alterations in the tissues which occur during disease are of far greater moment to the physician. They are })recisely similar to those which occur as a consequence of age. Not w^ithout reason has Virchoiv compared the retrogressive pro- cesses of disease w^ith a kind of premature old age. The ex- istence of the individual cell, like that of the organism in its entirety, must oscillate between birth and death. We must therefore regard development and decay as the main categories under which all moi-bid tissue changes naturally fall. But it would be unfair to omit all mention of the fact that the histolo- gical phenomena in the domain of pathology are far more various than those attending the normal course of growth and decay. § 5. Nearly every disease which is accompanied by ana- tomical lesions exhibits a complex co-existence and succession of progressive and retrograde processes. To these, taken together, the naked-eye appearances of a diseased lung or liver are due. Our task in the first part of this treatise will be to disentangle the threads of this complicated web, and to examine each of the progressive and retrograde processes singly and from ever}- point of view, so that, in the second part, we may be able to construct the morbid anatomy of particular diseases out of elements which are already familiar. GENERAL CONSIDERATIONS. T. THE EETKOGRADE METAMORPHOSIS AXD DEGENERATION OF TISSUES.* § (). The alterations to be considered in tlie first di^'ision of this work have this feature in common, that the tissues which •exhibit them have lost the wliole or a part of their significance as livino; and functionallv active constituents of the or onanism. The degree of this loss is different in each case. Some lead at worst to a certain limited, though perhaps very considerable, impairment of vitality, as, c.fj. amyloid degeneration and calci- fication; others again, as, e.g. fatty metamorphosis, cause a gradual but complete destruction of the independent life of the affected tissue ; under this head, too, we may include necrosis itself — i.e. the case in Avhich death precedes, instead of following, the structural change. AYe will begin with the last-named process. 1. Necrosis. § 7. No sooner does that peculiar inter-dependence and mutual connexion of the component parts of the human organ- * Nature begins lier labours with construction; we adopt the inverse •order, taking first the decomposition of structures ah'cadj formed. This is done for convenience sake. The reader is supposed to be famihar with normal histology, with the materials on which the processes of destruction and dissolution are exerted ; and, so far, it would seem to be indifferent whether we choose to start from the progressive or the retro- gressive series. Inasmuch, however, as we shall have to describe the histological phenomena exhibited by morbid growths, such as cancer, throughout their entire course, a previous acquaintance with many processes belonging to the retrogressive series, such as fatty degenera- tion, caseation, &c., is indispensably necessary. 4 NECROSIS OF TISSUES. ism wliicli results from their genetic unity, and which we call life, come to an end, than external influences assume a dominion over the body similar to that which they exert over inorganic substances ; in other words, the only force which still tends to maintain the body in its previous form is the force of cohesion. Owing, however, to the great proportion of water which enters into the composition of the body, this force operates but feebly ; hence death is closely followed by disintegration, which, though at first gradual, proceeds at an accelerating rate until dissolution is complete. So long as the body retains to some extent its out- ward form, we continue to speak of it as " dead."* § 8. In presence of somatic death the art of the physician is powerless. We might spare ourselves the trouble of studying the changes which accompany the death of the tissues, were it not that single portions of the organism are liable to die, an occurrence which we call necrosis, mortification, or gangrene. § 9. The death of a part is not always followed by the same series of anatomical changes. The variety of the causes which may lead to necrosis, as well as the situation and individual constitution of the necrosed parts, occasion very marked differ- ences, particularly as regards the proportionate amount of blood and water present, which have led to the recognition of two forms of gangrene, the dry and the moist. In the ensuing sections this distinction will be home in mind ; it will be shown, however, that the distinction is based rather on the clinical characters and coarser features of the process than on its finer anatomy. Note. — A large majority of the various forms of mortification may be looked upon as due to a complete arrest of nutrition. Among the chief conditions of undisturbed nutrition, a regular and continuous supply of blood takes the foremost place. If, therefore, the quantity of arterial blood which passes through any region of the body (thereby becoming venous) in a unit of time should sink below the normal standard, the nutrition of that region must needs suffer; should the current entirely cease, nutrition must cease with it. The affected part may nevertheless contain an excess of blood ; and this may be so great * Inorganic nature, into whose domain the constituents of the organism now return, is also called "dead"; but here the term is used metaphorically. In common language, the word "dead" implies that a body, though still exhibiting the organic type of structure, is no longer the seat of the organic functions. NECflOSIS OF TISSUES. 5 as to give the part a dark purple or livid hue. In such a case, the microscope shows us an extraordinary turgidity of the capillary vessels, associated with minute extravasations scattered throughout the paren- chyma ; in the smaller veins, which are also gorged with blood, we find blood corpuscles, solitary or in rows, intercalated between the layers of which their walls consist. On inquiring into the cause of such a disturbance of the circulation, we commonly find that the obstacle is situated in the aSerent arteries of the part. In a future page, those diseases of the vessels will have to be specially considered, which may give rise either to simple plugging (thrombosis, embolism) or to gradual contraction of the calibre of a vessel, or finally to a condition of its walls which so exhausts the vis a tergo of the heart in the larger arterial trunks that it sinks to a mere nothing in the extremities. {Special Parf, Chap. II.). Enfeeblement of the heart's contractions, consequent upon disease of its muscular substance, or due to general debility, such as follows typhus fever, is also capable of disturbing the circulation in the peripheral parts of the body to such an extent as to cause mortification. Senile gangrene, which affects the toes, feet, and legs as far up as the knees, is commonly caused by the co-operation of both causes, i.e. by changes taking jDlace in the muscular walls of the heart, together with disease of the vessels. Compression of the arteries {e.g. by tumours from without) must naturally exert a like unfavourable influence upon the circulation within the area of their distribution. Tonic spasm of its muscular coat very rarely contracts the tube of an afferent artery so far as to check the flow of blood through it. Yet gangrene of the extremities, following the consumption of large quantities of ergotized grain, is believed to be due to this cause. The stoppage of the blood current may also occur in the capillaries themselves. The most interesting example of this is when the capillaries of a part are compressed by exudation or morbid growth in its paren- chyma. So in diphtheritic inflammation, an exudation into the substance of a mucous membrane, or of the skin, causes death and sloughing of the part. Moreover, most of the necroses (so-called KaTk^o^qv) of the osseous system come under this head; collections of pus jjetween the periosteum and the bone, due to periostitis, compress the nutrient arteries which pass from the former to the latter, and so deprive the outermost layers of the bone of their supply of pabulum. The formation of pus in the Haversian canals will lead in like manner to squeezing of vessels and death of corresponding portions of bone tissue (caries). It need hardly be added that in these cases no con- gestion of the necrosed part can possiblj^ occur; on the contrary, we may invariably expect to find a marked degree of anaemia. An obstacle to the escape of blood through the veins rarely causes gangrene. For, to produce gangrene, it seems that the arrest must be complete; and this condition is hardly ever realised. At least we often see thrombosis of all the greater veins of the thigh after pregnancy, without its being followed by gangrene of the leg. Indeed, there is only one case whicli comes under this head, viz. when a part is jammed into a dispropor- 6 XECEOSIS OF TISSUES. tionately narrow and unyielding opening, as, e.g. a knuckle of bowel in the neck of a hernial sac. In this case, the pelding walls of the veins undergo compression before the arteries, and so the return of blood may have ceased long before its afflux is at all interfered with. We may accordingly expect to find the mortified part greatly congested. All the above causes of necrosis agree in making an arrest of the normal flow of blood through a parb the proximate antecedent of the arrest of its nutrition and its life. But nutrition may also be disturbed, apart from any interference with the circulation, in the islets of paren- chyma which are included in the meshes of the capillary network. Xearly all such troubles, however, are developed gradually ; the tissue changes to which they give rise contrast with the necrotic processes in the slowness with which life is extinguished. They will form the sub- ject of succeeding chapters. The only true necroses which come under this head are those involving organs, which, like the cartilages and the cornea, are absolutely non-vasoular, when these are wholly sejDarated from their connexion with neighbouring parts by suppuration. The circulation through those vessels which formerly supjDlied the organs with nutrient matter is not arrested ; it is only that transit of pabu- lum from cell to cell, on which both cartilage and cornea depend for their nutrition, which is brought to a stop. 'Eo allusion has yet been made to those cases of necrosis in whicli the death of a part is caused by chemical or mechanical agents operating from without, as, e.g. crushing, concussion, desiccation, corrosion, and septic poisons. In these cases, we have to do with violent disturbances of molecular arrangement which are incompatible with the continuance of vital activity in any form. § 10. A striking pecnliarity of living tissues is their ])Ower of retaining their form and characters in fluids capable of dis- solvino; albuminous substances and their derivatives. Hence it is a sure sign of death \vhen the tissues are no longer able tc) -withstand the solvent action of such fluids. Tliis feature is common to all o'^noTcnous chano;es, and it is one which is early recognisable ; the dead part loses its normal elasticity, its tiur/or rifalis ; it becomes flabby, soft, and doughy. Now, if a too rapid evaporation from the surface of the mortified pai't is pre- vented (and this office is performed by the cuticle, when present), we find that the 81 per cent, of water contained in the normal organism, together with the water which is set free on the spot by the very act of decomposition, is amply sufficient to dissohe all the solids of the body with the exception of the bones. AVo already know, moreover, that in most cases of gangrene the vessels of the mortified part are unusually gorged with blood. NECROSIS OF TISSUES. 7 Now, the blood contains more water than any other tissue of the body. Hence the mortified part will contain more than its duo proportion of water, at the expense of the healthy tissues ; it is therefore all the more able to undergo solution in its own fluids. The remaining naked-eye appearances are also due to this excess of blood. For, soon after death, the colouring matter of the blood deserts the corpuscles, and stains, first the serum, and next all those tissues which are naturally either colourless or nearly so. It saturates the walls of the vessels and the lax con- nective tissue round them, so that the course of the veins may be traced by the purple streaks and patches to which the livid marbling of the skin in gangrene of external parts is due. Finally, every part becomes equally saturated with blood, the fat of the 2'><^'-nniculus adiposus not excepted. In external parts, the reddish serum makes its way to the surface of the cutis. Tlio previous disintegration of the rete Malpighii favours a loosening of the impermeable cuticle, so that the accumulation of serum may occasionally lead to the production of what are known as gangrenous blebs ; more commonly, however, it simply strips off the cuticle in large shreds. In the latter event, unless evapora- tion be otherwise checked, a rapid desiccation of the most super- ficial parts — of those which are open to the air — takes place. Impregnated as they are with blood pigment, they present, when dried, a very dark, nearly black colour (Grangraena sicca; mummification.) Putrefactive changes are temporarily arrested wherever desiccation has occurred. Desiccation, therefore, is at once a means of killing living parts, as we see whenever a scab is formed, and of protecting parts already dead from further decay. The following statements, therefore, concerning gan- grenous changes in tissue, are all conditional on the presence of water in sufficient quantity for the solution of the parts ; they apply, therefore, to gangrene of internal parts, and to that of external parts, in so far as these are not exposed to desic- cation. § 11. The blood is the first of the tissues to undergo decom- position. A few Avords are enough to describe the morphological phenomena of the process. I have already said that the blood pigment forsakes the corpuscles and is gradually imbibed by all the tissues of the mortified part. We shall have to trace its 8 NECKOSIS OF TISSUES. Fig. 1. farther destiny liercafter. The colourless protoplasm swells up moderately and ceases to be visible. In a short time not a single unaltered blood corpuscle can be found.* In certain exceptional cases we may find blood corpuscles of an intense brown tint aggregated together in masses of variable size, even in advanced stages of mortification. The edges of such masses are almost always scalloped (fig. 1, «) ; the outermost layer of corpuscles is seen breaking up into minute coloured granules; and this mode of decomposition may be re- o-arded as the ultimate fate of all. § 12. Changes taking place in NUCLEATED CELLS constitute a second group of the phenomena incident to necrosis. We may start with the general proposition that the death of a lump of nucleated protoplasm is followed by its speedy dissolu- tion. Its disintegration is ushered in, and in some measm-e facilitated, by a phenomenon which we have Ions: recomiised in the fibres of striped muscle as " rigor mortis," and which consists essentially in a coagulation of those semi-fluid, viscid, albuminous matters in which all the formed constituents of the cell — (in the present case the nucleus and protoplasmic granules) — are embedded. Gangrenous disintegration of the tissues, a. Masses of aggregated blood cor- puscles ; h. Fibres of un- striped muscle; c. Fibres of striped muscle; d. Their break-up into Bowman's fllSCSj ■axnj' * It has been experimentally shown by Alexander Schnidt that in a ayer of blood barely a line thick, which is in contact with air, but not allowed to evaporate, the blood corpuscles soon disappear; in dogs' blood this takes from fifteen to eighteen hours, in horses' blood about three days, in ox blood, however, not less than eight or ten days. The blood first assumes a lake tint ; we then (in the blood of the dog) see the blood corpuscles first losing colour, then changing form, and appearing more numerous by isolation. The decolorised discs are then wholly dissolved. The decolorisation of the corpuscles, the passage of the colouring matter into the serum, and the solution of the colourless stroma, are all results of oxidation. {A. Schmidt, " Minor Researches in Physiological Chemistry." Virclww^s ArcMv, xxix.) NECROSIS OF TISSUES. 9 By tills coagulation tlie protoplasm is rendered incapable of movement; it stiffens in an attitude which corresponds to the "quiescent state" of the cell; the granules, too, which may previously have exhibited some sort of molecular movement, become stationary ; the whole structure puts on a dull and dusty look,* finally breaking up into granules of large relative size, which then shrink and disappear. The nucleus, which was at first rendered more distinct, also falls a prey to this disintegra- tion. § 13. The course of events is naturally modified in accordance with the previous physiological development of the cells. Our de- scription is unconditionally applicable to the cells of the connective tissue, of the rete Malpighii, and of those deeper layers of other epithelial membranes which correspond in position to the rete ; also to the secreting cells of glands, and to lymph corpuscles. But the limitary membrane with which the older epithelial cells are furnished offers a strenuous resistance to the solvent process. Hence these cells retain their form long after their nucleus and their protoplasm (here = cell-contents) have been broken up into granules ; so that epithelium cells, destitute of nuclei, are con- stantly to be met with in mortified parts. In this respect the cells of the epidermis take a foremost place; the duration of their resistance to the necrotic process being proportionate to the deofree of their cornification.t § 14. The FIBRES OF UNSTRIPED MUSCLE, tliough not endowed with a limitary membrane, retain their peculiar aspect for a com- paratively long time ; their nuclei are often only to be traced by an elongated mass of dots, while their marginal outlines are still as distinct as ever. The phenomena of rigor mortis have been but little studied in the contractile substance of unstriped * KiUuie failed to observe this change in the cells of the areolar con- nective tissue, but he saw it in the corneal corpuscles of the frog. ( W. Killine, " Researches on Protoplasm and Contractility." Leipzig, Engel- mann, pp. 121-130.) t We must bear in mind, however, that cornification is itself a gradual transition from life to death. I may add, by the way, that during cornification a shrinking and final disappearance of the nucleus may also be observed. 10 NECROSIS or TISSl'ES. muscle. Our ouly data on this subject are those given by Heidenhain.* He describes certain plicnomena of coagulation in the fibres of unstriped muscle, occurring from sixteen to eighteen hours after death. The cells first assume a granular or sandy aspect, due to the presence of a countless number of minute, dark, punctiform bodies throughout tlieir contents. These molecules, "Nvhich are too small to be measured, unite to form shaded figures of an irregular outline, ^vhicli in their turn coalesce to form coarser, highly refracting, elongated, straight or curved particles, embedded in a residual substance of greater transparency. These particles ai'e sometimes irregularly distributed throughout the cell, sometimes disposed with tolerable regularity in transverse lines equidistant from one another, giving the cell a coarsely striated apj)earance (fig. 1, ^>). I can confirm these statements from obsen'ations of my own. This mode of decomposition may constantly be observed in cases of so-called softening of the stomach ; a tumefaction and solution of the gastric walls, formerly regarded as due to disease, but which is now known to be of post-mortem origin {Elsdsser — fig. 1, h). The altered mus- cular fibres are farther destined to be converted into a viscid, mucoid substance, in which, however, the dot-like bodies de- scribed above lono; continue to be visible. § 15. "The phenomena of necrotisation in the fibres of striped MUSCLE are far more complex than those which have just been described. This is a fit occasion for discussing the phenomena of rio-or mortis in o^reater detail. From twelve to fourteen hours after death, all bodies, with the exception of those killed b}' charcoal fumes, sulphuretted hydrogen, or lightning, or which have suc- cumbed to putrid fevers and the exhaustion of lingering maladies, pass into a peculiar state of rigidity which lasts for about twenty- four hours, and which resolves itself, on closer investigation, into a well-marked shortening, thickening, and stiffening of the voluntary muscles. We find a like state of the muscles in limbs whose blood supply has been very suddenly cut off"; and we can induce it experimentally, not only by cutting off" the supply of blood, but also by the application of heat and cold, by over- * Heidenhaiu, " Coagulation of the Contents of the Contractile Fibre Cells after Death." (Researches in the Physiological Institute at Breslau, i. 199.) NECROSIS OF TISSUES. 11 exertion, mechanical violence, and chemical agents, and most rapidly of all, by means of distilled Avater. Nmnerons researches, the latest and most exhaustive of which we owe to TT". Kiiluie {I. c), render it certain that this rigidity of the muscular fibres is immediately due to the precipitation of a solid albuminous constituent from the muscular fluid. This muscle clot (myosin of Kiilme) forms a white and not very transparent mass, and so causes marked opalescence of those muscles which are in a state of rigor mortis, complicated, moreover, by a shade of brown. ^ow, although rigor mortis is the first step towards death, it is a step which is not irretrievable. It is quite possible to throw a fro2;'s leo' into a state of rigor mortis bv tyincr the afferent vessels, and then to watch it resume its normal condition on removal of the ligature. Should the case be one of per- manent death of the muscular fibre, the rigidity is followed by decomposition. The naked-eye phenomena of this farther change are, first, the fading of the bright red colour of the muscular tissue, which is rej^laced by a dirty red, or yellowish grey tint, unless it happen to be saturated Avith dissolved ha^matin ;. secondly, the cohesion of the muscle is impaired to such an extent that it finally becomes converted either into a greasy, jelly-like mass, in Avhicli no trace of its former fibrous structure can be detected, or into an easily torn, dirty grey, tindery sub- stance, in wdiicli some indications of longitudinal striation are still to be found. The microscopic appearances are even more constant. The transverse stride and nuclei are masked by a cloud of minute dark specks ; oil globules, and granules of reddish pigment appear partly within, partly outside, of the con- tractile substance ; the latter is torn across at intervals ; the framnents melt aw\ay from their edo-es to their centre ; the sarco- lemma holds out longest, and when it finally succumbs to the common fate, it contains only a few small, shapeless fragments of its former contents, which mingle with the rest of the cUbris (%. 1, c).- * Fall' states {Gentralhlatf, 1866, p. 434) that the transverse strire approach nearer to each other before they are swallowed up in the cloud of grannies, and that the complete solution of the fibres is not infre- quently preceded by a longitudinal splitting of the contractile substance. 12 NECROSIS OF TISSUES. It is only when the above mentioned jelly-like condition of the decaying fibres is especially well marked that w^e may expect to find the manner of their dissolution somewhat modified. It was in a case of fairlv circumscribed (Tano-rene of half the foot, due to frost-bite, that I first noticed that condition, and with it a break-up of the fibres into Bowanan's discs ; since then I have had an opportunity of confirming my original observation (fig. i,d). § 16. Nothing is at present known about the necrosis of NERVE- CELLS, and very little about that of the peripheric nerve- fibres. We know that the thicker nerve-trunks maintain them- selves in the interior of gangrenous parts for a relatively long time, while, on the other hand, their finer branches undergo very rapid decomposition. It is probable, from the analogy of rigor mortis, that a coagulation of the medullary substance precedes any farther changes. Accordingly the fluid matter between the axis cylinder and the neurilemma, which is normally quite homo- geneous, runs together to form globules of various sizes, which are separated by a clear fluid. The dark and wavy outlines of these drops impart a highly irregular aspect to the entire fibre (fig. 8, a), which has not inaptly been compared to the spiral curls of smoke from a pipe. We are still ignorant of the chemistry of the phenomenon ; wx do not know whether the drops of myelin (VircJioiv) are to be viewed as a deposit from the medullary substance, or merely as a change in its mode of grouping,* the observation itself being as old as Leeuwenhoeh The farther progress of putrefiiction is indicated by a general tumefaction of the nerve-trunk, in consequence of which the individual fibres grow very dim and the neurilemma indistinct, while the axis cylinder entirely disappears. Complete liquefac- tion occurs at some points sooner than at others ; this gives the fibres a vai'icose aj^pearance, like that presented by the fibres of voluntary muscle shortly before their complete disintegration. § 17. The adipose tissue plays a far more important part in the course of mortification. The liquid oil readily escapes from * G. Walter suggests (in Virclwiv's ArcTiiv, xx. 426) that a coagulation of the albuminoid substances present in the medullary sheath may cause the separation of the oily matters soluble in ether, the latter uniting to form globules of appreciable size. NECROSIS OF TISSUES. 13 the cells wliich normally contain it; tlie liberated oil globules coalesce to form larger drops, giving the sanies gangrcenosa (§ 22) the peculiar aspect of an emulsion, and permeating all the mor- tified tissues so thoroughly, tliat it becomes very difficult to get a specimen all whose chinks and crevices are not occupied by a countless multitude of oil globules. If we bring the adipose tissue itself under the microscope, we hardly see a single fat-cell which still retains its normal amount of oil ; it must, however, be added that it is equally hard to find one which has parted with the whole of its contents. The contained oil globules are mostly reduced to half their usual size ; they are often broken up into smaller globules. This residual oil is peculiarly prone to imbibe hsematin, so that not only the cell membranes and the lax connective tissue between the clusters of fat-cells, but the entire pamiiculus adijwsus becomes stained of a red, or reddish yellow colour. Crystals may form in the interior of the cells ; but they are far more often to be found in the oil which has been set free ; hence they are a constant ingre- dient of the gangrenous sanies (see § 23). § 18. The first change exhibited by the fibres of the loose COXXECTIVE TISSUE is a simple swelling. Tliis does not add to their transpai'ency, like the swelling caused by acetic acid ; on the contrary they become more opaque, and refi'act light more highly. Tliis change is usually associated with the imbibition of blood pigment, alluded to above, the depth of colour produced varying inversely as the amount of water present. For it need hardly be explained that the degree of swelling is exactly pro- portionate to the quantity of water in the tissue. The evaporation and re-absorption of the fluid from the parenchyma are at once announced by a corresponding desiccation of the fibrillar of the connective tissue. The coal-black substance into which the cutis is converted by dry gangrene exhibits, in fine sections, a ruby- red colour by transmitted light. Should the fibres continue to swell, they become granular, their outlines wax indistinct, and they finally melt away into a turbid slime. § 19. The formed constituents of the connective tissue offer a far more vigorous resistance than its basis substance. I refer less to the glassy, homogeneous membranes (capillaries, tunicas pro- pria?, basement membranes), concerning whose fate during mor- 14 NECROSIS OF TISSUES. iificatlon we possess no reliable data, than to the fibres and NETWORKS OF ELASTIC TISSUE. Their notoi'ious indifference to cliemical reagents of all sorts is equally shown towards the feebler agencies at work during mortification. The physician <3onfidently anticipates that pulmonary gangrene will reveal itself without the possibility of error by the appearance (among other symptoms) of the elastic elements of the lung tissue in tlic patient's sputa. Should the elastic fibres, howeverj become involved in tlie destructive process, they begin by losing their normal elasticity ; they become limp ; often, too, they swell, and may ultimately be converted into a jelly-like substance. Those firmer and more compact fibrilhi^ of connective tissue of v\'hich the tendons are composed, and which also occur in fibrous membranes (dura mater, tendinous, muscular and arterial sheaths, periosteum), behave like the fibres of yellow clastic tissue. The first indication which these structures (I refer more par- ticularly to the tendons) present of l)eing involved in moist o-ano-rene, consists in an unravelling of the parallel bundles of fibres from one another ; this must be ascribed chiefly to soften- in o- and disorfranisation of the connective tissue intercalated between them, in which the vessels run. At a later stage, how- ever, the so-called secondarj- and tertiary fibrillar are separated from one another, and the tendon is converted into a shagiiy mass of fibres, which bears the same relation to its normal struc- ture that carded hemp bears to a well-twisted rope. Even in this stage, however, the tendon, as a whole, is not easily torn ; it is only at a much later period that the fibres begin to break up into single granular and beaded strips ; these, in their turn, melt away into molecules of minute size, and so become in- visible. § 20. Cartilage is one of the most indestructible tissues of the body. The chemical composition of the inter-cellular sub- stance is very stable, and this, perhaps, is the main reason why large pieces of cartilage, e.g, detached articular surfjices, resist necrotic disintegration for long periods of time. When this nltimately prevails, it mostly takes the form of a gradual peri- pheric liquefaction, during which the cartilage becomes trans- parent and assumes a reddish tinge. This colour cannot certainly he supposed to be due in all cases to imbibition of the red ). y Margarin. a crystalline mix- ture of two solid fats, stearin and palmitin. It is peculiarly abundant in mortified tissues. It occurs in needles, either isolated or in clusters radiating from a common centre (fig. 2, c). 8 Triple Phosphate — ammo- niaco-magnesian phosphate — occm's only in alkaline or neutral sanies. The forms which it most frequently assumes are modifications of the rhombic vertical prism, which closely resemble coffin lids (fig. 2, cl). Products of gangrenous de- composition, a. Leucin; h. Tyrosin ; c. Fat-crystals ; d. Ammoniaco - magnesian phosphate ; e. Ganorrene- corpuscles (black pigment) ; /. Yibriones, ^i^. * Virclwiv says, with reference to the intimate connexion between these divers forms {Archiv viii. 337) : " On allowing leucin to crystallise from solution, we always see, to begin with, very minute roundish gran- ules appearing in even the smallest drops of a viscid material, differing from oil globules by their feebler lustre and paler outline. Two or more of these frequently unite to form large drusy {i.e. studded with minute crystals) figures, or shoot into radiating clusters. If crystallisation proceeds very slowly, they remain more independent ; their individual growth making them assume, more and more distinctly, the form of faintly yellow spherules, which often exhibit in addition a concentric lamination. They often show no sign of their being made up of a number of minute needles ; on the other hand, masses of closely-packed 2 IB NECROSIS OF TISSUES. e Pigment Granules, which, with the exception of iron sulphide, are all derived from the colouring matter of the blood, are found in the shreds which float in the sanies oozing from vascular parts, and in the tissues of such parts themselves. They exliibit a high degree of polymorphism. The most fre- quent variety is a rust-coloured pigment, occumng in the form of granules, either single or aggregated, vaiying from a yellow to a dark reddish-brown tint ; this is closely related to ha3matin in chemical composition, and is also met with in non-gangrenous, so-called pigmentary metamorphoses of tissue, associated with hsematoidin. It is only what are known as gangrene corpuscles that are regarded as peculiar to necrosis ; these are minute black particles of very irregular shape, only to be detected under high magnifying powers, and which set most reagents at defiance. It is by no means certain that these gangrene corpuscles are exclu- sively associated with putrefactive changes; on the contrary, there are good grounds for believing them to be identical with Melanin, of which more will be said hereafter (fig. 2, e). § 24. The occurrence of living organisms in gangrenous parts is deserving of especial notice. I have shown already that the process which we call putrefaction (Fiiulniss), and which plays so great a part in necrosis, is exclusively due to the presence and the vital activity of these humble organisms. Manifold have been the disputes as to the animal or vegetable nature of the minute, staff-shaped corpuscles which we see in a state of continual rotator}^, gjTatory, or to-and-fro move- ment (fig. 2, /). Even now that we know all about their development, this question cannot be considered settled. They originate as follows : their germs — dotlike particles of extreme minuteness exhibiting lively movements — settle at the junction of the putref)ang body with the air ; these germs become elon- o-ated, and undergo repeated constrictions, forming long, jointed threads, which are subsequently broken up into their component joints ; these constitute the staff-shaped Bacteria. They form a needles may be produced, whose surface is studded with distinct pro- jecting points." The larger spherules may also cohere. In doing so they flatten each other; so that we not unfrequently come across spherules flattened on one side, which have become accidentally detached during mounting (fig. 2, a). PATTY DEGENEEATION. 19 greasy scum on the surface of the putrefying substance, pene- trating into it to a depth of several Hnes. They consume a great deal of oxygen, which they obtain for the most part from the proximate principles of the organic matter, thereby causing their decomposition. We cannot allow them to be regarded merely as products of putrefaction ; neither can their presence upon the putrefying body be considered as purely accidental. A (1) Spores and mycelium of Bothrytis acinorum cultiva- tion in an infusion of flesh, a. A recent spore; l. The same after four hours; d. After forty-eight hours, both covered with vibriones, ^i^j. (2) Yibriones set free in an infusion of flesh from the mycelia of mucor, -^. (3) Growth of yeast from germs of vibriones. a. Germs; I, c, d. The same as vesicles which progressively increase in size, ultimately forming the well-known cell-colonies of yeast. (After Lildevs.) body may undoubtedly undergo decomposition in other ways as well, but it can only '^ putrefy" with the aid of Bacteria. 2. COXDITIOXS OF I^' VOLUTION. A. Fatty Degeneration, § 25. I have chosen to term the tissue changes, to which the following paragraphs will be devoted, " conditions of involu- tion," implying thereby that they agree in the association of a gradual metamorphosis and final annihilation of normal structure, with a corresponding diminution and final abolition of the normal function of the affected parts. 20 TATTY DEaENERATION. § 26. This definition applies in the first instance to a meta- morphosis of CELLS, which is characterised by the appearance of oil globules in their interior, and which has therefore been called FATTY DEGENERATION. There was a time when men disputed whether the dark- bordered droplets of oil, white by reflected light and soluble in ether, originated in the cell contents, or in the nucleus, or even in the nucleolus. At the present day, though no one would think of denying the possibility of a fatty degeneration of the nucleus, or of its nucleolus when present, and though Ave must assume that in every case of complete fatty metamorphosis of a cell both its nucleus and nucleolus are destroyed, yet it is universally acknowledged that the disturbance invariably begins in the pro- toplasm, and in the case of cells with a limitary membrane, in the cell contents. The protoplasm, which normally exhibits a very finely granular appearance, contains at first but a limited number of oil globules, little groups of from two to ten being usually seen in the immediate neighbourhood of the nucleus. These globules never unite to form larger drops, a phenomenon which is constantly exhibited by such particles of oily matter as have penetrated into the cell from without (see below, fatty infil- tration) ; they remain isolated from one another by thin layers of protoplasm. The more numerous they become the narroAver grows the outermost zone of the cell, which is still free from them ; at length this vanishes, and the oil globules reach the border of the cell. At the same time the nucleus, which had hitherto been recognisable as a bright spot amid the dark mass of oil globules, and which could be rendered evident by colora- tion with carmine, ceases to be visible (compare with this and the following sections, fig. 4). § 27. During the occurrence of these changes the cell has increased often to three or four times its former size ; it has, moreover, become perfectly spherical, and this, whatever may have been its previous shape, whether cylindrical, squamous, or fusiform. It is now known as a " granule-cell," * and this term * The term " granule-cell " is decidedly preferable to the older ex- pression " inflammatory corpuscle." Gluge, who found these corpuscles in the lung at the outset of pneumonic infiltration, regarded them as FATTY DEGENEEATION. 21 must therefore be taken to denote a spherical aggregation of oil globules, held together by an albuminoid basis. The presence of a large number of these granule-cells gives the fluid in which they are suspended, or the tissue in whose interstices they lie, a yellowish-white or butter-yellow tint. Thus the colostrum, i.e. the milk which is secreted during the first few days after confinement, is not white, but yellowish and glutinous ; it separates on standing into a clear serous portion, and a creamy fluid which rises to the surface. The latter is almost entirely p^^ty metamorphosis, made up of granule-cells, which owe Epithelium of pericar- their origin to a fatty degeneration ^^^^. ^9^ % ^^^^ of ^ . T ,. ^ ettusion mto its sac. a. ot the glandular epithelia, and are Cells which still exhibit called colostrum corpuscles. In like their normal form and ., r. 1 X 1- • arrangement: first ap- manner (to confine ourselves to physio- pearance of oil globules; logical examples) the corpora lutea of ^- Granule cells, one of the ovary owe their name to a fatty ^enW ^'toTe™'' I degeneration of the cells of the mem- Granule cells breaking brana granulosa, which takes place in ^P ^^^^ ^ily debris. all Graafian follicles which have expelled their contents and are undergoing retrograde metamorphosis. § 28. The last stage of fatty degeneration may be appro- priately called ^' emulsification." The granule cells break up, owing to the solution of their albuminoid cement in the sur- rounding fluid, w^hich always has an alkaline reaction. A lively oscillation of the oil globules (molecular movement of Bvoimi) announces their imminent disintegration ; the outermost globules next become detached from the circumference of the cell, and are uniformly distributed through the surrounding fluid, while the residual aggregate undergoes progressive diminution, until at length it disappears, without leaving a trace behind. (This succession of phenomena may be admirably seen in the cells of cancer juice.) The fluid emulsion in which the oil globules are characteristic of inflammation. They were afterwards shown to be nothing more than the epithelial cells of the lungs in a state of fatty degeneration, freed from their attachments by the oedema which pre- cedes the inflammation, and so destroyed. 22 TATTY DEGENERATION. now suspended, the oily detritus, has its physiological prototype in the secretion of the mammary gland ; the more uniform dis- tribution of the refracting particles giving it a whiter, or even absolutely white, colour, just as in emulsions which have been artificially prepared. § 29. If we inject milk into the abdominal cavity of a rabbit it disappears very quickly ; it is still more rapidly ab- sorbed from the subcutaneous areolar tissue. Milk, therefore, and consequently all fatty dehins, are capable of being absorbed, and are usually absorbed, unless absorption is prevented by some exceptional conditions. One of these deserves especial notice, viz. when the products of fatty degeneration are enclosed in a cavity whose walls are in a state of inflammatory irritation, and consequently inclined rather for productive than for absorbent activity. Those products have, under such circumstances, to undergo a farther series of changes. The fatty matters are partly saponified, partly deposited in those solid forms with which we became acquainted during our study of necrosis. Finally, an abundant deposit of cholesterin crystals takes place ; these give the dirty-white mass (whose consistency, according to the amount of fluid present, may be either friable or pulpy) a peculiar lustre (atheromatous pulp — atherombrei — griitzbrei). Cholesterin, which we now meet with for the first, though not for the last, time, is still, notwithstanding numerous investi- gations, a very enigmatical substance. Its presence in the brain and spinal cord, under perfectly normal conditions, in enormous quantity (40 parts in 1,000) does not allow us to dismiss it summarily as an excrementitious substance. Its constant presence in the biliaiy secretion is readily accounted for by the fact that the bile is one of the few fluids which is capable of holding it in solution. Chemistry informs us that, besides the bile, it is only solutions of soap and fatty oils which can dissolve it, and these only to a limited extent. This high degree of insolubility in animal fluids is one of the most striking properties of cholesterin ; it is the cause of our so often meeting with it in a solid state. The regular crystalline form which it assumes is that of a rhombic plate, whose angles are uniformly =79" 30' and 100" 30'. These plates tend to form aggregates with their longer sides FATTY DEGENERATION. 23 Fig. 5. Crystals of cholesterin, after Virchow. parallel, but without overlapping each other at every point. The various and interesting forms assumed by this substance have been exhaustively studied by VircJiow ; we must, however, refer our readers to the accompanying w^oodcut and to the original paper (Vircliow'^s Archiv, xiL 101). Micro-chemical reactions are very useful in enabling us to distinguish cholesterin with certainty from other substances which have the same crystalline form. These reactions are very characteristic. A drop of concentrated sulphuric acid, when allowed to flow gradually over the specimen, effects a progressive liquefaction of the cholesterin plates at their edges, and makes them assume a greasy appearance. After a little while the plate becomes flexible and quasi-membranous ; it is occasionally folded on itself; sometimes it shrinks together ; gradually, however, we see the mass melting at its periphery, while a dark reddish-brown globule is formed {Vv'choiv, Wiirzhurge)' VerJiancUungen, 1850, Bd. i. s. 314). The simultaneous action of sulphm'ic acid and iodine produces a fine blue colour during the first stages of the decomposition of the cholesterm. As regards the presence of cholesterin in the atheromatous pulp more particularly, the hypothesis that it is first taken up by the oily and saponaceous constituents of the emulsion, and then deposited when these are decomposed, un- doubtedly accords best with what we know of its properties; but this is a point which requires further investigation for its settlement. § 30, We have hitherto traced the course of fatty metamor- phosis mainly as it occurs in individual cells. We have yet to show how the phenomena of the process are modified in accordance with the primary modifications in the form of the corpuscular protoplasm. These modifications ai'e, of course, purely morpho- logical. Thus, for example, w^e cannot expect the aggregation of fat-granules to be perfectly spherical when the original cells are stellate, with long processes ; far removed, therefore, from the primitive spheroidal type. We may take the degenerated 24 TATTY DEGENERATION connective tissue corpuscles of the innermost tunic of the vessels as an example of the polygonal figures in which the granules may congregate. In like manner the fibres of unstriped muscle retain their primitive spindle shape after they are converted into masses of fat-granules. The protoplasm of the fibres of striped muscle has a pecu- liarly complex form, which is retained even after their fatty degeneration. The doubly refracting sarcous elements {Boimnan), which we regard as embedded in the protoplasm, constitute, m their longitudinal order, the ^Waricose fibrillee" of authors; and these are so disposed in the primitive fasciculus that their nodal points and their constrictions respectively lie in the same Fig. 7. Fig. Connective-tissue corpuscles of the tunica intima in a state of fatty degeneration, -^hj- Fatty degeneration of fibres of striped muscle, ■^. planes. Now, if we assume that the space which is necessarily left vacant in this arrangement of the sarcous elements is occu- pied by the viscid protoplasm, we must needs infer that the latter forms a system of varicose threads with chamfered edges, which are in contact with one another where they are thickest, in those planes, therefore, in which the varicose fibrill^ are thinnest. Larger accumulations of protoplasm exist only in the immediate neighbourhood of the nuclei, which displace the fibrill^ at those points where they are embedded, producing thereby fusiform spaces, which have to be filled in with protoplasm. It is in these little conoidal appendages of the nuclei that the first FATTY DEGENERATION. 25 oil globules make their appearance. We see them arranged in very fine and delicate beaded rows parallel with the long axis of the primitive fasciculus, and coinciding precisely with the varicose threads of the interfibrillar protoplasm. The transverse stride which, after all, are merely due to the uniform arrangement of the more highly refracting particles, must naturally grow indistinct in proportion as the yet more highly refracting fat- granules predominate, and so impair the effect of the groups of disdiaclasts on light {Bvikke's disdiaclast groups — sarcous ele- ments). In very advanced cases of the disease we see nothing but the oily cZe6m, contained, like some fluid, in the tube of sarco- lemma (fig. 7). § 31. The physico-chemical processes which underlie the fatty degeneration of cells have not, as yet, been very clearly ascer- tained. We may, however, repudiate the notion that the oil globules penetrate into the interior of the cells from without ; against this view we have the fact that muscular tissue in a moderate state of fatty degeneration does not contain a higher percentage amount of fatty matter than normal muscle. The only remaining alternative is that the oil globules are generated in the cell itself. But are they to be viewed as the result of some disturbance in the nutrition of the cell, or as products of the decomposition of its substance ? The most likely hypothesis is that we have to do with phenomena diametrically opposite to those which accompany cell development. We know from the composition of the yelk that the material of which the cells are built up consists of albuminous compounds, with a rich admix- ture of fatty matter. Further, we learn by chemical analj^sis that healthy muscle contains a considerable proportion of invisible fatty matter ; so that we are justified in assuming the existence of an amalgam-like compound of fat and albumen in cells. Fatty degeneration would thus be a "decomposition" of this amalgam, the liberated oil appearing in the protoplasm in the form of globules of appreciable size. The simultaneous enlarge- ment of the cell is explained when we reflect that the same quantities of fat and albumen require more space when separate than in their previous state of intimate combination. § 32. The minute changes which take place in the distal end of a divided nerve would powerfully corroborate tlie views enunciated above, were it clearly proved that the coagulation of 26 FATTY DEGEXEEATION Fig. 8. the nerve-medulla described in § 16 ouglit to be regarded as the first step in the dissociation of an amalgam of albuminoid and fatty matter. For, by the common consent of all those authors who have occupied themselves with this subject, the subsequent changes are only a continuation, or, in other words, a carrying out of that still enigmatical phenomenon. The large dark-bordered drops of my- elin break up in the course of from two to four weeks into globules of progressively smaller size, which can no longer be distinguished from oil globules, either by their microscopical or their micro- chemical characters. Side by side with them minute protein molecules of a paler tint make their appearance ; a fatty and granular detritus results, which remains enclosed for a time in the tubes of neurilemma, and is ultimately absorbed. The axis cylinder remains intact for about six weeks in the disintegrating medullary sheath. If at any time during this period the connexion of the peripheral portion with the central stump is re-established, the sheath fills again with meduhary matter, and the axis cylinder resumes its interrupted functions ; in the contrary event it becomes granular and splits up, even before the absorption of the oily dehris is quite accomplished. The empty neurilemma now collapses into longitudinal folds, exhibiting here and there an elongated mass of fat granules, in the interior of which a nucleus may be demonstrated with carmine. § 33. The fatty granular metamorphosis, or caseation of cells, may conveniently be regarded as a variety of fatty degeneration. The latter term is that chosen by VircJiow ; it is based upon a close resemblance between the yellowish white, dense, homo- geneous, rotten, or greasy mass, which is the final product of this metamorphosis and certain sorts of cheese. It used formerly to be thought that the substance in question Fatty degeneration of double-bordered nerve fibres in the periplieral part of a divided cere- l)ro-spinal nerve. a. After three days have elapsed; h. After a fortnight ; c. After three weeks ; d. After two months, ■^^. TATTY DEGENEHATION. 27 could only result from antecedent tuberculous disease ; it used to be viewed as a direct excretion of tlie 7nateries morhi from the blooclj and was hence denominated '^ crude " or '' raw " tubercle. The term " tuberculisation" was nearly synonymous with what we now call caseation. Reinhard was the first to overthrow the belief in the specific character of this deposit ; he erred, how- ever, in declaring it to consist invariably of inspissated pus. It was resers^ed for Firclioio to place the matter in its right light, by describing " cheesy necrosis" as a tolerably widespread mode of degeneration of tissues rich in cells. § 34. The reader will recollect that in describing fatty meta- morphosis, I stated that the presence of a certain quantity of water was essential for the actual disintegration of the cells, in oiTler to dissolve the albuminoid material which held the oil globules of the granule cells together. Should this fluid be wanting, as happens when large masses of newly formed cells are traversed by few or no pervious vessels, the process of fatty metamorphosis is somewhat modified; the two modes standing in much the same relation to one another as that in which dry gangrene stands tovv^ards the moist variety. The cells dry up, they shrink into comparatively small, shapeless, mostly angular bodies, in which, besides the oil globides, a considerable number of granules — the so-called protein molecules — may be distin- guished. The less the amount of water present, the more does the whole wither into a dense, yellowish-white mass, in -which the remnants of cells can be demonstrated, even after the lapse of years. True, we are unable to restore the withered cells to their old shape by the addition of Avater ; this usually breaks up the molecular aggregates, forming a sort of emulsion. Similar changes occur if the cheesy matter should subsequently absorb moisture and soften in the organism itself. This constitutes, as we shall see hereafter, a most destructive episode in the history of tuberculosis ; the softening occm'ring by preference in such portions of the cheesy deposit as come to the surface on the walls of the internal cavities of the body, whether in the respiratory or digestive tract, and are accordingly exposed to other sources of moisture besides the nutrient juices in which they are bathed. In parts w^hich do not communicate with free surfaces, as in the lymphatic and mesenteric glands, in the bones, the brain, and spinal cord, softening of the cheesy 28 FATTY DEGENERATION. deposits is far less common. On the contrary, an increase in density, a true petrifaction, often ensues, especially in cheesy lymphatic glands, owing to a deposition of calcareous salts in their interior. § 35. In conclusion, let us glance at the causation and the distribution of fatty metamorphosis. In the foregoing para- graphs we have often had occasion to touch on these points ; now, therefore, we may content ourselves with a general review. First, then, we may regard fatty transformation as being a regular mode of the retrograde metamorphosis of many tissues which are subject to rapid nutritive change. Among these, the epithelial structures naturally take a leading place. If we moisten the surface of any serous membrane and scrape it with a scalpel, the fluid we obtain will seldom fail to exhibit a certain number of epithelial cells which have undergone fatty degenera- tion, side by side with others which are perfectly normal. The epithelium of the mammary and sebaceous glands is peculiarly liable to undergo fatty metamorphosis in the ordinary course of events ; so also that of the lungs, and the renal epi- thelium of dogs and cats. Whether the white blood corpuscles, on completion of their span of life, finally succumb to fatty degeneration, is a question which must be left open; it is an undoubted fact that a certain number of granule cells are con- stantly met with in the iDlood of amphibia ; but these may of course have originated in the epithelial lining of the vessels. The fatty metamorphosis which forms an element in senile decay is intimately connected with the above varieties. The €nfeeblement of nutrition due to old age is especially manifested in parts where arrangements for the transport of nutrient matter are most complicated by nature, and in a certain sense most difficult. I allude, of course, to those great tracts of non-vascular tissue which occur in cartilaginous organs, and the transparent media of the eye. Hence it is that we so often find the cells of the laryngeal and tracheal cartilages in old people in a state of fatty degeneration, the capsules being occupied by one or more oil globules. To this group also belongs the arcus senilis, a fatty degeneration of the corneal corpuscles adjoining the sclero-cor- neal junction, and the gerontoxon lentis, an opacity situated at the junction of the posterior surface of the nucleus of the crystalline CLOUDY SWELLING. 2^ lens with its cortical portion ; an opacity which remains stationary for a long time, but which ultimately results in the formation of . Lymphatics ; c. Vascular buds ; d. Ditto, in connexion with a connective-tissue corpuscle; c. Free border, with epidermis. the boundary-line between two adjacent cell-territories, we see- the vascular bud taking an independent course. According to- Strieker J the outer surface of the capillaries is continuously coated w4th a thin layer of protoplasm ; the protoplasm is not confined to the nucleated points ; and this view would at once provide us- Avith materials for the development of our vascular buds. That these really consist of jorotoplasm is shown, on the one hand, by their optical similarity to the protoplasmic processes of the con- nective-tissue corpuscles; on the other, by the fact that these processes can take their place in the development of new vessels. When the new capillary is thrown open to the blood-current,. ^2 DEVELOPMENT OF CONNECTIVE TISSUE. the protoplasm forms a thin layer over the entire sm-face of tlie tube. It then stiffens, forming a membrane which differs in no respect from that of the parent-vessel, with which, indeed, it is uninterruptedly continuous. Should connective-tissue cor- puscles have taken part in the construction of the new vessel, thej take their place, after the metamorphosis is completed, among the constituent elements of the endothelial tube. Secondarij vascular isation is almost exclusively confined to the domain of pathology ; it may be regarded as a modification of the tertiary mode in so far as it also is associated with a gradual dilatation of the endothelial tube. It differs from it, however, in the greater prominence assumed by the apposition of new elementary parts to the wall of the vessel. The course of the future vessel is mapped out b}' a cord of spindle-shaped cells, arranged in parallel rows ; these cells undergoing direct <3onversion into endothelial elements when the axial lumen comes to be thrown open. The many varieties of this secondar}- mode of vascularisation will be more fully examined under the head of Inflammation and several species of tumours. § 72. The second constituent of the intermediate apparatus of nutrition is the connective tissue. From the embryological point of view, the term '' connective tissue" embraces that residual portion of embryonic tissue which is left between the blood- A^essels on the one hand, and the functionally active tissues on the other. The parenchymatous islets of the middle layer of the blastoderm are either used up or pushed aside during the development of the organs ; and in proportion as they undergo one or other of these alternatives, we find the organs provided with a larcrer or smaller amount of connective tissue. In some organs hardly any connective tissue can be shown to exist, as f.g. in the kidney and the testicle ; the lobules of the liver appear to be exclusively made up of capillary vessels and secreting cells. Yet it is possible to discover with absolute certainty small quantities of unformed connective tissue both in the testicle and in the renal parenchyma ; and where even this minimum is lacking, as in the hepatic lobules, the connective tissue is represented by the capillary walls themselves. For the cells of the endothelial tube are equivalent to those of the connective tissue ; indeed, we have already seen that the latter are capable of directly replacing the former in the tertiary mode of vascularisation. Moreover^ DEVELOPMENT OF CONNECTIVE TISSUE. 9^ Ranvier Las found that the cells of the lax subcutaneous con- nective tissue may exhibit a flattened form ; this shows that tlia connective-tissue corpuscles are generally disposed to adopt th& form of thin lamellae when they happen to lie in interfibrillar spaces of considerable size. The evidence as to the homology of the connective-tissue corpuscles with the cells of the endo- thelium is completed by the homology of their formative pro- ducts, products which both are capable of yielding in a certain measure, as we shall see hereafter. Of course I refer only to the- statlonary cells of the connective tissue, to the connective-tissue corpuscles of Vircliow ; my remarks must not be taken to apply In any sense to the mobile cells discovered by v. Recklinghauseyi. The connective tissue extends Avherever the vessels extend, and even beyond them. It gives an outer coat to the vessels, it serves to continue their walls into the interstices of the organic- structures, and inasmuch as all the vessels arc interconnected, the vascular system together with the connective tissue consti- tutes an elaborate framework, in which the remaining morpho- loo;Ical elements of the body are embedded. In a word, the- connective tissue Is so extensively distributed throuo;hout the l)ody, that it is impossible to make a cut at any point without damaging the connective tissue, without exposing it at number- less points of the cut surface. § 73. Let us now glance at the conditions regulating its- o-rowth. Observers are all but unanimous in holdinof that for the production of any (quantity of connective tissue a pro- portional quantity of embryonic tissue is required. The latter consists of nucleated particles of naked protoplasm, forming in the aggregate a very soft and elastic substance, of a pale- grey hue. It Is very readily generated wherever the need arises for an extension of the intermediate apparatus of nutrition ;. and it is certain moreover that the required amount of em- bryonal connective tissue Is produced by the intermediate appa- ratus of nutrition itself This is one of its most fundamental properties and functions, and unquestionably plays the most important part in morbid growth. It is only the mode of Its production which is still in urgent need of elucidation. I say '^ still," inasmuch as the importance of the question for our general conception of morbid processes is so great, that it may justly be regarded as the corner-stone of all past and present- M DEVELOPMENT OF CONNECTIVE TISSUE. systems of pathology. For tlie embryonal connective tissue, with whose genesis we are now concerned, is identical with the much-discussed embryonic tissue (Keimgewebe) of morbid growth, with the plastic exudation of the humoralists, witli Virchoio's "proliferation of connective-tissue corpuscles," with the accumulation of emigrant leucocytes discovered by CoJmheini. When we come to discuss the theory of inflammation we shall have occasion to become acquainted with the data afforded by morbid histology in reference to this question ; suffice it for the present to say that the possibility of the mignition of colourless blood-corpuscles, and the production of plastic exudations by their accumulation and aggregation, has been placed on a sure footing; while, on the other hand, the farther possibility of fission of the pre-existing stationary corpuscles is not excluded ; nay, must in certain cases be considered indispensable. § 74. The subsequent metamorphoses of the young con- nective tissue, the formation of intercellular substances of different kinds, and the resulting constitution of the various members of the connective-tissue series, I must assume the reader to have learned from books on normal histology (see Rolletfs article in Strieker s Handbook, Syd. Soe. transL, vol. i.). We will do well to distinguish rigorously l)etween such connective substances as constitute independent organs, or parts of organs, between the formed or functionally active connective substances (cartilage, bone, tendon, &c.), and the formless, passive connective tissue, which serves only to fill up gaps, and which the older authors -called "cellular tissue." Henceforth I shall employ the terni ^' connective tissue" to designate the latter variety only; it is to this variety alone that the statements made above concerning the ubiquity of connective tissue in the human body, concerning the affinity of its cells to those of the endothelium, concerning its significance as a proximate constituent of the intermediate apparatus of nutrition, refer. I must not be understood to question the relationship of this variety of connective tissue to the formed connective substances (geformte Bindesubstanzen) ; on the contrary, it will appear in the sequel that a clear idea of their relationship is of peculiar moment for the right interpreta- tion of many morbid phenomena ; I only want, with reference to the growth of organs, to establish a timely distinction between those organs which are made up of the connective substances, DEVELOPMENT OF LYMPHATICS. 95 and that apparatus which suppUes the necessary pabuhim for their growth, as well as for that of the muscles, nerves, glands, &c. This "connective tissue" Kar 'e^ox^i', must detain us for vet a moment while we consider how its corpuscles originate from em- bryonic cells. The form assumed by these corpuscles depends essentially on local conditions, upon the space available for their evolution. The great majority become spindle-shaped, corres- ponding to the elongated interstices left for their reception be- tween the fibres of the connective tissue. Whenever the basis- substance allows them to expand freely in all directions (as in mucous tissue) they readily assume a stellate form, and anasto- mose with one another by means of their processes. Should they lie in the narrow fissures between fibrous bundles and lamellae of larger size, they become flattened, forming epithelioid plates, or else they may continue, even in this flattened condition, to give off anastomosing processes, as in the cornea and tunica intima of the arteries. Thereupon a portion of the protoplasm very commonly stiffens into a homogeneous, colourless, highly refracting substance ; we get stellate figures, plates, and fibres, which must be carefully distinguished from the plates and fil)res of the intercellular substance ; the necessary criterion being readily afforded by their chemical properties, inasmuch as they do not, like the intercellular substance, swell up and disappear on the addition of acetic acid. It sometimes happens (liga- mentum pectinatuni) that the entire cell, together with its nucleus, undergoes the metamorphosis in question. More commonly, however, the nucleus remains unaltered, together with a residual portion of granular protoplasm, occupying, as a rule, the centre of the stiffened cell. This is how the stationanj corpuscles of the connective tissue originate; and in this state they remain during the whole life of the individual, unless they are roused to renewed activity by pathological irritation. § 75. We come now to the lymphatics and lymphatic GLANDS. This is the third and last of the chief constituents of the intermediate apparatus of nutrition — the last in point of time, not in point of importance. It is only when the rate of embryonic development enters on a slower phase, after all the other organs have been mapped out, and even developed to some extent, that we can detect any lymphatics. Lymphatic glands are still later in making their appearance. This is undoubtedly 96 DEVELOPMENT OF LYMPHATIC GLANDS. connected with the function of the lymphatics, as drains for the removal of superfluous pabulum. So long as there is no super- fluity of pabulum, inasmuch as it is all used up in the construc- tive process ; so long as the outer coverings of the embryo are not too thick to check the free transudation of fluid, there can be no need of lymphatics. Contrariwise, we might predict that anv obstacle to the escape of lymph must needs give rise to luxuriant growth of new tissue, to catarrhal and other secretions of all sorts from the aftected surface ; and this prediction would often be found to come true in the domain of pathology. JReck- Ungliauseii's beautiful researches into the lymphatics and the mode of their beginning in the tissues, have taught us that they are lined with precisely the same pavement of nucleated endo- thelia as the blood-vessels. This is also true of those still finer juice-canals which, according to the same observer, con- stitute the first beginnings of the lymph-path in the connective tissue, and communicate by minute pores with the apparently csecal ends of the larger lymphatics. These canals generally present the form of flattened, stellate lacunae, and are indeed, for the most part identical with those fissures and stellate inter- stices in which the flattened cells of the connective tissue {Ran- vier) lie. As the lymphatics extend farther into the connective tissue, the minute communications with the juice-canals, alluded to above, become simply dilated (KdUiker) ; and this affords additional evidence of the homology between the connective- tissue corpuscles and the cells of the endothelium. § 76. The state of things as regards the glands is far harder to determine than as regards the lymphatic vessels. We are still in want of a thoroughly reliable account of their development. The older views of Brescliet and Engel^ who traced their evolution from plexiform knots of lymphatic vessels, have been lately reproduced, and that too in a form incomparably more plau- sible.* I feel obliged, however, to reject them. The specimens prepared by J. Orth] have led me to concur with him in holding * Sertoli found that lymphatic canals lined with epithelium were first produced, that the connective tissue round them next underwent proli- feration, and that corpuscular aggregates in this proliferated tissue were then developed into gland-follicles. t /. Or/7?, " Lymphdriisenentwickelung." Inaugural Dissertation. Bonn, 1870. DEVELOPMENT OF LYMPHATIC GLANDS. 97 that the first rudiment of a lymphatic gland is a collection of embryonic tissue, very highly vascularised, which forces its way between the fibres of the surrounding connective tissue, thereby forming for itself a capsule. It is only after this has taken place that a clear sub-capsular space appears at its periphery, and interstitial fissures become visible in its interior ; the latter, by their connexions with the peripheric zone, partitioning the gland-substance proper into follicular cords and terminal nodules in the usual way. From a purely physiological point of view, the lymphatic gland presents itself as a local dilatation of the lymph-path, filled with a new and peculiar kind of tissue — the ^^ymphadenoid tissue." This is made up of lymph-corpuscles embedded in the well-known reticulum ; it is held to be the great breeding-ground for the colourless corpuscles of the blood ; and as it is generally agreed that the red corpuscles are evolved from the colourless ones, and that the migratory cells of the connective tissue are colourless corpuscles which have escaped from the vessels, the tissue of the lymphatic glands may be regarded as the common source of all the mobile cells of the entire intermediate apparatus of nutrition. Unfortunately how- ever, this hypothesis, like many others on the genesis of tissues, still rests on an uncertain basis. We must admit that the lymph- corpuscles in the glands have hardly ever been seen to divide, the assumption reposing mainly on the old and readily demon- strable observation, that the lymph contains fewer corpuscles before its passage through the glands than after it. But may not this increase in the number of corpuscles be due to emigra- tion from the blood-vessels ? There seems to be no reason why leucocytes should not escape from the vessels in a lymphatic gland as well as in any other organ ; nay, the very fact that the lymph-corpuscles are most abundantly generated during the digestive hyper^emia of the alimentary apparatus, in which, as wc all know, the lymjihatic glands take a conspicuous share, tells rather in favour of this theory than against it. For my own part however, I would rather not try, on such grounds as^^these, to overthrow the doctrine which has attained right of citizenship, and which is so very plausible a priori, that new cells originate in the lymphatic glands by fission of the lymph- corpuscles. I continue to regard the lymphatic glands as organs, which the intermediate apparatus of nutrition may be said to construct for 7 98 DEVELOPMENT OF THE SPLEEN. itself, with a view to the renewal of its mobile cells ; and it does this by causing the dilatation of circumscribed capillary areas at various points, followed by the emigration of colourless blood-cor- puscles. The number of the emigrant cells subsequently increases by fission, and this increase continues to add to the bulk of the glandular parenchyma so long as efferent canals for the removal of the superfluous cells are lacking. At a later period a certain equilibrium is established between the production and the removal of the cells — an equilibrium which can only be disturbed by pathological irritants.* § 77. The SPLEEN ranks with the lymphatic glands in its genetic history. The " formation of lymphatic sheaths," as the local emigration of colourless corpuscles and their accumulation round the vessels is usually termed — a phenomenon which my own observations have led me to adopt as the most probable mode of development of the lymphatic glands — is carried a step farther in the case of the spleen. In this organ, as in the lymphatic glands, the vessels begin by surrounding themselves with lym- phatic sheaths, which here receive the name of Malpighian corpuscles. The vascular walls then undergo perforation, and split up into fibres. In this wise a delicate spongy tissue is formed, through which the blood percolates, to be again collected on the opposite side of the filter by efferent veins, which permeate the spongy tissue in all directions. The function of the spleen is environed by the same doubts and conflicting opinions as that of the lymphatic glands, save that the splenic pulp is held to be at * I cannot refrain from calling the reader's attention to the valuable analogies presented by the development of the lymphatic glands (as described above) to the many formative disorders of the intermediate apparatus of nutrition {see next chapter). In the latter as in the former case, migration of cells, followed by their fission, underlies all formative activity. Emigration brings the cells into contact with the tissues, and affords them a comparative measure of repose; and these conditions seem to determine first their amoeboid motility, and secondly their fissi- parous multiplication. I am convinced however, that fission rather than migration is the proximate and effective cause of inflammatory production and the growth of histioid tumours. To this is due the colossal size which these tumours may attain, such enormous increase depending on the inadequate development of the lymphatics, which are thus unable to provide, as they do in the case of the lymphatic glands, for the due removal of the excess of cells. DEVELOPMENT OF CARTILAGE. 99 once the birthplace of young leucocytes, and the grave of such red corpuscles as are growing old. § 78. So much for the genesis of the conjoint blood-vascular and connective-tissue system. AYe mark the distinction be- tween its stationary and its mobile cells. To the former class belong what used to be called connective-tissue corpuscles, the endothelia of the blood-vessels and lymphatics, the stellate and anastomosing cells of the lymph-sinus and the splenic pulp, and finally the epithelia which line the serous cavities, since these are (according to Reclclingliauseri) in direct communication with the lymphatic sj^stem. The mobile cells are represented by the blood-corpuscles, and of these the colourless ones are pecu- liarly prone to accompany the nutrient fluid in its passage through the walls of the minuter vessels ; after traversing which, some, as" migratory corpuscles of the connective tissue," place themselves at the disposal of the growing organs to be employed in the constructive process, while others make their way back into the blood through the lymphatics. The stationary cor- puscles originate from the mobile cells ; how the latter originate is still unknown. The cells in the parenchyma of the lymphatic glands and the spleen have the best claim to be regarded as their normal source. Yet if we bear in mind how the lymphatic glands themselves originate, we shall probably have to admit, as a fundamental postulate, that all colourless corpuscles, when once they have escaped from the circulating current, begin to migrate and to undergo division. § 79. Passing on to consider the growth of the remaining organs of the body, we will devote our first attention to Cartilage and Bone. Everybody knows that in sections of young cartilage the cells are (wdtli hardly an exception) distributed through the matrix in groups, or at all events in pairs. The connexion of any two cells is evident from their each having a convex and a plane surface, the j^lane surfaces being opposed to one another. One is involuntarily led to think that they form the two halves of a globular body. That the appearances are really due to fission is shown from the occurrence of pairs of cells, which are still contained in a common capsule. Add to this visible pro- liferation of the cells, the intercalation of fresh intercellular sub- stance which separates the independent halves of the divided cell to the proper extent, and we have the well-known scheme, 100 DEVELOPMENT OF CARTILAGE AND BONE. according to which the growth of cartilage proceeds. I do not wish to cast any doubt upon the importance of these observed phenomena ; but I must guard myself strenuously against being supposed to think that the growth of cartilage is provided for, even in major part, by this internal multiplication of cells and intercellular substance. Cartilage grows mainly by peripheric apposition. The perichondrium furnishes embryonic cells, which proceed to surround themselves with a layer of hyaline inter- cellular substance, which becomes continuous with the matrix of the existing cartilage. The oftener this process is repeated, the more cells does the cartilage contain. Those cells which were originally peripheric are gradully pushed towards the centre ; and it is not till after this has occurred that the second factor in the growth of the cartilage comes into operation, sc, the gradual enlargement and subsequent division of the individual cells as they advance towards the centre of the mass. During this cen- tripetal movement each element divides from one to three times. The division always occurs at the thickest part of the cell, in a plane at right angles to its long axis ; hence the highly charac- teristic forms of the daughter-cells and their progeny. Half and quarter spheres, cones, &c., retain their peculiar shape throughout life, owing to the density of the matrix; for the same reason the cells which result from fission are never far apart, so that in the cartilages of an old man of ninety we ma}- still observe those appearances which, when we saw them in young cartilage, led us to attach so high an importance to the internal growth of the tissue ; in either case moreover we can determine with equal certainty whether the original cartilage-cell under- went fission once, twice, or three times, before assuming the final attitude of its repose. Quite independent of the phenomena of normal growth, is a peculiar metamorphosis of hyaline cartilage, which we find (apart from morbid states) wherever the cartilage ad- joins a growing bone. Whether the cartilage takes any active part in the development of bone, whether cartilage-cells, or even descendants of cartilage-cells, can be converted into marrow- cells or bone-corpuscles is still an open question. The metamor- phosis now under consideration must however be regarded as a passive participation of the cartilage, in so far as it re- places the unyielding hyaline substance by a soft material,., DEVELOPMENT OF MUSCLE. 101 which offers no resistance to tlie extension of the osseous trabe- culas and the ingrowth of the medullary papillae. The cartilage- cells again proliferate; and their proliferation, owing to the simultaneous liquefaction and partial reabsorption of the inter- cellular substance, assumes very considerable proportions. Each cell gives rise to from eight to sixteen very large daughter- cells. These are separated only by very thin trabecul?e of basis- substance, and form cylindrical columns, disposed at right angles to the surface of the growing bone. The vascular papilla) of the medulla penetrate into this soft, large-celled tissue as readily as though they were growing upon a free surface ; they break down all partitions ; and it is only where the form and position of the medullary cavity happens to allow it, that one or other of the stouter trabecular of the former matrix is retained as a sort of framework, on which layers of young bone-tissue are deposited. To conclude : here, as in sub-periosteal growth, the bone needs no antecedent condition for its development, beyond the presence of a vascularised embryonic connective tissue, which is everywhere produced upon its confines by the intermediate apparatus of nutrition, whether this bo represented by medullary tissue or by periosteum. I will say no more at present about the growth of bone ; ample opportunities for doing this will be afforded in the chapter on Diseases of the Osseous System. § 80. As regards the growth of the 3IUScular organs, we know that the first muscular fibres, whether smooth or striated, originate everywhere from embryonic cells. Where smooth muscular fibre is needed, the cells are converted into the well- known spindle-shaped or ribbon-like structures, while their nuclei assume the form of elongated cylhiders (staff-shaped nuclei). In the case of striped muscle, the cells, according to KoUiker, increase in length, their nuclei imdergoing repeated fission, until the proper length is reached. (According to other authors, each fibre results from the apposition of several cells.) The striped matter is then differentiated from the protoplasm, and becomes a cylinder whose diameter goes on increasing, while the nuclei are pushed to one side, where they combine with the residual protoplasm to form the muscle-corpuscles. The after-growth of striped muscle consists, according to KoUiker J of a simple increase in the length and thickness of the 102 DEVELOPMENT OF MUSCLE. existing fibres. Weissmanji and Ki'ihne describe in addition a peculiar splitting of the primitive tubes in tlie direction of their length. This phenomenon was studied ]n' Weissmami in the muscles of the frog, bv Kvlme in those of rats and mice. The latter observer describes a marked increase in the number of nuclei and the quantity of finely-granular protoplasm at the points where the nerves enter. Weissmann saw the nuclei arranged in a row, dividing the contractile substance of the muscular fibre into two parallel bands. Kiihne came across two muscular fibres in a single tube of sarcolemma. All these are facts which give us some sort of idea, though not a distinct pic- ture, of the longitudinal splitting of the muscular fibre. Not a word is dropped by either observer suggesting any after-produc- tion of embryonic cells, destined for the additive formation of new primitive tubes. In disease matters take a different course. The repair of divided muscles by muscular tissue is indeed still very doubtful ; beyond all doubt, however. Is the regeneration of the muscular fibre in myositis typliosa, which we shall have to consider more fully hereafter. But in this latter case the pheno- mena are so complicated that we are unable to affirm w^ith cer- tainty that the regeneration is brought about exclusively by the mediation of embryonic cells. We can speak more confidently about such organs as are made up of unstrlped muscle. During tlieir growth the cells increase in number as well as in leno-th and thickness. Slns^le fibres with forked extremities have often been met with in the walls of the pregnant uterus.* Inasmuch, however, as no mul- tiplication of nuclei, no double nuclei, have ever been detected in these fibres, it remains very doubtful whether we are justified, on the above data, in assuming a fissiparous multiplication of the smooth muscular fibres. The doubtfulness of this hypothesis is enhanced by a positive observation of KbllikiTs. He succeeded in tracing the origin and development of the muscular fibre through all its stages in one and the same specimen. (Cf. KoUiker, " Gewebelehre," 4te Auflage, page 567.) The embryonic cells required are furnished by the intermediate apparatus of nutrition, and are probably leucocytes which have emigrated from the vessels. * Moleschott and Piso in Moleschotfs *^Untersuclmngen," vi. 1-6. DEVELOPMENT OF NEKVE-TISSUE AND EPITHELIUM. 1 03 § 81. As regards the nervous system, it has been generally believed hitherto that the growth of nerve-fibres was everywhere dependent on the pre-formation of embryonic cells. That the repair of divided nerves took place by the intercalation of em- bryonic tissue between the cut ends seemed finally agreed upon ; indeed, it has not as yet been superseded by any fresh doctrine. On the other hand, a tendency has shown itself of late to refer the penetration of the nerve-ends into the growing parts of the body, and their consequent elongation, to an apical growth (Spitzenwachsthum) without any apposition of new elements. As regards the brain, Besser skilfully defends the position, that all the ganglion-cells of later growth exist pre-formed as so- called neuroglia-nuclei, in the very earliest stages of the develop- ment of this organ. § 82. One important question yet remains to be answered. How do the EPITHELIAL STRUCTURES groAv and renew their losses ? Unfortunately, no precise answer to this query can at the present time be given. We are justified, however, in provisionally adopting the following conclusions. A clear line must in the first j^lace be drawn between those epithelia which grow out- loards and those wdiich grow inwards. The former invest the entire free surface of the organism, the skin and mucous mem- branes, forming an uninterrupted whole ; the latter occupy cer- tain cavities dug out of the parenchyma of the body, and are known as gland-cells or glandular epithelia. Both systems ori- ginate in the same layer of the blastoderm ; throughout life they maintain this structural continuity, in such wise that the glandu- lar epithelium may be regarded as a direct prolongation and in- flexion of the surface-epithelium. Yet those who w^ould com- prehend the alterations of the tissues in disease must lay especial stress upon the fact that the antithesis in the direction of their growth alluded to above, exists from the very first, and that upon it is based the essential difference between the two systems. For the gland originates by the development of cellular protru- sions from that side of the epithelial lamina of the blastoderm which is turned towards the conjoint blood-vascular and connec- tive-tissue system : these protrusions divide and subdivide as they increase in length, and finally become hollow to a certain depth from the free surface. Their growth is decidedly central, and takes place by fission of the existing epithelial cells, which goes 104 DEVELOPMENT OF EPITHELIUM. on repeating itself over and over again in the club-shaped ends of the processes. The intermediate apparatus of nutrition takes no part whatever in the process ; nay, it is interesting to notice how it seems as it were to melt away before the advancing pro- trusions, contenting itself with the function of a mere stop-gap, the only function left open to it : it furnishes the interstitial con- nective tissue, the blood-vessels and the lymphatics, which, as we know, accommodate themselves humbly to the formal arrange- ment of the glandular tubuli, acini, &c. § 83. Matters take a very different course in the skin and mucous membranes. Their growth is regulated not by the epithe- lium, but by the conjoint blood-vascular and connective-tissue system, whose morphological elements (papillae, membranes, &c.) determine the form of the surface, upon which the epithelium exists only as a tegumentary investment. This must be borne in mind when we find (in the course of the ensuing paragraphs) that the matrix of the surface-epithelium is situated, not in its own substance, but in the underlying connective tissue. The cells of every epithelial stratum of considerable thickness exhibit certain characteristic variations in form, which may be viewed broadly as differences due to age — as phases of develop- ment. The youngest elements, remarkable for their small size, their softness and want of cell-membrane, are most deeply placed ; Pjq 24 t^^^y ^^0 01^ ^^^^ upper limit of the con- nective tissue. As we proceed out- wards, the cells increase progressively in size, their membranous investment grows more and more distinct, they The epithelium of the urinary exhibit a more or less characteristic bladder in section. ^^^^^ rj^j^^.^, ^^^^ -^ connected partly with variations in their function (cylindrical epithelium) ; it is partly due to a conflict between the forces which tend to make the cell grow uniformly in all directions, and the limitations of space which permit its growth to take place in certain directions only. A pregnant illustration of the results of this conflict is afforded by a vertical section through the epithelial lining of the urinary bladder (fig. 34). '\Yq can clearly distinguish three layers, each of which is made up of cells of a particular sort, differing characteristically from the other two. In immediate contact with the connective tissue is a single layer of small DEVELOPMENT OF EPITHELIUM. 105 round elements ; next to this we find pyriform cells of somewhat larger size, whose rounded heads are directed out- wards, while their pointed ends dip down into the interstices between the round cells of the deepest layer. That these cells belonged originally to the deepest layer, that they were raised into the second layer by the propulsive force of cells of later growth, while remaining attached to their place of origin for a time by their inferior ends, this is an assumption which flows most naturally, as I think, from their pyriform shape. The cells of the third layer present, at first sight, the strangest peculiarities of form. They are flattened, and provided on their under surface with angular projections and shallow depressions which correspond to the heads of the cells of the second layer in much the same way as the juga cei^ehralia and impressiones digitated of the tabula vitrea correspond to the convolutions and sulci of the brain. These forms can only be explained by supposing that a cell, be- longing to the second layer, is set free from its attachment to the connective tissue, that it protrudes towards the free surface, and that it is flattened and squeezed into the seams and irregularities of the second layer, by the centrifugal pressure of the urine which accumulates periodically in the bladder. We cannot account so satisfactorily for the morphological variety exhibited by the constituent cells of every epithelium. Authors are unanimous, however, on one point, sc. that the epithelial cells appear everywhere to originate immediately upon the connective tissue, to be subsequently extruded from their original seat by the pressure of new elements. This unanimity however refers only to the place ^ and in nowise to the mode of origin of the cells. To explain the latter — omitting for the pre- sent to take generatio cequivoca into account at all* — two hypotheses lie open to us. We may either suppose the new epithelial cells to lie produced by fission of the older ones, or to be extruded from the underlying connective tissue. There seems to be no a priori reason why the cells should not originate in both ways. It must however be admitted that the epithelial cells have seldom been actually seen to divide. The * J, Arnold {Virchow's Archiv, Bd. 46) has published some views on the regeneration of epithelial structures, which amount to a sort of generatio cequivoca; they are worked out with an amount of genuine care and research which render them worthy of the utmost attention. 105 DEVELOPMENT OP EPITHELIUM, mutual flattening of adjacent cells often misleads the observer into the belief that he has before him the results of fissiparous multii^lication ; the even line of contact between two cells pre- senting a deceptive likeness to a plane of division ; hence the most conscientious vigilance on his part is in this matter in- dispensable. On the other hand, it is probable for many reasons that the young epithelium-cells spring from the con- nective tissue. Burl:hardt was the first to indicate the top- most laye]' of the connective tissue as the matrix of the epithelial cells. When he described (in the year 1859) the way in which lie believed the young cells to emerge from the connective tissue, and to assume an upright attitude as the youngest of the epithe- lial cells, many of his readers had scruples about accepting his results. Since that time, the migration of connective-tissue cor- puscles has been directly observed by v. Becldinghausen in the cornea ; and this observation gives colour to the view that the renew^al of the epithelial cells is operated by a migration of their youngest elements from the connective tissue. The facts of morbid histology, so far from being antagonistic to this view, furnish many illustrations well adapted to shed light on the migratory process. I will only refer the reader to the interesting observa- FiG. 3 Transverse section through a dermal papilla surrounued by epider- mis. Migratory corpuscles may be seen both m the connective tissue and bet^veen the epithelial cells. After Pagensiecher. lions of Biesiadecki and Fagenstecher ; m cases of slight and DEVELOPMENT OF EPITHELIUM. lOT superficial cutaneous inflammation (eczema and vesication) tliey detected migrating cells in all the younger strata of epithelium, cells precisely similar to other amceboid corpuscles visible in the papillary body (fig. 35). One fact, and one only, is being continually urged against this hypothesis — of the fact itself there can be no doubt — it is this : new epithelium, as e.g. after partial denudation of any epithelial surface, originates by prefer- ence, perhaps even exclusively in connexion and immediate con- tiguity with pre-existing epithelium. It would seem, therefore^ since fission of the older elements cannot be shown to occur, that we are driven to assume that an embryonic cell can only develope into an epithelial cell when it is in contact with one of the latter kind. We must perforce adopt the theory of a sort of ^'epithelial infection.^'' This theory indeed would necessitate a twofold appli- cation ; for supposing such infection to occur when embryonal cells, colourless blood-corpuscles, &c., are brought in contact with a permanent epithelium, it must likewise occur when, con- versely, epithehal elements are brought in contact with a tissue composed of embryonic cells. The latter process indeed may actually be observed in the metastasis of cancer to lymphatic glands. § 84. This brings us to the end of our general summarv of normal growth. We have seen, that apart from the first founda- tion of the various organs (from which we learnt that any and every tissue might originate from embryonic tissue), their actual growth depends but in small measure on fissiparous multiplica- tion of their specific tissue-elements. We found this mode of increase in the gland-cells, in the fibres of striped muscle ; to some extent also in cartilage ; and we had grounds for suspecting that it also occurred in nerve-fibres. On epithe- lial surfaces there seemed to be need of an ''- epithelial infection," or at least of some sort of action of the older cells upon the immigrants. Everywhere else, the intermediate apparatus of nutrition, with its faculty of generating embryonic cells wherever required, sufficed of itself to maintain normal growth. It may be that it fulfils this function as a corollary of those obligations which are incumbent upon it in its nutrient capacity, allowing a certain number of colourless corpuscles to accompany the usual supply of fluid pabulum into growing organs, these corpuscles serving forthwith as materials for the constructive process. 108 ON NORMAL AS A § 85. Entering on the domain of 310RBID growth, we meet first of all with a series of abnormal states, which may be de- fined simplj as excesses of the normal growth of organs. These are either uniform enlargements, or partial protrusions or out- growths, identical in texture and composition with the organ from which they spring ; accordingly they only give rise to quanti- tative deviations from the normal standard of the affected parts. "We indicate this fact in our nomenclature by the prepositions virip and £K, which common use allows us either to prefix to the name of the proliferating organ itself (Jajperostosis^ eccliondrosis) ^ or to the word troplda ; the latter term denoting in addition that the products in question are due to nutritive conditions of a pecu- liarly favourable kind {Jiypertrophia). It is best however, not to prejudge their mode of origin in this way ; it is enough to express the simple fact by the words " hyperplasia^ hyperplastic^ The hyperplastic states (conditions of overgrowth) of the various organs will be described in the respective chapters of the special division of this treatise. The position which they occupy in the domain of morbid growth is broadly but sufficiently indicated by what has just been said. § 86. All new formations which are not of a hyperplastic nature, involve a qualitative departure from the normal stan- dard of development and growth. Hence it seems difficult at first sight to class them under physiological types. Our way is blocked, however, by obstacles of artificial origin, rather than by any which are inherent in the facts themselves ; among the most important being the traditional habit of regarding the morbid deviation as something foreign (hepov) to the organism, some- thing introduced into it from without, of ascribing to it a para- sitic life — even a kind of personality. This view, from which the term '^ heteroplasia " is derived, is justified in some measure by the two following considerations : — 1. Those new growths which are due to the introduction of a definite poison into the body manifest themselves under similar forms in the most diverse organs (e.g. syphilis, tuberculosis, enteric fever). 2. The circumstance that each organ is the seat of election of certain special kinds of morbid growth, which always occur under the same form with but trifling modifications, so much so that when they have reached a certain point in their development, we are able to infer their character and future TYPE OF MOKBID GROWTH. 109 destiny from their situation. It is wrong, however, and pre- judicial to the advance of real knowledge, when we allow the study and description of those features which are common to new growths in different organs to blind us to the right of each indi- vidual organ to have a morbid growth viewed as a disturbance of its own proper development — of its nutrition or of its degeneration. I must not be understood to question the utility, nay, the neces- sity of generalisations on the subject of morbid growth ; but such generalisations ought rather to tend towards establishino- the principles of development than towards the discovery of definite anatomical patterns on which any morbid growth — e.g. cancer — is constructed, in whatever organ it may occur. If I understand the times aright, men are weary of mere anatomical classifications based exclusively on outward characters. They w^ill agree with me in tliinking that the system has been brought into utter discredit by the inexhaustible variety of concrete forms. Henceforward therefore, while retaining the terms cancer, sar- coma, and so forth, and endeavouring to sketch in broad outlines the laws of their development and growth, without omittino- to take their influence on the organism as a whole into account, we will always fall back upon the description of the individual forms in the Special Part of this work, and keep alive to the fact that a knowledge of these concrete forms is at least as important for the practitioner as a correct appreciation of those general features which they possess in common. § 87. Having done with this digression, let us resume the thread of our discourse, by seeking the cause of every deviation from the rule of normal growth — the cause of heteroplasia — in an over-activity of one or other of the two factors which co- operate in the growth of organs. The intermediate apparatus of nutrition has the first claim on our attention. Many products of morbid growth originate from this alone — e.g. interstitial inflam- mation, tumours made up of granulation-tissue, sarcomata. In a second series, the epithelium steps in to rival the conjoint blood- vascular and connective-tissue system, and we have many oppor- tunities of testing the accuracy of our views of epithelial growth in the caricatures of it (Zerrbildern) presented by the ^-arious forms of carcinoma. It cannot be denied that this division of labour is prefigured in the physiological relation of the two systems to one another (as summarised in § 84). I cannot 110 INTERSTITIAL INFLAMMATION. tlierefore be blamed for basing at least the main divisions of the subject upon it. 3. Products of Morbid Growth derived exclusively from THE Intermediate Apparatus of Nutrition. 1. Interstitial Injiammation,^ § 88. When the organism is mechanically injured at any point, or exposed to any other sufficiently active source of irrita- tion, the aggrieved part undergoes a series of changes, to the . sum of which we apply the term " Inflammation." The name directs attention primarily to the important part played by the vascular system i-n the inflammatory process. The capillaries become congested; the affected part grows red and hot. It begins to swell ; the swelling is to be ascribed partly to the over- distension of the vessels, partly to the escape of various con- stituents of the blood into the tissues. The " inflammatory exuda- dation" — the material which escapes from the vessels, and infil- trates the tissues — is the more enduring product of inflammation, and claims our chief attention, owing to its important connexion with the course and issues of the process. § 89. The inflammatory exudation consists, apart from its fluid portion, of embryonic cells, which are characterised by the lively amoeboid movements they exhibit. It was generally believed a few years ago that these cells were produced exclusively by proliferation of the connective-tissue corpuscles at the seat of inflammation. The dazzling picture, in which we thought we could distinctly appreciate the course of cell-multiplication, exhibited in the immediate vicinity of the inflammatory^ exuda- tion, instead of the stellate corpuscles of connective tissue, first one, then two, then a progressively increasing number of round cells, arrayed in ranks, which grew longer in proportion as they approached the focus of inflammation, and finally mingled with * IntereUUdl, as contrasted witli catarrhal and parenchymatous in- flammation, the former of which, bo far as it concerns us, is an inflam- mation of mucous membranes {see Part II.), while the latter is identical with cloudy swelling (see § 36). INTEESTITIAL INFLAMMATION. Ill one another. But now we know that a great majority of these cells are colourless corpuscles which have emigrated from the vessels. This is shown by an experiment of Cohnliehri s. The mesentery of a living frog is stretched over a ring of cork, and subjected to direct inspection. We can see how the veins dilate ; how the colourless corpuscles first adhere to their inner surface, and then put forth processes which penetrate their walls ; how that portion of a process which has already escaped swells up, and forms a kind of bridge, along which the whole substance of the cell gradually creeps. Once through, the cells travel farther by the aid of their amoeboid contractility ; if a special point of the tissue is being irritated, that point becomes, in a general way, their goal. There they continue to accumulate ; the result of their accumulation being a certain quantity of that verv embryonic tissue which serves as the starting-point of all further changes (fig. 36). Fig. 36. ^ ; "\~;:^,\:x:g;if,ii^]j)..;iii|[^ A^/^^ (%[('^\r'\jp^^^ CoJinJieivi's experiment. a. Yein; hh. Adjoining connective tissue permeated by colourless corpuscles which have migrated from the vessel; c. Column of red corpuscles. An older observation, which was first duly appreciated by Billroth^ harmonises admirably with the above view of the deve- lopment of plastic exudation or infiltration. It has been found 112 INTERSTITIAL INFLAMMATION. that the vessels of inflamed parts are surrounded hy sl layer of young round-cells ; and this holds good even of those vessels which extend far into tissues which have as yet undergone but trifling change. On the other hand, we can give a satisfactory explanation of the drawing, which represents " connective tissue undergoing proliferation," by assuming that it exhibits the colourless corpuscles " during migration," in which case they would naturally select the lines of least resistance, and therefore those interfibrillar channels which are normally occupied by the stationary corpuscles of the connective tissue. ^ 90. The migration of the colourless corpuscles must not, how- ever, be regarded as the 07ili/ source of the inflammatory products. On the contrary the question, Whence can the blood obtain such a multitude of colourless corpuscles ? leads to a series of consi- derations which tend to make us very chary of rejecting any possible sources from which these cells may be derived. On this ground we gladly welcome the beautiful researches of Strieker, which prove, at least with regard to the cornea, that a few hours after it has been irritated with lunar caustic, at a period when the colourless corpuscles can be experimentally shown not to have penetrated as far as the seat of inflammation, the stationary corneal corpuscles exhibit a series of changes which can only be interpreted as steps in a progressive metamorphosis. They retract their processes ; their nuclei undergo multiplication ; their protoplasm increases in bulk ; between the fifteenth and the twenty-second hours they assume the appearance of mobile, multinuclear masses of imposing size, which remind us vividly of the so-called " giant-cells " (see § 67). It is but a step to the assumption that these may give rise to amoeboid cells by a seg- mentation of their protoplasm. The same author has directly observed the fissiparous multi- plication of the emigrant-cells at the seat of inflammation. Concentrating his attention on the cells which appeared to be at rest just outside the vessels, he noticed on their surface certain lines of shadow, which came and went and shifted their position for a time, until at length a shadow deeper than the rest became stationary in the middle of the cell. At this point the little body became contracted ; the contraction itself was more than once eff"aced ; when it finally passed into a complete division, the two halves crept asunder in opposite directions. The denser the INTERSTITIAL INFLAMMATION. 113 accumulation of cells, the ofteuer is this process of fission likelv to be repeated, but the greater also will be the difficulty of tracing it under the microscope. And this perhaps is the reason why it has hitherto been often assumed to take place, but never distinctly demonstrated. Our knowledge with regard to the som'ce of the embryonic cells in inflammation is obviously in a transition state. But if we reflect that the doctrines advanced in the preceding section constitute the o-roundwork of all the remainino; histoWical effects due to the " intermediate apparatus of nutrition," we shall perceive the immense importance to our scientific super- structure of every forward step in this department of inquiry. § 91. Continuing for a moment our consideration of the inflammatory exudation as a fait accompli^ we must notice the remarkable influence exercised on the connective-tissue fibres by the cells to which they afford a refuge. Billroth has made some statements on this point which I think worthy of great attention. The fibres are not merely pushed asunder, but they undergo [i certain degree of softening and fusion, so that instead of the tough web of which the cutis, even in its most delicate portions, is made up {e.g, in the prepuce), we find a delicate network which simulates the aspect of newly-developed intercellular sub- stance (fig. 37), for which indeed it has often been mistaken. Fig. 37. Tissue of cutis rarefied by inflammatory infiltration : after Billroth, ^i^. Passing to the further histological metamorphosis of the plastic exudation, upon which, as already stated, the ultimate 8 114 RESOLUTION. issue of tlic Inflammatory process depends^ we find three leading tendencies ; the first towards Resolution, the second towards Organisation, the third towards Suppuration. A. Resolution. § 92. Tt is clear that if our therapeutic skill availed to remove the cells which have migrated into an inflamed organ, that organ would return to the state in which it was before the inflammation set in. I put aside the alterations in the connective-tissue fibres described in the preceding section, alterations which might of course disappear with equal ease. The possibility of inflamma- tion issuing in resolution, and the means of bringing about this issue, are questions therefore of the highest practical interest. The first measure which would suggest itself a priori, would be to help the cells ip pursue the course they had already chosen, i.e. to let them migrate farther. Warmth and moisture would therefore be advantageous from this point of view. Elevation of temperature is known moreover to accelerate the movements of amoeboid cells. When the inflammatory exudation is mode- rate in amount, and the irritant cause has ceased to operate, wo may hope, by local elevation of temperature, to distribute the cells which have already migrated over a wider area, and to guide them gradually into the lymphatics. , The resolution of an inflammatory infiltration may also take place by fatty degeneration of its cellular elements. We have already seen how fatty degeneration converts cells of all kinds into a milky emulsion, to the reabsorptiou of which there is naturally no obstacle. A condition which appears to favour the commencement of fatty degeneration is the presence of fluid in abundance at the seat of inflammation. Busch has made the interesting observation that under the influence of cutaneous erysipelas some large sarcomatous growths underwent atrophy, and I had the opportunity of convincing myself in a similar case that the cells of the sarcoma succumbed to fatty degeneration. External warmth is well adapted for maintaining an enduring hyperaemia of this sort. Notwithstanding this twofold indica- tion, great caution is requisite in deciding on the exact moment at which to substitute warm for cold applications to an inflamed part. The object of applying cold is to bring about an artificial ORGANISATION OF INFLAMMATORY PRODUCTS. 115 contraction of the vessels, and so to clieck the progress of the exudation, to hinder the further migration of the colourless cor- puscles. It is not till we have followed out this indication to the utmost, that we ought to resort to the application of warmth. Warmth is a two-edged weapon. What guarantee have we that instead of a dissolution of the exuded matters, which is of course om- first object, there may not occur a greater concentration of amoeboid cells at the heated point, ie. suppuration and the formation of an abscess ? Within certain limits, warmth acts as a resolving agent ; beyond these, it stimulates the inflammatory process ; in the former case it promotes the farther migration of the already exuded white blood-coipuscles, in the latter it helps to renew the migratory process, and adds to its intensity. Note. — A therapeutic turn has been given to this section, to show the student how immediately the results of morbid histology may be brought to bear upon practice. ^ B. Organisation. § 93. Granting that the inflammatory exudation does not tend to resolution, the first alternative is its retention as a perma- nent constituent of the organic framework of the body. This retention is operated by the timely development of blood- vessels, and the conversion of the embryonic tissue into fibrillar connective tissue. The interstitial inflammations of internal viscera, which we shall hereafter meet with in the liver and kidneys, afford examples of this direct organisation on the largest scale. None of these examples can however be regarded as typical for the histological details of the process, because of pecu- liarities of local origin. The honour of serving as a type belongs exclusively to the process of repair in wounds, and primarily indeed to those which heal by first intention. To illustrate the universal distribution of connective tissue throughout the body, I stated above, that no incision could be made without implicating connective tissue, without the presence of connective tissue on the cut surface. The truth of this pro- position may be inferred from the consideration, among other processes, of the perfectly typical course of those phenomena which manifest themselves in the reunion of completely divided parts. These phenomena fall bodily under the head of inflam- 116 OEGANISATIOX OP mation, and are exliibitcd in precisely the same manner by tlie conjoint vascnlar and connective-tissne system, -whether the wounded organ be the skin, or a muscle, or perchance the hver. There certainly exists a mode of reunion which takes place with such extraordinary rapidity by the mere apposition of the cut surfaces, that no exuded matei'ial is required to complete it. The occurrence of this immediate iimoii {Macartneif) is confirmed by Thiersch in Pitha and Billroth's Manual of Surgery. It must therefore take precedence of union by first intention. Li the latter mode, a substance is usuall}' present which glues the edges of the wound together. It appears a A'ery few hours after the injury, and proves, both at first sight and on more careful investigation, to be the connective tissue of the cut surface, infil- trated with blood-corpuscles and serum, and swollen by imbibi- tion of the latter fluid. The next stage of the process consist:> in the migration of colourless corpuscles from the dilated vessels In the immediate neighbourhood. They permeate the whole of the cementing medium and the adjacent connective tissue, so that the divided parts are at length united by a continuous layer of embryonic tissue. The next step Is the re-establishment of the circulation, which has been violently interrupted. This takes place as a general rule by the method of ^^ secondary vascu- larlsatlon" (^ 71), starting from those capillaries which are still pervious. Thiersch has recently furnished us with the details of the process. Should his interpretation of them be confirmed, they will materially extend our ideas respecting the development of new vessels in general. Thiersch found the cut ends of the vessels, a few hours after the Injury, plugged by a corpuscular proliferation, and somewhat dilated, but seldom occupied by a blood-clot. Injecting the vessels at this stage with a warm solution of gelatin, and hardening the preparation In alcohol, he found : 1. Sticking to the surface of the club-shaped plug of gelatin, endothelial cells, some detached and isolated, others mider- going proliferation. 2. A peculiar configuration of the surface of the plug. This exhibited a number of thorny, seemingly broken-off splcula, which perforated the wall of the vessel, and proved on closer examination to be the radicles of a very beau- tiful system of intercellular canals, filled with gelatin. Thiersch sees in this system of canals a provisional nutrient apparatus, a preliminary vascularisation, and proceeds on this view to explain INFLAMMATORY PRODUCTS. 117 a fact wliicli is certainly very enigmatical, viz. that even parts which have been com])letely separated from the parent organism znay reunite with it, provided they are stitched on early enough. For us, the interest of his discovery lies first in the proof which it affords that the elements foi-ming the walls of those vessels from which new capillaries are about to sprout have their cohesion relaxed in a definite way ; and secondly, in the fact that his views corroborate the histological significance of the blood-vessels as "intercellular," not '^intracellular" canals. The last act in the process of repair by first intention, is the transformation of that portion of embryonic tissue which is not ■employed in the construction of vessels, into fibrous connective tissue. The cells first grow spindle-shaped, just as they do in the normal course of development ; but, owing to their immense number, and the close Avay in which they are packed, this metamorphosis into spindle-cells gives rise to an entirely new variety of tissue — the sjnndle-cell tissue. This term denotes a texture wholly made up of parallel rows of spindle- shaped cells, which are held together by the dovetailing of their pointed ends. The spindle-cell tissue forms as a rule cylin- drical or slightly flattened bundles, which interlace like the bundles of connective tissue. The only question is whether the protoplasmic substance of the spindle-cells undergoes direct transformation into gelatin-yielding fibres, or whether we are to assume with Rollett that the fibres are coined out of the intercellular substance. My own observations lead me to con- clude that when cicatricial tissue is formed from spindle-cell tissue, the greater part of the body of the cell is immediately converted into the substance of the fibre. After a certain time, althouo-h the nature of the tissue is still recoo-nisable in fine sections, it becomes impossible to isolate its component spindle- cells by teasing with needles ; it tends rather to break up into stiff", fibrous fragments of irregular outline ; and these, as is proved by their contained nuclei, are made up of cells which have become fused together. This phenomenon can only be explained on my view of the process. The fibrous bands of the cicatricial tissue are not merely the direct successors, in a general sense, but ■ the only successors, of the fasciculi of the spindle-cell tissue. As contrasted w^ith the normal development of areolar connective tissue, the entire process gives us the im- 118 SUPPURATION. pression of a reckless expenditure of capital, where a judiciou& employment of the interest would have yielded far better results. I say emphatically, hetter results, for the cicatricial tissue is far from being a connective tissue of ideally high quality. On the contrary, its fibres are stiff, inelastic, and misshapen ; its cells are represented by shrunken staff-shaped nuclei, and its vital capacity is proportionately reduced. Moreover, the cicatricial tissue exhibits an extreme proneness to contract in all its dimen- sions. This phenomenon, which is, on the whole, a very mis- chievous one, is termed induration, sclerosis, or contraction ; its occurrence is anticipated with such certainty, that upon it is founded the operation for entropion, by which an inverted eyelid is turned outwards. It need hardly be said, that this general diminution in bulk is a physical rather than a vital phenomenon; the removal of water has a great deal to do with it ; for the white, glistening tissue of a cicatrix is dry, compact, and harder k) cut than any other variety of connective tissue. C. Suijpuration. § 94. Pus is a fluid tissue. Numberless cells, the so-called pus-corpuscles, are suspended in a colourless serum to which they impart a greyish-white or yellowish-grey tint ; the liquor pnris holds albumen, mucin, pyin, and salts in solution. The Pus-corpuscles, a. From a liealthily-granulatiug wound; h. From an abscess in the areolar tissue ; c. The same treated with dilute acetic acid ; d. From a sinus in bone (necrosis) ; €. Migratory pus-corpuscles. cells are small and spherical, partly impregnated, partly sprinkled with fine granules which, as a rule, conceal the nucleus from view. On the addition of acetic acid the granules disappear, SUPPURATION. lia and the nuclear structures start into clear relief. There is usually more than one nucleus ; often three or four. In the latter case, the nuclei are small, not always strictly circular, and exhibit a peculiar lustre which suggests the homogeneity of their structure (fig. 38). These cejls were at one time considered to be of specific nature, and were hence termed pus-corpuscles. This was an error ; for we meet with similar cells in the blood, where a certain number of the colourless corpuscles are multi- nuclear ; and with regard to these, Vircliow declares that they are incapable of taking any farther part in the deyelopment of the blood. More recently it has been shown that saturation of the blood with carbon dioxide causes all the uninuclear colour- less cells to become multinuclear and then to undergo disin tegration. The presence of seyeral nuclei has not the same significance here, as that diyision of the nucleus which precedes the fissiparous multiplication of cells ; it seems rather to point to a breaking-up of the cell, preliminary to its total dissolution. Moreoyer, it is a mistake to suppose that pus contains only cells of this kind. Creamy pus indeed {pus honum et laudahile), such as is poured out on surfaces clothed with healthy granulations, contains a large majority of uninuclear cells, which I should not be able to distinguish from the migratory corpuscles of connec- tlye tissue. Sanious pus, on the other hand, such as is yielded by carious bone, contains, as a rule, cell-deriyatives, oil-globules, albuminous molecules, &c., rather than pus-cells. In fact, we find a series of transitional forms between the uninuclear and the multinuclear elements of pus, just as in the case of white blood- corpuscles ; the latter, incapable of further develop- ment, undergoing disintegration by fatty and granular meta- morphosis. According then as the pus is fresh or stale, according as it has been rapidly or slowly produced, or has undergone a slower or more rapid decomposition, do we find in it uninuclear or multinuclear cells or even cell-debris. § 95. When we hear it asserted that pus may be produced in various ways, when we find pus-formation in connective tissue, such as we have just now been considering, contrasted with pus-formation on mucous and serous surfaces, or in coagu- lated blood, &c., we must, in the present state of our know- ledge, accept such contrasts with a grain of salt. The great bulk of pus is everywhere formed by the migration of colourless 120 SUPPURATION. corpuscles from the vessels. We must bear lu mind liowever the following points of divergence : first, the path taken by the migrating cells tends in the one case towards a free surface, in the other, towards a point situated in the paren- chyma of the connective tissue ; secondly, that in the develop- ment of pus on mucous and serous membranes, the share taken in its production by the epithelium must not be left out of account. As regards the formation of pus in connective tissue, i.e. the suppuration of an inflammatory exudation, with which alone we are now^ concerned, we must keep in mind the same reservations and restrictions which we were obliged to establish in connexion wuth the process of plastic exudation itself. It is by no means proved that all pus-corpuscles are derived fi'om the vessels ; for on the one hand a formative irrita- tion of the stationary corpuscles of connective tissue has been shown to take place, and their break-up into migratory cells rendered highly probable ; while on the other hand, multiplica- tion of the exuded cells by division has been directly observed. Finally, we may look on suppuration as in reality the most direct continuation of the earliest phenomena of inflammation. Its essential feature is a tendency towards over-production, towards exuberance of o-rowth, wherebv colossal numbers of young cells are generated in a relatively brief period of time. The proximate cause of the suppuration of an inflammatory exudation, or, in ordinary phrase, of the passage of inflammation into suppuration, is often to be sought in the excessive afllux of pabulum to the inflamed part ; hence the antiphlogistic method of treatment endeavours in the first place to moderate or diminish this afliux. In other cases again, we find the cause in the quality of the irritant ; thus chemical agents, and particularly septic ferments, lead to suppurative inflammations. Conversely, we might anticipate that in indi^■iduals whose nutrient fluids had undergone septic infection (septicaemia), every inflammation would tend to assume a suppurative character. Finally, there is such a thing as individual predisposition, i.e. there are persons in whom the most gentle irritants excite suppurative inflammations. But this is by the way. We must return to the consideration of the anatomical course of the suppurative process. ^96. The next phase is the formation of an abscess. The SUPPURATION. 121 cells which were originally distributed with tolerable uni- formity through the inflamed parenchyma, forsake their seat of origin, and make their way from all sides towards a central point, which subsequently becomes the purulent deposit (abscessuSy apostema). This migratiou is due partly to the spontaneous motility of the cells, partly to a more or less vigorous transuda- tion from the vessels, which assists their transit and determines its direction towards a common centre. After this convero-ent current has been flowing for a time, the centre in question exhibits a nodular induration. In its interior the vessels are compressed, the parenchyma grows pale, the nutrition of the part ceases with the arrest of the blood-supply ; softening and fatty degeneration set in ; in the transuded fluid the fibres of the connective tissue melt away, and the cells are freed from their connexions. Fluctuation is now perceptible to the finger ; the purulent deposit is formed, or, in surgical phrase, the abscess is ripe. Having thus traced the dcvelojjment of an abscess, it seems liardlv necessary to define it as an interstitial cavity in the bod}- containing pus, were it not that purulent accumulations may arise in other ways as well ; these indeed arc not termed abscesses, but they are equivalent to abscesses in a histological point of view ; I allude to purulent effusions into closed cavities, such as serous sacs, joints, mucous bursae, and sheaths of tendons. This extended application of the term corresponds to very wide limits of variation in point of size and form, but it finds its justifica- tion in the identity of their subsequent course. ^97. By far the most frequent termination of an abscess is its rupture, tlie evacuation of the pus externally. The same forces which brought the pus together continue to push it for- ward in the direction of least resistance. The elastic reaction of parts which enclose the pus, and which it has displaced, operates in the same Avay ; and as the pus (thanks to the very extensive distribution of the connective tissue) is everywhere in contact wdth a tissue susceptible of being itself converted into pus, the pre-eminent frequency of this termination is quite intelligible. The pus then forces its way in the direction of least resistance ; this direction is in the last resort always outwards, the final result being perforation of the cutis, or of a mucous membrane. The matter once evacuated, the cavity of the aljscess becomes a 122 ORGANISATION AFTER SUPPURATION. free pus-secreting surface ; it falls under the category of ulcers, Avliich we shall presently have occasion to consider. ^ 98. But the pus is not always discharged externally. Kay, it maybe made capable of reabsorption, at any stage of its accu- mulation, by fatty degeneration of its corpuscles, and so be ab- sorbed. Moreover, some recent observations make it likely that this capacity for being reabsorbed belongs even to abscesses of old standing which have become cheesy, and whose size has con- tinued the same for long periods of time. The cheesy matter enters the blood-vessels and lymphatics in a minutely particulate form, and may then (as we shall see hereafter) give rise to miliarv tuberculosis. D. Organisation after Suppuration. ^99. The sum of all that has already been said concerning the nature of pus shows clearly enough, I believe, that this pro- duct is something alien, something which has become foreign to the organism, and against which it is not guarded by a protecting coat of epithelium as it is against the outer world generally. From the moment, therefore, that the abscess is constituted as such, the organism tends to restore its own internal unity and completeness (Insichgeschlossensein) which are disturbed by the presence of the abscess. To this end however the simpler means of organisation referred to above, sc, the production of vessels and connective tissue are not of themselves adequate. A new skin and cuticle have to be formed ; and this brings us to that most interesting variety of morphological evolution which is usuallv termed repair hj second intention. The term is primarily applied to the healing of wounds, when we have failed to restore the solution of continuity by precise apposition of the divided parts, when suppuration has compelled us to remove our sutures and strapping, or when the loss of substance is so great that the due approximation of the cut edges is impossible, and the paren- chyma is left unprotected, exposed to the action of the atmo- sphere, kc. Here too, however, the denotation of the term transcends its definition. Exactly the same phenomena recm' when the organism has to be shut off from an abscess, or any- thino- analogous to an abscess (^ 9G) : when a portion of the body has been converted by necrosis, burning, or corrosion into ORGANISATION AFTEll SUPPUEATION. 123 a foreign body, only to be got rid of by suppuration. To this group too belongs the process of repair in ulcers : in a word, repair by second intention is synonymous with organisation after suppuration. § 100. We .have to do with a free surface yielding pus. From countless points of this surface young cells are forcing their way ; these are accompanied by a fluid mainly transuded from the blood, and very rich in dissolved albuminous matters. Sooner or later the frontier-line of the secreting surface exhibits changes diametrically opposite to those which occurred when the plastic exudation melted into pus. The cells close up their ranks. A layer of embryonic connective tissue is formed, which intervenes between the parenchyma of the organism on the one hand, and the pus on the other. Any pus-corpuscles which may be secreted after the completion of this membrane must make their way through the layer of embryonal connec- tive tissue ; this waxes thicker, and rises into small globular protuberances, the so-called " fleshy wnrts," or " granula- tions." These granulations are the physical basis of all further evolution ; they produce both skin and cuticle, but before all, new vessels. § 101. Vasciilarisation, here as elsewhere, is the most powerful agent in organisation. The reason why the massing together of cells in large numbers is associated with increased frailty of the individual elements, lies in the great difficulty with which an abundant collection of cells, e.r/. the juis-corpuscles which unite to form an abscess, can be supplied with nourishment, if indeed their nourishment is possible at all. Should the collection be a large one, the elements nearest its periphery will continue to get what pabulum they require from the adjoining nutrient fluid^ and to rid themselves of their excrementitious products. The farther we advance inwards the greater do the obstacles in the way of this interchange become ; the excreta accumulate ; the pabulum has no access to the parts. The only way in which these disastrous results may be avoided is by vascularisation, i.e. the foi-mation of canals, through which the products of the oro^ans of sanoruification mav be carried into the midst of the territory requiring nourishment, and the excrementitious matters from the interior of the same territory may be removed. In this way even aggregates of embryonic tissue of considerable 124 ORGANISATION AFTER SUPPURATION. size may persist for some length of time, and maintain their connexion with the organism. g 102. As regards vascularisation, in the course of repair by second intention more particuhirly, the distribution of the em- Ijryonic tissue upon a level surface affords favourable opportu- nities for the access of pabulum. Never thelesSj an abundant development of new vessels sets in here at a very early period to promote this object. The histological details of the process are the same as in the secondary mode of vascularisation ; along certain lines running througli the parenchyma which is to be vascularised a closer aggregation of the cells becomes apparent ; a cord or row of cells becomes visible, pointing out the form and direction of the future blood-path. But how is a cylinder of cells converted into a tube ? How is the new vessel opened up ? These questions can only be answered by a reference to the discoveries of Thiersch, alluded to under the head of repair by the hrst intention. Since the pervious parent-vessels, on which both limbs of the newly-formed loops rest, are also shrouded hi ii dense mass of cells, the most enigmatical part of the entire process is withdrawn from direct observation. We know that at a certain time the blood makes its appearance in the axis of the cellular cord, that the cells of which the latter consists are pushed asunder by the stream, and proceed forthwith to form ■the Avail of the new vessel. I presume that the cells of which the wall of the parent-vessel is made up are everywhere loosened by the inflammatory irritation, thus ceasing to offer any special hindrance to the tunnelling of a channel for the blood. Some such hypothesis is indispensable for the due appreciation of the farther progress of vascularisation, during which the newly- formed vessels, which are still wholly made up of cells, give rise in their turn to new vascular loops. The development of capil- laries from within keeps pace with the formation of layer upon layer of new embryonic tissue upon the surface. The capillary loops, with their long parallel limbs, struggle vertically upwards into the granulations ; they reach nearly as far as the suj^pm^at- ing surface, their points of curvature being somewhat dilated <%39). § 103. This brings us to the point at which the formative process is most luxuriant. Supposing progress in this direction to be unrestrained, it may lead to another morbid deviation, sc. ORGANISATION AFTEH SUPPUEATION. 125 to the formation of the so-called ^^ proud flesh ** {caro liuumans)^ Avhereof more anon. As a rule however, a farther chano-e no\y occurs which is suited to check any excess of production on the affected surface, and to pave the way for cicatrisation. The em- bryonic connective tissue undergoes conversion into cicatricial tissue. The change begins in the deepest layers of the granula- tions, and exhibits the same phases and transitions with Avhich we were made acquainted in repair by the first intention. The first step is the formation of spindle-cell tissue. The plane in which the spindle-cells are stratified determines the direction in which the earliest fibrilla3 become visible. Xext, the formation of cicatricial tissue and its contraction succeed each other, as described in § 93. The phenomenon is the same ; but the results are more complicated than in repair by the first intention. For as it begins (as already said) in the deepest layers of the pyogenic membrane, the base on which the granulations are situated is the first part to undergo contraction. The raw surface shrinks ; and it is the vessels which are primarily affected by this shrinking, inasmuch as they penetrate vertically through the cicatrising base. They are compressed, their calibre is diminished ; nay, they undergo complete obliteration here and there. In proportion as this takes place the granulations lose in volume, they contain less juice, and the pus-formation grows feebler and more slow. Thus, by a really astonishing consilience of the various formative forces, the way is paved for the last step ; and this consists in the secretion of an epithelial covering, the skinninor over of the o;ranulatincT surflice. § 104. True that the cuticular investment usually sj^reads from the edges of the granulating surface towards its centre. To this rule however there are exceptions ; small patches of cuticle have often been noticed at some distance from the edge, j^atches which gradually increased in size and finally blended with the marginal skin. Even Avere there any difficulty in determining this fact with the unaided eye, all doubts would be removed bv carefully examining a vertical section through the edge of a granulating surface in process of repair (fig. 39) ; this shows conclusively that the raw surface gets its cuticle not by an inde- pendent ingrowth of the epithelium from the edges over the granulating surface, but by the conversion of the outermost layer of the granulation-tissue into epithelium. At e (fig. 39) the 126 ORGANISATION AFTER SUPPURATION. separation of the epithelium from the connective tissue is com- plete, at/ the boundary -line Is blurred, but even at^ we are still able, by the closer arrangement of the outermost cells to recog- nise the future epitliellum, althougli no dlflferentiation of the o o o o Vertical section through the edge of a granulating surface in process of reiDair. a. Secretion of pus ; h. Granulation tis- sue (embryonic tissue) with capillary loops whose walls consist of a layer of cells longitudinally disposed ; their thickness decreases as we approach the surface ; c. Cicatri- sation beginning at the base (spindle-cell tissue) ; d. Cica- tricial tissue ; c. Fully-formed cuticle — its middle layer consisting of grooved cells ; /. Young epithelial cells ; g. Zone of differentiation, -v^. elements, as regards their size, the character of their nuclei, &c., has yet set in. We come next to the suppurating surface ; it would seem as though the first foundations of the epithelium ORGANISATION AFTER SUPPURATION. 127 were laid by pus-corpuscles wlilcli had not been set free. If wo look for something analogous to this mode of epithelial develop- ment, we can only compare it to the primordial separation of the blastodermic tissue into epithelial and non-epithelial strata, and so regard it as a true embryonic difterentiation. The adjoining normal epithelium obviously cannot be deemed inert in the matter ; it must be considered to exert some sort of " epithelial infection " (§ 83). Indeed some such hypothesis is necessary to explain the greater frequency (according to Heine and Billroth the invariable occurrence) of cuticular cicatrisation from the margins. The newly-formed epithelium always remains thin and diy. It has never been hitherto observed to develope regular glands or hairs ; on the other hand, I am able to state from personal know- ledge that in some cases of epithelioma in scars, the peg-shaped protrusions of epithelium characteristic of this form of tumour start from the thin cuticle of the cicatrix. • § 105. These are the outlines of formative inflammation, when this runs its entire course in the intermediate apparatus of nutrition, and is combated by its means alone. Various modifi- cations of great interest and importance are determined by the peculiar structure of the individual organs, and must therefore be reserved for consideration in the Special Part of this work. In this place I will only allude once more to that singular devia- tion from the normal course of repair by second intention which consists in the growth of the so-called '' proud flesh." The caro luxurians may be defined as an overgrowth of the granulations. Instead of little warty prominences, which ought not to exceed a line in height or in breadth, we have fungous masses cropping uj^, characterised by being three or four times larger than ordinary granulations, partially dendritic in form, highly vascular, and possessing a certain joower of resisting external influences. These funo-ous cfranulations are distin- guished histologically by a peculiarly, high degree of differentia- tion of the embryonic tissue. In the first place, we have a more elaborate stroma throughout, a stroma resembling that of the lymphatic follicles. It is formed partly by the interstitial cement of the connective tissue, which fills up the lacunar net- work betw^een the spheroidal cells : this stiffens into fine cylin- drical threads : partly by a certain number of the cells them- selves. These assume a stellate form, and constitute the nodal 128 OEGANISATION ArTER SUPPUEATION points of the stroma at tolerably uniform intervals. This stroma can only be demonstrated by carefully pencilling out a fine section of o-ranulation-tissue hardened in alcohol. This arrano^ement constitutes of itself a structure of a liiMicr order, comparable in some degree to the connective-tissue stroma of the intestinal mucous membrane ; and the analogy is carried farther by the occurrence of certain spheroidal bodies which I must pronounce to be newly-developed lymphatic follicles (fig. 40). These lie in the midst of the parenchyma, equidistant on every side from the greater vessels. AVe can readily convince ourselves, by examining very fine sections which have been Lymphatic folUcle from a fniigons granulation (Caries fungosa). For explanation 8ee text. 3^^^. pencilled out, that these round nodules consist mainly of a very delicate reticulum in which minute lymph-corpuscles are em- bedded. The lymph-corpuscles are more firmly attached to the reticulum towards the periphery of the nodules than in their centre ; so that we usually have a border-zone, which it is difficult to clear up. Beyond this we find a zone, traversed by stellate corpuscles of considerable size ; so that if we could only prove that these structures were in communication with the lymphatic vessels, the evidence in favour of their being true lymphatic follicles would be complete. I may remind the reader that this communication still remains to be proved in the case of the tonsillar follicles as well. § 106. Nerve-fibres are not an integral constituent of granulations; yet surgeons are familiar with so-called "irritable OVERGROWTH OF CONNECTIVE TISSUE. 129 granulations," and I have succeeded in discovering an abundant supply of nerve-fibres in an exquisite example of these sent to mo bv Professor Billroth. 2. Xox-Inflammatory Overgrowth of the Coxxective Tissue. § 107. I have already (§ 85) relegated the hyperplastic conditions of individual organs to the corresponding chapters of the Special Part of this work, inasmuch as from a histological point of view they do not furnish materials for any generalisa- tion save only that they are quantitative excesses of normal growth. Now the interstitial connective tissue forms an excep- tion to this rule, because it is only a constituent of the various organs, and not itself an organ, and because its increase by way of overgrowth must therefore necessarily entail a qualitative change in structure. Strictly speaking, a large proportion of the processes included in the domain of interstitial inflammation may also be viewed as consisting in an overgrowth (hyperplasia) of the interstitial connective tissue. This applies especially to inflammatory infiltration and the conversion of the infiltrated products into connective tissue. In point of fact the non- inflammatory differs from the inflammatory form of overgrowth only by its slower rate of progress, if we set aside for a moment all thought of its causation. A hyperiemic dilatation of the vessels constitutes in every case the starting-point of the morbid process. This is associated with an emigration of colourless blood-corpuscles, which gives rise to an increase in bulk, a thickening of the connective tissue. Especially noteworthy is the extent to which the sheaths of the vessels arc in- filtrated ; they often attain from three to five times their normal thickness. The transformation of the infiltrated cells into fibrillar connective tissue is a work of time, and seems in many cases (kidneys, pia mater) not to occur at all. Mean- while the close analogy between this process and inflammation is self-evident, so that we cannot quarrel with authors and practitioners for continuing to call it " clironic inflammation." Wherever a definite source of irritation, e.g. a persistent or often renewed, though feeble mechanical irritant is the cause of 9 130 SPECIFIC INELAMMATIOX. the dlstiu'bance, I too am ready to call it ^' clironic inflamma- tion"; but where this is not the case, where, e.g. the phenomena in question are due to passive congestion, it would be utterly wrong to go on speaking of an inflammation instead of a simple hypertrophy or overgrowth. 3. Specific Inflammations. (Granulomata and Lymphomata.') § 108. As the present chapter will introduce us for the first time to the hackneyed word ^^ tumour," it is needful that we should give some brief account of its denotation and signifi- cance. As practitioners we incline to call any new growth a " tumour " in proportion as it lacks the known characters of the inflammatory process. Thus : — 1. The less evidence there is of its having been caused by an inflammator}- irritant, the more does the new growth exhibit a character of " spontaneity." Hero of course, as everywhere else in nature, no such thing as real " spontaneity " is possible. But we are still so far from having any clear insight into the etiology of tumours, that it is really a matter of choice whether we follow those who regard the tumour as the localisation of an antecedent dyscrasia (" Geschwulstkrankheit"), or those who consider the local mis- chief to be in every case the starting-point of the general disease. Billroth, in his Manual of General Surgical Pathology, has taken the former view ; while Virchoiv,* in his book on Tumours, adopts tlie .latter. With amazing care, Vircliow * Vircliow (Kraukh. Gesdiwillste, vol. i. p. 121) divides tumours resulting from proliferation of tissue (as opposed to cysts, &c.), into : 1. Histioid ; made up of some one tissue normally present in the body (Sarcoma). 2. Organoid ; made up of several tissues characteristically arranged to form an organoid structure ; e.g. connective tissue and epithelium in the glandular cancers. 3. Teratoid; made up of several organoid elements, corresponding, however imperfectly, to an entire system in the healthy organism (Dermoid of ovary). 4. Compound or mixed; made up of various dissimilar parts or tissues, not conforming to any plan of normal structure (Cystosar- comata, &c.). — Tr. SPECIFIC INFLAMMATION. 131 endeavours to prove the existence of at least a local j^redisposi- tion in each single case ; and although he has not succeeded in driving the arguments of humoral pathology wholly out of the field, he compels us to admit that some tumours at least originate in a local irritation. As examples we may take epithelioma of the lower lip, due to the persistent irritation of a tobacco-pipe held between the teeth; so also a number of sarcomata caused by pressure; enchondromata of the bones startino; from the seat of fractures, &c. Ao^ain — 2. The less decidedly the remaining cardinal signs of inflam- mation, such as pain, redness, rise of temperature, are associated with the growth, the more nearly does it approach the nature of a tumour. The practitioner's attention is roused and he is led at once to suspect some inflammatory complication, when a tumour causes pain, or when an active hypera3mia with rise of temperature accompanies its development. 3. The less a new formation contains within itself the condi- tions requisite for perfect recovery, the less does it participate in ihe nature of inflammation. Spontaneous cure is a very distinc- tive peculiarity of inflammatory processes. Our conception of a tumour implies that it should continue to grow if left to itself; and even should its size remain stationary, that it should at all events exhibit a. certain degree of permanence. This proposition may be formulated in conjunction with (1) in some such terms as these : inflammations do not originate spontaneously, though they get well of themselves ; tumours arise spontaneously, but are not susceptible of spontaneous cm'e. I am well aware that such a formula as this is very far from being axiomatic. Pedunculated tumours are often spontaneously detached ; nay even the spon- taneous expulsion of entire nodules of cancer has been known to occur. If we inquire into the natural grounds of this distinction, almost instinctively applied by the practitioner, we fiild them in the circumstances of histological development. Inflamma- tory products are generated at the seat of irritation mainly by the accumulation of the mobile cells of the conjoint vascular and connective-tissue system ; this accounts for the rapidity with which they appear, and for hardly a trace of their presence being left when they disappear ; the development of tumours is more nearly in accordance with the laws of normal growth; 132 SYPHILIS. hence their permanence and quasi-organic character. Bearing in mind that an increased afflux of blood plays a chief part in the phenomena of inflammation, we might designate inflamma- tions as disturbances of nutrition, tumours as disturbances of growth. Nevertheless, the opposition is one not of contra- dictories, but of contraries onh', which are connected by several series of intermediate members. One series conducts from in- flammation through the intermediate phases of inflammatory overgrowth and simple overgroAvth to those more complex forms of overgrowth which we call cancers. Another leads from simple inflammation through specific inflammation to those more perfect imitations of normal tissue, which we call sarcomata, enchondromata, myxomata, &c. , and which, taken together, form the histioid group. The former series is chiefly exemplifled in the disorders of the skin, mucous membranes, and glands ; the latter will be dealt with at once. § 109. The specific inflammations differ from ordinary inflammation in that they furnish either instead of, or together with the i^lastic exudation, certain products which exhibit special anatomical peculiarities. These are typical for each individual form, and may be referred broadly to the special quality of the inflammatory irritant. This irritant is in every case a specific virus, which may be introduced into the organism either by hereditary transmission or by contagion, or primarily developed in the organism itself. § 110. Syphilis. Constitutional syphilis maintains a ten- dency in the body to every morbid change that comes under the head of active hyperasmia, inflammation, and inflammatory pTOwth. In the earliest stao;es of the disease it is the more superficial organs, the skin and mucous membranes, which are chiefly affected ; in the later stages the deejoer j^arts become involved as well ; we shall come across examples of syphilitic inflammation when we come to treat of the morbid anatomy of the osseous and nervous systems, of the liver, and the testicle. These inflammations are all distinguished by certain peculiarities in their localisation, their distribution, and their course. One product however merits our esj^ecial notice ; it seldom occurs alone, but is usually associated with the simpder forms. I refer to the syphilitic gumma (syphiloma, Wac/ner). The gumma may be termed a specific jDroduct of syphilis ; its specific ana- SYPHILIS. 133 tomical character residing not in any marked deviation of the gummatous tissue from the familiar types of inflammatory Fig. 41. ^d}!k^^'^^ ' ^% Syphilitic disease of the liver, a. Left lobe; h. Right lobe; cc. Fibroid sheath which traverses the organ from the V. portse to the ligamentum suspensorium and contains gummata. f. growth, but rather in the circumscription of a more or less spheroidal nodule in the midst of a larger deposit of newly- formed embryonic tissue, a nodule which differs from the em- bryonic tissues round it in the farther course of its metamor- phoses. For while the latter undergo conversion into fibroid tissue, forming a cicatrix characterised by a tendency to extreme contraction (§ 93), the former, retaining the circular form of its cells, and occasionally producing an anastomotic network of corpuscles, undergoes a mucoid transformation of its intercellu- lar substance. The main stress however must not be laid on the 'production of mucous tissue, inasmuch as this is clearly a more phase in a slow degenerative change. The cells grow fatty ; their place is taken by round or stellate aggregations of fat-granules, which appear to be capable of lasting as such for long periods of time. The final result is a yellowish-white romided nodule of a soft and elastic consistency, embedded in a 134 SYPHILIS. deposit of newly-formed connective tissue ; this is the specific tumour of syphilis, the ^Hophus" or "gumma syphiliticum." The complete absorption of recent gummata may be effected by suitable medication. At a later period, the nodule becomes cheesy and the surroundino; connective tissue is converted into a tough, fibroid cicatrix, which may occasion the most extreme distortions of the affected organ by its subsequent contraction (fig. 41). Whether we are justified in calling the induration of the primary chancre gummatous I will not take upon me to say. The appearances presented (fig. 42) are those of an infiltration of the connective tissue with small cells, an infiltration distin- guished not so much by the number of the infiltrated cells as by the fact that these cells are very uniformly packed into all the interstices between the vessels on the one hand, and the fibres of the connective tissue on the other. This causes an elastic fe;^^.^s. Syphilitic induration, a. Vessels ; hi. and tlie other parts lefc unshaded are bundles of connective tissue which are dis- sociated by a uniform infiltration with small cells. ^. tension, giving the finger a sense of hardness, while the vessel* remain pervious and the nutrition of the parts is not interfered with. This invariable arrest of the cellular infiltration at a certain stage has undoubtedly something peculiar about it, and reminds us of gummatous tissue ; but whether similar indura- TYPHUS. 135 tions maj not also occur apart from syphilis cannot be decided until we know more about the minute structure of inflammatory indurations in general than we do now. XoTE. — BiesiadecJd refers the induration to a certain stiffness and dryness of the fibrous elements of the connective tissue ; earlier authors sought it in the quality of the exudation {Bicord's plastic ljmph> Michaelis' exudation flakes — ExudatsclwUen). § 111. The syphilitic deposit may also be taken as a type of the lesions caused by leprosy and glanders. In these disorders specific tumours are also formed, side by side with simple inflam- matory products ; the specific tumours continue for long periods in the lowest stage of tissue-development, without undergoing any change; they finally suppurate and burst, or else they undergo fatty degeneration and are absorbed. (For details, see chapter on the Morbid Anatomy of the Skin.) § 112. Typhus. The typhous process is found to differ from simple acute inflammation by the higher degree of development to which the individual cells of the infiltration attain — a degree which brings them nearer to the ''epithelial" type. The acme of the typhous changes (with the details of which we shall become acquainted when we investigate the morbid anatomy of the mucous membranes) is known as medullary infiltration* If the infiltrated matters are examined, they are found to contain cells differing from simple lymph-corpuscles in containing a greater proportionate amount of protoplasm. The protoplasm of the lymph-corpuscle is barely equal to its nucleus in bulk ; while in the cells we are now considering, it occupies at least as much, on an average rather more space than the nucleus. The typhous cell represents the lowest stage as it were, the first rudi- ment of epithelial development ; it would seem however that this augmentation of the protoplasm lacks the vigour and permanence of true epithelial development, inasmuch as the typhous cells maintain themselves at this acme but for a short time, and then succumb rapidly to degenerative changes. * These observations refer clearly to enteric fever {Ileotyphus, typhus ahdominalis). I have purposely retained the author's own term, not wishing to define strictly -^hat he has, perhaps not unintentionally, left rather vague. (Cf. § 370).— Tii. 136 TUBERCLE. 'Note. — From a strictly histological point of view the leukhasmic tumour is very nearly allied to the typhous product ; the former however cannot be classed among the products of morbid growth without farther evidence. {See Chapter I. of Special Part.) § 113. Tubercle. A tliircl type of specific inflammation is exemplified by tubercle. I have already pointed out, when speaking of fatty metamorphosis, that the morbid anatomy of the present day does not recognise as tubercle and tuberculi- sation, what these terms were generally understood to denote little more than ten years ago ; viz. every yellowish-white, friable or greasy, in a word, caseous mass, wherever met with. We restrict the term tubercle Kar 'iioxrjv to a definite nodule, very hard, grey and translucent when first formed, seldom ex- ceedino; a millet-seed in size, but ao:£:reo:ated too^ether in ^reat, nay countless numbers. The confusion, both of names and ideas, excited by the rigid distinction first pointed out by Rein- hardy but carried through by VirclioWj is not diminished by the circumstance that cheesy inflammation and miliary tuberculosis are very often actually associated with one another. Discoveries of extreme interest have very lately been made on this subject. A series of investigations, started by Villemain, carried on by Klehs and others, and in some sense concluded by CoJinheim, have shown that the introduction of " cheesy debris " into the imtrient juices is followed by " miliary tuberculosis." It matters not whether the cheesy matter be introduced by inoculation, or originate in the organism itself. On this view, the minutest particles of cheesy debris must be regarded as endowed with the properties of a virus, capable of causing the growth of tubercle by irritating certain (we shall presently see what) elements of tissue. So much is certain, that tuberculosis is the expression of a dyscrasia, of a morbid state of the liquids of the organism, which often spreads through the body from a single point, but which may perhaps in some cases be con- genital. There is hardly an organ in the body in vrliich tubercle is •.ot occasionally met with ; but its seats of election are the lungs and intestines. The extensive lesions of an ulcerative character, caused by the growth and especially by the degeneration of the tubercles, will be fully described in the Special Part of this TUBEECLE, 137 work. I must confine myself at present to what is really the same in all cases, sc. the minute structure of the grey miliary nodule, and what we know about its genesis. § 114. If we teaze out a miliary tubercle with cataract- needles, w^e readily succeed in isolating the following elements : Fig. 43. L-'^M^'^^^ •-© ^w "^ox:i Ky Elements slio-wn by teazing out a miliary tubercle. 1. The large tubercle-cells ; 2. The small tubercle-cells ; 3. Endo- genous cell-development; 4. Delicate reticulum from the interior of a miliary tubercle ; the cells partly removed by pencilling ; 5. Shreds torn from the adventitia of a small cerebral vessel in the neighbourhood of a miliary tubercle. Fission of the nuclei on the inner surface of the adventitia ; finely-granular protoplasm accumulated in a continuous layer of considerable thickness ; 6. Development of tubercle- cells ; 7. The border of a minute vessel, showing the deve- lopment of tubercle-cells in its adventitia. 1. (Fig. 43) — Large cells, either round, or more often roundly-polygonal, consisting mainly of a finely-granular, highly refracting, seemingly very dense material. The sharp outline, i.e. the smooth surface by which the cell is bounded, leads us to assume the existence of a cell-membrane, although this cannot be demonstrated by the appropriate methods (addition of water, crushing, detection of a double contour, &c.). Most of them 138 TUBEKCLE. contain a single round nucleus, not of great relative size, very lustrous, usually eccentric in position, though seldom causing any lateral protuberance on the surface of the cell. In some of the cells, we find two, three, or more such nuclei, which undoubt- edly originate by fission of the original solitary nucleus ; for we also meet with the intermediate stages of the process in the form of elongated, biscuit- (hourglass-) shaped, and even more deeply constricted nuclei. This fission of the nucleus is to Ije regarded as preparatory to an endogenous production of small cells, utterly unlike those just described ; the latter process indeed is not always carried through ; so that even in the oldest tuber- cles, we may occasionally meet with multinuclear giant-cells i^Langlians), 2. (Fig. 43) — Represents the second form of corpuscular elements, such as may be isolated in greatest number by teazino- out a miliary tubercle. They have nothing in common with those just described save their lustrous, dark-bordered nuclei. In all other points they differ from them, and chiefly in their size, which is far smaller, and which enables them during their endo- genous develoj^ment to exist three and more together in one of the parent-cells ; they differ moreover by the transparent, homo- geneous, and feebly-refracting character of their protoplasm ; the exact opposite of these properties being especially character- istic of the larger cells. It is the last-named of these dis- tinctions which enables us to recognise the young cell in the interior of its parent. The appearance of bright areolae round the nuclei of the latter coincides with the beginnings of endo- genous production ; we may regard the latter as complete when the bright area is marked off by a sharp line from the sur- rounding finely-granular and highly-refractive substance of the parent-cell. This phenomenon is illustrated in fig. 43, 3, representing appearances which are very commonly ob- served. These cells compose the main bulk of the miliary tubercle. What remains after their removal by pencilling and repeated washing, is the finely fibrous network represented in fig 43, 4, to which we shall have to refer hereafter. § 115. Let us now pass on to decide the second question, that concerning the mode of origin and development of the miliarv tubercles. We may expect a priori to find that this TUBERCLE. 13r> morbid product, like so many others, originates in the conjoint vascular and connective-tissue system. Numerous observations have shown, however, that no connective tissue in the organism is so well adapted for the growth of tubercles, as that whicli constitutes the adventitia of the capillary arteries and arterioles (Uebergangsgefasse). If e.g. we examine a tuberculous pia mater, we may readily convince ourselves that the grey nodules follow by preference the finer ramifications of the arteries. On the larger trunks they adhere, either singly or in little groups, forming one-sided protuberances ; on the finer branches, and those vessels which just exceed the capillaries in calibre, they present themselves as spindle-shaped varicosities involving the whole circumference of the vessel (fig. 44). The larger ones exhibit a whitish opacity, beginning at their centre and extending towards the periphery. This opacity is the visible sign of a fatty- granular metamorphosis, of a cheesy transformation, which con- stitutes the normal mode of degeneration to which the grc}' granulation is liable. We assume that it begins in the oldest, the first-formed and most central cells ; so that the chronological order of the changes which the miliary tubercle undergoes,, manifests itself by the formation of concentric zones, the outer- most of which consist of the tubercle-cells themselves, while the inner ones are made up of the products of their cheesy metamorphosis. Granting the truth of this assumption, it follows ex cmitraiio that we must look for the development of the tuber- cular elements at the periphery of the nodules. Miliary tubercles on a vessel from the brain. In the adventitia of the mintiter cerebral vessels, a number of very pale, flat, circular nuclei, furnished with nucleoli, are disposed at regular intervals. These may be demonstrated as 140 TUBERCLE. readily in detached slireds of the membrane, as in those vessels which are still intact. In the latter case, they appear as staff- shaped structures, embedded between the external contour of the vessel and its muscular layer. These nuclei are not naked ; they are surrounded by a small quantity of a finely-granular sub- stance, which is chiefly heaped up in the direction of the long axis of the vessel. A second contour, which surrounds the nuclei at a variable distance, may be rendered visible, according to //is, by the silvering process ; this would give the membrane the sio-nificance of a lymphatic endothelial tube, though all attempts to arrive at some reliable knowledge concerning its relations to the lymphatic system have hitherto failed. This membrane is the starting-point of the morbid growth, and that too in its capacity as a lymphatic endothelium. The first stage of the process consists in a marked augmentation of the residual ]3rotoplasm which surrounds the nuclei. A fissiparous multipli- cation of the nuclei coincides with it in point of time (fig. 43, 5). The nuclei recede from one another ; and while some of them may undergo repeated fission, others enter upon a peculiar change. They assume more of a globular shape in place of their former flattened, discoidal aspect ; as a result of this, they become smaller in size ; whereas they were pale and finely granular, they now assume a homogeneous lustre ; in a word they put on the appearance which has already been referred to as characteristic of the nuclei of the tubercle-cells ; at the same time, alterations set in immediately around tlie nucleus. The protoplasm begins to refract light more highly ; its density increases, so that the nucleus looks as if it were surrounded by a spherical envelope of ground glass ; the sphere is bounded by a line, indistinct at first, but which subsequently becomes sharper and more definite ; this limits the entire structure, and completes the tubercle-cell in all essential respects. Fig. 43, 6, represents shreds of the adven- tltia torn from the growing border of a small tubercle ; in the layer of condensed protoplasm we see on the one hand complete elements with others in process of development, and on the other, cavities which correspond to those elements in form and size ; the cells having dropped out during the mounting of the specimen. Fig. 43, 7, shows the edge of a small vessel in whose adventitia several tubercle-cells and mif^lei are em- bedded. TUBERCLE. 141 These cells are at first so sparingly produced that wide bridges of protoplasm intervene between them ; this also may be seen in fig. 43, 6. As they grow more plentiful, the bridges waste away, the newly developed elements touch each other, and are flattened to some extent by mutual contact. The quantitv of residual protoplasm is very trifling. What there is goes to fill that system of inter-communicating lacuna3 which is necessarily left between a number of spherical structures when in apposition ; it forms a delicate network in whose meshes the tubercle-cells are embedded. Such a network is shown in fio^. 43, 4, the O 7 7 cells having been partially removed by pencilling. It consists of fine round threads, which widen out here and there to form small three-cornered expansions. This always denotes that the con- tact between two adjoining cells has been imperfect, so that a wider film of protoplasm has been left between them. Even nuclei may still be met with in some of the nodal points of the reticulum. The entire structure therefore is in some respects like the finer trabecular networks in the interior of lym2Dhatic glands ; and on this ground alone I was formerly led to institute a comparison between the tissue of tubercle and that of the lymphatic glands ; and, in common with other anatomists ( Virchoiv), to regard tubercle as being actually a lymphoid or lymphomatous morbid growth. What mainly confirmed me in this view however was the similarity between tubercle and the formation of perivascular lymphatic sheaths; the latter process being, in my opinion, the fundamental element in the production of the substance of the ly m2:»hatic glands. Mean- while, however, it was found that the growth of miliary tubercles was inseparably connected, not indeed with the presence of a blood-vessel as such, but only with that of an endothelium. Specific irritation of the endothelia of the lymphatics, the serous membranes, and the blood-vessels (ScJiiippel) is the essential factor in the production of the miliary nodule ; and it is only because the lymphatics run by preference in the immediate neighbourhood, in the adventitia of the blood-vessels, that miliary tubercles also exhibit a preference for that locality. (For the development of tul)ercles on the serous membranes and in the lungs, see special chapters on the morbid anatomy of those organs.) 142 HISTIOID TUMOURS. 4. HisTioiD Tumours. § 116. On the capacity of the intermediate apparatus of nutrition for generating embryonic tissue at nearly any point in the body, are also based those higher products of tissue-genesis which we term " growths " in the strictest sense of the word, or more correctly histioid tumours. These are characterised by tho internal continuity of their constituent elements. The majority are made up of only a single tissue ; should they be composed however, of more tissues than one, the component tissues are never isolated, never marked off, as epithelium is marked off from connective tissue, but are in organic continuity with one another. The explanation of this internal continuity is to be sought in the original unity (Gleichartigkeit) of the material of which the tumour is built up, this material being in every case embryonic tissue. From this, by a subsequent process of differentiation, are developed tissues of a higher type, more particularly the connective substances — connective tissue proper, with those of its varieties which occur in inflammatory products (Fibroma and Sarcoma), cartilage (Chondroma), bone tissue (Osteoma), adipose tissue (Lipoma), mucous tissue (Myxoma) ; the higher anomalous tissue??, such as the muscular (Myoma) and the nervous (true Neuroma) are more rarely produced. Their mode of origin however is precisely the same as in foetal development ; i.e. a certain number of embryonic cells are converted into the specific elements of cartilage, bone, fat, or muscular tissue, while the remainder go to form connective tissue ; moreover, an adequate vascularisation partitions out the resulting structures into territories of nutrition, thus incorporating them with the organism as a whole. This ensures the interdependence of the tissues among themselves, as well as their connexion with the organism; the morbid product taking its place as an organ, though a malformed and unnecessary one. Growths of colossal size are often produced without in any way affecting the integrity of the body ; such growths only requiring removal hj the knife to reestablish the status quo ante. § 117. This last statement requires some qualification. Un- fortunately there exist, even among histioid tumours, a certain number to which we are compelled to ascribe a "malignant" character (Malignitas). HISTIOID TUMOURS. 143 AVe call a tumour '^ malignant," not merely because it en- dangers the life of its host, but because it threatens his life in one particular way, by exciting a definite constitutional malady which is incompatible with the due continuance of the general nutrition of the organism. The symptoms of this general malady (^Cachexia) are: prostration of strength, diminution in the amount of blood, watery blood, emaciation, earthy tint of skin, profuse sweating, diarrhoea, ha3morrhages, &c., to which the patient finally succumbs. All attempts to detect the cause of this general disease by cliemical or microscopical investigation have hitherto proved un- successful. How the malignant tumour gives rise to the cachexia is still unsettled. Those who regard the tumour as primarily a local disease are very naturally interested in identifying the marasmus in question (which is always secondary) with the constitutional tumour-dyscrasia (Geschwulstkrankheit) of the humoral pathologists, and in deriving both equally from the in- fecting action of the malignant growth. This view has especial claims upon our favour; for one thing at least remains beyond all question, viz. that a stimulus is propagated from the primary grov/th which excites the development of similar deposits else- where, and which gradually extends its influence over the entire organism. In this extension of the formative stimulus, the so- called " constitutional infection," we recognise three distinct stages. § 118. During the first stage its operation is confined to the immediate neighbourhood of the primary tumour. It determines the continued production of new foci at the periphery of the central growth, with which they subsequently coalesce. Malignant tumours therefore invariably extend by peripheric infiltration (§ 69, 3). We are obliged to assume that the impulse to morbid growth precedes the growth itself by a certain interval of time. This we learn from what is known as the tendency of malignant tumours to recur after extirpation. Suppose we remove the entire tumour, together with its zone of peripheric infiltration, with a view to arrest the mischief. The incision appeared after the operation to have been wholly within the limits of the healthy tissue; nowhere could we detect even a trace of pathological proliferation. Nevertheless, in the majority of cases we find, to our dismay, that a fresh tumour, similar in character to the 144 HISTIOLD TUMOUES. one removed, recurs at the seat of operation, from the very tissues which seemed at the time so entirely healthy. Unless therefore we adopt the theory of a dyscrasia, we are driven to assume that the tissues, even Avhen already affected by the forma- tive stimulus, afford no visible signs of this till after a certain time has elapsed. ^119. The second stage is characterised by the implication of those lymphatic glands which receive the lymph from the region primarily affected. There can be no doubt that some material stimulus is conveyed by the lymphatics. But what is it? We might think of cells. We know that even coarser particles, e.g, insoluble pigments, rubbed into the abraded cutis in tattooing, are taken up by the lymphatics, and carried to the nearest lymphatic glands, where they are deposited. But may we conscientiously resort to this analogy ? After recent injuries the lymphatics gape, and are well able to take up material particles. Are we justified even in suspecting the existence of some such condition of the lymphatics in the neighbourhood of a tumour? The pigment-granules are either heavy, sharp, or hard particles, which, in consequence of any one of these qualities, and aided by friction of the tattooed surface, are able to penetrate in any direction through the soft parenchyma of the body as far as the lymph -canals. We cannot say the same of cells. Tills analogy therefore must be put aside ; but its rejec- tion does not necessarily involve the rejection of the hypothesis that the lymphatic glands are infected by the transport of cells. On the contrary, thanks to the discovery that young cells are enabled by their amoeboid contractility to penetrate through the connective tissue in all directions, we are no longer at the mercy of the analogy above alluded to ; with a degree of probability verging on certainty we can assign the infection of the lymphatic glands, and of the entire body, to the tumour-elements them- selves, or to such young cells as have acquired infecting powers by direct contact with them. The implication of the lymphatic glands is held to be a proof of the infecting power of a tumour, and so flir as of unfavour- able augury. This outweighs the more sanguine theory (which has been started more than once), that the zymotic virus is shut out from the rest of the organism by closm'e of the lymph-paths in the interior of the . swollen glands. When we HISTIOID TUMOURS. 145 come to study the details of this sort of '^ closure by swelling," we shall find it necessary to admit that it may very probably retard the progress of infection. The delay, however, is never more than temporary; it never amounts to an arrest of the process. § 120. The third and last period in the propagation of the tumour shows us that even the sacrifice of several lymphatic glands has not j^reserved the organism from constitutional disease. The production of secondary deposits in other regions of the body is known as metastasis. Whether this designation is justified by the actual transfer of material particles from the seat of primary mischief and the diseased glands to more remote parts, is open to all the doubts previously expressed; the most active investio^ation has hitherto failed to demonstrate the tumour-elements in the blood, through which their transit must inevitably take place ; so that here also, prudence bids us confine ourselves for the time being to the hypothesis of some zymotic material existinor in the blood. Whoever rejects the theory of a dyscrasia, sees in this radia- tion of the formative stimulus from the seat of primary disease a summary presentment of the relation in which every malignant growth stands towards the organism. He who su2:)ports the doctrine of a primary constitutional disorder occupies a far more difficult position. He may insist however : 1st, that the cachexia cannot as yet be fairly identified with the constitutional Infection, and 2nd, that the formative stimulus must be the same for the ])rimary tumour as for the secondary deposits ; and that the difficulties in the way of explaining the origin of the primary tumour, save on the hypothesis of an antecedent dyscrasia, remain as great as they ever were. For my own part, I do not feel called upon to anticipate in any way the coming solution of this problem. § 121. Having agreed upon the clinical significance of malignity, we may proceed to Inquire, whether there are any anatomical signs by which malignant tumours may be recognised, before their malignity is proved by the occurrence of metas- tasis ; to this inquiry, we return the same answer as Waldei/e)', namely, that tumours tend as a rule to become generalised in direct i^roportlon to the vascularity of the soil in which they grow, and to the number of mobile cells present in their 10 146 SARCOMATA. interior, or immediately around tliem. Vio still liave ^^lenty to do in trying to increase the store of our experience concerning this most important subject, by the thorough histological investi- gation of every tumour which comes under our notice, combined with a careful record of the farther progress of each case. For the present, we will content ourselves with stating the degree of malignity of each individual species of tumour, so far as the experience at our disposal will allow. It will be seen that " cancerous " growths stand foremost in order of malignity, but that some of the histioid tumours (viz. sarcomata and enchon- dromata) are also endowed with a certain measure of malignity, which is not always assignable to their being combined with cancer. § 122. Before dismissing this important subject, several points nearly allied to malignity, but which ought not to be confounded with it, must be placed in their right light. First among these is the general question of danger to life. A tumour may, by its position, its size, its weight, &c., not only occasion the greatest inconvenience to its host, but may be the direct cause of his death without being entitled, on this ground alone, to be called malignant. A fibroid growth in the prostate obstructs the urethra and causes death by retention of urine ; a fibroid of the uterus endangers life by haemorrhage ; we are not justified on such grounds in terming either of these tumours malignant. Neither can the multiple character of a tumour be regarded as ijiso facto evidence of its malignity. "When we find sarcomatous growths in various parts of the skeleton ; when eruptive foci co-exist on the calvarium, the tibia?, the clavicle and the vertebral column, we may legitimately infer that the entire osseous system is diseased, and we may suspect a general disease of bone, analogous to the general aftection of the skin in the exanthemata ; but it would be a mistake to try to identify this primary generalisation of the growth with that secondary generalisation which is peculiar to malignant tumours. The two are independent of each other. a. Sarcomata. § 123. On comparing any sarcoma, as regards its colour and consistency, with muscular tissue, we find it hard to understand SARCOMATA. 147 !iow these tumours can ever have received the name of *• flesh- tumours" (sarcoma from (rdp0. It is true that in common parlance many things besides muscle are called flesh ; for instance, granulations are commonly spoken of as ^' flesh v," and if the name " sarcoma" were derived from this application ■of the term, the comparison might be regarded as a very a})t one, and that on more grounds than one. For the sarcomata are the most interesting of ail histioid tumours, just because they undoubtedly repeat that group of tissues with which we became acquainted among the heteroplastic products of inflammation. We meet once more with the round-celled embryonic tissue of granulations, and with its lymphadenoid variety (caro luxurians)^ with spindle-cell tissue, and the densely fibrous connective tissue of cicatrices. As a rule, we find several of these tissues in combination — combined however in such a way, that one of them constitutes the main bulk of the growth, while the others are present in smaller proportions. The tumour is named after its chief constituent, a j^otiori fit denominatio. Accordingly, we distinguish three main categories of sarco- mata, sc, round-cell sarcomata, spindle-cell sarcomata, and fibromata. The secondary constituents are never co-ordinate with the principal tissue ; they are either preliminary stages in its de- velopment, or products of its farther metamorphosis. These metamorphoses occur in the same order as in formative intlam- ination ; the round-celled tissue (granulation-tissue) stands first in point of time ; it is converted into spindle-cell tissue, which in its turn gives rise to fibrous tissue. We must not however slmt our eyes to the fact that the series of possible evolutional forms is not restricted to the histological products of formative inflammation. Cartilage, bone, mucous and adipose tissue are met with in sarcomata as results of their secondary metamor- phosis. Of course they occur only as subordinate constituents, and enable us to establish varieties ; the tumours in whicli they predominate, or in which they exist alone, forming the farther classes of the heteroplastic histioid growths, the myxomata, lipo- mata, enchondromata and osteomata. This shows us the close inter-connexion of all histioid tumours and helps us to unite tlicm into a single group. The origin and growth of sarcomata vary for each species ; 148 ROUND-CELL SARCOMATA. ^vo may affirm generally that growth by infiltration of surround- ing tissues, the so-called peripheric mode of growth, occupies a subordinate position ; central growth, increase by internal appo- sition, taking the first place. The fibromata afford exquisite examples of central growth ; the medullary round-cell sarcomata incline rather to the peripheric mode of increase ; the spindle- cell sarcomata, in this as in other respects (^sc. as regards malig- nity) occupying an intermediate position. It would be possible to constitute a long series of species and sub-species of sarcomata, were all those modifications to bo taken into account which are mainly due to the seat of the tumour. I prefer to confine my remarks to a limited number of typically recurring forms, and to relegate the consideration of the special sarcomata of individual organs and systems to the second part of this treatise. Among such special forms I place the ossifying sarcoma of the periosteum and the giant- cell sarcoma of the medulla of bone, the glioma of the central nervous organs, the cystosarcomata of the various glands, &c. 1 will also avoid all reference at present to the finer shades of difference between the leading forms ; in my own experience, there is hardly any tumour which has not some shade of differ- ence peculiar to itself; nay, I would go so far as to assert, that tumours exactly similar to one another can only occur at exactht the same point in the organism. Round-cell Sarcomata. § 124. I. — 21ie granulation-like round-cell sarcoma (sarcoma lobo-cellulare simplex). In texture and composition this form of sarcoma approximates most nearly to the type of granulation- tissue. It presents itself to the naked eye as a yellowish or reddish mass, homogeneous throughout, soft yet clastic, and occa- sionally very like fish-roe ; from its cut surface a scanty juice may be scraped ; this juice is nearly clear, or else contains but a small proportion of cells. The cells are small in size, round, and contain relatively large, sharply-defined nuclei, furnished with nucleoli. As a rule, there is but little protoplasm, and what little there is is quite naked ; to make it visible, and to convince ourselves that each of the seemingly free nuclei is really part of fc> ROUND-CELL SARCOMATA. 14) a cell, we are obliged to have recourse to liartlcning the tumour and staining it with carmine.* The structure of a round-cell sarcoma differs from that of ordinary granulations only in degree. Some of the vessels are wider and have thicker walls ; but where they break uj) into ca})illaries, they are quite as frail as those of gramdation-tissucj consisting frequently of no more than a single layer of cells. Their interstices are uniformly packed with the round-cells, and the scanty, soft, amorphous matrix of the embryonic tissue. Ju rare cases, the entire tumour is more highly diti'erentiated ; it recalls the papillose variety of granulations, exhibiting radiating stride, along which it has a tendency to split up. On a subsc- (|uent op})ortunity we will say more about these fasciculated round-cell sarcomata which spring by ])refercnce from the i)erl- osteum, where they are known under the name of Mirconia The simple round-cell sarcomata originate most connnonly from membranous ex[)ansi()ns of connective tissue ; they grow by 2)reference from the })erIosteum and the membranous invest- ments of the nervous centres ; we nuist however be jn'eparcd occasionally to recognise them in other ])arts as well, in the skin, the mucous and serous membranes, nay even in the glands. The simple round-cell sarcoma is closely related to the small-celled spindle-cell sarcoma, and thro'iHi this to the fibroma; it often passes continuously into these toims. In harmony with this is the comparative benignity which distinguishes this variety among all other round-cell sarconuita. § 12"). II. — 77/6' lij)iipluide)iOLd roHiid-cell sarcoma (sarcoma lymphadenoides, molle). This variety owes its softer texture mainly to the circumstance that its cellular elements are less closely aggregated than thoseofordinar}- granulation-tissue. On scrajnng its cut surface a juice, loaded with cells, is readily obtained ; on microscopical examination these prove to be round- * Vircliow is incUiied to ascribe the ai)pcavance of the seemingly free nuclei to an excessive frailty of the bodies of the cells ; and he takes the opportunity of adding an observation whicli all practical histologists should lay to heart (On Tumours, y. *20-l) ; '* this frailty of the cells is so .striking, that 1 have long been in the habit, -whenever a recent tumour t^ecms to consist mainly of largo, naked nuclei, with large, lustrous nucleoli, of at once suspecting that I liave to do with a sarcoma." 150 ROUND-CELL SARCOMATA. cells -with large, oval nuclei, Avliicli refract light but feebly, and are each provided with a j^oint-like nucleolus. On hardening the tumour and pencilling out a fine section, avc discover a deli- cate intercellular network, which forcibly reminds us of the reticulum of the lymphatic follicles, the alimentary mucous mem- brane, and the caro liLTurians (fig. 45 J. This network is stretched between the wide, thin-walled capillaries, and imparts a certain consistency to the entire structure, while permitting fluid to collect in abundance round the cells, and thus favouring their isolation. This form of sarcoma originates most frequently from the- subcutaneous, subfascial, and intermuscular connective tissue of the thigh. Xext in order of frequency come the lymphatic glands. In this case however we are met by the singular diffi- culty that the anatomist may be misled by similarity of structure into regarding the sarcoma as a simple overgrowth, however monstrous, of the glands ; while its clinical mark (one of extreme malignity) indicates its absolute identity with the soft variety of sarcoma. (^See Lymphatic Glands.) Fig. 45. Round-cell sarcoma, a. Lumina of vessels ; l. Parenchyma partially pGncilled out to sliow the delicate network formed by the hardened matrix, y^^. There are several varieties of the lymphadenoid sarcoma. The Upomatoiis variety (sarcoma lipomatodcs) is characterised by EOUND-CELL SARCOMATA. 151 having its cells partially converted by fatty infiltration into fat- cells. This transformation is always restricted to a limited number of the elements present ; inasmuch however as the altered cells arrest attention by their lustre and their size, it may very readily seem as though the vast majority, if not all, of the sarcoma-cells had been converted into fat-cells. The resem- blance to genuine adipose tissue does not go very far ; the lack of uniformity in the infiltration, and the promiscuous assemblage of very large and very small fat-cells, which are never united into clusters, make it impossible to confound these tumours with lipomata. The irqjxomatous sarcoma (s. myxomatodes). Small portions of mucous tissue are not unfrequehtly found embedded here and there in the substance of round-cell sarcomata. Such islets betray themselves even to the unaided eye by their transparent, jelly-like, tremulous consistency ; the microscope usually demon- strates an abundant proportion of mucous basis-substance, with a great number of round-cells wdiich do not anastomose with one another, embedded in it. Mucous softening" of the basis- substance may justly be regarded as a secondary metamorphosis to which all round-cell sarcomata are liable. The possibility of tliis change occurring at an early period in their development, and its extension through large portions of a tumour, justifies the term " myxomatous sarcoma." ^ay, the mucous tissue may so exceed the proper structure of the tumour in amount, that we might be led to think of a true myxoma, but for the presence of some few unaltered portions ; these, and more particularly the youngest products at the periphery of the tumour, and its striking metastases, place its sarcomatous nature beyond the possibility of question. The extremely rapid rate of growth which is charac- teristic of myxomatous sarcomata might be inferred from the fact that m.ucus, owing to its capacity for swelling by imbibition, takes up a volume disproportionately greater than that occupied by the scanty intercellular substance of the sarcoma. Mucous metamorphosis and fatty infiltration often co-exist ; such tumours are peculiarly prone to assume a colossal size. The lax connective tissue of the extremities and the subperi- toneal connective tissue are the seats of election of the mucous variety of sarcoma. The large-celled round-cell sarcoma is distinguished by the 152 ROUND-CELL SARCOMATA. approximation of its cells to the epithelial type, and by an inter- cellular network Avitli meshes of proportionate size (fig. 46). This tumour is very soft, cerebriform, and therefore easily con- founded with the next species. Fig. 46. The large-celled round-cell sarcoma, -iuu- (After Billroth). III. — The alveolar round-cell sarcoma {Bilbvth) (sarcoma mcdullare, carcinomatodes) represents a farther advance in the independent evolution of the cells, analogous on the one hand to the suppuration of an inflamed texture, while on the other it recalls that more sharply-defined contrast between the connective tissue and the corpuscular structures which we shall find in cancer. Characteristic of this variety is the occurrence of globular masses of cells, which are no longer held together by any proper matrix, but resemble the pus-corpuscles of a minute abscess in occupying a gap of appropriate size in the continuity of the connective tissue. This must not be taken to imply that the cells in any way resemble pus-corpuscles ; on the contrary, they are notably larger in size, they are provided with round, vesicular nuclei containing lustrous nucleoli, and verge far more nearly on the epithelial type, which in solitary instances they may even simulate in the most deceptive way. And here I go farther than many will be disposed to follow me ; I regard the ROUND-CELL SARCOMATA. 153 structure in question as being really a cancerous degeneration of tlic sarcoma (s. carcinomatodes). In my opinion, we are no longer justified in regarding that cancerous type of structure which is co-extensive with the clinical denotation of carcinoma, as based exclusively upon the primordial opposition between connective tissue and epithelium. ^^ Stroma " and ^' embedded cells" may be produced in more ways than one, and " epithelioid " is not synonymous with '^ epithelial "; though we may feel puzzled to explain how it is that those cells which separate from tlie parent soil in a more organic manner, slowly, and not sud- denly like the corpuscular elements of pus, should invariably exhibit this tendency towards a more epithelial type of develop- ment. For there is just this distinction between genuine suppu- ration and this simulacrum of it, that we cannot simply regard the globular aggregations of cells as being wholly outside of the nutrition of the body. Their continued existence without under- going fatty degeneration affords sufficient proof of this. 8. carcinomatodes occurs in the most diverse parts of the intermediate apparatus of nutrition ; it is most frequent in the marrow of bone, in the eye, in the subcutaneous tissue. A pecu- liarly malignant variety, characterised by the pigmentation of its cells, is known as 'pigmentanj cancer (s. alveolarc pigmcn- FiG. 47. Alveolar round-cell sarcoma, pigmented. &. An alveolus from which its proper globe of round-cells has dropped out ; c. Vessel, with pigmented endotheha ; d. Pigmented round- cells ; e. Spindle-cells, forming stroma. 154 SPINDLE-CELL SARCOMATA. tatum). The provisional diagnosis of this variety is based on tlie great softness and dark colour of the tumour. On micro- scopical examination we find, side by side Avitli the alveolar structure in which its growth culminates (fig. 47), parts of vari- able size, illustrating earlier stages in its development. Most common is an infiltration of the connective tissue with pig- mented round-cells ; the transition from this to the meduUarj structure being operated by circumscribed aggregations of such cells. In other cases a well-marked sarcomatous texture, oflener of the spindle- cell than of the round-cell kind, has obviously existed alone for a considerable time before the characteristic globes of cells can have been developed. This leads us to believe that the melanoses generally are very closely related to one another ; a view which will be more amply developed Avhen we come to speak of what is vulgarly known as ^'pig- mcntarv," or ''melanotic'' sarcoma. Spindle-cell Saecomata. § 126. IV. Tlie small-celled qjindle-cell sarcoma (s. fuso- cellulare durum) stands in the same relation to other spindle-cell sarcomata as the m-anulation-like sarcoma towards the remainino; round-cell sarcomata. It deviates least from the type of inflam- matory growth, closely imitating that sj^indle-cell tissue of recent cicatrices which constitutes the permanent link between ^^ranula- tion-tissue and the fibroid tissue of cicatrices. The characteristic element of its texture is a short and narrow spindle-cell, con- tainino; a roundlv-oval nucleus with or without a nucleolus. The protoplasm of the cell is finely-granular; it is thickest immediately around the nucleus ; a limitary membrane cannot be certainly shown to exist ; the smaller cells are undoubtedly devoid of one. The spindle-cells of which the tumour is made up are very regularly dovetailed into each other, the acute angle left vacant between the pointed ends of every pair of adjacent elements being filled by the pointed end of a third one, lying either behind or in front of them. No trace of any interstitial sub- stance is to be detected ; in no case is there more of it present than there is in granulation-tissue ; but this minimum, which is really nothing more than an amorphous and glutinous cement SPINDLE-CELL SARCOMATA. 15> to keep the cells together, cannot be supposed to be lacking even in spindle-cell tissue ; by its aid, and owing also to the harmonious coaptation alluded to above, bands of cells are formed, bundles of variable thickness, which constitute the proxi- mate structural elements of the spindle-cell sarcoma. The bundles very rarely radiate from a single centre; more com- monly we find a number of centres ; the various systems of fasciculi being interwoven wdth one another in the various lines indicated by the position of those points. As a general rule however, we are not able to detect any definite plan in accordance with which the bundles are combined to form a single whole. In every section we examine (fig. 48) we find some fasciculi divided longitudinally, others transversely, others- again in a more or less oblique direction. An attempt has been Wf "1 Spindle-cell sarcoma. A^essels gaping. The cellular bands divided, some transversely, some longitudinally, -j^^. made to connect the course of the cellular bands with that of vessels ; but this is altogether wrong ; for although the thicker fiisciculi invariably contain an axial vessel of considerable size, this is true of the thicker fasciculi only. With this exception, the vessels form networks, just as in other parenchymatous structures, permeating the cellular bands in all directions. More- over all the vessels of a sarcoma, including those of larger calibre, have as good as no proper walls ; they present themselves in transverse sections of hardened specimens as simple canals, tunnelled and drilled through the tissue. The small-celled spindlc-ccll sarcoma grows by preference from 156 SPINDLE-CELL SARCOMATA. fibrous membranes, fasciae, slieatlis of vessels and nerves, the subcutaneous and submucous connective tissues ; in a word, its seats of election are the same as those of fibroma ; indeed, the two not unfrequently occur together (e.g. in tlie uterus). More- over, in all such sarcomata there are parts where the spindle-cell tissue passes into fibrous connective tissue ; tumours occur, which arc made up of both these tissues in equal proportions ; so that the connexion between this variety of sarcoma and fibroma is so intimate as almost to amount to identity. V. The large-celled spindle-cell sarcoma is much more than a mere variety of the preceding form. It differs from it in one most important point ; the disproj^ortionate development of its cells as compared with all the remaining elements of its struc- ture. The spindle-cells may attain the very considerable thick- ness of '015", and a length so enormous, that their two ex- tremities, under a magnifying power of 200 diameters, are separated from each other by three times the diameter of the microscopic field. The thickest part of the cell corresponds in position to the large, roundly-oval nucleus, with its lustrous nucleolus. The protoplasm is finely-granular and soft in the neighbourhood of the nucleus ; as we recede from the nucleus it becomes more homogeneous. No cell-membrane can be shown to .exist; but the processes occasionally exhibit so marked a degree of tenacity, and so high a refractive power, that we must regard them as made up of protoplasm which has grown rigid. The name " spindle-ccU" implies the existence of two such pro- FiG. 49. Large-celled spindle-ccll sarcoma, after Virclov: SPINDLE-CELL SARCOMATA. 157 Fjg. 50. cesses; exceptionally however, we find three or more, giving the cell a stellate character ( Virchoiv). In typical examples of spindle-cell sarcomata the cells unite to form bands of considerable size, leaflets, and fasciculi. These may radiate in straight lines in every direction from a common base (radiating sarcoma, foliated sarcoma) ; or they may be elaborately interwoven with one another (trabecular sarcoma). These tumours may grow to a very considerable size without undergoing any farther modification of structure or composition. The enormous o-rowth of the cells is in some measure vicarious for the due production of fibrous intercellular substance ; and if we are disposed to agree with Mtuc SchuUze in viewing the latter as simply metamorphosed protoplasm, this would be a case in Avhich building materials had been generated in profusion, but not used. The large-celled spindle-cell sarcomata start from fascia and membranes, seldom from the inter- stitial tissue of Mandular orojans. Their malignity is restricted in degree ; they xQYj seldom recur after timely cxtir- ])ation. Of course they must be care- fully distinguished from cancers and medullary sarcomata with a radial structure. The only ^■ariety of the large- celled spindle-cell sarcoma is a tumour Avhich is met with in the skin of the cheek ; it is essentially a combina- tion of the round-cell with the spindle- cell type. Broad, fibrous bands of spindle-shaped cells diverge from one or more centres ; the intervals between them are occupied by the round-cell tissue. This arrangement is repre- sented in fig. 50. AVe see the colossal spindle-cells, with their long bodies and yet longer processes, enclosing long meshes in which the round-cells are embedded. VI. 21ie pigmentary or melanotic sarcoma (s. melanodes), starts most commonly from the choroid coat of the eye ; next in order of frequency from the skin ; both parts, in which Large-celled sarcoma. A place in which parallel rows of colossal spindle- cells are mingled with round-cells. a. Eonnd- cells; ?^ Vessel, ^^n- 108 SPINDLE-CELL SARCOMATA. tlio cellular elements are normally infiltrated with a certain amount of pigmentary matter. Pigmentation is usually explained by supposing that the morbid growth inherits the vital pecu- liarities of those cells from which it sprang. But this doctrine must not be too rashly accepted. The metastatic deposits, which, owing to the well-marked malignity of the melanotic sarcoma, are by no means rare, exhibit the same disposition to pigmentary infiltration, though developed in parts where no physiological pigmentation is known to occur. This transfer of a purely local peculiarity to the secondary tumours has been advanced both for and against the doctrine in question. For it, by those who hold that metastasis is caused by the transfer of material elements from the primary tumour to other parts ; against it, by the believers in a constitutional dyscrasia which generates black tumours, where it generates any tumours at all. We ought, in my opinion, to distinguish as clearly as we •can between the two following points : 1st, the exciting of the metastatic deposit by cells which have migrated from the primary tumour ; and 2nd, the pigmentation of the secondary tumour. AVith regard to the former, I refer the reader to the hypotheses and scruples enunciated in § 120; with reference to the latter, it must be understood that all the cells of a melanotic eirowth are originally colourless. No one will assert that they are directly descended from cells which have migrated from the primary tumour ; on the contrary, their local origin is beyond all ques- tion ; and as they nevertheless become pigmented, we must needs ascribe their pigmentation to a constitutional tendency Avhicli is independent of the seat of origin of the primary tumour. Etiological experience accords with this view ; it teaches us that an over-production of pigment is, at all events in the skin, a l)redisposing element in the causation of these tumours. This over-production manifests itself either in the growth of black Avarts which may degenerate directly into melanotic sarcomata, or in a black or brown staining of the skin, whether diffuse or circumscribed. The special predisposition of creatures totally devoid of pigment, e.g. of white horses, to become affected by melanotic sarcoma, may be explained on the theory of a vicarious j)igmcntation, the deposit occurring at a single point, and being therefore associated with a certain degree of tissue irritation. In all melanotic tumours the cells are the exclusive deposi- SPINDLE-CELL SARCOMATA. 159 tarles of the pigment. The histological details of pigmentary infiltration have been fully described in the early part of this AYork ; the reader may refer to the corresponding sections. I there repudiated, as regards melanotic growths, the hypothesis which derives pigmentation solely from antecedent haemorrhages, substituting the view that in such cases soluble blood-pigment was taken up from the blood. I arrived at this conclusion, apart from the lack of evidence in support of the hemorrhagic theory, from considering how pigment first originates in tumours which have existed for a considerable time as simple medullary sarco- mata, and have subsequently become melanotic; recurring as such after extirpation and giving rise to secondary deposits of the same kind. In such tumours we are often able to determine that the earliest traces of pigmentary infiltration appear in the epithelial cells lining the vessels. Can this be explained otherwise than by supposing that the epithelial cells take up the diffused colouring-matter from the blood? that it becomes concentrated and then precipitated in a granular form in their interior ? And when pigmentation of precisely the same kind makes its appear- ance at a later period outside the vessels, and finally extends throughout the entire parenchyma of the tumour, I cannot see any reason for doubting that here too the phenomenon takes place in the same manner as in the epithelial cells which line the vessels — by the absorption of diffused colouring-matter from the blood. § 127. In comparison with the general pathological relations of melanotic tumours which have just been discussed, their posi- tion in the anatomical scale is a question of subordinate moment What is vulgarly known as melanotic cancer has already been described (§ 125) under the name of alveolar round-cell sarcoma, or medullary melanotic sarcoma. The remainino; melanotic growths belong for the most part to the group of spindle-cell sarcomata. Their consistency is generally firmer ; their texture fiisciculated or foliaceous. Their well-marked tendency to pro- ject above the surface, to form tuberous and fungous elevations, a tendency which they have in common with the round-cell sarco- mata, distinguishes them veiy notably from the destructive carci- nomata. As regards their colour, we must bear in mind the principle above referred to (of the colourless condition of their elements when young), as a standard of comparison. Melanotic 160 riBEOUS SARCOMATA. sarcomata of great size occur, which betray their true character at first only by a black or brown marbling, a mottled or piebald appearance. The deep brown-black, sepia tint is confined to the most extreme degree of pigmentary infiltration. A fibromatous character is only exhibited, according to VircJioiCj by the melanotic fungosities of white horses, alluded to above ; tumours differing in their benign character from all other melano-sarcomata, which are invariably malignant. Fibrous Sarcomata. ^ 128. VII. The Fibroid. I cannot separate the fibromata from the sarcomata. Just as we sought the prototypes of the round- cell and spindle-cell sarcomata in the round and spindle-cell tissues of inflammatory proliferation, so we shall find the proto- type of the fibromata in the formed tissue of cicatrices. The common fibroid (desmoid) consists of a fibrous, reddish- white, stiffly-elastic substance, so dense and tough or even hard, that it creaks under the knife. Its structural elements are identical with those of cicatricial tissue. If we tear off a fine fibril from the cut surface of the tumour, and tease it out, we are amazed at the enormous bulk v>'hich it assumes, i.e. at tlie Fig. 51. Transverse section through a fibroma of the uterus. 3^—. a. Isolated cellular elements ; I. fasciculus teased out to show its component fibrilla?. -i^. enormous number of yet finer fibrilla) into which it allows itself to be broken up. The microscope shows us, moreover, that each FIBROUS SARCOMATA. 161 of these finer fibrillas is itself made up of other fibrillse of extreme tenuity, apparent to the eye as msre lines, though sharp and de finite lines (fig. 51^). Just as a well-plaited braid takes up infi- nitely less space than a tress of unkempt hair, even though the number of hairs may be the same in both, so we may suppose that in the fibroma the fine and finest fibrillar are very closely packed, taking up an amazing amount of space when separated by our needles. Between the fibrilla:?, which are composed of a gelatigenous material, and represent a fibrous intercellular substance, we can see the cells (fig. blh). These are usually small, roundly-oval, and furnished with lustrous nuclei. In fio^. 51«, I have fif^ured these elements under a high power, mainly because Virchoic has been led, by their great resemblance to the fibre-cells of unstriped muscle, to set up a " fibro-muscular tumour '* as a special variety of fibroma. I do not wish for a moment to ques- tion this resemblance ; it would be very difficult to draw a hard and fast line between spindle-cells and unstriped muscular fibres so far as their minute structure is concerned ; meanwhile I think it desirable to begin by comparing sarcoma with inflammatory proliferation, the spindle-cells of the tumour with those of the cicatrix. This furnishes us with a practicable basis for under- standing all the structural elements Avhich are met with in the fibroid. It is only the chief constituents of the tumour that have been hitherto described ; besides these we find : 1st, bands of spindle- shaped cells which traverse the tumour in all directions ; 2nd, rounded deposits of embryonic tissue which lie embedded here and there in the continuity of the fibrous bundles. I regard both of the above as transitional structures from which the fibrous tissue is developed in just the same way as the cicatrix is developed from the embryonic and spindle-cell tissues. In a single uterus, I found a number of fibromata, the larger ones consisting mainly of fibrous tissue, while the smaller ones were almost entirely made up of spindle-cell tissue. The appearance of the tumours on section deserves especial notice. The tortuous and interlacing bundles of fibres give it a most peculiar aspect. Microscopic examination (fig. 51) analyses the naked-eye appearances into their details, without shedding any light on the cause of this arrangement. In some cases, the 11 162 CAVERNOrS TUMOUHS. concentration of the morbid growtli around the vessels and nerves of a part appears to exert some influence on its internal arrange- ment. For instance, Billroth has described a fibroid tumour of the eyelids (which he afterwards sent to me for examination), consisting of a number of sausage-like cylinders, in whose axes the remains of minute nerve-trunks were distinctly traceable. Treading in his footsteps, Czerny has recently separated a group of sarcomata, under the name of ^' plexiform tumours," adding the announcement that the branches of the vessels might occa- sionally serve as well as those of the nerves to determine the singular composition of the growth. The most striking case however, is wdien all the vessels of a primarily myxomatous tumour are surrounded by comparatively thick sheaths, which consist throughout of round-cells. In the ordinary variety of fibroma, the course of the vessels does not seem in any way related to that of the fibrous bundles. It appears to me far more likely that as the fibroma (which is an exquisite example of the central mode of growth) increases in size, the newly- formed products are intercalated between the existing fibrous bands, which are thereby dissociated ; and that the incompletely laminated structure of the growth is thus accounted for by a repeated process of interstitial dissociation, and not by concen- tric addition of the newly-formed products. Fibromata ai'e justly counted among the most benign of all morbid growths. We shall find hereafter that the uterus is their favourite seat ; and we shall then become acquainted with a series of interesting modifications of the structural type which has been just described. § 129. YIII. — The cavernous tumour. The tissue of the corpora cavernosa penis, with whose structure the reader is sup- posed to be familiar, is the physiological prototype of the caver- nous tumour. We find the same network of white, glistening trabecular of connective tissue, in whose wide meshes (wide enough to be seen by the unaided eye) the blood is contained as in a sponge (fig. 52) ; we find the same elasticity of the trabe- cular network, which allows of periodical variations in the amount of the contained blood, causing alternate swelling and subsidence of the growth ; finally, I have convinced myself by a series of observations specially directed to this point, that the mode of origin of the spongy or erectile tissue is the same in both cases. CAVERNOUS TUMOUES. 163 I call the way iii which the cavernous tumour is produced, a ^'' cavernous metamorphosis." For I have arrived at the conclu- sion, which might have been anticij^ated a 'priori^ that every vascular tissue is suscej^tible of undergoing conversion into erectile tissue. So far, therefore, the cavernous metamorphosis may be regarded as a secondary phenomenon ; on the other hand, the intermediate tissue-changes are so decidedly characteristic of morbid growth that I cannot hesitate for a moment to place cavernous formations among the histioid tumours. Inasmuch moreover, as the process in question involves exactly the same tissue-changes as those which underlie the development of fibromata, and as the caver- nous tumour, when freed from its contained blood, presents all Fig. 52. % h^^ FuUy-dcveloped erectile tissue, -j^-^. From a cavernous tumour of the orbit. the characters of a fibroid growth, I have chosen to deal with it here rather than elsewhere. § 130. It is difficult to get an insight into the mechanism of a cavernous tumour. When any space contains a network or system of trabeculae, that portion of the space which is not actually occupied by the trabeculae themselves, must necessarily form another network or trabecular system. If we distinguish between a network and a parenchyma which occupies its meshes, each of these constituents must stand in the relation of a paren- chyma to its fellow. The transverse section of any trabecula of one of the networks must bo identical with the circumference of an islet of parenchyma as regards the other network, and vice versCu Fibres which in one of the two networks surround the 164 CAVERNOUS TUMOURS. trabecule at right angles to their length, would, if they con- tracted, diminish the islets of the parenchyma of the other net- work, whose trabecul^e would in their turn become shorter and thicker. Fibres Avhich correspond in their direction to the long axis of the trabeculse of one of the two networks, would, if they contracted, increase the size of the islets of the parenchyma of the other network and render its trabecule© thinner. We may also suppose the entire mass of a trabecular network partitioned out into trabecular substance proper and tetrahedral or cubical nodal pieces (connecting pieces, Yerbindungsstiicke), common to three or four contiguous trabeculse. Supposing the joint yolume of the two networks to remain constant, and the trabeculse of one network to become longer and thinner, this would necessarily entail on the one hand a diminution in the size of their own nodal pieces, on the other a shortening and thickening of the second network whose nodal pieces would simultaneously increase in size. When once w^e haye thoroughly grasped these rather difficult stereometric conceptions, we get at a yery natural theory of the mechanism of cayernous metamorphosis. True, it is far from easy to conceiye of a parenchyma traversed by an ordinary vascular network as being made up of a system of rounded trabeculse enclosing meshes between them. This is made easier Fig 53 ^^ imagining several vessels seen in transverse section (fig. 53^) ; the dotted curves (which may at the same time be supposed to represent the ^ — '^ / \ lines of contact of the capillary arches between a \''^>.^ \ ' and a) would then indicate the transverse sections """"'^k of the trabeculse of parenchyma. The vascular net- ^^ work would thus be made up of long trabeculse and small nodal pieces, the parenchymatous network of very thick but extremely short trabeculse and nodal pieces of colossal size. Now the cavernous metamorphosis is brought about as follows : in a circumscribed part of an organ, embryonic tissue- is converted into spindle-cell tissue and fibroid connective tissue along the course of the vessels ; this is folloAved by contraction taking place at right angles to the axis of the parenchymatous trabeculse, in the direction therefore of the dotted curves (fig. 53), causing elongation of the trabeculse, diminution in the size of their nodal pieces, and, as a necessary consequence^, CAVERNOUS TUMOURS. 165 dilatation of the blood-channels ; i.e. a shortening of the trabe- cul^e and an enlai'gement of the nodal points of that network which is constituted by the blood. § 131. Fig. 54 may serve to elucidate the above remarks ; it represents the development of a cavernous tumour from adipose tissue. We see three clusters of fat-cells which correspond to as many stages of the cavernous metamorphosis. The least altered cluster exhibits the well-known capillary network, which is made apparent, in the present instance, not by injection, but by the walls of the vessels being coated with numberless round connec- tive-tissue corpuscles. It is highly probable that these cells are colourless corpuscles which have migrated from the blood ; this part of the process might then be regarded as a very insidious inflammatory change limited to the immediate neighbourhood of the vessels. In the adjoining cluster the process is so far advanced that only scattered fat-cells are still intact, all else having been transformed into embryonic tissue. This is begin- ning to undergo conversion into fibrous connective tissue along the course of the vessels, which gape widely, especially at their nodal points. The third cluster shows the erectile tissue in its maturity ; (cf. fig. 52) ; what was the parenchyma is now a system of trabecula?, towards which the blood-containing spaces stand in the same quantitative ratio as that in which the parenchyma stood towards the vascular network in the least-altered cluster. Thus we see that the cavernous growth originates in a fibroid degeneration of the capillary portion of the blood-path ; it is a mistake therefore to derive it from an ectasy of the veins or arteries. This must not be taken to mean that the larger afferent and efferent vessels of the area under2:oino: deo^eneratlon remain unaltered. The arteries of the cavernous tumour more especially show an enormous thickening of their walls, a tortuous course, and a capacity for dilatation such as no healthy vessels, save the helicine arteries, ever exhibit. The annexed figure likewise informs us concerning their relation to the blood-spaces of the erectile tissue. They communicate with these spaces by as many apertures as there formerly were communications between the arterioles and the capillary network. The amount of blood In the erectile structure depends immediately on the degree in which the arteries are contracted. In fig. 54, besides 166 CAVERNOUS TUMOURS. the three degenerated clusters of fat-cells, we see an artery of larger calibre in transverse section. The vessel is firmly con- tracted ; the intima, much thickened, is thrown into four longi- tudinal folds ; the lumen is a mere slit : we can readily perceive how a farther contraction of the circular fibres would inevitably lead to its obliteration. I can assure the reader, that the very same artery, when fully dilated, would take up about twelve times as much space as it now occupies. Fig. 54. .5tir^#^ :/"^// The development of a cavernous tumour in adipose tissue. Three clusters of fat-cells, representing the various phases in the development of the tumour ; a divided artery is seen in the right upper corner. From the imnniculns adiposus of the cheek, -^hn- Cavernous tumours originate by preference in the adipose lavers of the oro-anism. On one occasion I found cavernous metamorphosis going on in the interior of a lipoma. It mar/ occur, as has been already said, in any organ of the body which possesses blood-vessels ; in any organ therefore except cartilage, the cornea, and the vitreous humour. It is not unfrequently multiple. Cases are on record of a cavernous tumour of the skin having been associated with similar growths in the muscles- and bones. CAVERNOUS TUMOURS. 167 Cavernous tumours are occasionally malignant ; but their malignity usually depends on a manifest complication with melanotic sarcoma, whose nodular foci are develoj^ed in the tra- beculae of the cavernous tumour. § 132. Cavernous metamorphosis of fibrous sarcoma itself is peculiarly interesting. Billroth was the first to speak of a ^' ca- vernous fibroid." I have already remarked, when speaking of the spindle-cell variety of sarcoma, that its vessels had as good as no proper walls, and therefore remained gaping on its cut surface. The same is true of the fibromata. Fibromata witli exceptionally wide and gaping vessels may even appear quite spongy. Billroth found that naso-pharyngeal polvpi, whose Fig. 55. 3» o,^-^ ooo Cavernous fibroid, after Billroth. polypus.) (Xaso-pliaryngeaT growth is peripheric, are especially prone to exhibit a cavernous habitus; and I can assert, from independent observation, that the cavernous tissue in such cases originates in i)recisely the same way as that which I have just described. Fig. 55 represents a vertical section through the circumference of a cavernous fibroid. Externally, we have a very vascular embry- onic tissue ; internally, the familiar trabeculas of the cavernous tissue ; while between the two are seen the transitional phases. I have placed cavernous tumours under fibromata on account of the identity of the histological processes which underlie the development of both ; should any one doubt the adequacy of 168 LIPOMATA. my reason, lie may find an additional motive for conforming to my view in tins second bond of nnion between the two forms. b. Lipomata or Fatty Tumouvs. § 133. Not only is the lipoma or fatty tumour principally made up of the characteristic elements of adipose tissue, the fat-cells, but it also agrees in structure with the normal fat of the human body by the union of these fat-cells into little spheroidal clusters which are parted from one another by septa of connective tissue. A stouter coat of connective tissue com- bines several such clusters into a lobule, also of globular shape ; and it is of such lobules that most fatty tumours appear to the naked eye to be made up. The ■pannkulus adiposus also exhibits a lobulated structure, but its lobules (the fjlandulce adiposce) never reach the considerable dimensions which are commonly attained by the single lobules and tubera of a fatty tumour. The indi- vidual fat-cells of a lipoma differ in like manner from ordinary fat-cells. They are considerably bigger, i.e. more distended with oily matter, which in its turn is more fluid, and contains more elain than usual. All the lipomata are perfect examples of central growth. Their enlargement, as well as their origin, depend in the last re- vsort upon an abnormal production of new clusters of fat-cells ; this is brought about by a moderate and sharply-defined proliferation of the connective tissue, leading to the formation of a circum- scribed corpuscular aggregate, followed by an infiltration of the newly- formed cells with oily matter. It would seem however, that the formative stimulus is most intense amid a collection of pre-existing clusters ; while it is certain that the vessels of the new clusters originate from the vessels of the older ones in the same way as do the vessels of papillomata. This explains why a lipoma is usually connected with neighbouring parts at one point only by a stout vascular pedicle, and has the rest of its external surface limited by a large-meshed connective tissue, or even by a smooth capsule ; this explains its peculiar, lobulated build — in a word, the central growth of the tumour. Lipomata occur by preference in those localities which are normally infiltrated with fat, such as the subcutaneous, sub- mucous, subsynovial, subserous, subfascial, intermuscular, and LIPOMATA. 169 intraorbital connective tissue. From this point of view the lipomata may be regarded as overgrowths of the normal layers of fat, excrescentiw memhrancu adiposce (^Morgagni) ; and if w^ choose to regard these layers as a connected system of adipose tissue, and not as a certain quantity of connective tissue infil- trated with fatty matter, we may claim for lipomata, together with polysarcia, the quality of hyperplastic tumours. For my own part, I look upon polysarcia as a fatty infiltration of pre- existing connective tissue, and on lipoma as a fatty infiltration of a growth of independent origin and development. § 134. The lipomata, like the papillomata, at first increase slowly, their growth proceeding in an accelerating ratio. They may attain a very considerable size. Tumours as large as a man's head and larger, are by no means rare. Moreover their central mode of growth involves their speedy emergence from the surrounding soft parts, and their protrusion towards the nearest free surface ; they push the skin before them, and finally project above the surface as tuberous or polypoid excrescences. The greater the size of a lipoma, the greater the probability that farther metamorphoses have taken place in its interior. We not unfrequently find a chronic inflammatory overgrowth and fibroid transformation of the interstitial connective tissue. In consequence of this the clusters of fat- cells perish en masse ^ the remaining lobules being separated by broad bands of fibroid tissue (Fibroid Lipoma, Steatoma Midler t). Retrograde changes are more commonly met with. Calcification of the fibrous matrix of the clusters stands foremost among these. It results in the formation of a spongy calcareous framework with exceed- ingly fine meshes, which permeates the entire tumour, or large sections of it, making it very hard and heavy. Yet more remark- able is the mucous transformation of the tissues of a lipoma, and the consequent possibility of a fatty tumour being converted into a myxoma. In persons who arc much emaciated, who have been exhausted by lingering disease, we often find the adipose tissue about the heart deprived of its fat, and in a peculiarly swollen and oedematous state, which, on minuter examination, proves to be due to mucous infiltration. Precisely the same phenomenon is met with in lipomata, and especially in the larger, pedunculated lipomata of the skin. The tumour acquires a transparent and colourless aspect; it becomes tremulous and 170 ENCHONDROMATA. jelly-like; the fluid which oozes from its cut surface contains mucin ; so that we are compelled to acknowledge the myxomatous cliaracter of the growth, and to call it (should the entire tumour have undergone this degenerative change) no longer a lipoma, but a myxoma. Lipomata, in common with fibromata, are very justly regarded as decidedly benign. A lipoma, once thoroughly extirpated, never recurs ; metastases to neighbouring lymphatic glands or to internal organs have never been observed. c. Encliondromata or Cartilage Tumours. § 135. The term enchondroma is applied to cartilage when it appears in the form of a tumour at some point in the body where no cartilage should normally exist. The substance of an enchon- droma therefore presents the peculiar elastic hardness, and the milk-white colour, translucent in thin layers, which are char- acteristic of cartilacre. As reo;ards minute structure, normal histology, as everybody knows, distinguishes between, se^'eral varieties of cartilage ; and particularly between hr/alhie cxirtilagcj Avhose matrix is homogeneous, and fihro-cartUage, whose matrix is fibrous. But the cornea also yields chondrin on boiling, and its tissue may very w^ell be regarded as a form of cartilage, whose cell-containing cavities are stellate, with branching processes {cartilage ioith stellate cells). All these textures may coexist in an enchondroma, yet hyaline cartilage as a rule predominates. One of the most characteristic and most frequent combinations is that of small rounded islets of hyaline cartilage passing at their periphery into fibro-cartilage or corneal tissue. The hyaline cartilage forming the nucleus of each islet differs in no respect from the well- known physiological type. The cells are either single, or arranged in pairs or groups, showing how the limits of each primary element have been extended by subsequent endogenous proli- feration. The capsules are not always distinct; their entire absence is a sioui that the matrix is bemnnino; to soften. The protoplasm of the cells is of variable form. It is usually stellate, and contains a nucleus ; this form may either be due to shrinking of the cells under the influence of reagents, or to the spontaneous contractility of the protoplasm ; the latter explanation being ENCHONDROMATA. 171 especially applicable when a conversion of the hyaline cartilao-e into mucous tissue is taking place. Under such circumstances, the formation of processes coincides with the disappearance of the capsules, and a mucous intumescence of the matrix. Virchow has observed cells with processes of colossal length in an enchon- droma undergoing this change (^Virclioius Archiv, 28, p. 238). Towards the periphery of these islets of cartilage, the cells decrease in size, they become flat and lenticular ; the matrix shows stria?, and is traversed by fibres of variable thickness, which resemble elastic fibres and are remarkable for their stifi- ness {jihro-cartilagc). Or else the cells may become spindle- shaped and stellate, they may anastomose with one another, and be obviously situated in a lacunar system provided with nodal points, while the intercellular substance retains its homogeneous- and transparent quality {cartilage unth stellate cells, corneal tissue). Neighbouring islets of cartilage are in contact by these outer- most zones of fibro-cartilage or cartilage wdth stellate cells, and are thereby united into groups, forming nodules or lobules as large as a pea, of which the entire tumour appears to the naked eye to be made up. § 13G. The above sketch of the microscopical appearances shows that enchondromata are also endowed with a lobulated structure ; but their lobulation differs very essentially from that of a lipoma, or even from that of a papilloma. The lobules of an enchondroma are co-ordinate with one another ; they have grown up side by side ; it is only this topographical juxtaposition of the lobules, and not any higher unity, such as a common vascular apparatus, or a growth b}- development ah intra, which unites them into a single whole. Although it is noteworthy, as seeming to point to an organic type of structure, that the individual lobules of which an enchondroma is made up, never exceed a certain size, yet this is explained by the simple fact, that cartilage generally — even in the normal course of development — is not deposited in continuous masses of large size, and — to use a teleo- logical form of expression — ought not to be so deposited. Cartilage being a non-vascular tissue, is nourished by the transmission of nutrient fluid from cell to cell. At a certain distance from the vessels which carry the blood, this mode of nutrition becomes impossible ; and unless some now arrangement be provided for the supply of the central parts, disturbances of nutrition in thoso 172 ENCHONDROMATA. parts must inevitably follow any farther growth. In the deve- lopment of the osseous system from cartilage we accordingly find a singular arrangement. When a cartilaginous epiphysis has reached a certain bulk, medullary spaces containing blood- vessels appear exactly in its centre ; and this gives the necessary impulse for the development of true bone, which accordingly begins at this very point (epiphysal nucleus). The formation of vessels and of true bone has also been observed in enchondromata. It is the rule nevertheless, that the individual portions of cartilage should never reach a size so great as to interfere with their being conveniently nourished from their circumference. § 137. This implies of course that the connective tissue which combines the lobules of the enchondroma into a tumour (the stroma) contains an adequate number of vessels, and that a sufficient quantity of blood passes through those vessels. This is the case in tumours of relatively small size, and at the circum- ference of the laro-er ones as well. But it is not the case in the interior of the latter. On the contrar}', the vessels appear to be compressed and obliterated by the pressure of the growing tumour. In cxcry enchondroma of considerable size — and some have been met with weighing five pounds — w^e may accordingly assume that a more or less complete obliteration of the vessels in its interior has taken place, giving rise to subsequent metamor- phoses of its substance. We nearly always find calcified patches in an enchondroma. The cartilao-e then exhibits the infiltration which has been described at length in ^ 49. This starts now from the matrix, now from the cells and capsules. The results are always the same to the naked eye ; the colour of the infiltrated parts becomes dark-yellow and opaque, their consistency granular and friable. It has already been mentioned that this calcification may occasionally be followed by a true ossification, as in the normal development of bone. Reference has also been made to the conversion of the cartilage into mucous tissue. This should be regarded less as a degenerative process, than as a change of type, as a conversion of one tissue into another tissue of equiva- lent quality, which may result in the partial or complete trans- formation of an enchondroma into a myxoma. It is far other- wise with that softening of an enchondroma which begins with a fatty metamorphosis of the cartilage-cells, their conversion into ENCHONDROMATA. 173 granule-cells, &c., these changes being farther complicated bv a mucoid softening and solution of the matrix ; the final result of the process being the formation of cavities, fluctuating points — in a word, of " cysts due to softening " — in the interior of the enchondroma, which are filled with a jelly-like viscid fluid con- taining a very large proportion of mucin. This cystoid degenera- tion of enchondromata {encliondroma ci/stmmi) ought certainly to be regarded as a consequence of impaired nutrition. § 138. Unfortunately however, this is not the last of the anatomical modifications of enchondroma. The complication of enchondroma with alveolar sarcoma (vulgarly called cancer on account of its alveolar structure) has yet to be considered. It is to this complication that enchondroma owes a certain reputation for malignity, a reputation which the growth ]Der se does not deserve. Cases are on record of medullary tumours appearing at the seat of operation and in other regions of the body after the removal of enchondromata ; such cases all refer to this com- bination of enchondroma with soft sarcoma. In such cases too, the superadded element of malignity can usually be recognised even iu the primary tumour. Medullary nodules of variable size are met with along the vessels in the stroma of the cartilaginous tumour. Still, it is an established fact that pure enchon- dromata are also liable to recur; a gradual extension of the growth along the lymphatics, metastases to the nearest lymphatic glands, nay, even to internal organs, have more than once been observed. Amono^ internal viscera the lunir is the favourite locality for secondary deposits of an enchondromatous nature. It must be remembered, however, that these secondary deposits are excessively rare, and always of extremely small size, even when the dimensions of the primary tumour were colossal. § 139. From a quarter to four-fifths of all enchondromata occur in the osseous system, and more particularly in the diaphyses of the long (tubular) bones. We shall hereafter become acquainted with the great variety exhibited by enchon- dromatous tumours of bone, both in the manner of their first appearance, and in their subsequent development ; here I will only allude to a single variety, the osteoid-cliondroma of Virchow^ inasmuch as it familiarises us with an essentially aberrant form of cartilage as its main constituent. In reckoning up the various kinds of cartilage, one tissue is usually omitted, which neverthe- 174 ENCHONDROMATA. less possesses tlie most substantial claim on our notice on the ground of its morphological constitution. I allude to that peculiar sort of connective substance (Bindesubstanz) which is called true bone after it has been impregnated with calcareous saltSj but which, before this impregnation, consists of a highly- refracting, dense and homogeneous matrix, in which the future bone-lacuna still exhibit more of a rounded or rather perhaps of a polygonal form, with very short processes. The trabeculas of an osteophyte {see Diseases of Bone) are composed of this tissue ; in thin layers, it lines the medullary spaces of such bones as are passing from the spongy to the compact state. It plays a great part in the repair of fractures by forming the main bulk of what is known as " callus." Its truly cartilaginous properties are however especially manifest when, as in the osteoid-chondro- mata, it forms tumours, often of colossal size. ^ 140. Osteoid cartilage may also originate independently of the bones : in a compound tumour from the back, Virchow found portions of well-marked osteoid cartilage side by side with myxomatous and lipomatous elements ; but as a general rule such tumours spring from bone. Their growth begins between the periosteum and the surface of the bone, but they sub- sequently penetrate through both the periosteum and the compact cortex. They usually present themselves as fusi- form or pear-shaped swellings of one of the extremities of a long (tubular) bone. They have been most often met with in the humerus and femur. Retrograde metamorphoses are less common in these than in any other of the heteroplastic tumours which we have hitherto considered. This immunity is connected with the very complete and uniformly efficient vascularisation of every part of the tumour, an advantage which the osteoid- chondroma enjoys in common with osteophytes and callus. The cartilaginous trabecule of the osteoid substance form a delicate framework, in whose meshes even the finest capillaries are free from all risk of being squeezed by the growing tissue. One metamorphosis only, and one which might be anticipated a priori, is met with in nearly every osteoid-chondroma ; I mean a transi- tion of its proper tissue into that of true bone. Hence it is that an osteoid-chondroma creaks under the knife, and that we are sometimes obliged to have recourse to the saw in order to divide it. The ossified portions are known at once on the cut surface MYXOMATA. 175 by their great firmness and density ; should the entire tumour liave been converted into bone, the osteoid-chondroma is said to have become an osteoma. As regards its innocence or mahgnity, we cannot venture to pronounce any decided judgment, owing to the small number of cases which have been hitherto recorded. The elements of pro- gnosis laid down for enchondromata may be held (at least pro- visionally) to be applicable to this variety likewise. d. Myxomata or Mucous Tumours. § 141. A summary of all that has been said in the sections treating of mucous tissue shows us that, although it is to be regarded as a thoroughly independent and vitally active member of the connective series, it nevertheless originates, in the vast majority of cases, by a secondary metamorphosis of other con- nective substances (§ 42) entering into the formation of tumours. We have become acquainted with a myxomatous variety of sar- coma, lipoma, and enchondroma respectively, understanding thereby tumours, circumscribed patches of whose proper sub- stance had undergone conversion into mucous tissue. It must be admitted that this order of sequence is an inference from the coexistence of these modifications ; but the possibility of a myxo- matous metamorphosis of cartilage, adipose tissue, and areolar connective tissue, has been established by observations so nume- rous and well authenticated, that we are quite justified in assuming the sequence to have been such as we have stated, and not of an inverse order ; moreover, we have good grounds for preferring such a conclusion (at least in the majority of instances) to the hypothesis of a simultaneous development of compound types of tissue. Bearing this well in mind, it seems at least prudent to restrict the term '^ mucous tumour" to such growths only as are exclusively made up of mucous tissue. Such tumours indeed are not common ; they are common enough however to warrant us in maintaining the group of tny.vomata as originally consti- tuted by Virchow. § 142. The definition of mucous tissue implies the existence only of a basis-substance containing mucus, or of one which has undergone mucous softening ; it involves no theory concerning the form and character of the cells ; it allows us therefore to set 176 MYXOMATA. iij:* a certain number of histological subspecies of the myxoma. The optical and physical properties of mucin are (§ 39) best dis- played when the number of cells, whether round or stellate, is small in proportion to the amount of intercellular substance. Accordingly the hyaline myxoma (fig. 56) is the most charac- teristic form of the entire grouj^ ; it is colourless, translucent, like a tremulous jelly. Should the cells predominate, either in the entire tumour or in single portions of it, we get a whitish, marrowy condition — the medullary my.voma. Fatty infiltration of the cells leads to the formation of a Upomatous myxoma (m. lipomatodes). Fig. 56. Hyaline myxoma of the subcntaueous connective tissue near the angle of the jaw. -^. § 143. The myxoma, like the lipoma, has a lobulated struc- ture ; it is made up of separate parts of variable size, which are separated from one another by partitions of connective tissue. Little is known at present concerning the arrangement of its blood-vessels ; injections of a hyaline myxoma of the cheek (as large as a closed fist) made by myself, lead me to suspect that myxomata are but sparingly provided with capillaries, that their vessels are mainly of largish calibre, and run in the thicker septa. Myxomata form nodular swellings which increase rapidly in size ; owing to this circumstance, as well as to the great softness of their tissue, they are often mistaken for soft cancer. They resemble lipomata in making for the surface by the shortest or easiest route ; here they form nodulated or fungous projections, and may even become pendulous or polypoid. Tlie subcutaneous areolar tissue of the thigh and back, and OSTEOMATA AND MYOMATA. 177 of the external genitals in the female ; the intermuscular con- nective tissue of the neck and face, are the favourite seats of myxoma ; next to these, it is most frequently met with in the bones and nervous system. In the nervous system (according to Vircliow) it is often multiple, myxomatous nodules being formed at several points at once in the connective tissue of the perineurium. As regards prognosis, myxomata, if we succeed in duly eliminating the myxomatous variety of sarcoma, may be classed among benign tumours. They do not recur after radical extirpation. e, Osteomata or Bony Tumours. § 144. Bony tumours in some respects resemble myxomata. Bone, though a living constituent of the body, and even suscep- tible of undergoing metamorphosis, resembles mucous tissue in being a "terminal" tissue, i.e. it usually winds up a series of other metamorphoses. The stromata of cancers may undergo ossification. Lilcke has actually recorded a case of epithelial cancer with a bony stroma ; we are acquainted with an ossifying sarcoma ; enchondromata and osteoid-chondromata may be con- verted into bone ; even the septa of connective tissue between the lobules of a lipoma may become ossified ; we are therefore obliged to repeat what was said in defining a myxoma, limiting the term osteoma to such tumours only as consist throughout and in all their parts of bone-tissue. If we distinguish with Vir- ch&Lo between a hyperplastic and a heteroplastic form of osteoma, we shall have to include under this head whatever tumour-like overgrowths of the bones we may come across. Heteroplastic osteomata are undoubtedly very rare. f. Myomata. Under this name we include all tumours which are mainly composed of true muscular fibre. According as the muscular fibres belong to the smooth or the striped variety, we follow Zenker in distinguishing between leiomyomata and rJiabdo?nyo}nata. I have found however, that it is just in the case of tumours that transitional forms between smooth and striped muscular fibre are to be met with. A large myoma of the retroperitoneal adipose tissue which I had an oppor- 12 178 NEUROMATA. tunity of examining, was made up of transversely striated spindle-shaped cells ; so too, a myoma of the vaginal mucous membrane, which showed an obstinate tendency to recur. Pure leiomyomata, when they occur in the bowel, the urinary bladder, &c., exhibit throughout the structure of muscular membranes. I assert boldly that no one who has once investigated a tumour of this kind is ever likely to confound simple spindle-cells with muscular fibre-cells. The remarkable uniformity in size and appearance of all the cells and nuclei, enabling them to unite closely into fibrous bands of very elegant texture, has something extremely distinctive about it. The naked-eye appearances, the interlacement of the fibrous bands, unquestionably remind one of the fibromata ; but I have never been able to recognise the exist- ence of a fibro-muscular tumour in Firchoiv^s sense of the word. In a myoma of the testicle, I found groups of ganglion-cells, and stroma-fibres. (See Testicle.) g. Neuromata, § 145. The term neuroma is used to denote any histioid tumour which may happen to be intercalated in the course of a nerve-trunk ; it is employed wnth especial frequency to denote fibromata and myxomata ; hence we must distinguish in limine between /aL^6? neuromata, such as these, and the true neuromata, which consist chiefly of newly-formed nerve-fibres and ganglion- cells. A tumour of this sort, as large as a hen's egg^ situated in the retiring angle between the ribs and the anterior circum- ference of the vertebral column, has recently been observed (^Schmidt, Frankfurt-am-Main). It merits especial notice, inas- much as it seems to be the first recorded example of a true neu- roma not of hyperplastic origin. True, its situation does not absolutely exclude all possibility of its having originated by over- growth of a sympathetic ganglion ; should this be its true character, it would come under the same category as those cir- cumscribed overgrowths of the greater cerebral ganglia (thala- mus opticus, corpus striatum) which have been more often met with, as well as those fusiform enlargements of the peripheric nerve-trunks, consisting of nerve-fibres, which Virchow has de- scribed under the name of true neuromata. COMPOUND HISTIOID TUMOURS. 179 h. Coinpound JSistioid Turnout's. § 146. In all the histioid tumours which we have hitherto examined, a single tissue could, with more or less of certainty be viewed as the dominant constituent, thus enabling us to decide on the character of the growth, and to give it an appropriate name. There can be no doubt however that compound tumours exist as well. When distinctly cartilaginous elements are found associated with lipomatous ones, when sarcomatous nodules ^re found (see above) scattered through an enchondroma, we are puzzled whether to call these things enchondroma lipomatodes or lipoma cartilagineum — sarcoma cartilagineum or chondroma sarcomatosum. This perplexity recurs when we come to inquire into the clinical character, prognosis, &c., of such tumours. As regards the latter question, we are justified in laying down the following propositions on the basis of several reliable observa- tions ; 1st, that the prognosis of compound tumours is less favourable than that of the seveial species of which they are made up; 2nd, that the presence of sarcomatous constituents renders a compound tumour at once equivalent to a sarcoma. A the normal type. As regards the hyper- trophy of the mamn.ry gland in lactation, I must refer the reader to the appropriate seiions of the Special Part of the present work. § 150. All otherforms of so-called glandular hypertrophy diverge in some way)r other from the normal standard. First, we have a group of^ases, with regard to which we are never sure what proportion f the total enlargement should be ascribed to morbid overgrowt of the gland-tubuli, and what to their coincident dilatation. To this group belongs the hypertrophy of the mucous follicles ii^atarrh of the stomach and large intes- tine, of the trachea ai bronchi. Tlie proliferation of the sub- epithelial layer of conn tive tissue which invariably accompanies every catarrhal inflamation of a mucous membrane leads to compression and closur^f the ducts which penetrate it, and so hinders the free dischai) of the secretions ; a certain degree of dilatation of the follich due to retention of secreted matters, thus contributing to thtrross result. As compared with this, the independent growtlof the glands, i.e. the growth due to fission of their epithelialements, plays a more or less subordi- nate part. It may coi^ie itself to furnishing the necessaiy epithelial lining for the and as it gradually degenerates into a mucous cyst. Cases ofliis sort are analogous to atheromata 184 GLANDULAH CAECINOMATA. of the sebaceous glands, in which we undoubtedly have more epithelium than is strictly required to line the cavity a a seba- ceous folHcle, but never — unless the atheromatous cyst has become an epithelial cancer — any centrifugal budding forth from the epithelial layer. § 151. Connected with the above are cases in vhich an in- dependent outgrowth of the secreting parenchyma undoubtedly takes place, but in wliich we may reasonably hesiate before we regard the newly-formed tubuli as true, i.e. ^ functionally capable portions of the gland. Both the seb-ceous and the sudoriparous glands may undergo a monstrous excess of develop- ment in circumscribed portions of the skin, ant (especially the former) form fungous tumours of great size, without any increase in the amount of secretion being observable or the surface. In the hypertrophy of the sebaceous glands mceover there is a marked deviation from the normal plan o^ structure, viz. a thickening of the connective tissue of the ollicular sacs. A farther extension of this peculiarity leads t subepithelial sar- coma of the glands, e.g. of the female brea^ a form of disease to wdiich Billroth has on this account applil the name of ade- noid sarcoma. § 152. With the complete emancipatio from the physiolo- gical purpose of gland-growth begins le domain of those tumours wdiich I call adenojiata. Apaifi'om its stroma, the adenoma consists of epithelial cells, whosfarrangement at once recalls the epithelial lining of the tubui' or acinous glands. The cells are, for the most part, grouped 'und a central axis, as though they really included a tubular men; but the lumen itself is either wholly wanting, or presenonly in an interrupted form, plugged with mucous or colloid mier, and most assuredly shut off from free communication w^ith the /erent duct of the gland. It w^ould seem as though Nature had (tcerned herself mainly wdth an unlimited production of new pdular tubuli, without much caring what became of them. S seems to forget that a proportionate development of blood- vesls and connective tissue is indispensable for the due perfection of glandular parenchyma ; and so, as the process continues, a ttf)ur extraordinarily rich in cells is formed, too scantily provid however with vascular connective tissue to enable its nution to be adequately carried on throughout its entire subsice, and which therefore GLANDULAR CARCINOMATA. 185 evolves within itself the causes of its own ultimate destruc- tion. We are at present acquainted with adenomata of the liver, mammary gland, sebaceous glands (Lupus), and the mucous follicles of the rectum. It is only in the last-named case that we find it hard to separate adenoma from columnar epithelioma (Cylinderepithelialki'ebs). (^See below.) As for the rest, we find practical means of distinguishing them from cancer, partly in the manner of their development, partly in their clinical history. Adenoma forms globular, sharply- circumscribed nodules, which replace a comparatively small portion of the gland from which they spring. Each single nodule increases by central proliferation ; it tends rather to push aside than to infiltrate the neighbouring parts. Adenoma of the liver actually surrounds itself with a capsule. Further, adenoma is to be regarded as a tolerably benign growth, which does not recur or give rise to secondary deposits, though our knowledge on this point is still in its infancy. § 153. Glandular cancer, with its many varieties, consti- tutes the natural termination of the histogenetic series which we have been hitherto considering. If we imagine the independent growth of the glandular epithelia waxing more luxuriant and more general, the regular elaboration of the gland-tubuli being more and more neglected for the sake of a proportionately more rapid penetration of the interstitial and surrounding connective tissue, we shall have a tolerably correct notion of glandular cancer. Its individual features however demand a more detailed examination. That the growth originates in the glandular epithelia has been recently established by numerous observations. The cells divide and multiply. The first result of their multiplication is an obliteration of the lumina of the respective tubes and acini, which are converted into solid groups of cells. These imme- diately proceed to put out buds in all directions, which bore their way into the neighbouring connective tissue. This is the common starting-point of the many varieties of glandular cancer, the more important of which will now be described seriatim, § 154. Soft cancer (carcinoma medullare, encephaloides — hitherto often confounded with the soft variety of alveolar sar- coma) produces cancer-cells in the greatest number, though not 186 GLANDULAR CAECINOMATA. always of the greatest size. Their round, vesicular nuclei, fur- nished with distinct, lustrous nucleoli, prove that these cells are truly descended from the mucous layer of the blastoderm ; they form elaborately twisted cylinders beset with clavate appen- dages which are best seen when the juice squeezed from the cut surface of a recent specimen (cancer-juice) is examined in serum (fig. 57). In these cylinders the boundary-lines between the individual elements cannot be detected. This is because the Fig. 57. Cellular aggregates from the juice of a soft cancer of the breast. After Billroth. protoplasm of the cells is absolutely naked, so that their imme- diate juxtaposition produces the optical effect of continuity. It would seem as though the speedy onset of fatty metamorphosis hindered the farther evolution of the epithelial type, for we seldom come across a cell of large size whose protoplasm does not already contain one or two oil-globules. The greater the number of oil-globules, the more distinctly can we trace the outlines of the cell, which are otherwise so difficult of demon- stration. The conversion of the cells into granule-corpuscles with fatty cUbris appears to take place in the usual way. Neither microscopical nor chemical investigation has yet succeeded in showing the existence of any specific elements in cancer-juice. The clear and colourless serum contains albuminates and albu- minoid matters in solution ; among these there may perhaps be GLANDTJLAR CARCINOMATA. 187 some ferment-like bodies, which are at present however wholly unknown, § 155. On examining what is left after the cancer-juice has escaped, on exploring the spaces in which the juice was con- tained, we are confronted by the second element in every can- cerous formation, the cancer-stroma (fig. 58). To demonstrate the stroma as perfectly as possible it is necessary to cut fine sections from various parts of the tumour, which must then be pencilled out ; a framework of connective tissue is thus dis- played, whose trabeculaB enclose oval spaces ; the shortest dia- meters of these spaces being at least twice the breadth of the Fig. 58. Stroma of soft glandular cancer pencilled out. a. Cylinders of cancer-cells seen in transverse section ; 6. Trabeculae of stroma ; c. A solitary spindle-cell which stretches obliquely from one trabecula to another, and serves, by deposition of basis-substance along its protoplasm, to give the impulse for the formation of a neTv trabecula ; d. Round-cells infil- trated into the substance of the trabeculas. ■^^. stoutest of the trabeculae, and at least five times the breadth of those of medium thickness. This implies that neither the thick- ness of the trabeculae nor the size of the meshes are the same in all cancers, but that a certai^i ratio may be said to exist between the width of the trabeculae and that of the meshes. This ratio is of value in distinguishing the individual varieties of cancer from one another. 188 GLANDULAR CARCINOMATA. As regards minute structure, the thicker trabeculae of the stroma usually consist of a striated connective tissue in which a laro-e number of spindle-shaped cells are embedded. These tra- beculse are not circular, but triangular, quadrangular, or poly- gonal in transverse section, the sides appearing concave, the ano-les pointed. The latter are occasionally produced into thin membranes, which stretch across the whole or a part of a mesh. The general impression left on the observer's mind is that of a progressive rarefaction of the stroma by the growing contents of the alveoli ; and this impression may be unconditionally accepted, at least as regards the earliest stages in the development of can- cer, when the growth is still confined within the lobules of the gland. At a later period, when the degenerated lobes and lobules have coalesced to form nodules of larger size, and these have already begun to penetrate b}^ infiltration into the neigh- bouring tissues, a formation of new trabeculse takes place in the older parts of the tumour ; this begins by solitary spindle-shaped cells becoming obliquely stretched across the larger alveoli, where they serve as guiding or nuclear centres for the subsequent appo- sition of the basis-substance of connective tissue. The soft form of glandular cancer has hitherto been found in the salivary gland, the mammary gland, the testicle, ovary, pro- state, thyroid body, nasal mucous membrane, and liver. In what measure, if at all, soft cancer of the stomach may originate in the follicular structures must remain for the present an open question. The soft glandular cancers are extremely malignant ; parti- cularly because they undermine the general nutrition of the organism more rapidly than any of the other forms, and so prove fatal by the cachexia to which they give rise. Metastatic deposits are only found as a rule in the corresponding lymphatic glands. § 156. The telengiectatic carcinoma (a variety of the so- called fungus hsematodes). Inasmuch as blood-vessels form an integral part of the stroma of every gland, and this stroma, as we have seen already, undergoes direct conversion into the stroma of the glandular cancer, it is easy to see that every such cancer must, at least in its earlier stages, contain blood-vessels. In a general way these vessels may be said to share the fate of the stroma, i.e. they undergo rarefaction so long as epithelial proliferation is in the ascendant, and when its products are softened and disintegrated by fatty metamorphosis, the vessels glandula:r carcinomata. 189 may even take on an exuberant development. Some cancers there are however — and these may rightly be termed telengiec- tatic — in which the development of vessels predominates from the very first. In a cancer of the testicle whose growth was extremely rapid, I found the stroma wholly made up of vascular ramifications. Fig. 59 represents a fragment of this stroma. I regard the double contour which may everywhere be traced at a little distance from the vessels, as the wall of a lymphatic sheath; such perivascular sheaths having been discovered by Ludwig and Tomsa even in the normal testicle. Here too I had Fig. 59. Stroma of a rapidly-growing cancer of the testicle. The section has been pencilled out. 3^. an admirable opportunity of studying the development of vessels from " coecal protrusions" as described by Rokitanski; and I was enabled to assure myself that these protrusions were strictly equivalent to those coecal appendages of the vascular system with which we became acquainted in connexion with tertiary vas- cularisation (§ 71). The protrusions, which are undoubtedly coecal, grow towards each other and coalesce when they come into contact, forming a new capillary loop (fig. 60). All telengiectatic cancers are clearly recognisable even by the unaided eye, owing to the frequency with which parenchymatous hagmorrhages occur in their interior. Haemorrhagic foci, varying in size from a pin's head to a hen's egg, and even larger, foci in every stage of retrograde metamorphosis, blood-cysts and patches of pigment of all shapes and sizes, characterise the cut surface of this variety of fungus haematodes. As regards malig- 190 GLANDULATl CARCINOMATAR. nitj, the telengiectatic form of glandular cancer agrees uncon- ditionally with the soft variety. § 157. The sarcomatous carcinoma represents the second possible combination of cancer with sarcoma (cf. sarcoma carci- nomatodes, § 125). If we imagine the epithelium of an open gland undergoing a degeneration precisely similar to that which ^ives rise to the soft form of glandular cancer, while the inter- FiG. 60. Stroma of a telengiectatic cancer of the testicle, consisting of wide capillaries with coecal appendages. ~^. stitial connective tissue simultaneously undergoes a sarcomatous degeneration, we get a compound tumour, whose place we are at first puzzled to define, uncertain whether to class it with sarco- mata or cancers. I place it among the cancers, inasmuch as the sarcomatous element is restricted to the primary growth ; when it recurs after extirpation, or forms metastatic deposits, it usually presents the uncomplicated features of soft glandular cancer. Its seats of election are undoubtedly the testicle and the kidney. I venture to assert that most soft cancers of the testicle hare a GLANDULAR CAHCINOMATA. 101 sarcomatous stroma. Its trabeculse are made up of the charac- teristic spindle-shaped cells, and are often so thick, that if we purposely take our section from the denser parts of the tumour, we may have to prosecute our search through several times the diameter of the microscopic field, before we come upon a deposit of cancer-cells. As regards malignity, this tumour also takes its place with soft glandular cancer. It is worth mentioning that it may grow to a colossal size. Kidnevs have been met with weio-hinp- ten, and testicles weighing fourteen pounds. § 158. Hard cancer (simple carcinoma, scirrhus, connective- tissue cancer) differs from the two foregoing varieties by struc- tural and evolutional peculiarities of such moment, that many of my fellow-workers will be most unwilling to admit it to a place among glandular cancers at all. As the epithet I have chosen indicates, it is essentially distinguished from those morbid growths which are akin to it by the greater firmness of its texture. The consistency of a cancer depends on the quantitative ratio between the cellular infiltration on the one hand, and the stroma on the other. Hard cancer owes its greater density to the tra- beculse of its stroma being thicker, and the interstices for the cancer-juice smaller, than they are in the soft form of glandular cancer. And yet its hardness varies within certain limits ; its degree being regulated partly by its age and the period of its development, partly by local idiosyncracies. Some hard glandular cancers are of such density throughout that great violence is required to tear them ; they creak under the scalpel (durities eburnea; scirrhus). These cancers are white and glistening; the microscope shows them to be made up of a dense, finely- fibrous connective tissue, which contains the nests of cancer- cells in a comparatively small number of fissures and alveoli. More commonly we find softer and harder portions included in the same tumour, and that in a certain definite order ; a hard, central nucleus being env^eloped by a peripheral zone of rela- tively softer — sometimes positively soft — consistency. . Examina- tion with the unaided eye alone is enough to make us suspect some connexion between this arrano;ement and the relative ag-e of the central and peripheral parts. The outermost layer of the tumour (which always occurs in an exquisitely nodular form) consists of a zone of extremely minute, reddish-grey foci, which 192 GLANDULAR CAECINOMATA. are embedded in the healthy parenchyma. Next to these come similar foci of progressively increasing size, which ultimately coalesce to form that part of the growth which protrudes like a circular rampart on the surface of section when the tumour is cut across. Farther inWards certain white lines, corresponding to the larger trabeculse of the cancer- stroma, grow more dis- tinct ; the reddish-grey infiltration fades, or is replaced by a yellow marbling, due to the conversion of the cancer-cells into granule-corpuscles (Carcinoma reticulatum of Muller). The vessels too of the stroma, which were hardly to be seen in the encircling rampart itself, become much more distinct, mingling red lines and dots with the white trabeculas of the stroma, and the yellow points of fatty change. Still nearer to the centre these appearances also fade, leaving a white and lustrous hard cicatricial tissue, which sends radiating prolongations from the centre of the tumour towards its circumference. So that, even with the naked eye, we can distinguish four zones which corres- pond to a like number of stages in the growth of the cancer ; a zone of development, a zone of acme, one of degeneration, and one of cicatrisation. Fig. 61. Carcinoma simplex mammae, a. Development of nests of cancer-cells; 6. Fully-developed cancer-tissue (cf. the next); c. Commencing cicatrisation ; it also represents the relation between stroma and cells in scirrhus ; d. Cancer- cicatrix. t^. GLANDULAR CARCINOMATA. 193 § 159. The microscope tlioroiiglily corroborates the evidence of the unaided eje. In fig. 61, the microscopic appearances presented by fine sections taken from each of the four zones of the tumour are shown. Fig. 61, «, is from the periphery of a minute nodule, situated in the zone of development ; the appear- ances which it presents used to be interpreted as follows. It was supposed that each row of small round-cells were at once the brood of a single connective-tissue corpuscle which formerly occupied the same point, and the forerunners of a group of cancer-cells, such as might be observed in their immediate neighbourhood. This developmental nexus has now been broken through. The rows of round-cells are viewed as colourless corpuscles which have migrated from the blood-vessels; and great efforts are being made to prove that the nests of cancer- cells originate exclusively from the pre-existing epithelia of the gland-substance. To my mind these efforts appear futile, so far as they are meant to show that all the cancer-cells are actually "descendants" of the epithelial cells. On the other hand I am quite willing to admit that in the hard form of glandular cancer, as in the other varieties, the glandular epithelia undergo fissiparous multiplication, contributing thereby, though only to a moderate extent, towards the enlargement of the acini or tubuli ; also, that the first nests of cancer-cells usually originate in immediate proximity to the glandular epithelia, thus giving no little colour to the assumption of an " epithelial infec- tion " of the round-cells wdiicli are heaped up in the connective tissue. In my opinion, the development of hard glandular cancer occurs by a slow interstitial inflammation, whose cellular pro- ducts are converted into epithelial elements instead of pus or con- nective tissue. The active participation of the glandular epithelia must be regarded as the primary cause of this inflammation, and as the exciting cause of the peculiar line taken by the products of inflammation in their development. Hence the glandular epithelium is and must remain the essential cause of the morbid action, even though its co-operation happen to be quantitatively insignificant. The precise way in which an epithelial direction is given to the development of the infiltrated products of inflam- mation must for the present be left undecided ; although, as has been already hinted, there are many reasons for assuming that young epithelial cells penetrate one by one into the interstices 13 104 GLANDrL.Vrv CAECIXO^irATA. of the adjoining connective tissue, where they infect hy contact the indifferent cells ^vhich these interstices contain. We are to some extent reminded of the way in Avhich the tegumentary layers of epithelium grow ; save that in them the migratory corpuscles of the connective tissue pass over entirely to the side of the epithelium, the boundary line between the epithelium and the connective tissue being thus preserved ; while in the present case, the migratory cells are infected while yet embedded in the connective tissue, thereby causing the penetration of the epi- thelium into the extra-epithelial tissues. § 160. Fig. 61, h, represents the stage of acme. The pro- liferated cells demand more space ; hence the fi]3res of the con- nective tissue are dissociated, and go to form the large and small trabecular of a tough stroma ; upon and within them ramify the blood-vessels of the cancer, whose calibre and fullness determine the intensity of the red element in the hue of the tumour. That it is fatty degeneration by which the cancer-cells are affected and to which they finally succumb, is clear enough from the mere examination of the juice scraped from a cancerpus tumour. In this, all stages of the degenerative process are exhibited side by side (§ 26), from the appearance of the first oil-globule in the protoplasm, to the complete disintegration of the cell. What appear to the naked eye as yellow streaks and dots (carcinoma reticulatum of Muller) are found under the microscope to consist mainly of granule-cells. In transverse sections, the thickening of the trabecule (of the stroma) which is associated with the diminution in number of the cells, attracts our chief attention. Fig. 61, <:•, represents a type of structure which is permanently characteristic of the so-called scirrhus, but which is met with in every simple cancer as a transitory phase. The trabecuh\3 are extraordinarily thick; they consist of a connective tissue with short fibres, and provided with spindle-shaped cells. After the total disintegration and removal of the infiltrated cells, this con- nective tissue has the field to itself. In the cancer-cicatrix, the oldest part of the tumour, Ave see bands of fibres crossing and inter-penetrating each other in every possible direction ; here and there a residue of fatty cltbris indicates the former position of a group of cancer-cells ; in other respects, the cancer-cicatrix exhibits no peculiai'ity which might serve to distinguish it from any other sort of cicatricial tissue (fig. 61, c?). GLANDULAPc CARCINOMATA. 195 The formation of a cicatrix brings the local history of the cancerous tumour to a close ; the same termination, when it occurs at the close of a formative inflammation, is known under the name of repair; yet we should not be justified in saying that the cancer underwent ^'repair" by cicatrisation; for while the reparative process is going on at its centre, new portions of the afi:ected gland are being continually drawn into the vortex of destructive change at the periphery of the growth ; so that the cicatrisation always lags far behind tlio infiltration. § 161. Hard glandular cancer occurs most frequently in the female breast, where it presents several varieties ; next in order of frequency come the glandular layer of the stomach, the liver and other open glands. As regards the time at which metastatic deposits begin to appear, nothing is known for certain ; as a rule, they occur within a year. Cases are on record of the radical extirpation of hard glandular cancer, not followed by any local return of the disease ; but such cases are among the rarest in surgery. § 162. Colloid Cancer [carcinoma alveolare, gelatiniform cancer (GaUertkrehs)'] consists of a soft, tremulous and jelly-like, transparent mass of a bright honey-yellow colour. Essentially a variety of hard glandular cancer, it differs from this, its nearest relative, by the entrance of colloid degeneration into the course of its development. To this colloid degeneration are due the peculiar aspect, the structure and other vital peculiarities of the tumour. First then, as regards structure. The familiar term '^ alveolar cancer " indicates sufficiently that it is the prototype of an alveolar texture. The stroma is a network with very regular, rounded meshes ; and if we inquire into the cause of this striking regularity, wo find it in the circumstance that every portion of colloid matter swells, tending, like fluid collected in a limited space, to assume a spherical form ; so that any paren- chyma which, like this form of cancer, is studded throughout with little portions of colloid matter, must eo ipso assume the form of a stroma with spherical meshes. Having reached a certain size, the colloid spheres by their continued increase in volume, compress the intermediate septa and cause them to waste ; two or more spheres coalesce and occupy a space whose original form Is slowly obliterated by a 19G GLANDULAR CARCINOMATA. gradual levelling of the septa wliicli intersect it, tending to make it assume a spherical shape ; so that ultimately a single large, but still globular alveolus is produced. A fine section (fig. 62) shows the entire substance of the tumour to be made up of a number of circular areas, some small, some large, corres- ponding to the colloid spheres, which are kept apart by septa of connective tissue. How the colloid matter originates, is a far more difficult ques- tion. That it is partly due to retrograde metamorphosis of the cancer-cells, may for the present remain undisputed, since every one of the smaller alveoli is found to contain a group of epithe- lioid elements, which are no longer to be seen in those of larger Fig. 62. Carcinoma gelatiiiosum. ■^. size, while there is nothing in their place beyond colloid matter ; also, because the colloid metamorphosis described in § 44 may actually be seen to take place in some of the individual cells. But I cannot admit that all the colloid matter present has been generated in this way. If we look impartially at the very characteristic appearances presented by colloid cancer (fig. 62) we notice that the groups of cancer-cells contained in the alveoli, are first of all in contact with the alveolar walls ; that they are subsequently separated from these walls by a progressively increasing number of layers of colloid matter ; and this without their number undergoing either GLANDULAR CAllCINOMATA. 197 increase or diminution ; we notice that they finally become dis- solved and disappear after dozens of colloid layers have already accumulated ; and a spontaneous conviction arises in our minds, that the major part of this colloid matter has been secreted at the junction of the connective tissue with the epithelium, without the fully-formed epithelial cells taking any active part worth men- tioning in the process. The hypothesis of a direct transudation from the blood cannot be entertained for a moment, the endos- motic equivalent of colloid matter being almost nil. On the other hand I am inclined to adopt the view put forth by Doiitrelepont (^Laiige7ibech'' s Archiv, sent in for publication in April 1870), who believes the colloid substance to be a product of the metamorphosis of the material which serves for the con- struction of epithelial cells, an albuminous compound of some kind, which would, in other forms of cancer, be employed in increasing the number of the cells. We cannot but think in this connexion of Arnold's theory of the origin of epithelial cells from amorphous matter ; the accumulation of colloid, supposing Arnold's view to be correct, admitting of being naturally ex- plained as an accumulation and subsequent transformation of this amorphous plasma. The concentric lamination of the colloid matter points to a certain periodicity in the rate of its secretion, while the fatty and granular debris marking out the limits of each layer, will have to be regarded as a bye-product of its manufacture. § 163. It is certain that vessels ramify upon the septa and trabeculae of the stroma in colloid cancer ; but these vessels are neither numerous nor large, and contribute but little, even when fully injected, to colour the mass of the tumour, so that colloid cancer always gives one the impression of being very scantily supplied with blood. As regards the course of the disease, and the dangers to which the patient is liable, this cir- cumstance is important, inasmuch as bleeding from the surface of a colloid cancer when broken-up and ulcerating is neither frequent nor abundant. As regards malignity, colloid cancer occupies a somewhat peculiar position. It has an extraordinary power of infection per contlguum. The infiltration of the connective tissue which goes on at its circumference often assumes proportions which are actually colossal. On the other hand, metastases to more remote 198 EPITHELIAL CARCINOMATA. parts are rare, as also are deposits in the neighbouring lymphatic glands, which for the most part remain unaffected. Localities : stomach, large intestine, liver, ovary, mammary gland. 11. Epithelial Carcixomata. § IG-i. Were we to take into account every variation in con- sistency, colour and texture, we should find it difficult to get any two specimens of epithelial cancer, taken from different parts of the cutaneous and mucous systems, which could be viewed as growths of an absolutely identical character ; so great is the influence of the parent-soil, especially in the case of epithelial cancer. We must content ourselves for the present with establish- ing two main categories, corresponding to the two leading forms of epithelium, the squamous epithelioma and the columnar epithe- lioma. The former occurs chiefly, but not exclusively, on sur- faces clothed with flattened epithelium, the latter on such as are lined with the columnar variety ; }'et squamous epithelioma is not excluded from mucous membranes clothed with columnar epithelium, e.g. the gastric mucous membrane. § 165. Squamous Epithelioma (epithelioma, epidermic can- cer, cancroid) forms a white, dense mass of somewhat dry quality, which presents on section either an aspect entirely homo- geneous, or affords at most but vague indications of its finer structure. To the finger it imparts a marked sense of resistance, which however is dull and inelastic ; on squeezing it forcibly from the side, contorted threads of a milk-white colour protrude from its surface ; these have been very aptly compared to the so-called " comedones " which may be squeezed from the seba- ceous glands upon the nose. These threads readily break up in water ; a cellular emulsion being formed resembling the milky juice of cancer ; but the suspended cells are all true speci- mens of squamous epithelium, indistinguishable from those which line the oral cavity. Certain peculiarities of a minor sort in the form of the individual cells will be more properly discussed when we come to consider the appearances seen in tranverse sections. The nuclei are always of large size, ovoid, double- contoured and furnis^hed with one or more large and lustrous nucleoli. EPITHELIAL CARCINOMATA. 199 § 166. Epithcliomata of the skin and mucous membranes, save when they originate in warts or cauHHower excrescences, (§ 148) always begin as flattened and indurated elevations of the surface. They extend progressively both in depth and in super- ficial area. -Should the growth have reached a certain maximum of development at its place of origin, it breaks open at this point. The surface, somewhat tuberculatcd from the first, grows rough ; erosions, fissures, and holes appear in great numljcrs, and exude a white, inodorous, pulpy fluid, mixed with pus. The tumoiu' Fig. tlo. Section tlirougli the growing edge of an epithelial cancer of the skin. a. The fully-developed growth ; c^dmdcrs of epi- thelial cells containing pearly nodules (concentric globes), seen in longitudinal section ; h. An enlarged sebaceous gland ; c. Commencing elongation of peg-shaped protru- sions of the epidermis in an inward direction. ^ jj. next falls in at its centre ; a hollow is produced, which is hence- forth masked, either by the dried secretions, or, when these are removed, by the sloughy shreds of the original tissue. In this' phase of its development, therefore, the epithelioma presents the appearance of an ulcer with a hard base, and hard, raised edges. At the periphery of the ulcer, we note the constant advance of the infiltration into neighbouring parts ; in its indurated border, we can studv the characters of its maturity ; while towards its 200 EPITHELIAL CARCINOMATA. centrcj we mark tlie disintegration of the morbid growth, and the phenomena of repair, wdiich are occasionally very distinct. In considering the development of this variety of cancer, it is convenient to distinguish between its first beginnings and its subsequent extension. Thin vertical sections through the raised border of an epithelioma of the skin, are best adapted for the more accurate determination of its point of origin (fig. 63.) Pro- ceeding from without inwards in our examination of this section, from c to a, the first indication we have of the beginnings of the morbid growth, is a striking enlargement of the sebaceous glands (c). These increase in length and breadth ; their cascal ends becoming irregularly nodulated and clubbed. At the very edge of the tumour (h) we have a colossal example of this change ; and a dispassionate investigation leads us to conclude that the tubuli of the swollen gland difi:er in no respect from the adjoin- ing protrusions of the cancroid growth (a). This resemblance is especially due to the fact that during the elongation and thicken- ing of the fundus of the gland, its character as a secreting organ is Avholly lost; we miss the central cavity and the oil-globules; we can see nothing but closely aggregated epithelial cells, and these of such dimensions as far exceed the normal standard of the sebaceous epithelia. These considerations make it credible that epithelioma of the skin may originate in the sebaceous glands ; but on the other hand, we must not forget that this " origin from sebaceous glands" must be regarded as only a part of the entire phe- nomenon, which consists in a thorough dislocation of the houndary- line (Grenzverrlickung) heticeen epithelium and connective tissue. On the one hand, we owe to Thiersch* the account of an epithe- lioma which sprang demonstrably from the sudoriparous glands ; on the other, we may see in any and every epithelioma, that it is not the glands alone which take part in the formation of the cancroid protrusions. Club-shaped processes of epithelium burrow into the underlying tissues from the deepest points of the epithe- lial stratum, from those convexities of the rete Malpighii which lie in the inter-papillary furrow^s ; and it is this phenomenon, to which the elongation of the existing epithelial protrusions {i.e. the glands) is quite subordinate, which stamps a common * Thiersch, Der Epithelialkreha. Leipzig, Eugelmanu, I860. EPITHELIAL CARCINOMATA. 201 character on every variety of primary epitheliomatous growth.* It is not therefore as glands, but as appendages of the epidermis, that the sebaceous and sudoriparous follicles take part in the proliferation. They lose their glandular character and are con- verted into what they originally were, solid aggregates of cells, forming peg-shaped appendages of the under surface of the epidermis. § 167. Opinions differ concerning the way in which the epi- thelial sprouts grow and penetrate mto the sub-epidermic layer of connective tissue. According to Thiersch^ Billroth and others, the sprouts grow exclusively by proliferation of their epithelial elements ; Kostev holds that their increase is additive, and due to a corresponding metamorphosis of the endothelial cells of the lymphatics, in whose interior the sprouts exclusively extend. For my own part, I cannot overlook the very striking fact, that active fission of cells and nuclei may be seen to take place in the sprouts themselves ; neither can I ignore the eloquent appearances exhibited by sections taken from the raised border of certain flat epitheliomata in a direction parallel to their surface, as Koster recommends. Fig. 64 exhibits the superficial lymphatic network of the cutis in its highly characteristic configuration, but with its interior occupied by cylindrical masses of epithelial cells. The lymphatics in this specimen are undoubtedly the channels along which the epithelial sprouts advance. It must not be inferred from this, that they perfoi'm a like office in the case of all cancers ; indeed we may find it necessary to admit that the interesting appearances discovered by Koster are only the micro- scopical expression of a fact already known, sc. that cancers and sarcomata of glandular organs (^e.g. of the kidney, the testicle, the lymphatic glands) are especially prone to penetrate into the interior of the blood-vessels and lymphatics, in which they sub- sequently extend. Whatever be our conclusion, the observatipn * From an examination of epitheliomata of the digestive tract, I have come to the conclusion, that the tubular glands of the mucous mem* brane, lined with columnar epithelium, play the same part as the seba- ceous glands of the skin. They extend inwards, and change their character, losing their central cavity, and forming solid aggregates of cells ; these aggregates consisting first of indifferent elements, subae- cpiently of true squamous epithelia. 202 EPITHELIAL CAECINOMATA. itself is a reliable one, and sheds miicli light on the way in which certain kinds of cancer penetrate into and extend through the parenchyma of organs. With this part of Kbster's theory, the in- dependent growth of the epithelial sprouts asserted to take place by Thiersch may very well be reconciled. It is only the addi- tive growth by metamorphosis of the lymphatic endothelia, which is radically incompatible with TJuet-sdCs views. I have always warned my hearers against the danger of adopting a Fig. 64. /|^B^k^i|^J\ Horizontal section through tlic proliferating zone of an epi- thelial cancer of the skin. Extension of the epithelial pro- trusions along the interior of the lymphatic ycssqIs. After Kuster. one-sided conclusion on this matter, and I do not even now see any reason for deserting the via media Avhich I have hitherto followed. In epithelium (as eg. also in cartilage) I distinguish between a primary and a secondary mode of growth ; the former consisting in the addition of young and small cells at the junc- tion of the epithelium with the connective tissue, the latter in an enlargement and proliferation of the cells in the middle of the epithelial layer. To the former of these two factors is due the growth in length and breadth, to the latter the sudden condensa- tion of the young stratum which is familiar to every microscopist. (Cf the skinning over of raw surfaces, fig. 39). The pheno- mena are the same in disease. The actual extension of the epi- thelial sprouts is due to the apposition of mobile cells derived from the nutrient apparatus (according to Kdsttr of proliferated endothelia) to their most advanced points. Their subsequent EPITHELIAL CARCINOMATA. 203 condensation unci conversion into tough, peg-sliaped processes of epitheliumj is in great measure a result of cell-proliferation in the axis of the sprouts themselves. § 168. Passing on to consider the structure of the tumour, (fig. 63a) we see at a glance that it is chiefly made up of the ejji- thelial cylinders already alluded to as '^ peg-shaped protrusions." The average diameter of these cylinders is one-seventh of a line ; their length is usually very considerable, though it is not often Fig. ^o. Section of an epithelial cylinder under a magnifying power of 500 diameters, a. The cylinder itself, cxliibiting the characteristic stratification of its cells, and tAvo pearly nodules, one of which is older than the other ; h. The stroma ; at c it contains a very large proportion of corpus- cular elements and contributes directly to the additive enlargement of the cylinder. that we have an opportunity of seeing the whole of any one- cylinder. They bifurcate, sometimes repeatedly, forming per- fectly dendritic structures. The arrangement of the epithelial cells, as seen in transverse sections, is highly characteristic. At the junction of the epithelium with \\\q connective tissue, at the periphery therefore of the protrusions, a layer of small, roundly- oval elements, often of a brownish tint, is found ; this inter- venes between the connective tissue on the outside^ and the more 204 EPITHELIAL CAPtCINOMATA. liiglily-developed squamous elements interiorly (just as in the healthy cutis). These small cells fill up all crevices ; everything is continuous, there are no breaks. And a tendency to concen- trie lamination prevails throughout. We may fairly assume that inasmuch as the infiltrated parenchyma is not capable of being stretched beyond a certain point, the peg-sliaped protrusions cannot attain more than a cer- tain definite thickness. Now supposing that new cells continue to be formed it is clear that the available space must sooner or later be exhausted ; pressure must arise in the interior of the tumour, which will be exerted both on the processes themselves and on the connective tissue of the intervening stroma. I regard this " compression due to growth " as a very important element in the life-history of all infiltrative growths ; for, in so far as it compresses the interstitial vessels, it must hinder the circu- lation of the blood, disturb the nutrition of the parts, and thus, as a rule, be the prime cause of degenerative changes. This part of its action is the same in epithelioma as in other tumours ; I am inclined moreover to assign it a share in the tendency towards lamination alluded to above, a tendency shown by the cells in the interior of the epithelial protrusions, and which culminates in the formation of the so-called " pearly globes or nodules." The pearly globes are produced as follows (fig. 63) : at intervals in the axis of the epithelial protrusions, one or two cells which retain their spherical form, serve as a nucleus to which the adjacent elements are applied like the con- centric scales of a bulb ; these elements being flattened out, so as to yield the optical effect of fine dark lines when seen edge- ways, just as in the hairs and nails. Large numbers of cells are thus squeezed into a small, globular space ; the entire mass presenting a homogeneous, intensely yellow and lustrous aspect, which recalls the colour of hair. Tlie individual nodules may rrrow to a considerable size ; and we shall find in what is known as '^pearly cancer" {see cysts of nervous organs, brain) a form of epithelioma in which the entire tumour is ultimately converted into an aggregate of pearly nodules. The cells of epithelioma are also liable to another interesting change, which is not, however, common ; they may become o-rooved. This term is applied to cells Avhose surface is beset EPITHELIAL CAECINOMATA. 205 with a large number of parallel ridges, only visible under high powers ; these ridges being suturally adapted to the correspond- ing grooves or furrows of adjacent cells, thereby causing an exceedingly firm union of the cells among themselves. § 169. The second constant element in the structure of epitheliomata is a stroma made up of connective tissue. Inas- much as the bodies with which it shares the space assigned to the entire tumour are of a cylindrical form, it must needs constitute a honeycomb-like framework, the open ends of tlie cells being directed outwards. The stroma consists at first of the parenchyma of the cutis or mucous membrane dislocated and frayed out. We learned on a former occasion (§ 83) to regard the epithelium, apart from its first differentiation in the embryo, as in every case a product of the connective tissue ; hence we may take it for granted that the stroma plays a very active part in epitheliomatous growth. We actually find, especially at those points where the growth of the epithelial protrusions is most active, that their apices are tipped with a luxuriant proliferation of cells (c) ; the stroma is richly provided throughout with young elements; moreover it is prone to take on an independent activity, which usually leads to the development of papillary excrescences. The stroma carries the vessels of the tumour ; they share its fate in all respects ; when the stroma wastes, they are obliterated ; when it developes a productive activity, they dilate (^see below). Fig. 63 shows a successful injection of the vessels, executed according to the directions given by Thiersch. § 170. We come now to the degeneration of epithelial can- cer. Its conditions are involved in the growth of the tumour itself. Attention has already been called to the possibility of the " pressure due to growth" interfering with the circulation, and so disturbing nutrition in larger or smaller sections of the tumour. These disturbances are first felt as a rule in such points of the tumour as are already subjected to unfavourable nutritive conditions. Such points are the centres of the epithelial protru- sions. The thicker the protrusions, the farther their axial cells are from the soil which gave them birth and which should nourish them. The circumstance that these are the first-formed and consequently the oldest cells operates in the same direction ; so that we usually find the phenomena of retrograde meta- 2()C> EPITHELIAL CARCIXOMATA. morpliosis beginning in tlie axis of the protrusions. The phenomena in question consist mainly in fatty degeneration of the epithelial cells, loading to the formation of a number of atheromatous abscesses. These are originally distinct^ but they gradually coalesce to form a single cavity extending through the entire length of the protrusion. Such cavities may be recognised on the surface of the epithelioma even with the naked eye as yellowish-white, comedo-like points. They ultimately burst ; the excavated protrusions open up and discharge their contents on the surface. The tumour thereupon collapses, and the ulcera- tion, the discharge of pus and atheromatous pulp, to which allu- sion has been already made, begins. Epithelioma does not belong to the most malignant group of morbid growths. At least cases of radical extirpation (?.^. with no attempt to spare surrounding parts) not followed l)y any return of the disease, have been vouched for by responsible observers. Such cases, indeed, are by no means common. Within a year from the operation, the cicatrix generally be- comes the seat of a new growth of analogous character. On the other hand, metastasis proper is comparatively rare. The nearest lymphatic glands are the first to be affected ; the internal organs not being involved until the primary mischief has attained dimensions so colossal, that the trifling metastatic lesions are unimportant in comparison. The metastasis is probably due in all cases to the immigration of young epithelial cells, which cause an '' epithelial infection " of the autochthonous elements of the conjoint vascular and connective-tissue system at the point where they settle. § 171. Columnar Epithelioma. Until very lately, obser- vers could not agree whether to regard the crypts of Lieherkuhn in the digestive tract as genuine tubular glands, or merely as crypts, i.e. csecal inflexions of the surface solely designed to increase its superficial area. The difficulty was mainly histo- logical ; for it was shown that these so-called glands were lined throughout with columnar epithelium of exactly the same kind as that which clothed the free surface itself and its papilln?. The results of pathological histology are not in any way adapted to allay the scruples thus aroused ; for the only affection from which we might expect to gain some conclusive evidence on this sub- ject, sc. columnar epithelioma of the digestive tract, involves the EPITHELIAL CARCINOMATA. 207 epitlielium of the ciypts and that of the papillae in so uniform a manner, exhibits so constant a ratio between the elevations and depressions of the dermo-epithelial bomidary-line, that it is absolutely impracticable to draw a hard and fast line between the two. This explains how it is that the very same morbid growth may, with equal fairness, be regarded as a destructive papilloma {Fdrster)^ or a proliferating adenoma (Klebs). To these two observers we owe what knowledge we possess concerning the finer details of the development of columnar epithelioma. The alteration invariably begins with a deepening of the glandular tubuli and an increase in the number of their terminal divisions. Here, however, it is important to note that this phenomenon from the very first, I feel almost inclined to add, designedly, presents the character of an extension of super- ficial area ; for we never find solid cellular protrusions like those in squamous epithelioma, but always protrusions of the existing cavity of the gland, which are lined with a single layer of columnar cells. The growth next proceeds to cause a positive. extension of surface ; i.e. to produce pajoillary excrescences from- the walls of the cavities. In this connexion, some statements made by Klehs are of great interest ; he says that acuminated and club-shaped outgrowths, consisting at first entirely of epithe- lial cells, rise from the fundus of the glandular tubuli (fig 6G). At a later period w^e find branching papilla^, which grow in all directions, and especially inwards, contributing thereby to the destruction of the affected parts. Fig. 66. From an adenoma of the digestive tract. Copied from Klehs. (Handbuch der Patholog. Anatomie, fig. 4.) The free surface of the mucous membrane has already begun 208 EPITHELIAL CAKCINOHATA. to take part in the process by a more or less exuberant prolifera- tion of papillae. The free surface however is to be regarded generally as a locus ininovis resistentice ; accordingly the tumour as a whole projects above it, first as a flat and uniform, later as a fungoid elevation. To enable us justly to appreciate its com- plicated structure, and more particularly to discriminate between the papillary outgrowths and the inter-follicular septa, which are likewise coated with columnar epithelium, we must make use of specimens teased out with needles, or sections of a certain thickness ; since, in very fine sections, there is no break in the continuity of the outline which passes from elevation to depres- sion and vice versa, without indicating the concavity or the convexity of the epithelial ridges (fig. 67). Fig. 6; Yertical section tkrougli a columnar epithehoma of the stomach. 3^^. § 172. I am aware that nearly all the mucous membranes, especially those of the larynx, uterus, bladder and others, have each their peculiar form of epithelioma, which differs from the chief types, from the squamous and columnar epitheliomata, in the same degree as the transitional forms of epithelium with which these parts are clothed, differ from the simple squamous epithe- lium of the skin, or the simple columnar epithelium of the stomach and bowel. For a detailed account of these finer variations I refer the reader to the special division of this work. CYLINDROMA. 209 Cylixdroma (Appendix). § 173. The question concerning the essential character of a tumour, termed by Henle siphonoma, by Billroth cylindromaj by Meckel tubular enchondroma, by Friedreich tubular sarcoma, by Forster and its most recent investigator Koster mucous cancroid, presents itself among all discussions concerning the fundamental nature of cancer and sarcoma, as an enio-ma of equal interest and difficulty which chance has thrown in the way, now of one, now of another inquirer. The number of names which have been applied to this growth, show clearly enouo-h that the different observers differ widely in their views concernino- it. Are we justified in assuming that all the cases which have been examined are really identical ? In fiivour of this assump- tion we have the fact of their common situation in the region of the fiice, particularly in the orbit and surrounding parts ; while the circumstance that the earlier observers devoted their chief attention to the most singular and not to the most essential constituents of the growth, may go some way towards explaining and excusing their differences of opinion. Those singular constituents are certain ^Mij-aline bodies" of considerable size, which may readily be isolated by teazing with needles. We are struck first of all with the strangeness of their outward form. Together with perfect spheres, we find specimens of a more cylindrical shape ; others again which are club-shaped and cactiform. The hyaline chains often seem to diverge from a common centre. I cannot now review the manifold hypotheses concerning the mode of origin and flirther development of these bodies, hypotheses in which the prevalent histogenetic theories are for the most part mirrored. I will only say that BillrotFs view, according to w^hieh they are perivascular sheaths of mucous tissue or fragments of such sheaths was the most generally adopted one, until Koster recently showed, from a very careful study of the development of the tumour as a whole, that the hyaline globes, cylinders, etc., were the product of a secondary, hyaline metamorphosis of the cellular trabeculse of a cancroid growth of the lym]3hatic vessels. He believes that we have to do in all cases with a cancroid proliferation of cells taking place in the lymphatic networks of the affected part. The endothelia of the lymphatics proliferate ; the canals are blocked by cellular cords 14 210 CYLINDROMA. resulting from tlieir proliferation ; anil the cords naturally ramify and anastomose Avitli one another like the lymphatics themselves. Thereupon, the hyaline degeneration sets in, beginning in the axis of the -cords. It may even be demonstrated in individual cells ; at a later period, however, the products of degeneration coalesce to form those larger globes and cylinders whose original cellular composition is at best but faintly indicated by the presence and stellate arrangement of a finely- granular material coinciding with the intercellular limits. The hyaline degenera- tion may implicate the whole of the epithelial coat, a hyaline cylinder of relatively large size appearing to be. embedded in the connective tissue of the stroma. The presence of blood-vessels in the axis of the hyaline cylinders, which I have succeeded in demonstrating in a tumour extending to the cerebral substance (fig. QS), is explained by Kbster by the well= known perivascular disposition of the lymphatic sinuses. Cylindroma is very liable to recur after removal, but it seldom gives rise to metastatic deposits; accordingly it deserves a place near the carcinomata. To distino^uish it from the glandular and epithelial forms of cancer, it may be allowed to retain the name of can- croid, which used formerly to be ap- plied to all the varieties of epithelial cancer indiscriminately. Cylindroma from the cortex cerebelli. SPECIAL PART, L-MOEBID STATES OF THE BLOOD AND THE OEGANS CONGEENED IN ITS EEXEWAL, PAETICULAELY THE SPLEEN AND LYMPHATIC GLANDS. a. Dyscrasi^. § 174. The blood plays sncli a weighty part in pathology that it seems necessaiy to explain why so little space will be devoted to a consideration of its morbid states in the present manual. The position of the blood in the domain of pathology is determined by its physiological significance. The blood is the medium through which the interchano-e of matter in the oriranism (StofFwechsel) is carried on. It is the nutrient fluid, which supplies each individual part of the body with the pabulum indispensable for its existence ; it removes the effete and hurtful products of the chemical processes associated with nutrition, and carries them to the excretory organs for elimination. Viewed in this light, the blood is the meeting-place of divers chemical compounds, some of which have already taken part in tissue- metamorphosis, while others are about to take part in it; of compounds whose presence in the blood is in every case only temporary^ and which thus give to tlie blood itself a certain variability of chemical composition, for which not the blood but the organs of the body are really answerable. Even if we view the blood as an organ, it is peculiarly liable to change in comparison with other organs. Our right to call the blood an organ cannot be disputed. For it has an independent origin from embryonic tissue in the area vasculosaj apart from other organs ; it possesses specific cells — the blood-corpuscles, which subserve a specific function — that of fixing the oxygen of the air. We must not allow ourselves to be led astray by the fact that the corpuscular elements are separated by a fluid inter- 212 MORBID STATES OF THE BLOOD, ETC. cellular substance — that the blood itself is a fluid. Its structural elements are themselves of very unstable character. The blood is rightly held to be that tissue whose losses are soonest remedied, whose morphological and chemical constituents undergo on the whole the most rapid change. We must recollect moreover, that it does not elaborate its constituent elements within itself, but draws its supply of cells from the lymphatic glands, the spleen, and according to Bizzozero, Neumann^ and others, from the marrow of bone, and its albumen from the alimentary canal. In this resjDCct too therefore, certain determinate organs are responsible for the composition of the blood. Accordingly the blood is kept in its normal state by the systematic co-operation of several factors ; by the due admixture and transformation of its histogenetic elements ; by the uniform and easy supply and removal of the more transitory nutrient and excrementitious substances ; finally by the rigid exclusion of abnormal or injurious matters from whatever source. Any irregularity in these conditions alters the composition of the blood, and gives rise to a dyscrasia; and indeed, the vast majority of blood- diseases are nothing more than such morbid alterations of its composition. § 175. But few of the manifold dyscrasise of the blood admit of being investigated anatomically; only those indeed which depend upon morbid changes in the visible elements which are suspended in the colourless liquor sanguinis. These elements are usuallv distino-uished as : 1. The red blood-corpuscles; flattened, biconcave discs, about four times as broad as they are thick, without nuclei, without a cell-membrane (?), made up of a colourless protoplasm (stroma), and a reddish-yellow fluid material (haemato-crys- tallin).* 2. The colourless blood-corpuscles or leucocytes, which are so rare in healthy human blood that for every 450 red cor- puscles we find only one white one. These cells are destitute of * Besides the discoidal blood corpuscles we always find a certain number wbicli have become spherical. These are characterised by their apparent smalluess, and their darker, almost reddish-brown hue, peculiarities readily explained by supposing that the same quantity of matter which was previously spread out into a shallow disc, has shrunk together to form a sphere. CHLOHOSIS. 213 a limitary membrane ; they are made up of a finely granular protoplasm containing distinct nuclear structures. We find either a single, round nucleus of considerable size, or from two to five smaller ones of lustrous aspect. In form the white cor- puscles vary, inasmuch as they are endowed with a high degree of spontaneous contractility ; in dead blood, they are spherical. Accordingly they are cells, which resemble in every respect the corpuscular elements of embryonic tissue and of pus, from which indeed they can hardly be distinguished by any anatomical criteria. 3. The elementary vesicles discovered by Zlmmermann^ cir- cular, colourless bodies with indistinct outlines, which owing to their small size and transparency are only to be detected under very high powers, but which are occasionally present in enormous numbers. 1. Chlorosis. § 176. The chlorotic dyscrasia is essentially characterised by a falling-off in the number of all the above-named stractures. Of all alike, so that the proportion of the red to the colourless corpuscles is in no wise altered. The blood as a whole seems thinner and more clear — one might almost say more watery than usual ; on evaporation, the percentage amount of solid residue is decidedly below the normal average ; all this however is due, not to any increase in the amount of water, but to a positive diminution in the number of cells. Where an organ depends for its colour on the blood it contains, as e.(/. the mucous membranes (conjunctiva) and certain parts of the skin — we observe a peculiar paleness, wdiich has caused the name of " green-sickness " to be given to the disease. The etiology of chlorosis is still involved in some doubt. So much is certain, that the chlorotic dyscrasia does not depend upon a premature destruction, upon an atrophy of blood-cor- puscles, but upon an inadequate sujDply of young and vigorous elements to take the place of those which have completed their term of existence, and are only fit to be cast out. But beyond this, we cannot tell whether a functional disturbance of the organs of sanguification (the spleen and lymphatic glands) or some disorder of the more remote factors in the process (e.r/. chylification) is to blame. Virchow's view is deserving of 214 MOREID STATES OP THE ELOOD, ETC. especial notice ; he finds that the aplastic state of the blood is associated with a certain aplastic condition of the circulatory apparatus as a whole, sc. the heart and arterial system (see below), so that chlorosis would have to be viewed as a con- genital, and not, as is generally held, an acquired disease. 2. Leukli icemia. § 177. The leukhasmic dyscrasia depends upon an alteration in the numerical proportion of the Avhite to the red blood- corpuscles. "We have already given 1 to 450 as the average ratio of white to red corpuscles. A moderate increase in the number of the colourless cells is consistent witli health and may be demonstrated e.g. after every full meal. But if the number of the white corpuscles undergoes so marked an increase in pro- portion to that of the red ones, that we find e.r/. one wdiite to ten red elements, or even an equal number of both, then indeed the condition becomes manifest even to the unaided eye as a decolorisation of the blood ; the blood assumes a paler, raspberry- like hue, and w^e are thus entitled to speak of ^' white blood " or leukh^emia. This most interestino; morbid state was described in 1845 by Vircliow and Bennett simultaneously ; the German pathologist however deserves the credit of having from the first recognised and explained its real meaning. According to him, we have to do w^tli an increased supply of colourless corpuscles to the blood, due to a morbid state of those very organs -vvhicli normally supply the blood with its colourless elements, viz. the spleen and the lymphatic glands. § 178. The SPLEEN has long been held to play an important part in the renewal of the blood ; in our time it has been regarded, now" as the grave of the red corpuscles, now as the birthplace of the white ones ; KdlUker has justly attributed both of these functions to it. Tlie excess of colourless cells in the blood of the splenic vein is an indisputable fact ; they are from fixe to ten times as numerous as in arterial blood. It is equally certain that the lymphatic glands, particularly those of the mesentery, are a source of white corpuscles. If we compare the lymph of the thoracic duct with that of the peripheral lymphatics before they enter the glands, we find that the former contains a far larger proportion of lymph-corpuscles. The afflux of leucocytes LEUKH^^MIA. 215 from tlie spleen and lymphatic glands is not uniformly rapid at all times. It is most active a short while after meals. This increased activity coincides with that transient hyperemia of the entire digestive tract which is caused by taking food, and which manifests itself in the spleen more especially as a perceptible intumescence of that organ. If w^e have the chance of examining a spleen under such circumstances, we find, besides a marked congestion of its pulp, a distinctly swollen condition of the Malpighian bodies. The mesenteric glands too are larger and contain more blood than usual. It is probable therefore that the increased supply of blood occasions a more rapid production of leucocytes in the Malpighian bodies of the spleen and in the mesenteric glands. The newly-formed cells mingle with the current of lymph or of blood as the case may be, and a transient leucocytosis is the result ; no sooner however does the digestive hyperjBmia of the abdominal viscera subside, than the lymphatic organs on the one hand, and the composition of the blood on the other, return to their normal state. § 179. Leukhaemia too is commonly associated with an en- largement of the lymphatic organs. The spleen here takes the lead. By far the greater half of all leukhasmiaB are purely splenic ; more rarely do we find the lymphatic glands diseased together with the spleen ; and an exclusive affection of the lymphatic glands is rarest of all. The leukhcemic spleen is originally a congested spleen. The blood, flowing more slowly, accumulates mainly in those anasto- motic channels of the pulp, which were first recognised by Billroth as a part of the blood-path through the spleen, and termed '' cavernous veins " on account of their easily demonstrable connexion with the efferent vessels. The lymphoid parenchyma of the pulp (the intervascular cords of Billroth) is also in- volved in the process ; in addition to the usual colourless cells of the spleen we find an unusual number of red corpuscles ; the Malpighian bodies too arc enlarged, though the alteration in their structure is not as yet very striking. With the naked eye, besides the dark colour, diminished consistency, and increased volume of the pulp, we perceive a distinctly lobed or rather tuberous condition of the surface of the organ. Each of these elevations corresponds to the area of distribution of a splenic arteriole (j-tenicillus), while the intervening depressions coincide 216 MORBID STATES OF THE BLOOD, ETC. with the insertion of the larf^er trabecula?, these takinor a lon'^'er time to accommodate themselves to the enlar^rement of the oro^an as a whole. The capsule too does not admit of any very sudden distension. In my notes of Virchoiv^s practical course (Berlin, 1857-58) I find a case of splenic leukhsemia in which the spleen (in the stage of parenchymatous congestion) was swollen till it measured one foot in length, two inches in thickness, and five inches in width ; and in consequence of this, a rupture of the capsule had occurred. The fissure, masked by clotted blood, was three lines in length, and passed at each end into a com- mencing dissociation of the capsular fibres, preliminary to an extension of the tear. § 180. As the disease advances, an overgrowth (hyperplasia) of the Malpighian bodies — or as we must call them nowadays, the lymphoid sheaths of the arteries — developes itself more and more. The first step in the process is an accumulation of leucocytes in their interior, produced by fission of those Fig. 69. Cut surface of spleen in the second stage of leukliajmic swell- ing. Enlargement of Malpighian bodies. Atrophy with pigmentation of the pulp. already present. This proliferation is followed by a dilatation of the delicate fibrous reticulum between the cells, and subsequently by a proportionate formation of new capillaries, so that the enlargement of the Malpighian bodies really implicates every one of their three constituents, and must therefore be regarded as a true overgrowth. The Malpighian bodies are now very distinct on the cut surface of the spleen as white, tough, resist- ant nodules ; they exhibit, more often than under normal con- ditions, a tendency to bifurcate, nay even to brenk up into a number of branches, a proof that they have not only increased LEUKH^EMIA. 217 in thickness, but have also extended either upwards or down- wards along the vessels to which they are attached (fig. 69). The overgrowth of the Malpighian bodies naturally contri- butes a new element to the existing causes of splenic enlarge- ment. The spleen attains the greatest length, breadth, and thickness of which it is susceptible. Inasmuch however as the morbid phenomena must run their course in a space limited by the size of the splenic capsule, it is self-evident that degenerative changes must coincide with the hyperplastic processes in order to make room for the latter. The former chiefly affect the pulp, which, wedged in between the continually growing Malpighian bodies, perishes in large portions at a time. This is always asso- ciated with an abundant production of pigment, which reaches its maximum in the immediate neighbourhood of the glistening Malpighian bodies, giving rise to an exceedingly variegated ^' granitic" marbling of the cut surface. The consistency of the organ conforms to that of its chief constituents, the Malpighian bodies ; it becomes peculiarly tough, more than leathery, almost wooden. In addition to all this, we have chronic inflammatory changes in the peritoneal coat which give rise either to smooth or reticulated thickenings of cartilaginous hardness, or else to highly vascular membranous adhesions connecting the spleen with the nearest abdominal viscera. § 181. With splenic leukhaimia Vircliow contrasts that rarer form to which he gives the name of lymphatic leitkhcemia ; it is characterised from the first by the predominant way in which the lymphatic glands are affected, while the splenic tumour is either secondary or altogether absent. The glands do not all swell at once ; the disease usually begins in an inguinal or axillary gland and spreads first to all the glands in the same region ; it then extends inwards in the direction of the thoracic duct, involving the mediastinal or retroperitoneal groups of glands ; then other peri2:>heral glands take on the morbid action, until every lym- phatic gland in the body is more or less enlarged. The indi- vidual glands often attain from three to five times, occasionally even ten times their natural size. Nevertheless, an anatomical investigation shows nothing beyond a simple overgrowth in every case. This indeed is clear enough from the fact that even in cases of extreme enlargement the lymph-paths remain open, and the lymphatic sinuses of the gland can be injected both 218 MOUBID STATES OF THE BLOOD, ETC. from the afterent lym})hatics, and bj direct puncture. An exa- mination of thin sections which have been pencilled out shows nothing which might not occur in a normal gland ; fine-meshed reticulum made up of thin, lustrous threads, permeated by capillaries and occupied by lymph-corpuscles. We notice only that the cortical nodules (Eindenknoten) and the medullary cords (Markstrange) are far broader, and the capsules and septa ' of connective tissue far thicker than they usually are. W. Midler asserts that in liy])erplastic enlargements of the lymphatic glands the delicate network of connective-tissue corpuscles which permeates the lymphatic sinuses of the cortex and the lymph- paths of the medullary substance, shows itself to be the essential histioplastic element, inasmuch as new layers of medullary sub- stance, in addition to those already present, are more particularly developed in its neighbourhood. I believe that this is principally true of leukhgemic overgrowths. (See below.) § 182. The pathological histology of leukhasmia is not ex- hausted with the consideration of these hyperplastic conditions of the spleen and lymphatic glands. The implication of other organs suggests that we ought rather to view those phenomena merely as the expression of a general tendency to the develop- ment of new lymphadenoid tissue. The presence of a certain quantity of unformed connective tissue seems in fact to be the only condition needful for the occurrence of the characteristic alterations. The cells proliferate, and form circumscribed deposits of variable size, which are white to the naked eye, and which can only be distinguished from small collections of pus by the circumstance that the cells are embedded in a network of delicate fibres of stiffened protoplasm, which leaves enough space round the cells for the transit of nutrient fluid. It need hardly be said however, that this very reticulum in which the cells are embedded, and which distinguishes the leukhpcmic product from a collection of pus, assimilates it to the lymphatic glands, raises it to the level of lymphadenoid tissue. (Cf leukhasmic swelling of the liver, kidneys and serous membranes in the corresponding chapters of the Special Part of this work.) 3. Melancemia. ^ 183. In the melan^mic dyscrasia, certain pigmentary par^ MELAN^MIA. 219 tides are found among the usual floating constituents of the blood ; in well-marked cases, they occur in every specimen of blood taken from the heart's cavities. Their shape is very irre- gular ; they are made up of yellow, brown, but most commonly of black granules ; most of them are small, smaller at least than red blood-corpuscles ; others are larger, and a few even exceed the red corpuscles considerably in size. Here and there we may succeed in demonstrating a trans- parent, colourless membrane investing the pigmentary aggregates and filling up the irregularities of their surface. In rare instances, this membrane is of considerable thickness, and then exhibits a concentric lamination. § 184. In the General Part of this w^ork I spoke at length about the mode in which pathological pigments originate. The remarks I then made are perfectly applicable to the pigmentary particles of melansemla. They are derived from the colouring- matter of the blood, and consist of condensed and altered liaBmatin ])reclpitated in a granular form. Both the circumstances and the locality of their production may be determined with some approach to certainty. Melanj^mlc pigment originates chiefly in the spleen, under the influence of the malarial cachexia (cachexia of intermittent fever). The morbid anatomy of intermittent fever starts from an active congestion of the liver and spleen. Both of these organs may attain a very considerable size in consequence. Neverthe- less, it is only after the hypersemla has lasted some time that signs of permanent disorganisation occur. One of these, a diffuse interstitial overgrowth of connective tissue, we shall become acquainted with among the diseases of the liver as an Induration of that organ. The spleen may either exhibit a kind of softening of its entire parenchyma, or an indurative condition which starts from a thickening of its capsule and trabecular network. In very severe cases, such as (thanks to the general use of Peruvian bark) only occur sporadically in Germany, this Is associated with a deposit of pigment both In the liver and in the spleen. This is directly traceable to the above-mentioned excessive and prolonged congestion of both organs. In the liver, the pigment makes its appearance just outside the vessels ; number- less minute extravasations into the capsule of Glisson and the hepatic parenchyma form the starting-point of the process. In 220 MOKBID STATES OF THE BLOOD, ETC. the spleen, whose peculiar structure excludes the possibility of extravasation, since the blood could only be extravasated out of one of its natural channels into another, the pigmentation occurs in the intervascular cords of the pulp — in those parts therefore where the blood flows most slowly. Even under normal condi- tions we may here observe the development of pigment-cells and blood-corpuscle-holding cells (cf. note to § 57). In the pig- mented spleen the intervascular cords are so thickly packed with the black, flaky masses (fig. 70, h) that the organ presents even to the naked eye a colour varying from slate-grey to black (the milza nera of the malarious districts of Italy). From hence the pigment-flakes make their way into the blood. We know that the intervascular cords are not shut Fig. 70. The melaneemic spleen. Transverse section from the middle of the organ, a. The cavernous veins of the spleen; h. The intervascular cords containing pigment ; c. A branch of the splenic artery. 3^. off from the cavernous veins by an impermeable membrane (fig. 70, a) ; we regard the former in the light of a filter with very fine pores intercalated between the arterioles on the one hand, and the venous radicles on the other, and which, in the spleen, takes the part of the capillary vessels and parenchyma of other organs. During this filtration the pigment-flakes are torn from their place of origin and pass into the blood, where their presence gives rise to the melanmiaec dyscrasia. The black particles are accordingly carried wherever the blood itself pene- trates. We find them in all the organs of the body, especially in those which are characterised by the narrowness of their capil- laries, e.c;. in the brain. All the flakes cannot pass through this THROMBOSIS. 221 organ ; the larger ones are arrested in transitu. The vessels give way behind the point of obstruction ; hemorrhage, inflammation and softening ensue ; in short we get a sum of anatomical dis- turbances associated with most severe clinical symptoms. The vetia mirabilia of the kidneys are likewise unfavourable to the free transit of the pigmentary particles; at least these organs stand next to the brain in the frequency with which they exhibit melanasmic j^igmentation, in the form of black dots and strisB in their cortical substance, corresponding in position to the Mai- pighian bodies and their afferent vessels. h. Coagulation of Blood in the Vessels (Thrombosis). § 185. One of the most important chapters of general patho- logy is taken up with the causes and consequences of the coagu- lation of blood in the interior of the vessels. We shall content ourselves with so much of it as is needful to understand the histology of the process. Coagulation is determined by two conditions ; retardation of the blood-current, and irregularities on the inner wall of the vessel which increase the friction between it and the passing- blood. Thrombosis often complicates many of those diseases of the vessels to which the ensuing section Avill be devoted. But coagulation from increased friction may indeed be often if not always referred to coagulation from stagnation ; and that wherever the irregularities in question afford even the smallest recesses in which the blood may pause. We shall return to this subject when we speak of endocarditis. § 186. The proximate cause of coagulation is in every case a precipitation of fibrin from the blood. The fibrin is not con- tained in the blood as such ; it is produced during the act of coaoculation itself. A. Schmidt has established the interesting: fact that the blood-corpuscles contain an albuminoid substance (globulin, fibrinoplastic matter) Avhicli forms an insoluble com- pound with a similar body (fibrinogen) contained in the liquor sanguinis, whenever the obstacles to coagulation are removed, or conditions favourable to coagulation are present. This insoluble compound is what we call "fibrin." Recently precipitated fibrin is a colourless substance mucli swollen by imbibition. Two parts of fibrin in a thousand are 222 MORBID STATES OF THE BLOOD, ETC. enoua*l"i to give the coagulum a jelly-like consistency. Recent fibrin is invisible under the microscope owing to its great homo- geneity and transparenc}'. These properties begin however to he modified from the moment that coagulation has occurred. The molecules of fibrin possess so high a degree of mutual attrac- tion, that the mass continues to shrink, squeezing out more and more of the fluid contained in its meshes. A highly character- istic change in the microscopical appearances is associated with this separation of the solid and liquid constituents of the clot ; in the homogeneous mass above alluded to, a number of little gaps and fissures make their appearance, between which the solidify- ing fibrin remains as a more or less delicate network composed of round threads. § 187. The above change maybe observed wherever the field is not obscured by too great an abundance of corpuscular ele- ments. But this is almost invariably the case when blood coao-ulates in the vessels. Red and white blood-corpuscles in vast numbers are entangled in the coagulated fibrin and mask the microscopic details of coagulation so completely, that we are unable to make out anything even in the finest sections through a hardened thrombus. We may consider it as settled that a pre- cipitation of fibrin underlies thrombosis ; that the subsequent contraction and the peculiar desiccation which the thrombus undercroes are certainlv due to the above-described chancres in the fibrin ; but the microscope fails to demonstrate the presence of fibrin among the innumerable cells of the intravascular thrombus ; and I may add that this fibrin never subsequently reappears. § 188. The recent thrombus is always of a dark red coloiu' and a jelly-like consistency, like any other blood-clot. Its shape depends on that of the cavity in which coagulation has occurred. Cylindrical plugs are very common, occupying the entire hnnen of a small vessel or one of medium size, and terminating in a conical point at the end turned towards the still pervious part of the channel (obstructing thrombi). Other clots do not block the vessel completely, but adhere to one side of its wall, exhibiting more of a ribbon-like aspect with a tongue-shaped end (lateral thrombi). Farther modifications are brought about by the secondary precipitation of fibrin which is everywhere caused by existing coagula when these are immersed in the blood-current. THROMBOSIS. 223 Layer upon layer is deposited, and by this continuous coagulafAon^ 1st, a lateral thrombus may easily be converted into an obstruct- ing one ; and 2nd, the coagulation may spread from one vessel to its neighbours. In the latter event, the intruding clot will at first be lateral, then obstructing, &c. The size and shape which the thrombus may ultimately assume cannot be determined a priori^ and can only be predicted with some degree of certainty in a few cases, c.a. after lio;ature of arteries. AVith reference to these we have the following law to guide us : the coagulation never extends beyond the nearest pervious collateral branch, whether in a peripheral or a central direction. The peripheral coagulation is not as a rule of much moment ; since, owing to the complete contraction of the arterial walls it usually forms a slender and barely perceptible thread. § 189. Wq may now proceed to consider the farther changes which occur in thrombi. A few preliminary remarks are indis- pensable however, about certain diiferences in their 'primary structure. 3Iuch depends on whether a thrombus has been formed rapidly, by some sudden accident, as e.g. when a vessel is tied and a certain quantity of blood, suddenly cut off from the current, coagulates forthwith ; or whether it has been produced more gradually. In the former case the coloT:rless and red corpuscles are so equally distributed throughout the clot, that on examinino; sections of it we find the colourless elements distributed at regular intervals throuo^hout the mass of red ones. It is far otherwise wdiere the coagulation begins and goes on gradually and slowly. As examples of this latter mode, we have the coagulation which begins in the superficial vessels of an amputated stump affected by diphtheritic inflammation, and which gradually spreads upwards into the veins ; the thrombosis which occurs in the left auricle in cases of mitral contraction ; thrombosis in varicose veins and aneurisms. In all these cases, with which we shall become more familiar when we study the diseases of the vessels, what is known as the "viscosity'' of the colourless corpuscles comes into play, giving rise to a concentric lamination of the clot. The colourless corpuscles are glutinous, i.e. their protoplasm tends to adhere to solid bodies, to penetrate into their pores. Most of all does it incline to unite with the protoplasm of other leucocytes ; so in the comparatively sluggish current of the veins we not unfrequently find the white blood- 224 MORBID STATES OF THE BLOOD, ETC. corpuscles joined in pairs ; and it is only on account of the rapidity with which the hlood is forced through the arteries, and repeatedly transmitted through a system of innumerable canals of very narrow calibre, that no permanent union between these elements normally occurs. Assumino- tliat a clot has reached a certain size, and that a fresh layer of coagulated blood has just been deposited upon its surface, it is clear that of all the blood-corpuscles which are carried past it, the colourless ones, owing to their glutinous properties, will be the first to adhere to it, and to become station- ary in its outer parts ; just as in RecJdlnghausen s experiments on suppurative inflammation, excited by the introduction of a finely-porous body into the subcutaneous tissue, the pus-cor- puscles penetrate into the pores, and thickly infiltrate the margins of the foreign hodj. Well, a layer of leucocytes is deposited which clothes the thrombus for a time, until a fresh deposit of red coagulum takes place. In other words, the blood coagulates by fits and starts, and between each recurrence, a large number olF leucocytes have time to attach themselves firmly to the surface of the clot. On making a transverse section through a clot of this kind we see at once that it i.-^ permeated in every direction by a system of transparent lines whi.-li exhi])it a more or less distinctly con- centric arrangement. These Hues correspond to the cross section of the layers of leucocytes which alternate with broader la}'ers of ordinary red blood. We must accordingly distinguish between two kinds of thrombi, basing our division on the differences in their primary structure : 1. Xon-laminated thrombi, originating in the sudden coagu- lation of an isolated quantum of blood. 2. Laminated thrombi formed by an intermittent, gradual, and long-continued coagulation. § 190. A clot is susceptible of further metamorphosis in two different directions, that of organisation and that of softening. Organisation, or transformation into connective tissue, has hitherto been chiefly studied in the non-laminated thrombi of the larger vessels. The following account must therefore be understood to apply to these only, and must not be supposed to include the oro-anisation of laminated clots, concerning which we are at present entirely ignorant. The thrombus attains its maximum size THROMBOSIS. 225 immediately after coagulation has taken place, when it still exhibits the dark-red colour and jelly-like consistency of a recent clot. It continues to contract from day to day till it shrinks up entirely, and after the lapse of a few months disappears, leaving not a trace of its former presence behind. This continuous decrease in size is associated with a decolorisation and condensation of its substance; it loses its original dark-red hue, until at length it comes to be only a shade redder than the wall of the vessel which contains it ; it grows drier and more tough ; whereas originally it lay loosely upon the walls of the vessel, at a later period it blends with them, assuming the character of a little plug of connective tissue, which seems rather to belong to the surrounding con- nective tissue and the wall of the vessel than to the blood. The progress of these alterations as seen by the unaided eye is eluci- dated by the microscope as follows : § 191. I have already said that in the recent non-laminated thrombus the colourless corpuscles are distributed among the red ones at tolerably uniform intervals. It used formerly to be supposed that all further changes started from these colourless elements. At the present day, the organisation of clots, in com- mon with many other morbid processes, is explained by the activity of migratory corpuscles. Artificial thrombi have been produced by tying arteries in the lower animals ; cinnabar has then been injected into the blood, and its leucocytes impregnated with this finely-granular material, which is easily recognisable under the microscope. It was found that those cells from which, on the second or third day after the occurrence of coagulation, the organising process appeared to set out, contained cinnabar ; the inevitable inference being that they had migrated into the clot from without. These cells then put forth processes in various directions which meet one another and unite to form a delicate protoplasmic network with nuclei in its nodal points (fig. 71, h.) Even at this stage the structure of the clot might be compared to that of a connective substance ; its corpuscular elements being represented by the leucocytes, and its inter- cellular substance by the mass of red blood-corpuscles and the fibrin. And this, if the phrase may be allowed, is the fundamental idea which underlies the whole organising process and which tends forthwith to realise itself. Shortly after this primary differentiation has taken place, the 15 226 MORBID STATES OF THE BLOOD, ETC. vascularisation of the tlirombus begins.* This conforms to the "tertiary'' type, i.e. the opening up of capillary channels along the threads of the protoplasmic network. A more or less com- plete vascularisation may be demonstrated in every thrombus over eight days old, whether by injection, or by the examina- tion of fine sections. The vessels are thin-walled capillaries with alternating nuclei (fig. 71, a); they get their blood mainly from the still pervious portion of the occluded vessel itself, whither also they return it, until other anastomoses are deve- Transverse section througli a clot produced by ligature of the crural artery, tMrty-seyen days after operation. Hardened in alcohol. Treated with dilute acetic acid and then with a little ammonia, a. Capillaries ; h. The cell-network of the colour- less blood-corpuscles. In the basis-substance we see the outlines of the red corpuscles. loped, though still in scanty number, with the vasa vasoinnn. An indispensable preliminary to the formation of such anasto- moses is the perforation of the non-vascular tunica intima of the vessel, separated as it is from the middle coat by its homo- geneous limitary membrane ; and this is clearly a harder task for nature to perform than we might at first imagine it to be (fig. 72). _ , § 192. The vascularisation of the clot guarantees it a more durable and organic connexion with the body ; it becomes hence- forth a member of the series of vascular connective tissues. But * See 0. Weber, Handbuch der Allgemeinen und Speciellen Chirurgie, redig. von Fiiha und Billroth. Bd. i., Lieferung.l, p. 143. THROMBOSIS. 227 liow do matters stand with regard to the intercellular substance of this very peculiar connective tissue ? The red corpuscles together with the fibrin make up the bulk of the recent thrombus. Hence it is to alterations in therrij that such changes in the clot as we are able to trace with the naked eye, must be chiefly due. The rapid escape of colouring matter from the red corpuscles explains the decolorisation of the clot ; Fig. 72. Longitudinal section througb. the ligatured end of the crural artery in a dog, fifty days after operation. Injected by 0. Weher. Tli. Thrombus. M L Middle coat; Z. Areolar coat. its shrinking and increased dryness are due to the contraction of the fibrin and the consequent expulsion of the contained fluid. What remains therefore is — 1st, instead of every red corpuscle, a flake of colom-less protoplasm ; 2nd, the fibrin as an invisible but nevertheless very firm cement which binds these flakes together. The two form a mass which is not easily torn and which is never fibrous ; from the first until about the 228 MORBID STATES OF THE BLOOD, ETC. eighth "vveek this constitutes the basis-substance of the thrombus. Moreover the original character of its constituent elements con- tinues to be recognisable for a long time. In a thirty-seven days' old thrombus after ligature I found the decolorised blood- corpuscles so little altered in shape that their numbers entirely masked the vessels and connective-tissue corpuscles ; and it was only after adding acetic acid, which made the whole specimen swell up violently and obliterated the outlines of the blood-discs, that the network of vessels and cells became distinctly visible. Then indeed its likeness to a vascular connective tissue became unmistakeable ; and I do not scruple, on the ground of its reaction with acetic acid, to admit the direct conversion of the stroma of the blood-corpuscles into the basis-substance of con- nective tissue. I may add that even after the addition of acetic acid, a judicious neutralisation with ammonia rendered the out- lines of the blood-discs once more distinct, so that both the con- stituent elements of the thrombus, the network of cells and vessels on the one hand, and the former blood-corpuscles on the other, could be seen side by side (fig. 71). § 193. The remaining histological alterations may be viewed as a cavernous metamorphosis {see § 129) of the thrombus. It used in former days to be described as a ^' sinus-like " (sinus- artig) degeneration. The blood-vessels grow wider and wider, while the parenchyma between them disappears and is replaced by a moderate quantity of colourless cicatricial tissue arranged in concentric laminae round the vessels. At a certain stage in the process the cavernous structure is exquisitely apparent (fig. 73). The vessels continue to grow wider and the septa between them thinner, until they wholly disappear and the thrombus accordingly ceases to exist. § 194. The softening of thrombi contrasts with their organi- sation in much the same way as suppuration contrasts with organisation in the case of inflammatory products. This remark applies to the clinical significance, as well as the naked- eye peculiarities of the process. As regards the latter, a decolorisa- tion of the primarily dark-red thrombus, plays here, as during its organisation, a prominent part. The colour begins to fade at its centre, and the decolorisation spreads from this point to the circumference ; it is associated with a certain degree of condensation which is not however, as it is during THROMBOSIS. 229 organisation, a permanent, but a transitory phenomenon, and passes straightway into the opposite condition, that of softening and liquefaction ; accordingly we find at a certain stage in the process a yellow fluid not unlike pus occupying the interior of the clot, and enclosed in a comparatively tough, flesh-coloured layer which adheres firmly to the wall of the vessel. The cir- cumstance that softening occurs chiefly in laminated thrombi gives rise to various modifications in the anatomical appearances. The strata of colourless corpuscles sometimes exhibit a singular Fig. 73. Part of a transverse section tlirougli an arterial thrombus three months old. a. Middle coat (its innermost layers only) ; h.y Lamella which separates the middle from the inner coat ; c. Intima ; d. Line of demarcation between the intima and the thrombus ; e. Thrombus ; /. Vessels cut across ; epithelium very distinct. 3^7;. proneness to take part in the softening, while at others they offer the longest resistance to disintegration. In the former case, the connexion of the colourless cells with one another is early broken. Even before the red corpuscles have had time to part with all their colouring matter, the thrombus breaks up into a reddish-grey pulp which may resemble anything between chopped meat and the lees of wine. If on the other hand the white corpuscles offer a more deter- mined resistance than the red ones, we first of all get a mass of cheesy colour and consistency, passing at a later period into a more spongy or loculoso decomposition of the whole of the softening thrombus. iao MOEBID STATES OF THE BLOOD, ETC. § 195. I have also endeavoured to ascertain the histological details of the softening process. Fig. 74 represents a transverse- section through a laminated coagulum, the centre of which has already undergone softening. The upper part of the drawing shows the boundary-line between the outer layers of the throm- bus which are still solid, and its central portion which is already diffluent. The lower part shows the almost mathematical regu- larity with which the colourless dissepiments and the layers of Fig. 74. rrom a section througli a softening thrombus, a. Layers of red blood-discs; 6. Colourless layers consisting of white blood-corpuscles fused together; c. The cavity due to softening, a^^j. red blood which they enclose alternate with one another. On a level with the softening edge of the clot the colourless striae pass into rows of independent leucocytes, while the compact masses of red discs lose their cohesion and mingle with the fluid products of softening. They have already lost their colouring matter and THEOMBOSIS. 231 have become cloudy, so that they can hardly be distinguished from the white corpuscles proper ; their stroma now becomes dissolved as well, giving the fluid products of softening a mucoid, often stringy consistency. The colourless cells also break up into minute granules. The resulting liquid contains therefore as a rule nothing but granular debris and oil-globules ; and to these it owes its yellowish-grey puriform aspect; true pus-corpuscles (even if we include the colourless corpuscles of the blood under this name) occur only in very small number, and there is no question of any proliferation of corpuscular elements ; so that to call the softening of thrombi a suppuration, though it does convey some idea of the naked-eye appearances^ fails entirely to hit the essential nature of the process. § 196. The softening of thrombi is in more than one respect dangerous. First among j)ossible mishaps, we have the chance that wherever the clot is freely exposed to the blood-current, bits of it may be detached and carried away. Should this come about, the fragments may be carried with the stream (a) from the radicles of the vena cava through the right heart into the lungs ; Q)) from the radicles of the pulmonary veins through the left heart into various organs of the body ; (c) from the radicles of the portal vein into the liver. The distance to which they penetrate into the circulatory tract which they have entered depends upon their size. It is obvious that only particles no bigger than blood-corpuscles can travel without hindrance throughout the whole circulatory system. Any particle of larger size than this must be stopped somewhere or other, blocking the vessel in which it is arrested (Embolism). Much might be said about the course emboli prefer to take. In the lungs they most frequently select those long, straight branches of the pulmonary artery which run along the inner surface of the middle and lower lobes to their edges and the neighbouring parts of their external surface. In the systemic circulation the larger emboli most frequently select the popliteal and Sylvian arteries. The embolus in these cases appears to follow the most direct route, that in which there are fewest turnings. It seems to happen not unfrequently that an embolus is driven against the projecting angle between two bifurcating divisions of an artery, and there broken up into smaller frag- ments like a floe of ice against the piles of an ice-guai'd. These 232 MORBID STATES OF THE BLOOD, ETC. fragments are distributed among the branches below the point of bifurcation. This affords an adequate explanation of multiple embolism in some one part of an organ while the rest is un- affected, as e.g. of a single Malpighian pyramid of the kidney, or a single lobule of the lung. Finally 0. Weber^s researches have established the fact that minute emboli may pass through the pulmonary capillaries to be ultimately arrested in the nar- rower capillaries of the kidneys. § 197. The consequences of embolism, the morbid changes which are produced in the organs whose vessels are plugged, will be more fully discussed in another part of the present work. I may say generally however that the primary and immediate consequence of every embolism is ansemia (ischaemiaj arrest of blood supply), but that this bloodlessness is immediately followed as a rule by extreme congestion. The more complete the ana- stomotic connexion of the plugged vascular area ^vitli neighbour- ing regions, the better is it fitted to play the part of a coecal appendage, a diverticulum of the circulatory apparatus, which is replenished with blood from every side, but which possesses no adequate outflow, so that the tension of the blood in its interior is higher than in all the other capillaries of the body. This secondary hyperjemia may lead to rupture of vessels, to haemor- rhagic infarctions ; in any case the blood stagnates ; it is not renewed and nutrition comes to a deadlock. The consequences of embolism therefore are all essentially bound up with disturbed nutrition; not a few indeed present the characters of true necrosis. (Cf Metastatic abscesses of the lung, the liver, the kidneys, embolic necrosis of bones, yellow softening of the brain, &c.) c. Inflammation and Tumours. § 198. The possibility of an inflammation of the blood (hsemitis — Piorri/^, was at one time seriously discussed. The increase in the number of leucocytes which may be shown to accompany leukhamia, caused Bennett in particular to assume that the blood as a whole underwent suppuration. All such theories however must be rejected by us, were it only on the ground that the contrast between blood and parenchyma, between nutriens and nutrieyidumy is indispensable for our conception of INFLAMMATION AND TUMOURS. 233 inflammation. Hence we can only admit the existence of in- flammatory — and we may add, of neoplastic processes generally — in those organs where the blood-corpuscles originate, viz. the lymphatic glands ; on the other hand, we not only admit, but most distinctly affirm, that such inflammatory action may influ- ence and alter the composition of the blood itself. § 199. A former attempt to define the leading characters of lymphadenoid tissue led us to the conclusion that it could not be better described than as a tissue in which an early phase of development — a phase very nearly allied to embryonic tissue — had become in a measure permanent. This circumstance must be borne in mind when we see how readily the lymphadenoid tissue may be induced to develope in any direction whatever, when prompted by an appropriate stimulus. Should the organs fi'om which the lymphatic glands derive their lymph be inflamed, this may give rise to suppurative, caseous, and indurative lym- phadenitis ; the specific inflammations are all reproduced in the corresponding lymphatic glands ; e.g. the syphilitic gumma, the mihary tubercle, the typhous product (§ 112) ; finally, almost all the carcinomata implicate the nearest lymphatic glands as a first step towards infecting the entire organism. Moreover, the morbid product, whatever it may be, manifests itself in the lymphadenoid tissue with a simplicity and completeness often lacking in the primary growth ; to this rule there are but few exceptions ; and hence it is that the lymphatic glands may be recommended as especially adapted for the investigation of the proper structure of a tumour. This however must not be taken to mean that the lymphatic glands are equally favourable for the study of the developmeyit of morbid growths ; on the contrary, this is just the point at which our knowledge fails us most, as will be cleai'ly enough seen from the following summary. § 200. I. Acute lympliadenitis. The internal condition of a lymphatic gland which, owing to inflammatory changes in the area of distribution of its afferent lymphatics, has become mode- rately swollen and tender, may be taken broadly to consist in hyperasmic distension of its vessels, together with an increase in the number of its contained lymph-corpuscles. Whence are these corpuscles derived ? We may adopt one of three hypotheses to account for the fact, and bring very weighty analogies in sup- port of each in turn. For instance, we may assume a migration 234 MORBID STATES OF THE BLOOD, ETC. of leucocytes to take place from the distended vessels ; or a pro- liferation of the existing cells ; or a transmigration of corpus- cular elements from the seat of inflammation. It is unfortunate that we cannot decide which of the three views is the right one ; for the settlement of this question would be most important for our knowledge of the physiological function of the lymphatic glands. On a j^rioi^i grounds we are tempted to believe in an autochthonous proliferation of the lymph-corpuscles. We may very plausibly suppose that we have before us only a quantitative excess of the normal proliferative activity of the gland ; of that process which satisfies the physiological requirements of the blood for young elements, and whose increased activity is per- haps intended to compensate for the disproportionate loss of colourless cells caused by their migration from the vessels in the inflamed region. But since erroneous preconceptions would in this matter be peculiarly hurtful, we must rigorously confine our- selves to the most temperate statement of observed facts. According to Billroth (fig. 75) a section through the gland (after hardening), from which the cells have been thoroughly removed by pencilling (or better still, by shaking), shows a very marked overgrowth of that system of soft, protoplasmic, stellate corpuscles which is stretched out between the walls of the lymph- sinus. The cells swell up in due form, they anastomose more freely with one another, their processes grow thicker, and the nodal points more numerous. A luxuriant proliferation of the nuclei accompanies these changes, so that we finally get the ap- pearance of multinuclear giant-cells, connected with one another by broad anastomoses. The reticulum in the interior of the lym- phatic cords and nodules (Lymphstrange und Lymphkolben) remains at first quite passive in presence of the comparative abundance of the infiltrated cells. A large number of its finer threads are torn across, and the whole tissue comes to consist of only a limited number of main trabecular, which seem to be rather stouter than usual. It is only when the swelling takes place very gradually that all the trabeculae of the reticulum undergo a reactive overgrowth ; of this I shall say more anon. As the reticulum disappears the lymph-corpuscles form globular aggre- gates of larger size. Such aggregates exist here and there even in the normal lymphatic nodules ; now however they per- meate the whole of the glandular parenchyma. These globular ACUTE LYMPHADENITIS. 235 masses of cells ought certainly to be regarded as centres of proliferation, although this does not admit of being directly proved. Whether the above-described transformation of the corpuscular elements of the retiform tissue of the lymph-path Fig. 75. Part of a section through the cervical gland of a dog swollen to the size of a hazel-nut in consequence of inflammation of the lips, artificially excited. -5^. After Billroth. Show- ing the septum of connective tissue, the sinus terminalis and the marginal row of lymphatic nodules (Lymph- kolben). into giant-cells admits of a like interpretation, must remain doubtful ; the earlier stages of cell-proliferation, namely fission of the nuclei and increase in the amount of protoplasm are indis- putably present. 236 MORBID STATES OF THE BLOOD, ETC. § 201. Simple swelling of the lymphatic glands passes directly into suppuration of their parenchyma, provided always that the production and accumulation of lymph-corpuscles be not checked in time. Not only does tlie reticulum of the lym- phatic nodules get worn progressively away, but the capillary vessels are ultimately torn across, and the corpuscular network of the lymph-path, rich as it is in nuclei and protoplasm, under- goes disintegration. The result is a richly corpusculated fluid, no longer distinguishable from pus, which fills all the cavities formerly occupied by the lymphadenoid parenchyma. When this occurs in a solitary lymphatic follicle, as e.g. in the intes- tinal mucous membrane, we call the resulting condition a folli- cular abscess ; when an entire gland is involved, we term it a suppurating [bubo. Its further progress comes under the head of suppurative inflammation and abscess-formation, as discussed in § 94. § 202. II. Chronic lymphadenitis. Chronic inflammation of the lymphatic glands differs from the acute form not so much in the slower rate of change, as in the permanent character of its results. Several very characteristic forms of chronic inflam- mation may be distinguished. First we have a true overgrowth of the lymphadenoid substance, which indeed is only to be observed in the tonsils and the follicular glands of the fauces. It consists in a uniform increase in amount of all the histological constituents of the follicle, sc. the reticulum, the vessels, the lymph- paths and the cells. Each single follicle attains from three to five times its normal volume, without exhibiting any striking alterations in its texture. The leukhsemic form, considered above (§ 181), is most closely related (from an anatomical point of view), to this true o^'ergrowth ; it differs from it in bearing more of a functional character, and also in the mode of its causation ; for it is not a result of repeated catarrh of the corresponding mucous surface. § 203. We come in the next place to a form of chronic enlargement which only occurs in individuals specially predis- posed, and which is therefore regarded as pathognomonic of what is known as " Scrofulosis." We employ the same word, in a more restricted sense, to denote the disease of the lymphatic apparatus ; since our general conception of scrofulosis embraces the primary lesions together CHRONIC LYMPHADENITIS. 237 with the morbid state as a -whole — the constitutional taint of the alFected person. Those primary lesions are sometimes charac- terised hj their destructive tendency, as in the lungs and the osseous system ; sometimes too, they exhibit no special charac- ters whatever. It is among the latter group that the glandular affection takes a prominent place, receiving the name of scrofu- losis KaT i^ox^jv. § 204. The tissue-chano-es which result in scrofulous enlar ere- ment of glands may be regarded in the light of a partial over- growth of the gland-substance, in so far as they consist, not in a uniform increase in bulk of all its structural constituents, but in a multiplication and enlargement of the cells only^ which make up the "enchyma" of the gland. I lay emphatic stress on the enlargement of the individual elements w^hich accompanies their increase in number, because it appears to me that this enlarge- ment is not only a constant phenomenon, but one which stands in an intimate relation to the numerical increase. For in the interior of the enlarged lymph-corpuscles a nuclear proliferation and endogenous cell-development take place, like that which we have already seen in the cells of tubercle, and that with which we shall hereafter become acquainted in the "typhous" deposit. It is interesting to trace the sequence of the morbid changes in the interior of a gland. We find that the first parts to become affected are those which are on the immediate brink of the stream of lymph, and which are consequently the first to be exposed to the pathological irritant brought from the peripheral seat of mischief. At a very early stage, the stellate corpuscles which traverse the lymph-sinus (across which they may be said to be stretched) begin to take part in the process by division of their nuclei and proliferation of new elements ; this occurs partly at the circumference of the gland round the terminal nodules (Endkolben) partly in its medullary substance ; in either case we have an infiltrated material of soft consistency, which appears of a dull-grey or reddish-grey hue to the naked eye, and which is present in largest amount, where, under normal conditions, a system of intercommunicating lacunse separatees the constituent parts of the gland from one another. As a result of this, the limits of contiguous lymphatic nodules (Lymphkolben) in the cortical substance, and of contiguous lymphatic trabecula3 in the medullary substance, are wholly obliterated ; and in proportion 238 MORBID STATES OF THE BLOOD, ETC. as the proper substance of the lymphatic nodules and trabeculaB takes part in the pathological proliferation, the cut surface ceases to present any distinction of parts, and the whole gland appears converted into a homogeneous substance of a dull-grey hue. This brings us to the culminating point of the whole pro- C3SS ; the scrofulous bubo is about as big as a walnut when the unaltered gland was no bigger than a bean ; according to the amount of moisture present, it may be either soft and flabby, or firm, elastic, and even springy. Meanwhile the process does not long remain stationary at this point. The newly-formed substance not only blocks the lymph-paths through the gland, but it also squeezes the blood-vessels to such an extent that the circulation is entirely arrested. It becomes impossible to force injection of any kind into those parts of the gland which are most swollen. With the arrest of the blood-supply nutrition of course ceases, and the gland falls a prey to '^ cheesy degenera- tion." Where this occurs, the grey mass loses its transparency; it then becomes yellowish-white, opaque, dry and friable. Should the entire gland have become cheesy, it resembles on section " a fresh potato — not indeed so moist, but quite as homo- geneous, and of the same yellowish-white colour" (VirchoWy Geschwlilste, vol. ii. 593). § 205. The fate of the cheesy glands (Tyromata) appears to depend in the main upon their situation. For while in the mesen- teric glands we nearly always observe a subsequent shrinking, due to the reabsorption of whatever fluid they may still contain, and sometimes also a deposition of earthy salts and consequent petrifaction, the lymphatic glands of the neck commonly end by undergoing softening. The cheesy deposit melts from centre to circumference into a yellowish whey, in which fatty-granular debis are suspended in flakes of variable size. When the whole of the cheesy matter has thus been liquefied, the parts imme- diately around the gland usually take on inflammatory action ; and this prepares a way for the escape of the '' scrofulous pus." When this has escaped, a '^scrofulous ulcer" is left with its flabby, overhanging^ bluish and congested edges. Finally the opening closes, and the point at which the abscess burst is only indicated by a puckered and stellate scar. Vircliow has recently described a third mode of retrograde metamorphosis which is certainly the most desirable one of the SPECIFIC FORMS OF LYMPHADENITIS. 239 three. It consists in the complete resolution of the cheesy matter. It takes place, in all probability, by a liquefaction of the gland at its periphery, followed by absorption of the result- ing fluid into the vessels of the capsule which are dilated by ^collateral hypersemia. § 206. We have yet to speak of chronic induration ; a pheno- menon which belongs to the category of inflammation. Attention has already been called to the fact that it is only the rapid accumulation of lymph-corpuscles in the lymphadenoid substance which causes rupture of the reticulum ; this of course implies the converse proposition, viz. that a sloio and gradual increase in the number of the embedded cells is not followed by any such damage to the retiform tissue. Nay, we find the chronic changes associated with a very marked " reactive " thickening and elonga- tion of all the trabeculas of the reticulum. The latter accord- ingly increases in bulk to such an extent that the corpuscular elements come at length to occupy very little room in comparison, and the entire gland becomes tough and fibrous. § 207. III. Sypliilis. The indurated chancre (§ 110)— the primary manifestation of constitutional syphilis — is followed by a chronic induration of the corresponding lymphatic glands; this is known as the "indolent bubo"; the induration however is due not so much to a hardening and quantitative increase of the reticulum, as to a very uniform though by no means luxuriant proliferation of young cells in all parts of the gland. Every vacant space is crammed with cells ; and here the matter >ends, at least for the time. Injection by simple puncture causes a similar, though of course only transient enlargement and hardening of the glands. This condition may remain unaltered for months and years together ; it seldom proceeds either to a more acute inflammatory activity on the one hand, or to casea- tion and necrosis on the other. Ultimately, however, a fatty degeneration of the cells sets in, the debris are reabsorbed, and the gland returns to its normal state. IV. Typlious degeneration (§ 112) of the lymphatic glands, as a specific result of corresponding lesions of the mucous mem- brane, will be discussed among the diseases of mucous membranes. The histology of the process is characterised by a cell-form which has already been briefly described in § 112. § 208. V. Sarcoma, Lymphadenoid sarcoma has its proto- 240 MORBID STATES OP THE BLOOD, ETC. type in the tissue of the lymphatic glands; hence these are among its most favourite localities. It begins as a simply hyper- plastic enlargement ; at a later period it assumes its true character as a progressive groAvth. Several subspecies may be based on its variations in consistency and colour, in rapidity of growth and malignity. The least malignant forms, whose growth is least rapid, and whose texture is hardest, are characterised by the simultaneous implication of a whole group of glands, e.g, of all the glands of the upper or lower cervical fossa. A highly lobulated tumour is produced, often of large size, every one of whose lobes corresponds to a swollen lymphatic gland. The vessels and nerves are variously dislocated, and the removal of the mass by operation rendered almost impracticable in con- sequence (Pseudoscrofulosis). A second variety, much softer than the first, and made up of larger cells, is especially prone to perforate the walls of veins and then to extend in their interior (cancer of veins). We some- times find all the veins in the front of the neck or in the groin filled with sarcomatous thrombi of this sort ; these of course afford excellent materials for embolic accidents. The precise mode in which this intravascular extension takes place has not yet been satisfactorily ascertained. From microscopic investigation one gets the idea that the first step is a coagulation of the blood, and that the farther growth of the sarcomatous mass proceeds as it were under cover of this clot. Others again assert that the clot is directly converted into sarcomatous tissue. A third set of lymphadenoid sarcomata are marked by their tendency to break through the limits of their parent-gland at an early period, and to cause extensive infiltrations of the loose areolar tissue in its neighbourhood. In rapidity of growth and malignity, these tumours do not yield the palm to any species of sarcoma, though they never exhibit an alveolar structure. As regards treatment, they ought not as a rule to be meddled with, although the observations on the fatty degeneration and absorp- tion of sarcomata in consequence of intercurrent erysipelas, given in § 92, referred to this very species. § 209. VI. Carcinoma. One of the most interesting pro- blems in histology is the discovery of the way in which a primary cancer infects a neighbouring lymphatic gland ; and should the a priori hypothesis, that it is due to a migration of cancer-cells CAHCINOMA. 241 from the primary growth, turn out to be well-founded, it is desirable to ascertain farther, the exact point at which these cells are arrested, and how they give rise to the first nests of cancer- cells, whether by proliferation or by infecting the adjacent lymph- corpuscles. After many investigations specially directed to this point, I can only say that the transformation of the lymphadenoid tissue into the substance of a glandular cancer takes place very simply; the trabeculae of the reticulum increase markedly in length and thickness (just as in chronic induration), its meshes become enlarged from ten- to twenty-fold, and are occupied by the specific elements of cancer instead of lymph-corpuscles. Thus the structure of the lymphadenoid tissue seems to pass directly into that of the cancer, the reticulum becoming the cancer-stroma while the lymph-corpuscles are converted into cancer-cells. Epithelioma of the lymphatic glands presents us with jDheno- mena of a much more complicated order. The law regulating the metastasis of morbid growths, se. that the lymphatic glands nearest to the seat of disease are the first to become affected, is obeyed with peculiar strictness by epitlielioma. Hence in epithelial cancer of the lips, the submaxillary lymphatic glands are the first to swell, in cancer of the penis or the labia majora the inguinal glands, in cancer of the scalp the cervical group of glands. The metastasis commonly goes no farther, as the extensive disturbances operated in the mean while by the primary growth usually kill the patient before any such further extension can occur. The swelling usually begins at the periphery of the gland. This becomes nodulated ; one of the nodular projections gradu- ally increases in size till it incorporates the rest into itself. The gland ultimately attains from two to three times its normal dimensions. In a group of glands we can usually see one which exhibits the first beginnings, another some intermediate stage, a third the highest degree of enlargement. The biggest lumps (equal to a pigeon's egg in size), nearly always contain a central cyst due to softening. The smaller and smallest ones are dis- tinguished by their white colour and their tough, dry consistency, which contrasts sharply with that of the unaltered portions of the glandular parenchyma. This normal parenchyma however, at least in the neighbourhood of the smallest nodules, is normal only in seeming. The microscope proves that it has already 16 242 MORBID STATES OF THE BLOOD, ETC. nnclergone some very interesting changes, which enable us to judge of the mode in which the mass of epithelial cells first originates. If we follow up the well-knowai epithelial cylinders to their origin, we shall find the earliest signs of the approaching change to consist in the aggregation of from two to five epithelial cells in spaces of unusual size, which are not bounded by the delicate lymphadenoid reticulum, but are meshes in that net- work of nucleated, protoplasmic corpuscles which traverses the Fig. 76. Epithelial cancer. Origin of the smallest nodules in the reti- form tissue of the lym^^h-path of the gland, h. Meshes of the reticulum ; a. Adjoining connective tissue. periplieral Ijmiph-sinus and the lymphatic channels of the medullary substance. I believe these epithelial cells to have migrated from the primary growth, and I regard the character- CABCINOMA. 243 istic changes which the cells of the reticulum in their neighboui'- hood have undergone, as a result of ^^ epithelial infecti(^n"; for they increase in size, and their anastomoses become broader, the final result of these changes being a structure (fig. 76) which recals in some degree that of the secreting network of the liver. The frequent occurrence of double nuclei points to an independent multiplication of the cells by fission. In the face of this appear- ance, and of the fact that the alteration is only met with in the neighbourhood of matm'e, concentrically laminated epithelial cells, can we hesitate to believe that the cells of the reticulum are actually converted into epithelial cells ? I ought to add, that the retiform structure persists for a long time, and may even be demonstrated in cancroid nodules which are large enough to be recognised by the naked eye. II -MOEBID ANATOMY OF THE CIRCULATORY APPARATUS. 1. Diseases of Akteries and Veins. § 210. Before entering on the pathological histology of the vascular system, I must say a few words about its normal struc- ture ; and this chiefly because current expositions of the subject leave several disputed topics undecided; inasmuch however as these ai'e most important for the due appreciation of morbid changes, I feel bound to express my opinion concerning them at the outset. As might have been anticipated a pnori, all the vessels of the body are constructed on a uniform plan — which is best elucidated by tracing the course of their development. Fig. 77. -J Let a — b represent a capillary loop, and a — ^ the boundary- line of a growing organ. The blood flows from a to b under a certain pressure, at a certain velocity, and with a certain tension of the vascular walls. Let the pressure, the velocity and the tension be each represented by unity. Now when the DISEASES OF ARTERIES AND VEINS. 245 progressive growth of the organ transfers its boundary-line from a — /? to y — 8, the capillary loop a — h will no longer suffice to carry on the nutrition of the extended vascular territory. A new capillary loop, c — d^ is produced. Like every vessel in the organism, this springs from a pre-existing vessel. Suppose, what is quite possible, that its two extremities are implanted into the capillary loop a — Z>, in just the same way as the loop a — h is connected with its parent-vessel. The enlargement of the blood-path entails an increase in the amount of blood, so that the current passes through c — (Sunder the same pressure, velocity and tension as it did through a — h. But these values do not continue the same for a — h. Taking a transverse section through a, we see at once that through it flows not only the blood which fills the capillary loop a — h under a pressure, velocity and tension each of which equals unity, but also the blood which goes to fill the loop c — d. Assuming that c — d equals a — h both in length and sectional area, the pressure, velocity and tension at a must each equal two. Continuing this train of reasoning, and assuming that with the farther growth of the organ, fresh capillary vessels are again and again projected from the old ones, the pressure, velocity and tension must increase proportionately in the afferent and efferent vessels ; greater demands will be made on the resisting power of the transverse sections a and h. We might accordingly expect to find the vessel increasing in calibre and its walls growing progressively thinner. It does in fact increase in calibre, but its wall does not grow thinner; a peculiar law, which regulates the growth of the entire vascular system, comes into operation at this point, a law according to which any in- creased demand upon the resisting power of the transverse section of a vessel, is met by a proportionate thickening of its walls (hypertrophy and dilatation). The wall of the vessel grows thicker, one limb of the capillary loop becoming an afferent artery, the other an efferent vein.* * Strictly speaking, our scheme is only applicable to cases in which a capillary area is provided with a single afiferent and efferent vessel, i.e. to reiia mvrahilia. In order to make it suit all the varieties of circulatory distribution throughout the body, it is necessary to add that anastomoses between neighbouring capillary areas render the forma- tion of larger and finally of absolutely large vascular territories possible, the artery of one area bringing enough blood for both, while one vein 246 CIRCULATORY APPARATUS. § 211. No one has ever yet seen the actual details of the process bj which a capillary vessel is converted into a small artery or vein. In this as in many other cases, v^e are com- pelled to draw our conclusions as to what actually occurs, by inference from what has gone before or what comes after. The wall of a capillary vessel consists of a homogeneous, glassy membrane beset at intervals with nuclei. By impregnating this membrane with silver nitrate we are able to prove that it is made up of plates accurately adapted to each other; to about the middle of each plate a nucleus is fixed by a little soft protoplasm. The plate itself may be viewed as a thin layer of hardened protoplasm. The capillary membrane passes uninterruptedly into a somewhat thicker, vitreous lamella which exists in all the arteries and veins, even in the aorta, at the junction of the internal with the middle coat ; this lamella may always be recog- nised in transverse sections, not only by its greater lustre, but by the uniform sinuosities of its double contour, which are due to the fact that owing to its deficient elasticity, it follows tlie variations in calibre of the vessel, not by alternate condensation and rarefaction, but by becoming folded and unfolded (fig. 73, h). On the inner surface of this membrane, the tunica intima and epithelial lining are developed ; on its outer surface the muscular coat and tunica adventitia. The necessary materials are fur- nished by proliferation of the cells of the capillary wall, as may readily be seen in the arterioles (Uebergangsgefasse). Fig. 78. Vertical section through the inner coat of the aorta. For explanation see text. 5^. The tunica intima of the larger arteries and veins exhibits the same appearances both in longitudinal and transverse sections ; suffices to return the blood from both areas to the heart. It is obrious that such modifications cannot alter the main gist of the observations made above. DISEASES OF ARTERIES AND VEINS. 247 I refer to the striated lamella of Henle, which present them- selves under a magnifying power of 500 diameters (fig. 78) as finely striated, wavy layers of basis-substance (of connective tissue), in whose interstices flattened, lenticular corpuscles are embedded. In these cell-containing spaces, the opposed surfaces of the basis-substance exhibit a peculiar, homogeneous lustre ; moreover, they present a double contom', which makes each cell appear as if surrounded by a special capsule. The plausibility of this view is enhanced by the appearances presented in hori- zontal sections (fig. 79) which show how closely this peculiar property of the basis-substance is connected with the distribu- FiG. 79. J'lliiUiii ' ^ ■ m Horizontal section through tlie inner coat of the aorta. For explanation see text. ■^. tion of the cells. The ceil-contaming spaces appear of a stellate form, with branching prolongations which anastomose with one another. The whole arrangement reminds us very forcibly of the cell-containing capsules of cartilage. But can we be sure that the stellate capsules of the intima are really closed cavities ? For it is undoubtedly true that in those morbid products which spring from the intima, the newly-developed cells are found out- side the ^^ connective-tissue corpuscles," as well as within them ; this forces us upon the horns of a dilemma; for either they cannot have sprung from these connective-tissue corpuscles, or else they must have escaped from the capsules. We may pro- visionally regard them as leucocytes which have migrated from the blood. The structure of the intima lias not hitherto received the attention which it merits ; on this ground, and also with a view to its diseases, which we are about to consider, I have lingered 248 CIRCULATORY APPARATUS. ratlier long over it. I may be all the more brief in my remarks concerning the two outer coats. The media, composed of smooth muscular fibres, constitutes the main bulk of all the larger ressels. The transverse, nucleated spindle-cells impart a highly characteristic, annulose appearance to the smallest arteries and veins ; in the larger vessels the muscular fibres are disposed in bundles in a framework of fenestrated lamellae of elastic tissue. From three to ten or more principal lamellae, separated by regular intervals, lie j^arallel to the surface of the vessel ; each lamella being connected with its neighbours on either side by oblique buttresses. Tliese buttresses are also fenestrated, so that the muscular bundles can pass uninterruptedly from one com- partment to another. The adventitia consists mainly of unformed connective tissue abundantly permeated by vessels and elastic elements (mem- branes and fibres). In the larger veins, it may sometimes contain longitudinal bundles of smooth muscular fibre. a. Inflamsiation. a. Acute Inflanimation. § 212. The phenomena of acute inflammation of the vessels are intimately connected with those of coagulation in their in- terior; for they are exclusively, or almost exclusively confined to parts where a softening blood-clot is in immediate contact with the inner wall of a vein or an artery, irritating the coats of the vessel by the diffusible products of its disintegration. This coincidence is so frequent, that it formerly led Dupiiytreyi to invert the real order of sequence — to regard the acute in- flammation of the vascular wall as the antecedent, and the coagulation of the blood as the consequent. Even the most weighty and thorough changes operated by acute inflammation are by no means striking to the naked eye. We notice a hyperasmic state of the vasa vasorum, particularly at the junction of the media with the adventitia, and a thicken- ing of the vascular coats to three or four times their normal diameter, so that an inflamed vein may not be distinguishable on transverse section from an ordinary artery. The normal smoothness of the inner surface gives place to a cloudy, opaque, or even velvety aspect. In rare cases, we notice little col lee- INFLAMMATION OP ARTERIES AND VEINS. 249 tions of matter, forming pustular elevations of the intima. The microscope tells us much more about the condition of a vessel thus altered. Its entire wall is in a state of inflammatory pro- liferation. Thousands of young elements, which may be sum- marily termed pus-corpuscles, lie between the fibres of the adventitia, between all the layers of the muscular coat, between the striated lamellae of the intima. In the adventitia, besides the cells, I have occasionally found larger aggregations of an amorphous, jelly-like material, which I regard as coagulated lymph ; here also, as well as in the outer layers of the muscular coat, extravasations occur, which extend along the vessel for a variable distance. It seldom happens that the pus-formation in the external coat goes so far as to cause abscesses. When it does, the abscesses are like long streaks of creamy pus following the course of the vessel ; they must not be confounded with vessels which may happen to be filled with softened thrombi. The intima is less constantly involved in the morbid process ; indeed I might almost say that in the majority of cases the intima is less altered than either of the other coats. It depends for its nutrition so much upon the blood which circulates in the vessel, that the occurrence of coagulation at once cuts off its chief source of pabulum, and leaves it a prey to necrosis, unless, as in the organisation of thrombi, vessels are forthwith developed in the coagulum. The passive behaviour of the intima must therefore be attributed to its lack of vital energy and nutrient material ; and this view is confirmed by the observation that the farther progress of the mischief not unfrequently results in a true necrosis of the intima and its detachment from the middle coat. § 213. Apart from thrombotic arteritis and phlebitis there is hardly such a thing as acute inflammation of the walls of vessels. On the other hand, I must remind the reader that the vessels are continuous by their adventitia with the general connective tissue of the organs — that, rightly understood, the walls of the vessels are really a part of that connective tissue, and are there- fore capable of taking a most active share in all inflammations, however acute, of the various organs in which they ramify. Indeed we shall find that in many of the inflammatory disorders of internal organs, e.g. of the pia mater, kidneys, &c., the chief seat of the morbid changes is in the adventitia and the imme- diate neighbourhood of the vessels. 250 CIECrLATOEY APPARATUS. (^, Chronic InJiammatioJi, § 214. Chronic inflammatory changes may occur in every part of the vascular system ; but they are nowhere so im- portant as in the internal coat of the arteries, where they give rise to the endoarteritis chronica deformans of Virchow. Tlie view that this disorder (also known as atheroma) is of an inflamma- tory character, is by no means of recent date. A peculiarly transparent material which projects above the level of the intima, and which, as will presently be seen, is nothing more than the altered intima itself, used to be regarded as an inflammatory exudation, and the entire process was accordingly viewed as an exudative inflammation. An obvious objection to this view is that the exudation, in its quality of liquor sanguinis, had no occasion to coagulate at the very moment when it was reunited with its parent fluid. Accordingly, RoJdtansJd started the theory that the substance in question, though really coagulated fibrin, had not exuded from the vasa vasorum, but had been precipi- tated at the inflamed point of the vascular wall (where it formed a deposit), from the blood-current itself. This position likewise came ultimately to be untenable. Lobsteiuj and after him Virchoiv, taught us to look for the essential part of tlie process in an altera- tion of the proper tissue of the intima, and to eliminate what- ever substances might afterwards have been deposited at the seat of mischief from the blood. Virchow laid the foundations of our present theory concerning the morbid change in question. § 215. It consists in a chronic inflammation of the inner coat of the vessel. True, we cannot detect all the cardinal symp- toms of inflammation, but only swelling and perhaps impairment of function ; but the finer alterations which the intima midergoes are throughout analogous to those which occur in connective tissue under the influence of prolonged irritation. There are many grounds for thinking that a mechanical irritation of the vascular wall may be at least one of the causes to which the morbid changes are due. For these are chiefly found at such points as are exposed to the fiill stress and impact of the blood ; <^.g. the upper curvature of the aortic arch, the points of origin and bifurcation of the vessels. Still, mechanical irritation must not be regarded as the sole cause of the disorder, though it determines its localisation. Among other predisposing causes are advanced age and free living, especially a free use of alcoholic INFLAMMATION OF AETEEIES AND VEINS. 251 stimulants. The etiology of gout is very similar to tliat of endoarteritis ; hence the two diseases are often found together. § 216. The common starting-point of all the lesions due to chronic endoarteritis is to be found in certain flat and smooth, seldom tuberous elevations on the inner coat of the arteries. They rarely project more than a line above the surface ; their margins are very irregular. At the point where a vessel is given off, they encircle it ring-fashion. They vary to some extent in colour and consistency, yet they may be generally described as bluish or reddish grey and cartilaginous ; sometimes they may exhibit more of a gelatinous or mucoid consistency. As regards the microscopic appearances, let me insist once more on the fact, of which we may readily assure ourselves by Fig. 80. Chronic endoarteritis. Section through an indurated elevation of the inner coat, which is ah'eady undergoing fatty de- generation in its interior. ■^; h. Junction of inner and middle coats ; a. Inner coat ; At c this is hyperplastic and thickened, while at d it has become converted into an athe- romatous abscess. For details see text. examining sections through the margins of the swollen part, that the outermost lamella of the intima, which is usually least altered, passes uninterruptedly over the surface of the swelling ; that the change consists therefore not in a deposit upon, but in an actual thickening of the membrane itself (fig. 80, a—c). We may further regard it as certain that we have to do with a pro- liferation in and from the connective tissue of the intima, which has caused a positive increase in its bulk ; young cells in countless 252 CIRCULATORY APPARATUS. numbers are e^-erywhere distributed between the lamellae ; here and there we come upon larger aggregations of such cells. From these nest-like deposits, as centres, new systems of concentric lamellae of connective tissue originate, which are intercalated between those already existing, thereby dissociating them from one another. For the production of fibrous intercellular sub- stance advances pari passu with the multiplication of corpuscular elements ; the latter never preponderate to such an extent as to make the products in any way resemble pus. We rather meet w^ith scattered patches in which a soft, mucoid character of the intercellular substance is associated with a retiform arrangement of the cells — patches, therefore, of mucous tissue. Taking the phenomena in their entirety however, we cannot but be struck with the close similarity of the morbid products to the normal texture of the intima ; hence we must regard the first stage of the process, the so-called sclerosis of the intima, as an infamma- tory overgrowth. § 217. With this inflammatory overgrowth of the intima, the process culminates. As often happens in the case of morbid growth, time brings about a disproportion between the means of supplying nourishment and the mass of material wdiich has to be nourished. Tlie intima contains no vessels. It draws its pabu- lum directly from the passing blood. The vasa vasorum, which are never lacking in any of the greater vessels, barely j^enetrate into the middle coat. Should the intima therefore become thicker, those of its layers which are farthest removed from the nutrient fluid, i.e. the outermost layers, those next to the middle coat — will be the first to suff'er from lack of nourishment. And here, two modes of retrograde tissue-metamorphosis may be observed side by side. Tlie first and most extensive of these is a fatty degemration of the cells, combined with solution of the intercellular substance. The naked eye detects in the interior of the hardened elevation, just upon the limits of the media, opaque yellowish-white striae, running in a direction parallel to that of the surface, and uniting to form a more equably yellow spot. Should the morbid change be more advanced, this is re- placed by a " focus of softening" of variable size, occupied by a friable or greasy pulp of the same yellowish hue. The presence of cholesterin crystals in large numbers gives this " atheromatous pulp " a spangled lustre. Should the focus of softening have INFLAMMATION OF ARTERIES AND VEINS. 253 attained larger dimensions bj the progressive liquefaction of the indurated tissue, should it e.g. be separated from the blood- current by only a thin layer of unaltered intima, we call it an atlieromatous abscess. When this layer at last gives way at its thinnest part, the pulp mingles with the circulating fluid, the base of the " focus of softening " is laid bare and we have an atheromatous ulcer. (For continuation see next section.) Figs. 80 and 81 are meant to elucidate the histological de- tails of atheromatous change. In fig. 81 we see, under a high power, that the fatty metamorphosis of the cells of the intima presents itself as a distension of the stellate interstices of its con- nective tissue with oil-globules. It would seem however, as though these preformed lacunas were the depositaries of all the Connective- tissue corpuscles of the intima in a state of fatty degeneration. 5^. fatty debris, including those derived from the younger and more scattered cells, since a vertical section through an atheromatous abscess (fig. 80) shows the oily dehns to be infiltrated into fusi- form spaces, separating the contiguous lamella} of the intima from one another. These fusiform cavities undoubtedly cor- respond in position to those points at which the cells are inter- calated between the lamellas of the intima (fig. 79). The greater the amount of oily debris, the longer and the thicker (in trans- verse sections) grow the spindle-shaped cavities ; the lamellse are forced farther and farther apart, and are finally softened and disintegrated; whereupon the oily matters forthwith unite to form a greasy pulp which fills the cavity due to softening (Erweichungshohle). (Fig. 80, d.) § 218. Tlie form and size of atheromatous ulcers naturally vary quite as much as those of the indurated sweUings which 254 CmCULATOEY APPARATUS. preceded them. They are at first sinuous ; i.e. a probe passes tlirough a small hole into a cavitj which bmTows some way underneath the surface. This cavity is that of the former abscess ; it may be more or less distended with coagulated blood ; as a rule it is empty. Moreover the thin membrane by which it is still roofed in, has a tendency to roll up from the hole to the margins of the cavity — the aperture increasing proportionately in size ; more rarely, it is detached in shreds ; in any event, the open atheromatous ulcer forms so marked an inequality of the surface, that it may readily give rise to coagulation ; the adherent thrombi may be of considerable length, hanging from the wall of the vessel into its interior.* § 219. The second mode of retrograde metamorphosis which is met with in association with atheromatous degeneration, also begins as a rule in the deeper parts of the indui'ated intima. It consists essentially in an impregnation of the intercellular sub- stance with earthy salts — a calcification. It gives rise to bone- like plates of variable size and form, often so large that e.g. the entire aortic arch is converted into a single bony tube. We not unfrequently find a number of small bony lamellae, not exceed- ing half-an-inch in any diameter, scattered through the intima ; the finger at once detects their presence. When shelled out of their capsules, most of them exhibit a saucer-like depression which corresponds to the curvature of the vessel ; their edges are sharp. These edges are the first to perforate the superjacent layers of the intima, forming jagged projections and affording fresh opportunities for the production of thrombi. The partial detachment of larger bony lamellgs in consequence of fatty degeneration of the surrounding parenchyma is not unusual; complete separation however is rare. I have never been able to convince myself that true bone is really formed, although this might fairly be inferred from the process being usually designated '^ ossification." The lamellae of the intima are simply calcified and may be restored to their * In the interior of an atheromatous deposit which was nearly quite softened, I observed a small, button-like, soft mass, which contained blood- vesselg and had evidently grown from the middle coat. On more careful examination I discovered a whole series of such buttons under the same indurated patch. They consisted, apart from the capillary loops, of hyaline mucous tissue whose cells had undergone fatty de- generation. (20th July, 1867.) INFLAMMATION OF ARTERIES AND VEINS. 255 previous state by treatment with dilute hydrocliloric acid ; its^ cells however have ceased to exist ; I have never seen anything worthy of being called a bone-corpuscle. § 220. So much for chronic endoarteritis in the narrower sense of the term. An adequate estimate of the extensive lesions which it causes, especially in the aorta — lesions which, in ad- vanced cases, may leave hardly a square inch of its surface intact — can only be formed from personal observation. To render our anatomical sketch of the disease complete, we ought to say something about two other processes, which the practitioner is not at the pains to distinguish very strictly from chronic endo- arteritis, inasmuch as they are in fact very commonly combined with it. First then, a fatty degeneration of the intima may exist, with- out any previous inflammatory overgrowth of the membranes — a morbid change which is simply degenerative from the first, and of whose immediate causes we know nothing. Histologi- cally, the process is exactly like atheromatous degeneration ; a fatty transformation of the cells (fig. 81) being followed by a gradual liquefaction of the lamella3. This ^' fatty erosion" (fettige Usur) of VircJioiL', starts immediately from the inner surface of the vessel, and progresses from within outwards, destroying the intima layer by layer. Moreover, the disease is- always confined to small, sharply circumscribed spots ; in the aorta and larger arteries it causes a very pretty marbhng of the surface, the affected parts being rough, opaque and velvety. " Fatty erosion '' is often met with in persons otherwise quite healthy. It must, however, tend directly to impair the resisting power of the vessels. Experience tells us that when once the intima is wholly destroyed, be the perforation ever so small, the muscular media, notwithstanding its thickness, is miable to cope with the pressure of the blood. The muscular fibres are sepa- rated from one another, and a transverse fissure results, through which the blood forces its way, either producing a dissecting anemism by peeling off the adventitia, or else bm'sting through it and escaping externally. This explains the frequency of hemorrhages into the most diverse organs, occurring in con- nexion with atheroma (e.g. the brain, kidneys, (fcc). Moreover, fatty erosion of the inner coat has a certain share in causing the transverse rupture of the aorta which leads to dissecting aneu- 256 CIRCULATORY APPARATUS. rism of that vessel. This accident is usually regarded as simply a result of the concomitant hypertrophy of the left ventricle. The rent is usually situated about a finger's-breadth above the semilunar valves ; it extends at first only through the internal and middle coats ; the adventitia is peeled from the media ; the blood tunnels its way between them, upwards as far as the heart, downwards as far as the descending aorta ; it never gets as far as the abdominal aorta. When the sac thus formed is stretched to the utmost, a second rupture occurs, either outwards into the medias- tinum, or (a rare event) inwards into the aorta at another point, so that for a short distance, the blood travels along two parallel canals. On examining the edges of the ruptured intima we occa- sionally find them in a perfect state of fatty degeneration ; further investigations however are required, before we can decide upon the frequency and causal moment of this complication. § 221. Another, and a tolerably constant complication of chronic endoarteritis is calcification of the middle coat. This is not so prevalent in those parts of the arterial system which are chiefly predisposed to endoarteritis (such as the aorta and its main divisions), as it is in the relatively thick muscular coat of the smaller and smallest arteries, in those of the arm and leg, in the temporal arteries with their branches. Here too the process is one of simple petrifaction ; calcareous salts are deposited in the muscular fibre-cells, which reappear unaltered when the salts are removed by acid. Even without the aid of the micro- scope the probable seat of the calcification may be determined ; since the distinctly annulose aspect of the infiltrated parts can only be attributed to the transverse arrangement of the muscular fibres (fig. 82). Calcification of the middle coat, as an independent affection, apart from atheromatous change, is more rare. In cases of calcareous metastasis (cf. § 51) all three coats of the vessel are uniformly infiltrated as a rule. § 222. Let us now inquire what influence the above-described alterations in the walls of the vessels may exert upon the move- ment of the blood through them. These alterations may be sum- marily classed under two heads : 1st, narrowing of the calibre of the vessel ; 2nd, rigidity of its tube. This rigidity, mainly due to calcification of the intima as well as of the media, causes a certain proportion of the vis a tergo of the heart to be in some INFLAMMATION OF AllTEEIES AND VEINS. 257 Fig. 82. A measure fruitlessly expended in tlie production of heat, and thus wasted so far as the propulsion of blood is concerned ; whereas it would, under ordinary circumstances, have been stored up in a potential form, as tension of the elastic walls of the vessels, ready to be reconverted at any moment into active energy. Rigidity of a vessel therefore, while consuming the propelling force of the heart, indirectly diminishes the velocity of the blood-current beyond the rigid point. Contraction of the tube from swelling of its w^alls produces the same sort of effect, and that directly, by opposing inclined planes to the current of the blood ; a variable propor- tion of the velocity is thus (according to well- known mechanical laws) partly converted into pressure, partly wasted as impact. Beyond the rigid and contracted part of the vessel there- fore, the movement of the blood is slower than it should be. This retardation of the current manifests itself especiall}^ in the extreme parts of the systemic circulation, in the toes, finger- tips, and nose. It may even amount in these parts to complete stagnation, and so lead to what is known as "spontaneous gangrene" (cf. § D) an accident to which old ]:)eople are liable. The state of things on the proximal side of the rigid and contracted part is the opposite of that just described. AYe know that the pressure of the blood at an}- point of the vascular system is proportionate to the resist- ance to be overcome. If the resistance is augmented (as it is both by rigidity and by contraction) the pressure increases proportion- Arteiia cruraUs ately in those parts of the vascular system w^hicli with its brandies. ^ 1 . T ,/ , , ,. -r "^ P Middle coat cal- are behmd the obstruction. Increase oi pros- citied. Natural sure in the entire aortic system is therefore a size. common result of atheromatous changes. This stands in a com- plementary relation to the diminution of jjressure and velocity beyond the contracted and rigid parts. It is self-evident how- ever that such increased pressure cannot last long without giving rise to farther consequences. Amoiig these may be noticed : 17 258 ClllCULATORY APPAIIATLS. 1st, hypertrophy of the left ventricle; 2iid, dilatation of the affected ^'esseIs. Each of these changes tends to compensate for the primary lesion ; hence it is that the hy})ertrophy is inversely pro})orlionate to the dilatation. b. Dilatation of the Vessels. a. Dilatation of Aj-teries. — Aneurisrii. § 22o. Attempts to introduce order among the infinite variety of forms presented by true aneurisms, i.e. aneurisms involving all the three arterial coats, used at one time to be based on the shape of the dilated vessels as a fundamentuni divisionis ; this led to the distinction of cylindrical, saccular, fusiform and vari- cose aneurisms. These attempts all failed. We should be more successful could we make use of the etiology, the mode of origin of the various aneurisms, as a clue to the diversity of the indi- vidual forms. But the etiology of aneurism is unfortunately ■N'ery obscure ; and it may be long before it is finally cleared up. Hypotheses indeed abound. E.g. nothing seems more tempting than to seek for the origin of the mischief in a lack of elasticity or of contractile power in the muscular coat. Of all the com- ponent elements of the arterial wall the muscular fibres are those in which nutritive change is most active, and which, we may fairly assume, are most susceptible of nutritive disturbance. Hence I willingly take refnge in the hypothesis of atony of the middle coat, to explain the uniform cylindrical or varicose dilata- tion of all the larger arteries which is frequently met with in old people, without the presence of any visible alteration in their walls. I likewise admit that it may have some, though indeed a less important share in the production of other forms of dilata- tion. The hypothesis of a simple disturbance of innervation, a paralysis of the muscular coat (Eokitanski) is less widely appli- cable. Here too however there is at least one case in which this explanation commends itself to us. I refer to the anastomotic variety of aneurism. The term denotes a varicose dilatation, elongation and twisting of the trunk and all the branches of an artery — the ectasy of a limited section of the arterial system* It occurs chiefly in the arteries of the scalp, e.g. the occipital and temporal arteries, and reminds us too forcibly of that dilata- l)ILATATtON 01' AKTERIES. — ANEURISM. 259 tioii of the ■vessoLs of the lioud which follows division of the cervical sympathetic, not to suggest a 2)artial disturbance of the vasomotor system as its probable cause. All these howe^■er are rare cases, and therefore comparatively unimportant. ^ 224. What is shortly called aneurism at the bed-side — an ectasy confined to a short part of the aorta or some other artery, has its causes shrouded in great obscurity. It is usually complicated with chronic endoarteritis. We must endeavour to ascertain how far this change is capable of contributing to the dilatation of an arterial tube. In the first place, we must reflect that an overgrow^th of the intima as such, augments the super- ficial area as well as the thickness of the inner wall of the vessel. The circumscribed patches of newly-formed connective tissue are not merely superimposed on one another; they likewise pene- trate horizontally between the existing lamellae of the intima, forcing them actively asunder as they grow. We are surely entitled to regard the growth of the inflamed intima in a hori- zontal plane as at least one factor in the dilatation of the vessel. For even thouo^h we assimi but a small value to its active co- operation, yet we must regard the intima, while it is under- going the fluctuations of internal change, as less capable of resisting the dilating impulse and increased tension of the blood, than it is in its normal state. I have already pointed out that atheromatous changes in the arterial walls cause a rise in the blood-pressure above and at the affected jDoints of the vascular system. To this must be ascribed in the first place that uniform dilatation of the aorta which is nearly always found in cases of extensive endoarteritis. For the production of a true aneurism however, it is the systolic rise in the blood-pressure which is chiefly important. This differs from that which occurs normally. The diseased condition of the arterial walls hinders that pro- visional transformation of velocity into elastic tension, which causes the systolic rise in the blood*pressure and its ^' other' mode,'' velocity, to be distributed over a longer interval of time* Accordingly, both these manifestations of energy culminate at the moment when the systole commences, and collapse imme- diately afterwards to a proportionate extent. With each ven- tricular contraction, the diseased artery is subjected to a dilating impulse, to which it can only oppose a passive, not, as before, an active resistance. The patient's throbbing pulse informs us 2bO ClilCULATOllY ArrARATtJS. tliiiL thruuglioufc the whole arterial .sybtem, a jerky propulsion of the mass of blood has taken the place of a rhythmic acceleration of its current. The brief though forcible shock, which the radial artery communicates to our finger, will be most intense in the aorta itself, since there the loss of energy by way of impact, which necessarily attends this mode of propulsion, does not yet besin to tell. Therefore it is that aueurismal dilatation is most common, first in the ascending aorta ; and secondly, wherever the local narrowing of an artery causes a special rise of pressure just behind the obstruction. With special reference to this point, 1 have examined all the peripheric aneurisms to which I could get access, and I have rarely failed to discover a more or less marked thickening of the intima below the dilated part, as the exciting cause of the lesion. Persistent contraction of those muscles among which the main branches of an artery are dis- tributed, may also cause aneurismal dilatation of the parent- trunk. Thus for example aneurism of the popliteal artery not unfrequently rewards the exertions of those lackeys who stand for hours together behind their masters' carriages (contraction of gastrocnemii). § 225. As regards the outward form of aneurisms, the uni- formly cylindrical or fusiform dilatation of the arterial tube is usually distinguished from the one-sided, saccular protrusion of its coats. The cylindrical aneurism becomes an invaghiating one when the aneurismal sac, at one or both of its extremities, overlaps the corresponding ends of the undilated part of the vessel. The saccular variety presents similar modifications. Should the sac overlap the parent-vessel on one side only, its ca^ ity is marked oft' from the interior of the vessel by a pro- jecting semilunar fold; should it overlap its parent-artery both i'lbove and below, or on all sides at once, it is said to have ^^a neck." Saccular aneurisms, those which project more from the convex than from the concave side of the ascending aorta — are by far the most common. They press from within against the sternum or the sterno-clavicular joint. Aneurisms of the transverse arch also spring more often from the convexity than from the con- cavity of the vessel. Here too we not unfrequently find aneu- risms with narrow necks which ultimately force their way out through the upper aperture of the thorax and invade the oeso- DILATATION OP AKTERIES. — xVNEUKISM. 2G1 pliagus or the trachea from the front. Aneurisms of tlie thoracic aorta spring by preference from the back and sides of the vessel and press against the spine. Aneurisms of smaller arteries are much less frequent ; among these the most common are aneu- risms of the popliteal, carotid and basilar arteries. § 226. The most interesting question for the histologist is that concerning the behaviour of the various structural com- ponents of the arterial tube during its gradual dilatation— the beliaviour of tlie inner, middle and outer coats respectivelv. Attention has already been drawn to the fact that tlie intima is usually thickened by previous endoarteritis. This enables it to take part in the dilatation without becoming notablv thinner. Aneurisms from fjur to six inches in diameter mav be lined with an internal coat of normal thickness ; nav, of more than Jiormal thickness in parts. It exhibits the most diverse stages of atheromatous degeneration side by side ; foremost among them however stands calcification ; calcified plates have been found involving one-half or even the whole of the circum- ference of the aneurism, converting it into a bony drum. More common is a tesselated mosaic of smaller plates, which are verj- liable to become detached at their edges, and so to give the first impulse to the formation of coagula. Fatty degeneration, tliough less widely distributed, is nevertheless of the utmost moment. For it is this — particularly when it results in the production of atheromatous ulcers — which ultimately leads to perforation of the intima at some point or other, and so exposes the integrity of the sac to the most serious risks. From the first outset of dilatation the middle coot remains entirely passive. The transverse bundles of smooth muscular fibres separate from one another and allow ever-widening fissures to gape between them. They finally succuml) to fatty degenera- tion. Even when an aortic aneurism is no bigger than the closed fist, it is a difficult matter to find any vestige or remnant of the middle coat in its walls. On the other hand the adventitia may be said, in the strictest sense of the word, to " guarantee the sac against rupture." The pressure of the growing aneurism acts upon this membrane in just the same way as a gradually increasing or oft-recurring pressure acts uj^on a stratum of unformed connective tissue else- where ; it stimulates it to a chronic inflammatory, or in other 2Q2 CIRCULATORY APPARATUS. words, to a reactive overgrowtli. The aneurism eomes to be invested on all sides by a close web of tough connective tissue, which supplies whatever deficiencies there may be in the inner coats, and serves as a bond of union between the outer surface of the aneurism and the neics;hbourin ■■••■■- ■■■" v ■••■•••■■■" Hypertrophy of left yentricle. Heart m situ. a. Left mammary line ; h. Y. cava superior ; c. Aorta ; d. Bulb of pulmonary artery; c. Eight auricle; /. Eight A'cntricle; g. Left auricle ; h. Left ventricle (normal size) ; o. Left ventricle (hypertrophied). On the other hand, a one-sided hypertrophy of the 7nc/Jit ventricle (fig. 84) occasions, not an elongation, but a widening and thickening of the entire heart. Looked at in front, the heart appears square, and as its long axis tends more and more to become vertical, the cardiac dulness extends to the ridit, presents itself over the lower part of the sternum; and stretches across the right border of that bone. The heart's apex is no longer formed by the left ventricle alone ; it is partly, or even 1)ISEASES Oi^ THE ItEAKT. — HYPERTROPHY. 271 wholly formed by the right one. The apex-beat often becomes indistinct ; in its stead We iind a basic impulse due to the contact of the conus arteriosus (fig. 84, d) with the chest-wall during each systole, in consequence of the enlargement of the base of the heart in its antero-})Osterior diameter. § 235. Hypertrophy of the heart is invariably due to over- work ; it is caused by mechanical hindrances to the onward flow of the blood. These increase the labour of the heart by augmenting the pressure Avhich at the beginning of each systole Hypertrophy of right Ycntricle. Heart in situ. References as in previous figure. The dotted line represents the outline of the hypertrophied right ventricle. acts vertically against the inner surface of the ventricle, and which has to be overcome by its contraction. We have already seen hypertrophy of the left ventricle associated with atheroma- tous degeneration of the aorta ; we shall soon become acquainted with lesions of the cardiac valves as by far the commonest causes of hypertrophy, and we shall find ourselves obliged to refer to the subject again and ag^in in discussing other organic diseases. As regards the histological details of hypertrophy of the muscular substance of the heart, the hypothesis that the 272 CIRCULATORY APPARATUS. individual fibres grow thicker, is very generally received. Never- theless, I have failed to discover any difference in the thickness of the muscular fibres of hypertrophied hearts ; so that I have at last been led to assume that a "partial splitting" of the fibres must occur ; an assumption which can only be admitted as regards the heart. The muscular fibres of the heart, as every one is aware, divide dichotomously ; they may also be said to reunite in the same way, forming networks or membranes with elongated, slit-like meshes. These meshes vary greatly in their size ; large, spindle-shaped lacuna3 alternating with slits and fissures of the smallest size. Some of the latter may even be regarded as situated in the substance of individual fibres. They are most frequently found in the thicker fibres, where these give off lateral branches (hg, 85, a) and I cannot but believe that the force Fig. 85. Network of niiisciiliir ilbi cs from the heart. At a is an inter- stice in a muscular hbre, which corresponds in position to the origin of a side branch ; by its gradual increase in size, it will add a new mesh to the network. exerted by the side-branch during its contraction contributes in some measure to the cleavage of the parent-fibre. B. Atroplifj of the Heart. § 23G. Inasmuch as the heart is undeniably the hardest- work- ing muscle in the body, and therefore consumes more nourish- ment than most other organs, disturbances in the general nutrition of the organism will necessarily make themselves felt in the heart at a relatively early period. Not only the involution of the body due to old age, but every cachexia, every form of marasmus, whether due to acute or chronic disease, may thus cause wasting DISEASES OF THE HEART. — ATROPHY. 273 of the heart, which manifests itself in thinness and atony of the muscular substance as a whole, and hence as a uniform atrophy of the organ. Besides this general form, we may have partial atrophy — atrophy confined to the outermost or innermost layers of tlie muscular coat, sometimes indeed limited to circumscribed patches ; these partial atrophies being due to local causes. Whether tlie change be partial or general, the muscular fibres grow thinner, more slender, and may even disappear entirely. Tliis most important result of atrophy presents itself under variously modified histological forms, which may be classed in as many distinct .groups. § 237. (1) Broim atrophy is characterised, as its anme indi- cates, by a change in the colour of the muscular tissue, which assumes a rust^^-brown or dark ochry hue, coincidentlv with its diminution in bulk. This peculiar phenomenon is caused by the deposit of a yellow, granular pigment in the interior of the fibres. It may either be uniformly distributed throughout the contractile substance, or the granules may be heaped up in fine lines be- tween the primitive fibrlllai and around the nuclei (fig. ^C)) ; their source is unknown ; we cannot tell whether they are simply the proper pigment of the mus- cular fibre condensed, or whether the colouring- matter of the blood has a share in their produc- tion. Brown atrophy is always general. It is most common in connexion with senile maras- mus, wasting from inanition, the tuberculous and cancerous cachexia?. § 238. (2) Yelloic atrophy consists in the transformation of the muscular tissue of the heart into fat. (Cf. § 30 and fig. 7.) In \)V0- portlon as the deposit of oil-globules is more al)undant, the muscular filjres grow pale, then yellowlsli, and lastly whitish and bacony. They lose their firmness. The tissue grows friable and rotten ; it breaks down readily under the finger; on the other hand the loss of bulk Is often inconsiderable. Yellow atrophy contrasts with the brown variety in the rapidity of its development. It presents itself under four forms : a. As a dlff'use degeneration of the entire muscular substance 18 Fig. 8(5. Brown atrophy of muscular fibres of the heart. Shred of a mus- cular layer ex- hibiting pig. ment - granules in the interior of the primitive fasciculi. -:-,}-. 274 CIRCULATOr.Y APPAllATUS. of the heart In the course of acute febrile diseases, the exanthe- mata, typhus (cf. § 112, note), &c. 13. As a fatty disintegration of the superficial, subpericardial layer of the cardiac muscle, in consequence of the nutritive dis- turbance caused by inflammation of the adjoining pericardium (see Pericarditis). y. In the form of numerous foci not exceeding a pin's head in size, disseminated tln-ough the innermost, subendocardial layer of the muscular substance of such hearts as have been subjected to a high degree of dilatation (valvular insufficiency). In such cases, the whitish dots and stri^ due to this • affection may be detected even through the endocardium, particularly upon the musculi papillares and columnas carneae near the apex. 8. As a single focus of fatty softening (even as large as a hazel-nut) usually situated in the substance of the wall of the left ventricle near its apex. The atony and friability of the degenerated parenchyma usually cause rupture of the heart, differing from rupture due to other causes by the very gradual manner in which the muscular substance gives way layer after layer. Atheromatous degeneration of the coronary arteries with plugging of one of their larger branches by a thrombus may be regarded in every instance as the cause of this dangerous lesion. § 239. AjypendLx, Fatty degeneration of the muscular sub- stance of the heart must not be confounded with that excessive infiltration of the subpericardial connective tissue with fatty matter which is commonly called " fatty heart." The latter is associated with general obesity, and may give rise to very serious troubles, even to death itself. For the masses of fat overgrow the heart from the sulcus circularis and transversus to such an extent as to conceal the entire surface of each ventricle with the exception of a small patch; it is hardly conceivable that the movements of the heart should not be hindered by so great a burden ; then again, the infiltration forces its way into the inter- stitial connective tissue of the myocardium itself. The latter phenomenon indeed is always confined to a limited patch ; the pressure is enough however to cause wasting of the corresponding portion of the heart's wall ; and it tends thereby directly to impair the functional powers of the organ. DISEASES OF THE IIEArvT,— MYOCARDITIS, 275 0. Inflammation. § 240. Myocarditis is one of the most obscure chapters iu general pathology, and morbid anatomy can only contribute very insufficient data for its elucidation. Experience has shown that the most trifling degree of inflammation affecting the striped muscles of the trunk and limbs — e.g. even that slight intumes- cence which we find associated with chronic rheumatism, and with regard to which it is not yet settled whether it really is more than a marked degree of hypera}mia — occasions the most violent disturbances of function. The muscle rests in a state of contraction. Any attempt to extend it is most strenuously opposed by the patient on account of the intense pain to which it gives rise. Now if we apply these results of our experience to the heart, it is obvious from the first that even the most trifling degree of diffuse inflammation ought immediately to be followed by an arrest of the heart's action and the consequent death of the patient, so that the inflammatory process could not attain the later stages of its evolution unless when circumscribed and partial. Some have even gone so far as to deny the possibility of a diffuse myocarditis. Herein they were undoubtedly wrong. I can positively affirm that an infkmmation uniformly involving every portion of the heart may exist. A male patient, 54 years of age, who had undergone a protracted course of treatment for con- stitutional syphilis, and had subsequently passed through an attack of double pneumonia, died suddenly a few days after his discharge from the hospital ; his death was so sudden as to rouse suspicions of apoplexy. At the post-mortem examination, 2c\^2iYt from some syphilitic lesions, I discovered a condition of the heart which I feel myself justified in unhesitatingly describing as a diff'use parenchymatous inflammation of its muscular substance. The heart was partially contracted; its walls were so stiff" that it could only be compressed by the application of a very laro'G amount of force. Even after the customary incisions had been made into its cavities, its walls did not collapse. At the same time a singular and unusual condition of the muscular tissue excited my attention. It had lost its bright red colour which was dashed with violet ; the cut surface was iridescent, its edges nearly transparent ; in consistency it resembled caoutchouc ; 276 CIECULATORY APPARATUS. yet the fibres gave way rather than allow themselves to be stretched. There were numerous ecchymoses under both peri- cardium and endocardium, which were probably due to great disturbances in the circulation through the muscle ; for the vessels were all empty, the lack of blood certainly contributing in some measure to the striking loss of colour. § 241. The results of microscopical examination were every- where the same ; the interior of the muscular fibres was occupied by a finely-granular deposit, not uniformly distributed, but forming little fusiform aggregations round the nuclei ; it might be regarded as " increased protoplasm." I have never seen a more pregnant illustration of Virchow's "parenchymatous in- flammation." ]\Ioreover the muscular fibres collectively were broken up ])y transverse clefts into short, oblong fragments, an appearance which is not unusual in the pathological histology of striped muscle. It must always be regarded as due to mechanical rupture. I have assured myself that similar appearances may readily be produced in the muscular fibres of the rabbit by forcible extension. In the present instance we are at no loss to find a cause for such extension, and it may be inferred that the rigid and infiltrated state of the fibres would make them all the more liable to be torn across in this way. It is self-evident also that these minute lacerations must impair the functional power of a muscle quite as much as the most extensive ruptures. § 242. Apart from the difiiise, parenchymatous form of myo- carditis, certain appearances in the muscular substance of the heart are usually regarded as "results of myocarditis," without our having any adequate knowledge of the chain of phenomena which lead up to them ; these are : abscess, and fibroid patch of the heart. The former of these I will describe at once : leavincf the latter for the chapter on Chronic Endocarditis. D. Abscess of the Heart. § 243. A circumscribed portion of the muscular substance, from the size of a pea to that of a bean, rarely larger than this, but occasionally as big as a walnut — is found to be deficient ; its place is taken by a tolerably thick pulp of a yellowish-grey or dirty-grey colour. This pulp consists, apart from numerous pus-corpuscles, mainly of the debris of disintegrated muscular DISEASES OF THE HEART. — ABSCESS. 277 fibres, albuminoid molecules, and oil-globules; it also contains larger shreds of the contractile tissue, in which, however, the transverse striation is no longer to be recognised. The affected part is, in the main, of oval form ; but sinuses bmTowing far into the muscular layer are also occasionally met with. The boundary of the deposit sometimes consists of a very soft layer of red- dish-grey material — granidation -tissue, according to Rohitanski Should the abscess approach the endocardium, it may peel it off; sometimes too, it forces its way between the lamellae of the cuspid valves. § 244. This condition may terminate in various ways. In very rare cases, the purulent pulp may become inspissated into a cheesy mass, and surround itself with a capsule of connective tissue ; the cheesy nodule ultimately becoming calcareous and establishing a toleration of its presence. More commonly the abscess bui'sts, and its contents escape. According as it ap- proaches the outer or the inner surface of the myocardium, it bm'sts either into the pericardial sac, setting up a rapidly fatal pericarditis, or into one of the cavities of the heai't itself In the latter event the bm'sting of the abscess is immediately followed by a rush of blood into its cavity which washes out the contained debris. This opens out wide contingencies of embolism, mainly in the region of the systemic circulation, inasmuch as the abscess is usually situated in the wall of the left ventricle. The abscess- cavity becomes a diverticulum, or an aneurism of the heart's cavities, if the name be preferred. (Acute aneurism of the heart.) How long this state of things may last, depends entirely on the thickness of the hitherto unaffected portion of the wall of the heart. For it is this alone, together with the visceral layer of the pericardium, which delays the inevitable ruptm-e of the heart and the fatal extravasation of blood into the pericardial sac. When the abscess, as often happens, is situated in the septum ventriculorum, the result is somewhat different. A communica- tion between the ventricidar cavities by a small opening does not seem to have any marked influence upon the circulation ; should the suppurative change however have extended upwards from the septum, should the pus have burrowed into the lax connec- tive tissue between the lamella) of the tricuspid valve, the burst- ing of the abscess may cause detachment of all the three flaps which are attached to the septum, sc. the inner curtain of the 278 CIRCULATOlir APPARATUS. tricuspid, the left flap of tlie piilinoiiaiy and the right flap of the aortic valves ; the result of course being insufficiency of the cor- responding valvular apparatus (cf. incompetence and stenosis of the valvular apertures of the heart, § 255). § 245. Appendix. The term " abscess of the heart," besides being applied to the large solitary lesion described above, is also employed to denote those small and scattered foci of softening, not exceeding a pin's head in size, which are occasionally found in connexion with pyemic, puerperal, glanderous and other forms of blood-poisoning, and which are always multiple. Some of them are usually situated immediately beneath the en do- or pericardium. They make their first appearance as greyish specks in the muscular tissue ; later, as minute cavities filled with a diffluent pulp. No true pus-corpuscles can be detected under the microscope, nothing indeed but vibrios {see § 24). At first, these vibrios are found packed closely between the muscular fasciculi \ they subsequently penetrate into their interior, the muscular fibres simultaneously undergoing disintegration ; in fact, transverse sections give one the impression that the con- tractile substance is actually breaking up into vibrios, since the substitution of a mass of vibrios for the muscular fibre takes place without any increase in its volume. The alterations do not admit of being traced beyond the formation of little abscess-like foci of softening, inasmuch as the affection occurs exclusively in the most violent and quickly fatal forms of the said toxasmic disorders* t:; Heteroplastic Tumours of the Heart. § 246. When we come to consider the morbid anatomy of serous membranes we shall become acquainted with a primary sarcoma of the pericardium. Apart from this, all cancerous, tuber- culouSj and sarcomatous affections of the heart are of metastatic origin. But even these are rare. The occurrence of milianj tubercles in the heart has only been known within the last few years. Recklinghausen discovered them in the muscular tissue of | that organ; indeed it is a general rule that all heteroplastic growths are principally met with in the connective tissue of the myocardium. I have recently met twice with mihary tubercles in the endocardium, near the free border of the mitral valve. DISEASES OP THE HEAUT.— ENDOCARDITIS. 279 Both cases occurred in children, in connexion with acute miliary tuberculosis of all the serous membranes and the pia mater. § 247. The large cheesy nodules in the myocardium which used formerly to lie called "tubercles of the heart" are in all probability, as Virchow has recently shown, not tuberculous but S3q)hilitic. Gummata of the heart are most commonly found in the septum between the ventricles. As a general rule, several nodules not larger than a pea are held together by a quantity of inflammatory connective tissue, forming a single tuberculated mass; we do however find solitary nodules of so remarkable a size, that they protrude into the cavity of both ventricles at once. § 248. Cancerous nodules — secondary to medullary or me- lanotic growths elsewhere — seldom grow to any size in the heart. We rarely find them larger than a hazel-nut. They all originate in the connective tissue of the myocardium, and force their way, according to their position, either inwards or outwards ; in the former case, they detach and occasionally perforate the endocar- dium, in the latter, they do the same to the pericardium. It has also been asserted that thrombi of the heart's cavities (polypi of the heart) are susceptible of undergoing cancerous degeneration ; but this assertion is grievously in need of being corroborated. /8. Endocardium. A. Acute Endocarditis. § 249i Attention has already been drawn to the fact that the endocardium, although the analogue of the internal coat of the' vessels, is yet far more delicate in its texture ; that it contains vessels — at least here and there ; that where these are lacking, the rich vascular network of the myocardium sends its terminal loops close under the thin lining membrane, so that we may regard the latter as standing in direct connexion wdtli the vasa rasorum. We cannot therefore be surprised to find that the endocardium is far more susceptible than the tunica intima of the vessels. Various anomalies in the composition of the blood, the py^emic, puerperal and typhous dyscrasi^ — but above all, the dyscrasia associated with acute articular rheumatism, act as 280 CIRCULATORY APPARATUS. inflammatory irritants upon the endocardium. According to Bamhergers estimate, 20 ^/o of ali the cases of acute articular rheumatism are complicated Avith endocarditis. As regards the more precise localisation of the process, we must first call attention to the fact, that the endocardial lining of the left heart is so preeminently liable to become affected that cases of endocarditis of the right heart belong to the curiosities of pathology. Next, there is a marked connexion between the seat of the disease and the mechanical irritation to which certain regions of the endocardial surface are exposed during the heart's contractions. Such are the lines along wliich the valve-flaps come into contact during their closure ; not the free edges of the valves, but lines which even in the normal state are very appa- rent on the sigmoid valves, lines which coincide with the free border of each flap only at its middle point (nodulus Arantii) and at its two extremities, but which are separated from it else- where by an interval of from half a line to one line ; on the cuspid valves the "line of contact" is everywhere one line off the free border ; it runs along the upper surface of each flap, correspond- ing exactly to the insertion of the upper ends of the forked chordge tendineas upon its inferior or ventricular aspect. It is here as a rule that we nmst seek for the earliest signs of morbid change. Starting from hence, the mischief may extend over a great part of the valve ; it may burst forth simultaneously at another point of the endocardial surface ; but the "lines of con- tact " of the valves are and continue to be its favourite seat. § 250. The textural change in acute endocarditis is made up of three factors of very unequal Aalue. In the first place, an implication of the vasa vasorum may be demonstrated wherever they happen to run in the neighbourhood of the inflamed part. Congestion and a considerable proliferation of the corpuscular elements of the adventitia may always be shown in trans- vei'se sections through the inflamed curtains of the mitral valve (fig. 87, &). Of far greater moment are the progressive changes which take place in the non-vascular, most superficial lamellag of the endocardium. Their connective tissue, owing to the pro- liferation of young cells in large numbers and a simultaneous softening of the intercellular substance, swells up to such an extent, that even with the naked eye we can detect a series of warty prominences on the surface of the valve (fig. 87, c). DISEASES OF THE IIEAllT. — ENDOCARDITIS. 281 These granulations are exceedingly frail. Not only does their mutual contact during the closure of the valves splinter and damage their soft tissues, but they speedily fall a prey to a finely-granular, not fatty, metamorphosis of their entire sub- stance ; this renders the vegetation so very brittle, that the blood-current easily washes large and small bits of it away. When this happens, a proportionate loss of substance, the ^' endocarditic ulcer," is produced, which usually penetrates clean throuo;h one lamella of the valve. The edo;es of the ulcer are always irregularly raised ; they exhibit, so long as the endo- carditis is on the increase, the primary stages of the process, which extends to the neig-hbourino; connective tissue. A similar extension occurs, though less frequently, at the base of the ulcer ; Fig. 87. Acute endocarditis. Section through one of the curtains of the inflamed mitral valve, a. Upper, a', lower lamella of the endocardium ; h. Intermediate layer, whose vessels are congested; c. Efflorescence of upper lamella; d. Deposit of fibrin; tV* the remaining lamella of the curtain becomes involved, and when this yields the valve is perforated. Perforation of a valve is one of the most dangerous accidents that can happen ; for the force of the blood-current may easily dilate the original opening ; or the curtain may bo detached on one or other side. In the cuspid valves, it occasionally happens that the whole edge of the curtain is detached together with the insertions of the nmsculi papillares. The perforation, like the ulcer, is invariably fringed with the inflammatory vegetations described above, which, in consequence of the fibrinous deposit of which I am now about to speak, may assume so great a size, that the opening in their midst can hardly be detected. This rapid course of endocarditis in its most usual form never issues in suppuration. This is anticipated hy the granular dis- integration alluded to above — a sort of necrosis of the newly- 282 CIllCULATOHY APPARATUS. formed substance. Tliis must uot be taken to mean that suppu- ration never complicates the morbid anatomy of endocarditis. Only, when pus is formed, it is ahvays confined to the loose connective tissue between the lamella? of the valves, and to the subendocardial connective tissue ; moreover it never collects in any quantity, but always takes the form of minute abscesses, no bigger than a pin's head, which cause pustular elevations of the endocardium. The third factor which plays a more or less conspicuous ])'Avi in every case of acute endocarditis, is the ])recipitation of fibrin upon the roughened surface of the aft'ected valve. I lay stress on the fact that fibrin alone is usually deposited ; the thrombus rarely contains any red corpuscles. I cannot help thinking that owing to the naked-eye resemblance of the fibrinous deposit to the proper outgrowth from the tissue, their real distinctness is often overlooked. The precipitated fibrin (fig. 87, d) fills up all the little inequalities of the surface, and increases the total bulk of the efflorescence to such a disproportionate extent, that it strikes the observer much more forcibly than the morbid change in the valve itself. To conclude ; the coagulation of the fibrin is not, any more than in an aneurism, to be regarded as a salutary phenomenon, as a first step towards recovery. The fibrin readily becomes disintegrated. It does not therefore operate as a check either to the progress of the ulceration, or to the perforation of the valve, while it enhances the risk of meta- static inflammations consequent on embolism of its detached fragments* B. Valvular Aneurism, § 251. The way in which the so-called valvular aneurism originates, is worthy of particular notice. Under this name — taken broadly — we understand any circumscribed bulging in the continuity of a valve. Conditions of this sort are not as a rule in any way Connected with endocarditis. They are Saccular or pouch-like inflexions of a valve, in wdiosd formation both of its lamellae (without any previous change in their structure) take part. The pouch invariably opens on that side of the valve which is exposed to most pressure when the valve is closed, while the sac itself is on the opposite side. In the aortic valves, we enter the aneurismal sacculus from the sinus of Valsalva ; in DISEASES OF THE IIEAIIT. — ENDOCARDITIS. 283 the cuspid valves, from the A-entriciihir cmity. Besides these, we occasionally meet with diverticula in the walls of the heart, near its orifices, precisely analogous to the aneurisms in (piestion, though a strict nse of lano-ua^e must of course forbid ns to call them " valvular." These are found at the origin of the coronary arteries and on the floor of the innermost sinus of Valsalva. The latter, by far the most common of these pouches, project into the right heart, sometimes above, sometimes below, some- times between the lamellae of that curtain of the tricuspid valve which is attached just opposite to them. The same three paths 'are open to aneurism of the membranous part of the septum ventriculorum^ which comes under the present category. It may force its way from the left ventricle, over, under or between the folds of the left curtain of the tricuspid valve, and so into the right ventricle. I have seen a case, in which an aneurism of the sinus of Valsalva, as large as a cherry, projected on the upper surface of that curtain, while on its under surface was one as large as a pea formed by the septum pellucidum. After this digression, let us retmni to valvular aneurism con- sequent upon endocarditis. This form is necessarily preceded by the complete destruction of one of the lamellge of the valve. The blood makes its way into the opening thus produced, forces the lamella3 asunder, and causes a more or less extensive pouching of that which is still intacti The endocarditic or acute valvular aneurism is thus essentially distinguished from the first variety by the fact that the pouch is formed, not by the entire valve^ but by one only of its lamellae. c. Perforation of Valves. § 252. Here too we must distinguish between destruction of the valve proper by inflammatory change, and a harmless variety of perforation, which is very often met with at the free borders of the semilunar valves. The latter depends upon a thinning of that portion of the valve which lies ahoce the actual "line of contact" (the line along which the valves touch one another during closure), and is in my opinion nothing more than an approximation of the sigmoid to the cuspid type of valve. For if we glance at the anatomical arrangements intended to prevent regurgitation of the blood, we see at once that they 284 CIRCULATORY APPARATUS. belong to two distinct types, that of the sigmoid and that of the cuspid valves. This difference of type may be dismissed in a few words. The sigmoid valves are dnplicatures of the intima, each of which forms a semicircular fold with its convexity directed towards the current; the terminal points of the lines along which the valves are attached, being all in the same hori- zontal plane. Accordingly they form pouches, which touch one another by their outer surfaces when they are filled with blood, and so close up the tube. The pecidiar way in Avhicli these flaps are attached, renders it impossible for them to move otherwise than ivith the current. The cuspid valves on the other hand, ' consist of moveable curtains, attached in the same horizontal plane, at right angles to the axis of the vessel; and these, so far as their mode of attachment is concerned, might be folded over to either side indifferently ; nevertheless, they too can only yield to the blood-current in one direction, inasmuch as the union of their free borders with the chordas tendinece prevents their being forced into the cavity of the auricle. It would indeed be matter for surprise had Natm-e, usually so simple in the methods she adopts, really contrived two kinds of valve in the present case, diff'ering from one another in principle ; we ought therefore to consider whether the apparent diversity of anatomical construction may not be reducible to a simple modi- fication of one and the same fundamental ty}3e. Now it seems to me that this type is to be found in the sigmoid form of valve ; not only because of its more frequent occurrence in the organism (valves of veins, &c.), but also because the innocuous variety of perforation which Ave are now considering, presents us with a modification of the sigmoid valve, tending to approximate it to the cuspid type. This perforation, as may be seen at a glance from the annexed figure, may be regarded as a partial separation of the free border of the valve, extending from the nodulus Arantii to its terminal attachment. Now during the closure of the valves, this free border acts as a retinaculum ; it hinders the valve from receding to too great an extent. One need only put the tip of one's forefinger into a sinus of Valsalva, to be convinced that the valvular pouch is narrower at its entrance than at the ^'line of contact;" i.e. that the free margin of the valve forms a shorter and straighter bond between the nodulus Arantii DISEASES OF THE HEART.-— ENDOCARDITIS. 285 and the wall of the vessel, than does the ^' line of contact." The free border of the valve therefore acts as a retinaculum in exactly the same way as the chordsB tendinea) of the cuspid valves. For the performance of this function it is clear that all that part of the surface of the valve which lies between the free border and the ^' line of contact," is superfluous. Hence the disappearance of this intermediate portion (only a few connecting strips of it being left) is an acknowledgment of the functional independence of the free border. In extreme cases (which are not, upon the whole, rare) of marginal perforation of the valves, a nearer approximation of the sigmoid to the cuspid type is brought about by the existence of an interval between the point at which the marginal part of the valve is attached to the wall of the vessel, and the point at Fig. 88. Fenestrated semilunar valves from the pulmonary artery. ^Natural size. which its ^' line of contact " is attached. So that the correspond- ing halves of the free borders of any two contiguous flaps, together with the fine threads which link them with the " line of contact," spring from a point of the arterial wall above the real insertion of the valve. This interval between the points of attachment of the retinacula of the valve-flaps, and that trans- verse plane of the vessel which it is the business of the valve to close (making it possible to retain the valves in a more vertical, and therefore in a more secure position), is the fundamental principle of the cuspid type of structure. Fig. 88 represents an extreme example of perforation of the sigmoid valves ; the bundles of tendinous threads stretched over the glass rod, which 286 CIRCULATORY APPARATUS. lias been passed from one sinus of Valsalva, over the point atwhicli the '' line of contact " of the valve springs from the wall of the vessel, into the next sinus, perform the same office as the musculi papillares of the ventricle. The point of origin of the ' ' line of contact " may now be moved further downwards without any uncertainty as to the perfect competency of the valves. The flap itself may become gradually flatter and more pointed, the nodulus Arantii being kept in its old position, while the angle formed by the two limbs of each ^Mine of contact" grows pro- gressively less and less obtuse ; this also is well shown by the specimen in the annexed figure. Briefly, the innocuous variety of perforation or fenestration of the sigmoid valves is, in my opinion, a connecting link between the sigmoid and the cuspid types. D. Chronic Endocajxlitis, § 253. In marked contrast to acute inflammation, and that softening of the valvular tissues which results from it, chronic endocarditis produces an extreme condensation and thickening of the endocardium. Most persons suffering from chronic endo- carditis give a histor}^ of former attacks of acute articular rheumatism. Hencp we may admit the possibility, nay the probability, that the endocardial changes may be of acute origin ; a lesion, however insignificant, situated in the " line of contact " of the valves, being continually exposed to mechanical irritation, might refuse to heal; and might serve in consequence as a starting-point and centre for a chronic inflammation, such as we often meet with in neglected ulcers of the skin. On the other hand, it is necessary to throw the identity of this process with chronic endoarteritis into strong relief In either case, the microscope shows an inflammatory overgrowth of connective tissue, followed by a secondary stage of calcifica- tion, or, more rarely, of fatty degeneration of the newly-formed products. The only special feature about chronic endocarditis is the marked tendency of the inflamed parts to contract. This tendency, of course, can only manifest itself in the dujDli- catures of the membrane, since their one-sided attachment allows a retraction of their free borders to take place. § 254. Every point of the endocardial surface may be the seat of chronic inflammation ; yet it affects the valves and the DISEASES OF THE HEAHT. — VALVULAr. DEFECTS. 287 apex of the left ventricle in sucli an overvvlielming majority of cases that I may fairly confine my remarks to these two localities, E. Valvular defects. § 255. Those coarser distortions of the orifices of the heart which are caused by chronic endocarditis are embraced under the general head of valvular defects. These are always made up of three distinct anatomical factors, which have to be considered separately in every case : 1. Thickening — the immediate result of overgrowth of the connective tissue. Slight degrees of thickening are extremely common at the base of the aortic valves and along the " line of contact " of the mitral ; they do not Fig. affect the functional activity of the valves. Higher deo^rees of the same alteration mve rise to rouo^h elevations, hardened by earthy deposit; along the '' line of contact" of the mitral valve these are usually confined to one surface only; in the \'^^^^ — ^^v^ aortic valves thev usually affect both. They '"'^1^^^.'^ cover the entire surface of the semilunar valves Ins^^fficiency and stenosis of the w^ith a layer several lines thick, so that instead aortic orifice, of three delicate, sigmoid flaps, we ultimately Thickening and find three rigid, tuberculated bodies festooned ^-^^ valve-flaps. round the wall of the aorta (fig. 89). Natural size. 2. Retraction. This results from shrinking of the hyperplastic connective tissue. Together with the thickening, it gives us the impression that the entire mass of the valve is crumpled into a small, elongated roller — that the curtain is rolled up. Curiously enough, the narrow borders of the aortic valve beyond the "line of contact" often remain unaltered, and hang from the free edges of the shrunken valves like flexible bands. At the mitral orifice, where the process extends to the chords tendineae, the shortening causes the valve to be dragged down into the ventri- cular cavity, thus fixing it in the attitude which it ought only to occupy after the close of each systole (fig. 90). 3. Adhesion. The tissue of the inflamed valve, notwith- standing its rigidit}^, is capable of a certain degree of internal movement ; it is in a state of inflammatory fluxion, wdiich allows it to adhere to its fellows, wherever they happen to touch. So long as the valvular apparatus retains its normal mobility, any two 288 CIRCULATORY APPARATUS. points which touch each other during the closure of the valve, are always separated when it opens; but the inflamed valves no Fig. 90. Insufficiency and stenosis of the mitral valve. The valve is converted into a rigid funnel, laid open at a ; the mnscnli papillares have been cut away from the ventricular wall. The cut surface at a shows the thickening of the flaps, which is also seen in the background ; at a moreover there is a nucleus of calcification. The chordfB tendineJB are thickened and fused together; the muse, papillares indurated and tendinous at their tips. longer, as a r always begins Fig. 91. Adhesion of the right and pos- terior flaps of the aortic valve. At a the line of union. The valve is com- petent, though it consists of only two flaps. ule, possess their full mobility; and adhesion between those points which are least separated during the opening of the valves. The coales- cence of two neighbouring flaps takes place along the " line of contact " from without inwards. In the sigmoid valves of the aorta the fusion always occurs first between the right and posterior flaps. When once it has extended as far as the nodulus Arantii, the partition between the adjacent sinuses of Valsalva sinks down, and the two flaps are fused into one ; this in some measure does the work of both, unless otherwise prcA^ented by tliickening and contraction (fig. 89). Fusion of the curtains of the mitral, stands foremost as regards frequency and mischievous effect. The auriculo-ventricular orifice is thus gradually narrowed from either side, till it finallv becomes DISEAS'^S OF THE IIRART. — VALVULAR DEFECTS. 289 a mere slit, the mitral valve forming a rigid diaphragm between the auricle and ventricle. The fusion of the chorda3 tendlnea^ (fig. 90) starts from their points of bifurcation and their oblique insertion into the under surface of the valve. Tliis contributes not a little to the rigidity and immobility of the valve. Clinical Applicatioxs of the above State:n[ents. It is obvious that the existence of valvular defects must cause pro- found disturbances, first in the movement of the blood, and secondly in the functions of the various organs. Valvular lesions, whether due to chronic changes or to acute endocarditis, may, from this point of view, be grouped under two heads : 1. Thickening, rigidity, calcification and coalescence of the valves prevent their being accurately applied at the right moment to the wall of the vessel or the ventricle (sc. in the case of the aortic valves, during the systole, in that of the mitral, during the diastole), so that the valve con- tinues to project into the corresponding orifice, narrowing its lumen {stenosis). The blood-current impinges upon this obstacle and so causes a murmur which is best heard at that point of the thoracic wall, to which it is most directly conducted. 2. Retraction, perforation and partial detachment of valves, and rupture of chorda? tendinea), prevent the valves from completely closing their respective orifices, at the moment when their tension ought to bo opposed to the regurgitant current of the blood ; an opening is con- sequently left, through which the blood returns into the cavity from which it has just been driven {Insujjlciency). The closure of the valves is normally accompanied by two audible sounds ; the first, systolic in rhythm, is due to the tension of the mitral valve ; the second, diastolic only, to that of the semilunar valves. Now if this sudden tension does not occur, the corresponding sound must also be wanting. In its place we may have a murmur caused by the regurgitation of the blood through the abnormal orifice ; a murmur which may indeed be intense, but must always be of short duration. Stenosis and insufficiency always occur together aa a result of chronic endocarditis ; acute endocarditis, how- ever, by cansing perforation and detachment, may be followed by in- sufficiency without stenosis. a. Stemsls and Insufidency of tho Aortic Valves (figs. 89 and 92). The left ventricle of an adult pumps about three ounces of blood (d; wineglassful) into the aortic system at each systole. The increased resist- ance offered by the contracted aortic orifice is transferred as an increase of" systolic pressure to the internal surface of the left ventricle, and, accord- ing to the law laid down in § 235, must lead to its hypertrophy. At the same time the stenosis will cause a systolic murmur which will be most 19 290 CIRCULATOUY APPAEATUS. distinctly heard over the right edge of the sternum on a level with the second intercostal space, inasmuch as the ascending limb of the aortic arch lies in close proximity to the thoracic wall at this point (fig. 92, c). The murmur is proj^agated into the arteries. Another series of pheno- mena manifests itself during the diastole of the heart. The insufficiency of the sigmoid valves allows a part of the blood which has just been driven into the aorta to regurgitate, as the pressure in the left ventricle, when it is relaxed, stands lower than that in the aorta. The familiar diastolic click of the healthy valve is no longer heard; its place is taken Fig. 92. "^ •>. \n\- ' h-i:. pposed surface of the parietal pleura (a— ^). During the expiration which follows, a portion of the pulmonary pleura {a, I) which lies in front of the point originally involved, becomes iri- 308 SEROUS MEMBRANES. fected during the recession of the lung. Lying as this does in front of the primarily affected spot, it will advance beyond this during the next inspiration, and will accordingly contaminate a fresh portion of the healthy parietal pleura {ft, 7) ; in a word, with each breath the patient takes, a new zone, both of the parietal and the pulmonary pleurae, must become contaminated. The extension of the irritant matter however, occurs with varying rapidity in the various regions of the pleural sac. It hardly amounts to anything in the neighbourhood of the apex and the posterior border, and increases in proportion to its distance from these points, reaching its maximum close to the free borders. The circumstances are somewhat modified in the case of the peri- Btaltic movements of the bowels. At the moment when a segment of Tlie same at the end of expiration. References as before, a, ft, y, see text. For intestine begins to take part in the wave of contraction passing from above downwards along the circular fil3res, it forms, in conjunction with the neighbouring segment which is already undergoing dilatation, an inclined plane, surrounding the entire bowel. Upon this plane the general pressure which exists in the abdominal cavity, breaks up into two components ; the one, acting at right angles to the axis of the INFLAMMATION. 309 bowel, tends to compress it, wliile tlie other operates along its axis in a direction opposite to that of the contractile wave. This movement is aided by the recoil from the contents of the bowel as they are forced downwards. The former element tends to bring the affected segment into contact with an area of the parietal peritoneum directly propor- tionate to the length of the mesentery of the affected segment (the attached end of the mesentery acting as a fixed point). These considerations, into which I cannot enter more at length, since they belong rather to the province of pathological physiology than of morbid anatomy, indicate most clearly, that a perforation of the very mobile small intestine is far more dangerous than one of the fixed appendix vermiformis ; that a perforation of the stomach is more serious when it occurs on its anterior aspect and on its greater curvature, than when it is situated on the posterior surfiice and lesser curvature ; that a pleurisy originating at the apex of the lung tends to remain circum- scribed, while a pleurisy of the free border rapidly transgresses its original limits, and so on. Inflammations of serous membranes are classified on the one hand as acute and chronic, on the other as adhesive, suppurative and indurative. As these varieties shade into one another by infinite gradations, I prefer to adopt a mixed classification of a more immediately practical character. § 269. — Recent wjlaimnation. The epithelial layer is ob- viously first exposed to the action of any irritant applied to the surface of the membrane. Hence the earliest phenomena of inflammation will naturally consist of changes in the epithelium. Accordingly these changes, together with a simultaneous transu- dation from the distended capillaries of the affected part, constitute the first stage of every acute inflammation, and the anatomical basis of what is shortly called a recent pleurisy, pericarditis, or peritonitis. The serous membrane is reddened ; the hypera^mia of the submucous capillaries is apparent even to the naked eye. That the capillaries of the serous membrane itself are gorged with blood and dilated, and that in consequence of this, the inter- mediate islets of parenchyma seem smaller than usual, may be demonstrated on any detached shred which is examined in iodised serum under a low j^owcr. The surface at the same time appears to have lost something of its natural polish ; this indi- cates that the epithelium has become detached, and that the emigration uf the colourless blood-corpuscles has already begun. We notice a moderate amount of a reddish, soft and elastic sub- 310 SEROUS MEMBRANES. stance ^vlucll either lies loosely upon some portion of tlie surface, or stretches in the form of threads and bands between the opposed lamellee of the serous sac, or else glues them to one another. The last-named phenomenon in particular, prevails wherever two serous surfaces are in contact without gliding far upon each other, as between the adjoining lobes of one lung, between the liver and diaphragm, between the spleen and stomach. Should there be much free fluid present, as generally happens in recent pleurisy, a portion of the ''recent inflammatory lymph" is usually suspended in it in the form of ragged flakes. If we take some of tliis matter, and examine it under a liigli power, we find laro-e masses of cells and nuclei, together with a lax web of slender fibres, wdiich prove on chemical examination to consist of a coao^ulated albuminous substance. a. Fig. 99 represents a large selection of the various forms of cells which were found in the "recent inflammatory lymph," and floating in the exudation, on the first day of a pleurisy excited artificially by the injection of iodine. Among them may be noticed free nuclei ^vith one or more nucleoli, nuclei undergoing division till they are disintegrated into a mass of little spheroids, circular cells with large nuclei and very little protoplasm, some of which are in process of fission ; other cells with a large pro- FiG. 99. ■* ° «>, §, Cells and nuclei from the recent inflammatory lymph, a. Their detachment from the homogeneous plates of the serous epithelia. -aJxr- {Mcli.) portion of protoplasm, and nuclei already divided. I do not wish to assert that all these structures are derived from the epithelium ; the great majority have probably migrated from the vessels in the manner described by Colmlieim (§ 89) ; but I must insist that some, at least, have originated from the epithelium. The tes- selated mosaic of cells (fig. 96) has been broken up ; the nuclei have lost their usual flattened form and have become globu- iNPLAMMATiOX. 3 1 1 lar; they have also become detached from the homogeneous plates. I camiot, without further reasons, consent to ignore positive results like those figured in fig. 99, a. ]n these cells the nuclei and protoplasm have not yet wholly separated from the homogeneous plates, but the moment of separation is evidently at hand; in one of the cells, the little plate has become quite convex on the side to which the nucleus is attached ; in another one, the nucleus is kept in its place only by a fine thread of protoplasm ; a third exhibits the simulta- neous multiplication of the nuclei by fission. The detached cells continue to undergo i)roliferation, as we have already seen ; in brief, the epithelia which are primarily affected by the irritant, react towards it just as connective-tissue corpuscles would react; the luieleated protoplasm on their under surface producing new masses of nucleated protoplasm by division. The homogeneous plate, deprived of its nucleus, is set free, and maybe recognised, even long after, floating about in the serous cavity. b. The coagulated albuminous substance, which is associated with cells and nuclei in the recent inflammatory lymph, has nothing whatever to do with the epithelium. It is rather to bo viewed as an essential constituent of the inflammatory exuda- tion. The high degree of tension to which the blood in the con- gested vessels of the serous membrane is subjected, naturally causes an exudation of the liquor sanguinis to take place. We may convince ourselves of the great ease with which such a transudation may set in and continue, in any hypersemia of artificial origin, whether it be active or passive. The exudation resembles the liquor sanguinis in qualitative composition, though its chemical elements are combined in different proportions. The proportion of albumen in particular is very variable, being now above, now below, the standard of the liquor sanguinis. From a histological point of view, we must confine our attention to that element of the exudation of which we have already spoken — the element which passes at once into the solid state — and which is briefly termed ^' exudation-fibrin.'' This term imj^lies the assumption that the fibrin of the blood makes its way to the surface of the serous membrane together with the liquor sanguinisj and that, on its arrival there, it is deposited in a solid form. Is this assumption correct ? Virchoio has put forth the view that exudation- 312 SEROUS MEMBKANES. fibriii; like fibrin generallj, is a product of the activity of the tissues themselves — that it is autochthonous — originating therefore, in the present instance, in the parenchyma of the serous membrane itself. I cannot agree to this. On examining the surface of the inflamed membrane by reflected light, a keen eye may here and there detect little punctiform elevations, closely set — minute buttons of a transparent substance. If the serous membrane is carefully peeled off and examined with a low power (fig. 100) v/e perceive at the first glance that the position of these nodules is everywhere determined by the course of the vessels. They form rounded masses of an amorphous and homogeneous material which looks as if it had oozed out of the capillaries and arterioles (Uebergangsgeftisse) at various points, like rosin from a fir- tree. I regard this appearance as very suggestive. I believe that it enables us to ascertain the immediate source of the exudation-fibrin, which is in fact identical with the fibrin of the blood. The form exhibited by the coagulated fibrin under the micro- scope is not always the usual one of a delicate reticulum of Fig. 100. 2:^. Inflamed peritoneum. Hypersemia and exudation. (Mch.) ■^. felted threads, such as exists in ordinary coagula ; the mass is often less fissured, and consists of broad, wavy fibres, differing from areolar connective tissue only in the absence of any regular arrangement of those fibres. On the whole, it is as easy to dis- INFLAMMATIOl:^. 313 tinguish the fibrin by its irregular appearance from every other constituent of the exudation, as it is difficult to convey any idea of the difference in words. It resembles neither a crystal, nor a cell, nor a fibre ; it is a coagulum, for the appearance of which I refer the reader to figs. 100 and 101. § 270.— Adhesive inflammation. The two issues which are common to every inflammatory process, towards organisation on the one hand, towards suppuration on the other (§§ 91-106) recur as usual in the case of serous inflammations. They are doubly interesting in the present case however, inasmuch as they are modified in accordance with the anatomical peculiarities of the tissue, and agree with the typical forms already described only in their essentials. So much must be borne in mind from the outset. Yf e have to do with two opposed surfaces of connec- tive tissue. Eow if these surflices produce the same material, and this material is capable of being organised, the two layers may readily become fused with one another ; indeed it would furnish matter for surprise were such fusion not to occur here and there. Indeed it is quite a usual outcome of organisation for the opposed surfaces to become united by bridges of connective tissue over an area of variable extent. Such bridges are called " adhesions," and the epithet '^adhesive" is transferred to such inflammations as tend from the first to result in organisation of the inflammatory products. ^ 271. The histological details of adhesive inflammation difter according as the inflamed surfaces of a serous membrane Fig. 101. il.U,iii,;:i;im;ii;!iiylii'- Adhesive inflammafcioTi. Diaphragmatic pleura, a. Muscular substance of the diaphraf^m; 5. Subserous tissue; c. Serous membrane; d. Boundary-line between the serous membrane and the exudation ; e. Exudation. -^ ^^y. {Mch.) 314 ^ SEROUS ^^lEMBrvAXES. are or ai*e not f^■cpai•atecl from the first by a con- siderable amount of free fluid. In the latter case, the surfaces remaining in absolute contact throughout, the recent hmph suffices as a rule to produce connective tissue, i.e. adhesions, from its own resources. This might well be thought para- doxical, so long as this substance was held to consist of fibrin only ; such an exudation, desti- tute of corpuscular elements, must necessarily have been considered incapable of undergoing organisation. We know now that fibrin is only one of the constituents of the inflammatory lymph. It forms a spongy framework (fig. 101) in whose innumerable pores the young cells, multiplied it may be by fission, are contained (fig. 101, e). These young cells are not so closely packed as to justify us in giving the name of embryonic tissue to the material which occupies the interstices of the fibrinous network ; it may be compared more aptly to mucous tissue, in that a certain quantity of a homogeneous, transparent intercellular sub- stance holds the cells asunder. But there is not a shadow of doubt that this material passes directly into connective tissue, that blood-vessels are de- veloped in its substance, and permeate it — in a w^ordj that it is physiologically equivalent to em- bryonic tissue. We may observe how^ the cells which were originally round, become spindle- shaped ; how their processes come in contact with each other and are fused together ; and how^ that, no sooner is a greater resemblance, even in out- ward feature, established between this and the well-knovrn forms of connective tissue (particu- larly inflammatory spindle-cell tissue, § 93), than the second act in the process of organisation, the development of vessels, sets in. There is no better opportunity than this, of studying the histological course of the secondary and tertiary modes of vascularisation. The specimens (figs. 102 and 103) w^ere taken INFLAMMATION. 815 from a false membrane bet^.veeii the adjacent lobes of the right king in a dog, on the fifth day after a pleurisy had been artificially excited by the injection of iodine. They illustrate in the plainest FiG. 103. r Development of vessels and opening of a path for the blood. The course of the vessel is indicated by a cord of cellular masses of protoplasm fused together. Some of the blood- corpuscles have already forced their way into the pro- toplasm. 3-^0. way the mode in which the vessels are developed ; their first appearance as threads of nucleated protoplasm formed by the fusion of cells arranged in rows, the excavation of a channel for the blood, (fee, exactly as I described them on a former occasion. Fi^s. 104 and 105 show that the extension of the vessels occurs Fig. 104. False membrane between two pulmonary lobes permeated on either side by a capillary network, a. Serous membrane ; h. Lung ; c. One of the capillary networks of the false membrane ; d. A limited number of afferent and efferent trunks, t^- (Afc/t.) 316 SEROUS MEMBRANES. primarily in a horizontal plane. It is only at a few points (at dd, in fig. 104) that tlie afferent and efferent parent-vessels make their way up through the serous layer, while in detached shreds of the membrane, examined from above, a vascular network of exceeding beauty may be observed (fig. 105). Fig. 105. 0^3 *J -^S^ Vessels in a false membrane seven days old. ~^. {Mcli.) In the primary mode of adhesion, that which we are now considering, each of the serous surfaces generates its own vascu- lar network. Thus the transverse section delineated in fig. 104 shows two networks in one and the same false membrane, separated from each other by a layer of tissue which is not yet vascularised. At a later period however, this becomes modified. For if the fusion of the opposed surfaces is not interfered with, the intermediate layer of connective tissue is gradually furnished with vessels, and the vascular networks ultimately unite by in- numerable anastomoses. So far we have traced the development of a layer of con- nective tissue between the serous surfaces, thin indeed, but very richly supplied with vessels ; and this without any active co- operation on the part of the fibrinous element of the exudation, and without the occurrence of any notable proliferation in the subepithelial layer of connective tissue. We can easily lay hold of this false membrane, and strip it from the serous surfaces on which it lies. The ease with which this can be done, sponta- neously reminds us of the ease with which the epidermis can occasionally be stripped from the inflamed cutis — and recals the fact, that up to this time the only real connexion between the INFLAMMATION. 317 serous membrane and the false membrane which covers it, is operated by the few and feeble afferent and efiPerent vessels. At a later period we find the state of things altered. The union between the serous and the false membrane grows more intimate, and finally becomes so close that any attempt to scrape or peel the latter oflp Avould be futile ; the false membrane assuming the character of an exceedingly intimate and wholly inseparable bond of union between the opposed surfaces. The adhesion is then complete. § 272. The phenomena which manifest themselves when the opposed walls of a serous sac are separated from the first by a considerable amount of exuded fluid, and when this separation is kept up for any length of time, are far more complicated. If we consider adhesion, not only as a result of, but as the mode of repair after inflammation, and in one sense as the goal towards which every superficial inflammatory product tends, and on arriving at which it may be regarded as mature, we must admit that the means for attaining this end which are at the disposal of the serous membranes, are far from being exhausted with " primary " adhesion. They may unite not oidy by the first or second, but by a third intention also. Of union by the first intention I have already spoken ; the second mode is analogous to the repair of wounds by the second intention, to organisation after suppuration, with which we shall deal hereafter. Union by the third intention is peculiar to serous membranes ; it stands between the other two. The surfaces which tend to cohere are held asunder, not by pus or air, but by a fluid, abnormal indeed as regards quantity, but differing in no essen- tial qualitative character from that which is normally present in the interior of a serous cavity. It has no irritating properties ; but it hinders union, and gives room for very considerable pro- liferation on the affected surfaces. The products thus formed have their source, not in the epithelial layer, but in the parenchymatous connective tissue of the serous membrane ; looked at broadly, they present, as RokitansJd has alreadv shown, the characters of a proliferation of embryonic tissue, of a granulation. But I must not anticipate. § 273. We are now entering upon the consideration of by far the commonest variety of pleurisy and pericarditis ; it is usually of rheumatic origin, and sets in with an abundant sero- 318 SEROUS MEMBllAXES. fibrinous eftnsion. \\e may suppose a loud, grazing friction- sound to liave been heard at first all over the affected region ; this became limited to the upper part of the serous sac, while tlie lower part w^as filled w^ith fluid. The extent of effusion might have been determined by percussion. The pyrexia was intense, and the patient succumbed wdien the disease w^as at its height, partly to the fever, partly to the obstacles in the way of the pulmonary or the cardiac movements. We lay open the pleural sac or the pericardium, and we find it filled to a greater or less extent wdtli a clear, straw- coloured fluid, in which are suspended soft shreds and flakes of a yellowish-white colour. The lining membrane is coated with a pale, yellow^ish or reddish, transparent or opaque, coherent and elastic, or brittle and friable substance, from which it is distinguished partly by its colour and consistency, partly by the fact that this matter can be stripped or peeled off' with varying degrees of facility. The aspect and general arrangement of this substance gives us the notion of a soft, plastic material having been introduced between the layers of the serous sac and subsequently moulded by the move- ments of the lungs or heart as the case may be. A portion of it has accumulated at those points wdiere it is least in the w-ay of the movements of the viscera ; it occupies all the chinks and corners, it fills up the inflexion of the pleural sac betw^een the diaphragm and the thoracic walls, it obliterates the cardiac sulcus and the fold of pericardium which is reflected over the great vessels. But wdiere the substance in question forms a thick layer on the surface of the heart or lungs, it exhibits a peculiar reticulated or villous aspect, such as might a prioii be expected from a consideration of the alternate apposition and separation of the visceral and parietal lamellae ; these appear- ances may be exactly imitated by squeezing a layer of putty between two plates of glass, and then tearing them apart. The ensemble of these characters indicates a close analogy with coagulated fibrin ; and there has long been a tendency to regard this material simply as fibrin exuded from the blood, and to assume that it subsequently formed the adhesions. Various protests against this assumption w^ere how^ever lodged at an early period. Reinhardt in particular denied the possibility of pure fibrin ever becoming organised, and was the first to describe liow it underwent transformation into a fatty-mucous, opaque INFLAMMATION. 319 material, which ended in becoming dissolved or caseous, and never in being developed into connective tissue. Notwithstand- ing his arguments, this misconception held its ground, until Roldtanski's teaching, to which allusion has been already made, paved the way for our present doctrines as developed by BiiJd. In accordance with their researches, we must divide the layer of exudation, which lies loosely on the serous surface, into two strata : 1. An upper one which, during the height of the in- flanuiiatory process, assumes a disproportionate thickness ; this layer really does consist of fibrin, and covers in the subjacent one at every point. The fibrin accumulates in greatest amount on those parts of the affected organ which undergo most displacement, as e.g. on the free borders of the lungs ; just as in whipping the blood to free it from its fibrin, the latter coagulates in flakes upon the stirring-rod. The appearance of the exuded fibrin under the microscope has already been described (§ 269). It forms the same coarse network as in primary adhesion (§ 271) ; it differs however in not being of i\\Q same thickness throughout, varying in this respect from a quarter of a line to six lines or more. 2. A deeper stratum of young connective tissue formed by a proliferation of the connective tissue of tlie serous membrane. We may assume that as soon as the serous surface is denuded of its epithelium, the inflammatory action extends into the connective-tissue layer of the serous membrane; but without attaining any considerable intensity till from the third to the seventh day of the disease. On examining sections, we find a number of connective-tissue corpuscles in the parenchyma of the serous membrane ; their numbers increase as we approach the surface on which they are set free. Upon this surface they appear embedded in a clear matrix, containing mucin, together with which they make up the layer of embryonic tissue which we are now considerino-. Both cells and matrix must be viewed as a true efflorescence from the serous membrane ; the true '^ plastic exudation " is really formed by them, and not, as used erroneously to be supposed, by the fibrin. § 274. As regards the external form of this recent " connective- tissue efllorescence," we need only remark that for obvious reasons, it cannot arrive at any independent finality. Judgino- from the analogy of recent layers of embryonic tissue occurring 320 SEROUS MEMBRANES. elsewhere, we may indeed infer that it tends to assume the form of a membrane roughened by villosities. But this tendency is counteracted on the one hand by the repeated mechanical dis- turbances to which it is exposed, while on the other it is rendered impossible at most points by the superimposed layer of fibrin. Hence the granulation-tissue forces its way up into all the inter- stices of the fibrinous stratum, grows round it and through it layer by la}'er, and thus attains a considerable degree of thick- ness earlier than it would otherwise have been able to do. Not- withstanding even this intimate penetration, in which the fibrin acts the part of a supporting framework, w^e must reject any claims to an active share in the organising process, wdiich may be urged on its behalf. Close upon the heels of this development of embryonic tissue comes vascular isation. An extraordinarily rich network of capil- laries speedily permeates the young false membrane. The newly- formed vessels are characterised by their exceptionally wide calibre, and as is often the case with young vessels, by the thin- ness of their walls. On the other hand, the afferent and efferent vessels of the serous membrane are few and narrow. The result is an arrangement resembling that of the retia mirabilia, where the blood-pressure is proportionately heightened by the interven- tion of a capacious channel between an afferent and an efferent vessel. A like result may be anticipated in the present instance ; — and that the blood in the newly-formed capillaries is really under a far higher pressure than in those of the serous membrane, is proved by the number of extravasations wdiich ensue both in the interior, and upon the surface of the false membrane, giving it a reddish and mottled colour ; while the free fluid is likewise tinged with red. Accordingly, the vascularisation of the false membrane leads in the first place to a state of things most critical as regards the general course of the disease — a state of things wdiich not only affords the most favourable conditions for the continuance of the exudative process, but also, by supphing an abundance of nutrient matter, favours to the utmost the formative changes in the false membrane itself. At this point therefore, the patient is threatened with an over-production of cells — with suppuration. The practitioner detects the unfavour- able turn the disease is taking, and expresses his fears by saying that it drags, that absorption has come to a dead-lock, &c. INFLAMMATION. 321 § 275. But we must defer considering the dangers of sup- puration for the present. Let us first of all take the course of the inflammatory process when it remains true to its original, adhesive character. We may justly inquire how, under the conditions described above, the process of exudation can ever come to a stop. Now one reason for its cessation lies in the conversion of the young embryonic tissue into fibrous connective tissue. This transformation, as was fully shown in § 93, is invariably associated with a certain amount of contraction which, in its turn, leads to the obliteration of a great majority of the newly-formed vessels, so that the blood-supply of the fulh'- developed adhesions represents but a very small fraction of the original capillary network. On the other hand, we must remember that although the fibrin, which is not merely applied to the surface of the young connective tissue, but sends countless processes into its substance, does not undergo organisation, it nevertheless shrinks uniformly and with great force. This shrinking sets in directly after its coagulation, and j^rogresses steadily when the conditions are favourable (and where could it find conditions more favourable than the present?), until it has attained the smallest volume of which it is capable, or until some other sort of metamorphosis has robbed it of its most characteristic proj^erty. It is obvious that this contrac- tion of the fibrin must affect the granulation-tissue with its vessels, which it covers and includes, and so must check the further progress of the transudation. Be this as it ma}', transudation is arrested, and absorption takes its place. The shreds and flakes of fibrin which are freely suspended in the exudation begin to undergo mucous and fatty degeneration ; — the soft, swollen material is found to contain innumerable oil- globules, Avhich may however originate in a fatty transformation of its contained cells. This degenerating fibrin presents a whitish and opaque aspect to the naked eye ; if the effusion happen to be absorbed with exceptional rapidity, a portion of fibrin may remain undissolved, and dvy up in some corner of the serous sac, where it becomes cheesy and remains for years in this condition. As a rule indeed, both the suspended fibrinous floccuh, and the fibrin which coats the connective-tissue efflores- cence on the walls of the cavity, undergo complete solution in the eff'used fluid before it disappears, and are subsequently 21 322 SEROUS MEMBRANES. absorbed into tlie blood together with it. The opposed serous surfaces are approximated until they touch each other, when the inflammatory products by which they are coated, coalesce. Soon too, the bridge along which the vessels of the parietal and visceral laminae anastomose with one another, is completed. This series of changes finally results in the formation of those well-known "bands of adhesion," which connect the cos- tal with the pulmonary pleura, the heart with the pericardium, the various abdominal viscera witli one another, and with the abdominal wall. Their minute structure has often been inves- tigated ; like the serous membranes, they are coated with a single layer of pavement epithelium ; in addition to this, they contain wavy bands of connective tissue, between which run long and slender blood-vessels ; newly-formed nerve-fibres have also been found on one occasion in an adhesion (VirchovS). What seems to me most important is the fact that in the present case, the continual shifting of the opposed surfaces on one another, the incessantly renewed approximation and separation of the two ends of the adhesion, exert a modifying influence upon the organisation of the embryonic tissue ; the resulting connective tissue, instead of assuming the character of ordinary cicatricial tissue with its short, inelastic and rigid fibres, approaching more nearly to the normal type of lax areolar tissue. Thus it is clear that the final result of the inflammatory organisation depends very materially on the external conditions under which it takes place ; and that in particular, a repeated stretching and relaxation of the cicatrix determines the produc- tion of a true lax areolar tissue in place of the inelastic cicatricial tissue. § 276. — Suj)piirative injlammation. We distinguish two va- rieties of suppuration, primary and secondary. Most abdo- minal inflammations, particularly those which are caused by perforation of the alimentary canal, or by infection from the organs concerned in parturition (puerperal fever), afford abun- dant opportunities for the study of the former variety. If the inflammation happen to be quite recent (as in the so-called j^eri- tonitis fuhninans) we may easily convince ourselves that in this, as in the adhesive variety, a stage of "recent agglutination" opens the series of morbid changes. In fact, the histological transformation of the fresh adhesive matter into pus, appears INFLAMMATION. 323 to take place as readily as that into connective tissue. The neutral cells which are present are pus-corpuscles from the moment when they are suspended in a serous fluid and proceed to divide and multiply therein. Their development into '^ specific pus-corpuscles," i.e. into young cells with several nuclei, is in no respect essential ; though it may nevertheless be frequently observed. The transition pre- sents itself to the naked eye as a yellowish- white discoloration and liquefaction of the reddish membranes and shreds, beginning at their edges, and terminating in their rather sudden dissolution into a puriform fluid. I have succeeded in demonstrating this more than once in peritoneal inflammations excited artificially ; at the same time however, 1 noticed that the stage of '' recent agglutination " in primarily suppurative inflammations was generally of very brief duration, passing very speedily into the essential phenomenon of suppurative inflammation, so. purulent exudation. The case is primarily one of ^'exudation" in the strictest sense of the word. Vast numbers of leucocytes migrate from the dilated blood-vessels ; they first of all infiltrate the connective tissue, and then — -as I am forced provisionally to assume in order to account for the occasionally enormous quantity of pus — undergo proliferation. As may be seen in fig. 106, which represents a vertical section through the serous investment of the uterus, all the interstices between the thicker fibrous strata are literally crammed with cells. The great variety of flask-shaped and analogous forms indicates moreover that these cells are ]iot quies- cent, but are undergoing amoeboid movements. The direction in which these movements tend is hardly open to question ; it is clearly upwards and outwards. One may figure to oneself how, through the membrane which is so abundantly infiltrated, a mighty stream of exuded liquor sanguinis is passing. This also will tend to make its way through the interstices between the fibres, and will consequently carry with it numbers of the corpus- •cular elements vdiich they contain ; these cells it will afterwards hold in suspension as pus-corpuscles, when it comes to rest in the serous cavity. In this manner does the exudation become purulent on its way from the blood-vessels to the free surface of the serous membrane ; this is the rationale of purulent exu- dation. 324 SEROUS MEMBEA^ES. At an early period, while the corpuscular secretion is still moderate in amount, the exudation is clear and deposits an abundance of transparent, gelatinous flakes of fibrin ; at a later stage, it consists of pure, greenish-yellow, thin pus. In examining the bodies of patients who have succumbed to puerperal peritonitis we often find the recent inflammatory agglutination in the upper regions of the abdomen, in the neighbourhood of the stomach and liver; lower down, about the kidneys and between the mesenteric folds of the upper coils of the small intestine, we meet Fig. Il6. Suppurative inflammation of the serous coat of the uterus. a. Serous membrane infiltrated with leucocytes; &. Surface secreting pus-corpuscles ; c. Muscular coat. -5^. with a tolerably clear exudation containing flakes of fibrin : this, towards the true j)elvis, exhibits streaks of pus which become more and more numerous, till, in the pelvic cavity itself, the fluid becomes entirely purulent. To the naked eye the serous membrane appears hyper^emic ; but the red hue of the injected vessels is toned down by a milky cloudiness which covers it as with a veil. Tliis is due to the purulent infiltration of the mem- brane itself § 277. Side by side with the primary form of suj^pm-ative inflammation, we may study those cases in wdiich a process, INFLAMMATION. 325 primarily adhesive, passes into the suppurative form. It has been ah'eady shown that this transition is favoured and ushered in (anatomically speaking) by the luxuriant vascularisation of the young false membranes, which furnishes materials for a more exuberant corpuscular proliferation, i.e. for suppuration, wlien the inflamed membrane is exposed to any fresh source of irritation. The practitioner is usually warned of the unfavour- able turn which the disease is taking, by the occurrence of a severe rigor and the hectic fever which follows it. Quite suddenly, as it seems, the cell-proliferation enters upon a more active phase. Every variety of cell, whether it be situated in the exudation, in the false membrane, or in the serous mem- brane itself, takes part in the process. The clear serum becomes turbid. ^Vhole shreds of the false membrane are loosened from their connexion with the underlying tissues and detached, pre- liminary to their liquefaction into pus ; denuded patches of the serous membrane itself undergo losses of substance, which how- ever, are always shallow. Such ulcerations are not uncommon on the costal pleura where it lines the ribs ; they extend into the subserous connective tissue, and more rarely to the perios- teum and bone, which is consequently laid bare and undergoes necrosis. Apart liowever from such accidents, the suppuration retains its superficial character even in its most acute forms. The suppurating surface of the serous membrane is analogous, not to a destructive ulcer, but to a productive and granulating- wound. The analogy with a superficial Avound holds good moreover as regards its limitation on the side of the serous cavity by a membrane of young connective tissue studded with granulations — the '' pyogenic membrane" of authors. The heal- ing process begins in exactly the same way, when the inflam- mation has been of the purulent order from the first. In the meantime, an accumulation of pus, often colossal in amount, has been forming in the serous sac. This is not sur- prising when we consider how large a quantity of pus may be secreted even by comparatively small ulcers ; and in the present case vv^e have an ulcerating surface which is measured not by square lines, but by square feet. It is common enough to see half a pailful of pus removed from an empyema by tapping during life or after death. The diaphragm is pushed down together with the liver or the spleen, the intercostal grooves are 326 SEEOUS MEMBRANES. effaced, the lung undergoes a diminution in size greater tlian could be produced bj its own elasticity ; it contains no air, and hangs in the pm^ulent fluid as a narrow strip of leathery tissue, hardly as broad as the hand. Finally, the pus seeks a mode of exit, just like an abscess. In the case of an empyema the spot chosen for perforation is usually one of the lower intercostal spaces ; here how^eyer the art of the physician usually interferes, disturbs the natural but somewhat tardy course of eyents, and determines the point of exit y/ith a trocar. § 278. As regards the further progress, i.e. the gradual repair of the morbid state, we may argue from our experience of union by the second intention, with this limitation, howeyer, that in the present case cicatrisation occurs on a scale pro- portionate to the colossal size of the ulcerating surface. We find the usual series of embryonic tissue, spindle-cell tissue, and rigid, short-fibred cicatricial tissue — each member of the series being deyeloped fi'om its predecessor, as is fully set forth in ^ dS et seqq. Tlie cicatricial tissue presents itself in no small proportions ; it forms a white and lustrous, fibroid stratum, from half a line to tln-ee lines in thickness, ydiicli clothes the serous cayity, and is stretched oyer the adjacent organs. This huge cicatrix contracts like any other scar, and causes mechanical effects of an imposing order. It is an admirable illustration of tlie gigantic results which nature is able to produce by the addi- tiye repetition of fractional moments of the same order. And yet the resistance to be oyercome during the healing of an empyema which has opened externally, is nothing less than that of the yaidted arches of the thoracic skeleton which haye to be dragged inwards, in a direction, that is, which the whole aim of their being is to resist. There is an erroneous impression, afloat, that the cicatrising process is able to help the expansion of Jthe collapsed lung. But experience teaches us, as might have been expected a priori^ that it is the fibroid tissue which serves permanently to compress the lung. Sooner than allow of any such expansion, the remaining thoracic viscera, sc. the heart, are dragged over to occupy the space which was formerly filled by the collapsed lung. Ko Torricellian vacuum is produced. The stress is borne by the neighbouring organs, which are dragged out of their places. The fibroid sac into NON-INFLAMMATORY TORMATIONS. 327 wliicli the pleura lias been converted must and will contract just as a urinary bladder contracts. And this contraction occurs with such force that not only are the soft and yielding thoracic organs compelled to follow it, but the ribs also are dragged downwards and inwards till they overlap one another like the tiles on a roof; the vertebral column itself undergoing a corres- ponding curvature. At the same time, the size of the cavity is proportionately lessened ; a few drops only of pus occasionally dribble from the fistulous orifice. And the process of repair is brought to a close by the total obliteration of the cavity. B. ISTOX-IXFLAMMATOEY FORMATIONS. § 279. Were I in this place to consider all the cancerous, sarcomatous, chondromatous and lipomatous affections which are occasionally met w^ith in serous membranes, I should be obliged, not only to recapitulate what has already been laid down con- cerning morbid growths in general, but to anticipate in great measure the diseases of the alimentary canal, the lungs, liver, &c. For the serous coat of any organ stands simply in the relation of adjacent connective tissue towards those heteroplastic growths which have their origin and seat in the parenchyma of the organ itself; and it is in this capacity that it shares in the neoplastic process. The present chapter will therefore be restricted to the consideration of such growths as originate primarily in the serous membranes and run their course mainly within their paren- chyma. § 280. Foremost among these stands that overgrowth of con- nective tissue which occurs in the -svalls of a serous sac during the continuance of a chronic dropsical effusion. The first stage of the process presents itself to our eyes as a milky cloudiness of the membrane. This is partly due to a moderate degree of thickening, but mainly to an alteration in the consistency of its fibres. Vircliow has given the name of " sclerosis " to that condition of the fibres of connective tissue, in which their bulk is but little altered, while their solid contents (i.e. their density) are considerably increased. Such fibres are stifFer tlian usual ; they are less capable of swelling by imbibition ; they are, upon the whole, more indifferent to reagents, and refract light 328 SEROrS MEMBEANES. more higlil}". It is this latter property \yhicli gives the sclerotic patches of the serous membrane their milky opacity. The essential nature of sclerosis is quite as obscure as that of the processes with which it is associated. As regards these, we do not know whether the transudation is simple or inflammatory ; as regards the sclerosis, whether the hyperplastic change belongs to one or other category. In my opinion we must draw as marked a line as we can between active and passive congestion ; hence we must seek the origin of the disease either in an inflammation, or in a passive disturbance of the circulation. In the majority of cases, our search will be successful. We cannot but admit, however, that passive congestion is a powerful predisposing cause of inflammation ; also, that in everj^ inflammatory hypersemia a statical element is evolved from the unquestionable dilatation of some portion of the circulatory tract. Accordingly, both sets of phenomeim are often intimately associated with one another, and are often so blended that it becomes a matter of the greatest difficulty to determine how much is due to the one, and how much to the other element. Instinctive tact and practical ex- perience are here our best allies. We usually regard the hydro- thorax of valvular disease as a passive transudation, while we take the dropsy of the tunica vaginalis propria testis (hydrocele) to be the type of an inflammatory dropsy. Between these ex- tremes we have dropsy of the pericardium and peritoneum, and dropsy of the ventricles of the brain ; the former more nearly related to hydrothorax, the latter to hydrocele. Efl'usions into bursas mucosae, the synovial sheaths of tendons, and the joints, are a debateable ground. The element of uncertainty, the dis- cretionary element, in this doctrine is due to the absence of available criteria for the determination of the exact point at which the transudation on the one hand, and the morbid gi'owth on the other, should begin to be called inflammatory. Julius Vogel attempted to establish a criterion for the inflammatory nature of the transudation in the presence of spontaneously coagulable albuminous substances {Hydrops fihrinosus^^ inflarn- matorius). But now we know that the fluid which accumulates in the pericardium during the death-struggle, and which cer- tainly is not inflammatory, contains fibrinogen. As regards the morbid product with which we are immediately concerned, an attempt has been made to erect it into an inflammatory forma- NON-INFLAMMATORY FORMATIONS. 329 i'lon 2^(0' excellence; a proceeding wliicli seems to owe the favour with which it has been receivedj only to the summary way in which it removes all scruples concerning the qucestio vexata of a definite boundary-line between hypertrophy and inflammation. To my mind, there really is no sharp line of demarcation between the two. Inflammation is but a perverted image of normal nutrition, and hypertrophy is but a minor degree of the very same perversion. Of course I do not presume to arrest all discussion by any dogmatic statement; on the contrary, I willingly admit that I do not feel myself in any w^ay ripe for a conclusive utterance on this subject. I seek only to justify myself for describing the changes with which we are now con- cerned, as simply hyperplastic, without attempting to prejudge their mode of origin and causation from the form which they assume. § 281. The " milky cloudiness " alluded to above, is pecu- liarly striking when it afffects the serous coat of a dark-coloured organ, especially the capsule of the liver or the spleen, and the visceral pericardium (tendinous spots of the heart). Were the brain not itself of a white colour, the sclerosis of the ependyma in chronic hydrocephalus would undoubtedly present itself to our eyes as a milky cloudiness. Sclerosis (to repeat what has already been said) is merely the lowest degree of hyperplastic overgrowth of connective tissue, as regards which it is still uncertain, whether we ought to consider it as a proliferative change, or as a simple condensation of pre-existing connective tissue. Besides sclerosis, we are acquainted with a whole series of connective-tissue proliferations, which have one feature in com- mon, viz. that they all tend to assume more of a circumscribed character. In closest relationship to sclerosis, we have the development of sharply-defined, flat elevations of cartilaginous texture. These are most common on the capsule of the spleen, Avhere they exhibit angular outlines and a yellowish- white translucency, and may attain a height of from half a line to one line. On the plem-a they are more circular and transparent, with a lenticular surface ; while on the tunica vaginalis of the testicle they are characterised by their often considerable size and hardness. These cartilaginous elevations are closely related to the cartilage of the cornea in their minute structure. Next 330 SEROrS MEMBRANES. to them stand fil/romatoiis outgrowtlis. These are especially prone to become polypoid. In the dropsical tunica vaginalis testis, and in the peritoneal cavity, "\ve occasionally meet with free fibrous bodies, varying in size from a cherry-stone to a hazel-nut, of a spherical or spheroidal shape and concentrically laminated structure ; these are simply the detached heads of such polypoid excrescences from the walls of the cavity. The softer dendritic vegetations^ which are less frequent on serous than on synovial membranes, are described by Rohitanshi as follows : — " Their first appearance is in the form of club-shaped hyaline vesicles (minute granulations of embryonic tissue, Ilindfleiscli) I these grow into an arborescent structure, and pro- duce connective tissue in their interior. The clavate extremities of the twigs and branches commonly become flattened into lenticular or melon-seed-shaped bodies, and sometimes exhibit a facetted surface. The primitive nodule often grows into a sacci- form cj'st, filled with serum, or with a fibrous network whose interstices contain fluid." \\q may call the latter form a pen- dulous myxoma. It constitutes a transition stage to the com- plete liquefaction of the contents of the nodule, which then becomes a pedunculated '^ cyst due to sofi:ening " (Erweichungs- cyste). The latter are most frequently met with on the perito- neum, and especially on that part of it which clothes the female generative organs — the broad ligaments, ovaries, and Fallopian tubes. § 282. The lipoma arhorescens of Midler is peculiar to serous and synovial membranes. I have already pointed out in detail (§ 133) the close analogy which subsists between the central growth of lipomatous tumours, and the dendritic type of struc- ture. We might fairly regard the Lipoma arhorescens as a lip>oma tuherosmn, broken up into its component elements ; but it is better to regard it simph' as a hyperplastic development of tlio familiar villous and polypoid fatty appendages of the serous and synovial membranes (o^^p. ejnploicce, glandidw Ilaversiance, S^'c). § 283. As regards the heteroplastic formations (cancer, tubercle, sarcoma) which occur either primarily or secondarily on serous membranes, there is only one question which interests us as histologists — that concerning the origin of the embryonic tissue, which as we know, forms the common basis of them all. These growths (when they really spring from the serous NON-INFLAMMATORY FORMATIONS. 331 surface, and have not been propagated per contiguiun from neigh- bouring organs) are all strikingly characterised by their very superficial position. Scirrlms looks like a pasty mass "whicli has been uniformly spread out over the serous surface" {Rohi- tanski) ; medullary cancer resembles scirrhus, or takes the form of roundish flattened protuberances ; colloid cancer occurs '- in the form of nodules, which occasionally grow to an amazing size, and are almost free in the serous cavity, i.e. adhere to its walls by a few insignificant vascular attachments " ; the spindle- cell sarcoma as a fungoid vegetation. Finally, the miliary tubercle looks very like a grey, miliary A^esicle. Most of these growths can readily be scraped from the serous surface with a knife ; the latter is left somewhat rough, but without any im- portant loss of substance. It is quite clear that the quantity of connective tissue which lias been requisitioned from the healthy serous membrane by the growth, is extremely small ; hence it is on serous membranes that we are best able to study Fig. 107. MiUary tubercle of the omentum, -^^q, {Mch.) the essential texture of these growths, with least risk of being misled by adventitious constituents. To what is this superficial localisation due ? It is due to tlie fact that these tumours, taken in the aggregate, are — at least primarily — outgrowths from 332 SEROUS 3IEMBIIANES. tlie epithelial lai/er of the serous membranes. Nothing hmders them indeed from spreading afterwards, not only into the paren- chyma of the serous membrane, but also through the parenchyma into neighbouring organs. Wherever connective tissue exists, a path is open to them. We must not forget however, that the epitheha of serous membranes are themselves connective-tissue corpuscles. § 284. One example will suffice to illustrate this highly peculiar mode of origin. I choose a miliary tubercle on the omentum. Fig. 107 represents a very small nodule (under a lo^v power), which has not yet grown out of the limits of its birthplace. It consists of a globular aggregate of cells, suspended from nine slender threads of connective tissue radiating from its periphery to the stouter and partly vascular trabecula3 Avhich form the boundaries of one of the larger meshes of the omentum. Let us examine one of the nine points at which the con- nective-tissue fibres join the nodule, under a higher power, (X 800). Here, at the edge of the formation, we may expect, if the nodule is still growing, to find a^^pear- ances which w^ill shed light u]3on the details of its origin. We find what is represented in fig. 108. The nodule grows by proliferation of the epithelial cells. The homogeneous lamella is raised from its bed on one side of the thread of connective tissue, while on the other, it has been shed altogether ; the place of the nucleated protoplasm is taken by larger and smaller groups of young cells, which have clearly sprung from it by a process of fission. The substance of the thread itself is unaltered up to the very edge of the nodule. Here it escapes our obser- vation; but in the interior of the nodule it is still connected with the other eight threads in precisely the same way as it was before the iiy ^'oliferation gi'owth of the tubercle. It obviously takes no of the serous part in the proliferation ; and up to this point ImcIi). ^^' ^^' ^^® ^^'® entitled to regard the whole of the new growth as a product of the serous epithelia. Should the centrifugal growth, at a later stage of its progress. Fig. 108. X'"^ ^ ^^ Origin of a mi- liary tubercle NON-INFLAMMATORY FORMATIONS. 333 reach the thicker trabecula3 (fig. 107, a) of connective tissue, then indeed non-epithelial connective-tissue corpuscles will con- tribute their mite to the additive enlargement of the nodule. But the size to which the nodule must needs attain before this can possibly occur, proves what the resources of epithelial growth can do without anv extraneous help. lY.-MOEBID ANATOMY OF THE SKIX. § 285. In studying the structural alterations associated with the various disorders to which the skin is liable, it is of advan- tao-e to consider that organ as made up of the epidermis and papillary body on the one hand, of the corium and subcutaneous areolar tissue on the other ; the morbid anatomy of the cutaneous 2;lands and the hair being considered by itself in an Appendix.* Tlie papillary body, apart from its other physiological functions, is the matrix of the epidermis. The two structures constitute a vegetative whole; and their continuity is strikingly apparent when, as in the case of most diseases, the vegetative relations of the parts are disturbed. So too the glands, the hair and the nails are all liable to special diseases of their own. Of course I neither care, nor do I wish to deny that the disorders of the various constituents of the integument pass into one another by manifold transitions, that they may coexist, that they may be pathologically identical. No classification of natural objects can lay claim to be absolute ; we must endeavour to select that w^hich fits the actual facts most closely. Thus for instance, a similar analysis of the structural constituents of mucous membranes would be far from conducing to a better knowledge of their pathology. 1. Diseases op the Epidermis and the Papillary Body. a. Inflammation. § 286. The integument of the body is peculiarly exposed by its position to all external influences of a hostile nature. We are not therefore surprised to find a long series of skin- * The nails will be dealt with among the horny overgrowths of the epidermis, the keratoses. INFLAMMATION. 335 diseases caused by external irritants. And here ^vc must not confine our thoughts to single impressions of a violent kind, such as blows and knocks, but include likewise those more chronic or recurrent irritations of the surface, trifling in themselves, which are caused by dirt, vermin, scratching, exposure to the weather, improper clothing, and the operation of chemical and mechanical irritants. These trivial sources of irritation are nevertheless powerful enough to affect the specially sensitive papillary body, richly supplied as it is with vessels and nerves, through its cuticular covering. The papillary body reacts to the stimulus by hyperaemia and inflammation ; its disordered state is shared by the epi- dermis, and we thus obtain a group of changes, which are confined, at least in their beginnings, to the papillary body and the cuticle. There is yet another cause to be considered. We know that in infectious diseases, when the general malady has reached a certain height, some individual organ is usually specifically in- volved. We express the fact by saying that the disease becomes localised, and with this phrase we connect some vague idea of an elimination of the materies morhi. It is true that these foci of disease are very commonly situated in secretory organs. In small-pox, measles, and scarlet fever, the skin is the selected organ ; it is supposed moreover that nettlerash, erysipelas, some forms of herpes, and a large proportion of chronic dermatoses, depend on the localisation of some constitutional disease. Now what occurs in ever}^ one of these cases is not a mere abnor- mality of the secretion, as might be inferred from the humoral- istic idea alluded to above, but hyperaemia and inflammation ; moreover, at least primarily, it is not the whole skin but only its most superficial layers which are involved. The papillary body, strange to say, is the chief seat of the disorder, even when the skin-lesion has been excited by causes operating from within, through the blood. Should this, like our former category, be ascribed to the greater sensitiveness of the papillary body ? By no means. We must look elsewhere for the causes of this locali- sation ; and for my own part I cannot help ascribing a peculiar influence in the matter to the distribution of the vessels. Normal histology has explained the way in which the vessels are distributed in the papillary body (fig. 109). Each papilla is 336 MOEBID ANATOMY OF THE SKIN. furnisKed with its own afferent and efterent caj^illaiy vessel : tlie two communicate either directly, by a simple loop, or — more commonly — by a number of loops. These vessels are all remark- ably tortuous ; it sometimes happens that the afferent and effererit trunks of a simple capillary loop are twisted round each other corkscrew-fashion till they unite at the apex of the papilla. The point at which they unite — the summit of the curve — is always much dilated. Everything points to the conclusion that in the cutaneous papilla the lateral pressure of the blood must be augmented and the current of the circulation retarded. Indeed we may look upon the vascular apparatus of the larger papillse, which are provided with several communicating loops, in the light of small retia mirabilia.* They stand towards the vascular network of the cutis in the relation of diverticula ; like the side- channels of a stream, in which the current experiences greater resistance, notwithstanding that the fall is the same in either case. This arrangement may have a physiological importance of its own, it may be of the utmost moment for the respiratory function of the skin ; apart from this however, it serves to explain how it is that hyperasmic conditions of the skin, to what- ever cause they may be due, are peculiarly intense and lasting, and lead to more serious consequences in the papillary body than elsewhere. What is true of the papillary body as a whole is peculiarly true of the smaller, but all the more thickly-set papilla which surround the orifices of the hair-follicles (fig. 109). Here too therefore, in connexion with hypersemic conditions of the entire tegumentary system, the dilatation of the capillaries, the slowing of the blood-current, and all the derived phenomena, attain their maximum intensity. In a word, the vascular apparatus of the subepithelial connective tissue of the skin is disposed in such a way as to bring the limitation of so large a number of derma- * In injected specimens of the kidney, I have often observed that the Malpighian glomeruli are also made up of two or three capillary tufts (Gefassbaumchen), each of which corresponds precisely to the capillary tuft of a papilla. It is not impossible that the Malpighian glomeruli may originate as papillary excrescences from the coecal ends of the uriniferous tubes. (?) {Cf. Eenle, Handbuch d. Systemat. Anatomie, Braunschweig, 1862. Eingeweidelehre, p. 310, a, h, figs. 237. 238.) ^-1 ( - ^r7M- ir^^ k«k ^4 '-■'. -^"^'^^-A -^' ..^-:^^^^^^^ '^..^^-^//i?( Vertical section through the skin of the lower lip (after Thiersch), a. Horny lamina of the epidermis, which is con- tinued into the hair-sacs as the inner root-sheath ; h. Seba- ceous glands; c. Sweat-gland; cZ. Vessels ; e. PapilljB of the roots of the hair. 22 338 MORBID ANATOMY OF THE SKIN. toses to the epidermis and papillary body under a common law. § 287. We include the large assemblage of these superficial dermatoses under the name of eruptions, exanthemata. Every exanthem begins with hypera?mia of the papillaiy body. This is the first sign we have that the part is being irritated ; it is the starting-point of all the subsequent excesses and abnonnalities in its nutrition. Even at this early stage, we are struck by the contrast between the manifold variety of the coarser anatomical appearances, and the monotonous uniformity of the microscopical alterations. The major part of general dennatology may be legitimately considered as so much morbid anatomy. There is nothing to hinder the anatomist from describing and distinguish- ing the various naked-eye appearances, sizes, and positions of the maculae, papules, bullae, pustules, &c., quite as elaborately as the professed dermatologist. Pathological histology however knows nothing of all this diversity ; here, as elsewhere, it shows from what simple elements nature can procure the most complex results. It recognises, strictly speaking, only two sets of morbid changes, which, either singly or in combination, make up the various exanthemata. These elementary categories may be designated as the ^^simple inflammatory" and the ^^hyper- trophic inflammatory," the latter serving as a convenient transition to the simple hypertrophies of the papillary body, such as warts, &c. These divisions coincide very fairly with those based on the time which each disorder requires to run its course; thus the simple inflammatory may be called rapid or acute, the hypertrophic inflammatoiy slow or clu'onic, while the non-inflammatory hypertrophies include those forms which seldom get well if left to themselves. We must bear in mind however, that the terms '' acute " and ^* chronic," as we now use them, are not synonymous with the same terms as employed by dermato- logists; that ice refer only to elementary lesions, and that an exanthem, which might justly be included in the chronic category of dermatologists, may really be made up of continual repetitions of an acute inflammatory process. It is desirable to guard against such misconceptions from the first. Even at the risk of saying the same thing twice over, we will narrow or extend the limits of the fundamental types of exanthematic ERYTHEMA. 339 inflammation so as to make them agree with those employed in cutaneous pathology, and leave it to our readers to simplify matters farther by means of such abstractions as have just been hinted at. § 288. — 1. The erythematous e.vanthem. Simple erythema, even when it amounts to a positive turgescencc of the cutaneous capillaries, would hardly be supposed likely to afford materials for histoloo^ical investi^iation, were it not for the recent obser- vations of R. Volkmann and Steudener (Centralblatt, 1868, 36) on erysipelas ; these observers prove that in the course of this essentially erythematous inflammation of the skin there occurs a very extensive migration of leucocytes into the cutis and subcutaneous areolar tissue ; true, these leucocytes disap- pear in two or three days by disintegration and absorption ; still, they serve to show how easily a simple erythema may pass into those higher grades of inflammation, which it invariably precedes. Moreover, even a transient erythema usually leaves some vestiges of its presence behind it. It is usually followed by a desquamation of the outermost layer of the epidermis, whether branny (desquamatio furfuracea) or follaceous (desquamatio memhixmacea). This phenomenon can only be explained by the close connexion which subsists between the nutrition of the epidermis and the changes occurring in the papillary body. Every hyperaemla involves a disturbance, an interruption in the nutrition of the epidermis. The details of this are not known. So much seems certain, that this disturb- ance causes a separation of the epidermis into an outer, less nourished, and an inner, better nourished layer. This separa- tion manifests itself as a real though imperfect cleavage, or rather loosening of the substance of the cuticle between its horny and its mucous strata, without the intervention of exuda- tion. When in the course of growth the oldest portions of epidermis come to be shed, a simultaneous detachment of the deeper and younger layers of the horny stratum bears witness to their premature death and consequent separation from their native soil. We distinguish between diffuse and circumscribed erythe- mata. It often happens that an erythema which is at first diffused, becomes concentrated in course of time at one or more 340 MOKBID ANATOMY OF THE SKIN. points of the cutaneous surface which lie within its area ; and in proportion as this occurs, we may anticipate further changes of an inflammatory kind at these points. § 289. — 2. The pajndar exantliem. By a papule we under- stand a slight elevation of the cutaneous surface, which feels like a little solid nodule seated on the skin. The papule originates by the passage of an inflammatory hyperemia into exudation, w^ithin a limited area of the papillary body. The exudation is not situated in the epidermis. This stretches unaltered over the enlarged papillae ; it is more tense and elastic than usual owing to its extension over a larger area. The exudation is situated in the substance of the papillf:e. They are saturated with an abundant supply of nutrient fluid — not with cells (at least in recent cases). We shall find here- after that formative changes are superadded when the papule ha& lasted for some time, and especially if it proceed to become a pustule. The individual papilli^ are markedly enlarged. It has been asserted that they undergo, not so much an elongation and thickening at their apices, as an expansion at their bases, so that the level of the surface is in some sort depressed within the area of infiltration. This assertion hardly admits of proof or disproof, inasmuch as any direct observation is as good as impracticable. For, like many other infiltrations of the connective tissue, this infil- tration disappears during or immediately after death. The elastic reaction of the stretched cuticle drives the exuded fluid back into the vessels as soon as the cessation of the vis a tergo allows it to do so. We find patches of skin which, a short time before, exhibited the eruption in all its distinctness, apparently quite healthy. For my own part, I believe that the shai'ply circum- scribed character of the papular elevations points rather to a turgescence of the slightly bulbous tips of the papillae. The affection is very prone to select the ring of small, closely- set papillae which surrounds the orifices of the hair-follicles. Such papules are circular in outline, of considerable size, and perforated at their centres by a hair. Hehra assumes that in these cases a minute quantity of fluid is previously exhaled between the horny and the mucous layers of the epidermis. Here too I must say that I failed to discover any fluid in the substance of the epidermis ; but the point does not seem to me of much moment. PAPULE. — WHEAL. 341 Most papules are redder than the surrounding skin ; this is no more than might be expected, since the formation of a papule is preceded by a concentration of the hyperaemia at the affected point ; the occurrence of exudation however, tends to check the hypertemia by taking up the available space, and so squeezing out the blood — the only constituent of the papilla which is free to escape. Thus it may happen that the papules are not redder than the surrounding surfiice, but of the same colour, or even paler. Papular eruptions are most common in connexion with measles. § 290. — o. The wheal stands in close anatomical relation- ship to the papule. Wheals {pomphi) are broad and flat elevations of the skin, firm to the touch, as may readily be perceived by passing the hand lightly over them. The smaller wheals, those no bigger than a lentil, are circular ; larger ones, often of very great size, are produced by the confluence of the smaller ones and accordingly exhibit the utmost irregularity of outline. The smaller wheals are of the same colour as the surrounding skin ; they are seldom redder. The larger however and especially the more raised the wheal is, the more does its redness appear to be pushed to one side and concentrated in a narrow band along its edge, while its central part grows more and more pale. Finally vfc may have white wheals with a red areola. These may be regarded as the highest stage in the development of the lu'tical exanthem. The wheal is an acute inflammatory oedema of the papillary body. The exudation is thinner and more serous than in the case of the papule ; hence too, the rash is so very fleeting, that it may readily be increased by scratching, while it quickly fades without any trace, if left to itself. The seat of the infiltration has been already indicated. In the higher degrees of pomphosis the papillary body is swollen to such an extent that the flow of blood through it is completely arrested ; the blood which is meant to supply the part is retained at its periphery, where it accumulates. The red areola of the white pomphus is there- fore due to collateral hyperasmia resulting from the imperme- ability of the capillary networks in the interior of the swollen region. 342 MORBID ANATOMY OF THE SKIN. Pompliosis, as a transient oedema of the papillary body, in- terferes less with the nutritive processes in the skin than any other exanthem ; it is never followed by any more profound disorder ; seldom even by branny desquamation of the cuticle. Among the external irritants best adapted to produce this eruption are the sting of the nettle and that of some insects ; among internal ones certain articles of diet (strawberries) and the specific cause of nettle-fever (Nesselfieber). § 291. — 4. The vesicular or bullous exanthem. The papule and the wheal showed us the exudation arrested in the peri- vascular connective tissue, on its way from the capillaries of the papillary body to the surface of the skin. The vesicle or bulla takes us a step farther. The exudation is now in the substance of the epidermis ; it accumulates between the mucous and the horny layers ; the latter is raised and arched out- wards like a knob. The terms ^^ vesicula " and " bulla " are both employed to designate this condition; their difference is one of degree only. The Aesicle includes those which are not bigger than millet-seeds ; the bulla includes all which exceed this size. A vesicle may be broadly said to originate in the transuda- tion of a fluid from the vessels, which forces its way up from the distended capillaries of the papillary body, passes through the rete mucosum, and is arrested by the horny lamina. The cells of the latter are so firmly united, partly by the close way in which they are packed together, partly too by a sort of sutural connexion of their channelled surfaces, that they form a con- tinuous tough membrane, impermeable to fluid, and well adapted for retaining and roofing in e^en larger quantities of it. The mucous layer is variously afl^ected in diflerent cases. If a bleb is developed very rapidly, as e.g. in gangrene, the soft bodies of the cells are mechanically stretched into slender threads by the force of the transuding current — threads which give a mossy roughness to the surface of the papillary body. Should the transudation take place more slowly, as" in Herpes and Ery- sipelas bullosum (Haic/ht), the deepest layer of the rete Malpighii remains unaltered, while the " intermediate" epithelium-cells are partly detached, partly pushed aside. The transuded fluid wells up with greater force from the apices of the papillae than from the interpapillary furrows ; hence the layer of cells above VESICLE. — BULLA. Mt alluded to is stripped from the papillae, while remaining attached to the bottom of the furrows. A system of cellular membranes and trabeculsD is thus formed ; these structures extend more or less vertically across the interval between the horny layer and the papillary body; the thickest ones spring from the interpapillary fissures ; they grow more and more slender in proportion as they recede towards the summit of the papillary elevations. These trabeculse are all made up of nucleated " in- termediate " cells, which have been stretched and flattened out mechanically. The thinnest bands consist of single cells, often drawn out into several processes. If the transudation is more copious, the trabeculce, whatever their size, are torn across, one- half adhering to the detached horny layer, while the other is retained by the papillary body. It is only in miliary vesicles that the fluid is contained be- tween the layers of the horny lamina {HaigJit) ; but the intimate connexion of this exudation with the perspiratory secretion makes us hesitate before reckoning miliaria among vesicular erup- tions at all. The fate of the vesicles is different in different cases ; they may burst and discharge their contents, or they may remain stationary until the hypersemia remits and allows the exuded fluid to return to the blood. The pressure of the stretched homy lamina, whose elasticity is well known, may contribute to the latter issue. That this force ought really to be taken into account, is plain from a consideration of blebs with a hypersemic areola. In these, the contents of the bleb compress the underlying vessels to such an extent, that the afflux of blood is checked, and stagnation consequently occurs at the margin of the bleb. The strata of epidermis which have once been sepa- rated cannot however reunite. Even when the horny lamina is closely applied to the underlying stratum, and the status quo ante has apparently been re-established, we still find that the affected lamellae wither and are shed before their time. Mean- while a new homy lamina is developed at the expense of the rete Malpighii. This continues abnormally thin for a long period ; the vessels of the papillary body shine through it so brightly that the size and shape of the former bleb may be recognised for weeks and weeks as a red spot. The histological details of this renewal — what part of the papillary body is mainly instrumental in the process, how strati* 344 MOHBID ANATOMY OP THE SKIN. iication is i^rodiiced, &c. — all these are questions wliicli normal histology must answer ; it has not answered them yet. This issue is known as "desiccation of the bleb:" it has to be dis- tinguished from another and less favourable one, which may be briefly called " suppurative metamorphosis." This trenches however on another department of our subject. Vesicular and bullous eruptions are extremely common ; they are caused by external and internal irritants of all sorts. Among the former may be enumerated heat, blisters and epi- spastic fomentations, mechanical irritants, scratching, and re- curring pressure ; among the latter. Herpes, Pemphigus, Measles, &c. § 292. — 5. The pustular exanthem. The term " pustule " is summarily employed in dermatology to denote every circum- scribed accumulation of pus under the epidermis. Accordingly the pustule is a sharply-defined straw-coloured elevation ; and if w^e add that it is always circular, often provided with a central depression or umbilicus, and girdled with a red areola, we shall have gone far to exhaust its denotation. Now it is obvious that such accumulations of pus may arise in the most diverse ways ; and this qualifies the value of the above defini- tion. We set aside for the present such pustules as are due to suppuration in the deeper parts of the skin (e.g. round hair- sacs) and confine otu' attention to those two varieties in which the starting-point of the suppuration does not extend below the level of the papillary body. a. We have just seen that pustules may originate from vesicles ; this occurs in Eczema, Impetigo, Herpes, Pemphigus, and Ecthyma. We may observe the gradually increasing turbidity of the vesicular contents even with the naked eye : by subjecting a drop of the contained fluid to microscopical examination w^e may convince ourselves that the opacity is due to the presence of detached epithelial cells and numerous pus- corpuscles. At a later stage, the pus-corpuscles predominate ; and when the process has reached its height, we are quite justi- fied in summarily calling the contents of the vesicle a rather thin and fluid pus. A vertical section tlu'ough the skin (fig. Ill) shows the outline of the papillary body in a state of good preservation, but with its substance permeated by a large number of young cells which accumulate at the apices of the PUSTULE. 345 papillae to such an extent, that at these points a layer of such cells extends uninterruptedly to the deepest stratum of the rete Malpighii. This can still be recognised on the sides of the papillas and in the furrows between them, if we make use of the yellowish colour and erect position of its columnar cells as a guide. The state of things over the apices of the papillge is very different. Here we can no longer distinguish any line of demarcation between epithelium and connective tissue ; it is only by dissecting the parts with needles that we find it possible to say : here is the boundary of the papillag ; there begins the cuticle. For my own part I cannot doubt that this is the main source of the young cells which we find in the contents of the vesicle. The irritated papillary body is in a state of the most exuberant proliferation ; the young cells travel towards the surface, where they are set free as embryonic cells and pus- corpuscles before they have time to become developed into epithelia. Some may possibly force their way through between the cells of the rete Malpighii ; the majority migrate outwards from the tips of the papillae where the rete has given way and where the relation between the secreting surface and the secreted products is precisely the same as on a granulating surface. The whole process is thus seen to be an acute purulent catarrh of the skin. If we take the preliminary vesicular stao-e into account we may speak of a catarrh originally serous, w^hich has passed into the purulent stage.* Recovery from this state may take place in various ways, according to the treat- ment adopted. If things are left to themselves, a scab is speedily formed by the drying up of the purulent contents of the bleb ; under this scab the formative actions become gradually slower, and end in the production of a new epidermic coat. The scab has been regarded by many as a sort of roof under cover of which nature could proceed undisturbed to the renewal of the epidermis. The hypothesis is as false as it is attractive. The scab is simply a mass of dead and dried organic matter, * The word "catarrh" is usually employed to denote the analogous morbid conditions which occur in mucous membranes. Accordingly I shall discuss the special histology of catarrh among the diseases of those membranes. 346 MORBID ANATOMY OP THE SKIN. which tends to undergo further decomposition and putrefaction so soon as it is supplied with enough moisture for the purpose. If we reflect that the papillary body in its catarrhal state yields enough flviid to set this i:)utrefactive process going, and that decomposing and therefore irritating matters are being con- tinually produced on the under surface of the scab, the surface which is turned towards the papillary body, we cannot but con- clude, and our conclusion will be justified by clinical experience, that so far from exerting any salutaiy influence, the scab is positively a hindrance to the reparative j^rocess ; peculiarly favourable conditions, such as a very rapid recession of the hypersemia, a very complete degree of desiccation, &c., being needed, to allow of the catarrhal process healing underneath the scab. The denuded surface is clothed in just the same way as it is after the desiccation of a vesicle. I have indeed observed that concentrically-laminated globes, the so-called '^pearly nodules," are exceptionally frequent in the new cuticle produced under such circumstances ; this hov>^ever is undoubtedly owing to tem- porary irregailarities in the process of stratification. § 293. The case is dift'erent when we have to do with an eruption which, for other reasons, has no tendency to get well ; when the vesicles and pustules are merely the acute beginnings of a chronic catarrh. For instance, some forms of eczema aff*ecting the legs are essentially due, not to external irritation, but to chronic disturbances of the circulation, to venous hyper- semia and phlebectasy. These afford us our best opportunities for observing chvonic catarrh of the skin. Its phenomena depend on a clu'onicity and increasing intensity of the hyperemia of the papillary body. This causes in the first place, and directly, the continuance of secretion from the affected patch. Large quantities of transuded fluid force their way to the surface ; the purulent character of this secretion standing in an inverse ratio to its volume, since the rate of production of the pus-corpuscles remains constant, while the transudation increases considerably in amount. Finally we get a fluid which is almost clear, and very rich in salts ajid albumen; its enormous quantity sets all bandages at defiance (" Salt Flux"). The skin undergoes a progressive alteration which may briefly be described as an inflammatory hyper- PUSTULE. — CHRONIC CATARRH. 347 trophy. This is also due to the hyperaemia of the papillaiy body ; at least it is always the papillae which begin by growing at the expense of the embryonic tissue produced at their apices, just as happens in the growth of granulations. We may occasionally observe, even with the naked eye, little red buds sprouting up, which exhibit all the histological characters of granulations, but which are merely the enlarged — or, if the term be preferred — the degenerated papillae of the skin itself.* § 294. As the disease progresses, the state of irritation which was originally confined to the surface, extends to the deeper layers of the skin, to the cutis and subcutaneous areolar tissue. This serves to connect chronic catarrh of the skin with those conditions which are described under the name of Elephan- tiasis in the second part of the present chapter. It is difficult to determine how far this may depend on the catarrhal irrita- tion of the surface, in what measure it may be considered as a reactive hypertrophy; and what share belongs to the predis- posing cause of the eczema itself, to the distm^bance of the circulation of the blood and lymph, and how far therefore the morbid changes deserve to be regarded as an independent disease ; I will therefore break off the thread of my exposition at this point and take it up again when I come to treat of Elephantiasis. At present I will only speak about the tendency towards recovery, and the actual process of repair, in chronic catarrh. We have traced a close analogy between the papillary body in its catarrhal state and the surface of a granulating wound ; the * This illustrates very strikingly the close connexion between hyper- plastic and heteroplastic evolution. Those who are inclined to dis- tinguish sharply, not merely between hyperplastic and hetcroiDlastic growth, but between inflammatory heteroplasia and heteroplastic tumours, between simple and iniiammatory hypertrophy, will do well to take this lesson, which skin-diseases offer, to heart. We may and ought to avail ourselves of these definitions for the purpose of giving clear- ness to our conceptions of the phenomena, but we must beware of ele- vating them to the rank of rigid formula. Kone such exist in nature, which reconciles all contrasts. In the present case, the development of embryonic tissue at the junction of the epidermis with the connective tissue, belongs, up to a certain point, to the normal plan of evolution of the skin; no sooner however does it overstep this limit, than it at onco converts the cutaneous surface into a granulating sore. 348 MORBID ANATOMY OF THE SKIN. analogy may be extended to its mode of healing, which closel}' resembles that of repair by the second intention. The phe- nomena exhibited by the cutis must be viewed as analogous to that '' cicatrisation from helow^^ which, as the reader may re- collect, plays so momentous a part in repair by the second inten- tion (cf. fig. 39, c, § 104). These phenomena consist of a very curious combination of two processes which act in opposition to each other, viz. the production of cicatricial tissue, and an in- crease instead of a diminution in volume. We shall have to return to the consideration of this point under the head of Elephantiasis. It cannot be doubted that these phenomena react upon the state of the surface ; on examining vertical sec- tions (fig. 110) we often find the remains of obliterated vessels, recognisable as pigmented striae, mounting obliquely towards the dermal surface ; we may legitimately infer that their obliteration must have hindered the supply of blood to the papillary body. It would however be a great mistake to ground any hopes of the healing of the affected surface on these processes in the cutis, as in the case of repair by the second intention. On the contrary, everything depends on the treatment to which the diseased part is subjected. Nature must be helped by astringent and sicca- tive remedies, but chiefly by a systematic application of pressure. Under such conditions recovery takes place by a gradual reces- sion of the proliferated papillae, and a skinning over of the entire surface. The diminution in size of the papillae is operated partly by the return of the infiltrated fluid into the blood, partly by the fatty degeneration and absorption of large numbers of corpus- cular elements. Intercellular substance appears between the cells ; hairs, glands, and nerve-fibres are no longer to be found : they have obviously perished in the stormy activity wdiich pre- vailed in the connective tissue around them : but nothing is known about the way in which they are destroyed. The papilla3 never reach their normal height ; in fact it is only the shallow undulations of the l^oundary-line between connective tissue and epidermis which indicate their existence (fig. 110). In marked contrast to a granulating sore, the skinning-over of the surface starts from several centres at once ; it proceeds from within outwards as well as from without inwards ; this anomaly is due to the presence everywhere of remnants of the old rete Malpighii, which may proceed directly to the formation PUSTULE. — SMALL-POX. 349* of a new horny lamina. The horny layer continues very thin for a long time, and we know how easily a renewal of the flux may rupture the delicate membrane and so re-establish the disease as soon as it is cured. It is worth notice that in cases of permanent recovery the deepest cells of the rete Malpighii exhibit a striking tendency to become infiltrated with pigment (fig. 110) ; this manifests itself to the naked eye as a brownish staining, diffuse or circumscribed, of the affected patch of skin. § 295. — h. The second variety of exanthematic pustule — the 2^ocJc — is undoubtedly the most interesting of all cutaneous Fig. 110. ^^:: Vertical section through the skin after chronic eczema. a. Horny lamina; b. Mucous layer of the epidermis; c. Pigmented layer of columnar cells ; d. Papillary body ; e. Cutis traversed by streaks of pigment. eruptions from a histological point of vie\^'. The pock is at one period of its existence a simple pustule, but that is before it has attained maturity ; moreover it arrives at this stage by so peculiar a road, that it is entitled on both grounds to an independent position. The pock originates as a papule on a very hypersemic base. This proposition, which is repeated by all text-books, may be allowed to pass unchallenged, if we choose to term every hard, nodular elevation of the cutaneous surface a papule. But it 350 MOHBID ANATOMY 0¥ THE SKIN. must be remembered that the small-pox papule differs very essentially from the papules we have already described (e.g. the papule of measles). The small-pox papule is situated, at least in great paii, in the substance of the epidermis, not underneath it. It begins, apart from the hyperaemic condition of the papillary body, as a circumscribed "parenchymatous inflammation" of the epidermis. I use this word under reserve. That peculiar <:loudiness and swelling of the cells which was discussed in § § 36 and 37, and which meets us here once more, has not in my opinion established itself on a very firm footing, as yet, in general pathology. The circumstance that the swelling leads as often to fatty degeneration as to endogenous multiplication, renders it doubtful whether it ought to be considered as a pro- gressive or as a retrograde metamorphosis of cells. The present ease is undoubtedly one of incipient productive activity, whicli may therefore rightly be called "inflammatory." It is neither in the deepest nor in the most superficial layer of the epidermis that the swelling begins ; its starting-point is in the middle strat:im, which we have already described as com- posed of " intermedi.ite cells," and as belonging to the mucous layer. These cells are no longer naked, like those smaller elements which are in immediate contact with the papillary body ; they possess a membranous investment whose surface already exhibits here and there that delicate grooving which was first discovered by M. Schultze. The presence of a limitary membrane renders it impossible for them to respond to the inflammatory stimulus by simple fission ; their proliferation must take place by endogenous development. But the first stage of endogenous growth is that same " cloudy swelling " which is followed by segmentation of the enlarged protoplasm and the transformation of the " segmentary sj^heres " into pus-corpuscles (cf the description in § QSj fig. 30). § 296. The shape of the individual pock is always circular ; more complex forms are always due to the confluence of adjoin- ing papules. This j^culiarity, as may be shown in the case of many pocks, is due to a concentric arrangement of their ele- ments round the orifice of a hair-sac or sweat-gland. These pocks may be distinguished from the rest even with the naked eye. They exhibit a central depression, the " umbilicus." Everybody knows that both the rete Malpighii and the PL^STULE. — SMALL-POX . 351 lioruy layer of the epidermis are prolonged into the hair- sacs. Now if the swelling — or still more that serous saturation of the rete Malpighii of which I am about to speak — extends to the circumference of the follicular orifice, then the horny epidermic lamina which lines the follicle (the inner root-sheath) will act upon the enlargement as a central retinaculum (or bridle) ; and will thus prevent the middle of the pock from rising to the same height as its peri- phery. The epithelium which lines the ducts of the sweat- glands is less tough than the inner root-sheath of the hair-sacs. It owes what cohesive j^ower it has to its being stratified in a plane which cuts that of the cuticular strata at right angles or obliquely. But the morbid change does not even involve the parts in immediate contact with the duct. At all events I have many specimens in my possession which exhibit the ducts of sweat-glands with the tissues immediately surrounding them as the retinacula of smallpox papules (fig. Ill, a).* g 297. The next step in the developmental process is the conversion of the papule into a pustule. This is invariably preceded by a serous infiltration of the epidermis. A clear fluid forces its way up from the papillary body, and raises the horny lamina of the cuticle ; it does not detach it from the mucous layer as in the production of a vesicle, but forces itself between the lamellce of the latter structure, pushing them asunder, and displacing them to such an extent, that from having been horizontal they come to occupy an oblique or vertical position (fig. Ill, h). This gives the upper part of the pock a chambered ap2:>earance, which has long attracted the notice of pathologists and has induced many to ascribe a loculose structure to the entire pock. This is decidedly incorrect. It is only the upper portion, the " dome " of the pock, which is * Aasjjitz aud Basch {Vlrclioiv's Arcliiv xxviii.) explain the umbilica- tion of tlie pustule in a way wliicli does not seem to me very plausible : '•' The swelling of the individual cells keeps^ extending in all directions from the affected centre ; consequently the efflorescence as a whole, increases in bulk ; the formation of pus in its centre proceeds but slowly at first, and the pus is enclosed by the peripheric accumulation of sv7ollen cells as by a capsule; the latter growing continually larger, without the pus-formation in its interior being able to keep pace with it." 352 MORBID ANATOMY OF THE SKIN. chambered. It is from this that we are able to obtain, either by a series of fine punctures, or by a single shallow horizontal incision, which separates only the horny lamina, that clear OJ. Pit p ai E O O -+5 w n,. lymph which plays so important a part in the propagation of cow-pox. § 298. Suppuration now sets in in the deeper layers of the PUSTULE. 33IALL-POX. oDo epidermis, where it follows immediately upon the pareirjhjma- toiis inflammation. A host of pus-corpuscles is generated by each of the swollen cells, and the chambered dome of the pock is soon filled with a yellowish purulent fluid in place of the transparent lymph which it previously contained. The pus- formation need not go beyond the epithelium. The pus dries up, and before the pock is thrown ofl", a new epithelial covering for the cutis is completed underneath it. As a rule however, the papillary body takes part with the epithelium in the production of pus. It may do this in two ways. We may distinguish between a catarrhal and a diphtheritic pus-formation. For the catarrhal variety I may refer the reader to § 292 and fig. 111. The suppiu'ation is superficial, the papillary body remains intact, and is roofed in during con- valescence by a layer of new cuticle which long continues thinner than the normal epidermis. This variety of pock heals without leaving any scar. Both anatomically and clinically it is a far less serious affection than the ^' destructive" pock. The latter consists, not in a mere secretion of pus from the papillary body, but in a liquefaction of its proper substance ; hence it results in loss of tissue, in ulceration and scarring. Bdrensprung has given an excellent description of the naked-eye characters of the diph- theritic pock, as follows : "In the second stage (of pock-forma- tion) an exudation takes place wherever simple hyperaemia existed ; those portions of the cutis which hitherto presented a lively redness, now assume a white colour which extends to the subcutaneous areolar tissue ; they seem im])regnated with a soft mass of exudation ; their edges are surrounded by a red areola ; the papillae too have lost their colour. In the third stage, the vesicles undergo conversion into pustules. On investigating the pock at this period, Ave can assure ourselves that all the infiltrated part of the cutis, together with its papilla), has been destroyed by suppuration. The pock exhibits a hemispherical, vaulted appearance, and contains, besides pus, shreds of the necrosed tissue. A fourth stage exhibits the pustules torn open at their apices, and emptied of their contents ; their place is taken by little open ulcers, which leave the well-known reticulated scars behind them when they heal." The microscope furnishes us with a very simple and tho- roughly explanatorv commentary on this succinct and luminous 23 354 MOHBID ANATOMY OF THE SKIN. description. Bdrensprung\s exudation is not sometliing amor- phous — not coagulated albumen or fibrin; it is made up of corpuscular elements — of pus-cells. We must recollect that even in the catarrhal variety of suppm'ation, the papillary body was abundantly permeated by young cells, some portion of which emigrated and were thrown off. In the present case, this in- filtration is excessive in amount; the cells accumulate in such enormous numbers in the interior of the papillae, that they not only mask, but compress, and so cause atrophy of all the other structures, the connective-tissue fibres, the vessels and the nerves. The blood cannot gain access to the infiltrated part ; hence its pallor. The annexed drawing (fig. 112) shows this state of things tolerably well. The vessels have been injected with gelatine and carmine. ^ - _ - ^^^ , JM Diphtheritic pock. a. The normal skin surrounding it, which is successfully injected. For further details see text. y^. Wherever the blood failed to penetrate during life, the injection lias also failed to enter ; so that to right and left of the pock vre see the capillary loops of the papilla well filled (« a), while the pock itself contains no trace of them. It looks as if a semi- circular piece of the cutis with its papilljB had been cut out of the capillary netvv'ork. The whole of this portion is infiltrated with pus- corpuscles in the way described above, and may be regarded as already dead: the only question is how long the fibres of the connective tissue, and the obliterated vessels which it contains, and wliich connect it with the neighbouring parts, will resist disintegration. They last longer in adults than in young people. In the former case an adherent slough is formed in the cutis ; in the latter, the infiltrated part soon melts into pus ; this dries into a crust; in either case however a superficial defect of the cutis remains — an ulcer — which heals by the second intention, and leaves a permanent scai*. SQUAMOUS EXANTHEil. 355 § 299. — 6. The squamous (wanthcm. I have referred on more than one occasion to the difficulties which beset our path whenever we try to separate the conception of inflammation from that of hypertrophy, as cetiological categories of morbid growth. The squamous exanthem undoubtedly originates in a chronic inflammation of circumscribed portions of the skin. These arc reddened, slightly swollen, and endowed with all the other attri- butes of inflammatory hyperasmia ; the result of this hypera3mic condition being, not an exudation into or under the epidermis, but merely an over-production of perfectly normal epidermic elements. This begins as an increased desquamation of horny eells, of " cuticular scales," upon the hypersemic, slightly raised patch of skin (squama^^ desquamation squamous exanthem). The secretion of cells however, soon assumes greater proportions ; white masses varying in size from a millet-seed to a lentil, and also discoidal plates, are formed, consisting of scales heaped up on one another, and firmly adherent to the parts beneath them (Psoriasis). Why, as the disease progresses, the epidermic cells cease to be simply cast off, why they should accumulate in thick scales, is elucidated by pathological histology as follows. The more exuberant tlie production of cells on the surface of the inflamed cutis, the more imperfect is the degree of development attained by each individual cell. The average height to which their development proceeds under such circumstances is that of the '^ intermediate cells," between the cylindrical elements of the mucous layer and the deeper cells of the horny lamina. That systematic hardening which we call " cornification," re- mains in abeyance ; in its place we have a simple desiccation of the soft protoplasm. During this desiccation the cells very naturally adhere to one another, and thus retain their connexion (which is purely mechanical) with the surflico of the body for a longer period. The silvery hue of the scales in psoriasis is due to the admission of air into their substance, simultaneously w^ith the desiccation of their cells ; and this also giv^es them their pecu- liarly spongy and porous consistency. If we pick off" the mass of scales, which may be done as a rule without employing much force, we find the papillary body under it almost entirely bare. The layer of epithelium which protects it is so thin that the least touch is enough to detach it, and to make the surface bleed : we 356 MORBID ANATOMY OF THE SKIN. must recollect notwltlistaiiding, that the continuity of the epithe- lial layer is still quite unimpaired, and that there is no trace of any exudation. Taking all these circumstances into account, we can arrive at only one conclusion with regard to the essential nature of the squamous exanthem, viz. that it is a morbid growth taking place upon a decidedly inflamed base ; and that this growth exhibits a ver}^ marked excess of, but — apart from the imperfection of the cornifying process — no qualitative devia- tion from, the normal course of cuticular development. The squamous exanthem is an inflammatory overgrowth, and serves, as such, to connect the foregoing sections with the ensuing one. /3 Hypertropln/. § 300. AVhat has been said above (§ 83) with reference to the physiological growth of epithelium and the extent to which the subepithelial connective tissue takes part in the process, may be transferred directly to the epidermis and papillary body. The papillary body supplies the epidermis with young cells : these are added to the rete Malpighii and gradually develope into epidermic cells. A morbid over-activity of this process forms the common basis of a great number of hypertrophic con- ditions, which we are now about to consider. I say " a great number," and I attribute the manifold variety of the appear- ances presented, to the circumstance that the embryo-cell which ultimately becomes an epithelial cell, is, before its emigration from the connective tissue, one of its homologous constituents, and is equally capable of contributing to the overgrowth of the papillary body, when it is produced in abnormal quantities. The very process which ultimately issues in the formation of epi- thelial cells, if it be interrupted at an earlier stage, must inevit- ably produce connective tissue. In including the overgrowth of the epidermis and papillary body in one and the same chapter, I have therefore been guided, not merely by the circumstance that they are in fact nearly always associated in nature, but also by the unity of the fundamental process which underlies them both. The series opens with those forms in which the epidermis alone is affected; it ends with those which are limited to the papillary body ; the intermediate forms being CALLOSITY. — CORN. 357 arranged according as one or other constituent is chiefly in- volved, the middle term corresponding to the equal implication of both. § 301. — The callosity (callositas) is a circumscribed thicken- ing of the horny layer of the epidermis. It forms a flattened superficial elevation of horny transparency, which slopes gra- dually down on every side. Its consistency depends on the amount of moisture present, and varies from the elastic and flexible to the horny and brittle. In its minute characters it differs from the normal structure of the horny layer, only in the number of superimposed strata of flattened and horny epidermic cells. If it be the function of the epidermis to protect the surface of the body from external influences by a coating which, however thin, is nevertheless very resistant, we may legitimately regard the callosity as a functional hypertrophy, analogous to the hypertroph}' of muscles from over- work. Observation tells us that callosities are exclusively produced at such points of the cutaneous surface as are exposed to severe or often-repeated pressure ; as e.g. the palm of the hand and sole of the foot. AYe should then ascribe the greater thickness of the horny layer, with which these parts are naturally endowed, to natural selection. The notion that a hyperasmic state of the papillary l)ody, and a consequent increase in the nutrition of the epidermis, are caused by external pressure on those parts, is far simpler ; and 80 far from being antagonistic to the former view, it rather serves to explain it. § 302. The corn (claims) is a modified callosity. Here too, external pressure acts as the eflicient cause of the over- growth. The difference in the results depends on a variation in its mode of action ; if the point at which the two opposing forces come into collision coincides accurately with the point of contact between the compressed part and the compressing agent, a callosity is produced ; if on the other hand the two points do not coincide, if the seat of conflict is withdrawn into the interior of the compressed part, in other words if the compressed part is capable of yielding to the pressure, a com results. Fig. 113 represents a vertical section through a corn under sx magnifying power of 20 diameters. Here too we have a 358 MORBID ANATOMY OF THE SKIN. trifling elevation of tlie surface ; it is, however, far smaller and more circumscribed than in the case of the callosity. The swelling which proceeds from the under sm-face of the thick- ened homy layer at this point, is of far gi'eater moment (a). This forms a truncated cone with its axis at right angles to the surface of the skin, into wliich it has penetrated for some distance. Its pressure has flattened the papillary elevations; the cutis itself is beginning to get thinner, and cases not unfrequently occur in which it is actually perforated. On turning our attention to the epidermis itself, we notice a striking departure from the usual plane of its stratification where the corn is thickest. For, coinciding with and exactly parallel to the curvature of the conical plug which is forcing its way into- Tertical section throiigli a corn (after Simon). The" papillary body at a is seen to be flattened by the pressure of the central part of the corn. .jV- the cutis, all tlie superjacent ,>trata of epidermis are bent with their convexity inwards, so that the centre of the com is in some sort differentiated from the parts around it. This inward curvature is also due to the external ju'essure : which may be said as it were to have manufactured a tool for itself out of the epidermis, with which it can proceed to operate against the deeper parts of the skin. § 303. The keratoses of Lehert form a com2}aratively rare^ but all the more interesting group of thickenings of the horny layer of the cuticle. Monstrous accumulations of homy matter on the surface of the skin are rendered possible in the keratoses^ KERATOSES. 359 by the fact that the stratification of the horny cells of tlie epidermis follows a different law from that by which it is normally governed. It is well known that under ordinary conditions, the strata of homy cells lie parallel with the surface of the bod}-, and that the papillae take no part in the finer subdivision of the cutaneous surface. It is only the deepest layer of cells forming the rete Malpighii, which accurately follows every elevation and depression; and which would therefore present, if taken by itself, a perfect mould of the papillary body. Between this and the horny layer is interposed the thick cushion of the " inter- mediate cells;" these are not stratified, and therefore furnish materials which are, from this point of view, quite neutral, for filling up all the inequalities of the layer below them, and so paving the way for the horizontal stratification of the layers above them. In the keratoses these "intermediate cells" are either quite absent or else disproportionately few in number. To the best of my belief they become prematurely horny, and this I regard as the essential physiological basis of the entire disorder. The absence of "intermediate cells" necessarily entails the absence of any transition from the one plane of stratification to the other : the horny layer of the epidermis is obliged in conse- quence to follow the rete Malpighii in its adaptation to all the elevations and depressions of the papillary body. Eacli layer of horny cells must therefore send into the layer which lies immediately above it, processes exactly resembling those which it receives from the layer immediately below it ; processes which correspond exactly to those which the papillary body projects into the deepest laj- er of the horny stratum. All the constituent layers are thus indissolubly united ; hence all the horny matter remains where it is produced ; hence too the possibility of those extraordinary thickenings of the horny lamina which charac- terise the entire group of keratoses. § 304. Following Lehert^ we distinguish a diffuse from a cir- cumscribed form of keratosis. The former results in the pro- duction of flat, horny scales, which often cover large areas of skin. Not unfrequcntly they resemble the scales of fishes ; hence the name Icldhyosls; occasionally tlicy assume a more protuberant, conoidal or prismold form, thus approaching the circumscribed variety of keratosis, the cornu humavum. That the great bwlk 360 MOHBID ANATOMY OF THE SKIN. of these scales is made up of horny cuticular cells is beyond doubt ; some authors indeed allege that they have succeeded in isolating fibres and lamellae, b}^ teazing out the scales after macera- tion ; but these fibres and lamella) must also have consisted of •epidermic cells. The mode of their occurrence will be self- evident from the ensuinp; observations. If we break an ichthyotic scale in two, we may detect a vertical striation on the fractured surface ; here and there too, something like stiff fibrils may appear to project. By macerating the scale in feebly alkaline licjuids, and then treating it very cautiously with needles, shaking it, &c., we may now and then succeed in breaking it up entirely into vertical prisms, or, if the term be preferred, into short and thick fibres. Every one of these fibres may be shown to consist of a certain immber of horny lamella) concentrically grouped round a central axis; when cut across, they may be counted on the cut surface like the annual rings of a tree. In the axis of the upper two-thirds of each pseudo-fibre we find nothing: in the lower third we find, either nothing at all, or a minute cavity which was once occupied by a more or less elongated papilla of the cutis. We infer fi'om this, that it is the papilla) which regulate the peculiar stratifica- tion of the horny lamellae. The axis of our concentric cylinder is continuous with that of the papilla ; and the almost vertical inclination of the lamellie is merely a repetition of its steep and sloping sides. This explanation does not cover all the phenomena of ich- thyosis. We must bear in mind that the surface of the skin also presents vertical planes where it is bent inwards to form the hair- sacs ; that these vertical surfaces are directly continuous with the sides of the papillae ; also, that the epithelial lining of the hair- sacs is merely a prolongation of the epidermis. Nothing is more usual than the extension of the ichthyosis to the hair-sacs when it happens to affect hairy parts of the skin. The horny lamellae which are thus produced, form, as might liave been anticipated, casts of the hair-sacs ; on transverse section they exhibit con- centric rings round an axial cavity. When the cavity is occu- pied by a hair, this appears in some sort as the axis of the laminated body ; this circumstance may be made use of as a guide ; but it must not lead us to imagine that the hair, as such, exerts any regulating influence upon the stratification of the KEEATOSES. 361 liorny lamella?. The hairs upon the affected patch are thin and caducous ; this points to a disturbance in their nutrition, due to the cornification of the hair-sac. The process extends as a rule, deep into the fundus of the sac; the hair-bulb proper alone remaining unaflPected. Fig. 114 represents a vertical section through an ichthyotic scale, and sllo^ys its connexion with the underlying skin. The specimen was taken from a calf affected with congenital ichthyosis ; it is preserved in the Physiological Institute at Breslau,* and is especially fitted to shed light on the relation of ichthvosis to the hair-sacs. 41 . n Fig. lU. ^ ^'K^os ^(f Ichthyotic scale ; Tcrtical section. Taken from a calf affected with ichthyosis, s^j- § 305. With Ichthyosis we may associate cutaneous horns {cornu humanum) as circumscribed varieties of keratosis. A monster of this description (9 inches in length) is preserved in the collection of the Pathological Institute at Bonn. As the tigure (fig. 115) shows, it is a rounded prism, longitudinally grooved, and spirally twisted like a ram's horn. Most cutaneous horns, though neither as long nor as thick as this one, present * Cf. Harpeck, description of the skin of a calf born with Ichthyosis cornea. Beichert u. Dulois-R-AjmoiuVs Archiv. Jahrgang 1862. Heft iii. T). 393. 36i> MOEBID ANATOMY Or THE SKIN. the same sort of appearance. On careful examination, each of the longitudinal grooves or furro\YS is found to correspond to a single cutaneous papilla — which is not ahvays elongated ; the horn as a whole springing from a group of papilla3 as its base, so that in this respect its structure agrees perfectly with that of an ichthyotic scale. V^e meet with horns, however, which are not of uniform thickness throughout, but conical, tapering to a point. There is an exquisite specimen of this variety too in the Bonn :pm a. Cutaneous Lorn 1' inclics long, from tlic coilecticii of the Pachological Institute at Bonn. Natural size, after 0. Weher. h. Another Lorn in tlic same collection, natural size. collection (fig. llj). The rarljcr abrupt increase in diameter as >vc approach the base of tljo horn, is due to the progressive addition of ]iew horny ]amel]a\ whicli overlie one another in an imbricate manner. Each of these lamellre again is made up of a series of elongated prisms, corresponding to single papillse ; it is only at the extreme periphery that we can obtain by maceration true Liraelloe. which exhibit the papillary moulding in somewhat KERATOSES. 36a less accentuated curves. It is clear that the process was origin- ally confined to a smaller group of cutaneous papillae, and spread, at first gradually, then with progressively increasing rapidity, to suiTounding parts. If we examine the under surface of one of these horns after its removal, we not unfrequently observe a number of small conical projections ; these were recognised by Virchoio to be- homy casts of hair-follicles. So that here also, as in ichthyosis, the morbid process may extend to the hair-sacs. The horny matter produced by the hair-sacs can never indeed contribute to raise the level of the surface ; so that it would be absurd to talk of the cornu humanum originating from the hair- follicles. Their implication in the process, however, induces a thickening of the horn at its base ; and as this is lodged in tlie very substance of the cutis, it raises the notion that the horn springs from a saccular depression — a dilated follicle — of the skin. This ex- plains much of what has been put forth concernnig the follicular origin of cutaneous horns. The necessary basis for the growtli of a horn is always a group of papilla3 ; and when we find horns springing from the fundus of a sebaceous cyst we are tempted to inquire, first, whether the cyst was really prior in point of time, and secondly, whether these horns also do not spring from a basis of proliferated papilla?. I have often -cQqw vast numbers of small, pointed papilla? on the inner surface of sebaceous cysts, whose grovrth must obviously have been secondary to the forma- tion of the cyst itself. § 306. Appendix. — The appendages of the horny layer of the cuticle — the hair and the nails — are, under ordinary circum- stances, the largest accumulations of horny matter in a compact form, to be met with in the body. After they have once assumed their proper shape, they are not liable to any im- portant change. At the utmost they can only undergo atrophy, i.e, they may split up and fall off prematurely : and even this is a result, not of any disease proper to the hair or the nails, but of some morbid condition of their matrix. The same may bo said of the opposite condition of hypertroplu' of the hair and the nails. Whatever points of interest these conditions may present to the histologist, v>'ill be considered, as regards the hair, in the chapter on the Hair-Sacs and Sebaceous Follicles ; — and as regards the nails, at once. SCA MORBID ANATOMY OF THE SKIN. Onychogryphosis (VircJiow) or the claw-like deformity of the nails which is associated with their simultaneous detachment from their bed, depends upon a hyperplastic state of the entire matrix of the nail. First stands that portion of its bed which forms the lower boundary of the onjchial fold (Nagelfalz). The long, horizontal papillae of this region furnish nearly all the substance of the nail, since this is no thicker at the finger-tip than it is at the edge of the lunula, up to which the papillae in question extend. This gives the nail its ridged appearance, very apparent by reflected light ; each ridge corresponding to a single papilla in the same way as the vertical fibres of the ichthyotic scale. Irregularities in the rate of growth, which may be alternately accelerated and retarded, give rise to transverse ridges and furrows. I ha\'e repeatedly observed that the remissions and renewals of nutritive activity during subacute pyrexial disorders leave traces of their presence by little trans- verse grooves and ridges upon the nails. The anterior part of the bed of the nail yields a thin layer of loosely-connected epi- dermic cells, upon which the body of the nail glides forward as upon a cushion ; it may be assumed as highly probable that these cells likewise contribute, though in trifling measure, to the growth of the nail in thickness ; this is rendered likely by the close adhesion of the nail to its bed : but it Is far from beinor proved, and Is even totally denied by Henle. Now if the matrix of the nail l^ecome hyperplastic, the anterior part of its bed furnishes layer upon layer of these loosely- connected epidermic cells ; the layers accumulate one ujion the other, they raise the nail from its bed, and compel it to assume a more or less upright position ; the hinder part of its bed, on the other hand, produces a thick and shapeless claw, several inches in length, spirally twisted, and somewhat incurved at its edges. Both of these conditions, which are so Intimately related, may occur together ; more usually, however, only one of them is present. § 307. Warts may be broadly defined as hyperplastic over- growths of the epidermis, in which the papillary body shares more or less ; we will begin therefore with a few introductory observations on the mode of growth of the papillary bod}^ It has already been stated that the very same cells which, after their migration from the connective tissue, are converted into WARTS. 365 epidermic cells by contact with the unaltered cuticle, are equallv capable, before their migration, of serving for the development of connective tissue. The details of the process are well shown in a fine section through the apex of a rapidlj-growing papilla of the skin (fig. 116). The boundary-line between connective tissue and epithelium appears very distinct at the sides of the papilla, where the small yellowish cells of the rete Malpighii are implanted in the fibrous texture of the papillary body, Fig. 116. Oo J Jl^l 0^0 i 4 A hyperplastic papilla of the cutis -with its epithelium. I'roiii the neighbourhood of an epithelioma of the lip. as described in treatises on normal histology. As we approach the apex of the papilla, this boundary-line fades and disappears ; for on the one hand, the rounded cells of the con- nective tissue accumulate at the expense of the intercellular substance, while, on the other, the epithelial elements pass by slow gradations from these rounded forms, through a more o66 MORBID ANATOMY OF THE SKIN. spindle-shaped variety, till tliey finally assume the shape of ordinary pavement-Gells. Thus the summit of the growing papilla is made up of embryonic cells passing externally into epithelium, and internally into connective tissue — a sort of '^ cambium " layer, such as exists in the stem of a plant between the bark and the wood. § 308. The common hard wart (Verntca) consists of a circular group of elongated papilliie, with their free extremities slightly enlarged and bulbous, their vessels dilated and extending close up to the epidermic covering. The latter, in marked contrast to ichthyosis, presents its normal threefold division, inasmuch as a thick layer of transition-cells fills up all the interstices between the enlarged papillaB, while the horny lamina invests the entire group with a common covering. At a later stage, when the wart attains an elevation of one line shove the surrounding surface, the horny lamina exhibits rents and fissures which correspond to the interstices between the enlarged papillae, and which gradually penetrate to the base of the wart. We are then able to see, without the aid of a lens, how many papilla) go to make up the wart. Their number varies from three to twenty and more ; the size of the wart varies accordingly, from that of a pin's-head to that of a split bean. It seems, moreover, as though this dismemberment of the wart were the first step towards its spontaneous cure ; the admission of air into its interior making the soft cells which it contains dry up together with the papillae. From an etiological point of view it may be interesting to know that the circular limit of the hyperplastic spot of skin corresponds to the area of distribution of a vessel of variable size. I can assert from personal observation that the very small, flat, discrete warts to which Asclierson has given the name of '^ Verruca? plana?," and which are usually met with on the face and hands of adults, are often grouped in a manner suggestive of the ramifications of a vessel. § 309. The cauliflower excrescences or papillomata of the skin, the smaller varieties of which are known as ^^ Porrum" or " Acrothymion," diifer from ordinary warts in that their constituent papillae are destitute of a common covering ; they are isolated from the first, each papilla growing in some measure independently. Their mode of growth resembles, upon the whole, CONDYLOMATA. Ml tliat of ordinary warts ; but in addition to the terminal, there is also a lateral apposition of young connective tissue, a dilatation and elongation of the capillary loops. An arborescent stroma of connective tissue is thus produced, whose outlines are repeated on a larger scale by the epidermic stratum. § 310. The smaller papillomata, such as the porrum, are very closely related, at any rate in outward form, to the pointed CONDYLOMATA. These too are destitute of a common covering for the thickly-set, hyperplastic papillae of the skin. They grow in just the same way, save that, as Biesiadeckl has shown, a histological factor, which is of secondary importance in tlie normal growth of epithelium, takes a more prominent part in the development of acuminated condylomata. I allude to a certain fission of the epithelial cells, which is exclusively observed in the middle stratum of the epidermis — wdiere cornifieation has not yet begun. The effect of this secondary growth of epithe- lium is barely appreciable in the normal development of the epidermis ; to it we may ascribe the peculiar swelling of the epithelial border (fig. 39, e) which occurs during the skinning- over of granulating wounds ; but it contributes most effectually to increase the thickness of the epithelial protrusions in epithelial cancer ; in the pointed condylomata the extreme softness of the epidermic covering arrests attention, and this is due to the ex- cessive development of the mucous layer. The red and fleshy aspect of the sycomata, which impart a sensation almost like that of mucous membrane to the finger, is also due to the fact that there is no thick horny layer to mask the colour and con- sistency of the young and vascular connective tissue. Flat condylomata (^Condylomata lata, Plaques inuqueuses), must be sharply distinguished, in a histological point of view, from the pointed variety. The overgrowth of the papillar}^ bod\' is more diffuse ; it is not confined to the tips of the papilla), as in the papillomata just described. The overgrowth of the connective tissue predominates over that of the epidermis. Flat, rounded elevations about one line in height and from two to five lines in breadth, are thus produced ; upon their surfi^ce the papillae form secondary prominences. The colour of these condylomata varies from a pale to a dirty red ; their epithelial layer is exceedingly thin ; it is only in the folds between the adjacent prominences that a sort of cheesy epithelial substance 368 MOKBID ANATOMY OP THE SKIX. accumulates, which undergoes further chemical changes and so o'ives rise to a most offensive smell. A catarrhal secretion of cells often takes place from the upper surface of the growth ; sometimes too, the suppurative process extends deeper into the connective tissue. § 311. In the soft or fleshy wakts (Verruca carnosa, 7noUis) the connective-tissue element of the growth preponderates to such an extent over the epithelial one, that most writers only refer to the epithelium because it not unfrequently presents a deeper pigmentation than usual of the rete Malpighii. Many of the soft warts are congenital and are known as " Mothers' marks" (Ncevi materni) ; others originate in advanced life, chiefly on the face and trunk. " The skin exhibits in these cases very gradual elevations, whose surface is usually flat, sometimes irregular, tuberculated or even warty. The epidermis and rete Malpighii, which extend over the gro^^^th, are seldom much altered; the cuticular investment is sometimes thicker than usual; but it never attains the same thickness as in the hard warts. If the growth be cut into, we see the cuticle spread over it in a uniform, rarely undulating layer. The growth itself is mainly situated in the cutis. It usually implicates the true papillary body and a certain part of the dermal tissue ; in rare instances it involves the entire thickness of the cutis, or may even penetrate into the subcutaneous areolar tissue. In every case however, it contrasts markedly with the tougher and whiter tissue of the cutis, inasmuch as its texture is more transparent, of a bright grey or yellowish hue, often reddish-grey, more soft and juicy, occasionally gelatinous ; not unfrequently too it is more coarsely vascularised. On investigating its structure, it is usually found to be very rich in cells , often indeed, it is all but entirely made up of relatively small cells with but little inter- cellular substance, and that little of soft consistency." The above description of the soft wart is borrowed from Virchoic ; he goes on to direct attention to the histological identity of the tissue in question with granulation — (embryonic) — tissue, using this as a basis on which to build his explanation of the intimate connexion between soft warts and cutaneous sarcomata (see below). § 312. Let us linger a moment over the pigmented fleshy warts. Virchow has taught us to distinguish broadly between EPITHELIOMA. 369 four varieties of abnormal pigmentation in the skin ; these are — 1. Simple pigmentation of the rete Malpiglui witliout marked changes in the cutis (freckles, &c.). 2. Pigmentation of the cutis without marked changes in the rete Malpighii and the epidermis. 3. Pigmentation of the rete where it invests a colourless overgrowth of the papillary body. 4. Pigmentation of the rete associated \Yith a simultaneous deposit of pigment in a hyperplastic cutis. The three last categories include all varieties of the pigmented mole ; the two last are included in the pigmented warts. The pigment is deposited in the form of yellow, brown, or black granules, partly in the cells of the rete Malpigiiii and connective tissue, partly outside them, freely distributed throughout the connective tissue of the papillary body. It sometimes accumu- lates in such quantities as entirely to mask all peculiarities of structure; nothing but pigment-granules boing visible. These form long striae in the substance of the cutis, accompanying the larger afterent and eiferent vessels. It is very unusual to find, besides tlic pigmentation of the rete Malpighii, the nuclei of the older epidermic cells of a uni- form black colour ; indeed the nuclei, even of pigmented cells, are generally free from colouring-matter. I have observed this i:)henomenon on one occasion only ; but I have failed to find any reference to it in books. y. Heteroplastic Growths. § 313. Two of the most important lietcroplastic growths vrhich affect the skin originate in the papillary body, or in the epidermis and papillary body together, while the remainder have their seat in the cerium proper. The growtlis in question are epithelial cancer and sarcoma. Epithelioma of the skin is very common ; hence we took it as our type of the disease, in § 164. Here tliercfore I will con- fine myself to the discussion of a few points, which were passed over on that occasion. And first a few words concerning the local etiology of the growth. Epithelioma of the skin occurs by preference at the junctio:i 24 370 MORBID ANATOMY OF THE SKIN". of the skin with a mucous membrane ; sc. on the lips, prepuce, anus, and vulva. When it occurs elsewhere, it is usually secondary, i.e. it is developed in parts which have been affected for years with some sort of morbid growth, without however exhibiting any of the characters of cancer. Among these are — 1. Some of the above-described overgrowths of the epidermis and papillary body, those more especially, which exhibit from the first a certain preponderance of the epidermic element, sc. cuta- neous horns, hard warts, papillomata ; this gives the classification we adopted in § 300 a very serious clinical significance. 2. Hypertrophy and dilatation of hair-sacs and sebaceous glands ; atheromatous cysts. 3. Cicatrices, especially of the scalp. The transition to epithelial cancer, as already stated, is in- augurated by an advance of the epidermic boundary, and con- sequently of the epidermis itself, inwards, towards the connective tissue — an advance Avhich gives the growth a destructive, rodent character. § 314. The following varieties of cutaneous epithelioma are based partly upon the locality, partly upon striking anatomical peculiarities of the growth. a. Warty epithelioma. One of the most interesting and frequent complications of the anatomical appearances described in § Wo et seqq. is that with papillary excrescences. The mode of transition from cauliflower vegetations to epithelial cancer has already been described (§ 148). Closely connected with this is the circumstance that at the growing border of an epithelioma, in the zone where the sebaceous glands begin to be enlarged, warts, and even small cauliflower excrescences are not seldom found ; and in this way the boundary-line between epithelium and connective tissue is displaced outwards, inverting the order of that displacement inwards, which occurs at the same time. Moreover papillary excrescences are often produced upon and within the epithelioma itself, the epithelioma being primary and the excrescence secondary. I need hardly say tliat in the production of these papillae the stroma takes a leading part. It would seem however as though the release of the stroma, which follows the degeneration, softening and expulsion of the tap-shaped epithelial protrusions, contributed to change the direction in which the development of the epithelioma takes SARCOMA. 371 place. It is certain indeed, that the capillaries are peculiarly dilated in the softened parts, and project towards the cavities corresponding to the old epithelial protrusions, forming a number of closely aggregated loops. The secondary papillae do not, as a rule, attain any great size; on the other hand they are very numerous, spreading uniformly over the whole of the ulcerated surface, or covering a great part of it in patches, like sedge upon a moor. So far as I know, no cauliflower growth of large size has ever been met with upon the surface of a cancroid ulcer. h. Cicatrising epithelioma. This variety also is based upon a peculiarity in the behaviour of the stroma — and that after it has undergone infiltration. The skin of the face in old people is occasionally the seat of a form of epithelioma in which the infiltration never assumes any considerable propor- tions ; it leaves no real ulceration in its train, but only a smooth scar. As its extension is exclusively horizontal, and proceeds from a single centre at a more or less uniform rate, it reminds us of a patch of lichen on a tree ; hence its popular name of ^^ rodent lichen" (Fressende Flechte). The point of histological interest about it, to which also it owes its general aspect, is that the residual stroma, which usually produces pus or papilloe, is directly converted into a stiff cicatricial tissue, with a great tendency to contract ; this remains coated with a thin layer of epithelium. § 315. Sarcoma of the skin exhibits certain peculiarities in the mode of its development, which necessitate a comparison of it with cutaneous epithelioma. Not the least important of the services which VircJioiu has rendered to the subject of the sar- comata, is his demonstration of the fact that cutaneous sarco- mata very frequently originate at such points as are predisposed thereto by other anatomical conditions. Among such local causes, the soft, fleshy wart occupies as prominent a place, as the hard wart, cauliflower excrescence, porrum, and cutaneous horn do with reference to epithelioma. Those h;)^erplastic conditions of the cutaneous sm'face therefore, in which the connective tissue predominates, always tlu'eaten to pass into sarcomata. Foremost among these are the soft, pigmented warts (ncevus pigmentatus) \ this disastrous tendency has long been known. They give rise, not to white, but to pig- 372 MORBID ANATOMY OF THE SKIN. mented sarcomataj so that the local predisposition extends its influence even to a collateral circumstance like this. Tumours which spring from soft Avarts usually continue to betray their origin for a long period, even in their broader outlines — pre- senting themselves in the form of true ''fungi," i.e. true mush- room-like proliferations, with a broad base and overhanging- edges. But even in tumours of large size, their origin from the papillary body may soon be established by minute examina- tion also. The cutis proper extends unaltered beneath the tumour ; and this even where it is displaced and dragged into the pedicle. Again, scars predispose to the development of sarcomata. The sarcoma of scars is also known as '' false keloid." By tho term Keloid, Alihert denotes a scar-like tumour of the skin. It forms oval protuberances of a red colour and tough consistency, often with claw-like prolongations ; its surface is smooth, and it is usually found in parts of the skin which were previously healthy. The tissue may be termed sarcomatous, and the arborescent distribution of the growth is ascribed by Collins Warren (Sitzb. d. K. Akadem. d. Wissensch. Bd. Ivii., 1868) to its localisation round the smaller arteries of the cutis. It is otherwise with the false keloid. This may be said rather to replace a scar than to grow out of one. In the regular course of the development of a scar, the presence of round-cell and spindle-cell tissue is only provisional ; they speedily give place to fibroid tissue. Now if either the one or the other element persists longer than its proper time, and if it accumu- lates in disproportionate amount, we get, instead of a scar, a tumour belonging to the sarcomatous series. Even fungous granulations (§ 105) may be viewed in this light ; and they form one extreme of a series of transitional forms, whose other extreme is represented by the most luxuriant and malignant sarcomata. In addition to the above, Virchow has directed attention to a local cause which determines the formation of many cutaneous sarcomata. Eepeated irritation and inflammation is one of the most frequent and eflicient excitants of sarcomatosis ; another proof that our comparison of the sarcomata with the products of inflammatory proliferation rests on a deeper foundation than the mere form of the cells {Virchow, Krankh. Geschwulste, Bd. ii. p. 246, seqq.). FIBROMA MOLLUSCUM. 373 § 316. Fibromata of the papillary body deserve especial notice. They differ from fibromata of other organs in their greater softness ; hence they derive their name of " Molluscum." Fibroma Molluscum (yirchow) is usually multiple, so that we ^re able to study every stage of its development in a single case (cf. VircJiowy Kr. Geschw. i., 325 and frontispiece). A small ^roup of papillae, perhaps even a single papilla (for this point is still siih judice) furnishes the materials for a roundish nodule, which may pass through every gradation of size, from that of a millet-seed to that of a man's head and upwards. In its interior the various stao-es of m'owth succeed one another as follows : the younger nodules, and the more recent portions of the older ones, consist of round-cell and spindle-cell tissue, while the older ones are made up of fibrous tissue. It is noteworthy that in its fibrous stage, the growth never exhibits that extreme tough- ness which is characteristic of old cicatrices or of the corps fihreux of the uterus. The molluscum always remains soft ; and this is due, as I can assert from personal knowledge, to a peculiar modi- fication in the development of the connective tissue, owing to its being complicated with oedema. The connective tissue as it approaches maturity, does not contract from all sides tovv^ards a single centre, in the usual way, and so shrink together as a whole ; it contracts round certain lines which traverse the mass, and which coincide in the main with the course taken by the vessels. We meet with this modification in the development of fibrous tissue wherever the islets of parenchyma undergo a metamorphosis requiring space for its completion; so e.g, it occurs in the development of clusters of fat-cells, in enchondromata, myxo- mata and colloid cancers. The connective tissue forming the stroma of these tumours represents the major part of the original basis of embryonic tissue, which, as the specific dif- ferentiation progresses, and the originally minor part under- goes a disproportionate increase in bulk, becomes converted into a narroAv framework for the reception of the islets of cartilage, granules of colloid matter, clusters of fat-cells, &c. The present case is simply one of oedema, due probably to some disturbance of the circulation, and occurring in the mol- luscum-nodule at an early period., The fluid requires space. Hence even in that early stage, when the mass consists of round- cells, elongated fissures make their appearance in the parenchyma- 374 MORBID ANATOMY OF THE SKIN. tons islets of the tumour (fig. 117). These fissures, which con- tain the dropsical fluid, increase in size ; soon we come to speak of bands of connective tissue stretched between the vessels ; and when the fibroid development is complete, the entire mass is represented by a network of thick trabeculae of connective tissue, whose meshes are bridged over by thinner fasciculi of fibres (fig. 117). It is self-evident that this structure must be quite as soft, nay, softer than ordinar}^ granulation-tissue. If therefore Fig. 117. IS/, ^%^Sv' Fibroma moUuscum. 1. Mature (after VircJiow) ; 2. Immature. Formation of clefts in the islets of parenchyma, -s-^y. At a. the lumen of a vessel- the word ^'molluscum" be derived from "mollis" (and this hardly admits of doubt), no fitter name could possibly be found; inasmuch as softness is, throughout the entire life of these tumours, their chief characteristic. 2. Diseases of the Corium and Subcutaneous Aeeolau Tissue. § 317. The position of the corium in pathological histology is actually determined by the important circumstance that it constitutes the greatest continuous accumulation of vascular connective tissue in the body. A priori therefore, we should expect to meet, not so muck with a series of novel and peculiar appearances, as with a very clear, I might almost say, typical evolution of the familiar histological potentialities of the inter- INFLAMMATION OF TILE CORIUM. 375 mediate apparatus of nutrition. 'Nov are ^ve doomed to disap- pointment. With the exception of mihary tubercle and enchondroma, there is hardly any product of the conjoint vascular and connective-tissue system Avhich does not attain to its fullest perfection in the corium ; some of these, particularly the specific products of leprosy, glanders, and syphilis, even exhibit a marked predilection for the skin. Lupus is exclu- sively confined to the skin ; but recent observations compel me to regard this as a growth which originates in the sebaceous and sudoriparous glands, and therefore to refuse it that place among the diseases of the corium to wdiicli most authorities consider it entitled. a. Inflammation. § 318. The corium proper, according to a very noteworthy investigation by Rollett^ is built up of thick bundles of fibres (of connective tissue) which traverse it obliquely, starting from the subcutaneous areolar tissue ; these break up as they advance towards the surface, and interweave with neighbouring fibres to form a web of extraordinary density. Moreover, the individual fibrillar are of exceedino; toughness, offerino- an obstinate resist- ance to softening and liquefaction. Owing therefore to the closeness of texture, as well as the toughness of its constituent fibres, the corium proper is little suited for the exhibition of such processes as claim much space in short periods of time, and in particular, of suppurative inflammations. When we come to consider those inflammations which start from the hair-sacs — acne and furunculi — we shall see how cumbersome an attitude is taken up by the corium towards each acute inflammation in turn. The behaviour of the subcutaneous areolar tissue is very different. It offers no obstacle to the spread of suppuration. The fibres of the areolar connective tissue are soft and readily dissolved ; between them are meshes and lacuna) (the " cells " of the '^ cellular " tissue) smooth internally, and occupied by fluid or clusters of fat-cells. In these meshes, around the fatty clusters, there is enough space to accommodate three times the amount of fluid which is usually present. Add to this that here, between the muscles and the skin, an extremely free communi- cation between neighboui'ing pai'ts is kept up by the lymphatics 376 MORBID ANATOMY OP THE SKIN. and blood-vessels ; in short, every facility is afforded for tlie extension of a subcutaneous suppurative process. We must keep tliese facts continually before our eyes in studying the acute inflammations of the skin. They shed a flood of light upon the course of phlegmonous abscesses, when the corium shows only too well its capacity for hindering the escape of the pus accumulated underneath it. No important novelty is contributed to pathological histology by the study of this form of inflammation. It simply exhibits suppuration and abscess- formation in its most typical form — and on the largest scale — such as has been described already in the General Part of this work (§ 94, et seqq.). The most exquisite example we possess of chronic inflam- mation affecting the skin, is aflbrded by the so-called Sclero- dermia adultorum (not to be confused with sclerema neonatorum or with elephantiasis). Rasmussen makes an infiltration of the perivascular sheaths with small cells the starting-point of the textural alterations (^Hospital- Tidende^ 1867). Extending farther, this leads to a more diffuse production of young con- nective tissue, which subsequently contracts and causes a peculiar puckering of the cutaneous surface. The skin grows smooth and shiny, and is very closely applied to underlying parts, e.g, to the condyles of the humerus in the neighbourhood of the elbow-joint; distortions and deformities arise in conse- quence, just as if the affected regions of the skin were cicatrices. We shall meet with precisely analogous conditions in the liver and the kidneys, where they receive the name of cirrhosis and granular atrophy. /?. Hypertrophy, § 319. One of the most peculiar and interesting of all the diseases to which the skin is liable. Elephantiasis Arabum, must be regarded as a hypertrophy of the corium and subcutaneous connective tissue. It owes its name to the striking resemblance between the lower extremity of a man aftected with this disease, and that of an elephant. The skin, prodigiously thickened, hangs in wide baggy folds about the leg and ankle, so that the toes can barely be detected peeping out from under them. On section, we recognise the famihar structure of the cutis, only ELEPHANTIASIS ARABUM. 377 on a larger scale. As regards its etiology, I will only remark at present, that we have many reasons for believing it to be a chronic inflammation. Oar description of eczema omhrum on a former page, was broken off abruptly at the point where it passed into chronic inflammatory thickening of the cutis. We reserved this for our chapter on Elephantiasis, because no anatomical difference of any moment can be shown to exist between these two forms of cutaneous hypertrophy. Moreover in those coun- tries where elephantiasis is endemic (the tropical and subtropical regions of the globe), it is a well-known fact that the disorder usually begins with phenomena having all the characters of erysipelas (see § 288). During this inflammatory stage the lymphatic glands, which receive their lymph immediately frcm the inflamed part, become swollen ; in erysipelas of the leg, the inguinal glands, in that of the arm the axillary, in that of the face the cervical glands. The swollen glands do not subside. The lymph-paths tlu'ough them remain permanently blocked. There ensues a stasis of the lymph ; the outflow of the super- fluous nutrient fluid is checked, and this must be regarded as the immediate cause of the hypertrophy. § 320. We will begin by giving a general sketch of the histology of elephantiasis, derived from recent investigations. Teichmann asserts that the above-described dilatation of the lymphatics may be traced to their origin in the j^apillse of the skin. Vircliow adds that an irritative condition of the corpus- cular elements of the connective tissue may be shown to exist from the very first, in parts affected with elephantiasis ; proliferation of nuclei and fissiparous multiplication of cells being found particularly in the radicles of the lymphatics. The smallest lymph-paths are richly lined with an epithelial stratum of un- usual thickness. This would point to a direct connexion between the morbid growth and its chief causal element, the dilatation of the lymphatics. I regret that I cannot speak of the first beginnings of elephantiasis from personal observation. I have only had the opportunity of subjecting its later stages to an adequate histo- logical analysis. Here too, the blood-vessels and lymphatics play a prominent part ; but what chiefly arrests attention is the increased bulk and simultaneous condensation of the existing bundles of connective tissue. How, we may inquire, is this 378 MORBID ANATOMY OF THE SKIN. brought about? The cutis is a web of fasciculi of connective tissue. In transverse sections these fasciculi are divided, some transverselj, some longitudinally, others at every imaginable angle. Now if we select a point at which a bundle of longitudinal fibres happens to abut upon a bundle which has been divided at right angles or obliquely (fig. 118), we find that the longitudinal fibres separate to include those which are divided transversely. Tig. 118. A V Elephantiasis. Connective-tissue bundles of the cutis seen in longitudinal and transverse section, a. Lymphatic spaces surrounding transversely- divided bundles; &. Protoplasm, at whose expense the bundles increase in length and thickness. -^. They form a framework whose trabeculas are ingeniously inter- w^oven with the fibres of the bundle which is cut across. This framework however is of a much softer and more delicate con- sistency than the main fibres. It refi'acts light less highly, and is not so susceptible of being stained by carmine. Of course the transition from the one variety to the other is extremely gradual. In other w^ords, the fasciculi of connective tissue in the skin affected by elephantiasis, divide at each end into a number of finer and softer fibres, which make up a framework for the reception of the central portions of other bundles, whose position in relation to the first set, is transverse or oblique. Repeated ELEPHANTIASIS AKABTJM. 379 examination failed to show any traces of embryonic tissue. If I am called upon to express an opinion as to the mode in which the cutaneous connective tissue increases in amount during the later stages of elephantiasis, I cannot deny the probability that the elongation of the fibrillae is primarily due to the progressive and gradual hardening of the soft material at their ends. This view indeed rests chiefly upon the absence of any other produc- tive process in the hyperplastic cutis ; it affords a very plausible explanation, however, of the naked- eye appearances. The fibres at first grow thicker at the expense of the same material to which their elongation is due. This seems at first sight paradoxical. But we must recollect that the soft ends of the fibres are at the same time the cement for the ao^o;lutination of such bundles as run in other directions. AVhy cannot the same material serve for the elongation of some fibres while it contributes to the increase in thickness of others ? The latter increase however has its limits. No sooner does the fibre attain an average diameter of half a millimetre than it separates sharply from the cement round it ; a true interstice is thus produced,, which isolates the fibre completely for a variable part of its extent. These interstices undoubtedly communicate with the lymphatic system, and contain those large quantities of clear, coagulable lymph, which flow from the recently divided surface of the affected skin. They attain their highest de- velopment at the junction of the cutis with the subcu- taneous connective tissue. Here too we find the thickest of the fibrous bundles. Higher up, in the outer portions of the cutis, the fibres are thinner ; no vestige of interfibrillar spaces can be seen, nor any of dilated lymphatics, such as one might expect to find, in accordance with the observations of Virchoio and Teichnann on the early stages of the process. The state of the capillaries is much more striking. The capillary network of the cutis is neither closer nor more abundant than usual ; on the contrar}^, it is obviously nothing more than the old capillary net- work stretched over a greater area ; the individual vessels however are wide and gaping ; their walls are intimately fused with the surrounding connective tissue. The lumina of i\\Q vessels in the dense substance of the cutis, closely resemble the channels excavated in worm-eaten wood. I am inclined to call this the first stage of cavernous metamorphosis, reminding the 380 MORBID ANATOMY OF THE SKIN. reader that Hecher has described a case of congenital elephantiasis in which the tissue distinctly exhibited a cavernous structure. This condition of the vessels however, occurs in all fibromata ; and for the conversion of an ordinary fibroma into a cavernous fibroma, a peculiar process of contraction has first to take place along the axes of the vessels (cf. § 129). The elephantiastic overgrowth spreads from the cutis into the subcutaneous areolar tissue ; first the fasciae, finally the inter- muscular and periosteal connective tissue, become involved. The more complex organs, such as muscles and nerves, which arc included in the growth, as well as the adipose tissue, undergo atrophy and disappeai'. The periosteal growth leads to enlarge- ment of the bones by the apposition of new layers of osseous substance. Numberless exostoses cover their surface ; affording ample proof of the possibility of true bone being developed, not from the periosteum only, but from the adjacent intermuscular connective tissue as well. On the other hand the papillary body is involved in the hypertrophy. The papillary body is, after all, only the outermost layer of the cutis. The skin in elephantiasis is therefore very often covered with overgrown papillae, and also with thorny projections, which make it look like an ox's tongue. The process, however, is always more widely spread in the deeper layers of the cutis, than in the papillary body ; the implication of the latter being always secondary. § 321. Pachydermia lymphangiectatica, an interesting variety of ordinary elephantiasis, has its seat of election in the scrotum, penis, mens veneris, and the anterior part of the perinasum. The hypertrophied skin is studded with innumerable vesicles, the largest of which is not bigger than a pea ; it is evident at the first glance, that these vesicles are not produced by detachment of the cuticle, as in the bullous exanthem, but that they are really cavities in the uppermost layer of the cutis itself. For their roof is comparatively tough; the clear fluid they contain, can be squeezed out of them, retui'ning in proportion as the pressure remits. On puncturing any one vesicle, true lymph flows from the puncture, often in enormous quantities, while the swollen cutis and all the other vesicles subside contemporaneously. This shows clearly enough that the vesicles are in connection with the lymphatic system ; but the histological investigation of vertical sections through the PACHYDERMIA LYMPHANGIECTATICA. 881 affected skin, affords additional evidence that it is tlie superficial, sub-papillary network of lymphatic vessels, which has undergone partial ampulliform dilatation. The vesicles are roofed in by the epidermis together with the papillary body. As a rule, the detached portion of the papillary body contains from four to six papillae ; in the smaller vesicles, these are still tolerably long and slender ; in the larger ones, they assume a broader and shorter form ; I have never seen them stretched to such a degree as no longer to be recognisable. All the vesicles are lined witli the well-known mosaic of endothelial cells ; and this places their origin from dilated lymphatics beyond all doubt. We have still to find out the special cause of the peculiar modification of the anatomical appearances. I feel myself obliged to look for it in the implication of the imstriped muscular fibres of the skin in the hyperplastic process. 'SVe know that the tract of skin which is peculiarly liable to be affected by pachydermia lymphan- giectatica is also very richly endowed with involuntaiy muscular fibres ; indeed the tunica dartos of the scrotum is an independent muscular membrane (cf. Neumann on the Distribution of the Fibres of Organic Muscle, in Wiener Sitzb. 1868, p. 651). Now in the case which I had an opportunity of examining, and which presented the anatomical features of the disease in their most tj^pical form, there was a very distinct overgrowth and proliferation of unstriped muscular fibres ; tliey were grouped in well-marked, compact fasciculi, Aviiich permeated the entire thickness of the corium — radiating obliquely from below upwards in all imaginable directions. The corium indeed, was made up of muscular and fibrous elements in nearly equal proportions. Setting aside the likelihood of compression of the lymphatic trunks by the actual contractions of this exuberant muscular layer (of those trunks which, passing vertically through the cutis, serve to connect the superficial with the deeper network of lymphatic vessels), and the consequent am- pullary dilatation of the superficial network; it cannot be denied that a somewhat similar effect would needs be produced by the mere elastic reaction of the muscular parenchyma, wlien this is developed, as in the present case, in a region singularly incap- able of yielding to the demands of new products, of whatever kind, for more space. Hence I am led to beheve that the over- growth of the muscular fibres is to be regarded as the chief 382 MORBID ANATOMY OP THE SKIN. cause of the lympliangiectasis, by hindering the circulation of the lymph in the substance of the corium proper. y. Heteroplastic Growths, § 322. A reference to the discussions embodied in the Oeneral Part of the present treatise will allow us to be very brief in speaking of those heteroplastic growths to which the skin is liable. This applies more particularly to myxomatous and lipomatous tumours, which originate by preference in the subcutaneous areolar tissue ; also to cavernous growths, to the sarcomata and fibroid tumours, which may occasionally be met with in the subcutaneous tissue. The various kinds of Carcinoma usually affect the skin only in a secondary manner ; for we either find a cancer of deeper parts, e.g. of a lymphatic gland, a muscle, or a bone, making its way outwards to the skin by continuity of tissue, or else a true metastatic deposit in the skin, formed during the later stages of carcinomatosi.^;. In the latter case, the disease usually assumes the form of flattened tubera vaiying in size from a pea to a hazel-nut, mainly confined to the skin of the trunk. The name of ^^ ivory cancer of the skin" (Alihert), or '^cancer en cuirasse " {Cruveilhier), is applied to a scirrhous or colloid cancer of the mammary gland, when this extends in small but closely aorcrreaated nodules over the entire skin of the front of the chest, converting it into a tough, white, translucent, smooth, and lus- trous rind, as hard as a board. § 323. The specific products of leprosy, of syphilis, and (sup- posing my own view to be wrong)* of lupus, form, in respect of their histology, a natural group, which, as we have already had occasion to see, is distinguished by its peculiar hybrid position on the border-land between inflammation and tumours. The acme of the tissue-development, the point at which it culmi- nates, is the production of an embiyonic tissue, which so closely resembles the familiar inflammatory proliferation of connective tissue, that Virchow has actually given it the name of granula- tion-tissue, and has embodied the whole in a class of " granu- * Cf. § 317, last sentence. SYPHILITIC GUMMATA. 383 lation-growths " (Grannlationsgewachse). Notwithstanding tliis, no one would dream of simply including them among the products of inflammation ; at the very least, they would be called " specific " inflammations. Their specific character does not however reside exclusively in their etiological relations ; it is also based on demonstrable anatomical peculiarities. The very way in which the embryonic tissue is brought together deserves special notice. It takes the form of nodular (tuberous) deposits in the connective tissue of the cutis. The individual nodules attain the size of a pea, or even that of a cherry or more. This would of itself be a phenomenon of extreme rarity in the history of simple inflammatory growth ; it would rather deserve to be termed ^^sarcomatous." Still more important is the way in icJiich the growth lingers on the confines between organisation and decay. By slow gradations — it would seem — the embryonic tissue passes, either into connective tissue, or into pus ; or its cells become fatty wdiile its intercellular substance under- goes mucous softening. We get a series of very charac- teristic intermediate forms, of which we appreciate the value when we attempt to distinguish between the individual members of the group. § 324. The syphilitic gumma has been fully described elsewhere. The chief anatomical criterion of its specific charac- ter was found to reside in the partial fatty degeneration of the granulation-tissue, in the production of cheesy centres amid a con- tinuous accumulation of newly-formed connective tissue. The gummatous deposit in the skin deviates from this type in the greater rapidity of its course, and in several other points also. Gummata of the skin are rarely single ; they are usually multiple, arranged in groups which occupy a certain tract of the cutaneous surface {Lupus syphiliticus). The nodules are seated in the parenchyma of the cutis, and even when they cause no visible projection, they may be detected all the more readily by the finger. The peculiar hardness which characterises them at first, speedily passes, as a rule, into the opposite extreme. The tendency of the cutaneous gumma to undergo softening, is well known. This end is reached by the co-operation of suppuration with fatty degeneration ; in this case, as in many others, they fonii links in one chain, suppuration freeing the cells from their organic connexion, while fatty degeneration indicates the imme- 384 MORBID ANATOMY OF THE SKIN. diate result of this isolation — sc. their atrophy and death. The focus of softening then gives way, and liberates its contents : a circumscribed loss of substance being left. Its floor and ^Yalls are infiltrated to the extent of a line and more with young cells ; this gives a dash of Avhite to their colour, and makes them tough and bacony. A thin fluid containing a few cells and some fatty debris, exudes from the raw surface ; the adjacent bundles of connective tissue are slowly dissolved, and the ulcer continues to increase in size until its further progress is arrested by vigorous anti-syphilitic treatment. Then, and not before, a permanent layer of embryonic tissue is formed upon the floor of the ulcer ; it is then, and not before, that the formation of a scar begins. Syphilitic scars have a strong tendency to contract. Causing the utmost distortion of neighbouring parts, they shrink them- selves to a mere nothing, so that after the lapse of a certain time it is often impossible to infer the previous existence of a syphilitic ulcer from the presence of a scar. This peculiarity too, has not been explained as yet by the results of microscopic in- vestigation. A syphilitic scar resembles all other scars both in its structure and development. The blood-vessels are invariably obliterated ; in injected specimens the syphilitic scar looks like a gap in the vascular network of the skin ; whether the power- ful contraction of the connective tissue may not be the cause of this total obliteration of tlie vessels, must remain an open question. So much for the development of a single syphilitic tubercle in the skin. The growth and decay of many such aggregated nodules lies at the root of syphilitic lupus. The nodules are now small and superficial, now deeply seated and large. In the former case they are usually grouped concentrically round the point which was first affected; discoidal ulcers result which become annular by healing from the centre, where a cicatrix is- formed {Lupus syphiliticus serpiginosus). In the latter case the ulcers grow deeper, they extend into the areolar tissue (Lujms syph. exulcercms). There is also a hypertrophic variety of syphi- litic lupus, in which isolated nodules of relatively small size are developed in an abundant matrix of newly-formed connective tissue. § 325. The pathological anatomy of Leprosy was shrouded in darkness till a very recent period. It was in 1848 that Danielssen LEPllOSY. 385 and BoecFs work on the Norwegian Spedalsked appeared in Paris, a work illustrated with admirable drawins^s. Since then Virclioio has taken the matter in hand, and has subjected it to a most exhaustive treatment in his work on Tumours. All the affections observed in the course of leprosy are based, histolo- gically speaking, on a common foundation. This is a change in the connective tissue which leads, in the skin, to the formation of the well-known leprous tubercles. After a pro- longed initiatory stage, during which the skin is reddened in patches and exhibits bossy swellings, a number of nodules arc developed in the substance of the cutis or in the subcutaneous tissue ; these vary in size from a hazel-nut to a walnut ; they arc hard, and more or less prominent according to their situation. They give the skin a tuberculated aspect ; occurring by pre- ference upon the face and hands, they lead to the most repulsive deformities. Microscopical analysis in the hands of Virchoiv yielded invariably the same results. The nodules consisted throughout of granulation-tissue, very rich in cells. This tissue extended from the rete Malpighii to the subcutaneous layer of adipose tissue ; it surrounded the hair-sacs and sebaceous glands, causing their atrophy by disturb- ing their nutrition. Hence it is that the tubercles of leprosy, even Avhen seated on the hairy scalp, are always hairless. The accom- panying woodcut is copied from fio;. 178 in VircJioiu's book on Tumours, and shows the leprous tissue under a considerable magni- fving power. Virclww adds that he has nowhere traced the progressive development of a simple sjnndle- shaped or stellate connective-tissue corpuscle through all the stages of nuclear and corpuscular prolifera- tion so perfectly as here. The cells divide; they grow smaller and more numerous ; the intercellular substance is represented by very narrow bands of a materia Avhich is rendered granular and cloudy by acetic acid, and whicl 25 Fig. 119. Tissue of leprous tubercles (after Virchovj). Cells un- dergoing division. 386 MORBID ANATOMY OF THE SKIX. must tliereforc contain mucin. The ultimate result of these changes is the texture represented in fig. 119, a, which may he regarded as embr^^onic tissue of the most typical kmd.* So far therefore, the leprous nodule, though distinguished from the syphilitic product by its size and its occurrence in a multiple form, agrees with it most absolutely in being composed of granu- lation-tissue. The agreement is absolute in this respect until retrograde metamorphosis sets in. The leprous product indeed, like that of syphilis, undergoes disintegration by a combined process of fatty degeneration and suppuration ; it differs from it in the long period of its precarious quiescence. For v\'e may fairly term the condition of a tissue precarious, when it contains a vast number of elementary parts requiring nourishment, parts which have taken the place of a parenchyma at once smaller in bulk and containing fewer cells ; and this without any adequate increase in the supply of nutrient material by a simultaneous formation of nevv' vessels. Retrograde metamorphosis or suppu- ration might be expected to set in at once. But neither of these changes seems in any hurry to begin. At last, after years have elapsed, the nodule becomes softer, its intercellular substance undergoes partial liquefaction, some of the cells are destroyed by fatty change ; but complete resolution can only occur if the growth was very limited in extent. The nodule passes into suppuration and ulceration only if it is exposed in an exceptional degree to violence and other sources of external irritation. A slight increase of cell-growth then converts the leprous nodule into pus, which is evacuated externally, leaving a proportionate loss of substance behind it. The leprous ulcer thus produced continues to discharge a thin and sanious pus, which usually dries up into brownish crusts. The same specific product of morbid growth underlies the other disorders incidental to leprosy. Thus e.g. the cutaneous anaesthesia is due to the growth of nodules upon the nerves ; the spontaneous disarticulations of the limbs are caused on the one hand by the gradual extension of the infiltration to deeper parts. * Hansen states (Nordiskt Medicidskt Arkiy. i., 13) that in the older leprous tubercles, cells are found which contain, besides a nucleus, a broTvnish oily spherule, together ^vith peculiar amorphous bodies of large size which seem to be entirely made up of such spherules. DISEASES OF HAIR-SACS AND SEBACEOUS GLANDS. 387 on the other by a painless suppurative disorganisation of the joints which finally results in complete separation. § 326. Glanders, communicated from the horse to man, manifests itself also by the production of nodular deposits in the subcutaneous areolar tissue. The deposits are entirely made up of embryonic tissue, and differ from the corresponding products of syphilis and leprosy in a speedier rate of change, terminating invariably in suppuration. o. Diseases of the Hair-Pollicles and Sebaceous Glands. a. Retention of Secretions. § 327. The hair-sac, with its appended sebaceous follicles, is one of the most ingenious anatomical contrivances in the body. The whole arrangement for the implantation of the hair into the skin, the ingenuity with which it is provided for in the interior of the hair-sac — all this agrees wonderfully with our notions of the adaptation of means to ends. But, as in the case of many an ingenious contrivance due to human skill, the advantages are not without corresponding drawbacks. Both are easily put out of order. The way in which the growing hair moves upwards along its sheath, at whose narrowest part it is brought in contact with the openings of the sebaceous glands, which oil it with their secretion, and protect it against the adverse influences with which it will have to contend upon its liberation — all this looks wonderfully cunning and practical. But the very closeness of this contact between the hair and the neck of the follicle has its dangers. It wants but little to stop up the mouth of the follicle completely. A trifling swelling of the subepidcrmic connective tissue, a slight increase in the number of epidermic cells pro- duced, is quite enough to fill the small amount of vacant space which still exists in the neck of the sac. The excretory duct once plngged, the secretion cannot escape, and a whole series of disorders of the hair-sacs, due to retained secretions, are the result. These we will now proceed to describe. § 328. Pausing for a moment to consider the etiology of retention, we find tliat a closure of the hair-follicle by dirt from 388 MORBID ANATOMY OF THE SKIN. without, is comparatively rare. Any substance which could not be expelled and pushed aside by the vigorous advance of the o-rowinfif hair, Avould have to be endowed with a very extra- ordinary degree both of penetrating power and viscosity. A far more important cause of retention is the over-secretion of epi- dermis and tumefaction of the subepidermic connective tissue about the mouth of the hair-sac, to which allusion has been made above. In one of the disorders which we shall have to consider^ ^ iz. acne, both of these phenomena are simultaneously produced by one and the same cause, sc. a subacute inflammatory state ; and it seems fair to assume a like mode of causation in other eases Avhich are complicated by inflammation. All these causes however, sink into insignificance in the face of a circumstance which throws the very question as to the mechanism and causes of occlusion into the remote background ; I mean the circum- stance that the structure of the hair-sac affords the most favour- able opportunities for an accumulation of secreted matter, without nny previous occlusion of the efferent duct. The hair-sac {see fig. 109) is club-shaped in form; the diameter of its fundus exceeds that of its mouth ; its walls face pnrtially downwards ; indeed that portion of the follicular w^all which immediately surrounds the hair-root, may be decidedly said to be turned awa^ from the surface of the skin. Hence the secretions from the wall of the follicle find their escape hindered by that wall itself. It is only the vigorous growth of the hair which prevents the cells shed by the epidermic lining of the follicle, from remaining in its interior. The hair drags- them with it as it grows ; the upward and outward direction of the little scales of its cuticle contributing to this result. The hair may be said to scour out the little recess in which it grows. But it is obvious that this self-cleansing apparatus is only adapted to cope with a very moderate amount of epidermic desquamation on the part of the follicular lining. The least increase of this must necessarily lead to the retention of the secreted matter. Accordingly the question as to what stops up the follicle becomes futile. We ought rather to inquire how it is that the secretions are not usually retained — considering the peculiar structure of the hair-sac. In my opinion, this is the point of view which we ought to take up, with reference to the etiology of retention in the hair-follicles, which is otherwise so COMEDO. 389 -enigmatical. The starting-point of the disorder consists in over-secretion from the follicular lining ; and this serves also to explain the occurrence of retention. In the majority of instances the over-secretion in the hair-sacs is merely a part of a general disorder of the whole cutaneous surface, in which its recesses take part in their due measure. Persons whose skins are naturally greasy, whose hair and nails grow fast, whose heads are always full of scurf — young men at the time of puberty — are therefore specially predisposed to diseases caused by retention of secretions in the hair-sacs. Moreover we often find them in the neighbourhood of epitheliomata and warts — wherever indeed a proliferation of cuticular elements is an essential feature of the anatomical alterations. § 329. Granting therefore that we have to do with over- secretion in the interior of a hair-follicle, we next proceed to inquire whether this affects the follicle in its entirety or only a portion of it. The former is the case in comedo. This term is applied to a condition in which the entire length of the hair-sac is uniformly distended by an accumulation of epidermic pro- ducts. The skin may easily be raised from its bed at this point. If we squeeze it firmly on each side of the comedo, a small whitish plug is driven out of the sac, which exhibits a black spot on its free end, and has accordingly been compared to a living organism — a maggot — (comedo). Of course, the appear- ance in question is due to the impregnation of the free end with dirt from without. If we put the plug in a drop of water and examine it microscopically, we find nothing beyond epidermic scales, which here and there exhibit an opaquely- dotted appearance due to the presence of oil-globules. Besides this we find free oil-globules, furnished by the sebaceous glands. According to Gustav Simon a very small six-legged parasite with a long abdomen, the acarus foUiculorum^ is more common in these than in normal hair-sacs. I have never seen it. Come- dones are usually found on the alge and bridge of the nose, and on the shoulders — wherever the skin is coated with down only. They do not affect the hair-follicles of the scalp and chin. § 330. If the over-secretion is restricted to the fundus of the sac, the resulting appearances are somewhat different. The epidermic masses form concentric laminse round a central nucleus, 390 MORBID ANATOMY OF THE SKIN. consisting of a spheroidal aggregate of cells; an epidermic globe is thus produced, which differs from the ^^ pearly nodule" of epithelioma only by its greater size. Should the globe attain the dimensions of a millet-seed, it communicates a yellowish- white tint to the overlying epidermis, and receives the name of Milium oc Geutum. § 331. A third variety is the Melicebis, so called from the honey-like character of the follicular contents ; this is due to a more abundant admixture of oily matter from the sebaceous glands with the epidermic products. If the nodule project markedly above the sm-face, if the distended follicle protrude more and more above the level of the surrounding skin, and if the connective tissue of the papillaiy body take part in the hyperplastic process, the MoLLUSCUM contagiosum results. This is a wart-like prominence as big as a pea, differing from other soft warts Avhich resemble it, only in having its centre occupied by a dilated hair-sac which secretes fatty and epidermic products in abundance. The hypothesis of an antecedent occlu- sion of the hair-follicle is least of all — be it said in passing — applicable to molluscum contagiosum. In the larger molluscous tumours, the follicular orifice is often found gaping to such an extent that the contained matters ma}' be squeezed out with the utmost ease. It has been asserted that these matters are capable of transferring the disease to the skin of a healthy person. The assertion rests on a very doubtful substratum of evidence ; it has given rise however to the questionable epithet '^ contagiosum." § 332. The Acrochordon is a small cutaneous polypus, often with a very long pedicle. It looks as if a small, crooked, brown wart were hanging from the skin of the neck or trunk. On examining the head of this little tumour, we find in its interior one or two hair-follicles much distended with sebum, &c. We may reasonably assume that this retention gave rise to a warty projection, which subsequently became polypoid. The length of the pedicle, which is often very striking, is usually due to accidental causes — particulai'ly to a bad habit of playing with and pulling at such tumours. § 333. We come finally to the Atheromatous cyst, the highest degree to which the simple retention of secreted matters in a hair-sac is capable of attaining. The follicle is distended ATHEROMATOUS CYSTS. 391 by the accumulated secretions till it reaches the size of a pigeon's egg, or even a child's fist. It becomes a retention-cyst, in which we are able to distinguish between a secreting cyst- wall and secreted contents. The former is composed of a connective tissue rich in cells, lined by from two to three layers of pavement epithelium. Its thickness is in inverse proportion to the size of the tumour ; it may ultimately become as thin as a serous membrane. Nevertheless we must always regard it as u hyperplastic product, inasmuch as the sac of connective tissue in which it originated, is the thinnest of all the layers and sheaths of the hair-follicle. This sac must therefore have undergone a striking increase, both in superficial area and in thickness : and althouo;h I am far from wishin(T to assert that this increase in size is the cause of the over-secretion and reten- tion, it nevertheless seems to me a very important fact, that in proportion to the gradual increase in the production of epi- thelium, the area, not only of the epithelial layer itself, but that of the organ which I regard as the matrix of the epithelium, has also undergone an increase. Moreover it is clear that the increased production of epithelium is at once the cause and the consequence of the dilatation of the folHcle, the case falling nnder the category of those circles of cause and effect with which we are familiar in the pathology of physiological cysts, e.gf. the urinary and gall-bladders. The contents of the cyst are now friable and greasy, now more honey-like, now a stiffl}" gelatinous, transparent and concentrically laminated mass. On one occasion I came across a cyst which admirably illustrated the popular German name of GrutzheuteJgescliiculst. In a thin fluid like the yolk of a raw egg, a number of grey, translucent granules, not unlike boiled groats, were suspended. All athero- matous cysts of any size usually contain cholesterin in large quantities, which gives the grueliy matter a spangled lustre. The microscope shows us that all matters resembling boiled groats or jelly, all the white, friable contents of the cyst, are made up of epidermic cells in a partial state of fatty degeneration. The yellow constituents are granule-cells and oily debris; the glittering scales, as has been already stated, are cholcsterin- plates. We sometimes find a certain number of fine lanugo- hairs ; these have obviously grown either from pre-existing oj* from newly-formed hair-roots. Upon the whole, the hair is 392 MORBID ANATOMY OF THE SKIN. strikingly passive in all disorders due to retention. At first it acts merely as a plug to complete the closure of the follicular orifice. The greater the subsequent accumulation of epidermic masses, the more does the middle part of the hair waste ; its o-rowth is either whollv arrested, or continues for a while in a meaffi'e sort of way. § 334. Before leaving the present subject, some allusion ought to be made to a phenomenon, which is peculiarly frequent in association with atheromatous cysts, but which also possesses a certain degree of general interest in reference to the pathology of the hair-sac : I refer to its displacement. The normal hair-sac — so at least we are taught by normal histology — is embedded in the substance of the true skin ; it is only the longest and most vigorous hairs which push their roots into the subcutaneous adipose tissue. This statement needs qualification. It is true that in a cross-section through the healthy skin, the great majority of the hair-sacs really do not extend beyond the limit of the cutis. No sooner however is the hair-sac enlarged to any considerable extent, than it forces its way out of the cutis and becomes subcutaneous. Accordingly even the smaller atheromatous cysts are all situated, not in the substance of the cutis, but underneath it. We observe a pre- cisely analogous displacement of the follicle in Iujdus, in hyper- trophy of the sebaceous glands, &c., so that its cause is really worth inquiring into. And here an old observation of my own, which I made during the investigation of a colossal myxoma (twelve pounds in weight) from the skin of the back, comes in very appropriately. This tumour had originated in the subcutaneous areolar tissue ; the skin over it was very tightly stretched. On removing any part of this cutaneous investment and examining its under surface with a powerful lens, it became at once apparent that the hair-sacs with their appended sebaceous glands were pro- jecting from it. Some were quite free ; others lay in shallow, funnel-shaped depressions, formed by the dissociation of the fasciculi of the dermal connective tissue. The general im- pression conveyed was, that pre-existing recesses had been opened up from below by the stretching to which the skin was exposed, just as the mouths of the uterine glands become funnel- shaped when the mucous lining of the organ is distended from ACNE. — SYCOSIS. 393 ■within during pregnancy. This led me to subject bits of healthy skin to a renewed examination ; and I then found that wherever ii hair-sac of medium or large size (I except only the smallest lanugo-hairs) was implanted in the cutis, it lay, not so much in its substance, as in a sort of prolongation of the subcutaneous connective tissue. Now should a follicle of this kind increase in size from any cause, it must separate the fibrous bundles of the corium from one another quite as effectually as dilating pressure from below ; the recess is opened up ; and the above-mentioned prolongation of lax connective tissue acts as a gubernaculum to guide the hair-sac in its descent into the subcutaneous tissue.* /3. Inflammation. § 335. The state of things in the interior of the hair-follicle, and especially the retention of its secretion, cannot continue without reacting on surrounding parts. We have seen that in molluscum contagiosum, as well as in atheromatous cysts, hyperplastic changes in the surrounding connective tissue were excited by the retained secretions, changes wdiich ultimately resulted in swelling and thickening. Inflammation of the hair- gacs — or rather inflammatory processes starting from the hair-sacs — proves however, that this reaction of the environment against the morbid state of the follicle, may also assume an acute and heteroplastic character. § 336. What is known as Acne, presents us with a series of anatomical phenomena, consisting essentially of retention of secreted matters on the one hand, and of a perifoUicular inflam- mation on the other. This eruption is very common as an accidental complication of comedones and milia. It may be that the products resulting from decomposition of the stagnant con- tents of the follicle act as irritants upon the cutis. A more luilikely supposition is that the perifollicular inflammation is primary ; that it causes swelling of the subepithelial connective tissue about the neck of the hair-sac ; and so, by stopping up its mouth, brings about an accumulation of secreted matters as a * Wertheim had already pointed out (in 1864) the mode of implanta- tion of the hair-sac, and shown that it passed directly into a fasciculus of connective tissue coming from the deeper layers. (On the Structure of the Hair- Sac in Man, &c. Sitzber. der Kais. Akad. Bd. L. April.) 3M 3I0IIBID ANATOMY OP THE SKIN. secondary phenomenon. In e\'ery pustule of acne, we must distinffuisli anatomically between the alterations in the central hair-sac, and those in the surrounding connective tissue. The root and root-sheath of the hair remain passive throughout, save that a large number of epidermic cells in a state of fatty de- fifcneration collect between them. All the more strikinoj is the active part taken by the sac of connective tissue in the inflam- matory process. It appears to be completely converted into pus ; for in the matter squeezed from a ripe acne-pustule, I have never found an}^ trace of it ; nothing but the hair, together with the pus-corpuscles and epidermic cells ; and this although the residual loss of substance is twice or three times as large as the original hair-sac. The vessels of the follicle, owing to the liquefaction of the connective tissue in which they lie, undergo maceration ; the cells which line the sac appear to share in the inflammatory proliferation, and the wails of the sac to lose their cohesion in consequence ; for when the escape of the pus relieves them from compression, they nearly always give way. The true seat of inflammation is the surroundino; connective tissue of the cutis ; hypercnemia, plastic infiltration, and sup- puration, following one another in an area extending from half a line to two lines from the follicle. The pus collects round the latter, and long before we can detect it shining through the cuticle, a drop of it exists in the depths of the cerium, which may be evacuated by a puncture {G. Simoii). It is not till a later period, that the little abscess begins to point. The mouth of the follicle opens very gradualh*, the bundles of connective tissue which surround it yield very unwillingly. The pus-cells burrow between them and tlie epidermic portion of the hair-sac, and accumulate round the shaft of the hair, pushing the epi- dermis before them. Finally, the process culminates in the speedy rise of a somewhat abrupt, straw-yellow pustule. If the pustule be punctured and kept from drjang up, it gradually empties itself of its own accord. As a rule, a firm pinch expels both the pus and the follicle which contains it. The proliferative activity in the skin rapidly subsides thereupon ; the bundles of connective tissue come tocrether ao^ain, and the little hollow which was formerly occupied by the follicle is filled up with a small quantity of cicatricial tissue. Sycosis is merely a variety of acne. While the latter is FURUNCULI. — ANTHRAX. 395- chiefly confined to those regions of the skin which are coated with down only, the former attacks the hairy scalp, the beard^ the eyebrows, &c. No previous retention of secreted matter in the affected follicles can be shown to occur. Kblnier finds the source of irritation in a vegetable parasite which invades the hair-follicle ; I agree with Hehra in believing that this parasite is very seldom to be found. § 337. The assumjDtion that furuncular inflammation in- variably starts from a hair-follicle, is certainly not universally received ; every one must admit the occasional possibility of such an origin ; and if it be an accident, it is undoubtedly a very singular one, that I myself should never have been fortunate enough to meet with any other mode of origin. Considering how common furunculi are, it is clearly easy to get any quantity of the so-called '^cores'' for examination. These, however, da not suffice to decide the vexed question as to the origin of the inflammatory process. For this purpose it is necessary to have recent specimens with the whole of the neighbouring skin for examination ; and these are not readily to be had. Whenever I had an opportmiity of examining such materials, I invariably found, in the focus of inflammation, one of those funnel-shaped protrusions of the subcutaneous connective tissue into the cutis, which serve, as has already been shown, for the reception of hair-sacs (§ 334). Bardelehen'' s account is very similar (^Bar- deleben, Lehrbuch der Chirurgie, vol. ii. p. 17). Furunculi differ from acne and sycosis in the extent of the inflammation ; this is not confined to the substance of the cutis, but, though reaching its maximum intensity in that structure, spreads at the same time into the subcutaneous connective tissue. Once upon this very irritable soil, the inflammation rapidly extends over disproportionately large areas. The hyperasmia, together with a vigorous lymphatic saturation, suffice of them- selves to cause the nodular swelling (perhaps as large as a pigeon's egg), wdiich can be felt through the tense and diffusely reddened skin. Li marked contrast to the wide extent of these preliminary stages, the inflammatory proliferation is really confined within narrow limits. It extends but a little way from the circumference of the above-mentioned protrusion of subcutaneous connectI^'e tissue into the substance of the cutis. Within this area, however, the 306 MORBID ANATOMY OF THE SKIN. plastic infiltration assumes such proportions, the accumulation of pus-cells is so dense, that the blood-vessels undergo compression. In one variety of the furunculus, the Anthrax, this goes so far as actually to cause the death of the infiltrated part, which grows as black and dry as boot-leather ; in ordinary furunculi the process does not go beyond simple necrobiosis ; many of the cells show signs of fatty degeneration. In either case, however, the mfiltrated part is gradually cut off from the surrounding con- nective tissue by a process of suppurative demarcation, and expelled from the skin — a termination usually hastened by opera- tive interference. It constitutes the familiar "core" which, when teazed out under the microscope, exhibits nothing beyond disintegrating cells and a few fibres of connective tissue amid a mass of debris. After the expulsion of the core the sinuous ulcer which remains, heals by the second intention, leaving a stellate scar. y. Hypertrophy. § 338. Active enlargements of the hair-follicles, due to morbid growth, must be distinguished fi'om their passive enlargement, due to retained secretions. Next, they must themselves be divided into true and ftilse hypertrophies ; the former retaining the original anatomical and physiological character of the parts ; while in the latter, the increase in size is associated with some specific modification of structure which arrests their normal functional activity. The hair-sacs and their appended glands thus become foreign to the organism ; they pass into the category of heteroplastic tumours. The consideration of these "false" hypertrophies will therefore be deferred for the present. § 339. A true " overgrowth of hair" can only be said to exist in hairy moles, the so-called "mice" (iicevus spilus). These brown, hemispherical or flattened elevations of the skin, sometimes of considerable size, would seem to offer peculiar facilities for the most luxuriant growth of hair. Not only are the individual hairs very stout, but, if we happen to possess a mole of om' own, we notice that its hairs are shed and renewed much oftener than those of the head and beard. If we make a vertical section through one of these nsevi, we find at least one- fom'th of the hair-follicles, which are very thickly set, furnished OVERGROWTH OF SEBACEOUS GLANDS. 397 with a little accessory sac occupied by a new hair In a more or less advanced stage of development; we find the appearances which KoUikei' has figured in his Handbook (figs. 79 and 80). I cannot but seek the essential feature of the ncevus sjnhis In this overgrowth of hair. The sebaceous glands are in nowise implicated. § 340. Once, and once only have 1 met with a true over- growth or THE SEBACEOUS GLANDS, and I question whether the growth described by F'drster under the name of " glandular tumour" of the sebaceous follicles is a true hypertrophy at all, since it exhibits a certain rodent tendency which is only asso- ciated with the false hypertrophies, with lupus and cancroid. The tumour Avhich I examined was sent me by Professor Wernlier of Giessen ; it was as big as a pigeon's Qgg, and attached by a broad base to the hairy scalp ; it was freely moveable. The skin over it was pitted ; the holes could be seen with the naked eye ; they were the mouths of hypertroj^hied sebaceous follicles ; no hairs were present. Sections of the tumour forcibly reminded me of slmilai* sec- tions from a normal mammary gland. Amid the thick trabecular of a very tough stroma, there lay acini consisting of from three to five terminal follicles with a common efferent duct ; among these were scattered wider ducts, cut across transversely and obliquely. Each acinus contained very small, round, epithelial cells ; the ducts were filled with solid and liquid fattv matter. The growth as a whole was of a homologous character ; it was nothing more than an overgrowth of the normal type of a seba- ceous gland, similar to that which is normally carried out in the mammary gland. § 341. This is the place to say a few words about a true HYPERTROPHY OF THE SUDORIPAROUS GLANDS, by Way of appcudlx to the present section ; for I do not intend to devote a separate chapter to these structures. The false hypertrophies of the sweat-glands, like those of the sebaceous follicles, fill under the head either of epithelioma or of lupus. True hypertropliy of the sudoriparous glands gives rise to a flat, fungoid elevation of the skin, which, smooth and hairless. Is not unlike a soft wart. On cutting into it however, we see at once that neither the papillary body, nor any other part of the cutis, is involved. The sweat- glands, as everybody knows, lie at the junction of the skin with the subcutaneous connective tissue ; it is here therefore that the- 398 MOEBID ANATOMY OF THE SKIN. main body of the tumour is really situated ; it consists of a pad of sweat-glands, from three to four lines in thickness, and of corresponding Avidth. Each single gland may attain to the diameter of one line ; the adipose tissue seems to be partly pushed aside, while the bands of connective tissue between the individual glands are thickened. The occurrence of small cysts, full of clear mucus, must be regarded as a sign of retrograde metamorphosis. They originate in the total liquefaction of single glands, and occupy exactly the same space. 0. Heteroplastic Tumours. — Lupus. § 342. The undoubted participation of the hair-sacs and sebaceous glands in the genesis of epithelial cancer was satisfac- torily proved in § 166. The hair-sacs and sebaceous glands were shown to behave just like all other protrusions of the epi- dermis into the cutis ; like the sudoriparous glands, and the downward processes of the rete Malpighii which occupy the interpapillary furrows. There exists, however, a true adenoma of the sebaceous and sudoriparous glands, a tumour which, in common with all adenomata, is closely related to epithelial can- cer, but Y/hich differs from it, like ail other adenomata, partly in its structure, partly by its more local and ametastatic cha- racter : I refer to Lupus. § 343. If my views of lupoid growth should seem to be more in accordance with the older than with the more recent observations on the subject, this is probably due to the great reluctance of recent authors to see anything peculiar in lupus, any departure from the common type of inflammatory growth. In reality the lupoid tubercles are so characteristic, not only in their mode of origin, but in their structure also, that I readily pledge myself to recognise lupus, quite as certainly as cancer, by microscopic analysis alone. It is true that the cells of the lupoid tubercle are, on the whole, of small size and round, that they are closely packed, and held together by a mucoid cement ; so that if it were desired to find a name foi* the tissue of which they consist, that of embryonic tissue might well he chosen as the fittest. But ought we on that account to neglect the manifold variety of internal stinicture, and the very singular mode of origin, of this embryonic tissue ? LlPUS. 301) First, as to structure. Every lupoid tubercle, whether it be situated in the cutis or in the subcutaneous connective tissue, presents a well-marked acinous composition. This is easily proved by examining sections of a piece of skin infiltrated with lupus, after it has been hardened in alcohol, steeped for eighteen hours in a strong solution of carmine, and finally cleared up with appropriate agents, among which Canada balsam is the best. In the smaller tubercles we distinguish from two to three, in the larger ones — those abotit the size of a hemp -seed — from seven to ten roundly-oval, tortuous bodies, everywhere studded with roundish projections ; these bodies arc bulbous at one end, tapering off at the other to converge towards a common centre (fig. 120, a). These bodies are made tip of cells of considerable size, whose protoplasm has resisted the carmine, and whicli accordingly appear white, in marked contrast to the remaining parenchyma of the nodule in which they are embedded. This residual parenchyma (fig. 120, h) consists entirely of true em- FiG. 120. Lupus. Vertical section, showing tlie passage of the health j skin into that which is most infiltrated, a. Acinous nodules ; h. Embryonic tissue of the lupus-nodule ; c. Altered hair- sacs and sebaceous glands. -^. bryonic tissue ; the cells are small, perfectly round, lustrous and readily tinted by carmine. Here too the vessels of the lupoid nodtde, as described by some authors, ramify : they form a net- work round the bulbous ends referred to above, towards wln'ch they stand in the same relation as that taken up by the vessels towards the terminal follicles of an acinous gland, thus confirm- ing my view of the acinous structure of the lupoid nodule, ^ § 344. We have next to ascertain the cause of these highly characteristic appearances ; the notion that tlie acinous composi- 400 MOEBID ANATOMY OF THE SKIN. tion of the nodule may be due to the degeneration of some pre-existing structure of the same sort — such as that of the sebaceous glands — suggests itself spontaneously. Now if we make vertical sections through the advancing border of the lupus, sections which include both healthy skin and that which is completely diseased, we see at a glance, that the sebaceous glands do really take a very important part in the disease. It has long been known that at the extreme periphery of the aifected region they s\yell np and shine through the cuticle as white nodules. This swelling is due, partly to a proliferation of the glandular elements, partly to the fact, that instead of undergoing fatty degeneration, the cells grow large and vesi- cular, distending the body of the gland even to five times its normal bulk. The root-sheath of the hair also takes part in this- degenerative change by producing, instead of the usual flattened epidermic cells, large vesicular corpuscles like those produced by the sebaceous gland. This productive activity, however, is not as a rule exhibited by the entire root-sheath in the same degree; it is now confined to the fundus, now it involves the fundus together with one or more points above it ; this very soon gives the hair-sac proper a varicose and knotty aspect. The hair perishes. Glands can no longer be distinguished from hair- sacs ; they are all exactly alike. Yet up to this point the con- dition is in no sense peculiar to lupus ; since the metaplastic enlaro-ement of the cells is also found in the neiohbourhood of leprous, syphilitic, and especially epitheliomatous diseases of the skin. The characteristic part of the disorder is that which imme- diately ensues. § 345. Lupus has been held on various grounds to be a pro- liferation of the corpuscular elements of the rete Malpighii (Berger^ Dissertatio inaugur. Greifswald ; and Polilj Virclioics Archiv, Bd. vi.). I may be said to agree with this view in one sense, inasmuch as I too seek to localise the proliferation at the junction of the epithelial and connective-tissue layers ; but I do not limit it to the rete Malpighii, i.e. to the boundary-line between connective tissue and ej^idermis in its stricter sense ; on the con- trary, I regard it as concentrated in the glandular inflexions of the epidermis. The process begins as a luxuriant corpuscular proliferation in the interstitial and capsular connective tissue of the sebaceous and sudoriparous glands. This proliferation extends LUPUS. 4h1 to a variable distance into tlie siuTounding parts ; its progress may be admirably watched in the adipose tissue which invests the deeper sweat-glands; little round corpuscles make their appearance between adjacent fat-cells, which they engirdle, before entirely covering and masking them from view. On the other hand, the cell-growth often extends deep into the subcutaneous connective tissue along the afferent vessels ; in the interior of the gland itself, the mass of newly-developed embryonic tissue also exhibits a dendritic arrangement, the parent-trunk coinciding- with the point of entrance of the afferent vessel. In proportion to this exuberant cell-growth at the peri- phery of the glandular tubes and acini, the latter themselves increase in bulk ; their shape is altered, they become knotty and bulbous, as described above ; their cavities are obliterated, and only their general arrangement can be traced ; the parenchyma being grouped round a central point which corresponds to the efferent duct. The cells of which the degenerated acini consist, are not the same large, vesicular elements, which took up so much space during the stage of primary enlargement. Their size is only about double that of the embryonic cells ; they are con- centrically aggregated into little groups ; we notice indications, as it were, of a tendency towards a higher degree of epithelial development ; but the cells never get beyond the stage of those which make up the rete Malpighii. § 346. It may be objected that lupoid nodules are not always superficial, that they are often met with deep in the subcutaneous connective tissue. To this objection I rejoin, that the sweat- glands, in particular, may even normally lie very deep, and that as they increase in size, they are necessarily dislocated in a down- ward direction, just as happens in the case of atheromatous cysts. Finally, I must not omit to state that the development of granulation-tissue, in what is known as the hypertrophic variety of lupus, extends far beyond the limits of the glands, and tliat this granulation-tissue is capable of being converted into mature connective tissue, forming indurations like those in elephantiasis. But the lupoid nodule proper is always an adenoma of a sebaceous or sudoriparous gland. The further destiny of the lupoid products is usually this : the parenchyma proper undergoes fatty degeneration Avhile the intermediate granulation-tissue is converted Into pus. The little 2«> 402 MOEBID ANATOMY OF THE SKIN. abscesses thus formed, burst, and discharge their contents. Tumours and cicatrices follow the same law as in leprosy and syphilis. e. Atrophy, § 347. The falling-oflP of the hair of the head in old age is due to a total involution of its place of origin, i.e. of the hair- sacs and the roots of the hair. The former are dilated and shortened, the latter grow smaller, and either disappear or are only capable of producing and nourishing a lanugo. Premature baldness is invariably connected with a dis- ordered relation between the production of epidermic cells from the hair-sac on the one hand, and from the hair-root on the other. If cells are formed in excessive numbers by the lining of the sac, the lateral pressure to which the hair is exposed in the interior of the follicle, interferes with the nutrition of the shaft, and causes it to wither and become spontaneously detached from its root. This occurs in the '^defluvimn capillorum" which is met with in the course of constitutional syphilis, or after acute diseases, such as typhus abdominalis. The second and far rarer case is when the productive activity of the root sinks below its normal standard. The hair-follicle is in nowise altered, but the normal degree of lateral pressure exerted upon the shaft by the narrowest part of the follicle (just below the point at which the sebaceous glands open into it) is too great to be overcome by the diminished upward strain of the growing haii\ The latter is accordingly arrested at this point ; its cells undergo a finely-granular metamorphosis, preliminary to a solution of continuity which is effected by the least traction upon the shaft from without (as in combing the hair). The remaining stump is very soft ; it becomes swollen and knotty, owing to the fact that the materials furnished by the root, though inadequate for the construction of a normal hair, yet form, in course of time, a shapeless corpuscular aggreo-ate of considerable size. {Alopecia areata. Area (7ehi.) Y.-MOEBID ANATOMY OF MUCOUS MEMBRANES. § 348. From the mouth to the anus, there extends a system ■of membranous canals, which, owing to their free surface beino- always moist, and coated A^dth a thin layer of mucus, have re- ceived the name of the Mucous System. The membranous walls of these canals are in direct continuity with the skin ; like the skin, they serve to shut off the organism from its environment the I from the not-I ; this must always be kept in view ; we must bear in mind, for instance, that whatever a man may have taken Into his stomach, is still only at the gates of the organism, not in its interior. Not only is the skin continuous in a general way with the mucous tract at the oral, nasal, ocular and aural apertures, at the anal, urethral and vaginal orifices, but each individual layer of the skin may be traced into a correspondino- layer of the mucous membrane ; the epidermis into the epitlie- lium, the cutis into the mucosa proper, the subcutaneous into the sub-mucous tissue.* Moreover each layer retains its general character ; the epithelium continues to serve as a protective covering which shuts olf the organism against tlie world without, the mucosa represents the proper connective tissue of the mucous membrane, the submucous is a lax areolar tissue which facili- tates the movements of the mucosa upon the muscular coat. But within these limits of homology, both the structure and the fanctions of each layer are modified in accordance with the |)hysiological duties of the various div'isions of the mucous tract. First, as regards the epithelium. At all tlie mucous orifices the horny lamina of the epidermis disappears, so that the ;itrial * The fourth layer of the mucous tract — the muscular coat — docs nob form, any part of the mucous membrane proper ; it corresponds to the locomotive apparatus of the body in its entirety, to the osseous and muscular systems ; the fifth layer consists in either case of serous membrane, forming on the one hand the visceral, on the other, the parietal lamina of the same serous sac. 404 MUCOUS MEMBRANES. chambers of the mucous tract (the buccal cavityj pliarynx and oesophagus, conjunctiva, vulva, preputial sac, bladder and ureters) are lined only by the mucous layer of the cuticle, the so-called laminated pavement-epithelium. This laminated pavement- epithelium consists, like the rete Malpighii, of a single layer of small, columnar cells, and a stratum of variable depth of larger pavement cells, which grow flatter as they approach the free surface, where they are finally shed. As reo;ards the meanino; of this diminution in thickness of the epithelial layer in the vestibular portions of the vegetative tract, there cannot be two opinions. It is the first step towards an increased facility of osmotic interchange between the fluids and gases contained in the cavity, and those contained in the blood. Wherever such interchange is more active, wherever absorption or secretion are going on, wherever it lies at the root of the general nutrition of the organism, the pavement cells disappear entirely, and the columnar cells alone remain. Thus the ali- mentary canal from the cardia to the anus, the respirator}- passages, the female generative organs from the external o^ inwards, are lined with columnar epithelium. Its cells are larger than the columnar elements of the rete ; the}- exhibit manifold varieties of external form, in accordance with the functional necessities of particular regions ; inasmuch, however, as they are planted immediately upon the connective tissue, and as between their bases only a few reserve cells, to replace those which are shed, are here and there apparent — cells which might certainly be demonstrated in the rete Malpighii also — I cannot see any objection to their being viewed as the anatomical equi- valent of the columnar cells of the rete, notwithstanding any modifications of size and form which they may present. Like the epithelium, the proper substance of the mucous membrane undergoes adaptation to the special functions of the individual portions of the tract. In parts devoted merely to the transmission and storage of their contents — in the oesoj^hagus, biliary and urinary passages, vagina, &c., we find an equable layer of tough fibrill^e of connective tissue, terminating in a smooth and even surface underneath the epithelium, while on the other side it is uninterruptedly continuous with the bundles of the lax submucous connective tissue. Its texture is very different where the tract is devoted to absorption or secretion. CATARRH. 405 Here the mucosa lodges tlic most important glandular organs, while its surface and its component tissues are modified in accordance with the functions which it has to perform : e.cj, for purposes of absorption it is important that as wide an area as possible should be brought in contact with the chyme ; we find this requirement met b>^ the villi with Avhich the alimentary inucous membrane is beset from the duodenum downwards, each villus containing a lymphatic radicle in its axis ; and in order still more to facilitate absorption, we find the layer of connective tissue which intervenes l^etween the vessels and the epithelium, presenting in a very high degree the properties of lymphadenoid tissue, with whose structure we first became acquainted in the lymphatic glands. The absorbent apparatus includes moreover the numerous follicular (conglobate, Ilenle) glands ; the solitary glands, the patches of Feyer^ the tonsils, and the saccular glands at the root of the tongue. These may be said to form the first stage on the road, which the matters to be absorbed by the lymphatic system have to traverse. Should these matters happen to be pathological irritants, their path is marked by liypera^mia, inflammation and morbid growth ; hence it is, that in so many of the general disorders of the entire alimentary tract, we find these follicular structures peculiarly involved. Of the secreting glands, it is only the smaller ones, the simple tubular glands, which are situated in the thickness of the mucous membrane, while those of larger size, the follicular mucous glands, are mainly embedded in the submucous tissue. Nevertheless, some mucous membranes are inordinately rich in glandular structures; e.cj, the gastric mucous membrane has five-sixths of its bulk made up of gland-substance. About the submucous tissue there is not much to be said ; we shall find it a peculiarly favourable locality for the develop- ment and spread of morbid growths, Avhen these come to be discussed. a. Inflammation. 1. Catai'ihal Inflammation. — Catarrh. § 340. The larger half of all the diseases to which humanity is liable, consists of catarrhal affections of mucous membranes. 40(3 MUCOUS MEMBRANES. or of disordei^ conii)licated by tliem. The term '*' catarrh " la} -^ stress on only one, tliough certainly the most prominent phe- nomenon of the disease, sc. the increased secretion from the mucous surface. We must hear in mind, however, that the increased secretion can never occur without a simidtaneous liypersemia of the mucous membrane, and that this hyper99mia is the proximate cause of the increased secretion, and the more or less remote cause of farther troubles, of swelling, ha3mor- rhage, pigmentation, hypertrophy, (fcc, all of which must be included in any complete view of the morbid anatomy of mucous catarrh. Hyperemia must accordingly be regarded as the anatomi- cal basis of catarrh. It may either be active or j^assive. In the former event, it is the primary result of some antecedent irrita- tion ; in the latter, it lasts for a long time before catarrhal, inflammation is set up — it acts as a predisposing cause ; (I am thinking of the bronchial catarrh of heart disease, of the gastro- intestinal catarrh associated with portal obstruction, of the catarrhal affections of the rectum and bladder due to piles). AVhether we are justified in assuming that the catarrh ij^ actually excited in these cases by some special exacerbation of the existing hyperai'mia, or even by some modification in its passive character, I cannot take it upon me to decide. To my mind, it appears more profitable to inquire how far, and in what localities, the normal structure of the mucous tract favours the origin or the continuance of hyper?3mia. And first, we must recollect that owing to the tenuity and permeability of the epi~ thelial stratum, the access of external irritants to the irritable- elements of the mucous membrane is far easier than in the skin ; moreover, that there is no elastic covering, like the horny lamina of the cuticle, to check the turgescence of the capillaries ; nay, the softness of the parenchyma sets no limit to their disten- sion. The relations in which the contractions of the muscular coat of the bowel stand towards the distribution of blood in the mucous coat, are of peculiar interest. The small arteries and Aeins, which carry the blood to and from the capillary networks- of the gastro-intestinal mucous membrane, penetrate, as is well known, obliquely through the muscular coat. Here they receive a sheath of loose connective tissue, which, in the case of the arteries, is tolerably wide, so that a considerable space is left CATAHRH. 407 between the vessel and the muscular fiisciculi ; in the ease of the veins, on the other hand, it is exceedingly slight ; these are accordingly liable to be compressed, whenever the muscular coat contracts. Hence every such contraction must hinder the efflux of blood from the alimentary mucous membrane ; its vessels are congested, the congestion lasting as long as the contraction, and being liable to assume a more chronic character if the contractions are often repeated. The beariiigs of this arrangement upon the digestive process are very obvious. The peristaltic contractions, besides pushing on the contents of the bowel, help both secretion and absorption by exciting and keep- ing up a hyperiemic state of the mucous membrane ; they aid secretion, by supplying the open glands w^ith raw material in greater abundance ; they help absorption, by causing that injec- tion of the capillaries of the villi, which, according to KoUiker, co-operates so weightily towards the filling of the axial lymphatic space. Mean^vhile, we must remember that every physiological hyperaemia is a gift of the Danai to the organ which is liable to it ; since the least derangement of the machinery converts its benefits into curses. So in the present case. 'No mucous mem- brane exhibits catarrhal disturbances of circulation in so intense a degree as that of the stomach and intestines ; for the irritant which affects the mucous membrane excites peristaltic contrac- tion quite as promptly, and far more powerfully, than the food. Dysentery and cholera afford colossal examples of the harm which may accrue in this way ; the intense oedema of the mucous membrane of the large intestine in the former disease, the hfemorrhages, even the diphtheritic lesions, are partly due to the violent tonic spasm of the muscular coat ; and if we go on to assume that in cholera, an excess of peristaltic activity contri- butes in some measure towards the copious flux from the gastro- intestinal surface, we shall have got at a causal nexus between two of its most familiar symptoms. But we need not go so far afield in search of illustrations ; the phenomenon exhibited on so great a scale by cholera and dysentery, is repeated on a small one in every catarrh, however trifling. We shall come across it again when we discuss the patholog}' of haemorrhage from mucous surfaces, and that of gastric ulcer (perforating ulcer of the stomach). It is onlv the vesical and uterine mucous membranes which 08 MUCOUS MEMBEANES. are subject to similar conditions. Menstruation is associated with clonic contractions of the muscular coat of the uterus. Some mucous membranes, however, are not well adapted for the occurrence of hjpergemia. The more abundantly a mucous membrane is provided with elastic fibres, the more does it resist distension bv congestion and oedema; indeed the tendency of tlie membrane to return to its normal volume, increases in pro- }>ortion to the stretching which it undergoes ; this is a necessary result of its elasticity. Many of the phenomena exhibited by the respiratory mucous membrane, which is peculiarly rich in elastic fibres, nmst be ascribed to this cause. Sudden and great swelling onlj- occurs in parts furnished with a very lax sub- nmcous areolar tissue, in the folds about the laryngeal orifice, ])articularly the ary-epiglottidean ligaments, and certain portions of the mucous lining of the nasal cavities. The swelling in such cases howe^•er, is not situated in the mucosa ; it is due to oedema of the submucous connective tissue. It disappears very rapidly as soon as the clastic reaction of the stretched membrane pre- ^•ails over the tension of the dropsical effusion kept up by the blood -pressure ; especially after death, when it is often quite impossible to demonstrate the existence of an oedema, which manifested itself most unequivocally during life, and which may even have been the cause of death (oedema glottidis). § 350. It is obvious that the swelling of the catarrhal mucous membrane, the second anatomical element in this variety of inflammation, depends, at least in some degree, upon the hypera3mia ; i.e. so far as it is due to over-distension of the vessels, and the abundant saturation of the mucous membrane with serum. The latter element is very prominent in all forms of catarrh due to passive congestion ; it is recognised by the bacon}' lustre of the swollen membrane, and by the flow of clear serum from its cut surface. The swelling is much greater when tlie submucous tissue also is involved ; this is most common in the caecum. For the pathological histologist, these passive forms of swell- ing are less interesting than the active varieties; i.e. the enlarge- ments of the LYMPHATIC FOLLICLES duc to corpuscular prolifera- tion in their interior. Owing doubtless to the intimate connexion of these glands with the process of absorption, we find catarrh of a mucous surface almost ahvavs associated with a more or less CATARRH. 409 onnective tissue, and then on to the free surface. Should the bleeding be arrested, some of the extruded blood-corpuscles are retained in the parenchyma, where they are converted into a brown or black pigment. Accordingly i\\(i mucous membrane CATABKll. 415 comes to exhibit throughout, a brown, yellow, grey, or even black hue ; the distribution of the pigment following the law which has just been set forth ; it is only in rare and very severe cases that it is more uniformly distributed, so that the stomacli, for instance, looks as if it had been flooded with ink. § 354. A series of peculiar phenomena is due to the possi- bility of serous transudation from mucous membranes lined with laminated pavement-epithelium. The outermost, compact layer of cells, resists the passage of the serum for a time ; it is stripped from its bed, and so forms vesicles or bullae Accord- ingly, in catarrhal affections of the buccal cavity, we not unfre- quently see the mucous membrane of the lips, gums, tongue and cheeks studded with transparent, watery blebs, some as large as a pea, while the majority are no bigger than a millet-seed ; in about tw^enty-four hours' time they burst and discharge their serous contents. Here the matter may end ; or the raised por- tion of epithelium may become altogether detached, leaving a small, circular defect, an excoriation, behind. The denuded patch of mucous membrane proceeds to secrete pus ; its epitlielial border becomes sodden, and appears to the naked eye as a sharp, w^hite margin ; the entire patch is surrounded by a hyperasmic areola, and the circumscribed purulent catarrh lasts until the cessation of the general catarrhal state. These " ulcers " may increase considerably in size ; the greater part of the buccal surface may thus come to be quite raw, wdiile the smaller })art continues normal (scurvy, putrid stomatitis). Analogous conditions are met with in all the atrial chambers of the mucous tract (see § 348). We are most familiar v,'ith those about the os uteri externum and the glans penis. § 355. Complete and incomplete degeneration^ cJironic catarrh^ and hyperplastic conditions of the mucous membranes. What has been said above concerning catarrhal inflammation, refers to its acute variety, which runs a definite course. After this is com- pleted, the mucous membrane may return entirely to its normal state. In this connexion, the behaviour of tlie parenchymatous connective tissue of the mucous membrane is most important. We have already seen (§ 352) how actively the subepithelial connective tissue takes part in the catarrhal process. The fleshy thickening of the catarrhal mucous membrane was due, i]i no small measure, to an infiltration of the subepithelial connective 416 MUCOUS MEMBRANES. tissue witli corpuscular elements (fig. 121, h). All these cells must be removed before the mucous membrane can be said to have returned entirely to its normal state. Some of them undergo fatty degeneration ; others may be taken up by the lymphatics. But weeks may elapse before this is effected ; and during the interval, the mucous membrane offers a dimhiished capacity of resistance to fresh sources of irritation. For the irritability of an organ is proportional to the number of elements susceptible of irritation, -svliich it contains. This is not always sufficiently remembered either by the physician or his patient. The latter is in much the same position as a person whose mucous membranes are predisposed to catarrhal inflammation by a passive hypera3mia. There is always a risk lest the catarrh should return on the slightest provocation, and that in exactly the same part which it has apparently forsaken. The relapse is usually more obstinate than the primary disease ; the vulner- ability of the mucous membrane, and the consequent risk of a fresh relapse, increases and lasts for a longer time after every recurrence of the inflammation. Every relapse adds to the number of cells in the connective tissue of the mucosa ; the epithelium too, and the glandular apparatus, come gradually to take part in the chronic thickening ; the mucous membrane becomes hypertrophied. Hypertrophy, viewed in this light, is therefore a result of catarrh ; it may also be regarded as a structural cause which predisposes to catarrh, inasmuch as the phenomena which, when taken together, constitute catarrh — sc. hyperaemia, swelling, hy2:)er-secretion — have already reached a certain pitch, at which they have become stationary ; so that a very trifling provocation suffices to raise them to the level of catarrhal inflammation. (Chronic catarrh.) § 356. Let us now consider the anatomical factors of HYPERTROPHY OF THE MUCOUS MEMBRANES OUC by OUC. a. The overgrowth of the connective tissue is particularly striking where (as in the gastric mucous membrane) its amount is normally insignificant, where it is a mere cement, holding the closely - packed tubular glands together. The narrow septa between the glandular orifices, as the most superficial locality of this cement, are often the theatre of a very luxuriant overgrowth of young connective tissue; they form villous and lamellar elevations, to a heiccht of one line above the mucous surface, CATARRH. — HYPERTROPRY. 417 wlicn they may be recognised even with the naked eye. The overgrowth of the connective tissue however — both in its microscopical and naked-eye effects — is thrown very much into tlie background by the overgrowth of the glands ; one is prone to forget that the connective tissue which invests the enlarged glands, which forms the pedicle of a polypus, &c. , is itself, in the main, a new formation. h. The EPITHELIAL LINING of the hypertrophied mucous membrane is quite as continuous as in the healthy state. Hence we may assume that it increases in a horizontal plane, so as to keep pace with the increased area of the mucous membrane itself. It appears, moreover, to adhere more firmly than usual to the connective tissue ; for without showing the least breach in its continuity — without e.g. the loss of a single columnar cell from the respiratory mucous membrane — it allows the passage, not only of considerable quantities of transuded fluid, but also of great numbers of young cells, which migrate from the deeper parts to the surface, where they mingle with the secretion as pus and mucus-corpuscles. c. The increase in bulk of the open glands is usually re- garded as a functional hypertrophy. Just as the bulk of a muscle increases by exercise, so are the glands supposed to grow in consequence of continued over-secretion. In opposition to this view, I would lay more stress upon the retention of secreted matters, and the passive distension of the glands which ensues. The overgrowth of the subepithelial layer of connective tissue may very plausibly be regarded as a mechanical obstacle to the escape of the secretions. It may compress, narrow, dislocate, occlude the eff'erent duct, while the body of the gland, especially when situated in the submucous connective tissue, underneath, the mucous membrane, may increase in size unchecked. I must not be understood to reduce the glandular hypertrophy to simple dilatation. In the majority of hypertrophied glands we can readily see an elongation or twisting of the tubuli, an increase in the number of acini, as well as a luxuriant cell-growth both within and around the glands. But none the less do I mark, tliat the tubes and acini of the hypertrophied glands are in- variably wider, and contain a larger accumulation of secreted matter than they ought to do ; and I look for the stimulus which causes the morbid growth, in a centrifugal pressure of the 27 418 MUCOUS ME:.[BRANES. secretions, v/liicli are perhaps unable to escape v>'itli due rapiditVy owing to the narrowing of the efferent duct, but which, in any case, do not escape fast enough. § 357. From this point of view we can readily see how, under certain circumstances, the dilatation may preponderate over the hypertrophy, and how it is that we so often find cystoid DEGENERATION associated with glandular In^^ertrophy, in mucous membranes affected by chronic catarrhal inflammation. The two conditions complicate one another in various ways, giving rise to a series of coarser alterations of the mucous surface, which we may now briefly consider. What is known as the etat mamelonne of the gastric mucous membrane, is due to the fact that the mucous membrane, whose glandular layer is hypertrophied, comes to be too large for the area of its bed, and is therefore thrown into folds with intervening hollows. This plication of the mucous membrane is to some extent — as in the pyloric region — physiological ; hence the ^' etat mamelonne" is at first only a quantitative excess. It is only with the aid of the microscope, that we can draw the line between quantitative and qualitative deviations from the normal standard. The dilatation of the hypertrophied tubes, which is usually very striking, serves as a reliable criterion of the morbid nature of the alteration. Higher degrees of the ^' etat mamelonne " pass directly into polyposis ventriculi. We commonly find a number of transitional forms side by side in the same stomach. The folds are subdivided into smaller areas by furrows which cross them at right angles ; these are best seen at some distance from the pylorus, about the middle of the stomach : the overgrowth of the glandular layer pro- gresses steadily within these areas. A flattened, roundish tubercle soon projects above the surface. The higher it grows, the more disproportionate is the enlargement of its free ex- tremity ; it becomes fungoid and is finally converted into a polypus, with a globular head rather larger than a pea, and a very thin stalk. We occasionally find as many as thirty such polypi upon the mucous membrane of the stomach, with which moreover they ^'ividly contrast by their dark-red hue ; fi'om four to six of them are often seated on a commoii base ; next to cancerous products, they cause the greatest and most striking alterations in form, to which the gastric mucous membrane is CATARRH. — POLYPI. 419 liable. In their interior we find, besides the dilated tubuli, true cysts scattered here and there ; these are filled with a watery- fluid or with mucus. The intertubular connective tissue, to- gether with the walls of the tubes themselves, forms septa which take up as much space in j^roportion to the degenerated tubes, as the septa of an inflated lung in proportion to tlie alveolar cavities. It was characterised moreover, at least in the cases which I examined, by containing a large number of peculiar, roundly-oval, very lustrous bodies, hardly affected by reagents, whose histological significance I have not yet been able to determine. § 358. The '^ etat mamelonne " of the stomach leads on the one hand to '^ gelatinous " or ^^ cystoid " degeneration of the mucous membrane, on the other, to the formation of mucous polypi. Gelatinous degeneration, which has hitherto been ob- served only in the mucous membrane of the alimentary canal, comes about as follows : the crypts of Lieherhuhn are distended with mucus, and converted into retention-cysts as big as a millet-seed ; this change is limited to a circumscribed patch, which may, according to Virchoiv, attain the size of lialf-a- crown. The septa between adjoining cysts become atrophied; the cysts coalesce to form larger cavities; until at last the affected part comes to be mainly made up of mucus, the patch assuming a jelly-like colour and consistency. In mucous mem- branes which are more scantily provided with open glands, as e.g, in the cervix uteri and external os, the affection does not proceed so far as to cause gelatinous degeneration ; the distended glands tend rather to project singly above the mucous surface, forming vesicular elevations, or even pendulous cysts (the so-called ovula Ndbothi) ; these, in conjunction with the hypertrophied mucosa, which pours out an abundant secretion and is permeated by dilated vessels, constitute the sum-total of structural changes to which the term " chronic catarrh " or " chronic metritis " is applied. § 359. Mucous POLYPI, in the strict sense of the term, are jelly-like tumours, permeated by thin-walled capillaries which give them a reddish hue, and attached to a mucous surface by a more or less distinct pedicle. In outward form they are either smooth and rounded, or lobulated and fissured. When cut into^ the surface of section resembles their external surface in colour 420 MUCOUS MEMBHANliS. and consistency ; it exhibits in addition, fibrous bands of a milk- Avliite colour, radiating from the root of the polypus to its periphery, as well as mucous cysts of considerable size, which feel hard and elastic before they are cut open. Microscopic examination shows, first, a continuous layer of columnar epithe- lium investing the outer surface of the polypus. The main bulk of the tumour is made up of hypertrophied glands ; we find tubes whose walls frequently bulge outwards to a variable depth, and which terminate in clusters of fully -developed gland-follicles. The tubes are lined with well-formed columnar epithelium ; and filled with concentrically laminated masses of viscid mucus. Besides the mucous glands, we find a certain amount of soft connective tissue, rich in cells, which is dense and fibrous only in the pedicle and the bands which radiate from it. The pedicle is chiefly made up of the afferent and efferent vessels ; no nerves have hitherto been found in it. We may accordingly take it for granted that mucous polypi originate in a circumscribed hyper- trophy of the mucous membrane, which mainly involves its glandular elements. The mucous lining of the nasal fossae is their favourite seat ; next comes the mucous membrane of the uterus. More rarely they spring from the small and great intestines, the larynx and respiratory passages, the female urethra, the external meatus, the sinuses of the upper jaw and frontal bone. § 360. Chronic catarrh exerts a very singular influence upon the DUCTLESS GLANDS of the mucous membrane ; and this in- fluence is closely connected with the chronicity of the disease. It is only in the tonsils that a true hypertrophy, strictly analogous to the simple hypertrophic alterations considered above, is caused by repeated acute congestion of the pharyngeal mucous membrane. It consists in an equable and uniform overgrowth of all the histological elements of the follicles ; of the reticulum, the vessels, the lymph-paths and the cells. The individual follicles may become from three to five times larger than normal. The size and shape of the entire tonsil undergo a corresponding alteration. It forms a globular and often pedun- culated tumour, which may project so far into the pharynx as even to interfere with the breathing. Its surface is smooth ; even those depressions are effaced which correspond to the orifices of the little crypts round which the follicles are grouped. CROUPOUS INFLAMMATION. 421 These orifices are generally round and open ; they are now stopped up and distorted by the swelling. § 361. Similar conditions are never met with in the other follicular glands of the alimentary tract. On the other hand we sometimes find, in persons who are especially predisposed, a very singular and important phenomenon : organic inflamma- tions in general, but particularly catarrhal affections of the mucous membranes, causing an enlargement of those lymphatic glands which are nearest the seat of mischief, an enlargement differing from that " acute swelling " which I have already described, by its gradual progress and its obstinacy, and differ- ing from true hypertrophy, by the exclusive proliferation of the corpuscular elements, and the consequent disorganisation of the entire gland ; distinguished moreover from both alike, by the enormous size to which the gland may attain. I refer to the scrofulous or cheesy degeneration described in § 203 et seqq. , which, when restricted to the mesenteric glands, gives rise to the symptomatic aggregate known as Tabes mesenterica. Some- times indeed, it occurs in the solitary and agminated follicles of the intestine; but these are so intimately connected with " tuber- culous" degeneration of the intestinal mucous membrane, and so constantly associated with it, that it would be inconvenient to treat of them apart. (^See Tuberculosis of mucous membranes.) 2. Croupous Inflammation (Inflammatio pseudo-memhranacea). § 362. Croupous inflammation of a mucous membrane differs from catarrhal inflammation in one essential particular only. The hyperasmia and swelling may be more intense ; but it is only in the inflammatory products, that we can discover any qualitative difference. These j^roducts exhibit the naked-eye characters of a coagulated albuminous substance ; they take their name of "fibrin," or "fibrinous exudation," from the chief representative of spontaneously coagulable substances. The material in question is yellowish-white, tough and elastic ; when stretched, it is not drawn out into threads, but gives way suddenly and is torn across. On the addition of acetic acid, it clears up and swells like fibrin ; its reaction therefore is precisely the opposite of that of mucus, which is rendered opaque and ropy by acetic acid. Morphologically too, the 'i2'2 MUCOUS MEMBRANES. impression conveyed is that of a substance exuded upon tlie mucous surface, and coagulated at once by contact vritli the air. For the material in question furnishes a characteristic membranous investment for the mucous membrane (" false membrane ") which adheres to the surface as closely as gypsum to a mould. The under surface of the false membrane presents an accurate impression of every irregularity of the mucous surface ; should the entire circumference of the mucous tube have been involved, the false membrane forms a tubular cast ; should the canal have been of small calibre, the cast is solid and cylindrical ; should the disease have been circumscribed, it forms a rounded plaque. In thickness, the false membrane varies from a mere bloom -like efflorescence to a rind a line in depth ; it sometimes presents a I'eddish mottling, due to minute extrava- sations occurring simultaneously with the exudation. § 363. All the remaining properties of the false membrane, particularly the histological quality of the seeming fibrin, and the firmness with which the membrane adheres to the mucous surface, vary with its place of origin, and find their explanation in the normal structure of the affected part. Of all the mucous membranes of the body, none is more liable to croupous inflam- mation than that of the larynx ; next in order of frequency come the tracheal and pharyngeal mucous membranes, whose liability is nearly on a par, so that ^Ye find laryngeal croup com- ])licated, now with croup of the air-passages, now with that of the pharynx ; enabling us to distinguish between a laryngo- tracheal and a pharyngo-laryngeal variety. At the bed-side the former is termed ^^ croup" (Braune) par excellence; the latter, most erroneously, "diphtheria" (diphtheritis, Rachenbraune, pharyngeal croup). The physician has every reason to keep the two varieties apart. In their clinical characters, in the dangers to which they expose the patient's life, and above all as regards their treatment, they differ so essentially, that in spite of their anatomical identity, on which it is my business to insist, I should feel bound to oppose any attempt towards a clinical fusion of the two diseases. § 364. We w^ill begin by discussing pharyngeal ceoup, commonly called diphtheria. The morbid process is always insular. At various points of the isthmus faucium, soft palate, and uvula, of the tonsillar surface, palatine arches, and glosso- CROUPOUS INFLAMMATION. 423 epiglottidean folds — we notice circumscribed spots of a milk- white colour, on an intensely hypera3mic base. The white spot soon rises to a height of half a line at most above the level of the mucous surface, and the false membrane is complete. On attempting to pick it off with a blunt instrument, we find this to be impracticable during its earlier stage ; if we use violence, we lacerate the surface and cause bleeding. At a later period, the membrane separates of its own accord ; its edges are first of all loosened by a moderate degree of suppuration, and the entire patch is then liberated from its base. The circumscribed catarrli which persists for a time upon the denuded base (often erroneously called an "ulcer"), ceases spontaneously; if not meddled with, it leaves neither loss of substance nor scar. A secondary extension of the false membranes is very rare ; they are never known to recur on the same patch, unless previously stripped off before their spontaneous maturation. § 365. These striking and important peculiarities are satis- factorily explained by microscopical examination. We learn from this, to our astonishment, that the false membranes do not consist of fibrin. If little shreds of a false membrane are soaked in a weak ammoniacal solution of carmine, then washed and teazed out with needles, we may readily assure ourselves that the naked-eye appearance of coagulated fibrin is produced by cells, and nothing but cells, which have undergone a peculiar degeneration of their proto])lasm, and an equally peculiar fusion with one another. But for the reddish dots which indicate the nuclei, we might fairly doubt the corpuscular nature of these angular, lustrous, firmly united flakes. As it is, however, we must consent to the hypothesis of some metamorphosis of the corpuscular elements, concerning whose place in general patho- logy we can at present only guess. The external appearances may be aptly rendered by the term " glassy swelling," employed by Weber to denote amyloid infiltration. It seems certain that the cells contain more solid matter than do normal cells ; now if tliis excess of solid matter were fibrin, we might speak of a ^^ fibrinous degeneration" ; inasmuch, however, as we are quite ignorant of its nature, the term "fibrinous degeneration" can only be applied to the naked-eye appearances ; even with this limitation, it would involve a tacit assumption which it is better, in my opinion, to avoid. 424 MUCOUS MEMBRANES. Let us now examine a vertical section, in order to arrive at some idea concerning the structure and origin of the false membrane. The section (fig. 122) embraces the entire thickness of a false membrane, together with the mucous surface on which it lies.* We see at a glance that the entire false membrane is really made up of the elements described above. Originally spherical, they have come into contact with one another at various points and have become welded together into a plump network, con- sisting, in a manner, of "connecting pieces" only, without any Fig 122 -^^ ri-4^~^ ^ Vertical section through a croupous plaque on the isthmus faucium, with the mucous fold on which it rests, a — h. False membrane ; c. Normal mucous membrane. -3^. trabeculae. All the more elaborate is the system of crescentic and branching fissures which permeate the false membrane, taking the place of meshes. In certain lights they appear dark, * Deceptive appearances can only be avoided by making the sections exceedingly thin and absolutely vertical. The following is the best method of preparation. The specimen is immersed in a mixture of glycerine and gum-arabic, which must be clear and viscid. After the fluid has had time thoroughly to permeate the specimen, the latter must be taken out and thrown into alcohol. The gum now becomes quite hard, owing to the extraction of the glycerine; and the specimen is quite ready for being cut into sections of any required thinness. On soaking the sections in a watery fluid (say the carmine solution) the gum is dissolved out, and the tissue alone is left. CROUPOUS INPLAMMATION. 425 and so might readily be mistaken for the positive j^art of the structure; the possibility of error can only be excluded by staining the preparation with carmine. The cells are of variable size ; their dimensions increase as they approach the surface ; at the extreme periphery of the membrane they are nearly twice as large as lymph-corpuscles ; farther inwards they become smaller, the smallest ones lying immediately upon the mucous surface ; here too, the degeneration is less marked ; they can hardly be distinguished from the normal cells which are still embedded in the parenchyma of the mucous membrane. This gradual transi- tion naturally masks the boundary-line between the surface and the false membrane, though it never quite obliterates it. It proves most undeniably, however, that the false membrane is pro duced by the secretion of young elements upon the irritated mucous surface, followed by their gradual stiffening, sclerosis, glassy swelling, or whatever term we may choose to apply to their degeneration. Accordingly, the false membrane occupies the precise position which belongs of right to the epithelium ; the degeneration in question taking the place of the normal evolution of epithelial elements. What becomes of the original epithelial investment of the affected region? Has it been simply shed, or does it, too, take part in the formation of the false membrane ? E. Wagner has attempted to solve this pro- blem in a recent and very valuable investigation, and has raised the participation of the epithelium in the morbid pro- cess to the rank of a certaintv. He describes a very sinofular metamorphosis of the pavement-cells (fig. 1 23), in consequence of which the protoplasm disappears at certain points, appa- rently receding to certain branching lines, where it assumes a homogeneous aspect, and refracts light more highly than ordinary protoplasm. The nucleus disappears; the entire cell being represented only by a network of great delicacy, resembling the antlers of a stag in shape. I believe that I have myself seen this metamorphosis — at least in its earlier stages — along the edges of the false membranes ; but I cannot ascribe to it any far-reaching significance as regards their development ; the thin stratum of epithelium does not seem to me to possess sufficient resources of its own for the construction of a false membrane. But I am willing to let the future decide on the precise range of Wagner^ s discovery. 426 MTJCOTJS MEMBRANES, § 366. The intimate connexion between the secreted products and the secreting surface in pharjaigeal croup, is the cause of the close adhesion between them at the outset of the disease. When the normal state is re-established, the morbid cell-metamorphosis comes to an end ; the cells secreted by the mucous membrane remain unaltered, forming, together with a small quantity of serum which is simultaneously poured out, a thin layer of puru- lent fluid ; and this of itself involves the detachment of the false membrane. Notwithstanding the superficial character of pharyngeal croup, it is a very dangerous affection, owing partly to the Fig. 123. Fibrinous degeneration of pavement- cells (after E. Wagner). constitutional disturbance which attends it, partly to the risk of larpigeal complications ; the pharyngeal angina being associated with a laryngeal angina, due to a swelling of the submucous connective tissue, which may assume alarming proportions. § 367. Croupous inflammation of the larynx and trachea presents us with a serial succession of simple catarrh and pseudo- membranous exudation. Even in its catarrhal stage it is capable of giving rise to the familiar group of symptoms in their highest intensity — nay, even to death itself. The laryngeal mucous membrane is acutely inflamed, and proportionately swollen ; it secretes a viscid and tenacious mucus, rich in cells ; this forms a thick, adhesive, yellowish layer, contracting the already nar- row chink of the glottis to such a degree, that we need hardly CEOUPOUS INFLAMMATION. 427 recur to the assumption of reflex spasm of the glottis to account for death by apnoea. Accordinglj, a number of physicians have gone so far as to deny the occurrence of a fibrinous exudation altogether. We must not fall into this error. The development of a false membrane is connected in the closest manner with the catarrhal state, and constitutes the anatomical acme of the mor- bid process. We often find the two conditions side by side, a layer of catarrhal secretion being interspersed here and there with patches of fibrinous exudation. Acetic acid enables us to distinguish at once between the muco-purulent and the fibrinous elements ; no uncertainty is therefore possible upon this point. Histological examination of the false membrane shows, first of all , that here too, corpuscular elements predominate. These are far more easily recognisable than in the pharjmgeal false membrane ; they resemble for the most part, the cells of ordinary embryonic tissue. In vertical sections (fig. 124) however, we find that these em- bryonic cells are not the only constituents of the false membrane. It presents an exquisitely laminated structure, the corpuscular layers alternating at tolerably regular intervals with layers of fibrin ; these alternate layers recurring from one to ten times, in proportion to the thickness of the membrane. Whether I am justified in calling the alternate layers " fibrinous " or not, must remain open for the present. I call them so from the first im- pression which their configuration makes upon the observer's mind, and with the reservation that I mean no more by the word than a fiuid albuminous substance, which has coagulated after transudation on exposure to the air. The substance in question is lustrous and homogeneous ; I have not been able to resolve it into cells, like those of the pharyngeal false membrane ; it forms thin plates with upward and downward processes which penetrate into the interstices between the contiguous cells, form- ing by their anastomoses a beautiful network, whose meshes correspond very nearly to the individual cells (a). Under such circumstances, I think we may fairly infer, that a fluid, in which a large number of cells are suspended, and which holds the '^ fibrinoid " substance in solution, has been secreted by the mucous surface ; further, that the coagulation of tliis fluid has fixed the cells in their original position, while the extension of the coagulation to the lacunar interstices between the spheroidal bodies of the cells, has given rise to the appearance of a network. 428 MUCOUS MEMBRANES. Hence the difficulty of accounting for the place and mode of origin of these cells. The epithelium has long since disappeared ; it must have been stripped oif at the very outset of the process by the development of the false membrane, just as in the pharj'nx ; admitting the possibility of a fibrinous degeneration, such as is described by Wag7ier (see § 365), the uppermost stratum of the network might perhaps be regarded as consisting of the bodies of the columnar epithelia, after their branching and stiffening ; this view would lead us, however, to ascribe a diffe- rent origin to the different layers of the network ; a lack of uniformity which would be most undesirable. And yet the mucous membrane of the trachea, stripped of its epithelium. Fig. 124. .c^iL^ r-.^-r^-r loXf^: Tracheal croup, o. The undermost layers of a false membrane ; &. The basement-membrane; c. The sub-epithelial em- bryonic tissue ; d. Efferent duct of a mucous gland, pour- ing out a clear mucus, and peeling off the false mem- brane. ToVxJ- with its homogeneous basement-membrane, reminds us too forcibly of the ^^ open palm " of Charles YII.* not to make the lacuna in our interpretation very sensible. Our only hope lies *In Schiller's Jungfrau von Orleans (Act i. sc. 3) King Charles is made to exclaim, despairingly : *' Kami ich Armeen aus der Erde stampfen, Wachst mir ein Kornfeld in der flachen Hand ? " " Can I raise armies from the earth with a stamp of my foot, or grow a cornfield in my open palm ? " For this reference 1 am indebted to the kindness of Professor Buchheim. — Te. CROUPOUS INFLAMMATION. 429 in the highest magnifying powers. With one of Havtnack''s immersion lenses, I have sneceeded in making out that the ^'homogeneous" basement-membrane is not really homoo-ene- ous, but perforated by a large number of very fine pores. Through these pores the cells, of which there is usually a certain quantity stored up between the basement-membrane and the elastic layers, make their way to the surface. The apertures indeed are small ; but is there any aperture so small as not to allow the body of a young embryonic cell to slip through it ? Those who, from personal observation, are familiar with the amoeboid movements of these cells, will agree with me in answer- ing this query in the negative ; they will also admit that the "homogeneous" basement-membrane presents no obstacle to their migration. § 368. The presence of this basement-membrane underlies, moreover, another important peculiarity of the croupous mem- branes of the trachea, sc. that from the very first they adhere less closely to the mucous surface than the false membranes of the pharynx. Not only does the boundary-line between mucous membrane and false membrane, between the secreting surface and the secreted products remain clear and distinct throughout, but the smoothness of the surface gives little chance of any lasting union ever being brought about between the two. Con- sider moreover the activity of the mucous follicles ; the free escape of their secretions is often hindered by the superjacent fiilse membrane, which they accordingly detach by accumulating underneath it (fig. 124). The upshot of all these conditions is the ease with which false membranes of the trachea may be peeled off, a property on which all our therapeutic measures, inadequate as they are, repose. Indeed the separation of the false membrane not unfrequently proves the immediate cause of death ; the membrane, wholly or partially detached, becoming rolled up and completely blocking up the tube. The membranes in tracheal croup may undergo softening as well as separation. A gelatinous transformation of the network, together with a flitty-granular disintegration of the embedded cells, arc the chief factors in this process. Some observers have detected fungoid vegetations in the softened pulp, and have accordingly ascribed more of a putrid character to this liquefaction. The naked-eye appearances justify us in calling it a true '' melting," inasmuch 430 MUCOUS MEMBRANES. as the membrane does not merely become fluid at its edges, but exhibits thinning and perforation at various points in its con- tinuity as well, the perforations ultimately becoming confluent, I have only seen one case of this kind ; I recollect that the fluid l^roducts of softening yielded a precipitate of mucin on the addition of acetic acid ; and this led me to speak of a ^^ mucoid "^ softening of the false membrane. § 369. Having discussed the croupous process as it presents itself in the pharynx and trachea, we may conclude with a few words about laryngeal croup. A croupous inflammation, con- fined, throughout its entire course, to the larynx, is of rare occurrence ; iievertheless, the laryngeal is the most common variety of croup, inasmuch as it nearly always complicates croup of the air-passages, and may also complicate that of the pharynx. Tlie characteristic features in the morbid anatomy of laryngeal croup are due to the fact that the mucous lining of the larynx agrees in its structure, partly with that of the pharj^nx, partly with that of the trachea. Both surfaces of the epiglottis, and the true vocal chords, are coated with a laminated pavement-epithe- lium, which is not marked ofl" from the connective tissue by any homogeneous basement-membrane. Hence the false membranes adhere more firmly to these, than to any other points in the interior of the larynx. How often do we find, in making a post- mortem examination, that the tracheal false membrane, continu- ous with that of the laryngeal funnel, is quite loose as far up as the rima glottidis, where it is firmly attached ; and we feel sure that its spontaneous detachment at this point would have required a very long time for its accomplishment. Yet it is just the true chords Avhich are especially liable to become inflamed, while the ventricle of Morgagni, for instance, is hardly ever affected. From an etiological point of view it seems to me very important to lay stress upon the preference which the disease exhibits for the prominent parts of the mucous membrane, while its recesses are, for the most part, intact. It is as though the pharynx had been lightly brushed over with some corrosive agent, or as thougli some irritant gas had been retained for a short while in the upper part of the respiratory passages. I DIPHTHERITIC INFLAMMATION. 431 3. Diphtheritic Inflammation. § 370. After the exclusion of what is commonly known as- ^^ pharyngeal diphtheria"' from the domain of diphtheritic in- flammation, the extent of the latter remains comparatively limited. We have already touched upon the essential features- of the process, in our account of the ^' diphtheritic pock" (§ 298). It consists of an infiltration of newly-formed cells into the sub- epithelial connective tissue, as contrasted with the entire mucosa ; an infiltration so abundant as to compress the vessels, and to arrest both circulation and nutrition. Inasmuch as a certain amount of corpuscular infiltration of the subepithelial connective tissue occurs in connexion with every catarrh, as well as ^s^ith the croupous form of inflammation, diphtheria may be regarded as merely a quantitative increase or excess of this morbid pro- liferation ; true diphtheria having no claim to be regarded as a specific process in the same degree as croup. To the naked eye, it presents certain characters which have led to its being contrasted with the '^ Inflammatio pseudo-membra- nacea" as an ^^Inflammatio membranacea " ; I refer to the formation of a tough, felted membrane of a greyish- white colour, often mottled with shades of red and green (due to blood-pig- ment), raised to the height of about half a line above the level of the mucous surface, penetrating downwards into its substance to the same extent, and intimately blended with it. This mem- brane is not a deposit upon, or a secretion from the mucous surface ; it is the mucous membrane itself, so much of it at least as has been at once tumefied and deprived of blood by the excessive corpuscular infiltration. This condition has been compared, not inaptly, to mortification caused by a chemical irritant, to a corrosion, and the diphtheritic membrane has been called a ^^ diphtheritic slough" ; the membrane is indeed a caput mortuum^ it cannot enter upon any changes save putrefaction and decomposition ; we have only to inquire how it is set free from its close organic union with the mucous membrane, and cast off. Simple inspection is enough to show us that a sharp line of demarcation separates the living tissue from the dead ; but a number of connective-tissue fibres, blood-vessels, nerves, and elastic fibres, pass from the living into the dead parts ; and these must all give way before separation can occur. The means 432 MUCOUS MEMBRANES. at the disposal of the organism are inflammation and sappnra- tion. We call this form of inflammation ^'reactive," meaning thereby that it is supposed to respond, as it were, to tlie irritation exercised on the surrounding mucous membrane by the diph- theritic slough; some portion, ho^Yever, of the hyperagmia may be interpreted as a collateral fluxion, occurring in harmony with statical laws (^i.e. of a passive, not an active kind). The pus collects between the slough and the healthy tissue ; the former begins to separate at its edges or at its centre, according as the fibrous bridges alluded to above, melt and give way in the former or the latter order. When the separation is complete, an ulcer is left, which tends speedily to cicatrise ; a recrudescence of the morbid process not unfrequently occurs, a new slough is formed, a renewed necessity arises for a sequestrating suppuration, the resulting loss of substance being far more considerable than it Avas in the first instance. The scars which are ultimately left are very prone to contract, so that the risk of a subsequent stricture of the mucous tube (particularly of the large intestine after dysentery) is directly proportionate to the extent of the previous ulceration. § 371. It is worthy of note that diphtheria affects such mucous membranes as are already in a state of violent catarrhal inflammation, and whose surface is at the same time in ^^er- manent contact watli putrescent, decomposing substances. In dysentery, which begins as a simple catarrh of the greater bowel, accompanied by excessive spasmodic contractions of its muscular coat, the diphtheritic process primarily affects the free borders of the mucous folds over the tceiiicu longitudinales and the plkce sigmoidece ; also those natural flexures of the intestinal tube where most resistance is offered to the passage of the faeces, sc. three successive points in the sigmoid flexure, the coecum, the hepatic and splenic flexures of the colon. Now the circumstance, that at these points the inflamed mucous membrane is longest and most closely in contact with putrid matters, must surely aid in the localisation of the diphtheritic process. In much the same way, diphtlieria complicates those catarrhal affections of the urinary passages which are due to retention. Whether the retention be caused by stricture of the urethra, by enlarged prostate, by paralysis of the detrusor muscle, &c., the stagnant urine becomes decomposed, and sets up a catarrh passing into HEMORRHAGE. 433 diphtheria of the mucous surface. Contact with putrid matter also contributes to cause those diphtheritic lesions which occur; not on a catarrhal, but on a denuded surface. I refer to diph- theria of the womb and vagina immediately after parturition, when the shedding of the decidua has left the uterine parenchyma unprotected and raw, like an amputated stump ; I refer to the diphtheria which occasionally complicates the second stage of Asiatic cholera, after the violent catarrh of the first stage has stripped the mucous membrane of all its epithelium, and left it a prey, in this its "flayed" condition, to the direct influence of the intestinal contents ; finally I refer — although this has really nothing to do with the mucous tract — to that diphtheria of wounds which is known as hospital gangrene. On the other hand, it cannot be denied that the element of putridity may also reside within the organism ; that there is a state of the fluids in the individual which predisposes him to become affected by diphtheritic inflammations — or, to speak more accurately — which predisposes any inflammation, otherwise excited, to take on a diphtheritic character. Many diphtheritic inflammations of the pharynx and alimentary canal, complicating the last stages of maladies which profoundly affect nutrition, may be thus explained. In conclusion, I must not omit all reference to a statement which has over and over again been repeated (Letzerich), to the effect that diphtheritic inflamma- tion is due to the germination of a fungus upon ulcerated and mucous surfaces. Although I am by no means hostile to this view, I do not reofard it as well enouojh established to warrant my bestowing any lengthy notice upon it on the present occasion. b, HEMORRHAGE. § 372. I am by no means sure that my grouping the various matters which I propose to discuss in the present chapter, under the common head of " Haemorrhage," will meet with universal approval. The reader's attention has already been called (§§ 353 and 240) to the facilities afforded by the arrangement of the capillaries in the gastro-intestinal mucous membrane, for the occurrence of hypera^mia and hoemorrhage. In the more lively contractions of the muscular coat, which accompany catarrhs even of trifling intensity, but which are especially characteristic of 28 434 MUCOUS MEMBRA^"ES. their dysenteric fornij we saw a reason for tlic extravasation of blood either into the parench3'ma of tlie mucous membrane, or upon its surface. Now on the gastric and duodenal mucous membrane tliere occur a series of conditions, characterised by loss of substance, which may ver}' plausibly be referred to ante- cedent parench}Tiiatous hasmorrhages — to hsemorrhagic infarc- tions of the mucous membrane. This view is generally adopted to explain HiE:\roEKHAGic erosions. Under this term we under- stand certain sharply- circumscribed, circular defects of the mucous surface, no larger than a pin's head, which commonly occur in great numbers, their favourite seat being on the free borders of the mucous folds in the pyloric region. Tlie fr*e- cjuency of hgemorrhagic infiltrations of the same size and shape, existing side by side with the erosions, raises the probability of their originating in this way to a certainty. Moreover there is usually a history of attempts at vomiting, to account for the presence of the hasmorrhagic extravasations ; so that we may fairly assume the sequence of phenomena to have been something like this : the act of vomiting, by temporarily arresting the return of blood, causes minute extravasations from the superficial venous radicles of the gastric mucous membrane ; these occur on the free borders of the folds, the extreme parts of the congested area, where the blood- pressure must attain its maximum intensity. The extravasated blood-corpuscles infiltrate a circumscribed patch of the mucous membrane to such an extent as to compress the capillaries, thus putting a stop to circulation and nutrition. The hannorrhagic infarction becomes a caput mortuum, its organic union with the healthy mucous membrane is at an end, and its actual detachment becomes merely a question of time. When we reflect] how easily the gastric juice can dissolve such dead parts as these hemorrhagic infarctions, we shall readily understand how it comes about that a very few hours after the bleeding has occurred, we should find, in place of the infarction, that sharply-defined and regular loss of substance, to which CruveiUner gave the name of " erosion hemorrhagique.'' § .^j73. I agree with many other observers in assigning a similar mode of origin to the simple (chronic, circular, perforat- ing) ULCER OF THE STOMACH. On IJecembcr 4th, 186."), a man was admitted into the surmcal wards at Bonn with a stran^ju- ]ated inguinal hernia. He had bee?-; vomiting continually fi'om I GASTRIC VLCEm. 435 -5 A.M. UnsuceesstuI attem2:)ts had been made to reduce the liernin. At 7 P. 31. operation, followed by relief. 0]i the even- ing of Dec. 5, an enema was followed by a copious stool of a dark-brown colour ; on the 6th another stool was passed, con- •sisting of black, altered blood. During the night between the Cth and 7th, nausea and retching ; on the morning of the 7th vomiting of lumps, streaked at first with bile, and later with blood; this frequently recurred throughout the day, and la.^* .x'l with brief intermissions until the patient's death at 9 p.m. At the post-mortem examination, performed one hour after death, the stomach presented, besides several hannorrhagic infarctions of smaller dimensions, two circular foci of equal size, symme- trically disposed on either side of the middle line of the lesser curvature ; of these, one was a perfect example of a simple ulcer, while the other presented the appearance of a hannorrhagic in- farction of the gastric mucous membrane of corresponding size. For prolix hypotheses concerning the possible or probable mode of origin of gastric ulcer, which would outrun the limits of this manual, I substitute the above plain record of a case with a post-mortem. And this I do, partly in order to substantiate the view which I have adopted, partly also to point out how very unstable all those theoretical arguments must be, seeing that the results of a single post-mortem are still of such import- .ance in the settlement of the question. § 374. The simple ulcer accordingly originates in a ha-mor- rhagic infarction. This involves the entire thickness of the mucous membrane. In fine sections through the above speci- men, I was everywhere able to demonstrate the bodies of the tubular glands bathed in blood-corpuscles, as though embedded in the clot. The solution and removal (digestion) of the infarc- tion by the gastric juice, leaves a corresponding loss of sub- ^;tance ; the simple ulcer is complete. It may get bigger, it may go on to the dreaded issue of perforation ; or it may, on the other hand, contract and cicatrise ; I re^^eat however, that it is d'omplete in all essential particulars the moment the infarction is iletached. First amono^ its essential features is its circular outline. I ought to say, the circular outline of its base, for its shape as a whole is that of a very shallow cone, whose base is directed towards the surface. of the mucous membrane, while its apex is 43G 3IXJC0US MEMBRANES. excentric in position, penetrating into one of the deeper layers of the gastric wall. If we would know the cause of this conical or funnel shape, we must go back to the ha^morrhagic infarction as the starting-point of the lesion. Like every other hiemor- rhagic infarction (of the lungs, kidneys, &c.), this is limited to the area of distribution of a single vessel ; now the vascular territories of the stomach possess the form of shallow, obliquely truncated cones, whose apices are directed upwards in tlie upper half of the organ, downwards in its lower half. This explains how it is that the deepest point of the funnel-shaped crater is- situated, not inider the centre of the hole in the mucous membrane, but nearer its upper or its lower edge as the case may be. Another, not less characteristic feature of the simple ulcer, is the exceeding sharpness of its edge, and the absence of any raised border. The nmcous membrane looks as though a hole had been cut in it with a punch. The submucous tissue is as clean and white as though it had been carefully dissected ; and if the idcer perforates it also, the perforation is circular and sharply cut, showing the muscular coat with its transverse bundles as if dissected out. It would seem as though the formative reaction at the base and edges of the ulcer were quite insignificant ; moreover, that the digestive solution followed so closely upon the heels of the plastic infiltration, as to prevent our ever getting a glimpse of the latter at all. The very chronic character of the process, which often drags through more than one decennium, is in favour of the former assumption ; while the latter is sup- ported by the fact that the simple ulcer is only found in the stomach and the upper part of the duodenum, i.e. only in that part of the alimentary canal where its contents are acid, and where the solution of albuminous substances takes place most rapidly. § 375. As regards the further progress of the simple ulcer, the possibility of its cicatrisation has already been referred to. The smaller and more recent the lesion, the sooner may the formation of the "stellate cicatrix" be expected to occur ; i.e. of that minute, white, flattened scar, which replaces a loss of substance perhaps ten times as large as itself, and which must necessarily conti'act and pucker the neighbouring mucous mem- brane. Ulcers of larger size may also become cicatrised, but this does not commonly occur ; when it does, it may lead to such GASTRIC TJLCER. 437 extensive contractions of the stomach at its middle part, as to subject the patient to a fresh series of troubles. On the other hand, the gradual extension of the original ulcer exposes the patient's life to three sets of risks. For when the ulcer continues to increase in depth slowly but un- ceasingly — 1. It may open into a large vessel, and so cause fatal bleed- ing into the stomach. Such an issue is most frequent in the case of those ulcers which are situated on the posterior aspect of the stomach, just over the course of the splenic artery ; some- times, however, it is the trunk originallj' supplying the affected area which is laid open j^er diabwsin; the haemorrhage then occurring from a branch of the coronary or gastro-epiploic arteries. 2. It may open into the peritoneal cavity. This usually occurs by a circular hole of fair size, which can hardly be pro- duced otherwise than by necrosis of £he base of the ulcer, and detachment of the necrosed part. This accident is most common in the case of duodenal ulcers ; next in order of frequency come ulcers on the anterior wall of the stomach, inasmuch as during the various movements and changes of place which the organ undergoes, its anterior surface moves up and down over a con- siderable area of the opposite peritoneal surface, a circumstance very unfavourable, nay, antagonistic to any prophylactic adhesion. The possibility of such conservative peritonitis is clearly shown by ulcers situated on the posterior wall of the stomach and in the pyloric region ; these are almost invariably found to have con- tracted adhesions to neighbouring viscera, such as the liver, pancreas, spleen, &c., before the occurrence of perforation. This wards off the risk of a rapidly fatal peritonitis ; the result is one which we, as physicians, would endeavour to compass if we could. We must not shut our eyes to the fact, however, that this very Ijridging-over of the interval between two layers of peritoneum opens a new "field for the destructive activity of the ulcer, which may proceed — 3. To burrow into a neighbouring organ and destroy it layer by layer. The spleen and the left lobe of the liver are most liable to be thus invaded ; and as the destructive process advances with greater ease in their soft parenchyma, than in the walls of the stomach and the eoimectivc tissue of the adliesion, they ^m MUCOUS MEMBRANES. speedily become Iiollowed out into large cavities, '»\ hicli commu- nicate with the stomach by a narrow opening. More rai'ely does the ulcer burrow into the head of the pancreas ; rarest of all is adhesion between the stomach and colon, whereby these divisions of the alimentary canal are made to communicate, giving rise to the symptoms of licnteric diarrhoja. I have seen a case in wliich adhesion and subsequent perforation united the pylorus with the gall-bladder : gallstones being subsequently formed and discharged by vomiting. c. SPEciric Inflammation. § 376. The typhous process, in by far the most frequent mode of its occurrence, ileotyphus (typhus (ibdominalis) is asso- ciated with certain changes in the mucous membrane of the intestme, which undeniably possess special anatomical pecu- liarities. Like those of syphilitic gummata, leprosy, and tubercle, these special characteristics arc manifested rather in the coarser anatomy, than in the finer structure, of the morbid products. The attention of physicians has only been directed to them since the thiixl decade of the present century. They were originally described as " inflammation of Peyer's patches *' ; then Heusinger pointed out their similarity to medullary cancer; Rohitanski compared the aspect and consistency of the altered patches to the cerebral medulla of young children, and introduced the term " medullary infiltration," which is still in use, to designate their appearance when mature. Concerning the relation of the intestinal and other anato- mical changes (splenic enlargement) to the constitutional dis~ order, great differences of opinion still exist. The Vienna school considered the changes in the bowel as a mode of eliminating the peccant matters from the blood ; at the present day, we have only two alternative opinions from wliich to choose; we may regard the bowel-lesions as standmg in the relation of an exan- them towards the constitutional disorder, or we may ascribe them * For reasons alluded to in § 112, note, I have kept the generic term " Typhus '* employed by the author. It is self-evident that the chapter refers solely to abdominal tj-phus or enteric fever. — Tr, TYPHUS. 439 to the local action of the typhoid poison, ioasmuch as they are produced in those very organs which arc probabh', according to recent investigations (enteric fever from drinking-water)^ the channels through which the poison is introduced into the system. § 377. Several stages have been distinguished in the course of abdominal typhus ; the catarrhal stage, the stage of medullary' infiltration, the stage of degeneration, and that of ulceration. We will retain these divisions, premising however, that the general catarrh of the alimentary tract which ushers in the pro- cess, may continue, without undergoing any marked abatement, until the final stage. Strictly therefore, the division into stages is only applicable to the special alterations in the lymphatic follicles, on which indeed the attention of the anatomist is con- centrated from an early period. During the catarrhal stage, (which seldom comes under observation), all the Peyer's patches,, and the solitary follicles of the small and great intestine, become swollen in the manner described in § 350. The greyish, pearly nodule, surrounded by its close web of vessels, is the acme of the process in this direction ; thereupon, the swelling for the most part subsides entirely, particularly in the solitary glands ; here and there, especially m Peyer's patches, the character of the swelling undergoes a change, without the occurrence of suppura- tion and expulsion of the follicles ; the latter passing into the state of "medullary infiltration." This " medullary infiltration " is mamly distinguished, on the one hand by an enlargement of the follicle, which may attain even six times its normal size, on the other by an extension of the morbid process to tlie perifollicidar connective tissue. The follicles wliich make up a Peyer's patch, coalesce \^ith the interstitial con- nective tissue to form a soft, rose-coloured, seemingly homoge- neous mass, which closely resembles the medullary substance of the foetal brain; the entire patch forms a flattened elevation, about two lines in height, of an elongated oval outline; it is marked ofP from the surrounding mucous membrane by a pre- cipitous border. The solitary follicles are converted by the infil- tration into marrowy nodules, from two to fom* lines in diameter ; it is in these, that the extension of the morbid process to the mucosa is most strikingly apparent ; since the greater part of the nodule is obviously made up, not of the follicle itself, but of the mucous membrane which covers it. 440 MUCOUS MEMBUANES. § 378. What light does the microscope throw upon tliis ^^ medullary infiltration " ? Does it enable us to detect any typical tissue-change, which, independently in some measm'e of pre-existing structure, is able to generate " typhous " products wherever connective tissue or lymphatic elements may happen to exist? May we speak of a ^Hyphous" product in the same sense as of a cancerous, sarcomatous, or syphilitic product? I feel myself entitled to the credit of having done my best to penetrate into the anatomical essence of the typhoid process, with the aid of the most recent methods of investigation. The results, however, have not proved equal to my expectations. Other observers have described corpuscular and nuclear proliferation as the only demonstrable appearances. I will venture a step farther, and call attention to some points which, in the general absence of " peculiarities," seem to be worthy of being put on record. First then, let me refer to the enormous dilatation of the capil- laries and arterioles in the parts affected with medullary infiltra- tion. The double contour of their walls is represented merely by a sharp line of demarcation between the parenchyma and the blood ; the blood seems occasionally to have become quite stag- nant, if we may judge by the appearance of the colourless cor- puscles, which, just as in cases of slow coagulation, have become aggregated into little clusters, occupying, without any admix- ture of red ones, the whole interior of a capillary vessel for short portions of its course. Notwithstanding this however, ecchymoses are rare ; probabl}' because the elastic reaction of the proliferated parenchyma is too powerful to allow of their production. As regards the morbid products themselves, I have already pointed out (in § 112) that the process does not consist merely of a numerical multiplication of elementary parts, as in catar- rhal inflammation, but that in addition to this numerical increase, which is undoubtedly very considerable, there is an increase in the size of the individual elements, a tendency towards the pro- duction of a specific '^typhous" cell. The individual evolution appears indeed to culminate In the 2:)roduction of this *^ typhous" cell, a structure which differs from the simple lymph-corpuscle, by containing a larger proportionate amount of protoplasm. The protoplasm of a lymph-corpuscle barely equals the contained nucleus in amount; whereas in the ^Hyphens " cell, it always takes up as much, on an average even more space than the TYPHUS. 441 2iucleus. The ^^ typhous'' cell represents the first step towards, as it were a foreshadowing of, epithelial differentiation : it would seem, however, as though this augmentation of the protoplasm lacked the solidity and durability of epithelial development, inas- much as the "typhous" cells remain but a short while at their acme, and speedily fall a prey to necrobiotic change. Fhially, as regards the peculiar rosy, homogeneous tint of the entire mass, it is explained by the dark-red hue of the turgid capillary netw^ork being toned down to a uniform flesh- colour, bv the homoo-eneous medium throuo:li which we sec it. § 379. The anatomical alterations culminate in medullary infiltration. This "is followed by retrograde metamorphoses, which may set in in diverse ways. The great majority of the infiltrated patches gradually return to their normal state by a ^^colliquative softening.*' The " typhous " cells become disin- tegrated into oily dthris^ which are absorbed as chyle. There- upon the swelling disappears, the follicles being the first to sub- side ; the Peyer's patch presents a reticulated aspect (surface reticulee) owing to the collapse of the follicles ; the little hollows which correspond to them forming the meshes of a network, whose trabeculas are represented by the interstitial connective tissue which still continues infiltrated. When the latter is also freed from the infiltrated products, nothing more remains to be done save a gradual restitution of the lost parts, which appears to begin at once. § 380. But this " colliquative softening " is not the only way in which the morbid products may be got rid of; another and a more severe issue, is " sloughing '* of the deposit. We found that nearly all the lymphatic structures in the wall of the alimen- tary canal were implicated during the catarrhal stage ; we found u marked limitation and concentration of the process in the stage i^{ medullary infiltration ; now in the stage of sloughing, a further and much the most striking reduction in the extent of the mor- bid process, takes place. Small portions of single Feyerian patches, portions varying from a lentil to a size of from three- fourths to five-fourths of an inch, with here and there a solitary gland, assume a yellowish-white, opaque tint instead of their former reddish and tran>hicent aspect ; they are detached from the surrounding tissue by a sharp line of demarcation, and then pass into a state of cheesy necrosi-. When once this hns occurred, 442 MUCOrS 3IEMBRANES. recovery caii only take place by expulsion of the necrosed pai'ts and consequent ulceration. An increased degree of congestion at tlie edges of the slough, is followed by suppuration, and detach- ment of the dead part ; the latter continues, however, to hang on for a long time to the base or edges of the ulcer, and acquires a yellow, green, or brown tint, by contact with and imbibition of bile-pigment. It finally comes away in shreds, leaving an ulcer w-hose size is determined by that of the slough, and whose floor is usually composed of the deepest layer of the submucous con- nective tissue. In severe cases the ulcer penetrates still more deeply, and the expulsion of the sequestrum coincides with per- foration into the peritoneal cavity. In such cases we may infer that the infiltration extended from the first, not only through the entire thickness of the submucous tissue, but also through the interstitial connective tissue of the muscular coat, to the sub- serous and serous layers. The healing of these typhoid ulcers follows at once upon the sequestrating inflammation. Xo sooner is the slough thrown ofi:', than a small quantity of embryonic tissue springs up on the floor of the ulcer : the precipitous abruptness of its edges is under- mined by a colhquative softening ; the collapsed border over- hangs a portion of the denuded floor, to which it speedily becomes attached by cicatricial tissue ; the central part, which is still naked, comes at a later period to form a smooth, lustrous surface, with pigmented edges, on which neither villi, glands, nor any of the other component elements of a mucous membrane, are ever regenerated. By transmitted light, these patches appear thin and transparent ; this is due to the absence of a mucous layer. As regards the intestinal haemorrhages which occasionally complicate abdominal typhus, it may be remarked that the frequent, trifling, and harmless ones, occm' by diapedesis from the over-congested edges of the ulcers ; the more severe bleed- ings, from those larger vessels, wliich served at one time to con- vey blood to the necrosed tissues, and which are now hable to be torn, perhaps in consequence of premature detachment of the sequestra by passing f^cal masses. § 381. So much for the morbid changes in the mucous membrane. In constant association with them, we find an affec- tion of those mesenteric glands which draw their lymph from the TYPHUS. 4:U infiltrated portions of the bowel. As tlio ileiun is always most intensely affected for about twelve inches above the ileo-coeeal valve, it is here that we may expect to find the most perfect examples of the morbid changes in the lymphatic glands. In their histological characters these faithfully reproduce the primary disorder. A moderate degree of catarrhal swelling is followed by a medullary intumescence of colossal proportions^ nearly approaching those of scrofulous enlargement. It becomes impossible to distinguish the boundary- line between cortical and medullary substance with the naked eye. The microscope shows that the follicles and their prolongations into the medulla (the lymphatic nodules and trabecular) are the chief seat of morbid change, while the lymph- sinuses, and especially the connective tissue, are infiltrated with ^^ typhous" elements to only a mode- rate extent. Here — i.e. in the lymphatic nodules, of which from fifteen to twenty may, as w^e know, be counted in a longitudinal section through a gland of average size — we meet, first, with that mordinate dilatation of the capillary network which seems to me to be the most characteristic feature of the medullary con- dition. Side by side with this dilatation, we may often note an obvious ^^ plugging"' of many capillaiy loops, and even of some of the larger vessels, with a dark, granular matter, concerning whose nature I am still in doubt. Further, the condition of the adenoid reticulum is very singular. All its trabeculse are from three to fom- times thicker than usual ; the nodal points are especially swollen, the nuclei themselves A'esicular ; the old anastomotic network of corpuscles has obviously returned to hfe, the shrmiken cells have grown plump hj the absorption of pabu- lum, the nuclei are ready to resume their function as cytoblasts. The continuity of the network is already interrupted at many points ; the resulting gaps being occupied by globular aggrega- tions of cells. The proliferation is mainly fissiparous, though the endogenous mode is also not unfrequent. The edges of the lymphatic trabeculie — the brink of the stream of lymph — are often so thickly studded with mother-cells, that these even out- number the ordinar}^ l^anph-corpuscles. Here too, the process ultimately tends to the development of the maximum number of ^'typhous'" cells. The acme once reached, every space in the interior of the gland which is not pre-occupied by the vessels — among others the lymph-path itself — is gorged with these U4 MUCOUS 3IEMBRANES. elements. It is impossible, even with the best injecting fluids, to fill the lymph-path of the infiltrated gland; indeed injection serves to show the stage at which the process has arrived. Here too, the law which regulates all other progressive changes in the lymphatic glands (scrofulosis, cancer, &c.) is found to hold good, viz. that the swelling should begin at the periphery of the gland, in those parts of it which are nearest the seat of primary disease from which the infecting lymph is drawni, spreading gradually from thence to the entire parenchyma. The degenerative changes follow the same order. These almost always consist of a ^' colliquative softening," with complete fatty degeneration of all the " typhous " cells. Inasmuch, however, as all the lymph- corpuscles and connective- tissue corpuscles, i.e. nearly all the normal corpuscular elements of the gland, have been converted into " typhous " matter, we may readily understand how it comes that hardly anything is left beyond the capsule and the blood-vessels. The uttermost limits of collapse are reached; the antecedent congestion has already given rise to distinct extra- vasations with subsequent pigmentation in the capsule, so that a slaty discoloration figures among the characteristic features of the shrunken ^^ typhous'* gland. The occurrence of cheesy necrosis at one or more points of a mesenteric gland in abdominal typhus, must be regarded as a rare phenomenon. Virclww has repeatedly called attention to its possibility. The cheesy slough is then detached by a suppurative inflammation, and a minute abscess results. This may burst into the peritoneal cavity ; hence the risk of peritonitis ; on the other hand, the pus may become inspissated, and finally cal- careous. The earthy nodule is invested with a capsule of connective tissue, like any other foreign body, and the process is at an end. § 382. All the remaining forms of sweUing, productive ac- tivity, ifcc, which are associated with the ^^ typhous" process, are found, upon analysis, to consist of the same series of progress! ^'e and retroojressive chano-es. We know least about the fine anatomy of the splenic enlargement ; the relative proportion of congestion to morbid growth, has not yet been ascertained for tlie different stages of the disease. True medullary infiltratIo]i lias been detected here and there in the Malpighian corpuscles. The ^'typhous'' deposits which are occasionally met with in the TUBERCULOSIS. 445 serous membranes, the liver, and the kidneys, are precisely analogous to the changes in the intestinal mucous membrane. The alterations in the fibres of voluntary muscle {Zenker) will be fullv described hereafter (§ 756). 2. Tuberculosis. § 383. Before beginning the study of tubercidosis as it occurs in mucous membranes, we must learn to discriminate carefully between tuberculous disease of mucous membranes, and those diseases of the mucous membranes which occur in tuber- culous patients. It is only in a few instances that the develop- ment and decay of tubercles constitute the sum-total of the morbid changes ; in a somewhat larger proportion of cases, they form the leadino- feature of the disease : as a general rule however, the actual growth of tubercles occupies a relatively subordinate position, in comparison with the non- tubercular alterations, serving as a sort of excitant or guiding impulse — as a standing Avitness to the specific and incurable nature of the malady. § 384. Tuberculosis of i'he uro-genital mucous mem- brane affords the best example of the changes which tuberculosis per se is capable of effecting — of the disturbances which may be ascribed exclusively to it. The tuberculous ulcer of the lu'inary bladder is a shari^ly-circumscribed, more or less circular defect in tlie mucous membrane, with a dirty -yellow, "bacony"' infil- tration of its base and edges. On closer examination, this bacony infiltration proves to consist of ^^true" tubercles; miliary nodules, some grey, some cheesy, packed closely together, form the floor and edxres of the ulcer, while i\\Q vouno^est and smallest granulations serve to extend the process, and are scattered, far in advance of the rest, through the healthy parenchyma of the mucous membrane. In fact, the growth of miliary tubercles takes the place of the " plastic infiltration'' of common inflam- mation ; while their cheesy metamorphosis, softening, and dis- integration, stand for the subsequent destructive suppuration. Side by side with the older and mature ulcers, we usually find the first beginnings of the disorder in the form of solitary, grey or cheesy, miliary nodules, disseminated through the most super- ficial laver of the connective tissue of the mucosa ; others 44() MUCOUS MEMBRANES. again, forming small clusters, and already exhibiting a minute (3entral cavity. The gradual and uniform extension of the growing and softening tubercles from these centres, necessarily gives rise in the first place to a circular ulcer, the " lenticular tuberculous ulcer." Several such ulcers, becoming confluent, form secondary ulcerations of larger size, whose outlines are most irregular. These gradually extend over progressi^'ely \vider areas of tlie mucous surface, until at length the de- nuded parts exceed the healthy surface in amount, the rela- tively intact portions forming narrow borders between adjoiniiig ulcers. § 385. These observations, which primarily refer to tu)>er- culosis of the urinary bladder, may be transferred to any part of the uro-genital tract, and particularly to the lining membrane of the ureters. The anatomical appearances in the latter case however, are markedly complicated by the introduction of a catarrhal element. The tuberculous ureter is at first only in a state of catarrh ; the swollen mucous membrane pours out a thick, viscid, purulent secretion ; and the swelling, together with the discharge, may affect the state of the urine, causing the chief clinical symptoms of tuberculous disease of the ureters, before a sinofle tubercle is formed. Tuberculosis of the womb is second- arily complicated with an overgrowth of the connective tissue, partly in the submucous, partly in the muscular layer, which may attain very considerable proportions ; hence a positive en- largement of the organ as a Avliole, is associated with a progressive loss of substance from its inner surface. Even more peculiar is the complication of tuberculous ulceration of the bowels with a papillar}^ and polypoid hj^pertrophy of the unaffected residue of the mucous membrane. This may assume such proportions, that the entire membrane may be masked by the dark-red, congested polypi, as large as peas, between whose bases the ulcerated surface itself may escape notice unless looked for. The com- ])lication is not, however, a common one. Far more common, and much more difficult to distinguish from the tubercular affection proper, is the combination of tuberculosis with that scrofulous overgrowth of the Ijanphatic follicles with which we have already become familiar, as it occurs in the lymphatic glands (§ 203, et seqq,). § 386. The very same regions of the digestive system whicli TUBERCULOSIS. 447 we found to be affected in abdominal typ]iu<, arc also the favourite seat of tuberculosis, sc, the lymphatic glands, Fever's patches, and solitary follicles in the neighbourhood of tlie ileo- eoecal valve. The process however is not restricted, as in abdominal typhus, to the lymphatic structures and the parts immediately surrounding them ; it starts from them indeed, but only to extend farther according to a special law of its own. Now it is just these primary' changes in the closed follicles which are not of a tuberculous nature. The grey intumescence which oauses enlargement of the individual follicle to about three times its normal bulk, depends upon the same one-sided kind of pro- liferation of the corpuscular elements in the lymph-paths and the reticular parenchyma of the follicles, with which we arc familiar as the cause of the scrofulous bubo ; the subsequent caseation, it is true, differs in no respect from the degenerative change to which the true tubercles themselves succumb ; so that when once this stage has been reached, it is no longer possible to distinguish between the two processes. It is wortliy of note, moreover, that the disorder of the corresponding mesenteric glands is purely of a ^^ scrofulous" kind, and cannot be con- founded with the very different anatomical aj^pearances presented by genuine tuberculosis of a lymphatic gland. The cheesy follicles soften from without inwards, and when the cheesy matter is wholly dissolved, we find a sharply-circum- scribed hemispherical defect, the so-called '' cleansed ulcer," environed by relatively healthy tissue. The close proximity of the neighbouring follicles to one another in a Peyer's patcli, may lead, even at this early stage, to a coalescence of several of these minute ulcers to form those larger defects which, from their being bounded on all sides by segments of a circle, with their convexities outwards, liave been called '' racemose ulcera- tions." § 387. On examining fine vertical sections through the base and edges of one of these ulcers, we notice that it is everywhere surrounded by a tolerably wide zone of corpuscular infiltration of the coimective tissue. But neither in the corpuscular elements themselves, nor in the mode of their arrangement, can we detect anything specific. It would seem, moreover, that the gradual extension of the ulcer is essentially due to the progressive advance of the infiltration into the neighbouring tissues, and tlie 448 MUOOITS MEMBRANES. subsequent resolution of the infiltrated matters upon the ulcerated surface. Tlie specific, "tuberculous" element, is accordingly quite subordinate in tuberculosis of the intestines. But it would be a great mistake to suppose it wholly absent. Careful investi- gation shows — 1st, The presence of a certain number of miliary nodules in the tunica adventitia of all the non-capillary vessels, and especially of the arteries in the neighbourhood of the ulcer. 2nd, The strictly tuberculous nature of those granulations which occasionally spring up on the opposite surface of the intestinal wall, in the subserous and serous connective tissue, and which enable us to ascertain from the outside, the exact position of the morbid changes in the mucous membrane. The observa- tions recorded in § 115, led me to investigate these struc- tures very thoroughly ; and I have assured myself that here too, it is the lymphatics which undergo tuberculous degeneration, and that the sheaths of the vessels are so manifestly chosen by the tuberculous products, only because they also contain the efferent lymphatics of the bowel. The development of miliary nodules upon the branches of the vessels or lymphatics is of especial moment in the present instance, inasmuch as it determines the direction in which the ulcer of the intestinal mucous membrane must extend. For, in marked contrast to the invariably axial configuration of the typhoid ulcers, which do not overstep the limits of a Peyer's patch, the tuberculous ulcers exhibit a decided tendency to spread transversely. They are always tending to become zonu- lar ; originating in Peyer's patches, where also they attain their greatest width, they push their way over the lateral margins of the patch, till their extremes unite on the opposite side of the bowel. If we compare the distribution of the blood-vessels with this mode of extension, we cannot fail to see a certain parallelism between them. The arteries and veins reach the bowel betweeii the layers of the mesentery, on the side opposite to the Peyer\s patch ; from this point they radiate in an arborescent form, their trunks and main branches coursino* ti'ansverselv across the intestinal tube, while their finer ramifications meet on the outer side of the canal, where the patches are situated. The vascular territories of the intestinal wall are accordingly transverse and not axial, and any morbid change which is conterminous with a yascular area, must eo ipso extend in a transverse direction. TUBEECULOSIS. 449 Now the discovery of miliary nodules upon all the ramifications of the afferent vessels makes it clear that tuberculosis belongs to this category ; hence too, we see why it extends across, and not along the bowel. § 388. As regards the further consequences of tuberculous ulceration of the bowels, I need only say that hsemorrhage and perforation may occur, just as in abdominal typhus. The tuber- culous infiltration of the vascular wall on the one hand, and of the serous membrane on the other, and the necrobiotic detach- ment of the infiltrated part, necessarily lead to perforation, now into the blood- channel, now into the peritoneal sac. In either case, however, this accident presupposes the absence of those natural safeguards which usually ward off any such extreme issues ; in the former instance, timely coagulation of the blood in the endangered vessel, in the latter, timely adhesion of the serous coat to some other part of the peritoneal surface. I have seen a case in which five tuberculous ulcers of the ileum had perforated, not however into the peritoneal sac, but into other divisions of the bowel, which had previously become adherent opposite the seat of ulceration. This, of course, put a stop to all peristalsis, the products of digestion circulating without any order through numerous false passages in the abdominal cavity, inasmuch as the fistulous communications were in some cases wider than the calibre of the intestinal tube itself. § 389. Passing now to tuberculosis of the laeyngeal and BRONCHIAL mucous membranes, we enter on a debatable ground, where it becomes extremely difficult to ascertain how much of the morbid process is really tuberculous. Virchow does not scruple to assert that " tuberculous " ulcers of the larynx actually originate from miliary tubercles ; he assigns their production, and extension both in breadth and depth, to a process identical with that which we learnt to know in con- nexion with tuberculous ulceration of the mucous lining of the urogenital tract. Other observers, as e.g. Ri/hle, utterly deny the presence or participation of miliary granulations in the process ; indeed Virchoiv is at the pains to explain, that miliary nodules are so rarely to be detected in these " tuberculous " ulcers, because they are here especially frail and perishable: this explanation is equivalent to an admission that they are very seldom to be seen. 39 450 MUCOUS MEMBRANES. Now if we undertake a painstaking histological analysis, by examining vertical sections through the affected parts of the laryngeal and tracheal mucous membranes, and endeavour to eliminate wliatever is decidedly non-tuberculous, we must begin by refusing a specific character to any morbid change in the closed follicles. The larynx proper, indeed, is not, strictly speaking, furnished with closed follicles ; but they are plentiful above the epiglottis, at the base of the tongue, on the isthmus faucium and the upper part of the pharynx ; and tuberculous ulceration of the larynx proper is very commonly associated with ulcers due to scrofulous inflammation, proliferation and disintegration of these pharyngeal follicles. Further, the laryngeal and tracheal ulcerations which start from the orifices of the mucous glands, are not to be considered tuberculous. I have elsewhere explained more fully (§356) how chronic catarrh of the mucous membrane ma}' give rise to dilatation and hyper- trophy of the mucous glands. I will now proceed to describe another way in which these organs may become involved in chronic catarrhal alterations of mucous surfaces ; and this is one which, hitherto at all events, I have only met with in this par- ticular region and in this particular case. Accordingly I must regard it provisionally, as peculiar to the laryngo-tracheal mucous membrane, and more especially as a very important factor in that aggregate of anatomical changes which we include under the name of laryngeal phthisis. If w^e separate the cut edges of a trachea whose mucous lining is in a state of chronic catarrhal inflammation, and wipe awa}" the mucus from its surface, we may readily detect with the naked eye, the orifices of the mucous glands. In the inter- vals between the cartilages they are very closely set ; here too, they are especially wdde ; on a level with the rings they are fewer in number and more narrow ; here and there, indeed, they may even be quite absent. Now if we squeeze the trachea gently from below", these openings are seen to exude small quantities of viscid mucus, which present a sharp outline and resemble grey, translucent dewdrops. Should any one of these drops, on more careful inspection, exhibit a narrow straw-coloured border, this indicates that the ulceration in question has already begun. For this yellowish border consists of pus, pus produced by the subepithelial connective tissue of the follicular duct, and dis- TUBERCULOSIS. 451 charged into its cavity. During the extrusion of the accumu- lated secretion from the gland, this little drop of pus was the first to escape ; it then became uniformly spread out round the edges of the drop of mucus which followed it. The j)us-formation in the efferent duct may continue for a time as a purulent catarrh, but it must certainly pass, and that soon, into a pus-formation with loss of substance — into ulceration. A circular, shallow, funnel-shaped ulcer is formed, girdled by a narrow zone of a bright-yellow colour, which marks it off sharply from the hyperaemic mucous membrane round it. In the centre of this defect, the dilated orifice of the duct, or the gland itself after suppurative destruction of its elements, forms a rounded hollow of proportionate size, which is, at the same time, the deepest part of the floor of the ulcer ; thus we see that the catarrhal ulcera- tion of the gland- ducts is really peculiar enough to warrant our distinguishing it from allied conditions. It is only when the ulcer proceeds to extend in depth and breadth that its primordial characters become effaced. The coalescence of contiguous ulcers produces e. g. racemose outlines, like those which are usually held to be characteristic of the " tuberculous " ulcer ; indeed the racemose form is even more distinctly marked in these cases than in tuberculous lesions of the bowels. The extension of the ulcer in depth is favoured by the suppurative destruction of the body of the mucous gland. A suppurative inflammation of its capsular and interstitial connective tissue, leads to the disinte- gration and solution of the acini ; the entire gland melts away ; and when we reflect that the mucous glands of the air-passages are situated, not in the mucous, but in the submucous layer, we can readily perceive that these ulcers must be especially prone to produce " excavations." As a fact, we soon find the floor of the ulcer close to the tracheal rings, or the laryngeal cartilages ; and this paves the way for a fresh series of lesions. The cartilages of the larynx and trachea, owing to their non- vascular texture, and their obviously sluggish nutrition, are more disposed te undergo necrosis en masse than a gradual destruction by successive layers. When the inflammatory irritation reaches the perichondrium, it not unfrequently happens that before the cartilage itself has time to undergo any marked alteration in its form, colour and consistency, the entire mass is isolated by a suppurative perichondritis; it becomes a sequestrum, and is 452 MUCOUS MEMBRANES. ready for expulsion, as soon as the abscess-cavity communicates with the floor of the ulcer by an aperture large enough to allow of its passage. (Arytsenoid cartilages.) As a general rule indeed, this catastrophe is preceded hy a stage of true ulceration ; the cartilage is laid bare, though only on one side, that which forms the floor of the ulcer — while everywhere else the perichondrium continues intimately united to its surface. The advance of the destructive process may then be admirably traced in vertical sections ; the outermost layers of cartilage -cells are transformed by fusion into groups of pus-cells, while the cartilage-cavities have simultaneously increased in size at the expense of the matrix to such a degree, that just before they burst they are actually in contact with one another. Hence the floor of the ulcer, so far as it lies in the cartilage, is lined throughout with dilated car- tilage-capsules full of pus. Meanwhile these alterations, though very important, are confined within relatively narrow limits. The third or fourth row of cartilage -cells (counting from the floor of the ulcer) is quite intact ; at most, the nuclei may be beginning to divide. In the trachea, the course of the ulcera- tion may lead to the denudation of the majority of the rings on their inner surface ; one ring after another becomes detached from its extremities to its centre ; the separation extending in- wards till it is complete, when the entire ring is coughed up. § 390. Seeing that the most severe and extreme lesions of the larynx and trachea may be produced by simple catarrhal inflammation and ulceration, we may be tempted to inquire what there is left for tuberculosis to accomplish ? Are tubercles pre- sent at all in " laryngeal phthisis " ? and if present, what part do they play ? It is quite clear that my own observations are op- posed to any unconditional transfer of the results, arrived at by studying tuberculosis of the urogenital mucous membrane, con- cerning the mode of origin and extension of "tuberculous" ulcers, to the mucous lining of the larjmx. On the contrary, I feel bound to insist that the actual destruction in the latter case is operated, not by the breaking- down of tubercular deposits, but by the known resources of inflammatory proliferation. Nevertheless, I am quite convinced, that here too, miliary tubercles may un- doubtedly be developed ; grounding my belief partly on the authority of Virchow, who has actually observed true " tuber- culous " ulcers in the larynx, partly on certain appearances seen PAPILLOMATA. 453 in vertical sections through the ulcers described above, appear- ances which I may be allowed provisionally to regard as due to an eruption of miliary granulations. For in these ulcers of the larynx and epiglottis, we very frequently meet with spheroidal clusters of cells, situated well below the surface, in the midst of con- nective tissue which is still intact. These deposits resemble a single gland-acinus in size ; when soaked in carmine solution, they absorb the colouring-matter far more greedily at their edges than towards their centre, a fact which points to a globular mode of grouping, and reminds us ver}^ forcibl}^ of the behaviour of miliary tubercles under the same conditions. These tubercles, indeed, are so sparingly disseminated, the}^ appear so very insig- nificant in comparison with the inflammatory infiltration of the ulcerated surface itself, that I would only regard them as a pledge of the connexion of the morbid changes with constitu- tional tuberculosis. At most, they could only be raised to the dignity of permanent inflammatory irritants, and so made re- sponsible for the obstinacy and proneness to recur which is so especially marked in these catarrhal inflammations. The occurrence of true miliary tubercles on the minute bronchi, in the neighbourhood of so-called tuberculous cavities, will be discussed in the chapter devoted to the respiratory organs. d. Tumours. 1. Papillomata. § 391. Papillomata of the mucous membrane must be care- fully distinguished from those tuberous and polypoid elevations of the mucous surface which are due to glandular hypertrophy and dilatation. They exhibit many varieties of external form and situation. a. On the mucous lining of the oral cavity, in the vagina, just within the anus, in a word, on the transitional semi- mucous surfaces, we find the papillary types of the skin but little modified. Instead of the ordinary wart we have roundish, sessile, berry-like bodies, attached to the gums or the inner surface of the cheeks ; they are very similar to condylomata, differing only in the greater toughness of their epithelial cover- 454 MUCOUS MEMBRANES. ing. Condylomata, both flat and pointed, occur in forms whose purity of type is proportional to the resemblance of the auto- chthonous epithelium of the affected part, to that which clothes these tumours. Nevertheless, the pointed condylomata keep very strictly to the muco- cutaneous boundary -line ; while the broad and flat variety is met with here and there, both in the oral cavity and in the vagina. h. On the mucous membrane of the gall-bladder, the urinary bladder, and the os uteri externum — in regions, therefore, which are normally lined with columnar or transitional forms of epithelium— the papillomata are also invested with columnar epithelium. Papilloma of the bladder, also called villous cancer, or more correctl}', villous tumour of the bladder, always springs from the trigone between the openings of the ureters. At this point a rounded, ver}^ soft tumour rises from a broad base to a height of about an inch above the mucous surface. It is clothed with so thick a layer of columnar cells, that the very wide capillaries which shine through onl}^ succeed in giving it a rosy tint, making the entire mass look not unlike an encephaloid tumour (Markschwamm). In point of fact, however, the growth has nothing whatever to do with cancer ; on the contrary, the most superficial examination is enough to show that it consists of a number of arborescent groups of villi, and of nothing else. This quite agrees with recorded cases of extirpation of papil- lomata of the urinary bladder, not followed by any return of the disease. Each of the component villi is characterised, on the one hand by containing an enormously wide and very thin- walled blood-vessel in its axis, which forms a loop with a varicose dilatation at its flexure, on the other by the triple or quadruple stratum of columnar cells already alluded to, which lie so close upon the vessel that the villus cannot justly be said to possess a framework of connective tissue at all. Papillomata growing from the external os, contain more connective tissue and fewer blood-vessels ; their epithelium too is more scanty. The stout, club-shaped terminations of the dendritic growth, are clothed with a single layer of columnar cells ; nothing like a varicose dilatation of the vessels can be anywhere discerned. The description of ''papilloma cysticum" given in § 70 is taken from this variety. CARCINOMATA. 455 In the human gall-bladder we only meet with excessively minute and insignificant papillomata. On the other hand, Virchow has placed upon record the case of a cow, whose gall- bladder he examined ; its thickened walls " were beset with such multitudes of partly villous, partly cylindrical, solid out- growths, that the mucous surface over a certain area seemed to have entirely disappeared." § 392. The relations of these papillomata to epitlielial cancer of the mucous membrane, are both interesting and important. Not only has it been show^n that a papilloma maj^ pass into an epithelioma, and that an epithelioma may be secondarily com- plicated by papillary proliferation from the edges and base of the ulcer, but it has been repeatedly asserted that the mucous membrane over a cancer which is forming in the submucous tissue, is prone to become the seat of papillary growth. For my own part, I have never observed anything of the kind, and I cannot therefore express any opinion concerning the intimate connexion of these two phenomena. Virchoiu regards the de- velopment of the papillomata as a simply hyperplastic change to begin with, excited by the irritation of the adjoining cancerous formation ; the possibility of its conversion into a true villous CANCER only beginning, when the carcinoma is propagated by continuous infiltration from below, to the connective tissue of the papillae. He goes on to say, that the stomach and urinary bladder are the chief seats of these true villous cancers, which are probably identical with our own columnar epitheliomata. 2. Carcinoinata. § 398. The mucous surfaces, lined as they are with epithe- lium, are everywhere disposed to the production of epithelio- mata ; to that of glandular cancer only in so far as they happen to contain open glands. To this latter circumstance must be ascribed the striking differences between the average liability of various regions of the mucous tract to cancer. Moreover, the epithelial form seems to prefer the points of junction between the several divisions of the mucous tract ; this is mainly owing to the pre-eminent exposure of such localities to mechanical irritation of some sort, which need not necessarily be abnormal. § 394. Starting from those orifices of the mucous system 456 MUCOUS MEMBRANES. which are situated in the head, we find, apart from those can- cerous affections of the lips, ej^elids, and alae nasi, which property belong to the skin, a true soft glandular cancer of the MUCOUS LINING OF THE NASAL Foss^. In adults, tliis is de- veloped on a soil previously made ready for it by a chronic hypertrophy of all the structural elements of the mucous mem- brane ; in children, it occurs without an}^ preparatory stage. It forces its way by preference into the antrum of Highmore, dis- tends the upper jaw, and manifests itself as one of the several varieties of what is known as '* cancer of the upper jaw." The patient succumbs so rapidly to the attendant cachexia, that surgeons are now very sh}^ of all operative interference. The tumour is wholly made up of imperfectly developed gland- tubuli, produced by an excessive proliferation of the epithelium of the mucous follicles. § 395. In the oral cavity, the tongue is a favourite seat of cancerous disease. It usually takes the form of a squamous epithelioma, which however, in accordance with the greater delicacy of the normal squamous epithelium of the tongue, is distinguished from the harder squamous epitheliomata of the skin by its softness, and a tendency to speedy disintegration. The quantity of blood-vessels, lax areolar tissue, and above all, of wide tymph-paths with which the tongue is furnished, ren- ders its parenchyma peculiarly favourable to the extension of the morbid growth by infiltration. Hence the local mischief assumes a former place in the history of the disease. The primary nodule is nearly always situated on one or other edge of the tongue. It is said that the irritation of a ragged and decaying tooth may have some share in causing the cancer. This primary nodule is usually extirpated by a V-shajDed incision. The disease soon recurs however, and the operation has to be repeated ; with each repetition, the interval between the extirpation and the return of the disease grows shorter, until at last the entire tongue is destroyed. Metastatic deposits may occur both in the nearest lymphatic glands, and in the lungs ; these secondary deposits however, are always of very subordinate importance. What is known as soft cancer of the tonsils, is a soft lymphadenoid sarcoma which is very prone to invade the pala- tine arches and the isthmus faucium (Choanen). § 396. At the entrance to the RESPiRATORy tract we meet CAKCINOMATA. 457 with a tolerably soft variety of squamous epithelioma, which differs from that of the tongue in its tendency to develope papillary outgrowths. In the substratum of the laryngeal mucous membrane, the tumour meets with a soil as ill-adapted as possible for any extension by way of infiltration. Next to a submucous layer made up of perfectly inelastic fibres, comes one of fibroid tissue ; beneath this, and throughout the whole of the submucous and mucous layers, networks of elastic fibres are abundantly distributed. What wonder then if the growth tend rather to extend outwards, to form papillary excrescences, for years and years before it penetrates into the deeper structures of the neck ? § 327. In the cesophagus, a hard squamous epithelioma gives rise, first to a zonular tumour, and then to a zonular ulcer with an infiltrated base and edges ; the ulcer extends ; the mucous membrane may come to be deficient all round the tube for a width of two to three inches ; while the base of the ulcer may invade, and eat its way into, the neighbouring air-passages from without. A perforation through the floor of the ulcer into the respiratory passages is a very grave accident. This abnormal communication between the alimentary canal and the respiratory passages is usually situated, n'ot in the trachea, but in the posterior wall of the left bronchus. The left bronchus, as is well known, crosses the oesophagus in its middle third, and this is the point usually selected by oesophageal cancer. It has justly been supposed that a mechanical cause of some kind must contribute to localise the disease at this particular point ; and that cause is to be sought in the fact that every morsel of con- siderable size, in passing down the oesophagus, squeezes its anterior wall against the posterior wall of the unyielding bronchus. Of course perforation of the air-passages is only one among many dangers to which the victim of oesoi^hageal cancer is exposed. The zonular tumour may prove fatal by causing stricture ; the extension of the morbid process to the mediasti- mum may, during the inspiratory fall of tension in the thoracic cavity, occasion the entrance of air from the oesophagus into the lax areolar tissue which adjoins it, and so give rise to true emphysema of the entire subcutaneous tissue ; the base of the ulcer may become converted into a regular diverticulum, in which the food may lodge and become decomposed, &c. 458 MUCOUS MEMBRANES. Compared with carcinoma of the middle third of the oesopha- gus, cancerous affections of the cardia and other regions are uncommon. I have met, however, on two separate occasions, with a very superficial and much softer variety of cancer, which had invaded large sections of the oesophageal tube in a very diffuse way. § 398. The stomach has an especially rich repertoire of carcinomata ; we find, with nearly equal frequenc}^ a soft, a hard, and a colloid form of glandular cancer, as well as a columnar epithelioma. All the varieties of glandular cancer agree in their origin from the mucous membrane proper, extend- ing secondarily to the submucous tissue. I lay stress upon this fact, because an essential distinction used to be drawn between " submucous " and " mucous " cancers of the stomach. It is true that the transition above alluded to usually occurs at a very early period, and that the cancerous proliferation advances much more rapidly in the wider spaces of the submucous tissue, with their numerous lymphatic networks, than in the mucosa proper. Hence it is, therefore, that the cancer frequently takes the form of a laminar infiltration of the wall of the stomach, over which the mucous membrane extends, either unaltered or simply atro- phied, and is freely moveable, while it is bound down to the subjacent growtli at one point only. Now it is from this point that the morbid process originally sets out ; this is the oldest part of the disease. In most of the cases which come under our notice, it is occupied b}^ an ulcer, which has destroyed the place of origin of the cancer, and has accordingly made it impossible to decide, whether the glandular elements of the mucous mem- brane had any share in the first development of the disease, or not. All the more valuable are the statements made by Waldeyer {Virchoivs Archiv., vol. xli.), who succeeded, not- withstanding these obstacles, in establishing the origin of the morbid growth from the mucous follicles and peptic glands. A very usual post-mortem appearance in soft cancer of the stomach, is that of a single ulcerated patch, several square inches in area, surrounded by a border of mucous membrane thickened by infiltration with cancerous elements. The tumour has originated, as very often happens, on the lesser curvature, and has extended downwards from this point both along the anterior and the posterior wall of the organ. The ulcerated CAROINOMATA. 459 surface itself is covered with shreds of tissue, which float when a stream of water is poured over tliem. They are the remains of the cancer- stroma, which resist destruction longer than the cancer-cells. They now become detached, principally owing to the action of the gastric juice, and so give rise to those patho- gnomonic hsemorrhages in which the blood escapes a drop at a time, coagulates forthwith, and assumes a brownish-black tint ; innumerable particles of this altered blood giving the contents of the stomach — the vomited matters — the appearance usually described as resembling coffee-grounds, chocolate, &c. On examining a vertical section through the thickened border of the ulcer, we see how, on the sound side, the glandular layer of the mucous membrane is stretched by the tumour, how over the most prominent part of the raised border its thickness is sud- denly reduced, the glands being as it were compressed at both ends, and the contiguous ones forced asunder. At last the mucosa proper is only represented by an interrupted chain of wasted glands ; between which and the muscular coat, the entire thickness of the cancerous mass, which may attain from four to six lines, intervenes. On the other side of the boundary, the transition to ulceration is effected by fatty degeneration of the cancer-cells. Even the unarmed eye can detect the yellow dots and striae of the decaying cancer-tissue, and trace them all round the floor and borders of the ulcer. The disintegration itself may be hastened by the action of the gastric juice upon the necrobiotic tissue ; at least the process is usually more sluggish in the precisely analogous affections of the uterus, urinary bladder, &c. The course of the scirrhus ventricnli is very different. This variety of cancer is far slower in its rate of growth ; starting from the lesser curvature, its favourite place of origin, it suc- ceeds for the most part in extending round the entire circum- ference of the stomach. The submucous and mucous layers are converted into a white, fibroid band, from two to three lines thick, which, wdien the girdle is complete, gives the middle of the stomach the appearance of a rigid tube from one to two inches in diameter, to which the fundus is attached like a loose bag. The microscope shows a very marked resemblance between the arrangement of the epithelial elements and that of glandular epithelium. Not that the cells and cell-nests are either very 460 MUCOUS MEMBBANES. large or very numerous ; on the contrar}^ the stroma of con- nective tissue decidedly predominates. But the form of the cell-nests is comparatively regular ; they are elongated tubuli, circular in transverse section, in which the epithelial elements, of small but uniform size, are disposed almost radially, though an axial lumen may not be discoverable. Colloid cancer of the stomach is also distinguished by its prevailing tendency to cause destruction, as opposed to ulcera- tion ; even before giving way, it invariabl}^ becomes zonular. It may thus give rise to very serious stenosis. The ulcerative process is a slow disintegration, proceeding from within out- wards, without haemorrhage or abundant secretion of any sort. Were it not for the risk of extension to the peritoneum, colloid cancer of the stomach would agree with scirrhus in the com- parative innocence of its primary manifestations. As regards the minute structure of this form of cancer, the horizontal sections recommended by Koster are so far important, that they undoubtedly shift the onus of infiltrative propagation to the lymph-paths of the gastric walls. This observer is inclined to transfer the results which he has obtained from the investiga- tion of Cylindromata (§ 173), with reference to the share taken by the endothelia in the process of morbid growth, to colloid cancer of the stomach. My notions concerning hard glandular cancer, as laid down in § 159, make it quite obvious that I can have no a priori objections to this view. I would regard these appearances as indicative of an " epithelial infection " of the endothelial elements of the lymphatics, starting originally from the glands. But I must beg the reader to observe that my attitude, especially as regards the colloid variety of cancer, is one of expectation. §399. The spread of these three varieties of cancer OF THE stomach TO NEIGHBOURING ORGANS is of high cliuical importance and anatomical interest. The muscular coat is in- volved after the submucous laj^er. The cancerous infiltration follows the narrow bands of interstitial connective tissue between the muscular fasciculi. These fasciculi themselves, owing per- haps to the continued irritation to which they are exposed, undergo a hyperplastic thickening. This is the rule at least in the colloid and scirrhous forms of cancer. In vertical sections through the walls of the stomach, we can trace, even with the CAECINOMATA. 461 naked eye, the progressive!}" increasing thickness of the muscu- lar bundles as we pass from the healthy to the diseased tissues. If we add to this the amount of additional matter produced by the cancerous degeneration of the interstitial tissue, we can be at no loss to account for the muscular coat attaining from three to five times its normal thickness. Having traversed the muscular coat, the cancer reaches the visceral peritoneum. The first nodules then make their appearance in the subserous connective tissue. Their arrange- ment often shows very clearly their original dependence on the course of the muscular fasciculi ; i.e. they lie parallel to these, in lines which correspond to the intermuscular septa of con- nective tissue. Soon, however, the adjacent nodules coalesce with one another, and we get irregular, flattened lumps, wdiich present the special characters of the particular variety of cancer to which they belong, in their least complicated form. This extension to the peritoneal coat is almost alwaj^s the signal for a general degeneration of the entire sac. It is probable that the mutual friction of the viscera may detach bits of the cancerous nodules and carry them hither and thither over the smooth surface of the membrane, until they find their way into some fold or recess where they give rise to the development of a fresh nodule. The general effect — as Virchoiv puts it — is that of seeds having been scattered over the peritoneal surface, falling here and there, and germinating. In this respect, soft and scirrhous cancer behave in precisely the same way. The colloid variety takes up a position of its own in this as in other matters ; it performs the giant task of converting the wiiole peritoneum into a mass of colloid cancer, continuously, without any break, by a simple process of infiltration. The thickness which a single peritoneal lamina attains w^hen the infiltration is completed, amounts to two or even three lines ; the omentum, as a duplica- ture of the membrane, is converted into a plate an inch thick, and as hard as a board ; the mesentery and the various ligaments follow suit. It is self-evident that under such conditions, the most important disturbances of peristaltic action are unavoid- able. The phenomena are usually complicated, moreover, b}^ in- flammatory accidents, by an abundant sero-fibrinous exudation, by small haemorrhages and adhesions. Similar accidents also occur in the course of soft and scirrhous cancer. The scirrhous 462 MUCOUS MEMBRANES. variety however, exhibits a very remarkable peculiarity in addi- tion, doubtless connected with minuter tissue-changes, but the main feature of which has hitherto evaded all direct elucidation. I refer to the contraction of the connective tissue in the neigh- bourhood of the scirrhous nodules. The narrowing of the gastric cavity, which coincides in point of time with the thickening of its walls, and which has already been alluded to, must be ascribed to this contraction. In this locality however, there is no hope of ever arriving at a better knowledge of the process. The phenomena are far more open to investigation as they occur in the peritoneum. We may expect, in particular, to get at some reliable results by examining the transparent texture of the epiploon. This, in point of fact, shrinks into a rigid cord, with cancerous nodules scattered through its substance, which may even, supposing the ascites moderate in amount, be felt through the abdominal walls in the region of the transverse colon. If we spread it out, and try to ascertain the cause of its shrinking, it reminds us, under a low magnifying power, of a cloth, spread out flat, and then clutched and crumpled together from a single point, from which the folds all radiate ; but instead of the crumj^led nucleus, we find the smooth, white, scirrhous nodule, forming the centre of these radiating folds. For my own part, I feel convinced that the pre-existing connective tissue really is in some sort used up in the present case, and that the scirrhous nodule, moreover, represents the quanity of connective tissue so employed ; but I am not able to offer any opinion about the way in which this is brought to pass. This degeneration of the peritoneal sac naturally leads to rigidity and contraction of the mesentery, and consequently to the most serious disturbances of the intestinal peristalsis ; more- over, very intimate adhesions usually form between the abdo- minal viscera, so that the small intestine, for instance, is often found as it were rolled up into a ball, in the interior of which its canal forms the most labyrinthine convolutions, offering difficulties, almost insurmountable, to its being traced out by dissection. § 400. Instead of the various forms of squamous epithelioma which we have repeatedly encountered between the lips and the cardiac orifice, we meet, below the cardia, with a columnar ejjitJtelioma. Its favourite seat is in the stomach, and most CARCINOMATA. 463 commonly in its p3'loric part ; indeed it is often localised on the fold of mucous membrane which separates the stomach from the duodenum. In this region it gives rise in succession, to a flat tuberous elevation, a fungoid tumour with a broad base, and finally a polypus ; the latter is often quite spherical, larger than a pigeon's egg, with a relatively short pedicle. In this its final form, the tumour is admirably fitted to block up the duodenal canal, and so, i.e. by hindering the introduction and digestion of food, to cause acute marasmus ending in death, unless the growth is speedily softened and broken up. When this occurs, a smooth excavation is left, in whose edges the further extension of the growth may be traced. And here it is closely related to that adenoma of the alimentary tract which I have described more fully in § 171. § 401. In the lower divisions of the digestive tube, w^e have a soft glandular cancer of the colon, which tends to produce zonular ulcerations with a fibroid and therefore firmly-contracted base, and so to cause stricture of the bowel with its conse- quences. In the same region w^e find a superficial adenoma — a variety w^hich is also met wdth in the rectum {Klehs, Ley den). Squamous epitheliomata of the rectum immediately above the anus, frequently attain a very considerable size as cauliflower growths, before thej^ start from the mccous follicles to invade the deeper parts (§ 166, note 2). § 402. The uterus exhibits a greater liability to cancerous disease than any other part of the urogenital tract (if we class cancroid of the penis among tumours of the skin). A good half of all the cases of so-called uterine cancer are epitheliomata. These originate either from the mucous lining of the cervix or from the portio vaginalis ; in either case, it is long before the boundary-line betW' een the portio vaginalis and the canal of the cervix is overstepped. Cancroid of the portio vaginalis very commonly originates as a soft papilloma, or cauliflower growth ; the transition to deeper parts being effected, as in papillomata of the skin, by the dislocation of the epithelial boundary into the subepithelial connective tissue. Epithelial cancer may give rise to very extensive lesions in the uterus. The muscular coat offers most resistance. When this has given way, the lax areolar tissue between the organs of the true pelvis offers a most favour- able soil for the luxuriant extension of the morbid growth. We 464 MUCOUS MEMBRANES. find a cavity several inches in diameter, whose internal surface is coated with the most offensive products of putrefaction, bounded above by the still undestroj^ed remnant of the fundus uteri, in front by the posterior wall of the bladder, behind by the anterior wall of the rectum ; while the vagina, whose upper half is also involved in the destructive process, maintains the cavity in communication with the exterior. At a later period, perforations occur in the floor of the ulcer ; that which lays open the bladder gives rise to a vesico-vaginal fistula, that into the rectum, to a recto-vaginal fistula, while the perforation of the peritoneal sac excites peritonitis. It is this latter accident indeed, which often brings the lamentable sufferings of such patients to a close. § 403. The glandular cancers of the womb are situated in the body of the organ. They cause its enlargement, which is often considerable and tolerably uniform ; the true pelvis is filled up, the rectum and bladder compressed and displaced. On opening the organ, its cavity is found to be distorted by the cushion-like convexity of its protruding walls ; the walls them- selves, throughout their entire thickness (up to 3 inches), are of a uniform marrowy-white colour ; the line of demarcation be- tween the mucous and muscular coats is obliterated, the pro- liferating gland-tubuli having made their way through the entire thickness of the latter layer. § 404. In the urinary bladder, the villous cancers which grow from the trigone are especially worthy of note {see § 392). Besides these, a squamous epithelium is occasionally, though rarely, met with in the calyces and pelves of the kidneys. It usually extends at a comparatively early period to the tips of the adjoining papillae, and spreads, forming a milk-white zone of infiltration from two to three lines in thickness, into the renal parenchyma— a true "phthisis renum cancrosa." END OF VOL. I. UNIVERSITY OF CALIFORNIA LIBRARY Los Angeles This book is DUE on the last date stamped below. 2 WK from Kece^ot Cirti or MAY 3 /l972 , BfilO JUN3 19l9i»WB nM BIOMED LIB. eiflMED AUG 1 8 19' wm ciFp 5 1981 Form L9-42m-8,'49(B5573)'444 181 DAY BIOMED APR '^ 5 1986 RECD OMQ »0*»ED jL^ft DEC 2WKSFRnMPF''P't>-' MAY 7 1986 ^»OM-RENEWABI.E THELIBRAmr UNIVERSITY OF ^ ' ^ ^T^oRNIA I.OS A?f 3 1158 00693 7402