niki ea ain A ir a eS ar emer acc gece ear aes = : era Nr eer pes io pe Ae NS Tee sein ort amor ee ates ed ceca a PM Sain pt tld Deine eet tot Pe e ee omen a ane Seen Peete Tells ; RN Le en eas PRET oe ate or aoe a, < ; act CVS eee ie o ‘ ESM pt RESIS cmap ee eS . B bah i 4 Lectern ster Te I RTT TUTTE TT Sata j ARMA A ce Cra kan Coe? et Be gees rye - Cornell Mniversity Library THE GIFT OF DATE DUE we 'The Modern Practice of Midwifery. THIND AMERICAN EDITION NOW READY. Course of Lectures on Obstetrics By WILLIAM TYLER SMITH, M.D., Physician, Accoucheur and Lecturer on Midwifery and Diseases of Females in St. Mary's TTospital Medical School ; Member ofthe Royal College of Physicians ; Vive-President of the Med. ical Society, London ; Idonorary Icllow of the Obstetrical Society of Dublin, §e. WITIL AN INTRODUCTORY LECTURE ON TUE HISTORY OF THE ART OF MIDWIFERY, O'™ Gy AUGUSTUS GARDNER, AML OLD, Late Instructor on Obstetrics in the N. Y. Preparatory School of Medicine; Author of “The Causes and Curative Treatment of Sterility,” ete. ILLUSTRATED BY ENGRAVINGS. > > The above Course of Lectures on Obstetrics, lntely published in the columns of the London Lancet has been careiully revised by the author, aud by the addition of two new chapters and frequent wmpl fic: tions, and some score of new engravings, has Leen arranged to form one of Churchili’s Celebrated Mau- uals f r Students. The Pubiisher has the pleasure to amounce, that in accordance with the general high estimate of their value and the frequently exvressed desire that they mizht be made available t» the proter- tion, he made arrangements with the distinguished practical accoucher aud obstetric student, Augustus K, Garducr A. M., M. D., Follow of the New-York Academy of Medicine; N. Y. Jatuological Suc.ety; Author of the ‘Causes «nd Curative Treatment of Sterility,” &+, &c., to revise these Lectures, and properly arrange them for the use of the American Student, w10 to secure such a result, has inter persed copious annotations throughout the work, and added a Preliminary Lecture on the History of the Art of Mid- wifery, and the Os aud Crevix Uteri in its Obstetric Relntions, In its publication no expense has been spared in typography, paper or iliustation. Numerous wood cuts have bean added by the cditor illustrative of practical points; thus rendering it the most profusely illustrated work on Obstetrics ever published, and entitling it in every respect to be consi ered ay the Modern Practice of Midwifery. As now issued it occu- pies nearly 800 payes royal octavo, handsomely bound in cluth, bevelled boards. EXTRACTS FROM LEADING AMERICAN MEDICAL JOURNALS, From the Savanwan Journat or Mepicine. “Tt is especially adapted for polishing up rusty practitioners and keeping them well posted up in the dis- courses of their contemporuries.”' From the Mentoat, anp Sureroat. Rerorter. ' “The original lectures though previously quite soluble, have been much improved by the additions of Mr. Garaner. * * * In many points he h.s materially improved thé original by additions, which though small, would have been much merited by the 1eader.” From the Matnr Mrnioar axp Sureicat Rerorter. “We mnst admit. that we have never before seen so comprehensive a text-book, onthe art and science of Obstetr.cs. Ibis a matter for congratulation with the whole profession, that we have so valuable a work.” From the Cincinnati Lancet axp Onserver. “There is so much virtue in most of these Lectures tuat the work will commend itself largely to the professivn.” From the Pexixeriin ann INDEPENDENT MEp. Jour. “It igs a very complete compendium ot the kuowledge extant.” From the Boston Mepican anp Surgical Jovgnat.. “Dr. Smith’s style is pleasant, his cnvli-h good, his mode of expression clear and elegant, and his work as a whole. very readable, as well a3 practivally iustructive."" From D. F. Conpinr, Am Jour. Med. Sciences. “The name, Dr. Smith, is a sufficient ¢uarantve for the general accuracy of the theoretical teaching and practical directions of this manual, * * * The Editor has fulfilled his duties, on the whole, in an accept- able manner. The preliminary 1 -cture on the ‘ Hi-tory of the Art of Midwifery” is. to say the least of it, interesting and instruct:ve. while his pee ann tations, together w.th his Je ture upon the Os and Crevix Uteri demanded iu cases of rigidity of the latter purts are, in the main, sound and judicious.” From Prof. C T Ex..ior, N Y. Jour. of Medicine. “ Weare cf those who rre only too happy to see English books reproduced in this country, wen. as in this case, the additivus are such ar to justify the use of the annocators mame on the title page. * * * We can confident y recommend alike the book anJ the annotations to the'study of the student and the library of the professioual man." From A. T. Woopwagp. M. D., Prof. of Obstetrics, &c. in Castleton Med. College “T deem it, all in all, the very best Text-book I have ever had the pleasure to peruse, and worthy of the auchor an | editor who have contributed so much to the profession.” It will be sent by mail or express, free of covt, for $5 pe- copy Orders should be addressed to ROB’T M. DE WITT, Pubiisher, 13 Frankfort Sireet, N.Y. Sr RIL SY : ITS CAUSES AND CURATIVE TREATMENT, With vn Peeliminary Statement of the Physiology of Generation. COLERED LiTHCGRAPHS AND NUMEROUS WOOD CUT ILLUSTAATIONS. By Avausrus K. Garpner, A. M., M. D., Permanent Member of the American Medical Association, Fellow of the New York Academy of Medicine, §c., §c. This is one of the ablest and most valuable Meuical Works ever published on a subject of vital import. ance to all those who have heretofore supposed Stenittry to be incurable. i ; It is clearly aud coucisely written, und illustrated in a manner to make it easy of comprehension to readers of all classes. We give a portion of the CONTENTS. I.—PHYSIOLOGY OF GENERATION, In what reproduction consista—Fecuniation in plants and fish—Stated times of impregnation in animals and women—That the woman who men- struates is capable of being fecundated—Identity of fecundation in all animal Jife—Theory of producing sexes at will—Proportion of male to female births— Deseription of the ovam—Male life principle—The female organs of reproduction—Their fauctious—Man- ner of menstruation-~The human egz—Anatomy of evg—Man jn his first estute-—Semen—Its composition —Development cf Spermatozoa—Manner ¢ f union of the male aud female life giving principle—Action of uterus in_congress—Bischoff's and uthers' views— Distinct ve duties « f the divisions of the germ vesicle —Growth of development ceases and the growth of augmentation commences. II —PATHOLOGY OF STERILITY. Fecndation—How insured —Circumstances prevent- ing—Affections of the vagina—impotence of ma‘e from malformations, disense, &c—Effects of various viginal discharges—Various appearance of hymen— Cunstriction of, and strictures in the vagina—Prolap- sus, malpositions, flexiuns and versions of uterus— Affections of os and cervix uteri—folyphi of uterus —Value of the speculum in diagnosis— Diseases of the os and cervix, the analogue of various skin Giseases— A scroijulous diathesis having a marked tendency to uterise disease, also to fecundation—Symptoms of uterine disease—Character of vaginal discharges— Cause of death of spermatozoa—Failing of the womb Leucorrhea an evidence of a strumous diathesis— Speculum os weri ; Effects of inordinate sexual inter- course; Liseases of cavity of the uteris; Uterus ossified; Metritis ; Diseases of the fallopian tuves ; Stricture ; Rupture ; Obliteration ; Disease of fimbriated extrem- ity; Volypi; Disease: f ovary ; Tumors in aud around; Herniaot, absence cf, atrophy ; Rheumatism and neu- ralgia of ute'us and appendages ; Influence of fatness . as Causing sterility; ‘‘ Free martins ;" the female of male and female twins, barren ; Mental muanifesta- tions of the diseased; Absence of sexual uppetites from over stimulation, venereal excesses, muastur- bation, &c, III.—-THERAPEUTICS OF STERILITY. Treatment and cure sometimes synonymous ; Re- quisites for fecundation ; Operations on Hymen ; Strictures of vagina treated ; Sensitiveness of vagina from urethral tumors relieved by loca) auzsthetics ; Removal of urethral tumors by knife, ligature, cautery; Eversion of the uterus treated by Sim, - son's uterive supporter ; Polypi; Various modes of treatment ; excision, forsion, caustics curette ; Little danger of hemorrhage from; Removal by Chaissa- gnac's ecrasseur: By galvanism; Hydatids; How removed ; New form: f speculum ; U'cerations treated by local injections of cold water; Infusions of tan- nin ; Caustic applications; alteratives ; Sexual inter- course not necessarily interrupted , Issues upon os uteri, Leeches and their danger, Stricture ot cervix, and fissures of 03; Dysmenorrhe.; lustrument for d.vision of strictures; Sponge Teuts ; Catarrh of the womb; Treatment by injections; Dangers of; Ob- literation of the cavity of the uterfs ; 1 rubing fallo- pian tube; Treatment for affections of the ovary; excessive fut; Torpor of uterine system; Applic.- tion of electricity ; Syphilfffe taint; Sobriety of body and mind recommended. Mead the folsowing from some of the most eminent members of the Profession : Dr. Joun W. Francis, New York, writes to the author : ‘* You have chosen a subject of great intricacy, but have manifested by your labors an eurnestness in its investigation commeusurate with its practical imp: r- tince to the happiness aud well-being of the social st ‘te. Your anatomical and pathological expositious must have been the result of close observation, cautious reflection, and professional devotion.” De R. S. Kissam, New York, writes: ‘Its simple and perspicuons style will commend it both to the professional and general reader, thus conveying to the afflicted the knowledge that svegiviry is wot always au incurable condition.” Prof, J. Wumpuneys Storer, Boston. writes: “I have read it with no little interest, and-would recom- mendit to the Medical Student asa valuable compend, exuibiting great familiarity on the part of the author with bis subject, which is rendered perfectly intelligible to all by tue clearness and simplicity of manner with which itis treated. “ Many practical suggestions, py with regard to the treament of the derangments spoken of, TK, are distributed throughout the wo Prof. J. V. P. QuaokeNnusu, Albany, writes: valuable addition to my library. In novelty, tration, it compares favorably with the best European works, publications."" Prof. Tuos. G. Pripuzav, Charleston, S. C., says : Smith, Meigs, &c.” wich cannot but be of importance to the members ofthe profession.” t ‘fam very much pleased with the work, and consider it a literary ability, typographical appearance, and beauty of illus- and the profession demands and requires such - “It should have a place in every library with Tyler ‘ux Mevioat Press speaks of the book in the most flattering terms, “ Ltisjust such_a book as the Profession wants on this generally ignored subject.” ical and Surgical Journal. “Dr. Gardner has mide the Diseases of Females an especial object of attention, that he has profited by his opportunities. [Philadelphia Med- and this book proves It is an excellent work, wuich we recommend to all practitioners, | young and old." LY. I. Juurnal of Medicine, Manchester. Price $3; for-which amount we will mail a copy, pre-paid, to any distance within 3,000 miles R. M. DE WITT, Publisher, 13 Frankfort Si, N.Y, aa CELLULAR PATHOLOGY AS BASED UPON PHYSIOLOGICAL AND PATHOLOGICAL HISTOLOGY. TWENTY LECTURES PATHOLOGICAL INSTITUTE OF BERLIN MONTHS OF FEBRUARY, MARCH AND APRIL, 1658. BY RUDOLF VIRCHOW, PUBLIC PROFESSOR IN ORDINARY OF PATHOLOGICAL ANATOMY, GENERAL PATHOLOGY AND THERAPEUTICS IN THE UNIVERSITY OF BERLIN ; DIRECTOR OF THE PATHOLOGICAL INSTITUTE, AND PHYSICIAN TO ' THE CHARITE HOSPITAL, ETC., ETC. TRANSLATED FROM THE SECOND EDITION OF THE ORIGINAL, ’ BY FRANK CHANCE, B.A., M.B., Canvas. LICENTIATE OF THE ROYAL COLLEGE OF PHYSICIANS ; PHYSICIAN TO THE BLENHEIM FREE DISPENSARY AND INFIRMARY, WITH NOTES AND NUMEROUS EMENDATIONS, 2 PRINCIPALLY FROM MS. NOTES OF THE AUTHOR, AND : BMlustrated by 144 Hngrabings on Wood. SEVENTH AMERICAN EDITION. NEW YORK: ROBERT M. DE WITT, PUBLISHER, 18 FRANKFORT STREET. a SE Le VS\ (GO A\.2643%85 De f o tea F GD TO JOHN GOODSIR, F.RS., Ere., PROFESSOR OF ANATOMY IN THE UNIVERSITY OF EDINBURGH, AS ONE OF THE EARLIEST AND MOST AOGUTE OBSERVERS OF CHELL-LIFHRH, BOTH PHYSIOLOGICAL AND PATHOLOGIOAL, THIS WORK ON CELLULAR PATHOLOGY Os Dedicated AS A SLIGHT TESTIMONY OF HIS ‘DEEP RESPECT AND SINOERE ADMIRATION, BY THE AUTHOR. AUTHOR’S PREFACE. Tux lectures which I herewith lay before the medical public at large were delivered in the early part of this year, in the new Pa- thological Institute of the University of Berlin, in the presence of a somewhat numerous assembly of medical men, for the most part physicians practising in the town. The object chiefly aimed at in them, illustrated as they were by as extensive a series of microscop- ical preparations as it was in my power to supply, was to furnish a clear and connected explanation of those facts upon which, accord- ing to my ideas, the theory of life must now be based, and out of which also the science of pathology has now to be constructed. They were more particularly intended as an attempt to offer in a better arranged form than had hitherto been done, a view of the cellular nature of all vital processes, both physiological and patho- logical, animal and vegetable, so as distinctly to set forth what even the people have long been dimly conscious of, namely, the unity of life* in all organized beings, in opposition to the one-sided humoral and neuristical (solidistic) tendencies which have been transmitted from the mythical days of antiquity to our own times, and at the same time to contrast with the equally one-sided interpretations of a grossly mechanical and chemical bias—the more delicate mechanism and chemistry of the cell. In consequence of the great advances that have been made in the details of science, it has been becoming continually more and more * See Lect. I, p. 40 and Lect. XIV., pp. 822-824.—Transg, vi AUTHOR’S PREFACE. difficult to the majority of those who are engaged in practice, to obtain in the subjects treated on in these lectures that amount of personal experience which alone can guarantee a certain degree of accuracy of judgment. Day by day do those who are obliged to consume their best energies in the frequently so toilsome and so ex- hausting routine of practice find it becoming less and less possible for them, not only to closely examine, but even to understand the more recent medical works, For even the language of medicine is gra- dually assuming another appearance; well-known processes to which the prevailing system had assigned a certain place and name in the circle of our thoughts, change with the dissolution of the system their position and their denomination. When a certain action is transferred from the nerves, blood, or vessels to the tissues, when a passive process is recognized to be an active one, an exudation to be a proliferation, then it becomes absolutely necessary to choose other expressions whereby these actions, processes, and products shall be designated; and in proportion as our knowledge of the more deli- cate modes, in which the processes of life are carried on, becomes more perfect, just in that proportion must the new denominations also be adapted to this more delicate ground-work of our knowledge. It would not be easy for any one to attempt to carry out the necessary reform in medical opinion with more respect for tradition than I have made it my endeavour to observe. Still my own expe rience has taught me that even in this there is a certain limit. Too great respect is a real fault, for it favours confusion; a well-selected expression renders at once accessible to the understanding of all, what, without it, efforts prolonged for years would be able to render intelligible at most only toafew. As examples I will cite the terms, parenchymatous inflammation, thrombosis and embolia, leukemia and ichorrhemia, osteoid and mucous tissue, cheesy and amyloid metamorphosis, and substitution of tissues. New names cannot be avoided, where actual additions to experimental (empirical) know- ledge are being treated of. On the other hand, I have already often been reproached with endeavouring to rehabilitate antiquated views in modern science. In respect to this I can, I think, say with a safe conscience that I am just as little inclined to restore Galen and Paracelsus to the position 4 AUTHOR'S PREFACE. vii they formerly held, as I am afraid openly to acknowledge whatever truth ‘there is in their views and observations. In fact, I find not only that the physicians of antiquity and the middle ages had not in all cases their senses shackled by traditional prejudices, but more than this, that among the people common sense has clung to certain truths, notwithstanding the criticism of the learned had pronounced them overthrown. What should hinder me from avowing that the criticism of the learned has not always proved correct, that system has not always been nature, and that a false interpretation does not impair the correctness of the fact? Why should I not retain good expressions, or restore them, even though false ideas have been attached to them? My experience constrains me to regard the term fluxion (active congestion—Wallung)* as preferable to that of con- gestion; I cannot help allowing inflammation to be a definite form in which pathological processes display themselves, although I am unable to admit its claims to be regarded as an entity; and I must . needs, in spite of the decided counter-statements of many investi- gators, maintain tubercle to be a miliary granule, and epithelioma a heteroplastic, malignant new-formation (cancroid), Perhaps it is now-a-days a merit to recognise historic rights, for it is indeed astonishing with what levity those very men, who herald forth every trifle, which they have stumbled upon, as a discovery, pass their judgment upon their predecessors. I uphold my own rights, and therefore I also recognize the rights of others. This is the principle I act upon in life, in politics and in science. We owe it to ourselves to defend our rights, for it is the only guarantee for our individual development, and for our influence upon the commu- nity at large. Such a defence is no act of vain ambition, and it involves no renunciation of purely scientific aims. For, if we would serve science, we must extend her limits, not only as far as our own knowledge is concerned, but in the estimation of others. Now this estimation depends in a great measure upon the acknowledgment accorded to our rights, upon the confidence placed in our investiga- tions, by others; and this is the reason why I uphold my rights. In a science so directly practical as that of medicine, and at a time * See the Author’s ‘Handbuch der speciellen Path. und Therapie,’ Vol. I. p. 141. t | vill AUTHOR’S PREFACE. when such a rapid accumulation of facts is taking place, as there is in ours, we are doubly bound to render our knowledge accessible tc the whole body of our professional brethren. _We would have reform, and not revolution: we would preserve the old, and add the new. But our contemporaries have a confused idea of the results of our activity. For only too much it is apt to appear as though nought but a confused and motley mass of old and new would thereby be obtained; and the necessity of combatting rather the false or exclusive doctrines of the more modern, than those of the older writers, produces the impression that our endeavours savour more of revolution than reformation. It is, no doubt, much more agreeable to confine oneself to the investigation and simple publica. tion of what one discovers, and to leave to others ‘to “take it to market” (verwerthen—exploiter), but experience teaches us that this is extremely dangerous, and in the end only turns out to the advantage of those who have the least tenderness of conscience. Let us undertake, therefore, every one of us to fulfil the duties both of an observer and of an instructor. The lectures, which I here publish with the view of accomplishing this double purpose, have found such very patient auditors, that they may perhaps venture to hope for indulgent readers likewise. How greatly they stand in need of indulgence, I myself feel very strongly. Every kind of lecture can only satisfy the actual hearers; and especially when it is chiefly intended to serve as an explanation of drawings on a board, and microscopical preparations, it must necessarily appear heterogeneous and defective to the reader. When the intention is to give a concise view of a comprehensive subject, it necessarily becomes impossible to bring forward all the arguments that could be advanced, and to support them by the requisite quo- tations. In lectures such as these too the personal views of the lec- turer may seem to be brought forward with undue exclusiveness, but as it is his business to give a clear exposition of the actual state of the science of which he treats, he is obliged to define with precision the principles, the correctness of which he has proved by his own experience. I trust therefore that what I offer may not be taken for more than it is intended to be. Those, who have found leisure enough to keep AUTHOR'S PREFACE. 1x up their knowledge by reading the current medical literature, will find but little that is new in these lectures. The rest will not, by reading them, be spared the trouble of being obliged to study the subjects, which are here only briefly touched upon, more closely in the histological, physiological and pathological works. But they will at least be in possession of a summary of the discoveries which are the most important as far as the cellular theory is concerned, and they will easily be able to add their more accurate study of the in dividual subjects to the connected exposition which I here give them of the whole. Nay, this very exposition may perhaps afford a direct stimulus for such more accurate study; and if it do but this, it will have done enough. The time at my disposal was not sufficient to enable me to write out and revise a work like this. I was therefore constrained to have the lectures taken down in short-hand, just as they were delivered, and to publish them with but slight alterations. Herr Langenhaun has executed his stenographical task with great care. As far as the shortness of the time permitted, and wherever the text would other- wise have been difficult of apprehension to the inexperienced, I have had woodcuts made from the drawings on the board, and more par- ticularly from the microscopical preparations which were sent round. Completeness in this respect could not he attained, seeing that, even as it is, the publication of the work has been delayed some months in consequence of the preparation of the woodcuts. RUD. VIRCHOW. Misproy, August 20th, 1858. AUTHOR’S PREFACE TO THE SECOND EDITION. ‘THE present attempt to bring the results of my experience, which are at variance with what is ordinarily taught, before the notice of the medical publie at large, in a connected form, has produced unex- pected results; it has found many friends and vigorous opponents. Both of these results are certainly very desirable; for my friends will find in this book no arbitrary settlement of questions, nothing systematical or dogmatical, and my opponents will be compelled at length to abandon their fine phrases and to set to work and examine the matters for themselves. Both can only contribute to the impul- sion and advancement of medical science. But still both have also their depressing point of view. When one has laboured for ten years with all the energy and zeal of which he was capable, and has laid the results of his investigations before the judgment of his contemporaries, one is only too apt to imagine that a considerable part, that perhaps the greater and more import- ant portion of them, would be pretty generally known. This was, as I have learned by experience, not the case with my labours. One of my critics attributes it to my bringing forward too many argu- ments and lengthy cases in support of my views. It may be so, but then I might perhaps have been allowed to expect that other critics would have sought for the proofs, which they did not find here in xi xl AUTHOR’S PREFACE TO THE SECOND EDITION. sufficient abundance, in the original works. For I had in the preface to the first edition expressly pointed out that those who had kept up their knowledge, by reading the current medical literature, would here find but little that was new to them. In this new edition I have contented myself with improving the language, with expressing in more precise terms what was liable to be misunderstood, and with expunging repetitions. There no doubt, still even now, remains a great deal requiring correction; but it seemed to me that the whole ought as far as possible to preserve the fresher impress of oral discourse, and of the unshackled range of thought which there prevails, if it were for the future still to serve as an active ferment to the labourers in the so very various fields of medical science and practice. For the book will have fulfilled its object, if it assists in the propagation, not of cellular pathology, but in general only of independent thought and investigation. RUD. VIRCHOW. Beri, June Tih, 1859. TRANSLATOR’S PREFACE. Proressor Vircrow and his works are so well known wherever the science of medicine is studied, that I think it quite unnecessary to give any account of them here. When I arrived in Berlin in March, 1858, these lectures were in the course of delivery, and I was present at a few of the concluding ones. Subsequently, whilst attending the lectures, classes, and post- mortem examinations* which are held in the Pathological Institute by Professor Virchow, I had ample opportunities for seeing practical illustrations of most of the doctrines advocated in this book. It was natural, therefore, that I should feel a desire to translate these lectures, the more especially as I had every reason to suppose that the views put forward in them still remained unknown—in con- sequence, no doubt, of their German dress—to a large proportion of the English medical public, although they had already, many of them several years previously, appeared in Professor Virchow’s larger works. The translation will in many instances be found to differ somewhat from the original, for numerous additions, subtractions, and substi- tutions have been made, many of them at the suggestion of the Author, many at my own, but all with the Author’s sanction. A few notes will be found, especially in the later lectures. Of these some are literal, some free translations of, or are based upon, answers I received from Professor Virchow to questions I had put to him, whilst others (pp. 352, 406, 415-416) were made entirely at * From 700 to 800 bodies are examined annually in the Institute. xiii xiv TRANSLATOR’S PREFACE. his own suggestion, and are literal translations of his words. In all cases, however, the notes have been submitted to the Author, and approved by him. An index too, I thought might be of service, and I have therefore added a tolerably full one. I cannot sufficiently thank Professor Virchow for the very great trouble—a trouble of which nobody but myself can have any idea~ which he has taken in revising this translation, nor for the exceeding courtesy and kindness with which he has replied to the very numer- ous questions—many of them put for my own private information— which I have plagued him with. He has written me fully fifty let- ters, most of them very long ones; and when I reflect that he daily passes eight or nine hours at the Charité, that he reads all the more important German, French, and English medical works which appear, and is besides constantly engaged in publishing something fresh, I can scarcely conceive how he has managed to find time to write these letters, of which a large proportion reached me by return of post. To Dr. Harris I must return my best thanks for the assistance he has rendered me in reading the proof-sheets, and correcting any errors of language into which I might have fallen, and also for kindly permitting me to consult him whenever I met with any diff- culty—a permission of which I have availed myself most freely. The engravings will, I think, be found to be pretty faithful copies of the original woodcuts. 51 WiroLe STREET, August 10th, 1860. LIST OF WOOD-ENGRAVINGS. ma, 1. Vegetable cells from a young shoot of Solanum tuberosum .. . 2. Cartilage-cells from the margin of ossification of growing cartilage. 8. Different kinds of cells and cell-formations, «. Hepatic cell. 5. Con- nective-tissue corpuscle. ¢. Capillary vessel. d. Stellate cell from a lymphatic gland. e. Nerve-cell from the cerebellum . , F . 4. Formation of vegetable cells, according to Schleiden i 3 . 6. Pigment-cell (from the eye), smooth muscular fibre-cell (from the intes- 12. 13. 14, 15. 16, 17. 18, tines), portion of a nerve-fibre with a double contour . : . Cartilage from the epiphysis of the humerus of a child . Cortical layer of a tuber of Solanum tuberosum é “ . i x . Longitudinal section of a young shoot of Syringa . 3 . . . Pathological proliferation of cartilage from a costal cartilage . . . Young ova from the ovary of a frog a od . . . ‘ . Cells from catarrhal sputa (pus- and mucus-corpuscles, and a pigment- cell) ‘ _ ‘ ‘ . ‘ é ‘4 é ‘ . . “ Diagram of the globular theory . . - . 7 : a Diagram of the investment- (cluster-) theory . . Cylindrical epithelium from the gall-bladder_ . 3 ‘ : . Transitional epithelium from the urinary bladder. 7 a - ‘ Perpendicular section through the surface of the skin of a toe (epidermis, rete Malpighii, papille) . : ‘ . é : 3 3 = Diagrammatic representation of a longitudinal section of a nail in normal and pathological conditions . ‘ : 4 . . . . é A. Development of sweat-glands. ZB. Portion of the duct of a sweat- gland. @ z ‘ q . ‘ 5 7 % ‘i “ i xv PAGE 31 382 35 36 389 41 45 47 48 49 49 53 53 58 59 60 65 68 Xvl vIG. 19. 20. 21, 22, 23. 24. 25. 26. 27. 28. 29. 380. 31. 82. 33. 34, 36. 37, 38. 39. 40. 41. 42, 43. 44. 45. 46. 44. 48. 49. LIST OF ENGRAVINGS. PAGE A, Bundle of ordinary connective tissue. B. Development of connective tissue according to Schwann’s plan, C. Development of connective tissue according to Henle’s plan. ‘ - 3 5 . . 40 Young connective tissue from the embryo of a pig . . . » 42 Diagram of the development of connective tissue . . . . - 18 Section through the growing cartilage of a patella . : . ‘ . 14 Primitive muscular fasciculi in different conditions . . e . 79 Muscular elements from the heart of a puerperal woman . : : . 81 Smooth muscular fibres from the urinary bladder. 7 : : « 88 Small artery from the base of the cerebrum . 5 ‘ x . 86 Diagrammatic representations of hepatic cells. A. Physiologie appear- ance. B. Hypertrophy. C. Hyperplasy . . o 94 Portion of the ead of the liver of a rabbit, with the out in- jected . : . . . . . " . - 459 129. Line of demarcation in a piece of necrosed bone, from a case of pxdar- throcace, bone-territories 2 . . . . 5 - 462 130. Periosteal growth of the cranial bones ere bone of achild) . . 468 131—132. Soft osteoma from the jaw of a goat - _ . ° - 472, 474 123—134. Ricketty diaphysal cartilage, transformation into medullary and osteoid tissue; calcification and ossification . oe : - 478, 480 135. Fracture of the humerus in process of healing; formation of callus . 484 136. Interstitial formation of pus in puerperal inflammation of muscle . . 490 137. Purulent granulation from the subcutaneous tissue of a rabbit, round about aligature. . . F . : . . 2 2 - 496 138. Development of cancer from connective tissue in carcinoma of the breast. : ‘ . . . . 7 . . . . « 499 aX 139. 140. 141. 142. 143. 144. LIST OF ENGRAVINGS. PAGa Commencing cauliflower growth (cancroid) of the neck of the uterus . 516 Development of tubercle from connective tissue in the pleura . : » 521 Mass of cancroid from a tumour of the under lip, with epidermic pearls . 528 Cancer-cells . . 5 . : . é . * ‘ » 529 Cancroid of the orbit ‘ f ‘ a . . ° m : - 5380 Sarcoma of the breast . ° ° ° . . . ° . . 5381 CONTENTS. a PAIGE Avruor’s PREeracE . . r 3 é é 5 oe OX Avtsor’s Prerace to THE Seconp Epirion . ‘i - xi TRANSLATOR’s PREFACE : ‘ ° : ‘ 2 . Xili List or Woop EN@Ravines ' : ‘ 7 i . XV LECTURE I.—Cetts ayp tae CrttuLar TrrEory . . 2 Introduction and object. Importance of anatomical discoveries in the his- tory of medicine. Slight influence of the cell-theory upon pathology. Cells as the ultimate active elements of the living body. Their nature more accurately defined. Vegetable cells; membrane, contents, nucleus. Animal cells; capsulated (cartilage) and simple. Nuclei of. Nucleoli of. Theory of the formation of cells out of free cytoblastema. Constancy of nucleus and its importance in the maintenance of the living cell. Di- versity of cell-contents and their importance as regards the functions of parts, Cells as vital unities. The body as a social organization. Cellu- lar in contradistinction to humoral and solidistic, pathology.—Explana- tion of some of the preparations. Young shoots of plants. Growth of plants. Growth of cartilage. Young ova, Young cells in sputa. LECTURE II.—Puystotogicat Tissurs . ‘ ‘ . 51 Falsity of the view that tissues and fibres are made up of globules (ele- mentary granules). The investment theory (Umhillungstheorie). Equi- vocal [spontaneous] generation of cells. The law of continuous deve- lopment.—General classification of the tissues. The three categories of General Histology. Special tissues. Organs and systems, or appara- tuses.—The EpitueiiaL Tissues. Squamous, cylindrical, and transitional epithelium. Epidermis and rete Malpighii. Nails, and their diseases. Crystalline lens. Pigment. Gland-cells——The Connecrive Tissurs. The theories of Schwann, Henle, and Reichert. My theory. Connective tissue as intercellular substance. Cartilage (hyaline, fibro- and reticular). Mucous tissue. Adipose tissue. Anastomosis of cells; juice-conveying system of tubes or canals. xx1 xx CONTENTS. PAGR LECTURE Il1.—Pursiotocicat anp Patnotogican Tissues 77 The higher animal tissues: muscles, nerves, vessels, blood.—Muscles. Striped andsmooth, Atrophy of. The contractile substance and contractility in general, Cutis anserina and arrectores pilorum. Vessels. Capillaries, Contractile vessels. Nerves.—Pathological tissues (Neoplasms), and their classification, Import of vascularity. Doctrine of specific elements. Physiological types (reproduction). Heterology (heterotopy, hetero- chrony, heterometry), and malignity. Hypertrophy and hyperplasy. Degeneration. Criteria for prognosis.—Law of continuity. Histological substitution and equivalents. Physiological and pathological substitution, LECTURE IV.—Notrerition anp irs CHANNELS a . 101 Action of the vessels, Relations between vessels and tissues. Liver. Brain, Muscular coat of the stomach. Cartilage. Bone.—Dependence of tissues upon vessels, Metastases. Vascular territories [Gefassterritorien] (vas- cular unities). Conveyance of nutriment in the juice-conveying canals (Saftkandle) of the tissues. Bone. Teeth. Fibro-cartilage. Cornea, Semilunar cartilages. LECTURE V.—Nourrrtion, anp ConvEYANCE or THE Nv- TRITIVE JUICES . j ‘ ‘ . . ‘ . 119 Tendons. Cornea. Umbilical cord.—Elastic tissue. Corium.—Loose con- nective tissue. Tunica dartos.—Importance of cells in the special dise tribution of the nutritive juices. LECTURE VI.—Norririon anp CrrctLation . : . 146 Arteries. Capillaries. Continuity of their membrane. Its porosity. Hee morrhage by transudation (per diapedesin). Veins, Vessels during preg nancy.— Properties of the walls of vessels: 1. Contractility. Rhythmical movement. Active or irritative hyperemia. Ischemia. Counter irritants, 2. Elusticity and its importance as regards the rapidity and uniformity of the current of blood. Dilatation of the vessels. 3. Permeability. Diffusion. Specific affinities. Relations between the supply of blood and nutrition. Glandular secretion (liver). Specific action of the ele- ments of the tissues.—Dyscrasia. Its transitory character and local origin. Dyscrasia of drunkards. Hemorrhagic diathesis, Syphilis. LECTURE VII.—Tuz Broop. ; z ; . 166 Fibrine. Its fibrille, Compared with mucus, and connective tissue. Hoe mogeneous condition.—Red blood-corpuseles. Their nucleus and con- tents. Changes of form. Blood-crystals (Hematoidine, Hemine, Ha- matocrystalline).—Colourless blood-corpuscles. Numerical proventiet, Structure. Compared with pus-coryuscles. Their viscosity and aggluti- nation. Specific gravity. Crusta granulosa. Diagnosis between pus- and colourless blood-corpuscles. CONTENTS, xxiii PAGE LECTURE VIII.—-Bioop ann Lympo . ‘ : . 189 Change and replacement of the constituents of the blood. Fibrine. Lymph and its coagulation. Lymphatic exudation. Fibrinogenous substance. Formation of the buffy coat. Lymphatic blood, hyperinosis, phlogistic crasis. Local formation of fibrine. Transudation of fibrine. Forma- tion of fibrine in the blood. —Colourless blood-corpuseles (lymph-corpus- cles). Their increase in hyperinosis and hypinosis (Erysipelas, pseudo- erysipelas, typhoid fever). Leucocytosis and leukemia. Splenic and lymphatic leukeemia—The spleen and lymphatic glands as blood-making organs. Structure of lymphatic glands. LECTURE IX.—Pyaa anp Levcocrrosis '. . 211 Comparison between colourless blood- and pus-corpuscles. Physiological reabsorption of pus; incomplete (inspissation, cheesy transformation), and complete (fatty metamorphosis, or milky transformation). Intravasae tion of pus.—Pus in the lymphatic vessels. Retention of matters in the lymphatic glands. Mechanical separation (filtration). Coloration by tat- tooing. Chemical separation (attraction): Cancer, Syphilis. Irritation of lymphatic glands, and its relation to leucocytosis.—Digestive and puer- peral (physiological) leucocytosis. Pathological leucocytosis (Scrofulosis, typhoid fever, cancer, erysipelas).—Lymphoid apparatuses: solitary and Peyerian follicles of the intestines. Tonsils and follicles of the tongue. Thymus. Spleen.—Complete rejection of pyaemia as a dyscrasia suscepe tible of demonstration morphologically. LECTURE X.—Merasraticat Dyscrasta ; ‘ . 230 Pyzmia and phlebitis. Thrombosis. Puriform softening of thrombi. True and false phlebitis. Purulent cysts of the heart.—Embolia. Import of prolonged thrombi. Pulmonary metastases. Crumbling away of the emboli. Varying character of the metastases. Endocarditis and capil- lary embolia. Latent pyeemia.—Infectant fluids. Diseases of the lym- phatic apparatuses and secreting organs. Chemical substances in the blood; salts of silver. Arthritis. Calcareous metastases. Diffuse me- tastatic processes. Ichorrhemia. Pyaemia as a collective name.— Chemical dyscrasiz. Malignant tumours, especially cancer. Diffusion by means of contagious parenchymatous juices. LECTURE XI.—Piementary ExLements in tHe Broun. NERVES : ‘ ‘i ‘ ‘i ‘5 - : . 255 Melanemia. Its relation to melanotic tumours and colorations of the spteen.—Red blood-corpuscles. Origin. Melanic forms. Chlorosis— Paralysis of the respiratory substance. Toxicemia.—The nervous sys- tem. Its pretended unity.—Nerve-fibres. Peripheral nerves: their fas- ciculi, primitive fibres, and perineurium. Avxis-cylinder (electrical sub- stance). Medullary substance (Myeline). Non-medullated and medul- lated fibres. Transition from the one kind to the other: hypertrophy of the optic nerve. Different breadth of the fibres, Their terminations, Pacinian and tactile bodies. xxiv CONTENTS. PAGE LECTURE XII.—Tsz Nervous System . i , . 280 Peripheral terminations of the nerves. Nerves of special sense. The skin and the distinction of vessel-, nerve-, and cell-territories in it. Olfactory mucous membrane. Retina. Division of nerve-fibres. The electrical organ of fishes. Muscles, Further consideration of nerve-territories.— Nervous plexuses with ganglioniform enlargements. Intestines.—Errors of the neuro-pathologists.—The great nervous centres. Grey substance. Ganglion- [nerve-] cells containing pigment. Varieties of ganglion- cells ; sympathetic cells in the spinal marrow and brain, motor and sensi- tive cells, Multipolar (polyclonous) ganglion-cells. Different nature of the processes of ganglion-cells. LECTURE XIJI.—Srmovan Corp anp Brain . ‘ . 802 The spinal cord. White and grey matter. Central eanal. Groups of gang- lion-cells. White columns and commissures.—The medulla oblongata and the brain. Its granular and bacillar layer—tThe spinal cord of the petromyzon and its non-medullated fibres.—The intermediate substance (interstitial tissue). Ependyma ventriculorum. Neuro-glia. Corpora amylacea. LECIURE XIV.— . a . - 409 Amyloid (lardaceous or waxy) degeneration. Different nature of amyloid substances: concentric and laminated amyloid bodies (brain, prostate), and amyloid degeneration properly so called. Its course. Commence- ment of the affection in the minute arteries. Waxy liver. Cartilage. Dyscrasic (constitutional) character of the disease, Intestines. Kidneys: the three forms of Bright’s disease (amyloid degeneration, parenchyma- tous, and interstitial nephritis), Lymphatic glands. Functional disturb- ances of the affected organs.— Inflammation. The four cardinal symptoms and their predominance in the different schools: the thermic and vascue lar theory; the neuro-pathologists, exudations, Inflammatory stimuli. Lesion of function. Exudation as a consequence of the activity of the tissues; mucus and fibrine. Inflammation as a complex irritative pro- cess, Parenchymatous and exudative (secretory) form. LECTURE XVIII.—Normat anp Parnotoeica, New ForMAtIoN . : : : ‘ ‘ : ; . 438 The theory of continuous development in opposition to the blastema and exudation theory—Connective tissue and its equivalents as the most general germ-store of new formations. Correspondence between embry- onic and pathological new formation. Cell-division as the most general starting-point of new-formations.—Endogenous formation. Physalides. Brood-cavities.—Different tendencies of new-formations. Hyperplasia, direct and indirect. Heteroplasia. Pathological formative cells, Differs ence in their size and in the time required for their full development.— Description of the development of bone asa mr del formaticn. Differ- XXvi CONTENTS. PAGE ence beuween formation and transformation. Fresh and growing, in opposition to macerated, bone. Nature of medullary tissue—-Growth in length of tubular [long] bones; proliferation of cartilage. Formation of marrow as a transformation of tissue; red and yellow, normal and inflammatory marrow. Osseous tissue, calcified cartilage, osteoid tissue. Bone-territories: caries, degenerative ostitis. Granulations in bone. Suppuration of bone. Maturation of pus. Ossification of marrow.— Growth of long bones in thickness: structure and proliferation of the periosteum.—Granulations as analogous to the medulla of bones, and as the starting-point of all heteroplastic development. LECTURE XIX.—PatusotocicaL, AND ESPECIALLY Hers- RroLogous, New Formation . s ‘ . . . 471 Consideration of some forms of pathological formation of bone. Soft oste- oma of the maxilla. Rickets. Formation of callus after fracture.— Theory of substitutive new formation in opposition to exudative. De- structive nature of new-formations. Homology and heterology (malig- nity). Ulceration, Mollities. ossium. Proliferation and luxuriation. Medulla of bones, and pus.—Suppuration. Its two forms: superficial, occurring in epithelium ; and deep, in connective tissue. Eroding suppu- ration (skin, mucous membrane): pus- and mucus-corpuscles in their relations to epithelium. Ulcerative suppuration. Solvent properties of pus.—Connection of destruction with pathological growth and prolifera- tion, Correspondence of the first stage in pus, cancer, sarcoma, ete. Possible duration of the life of pathologically new-formed elements, and of pathological new-formations considered as wholes (tumours). Compound nature of the larger tuberous tumours (Geschwulstknoten), and miliary character of the real foci (Heerde). Conditions of growth and recurrence: contagiousness of new-formations and import of the anastomoses of cells. Cellular pathology in opposition to the humoral and neuristic. General infection of the body. Parasitism and autonomy of new-formations. LECTURE XX.—Form anp Nature or ParnonocicaL New-FORMATIONS . ‘ ‘ . ; ‘ . 50% Nomenclature and classification of pathological new-formations. Consist- ence as a principle of division. Comparison with individual parts of the body. Histological division. Apparent heterology of tubercle, colloid, etc. —Difference of form and nature: Colloid, Epithelioma, Papillary tumour, Tubercle.—Papillary tumours: simple (condylomata, papillomata) and specific (villous cancer and cauliflower-tumour).—Tubercle: infiltration and granulation. Inflammatory origin of tubercle. Its production from connective tissue. Miliary granules, and solitary masses, The cheesy metamorphosis.—Colloid: myxoma. Collonema. Mucous or gelatinous cancer.— Physiological types of heterologous new-formations: lymphoid nature of tubercle, hzematoid of pus, epithelioid of cancer, cancroid, pearly and dermoid tumours, and connective-tissue-like of sarcoma. Infec- tiousness according to the amount of juice.—Comparison between patho- logical new-formations in animals and vegetables. Conclusion. LOT URE 1, FEBRUARY 10, 1858. CELLS AND THE CELLULAR THEORY. Introduction and object—Importance of anatomical discoveries in the history of medicine—Slight influence of the cell-theory upon pathology—Cells as the ulti- mate active elements of the living body—Their nature more accurately defined —Vegetable cells; membrane, contents, nucleus—Animal cells; capsulated (cartilage) and simple—Nuclei of—Nucleoli of—Theory of the formation of cells out of free cytoblastema—Constancy of nucleus and its importance in the maintenance of the living cell—Diversity of cell-contents and their importance as regards the functions of parts—Cells as vital unities—The body as a social organization—Cellular, in contradistinction to humoral and solidistic, pathology. Explanation of some of the preparations—Young shoots of plants—Growth of plants —Growth of cartilage—Young ova—Young cells in sputa. GENTLEMEN,— Whilst bidding you heartily welcome to benches which must have long since ceased to be familiar to you, I must begin by reminding you, that it is not my want of modesty which has summoned you hither, but that I have only yielded to the repeatedly manifested wishes of many among you. Nor should I have ventured either to offer you lectures after the same fashion in which I am accustomed to deliver them in my regular courses. On the contrary, I will make the attempt to lay before you in a more succinct manner the development which I my- self, and, I think, medical science also, have passed through in the course of the last fifteen years. In my announce- ment of these lectures, I described the subject of them in 27 28 LECTURE I. such a way as to couple histology with pathology ; and for this reason, that I thought I must take it for granted that many busily occupied physicians were not quite familiar with the most recent histological changes, and did not enjoy sufficiently frequent opportunities of examining microscopical objects for themselves. Inasmuch as, how- ever, itis upon such examinations that the most import- ant conclusions are grounded which we now draw, you will pardon me if, disregarding those among you who have a perfect acquaintance with the subject, I behave just as if you all were not completely familiar with the requisite preliminary knowledge. The present reform in medicine, of which you have all been witnesses, essentially had its rise in new anatomical observations, and the exposition also, which I have to make to you, will therefore principally be based upon anatomical demonstrations. But for me it would not be sufficient to take, as has been the custom during the last ten years, pathological anatomy alone as the groundwork of my views; we must add thereto those facts of general anatomy also, to which the actual state of medical science is due. The history of medicine teaches us, if we will only take a somewhat comprehensive survey of it, that at all times permanent advances have been marked by anatomical innovations, and that every more important epoch has been directly ushered in by a series of import- ant discoveries concerning the structure of the body. So it was in those old times, when the observations of the Alexandrian school, based for the first time upon the anatomy of man, prepared the way for the system of Galen ; so it was, too, in the Middle Ages, when Vesa- lius laid the foundations of anatomy, and therewith be- gan the real reformation of medicine ; so, lastly, was it at the commencement of this century, when Bichat deve- loped the principles of general anatomy. What Schwann, wv IMPORT OF THE CELL-THEORY. 99 however, has done for histology, has as yet been but in a very slight degree built up and developed for pathology. and it may be said that nothing has penetrated less deeply into the minds of all than the cell-theory in its intimate connection with pathology. If we consider the extraordinary influence which Bichat in his time exercised upon the state of medical opinion, it is indeed astonishing that such a relatively long period should have elapsed since Schwann made his great dis- coveries, without the real importance of the new facts having been duly appreciated. This has certainly been essentially due to the great incompleteness of our know- ledge with regard to the intimate structure of our tissues which has continued to exist until quite recently, and, as we are sorry to be obliged to confess, still even now prevails with regard to many points of histology to such a degree, that we scarcely know in favour of what view to decide. Especial difficulty has been found in answering the question, from what parts of the body action really pro- ceeds—what parts are active, what passive ; and yet itis already quite possible to come to a definitive conclusion upon this point, even in the case of parts the structure of which is still disputed. The chief point in this appli- cation of histology to pathology is to obtain a recognition of the fact, that the cell is really the ultimate morpholo- pk ap . gical element in which there is any manifestation of life, ‘and that we must not transfer the seat of real action to _ any point beyond the cell. Before you, I shall have no particular reason to justify myself, if in this respect I make quite a special reservation in favour of life. In the course of these lectures you will be able to convince yourselves that it is almost impossible for any one to ——— entertain more mechanical ideas in particular instances 30 LECTURE I. individual processes of life. But I think that we must look upon this as certain, that, however much of the more delicate interchange of matter, which takes place within a cell, may not concern the material structure as a whole, yet the real action does proceed from the structure as such, and that the hving element only main- tains its activity as long as it really presents itself to us as an independent whole. In this question it is of primary importance (and you will excuse my dwelling a little upon this point, as it is one which is still a matter of dispute) that we should determine what is really tc:be understood by the term cell. Quite at the beginning of the latest phase of his- tological development, great difficulties sprang up in crowds with regard to this matter. Schwann, as you no doubt recollect, following immediately in the footsteps of Schleiden, interpreted his observations according to botanical standards, so that all the doctrines of vegetable physiology were invoked, in a greater or less degree, to decide questions relating to the physiology of animal bodies. Vegetable cells, however, in the light in which they were at that time universally, and as they are even now also frequently regarded, are structures, whose identity with what we call animal cells cannot be ad- mitted without reserve. When we speak of ordinary vegetable cellular tissue, we generally understand thereby a tissue, which, in its most simple and regular form is, in a transverse section, seen to be composed of nothing but four- or six-sided, or, if somewhat looser in texture, of roundish or poly- gonal bodies, in which a tolerably thick, tough wall (membrane) is always to be distinguished. If now a single one of these bodies be isolated, a cavity is found, enclosed by this tough, angular, or round wall, in the interior of which very different substances, varying ac- VEGETABLE CELLS. 31 cording to circumstances, may be deposited, e. g. fat, starch, pigment, albumen (cedl-contents). But also, quite independently of these local varieties in the contents, we are enabled, by means of chemical investigation, to detect the presence of several different substances in the essential constituents of the cells. The substance which forms the external membrane, and is known under the name Fig. 1. of cellulose, is generally found QO) & to be destitute of nitrogen, and 4 C) »)& yields, on the addition of iodine d sulphuric acid lis #3) and sulphuric acid, a peculiar, Vie very characteristic, beautiful blue tint. Iodine alone produces no colour ; sulphuric acid by itself chars. The contents of simple cells, on the other hand, do not turn blue ; when the cell is quite a simple one, there appears, on the contrary, after the addi- tion of iodine and sulphuric acid, a brownish or yellowish mass, isolated in the interior of the cell-cavity as a spe- cial body (protoplasma), around which can be recognised a special, plicated, frequently shrivelled membrane (pri- mordial utricle) (fig. 1, c). Even rough chemical analysis generally detects in the simplest cells, in addition to the non-nitrogenized (external) substance, a nitrogenized internal mass ; and vegetable physiology seems, there- fore, to have been justified in concluding, that what really constitutes a cell is the presence within a non-nitro- Fig. 1. Vegetable cells from the centre of the young shoot of a tuber of Solanum tuberosum. a. The ordinary appearance of the regularly polygonal, thick-walled cellular tissue. 6. An isolated cell with finely granular-looking cavity, in which a nucleus with nucleolus is to be seen. c. The same cell after the addition of water; the contents (protoplasma) have receded from the wall (membrane, capsule), Investing them a peculiar, delicate membrane (primordial utricle) has become visible. d. The same cell after a more lengthened exposure to the action of water; the interior cell (protoplasma with the primordial utricle and nucleus) has become quite contracted, and remains attached to the cell-wall (cap- sule) merely by the means of fine, some of them branching, threads. 32 LECTURE I. genized membrane of nitrogenized contents differimg from it. It had indeed already long been known, that other things besides existed in the interior of cells, and it was one of the most fruitful of ‘discoveries when Robert Brown detected the nucleus in the vegetable cell. But this body was considered to have a more important share in the formation than in the maintenance of cells, because in very many vegetable cells the nucleus be- comes extremely indistinct, and in many altogether dis- appears, whilst the form of the cell is preserved. These observations were then applied to the consider- ation of animal tissues, the correspondence of which with those of vegetables Schwann endeavoured to de- monstrate. The interpretation, which we have just mentioned as having been put upon the ordinary forms of vegetable cells, served as the starting-point. In this, however, as after-experience proved, an error was committed. Vegetable cells cannot,.viewed—in their entirety, be compared y with all animal cells. In animal cells, we find no such distinctions between nitrogenized and non-nitrogenized layers; in all the essential con- stituents of the cells nitrogenized matters are met with. But there are undoubtedly certain forms in the animal body which immediately recall these forms of vegetable cells, and among them there are none so characteristic as the cells of cartilage, which is, in all its features, ex- tremely different from the other tissues of the animal body, and which, especially on account of its non-vascu- larity, occupies quite a peculiar position. Cartilage in every respect stands in the closest relation to vegetable tissue. In a well-developed cartilage-cell we can dis- tinguish a relatively thick external layer, within which, upon very close inspection, a delicate membrane, con- tents, and a nucleus are also to be found. Here, there- ANIMAL CELLS. 33 fore, we have a structure which entirely corresponds with a vegetable cell. It has, however, been customary with authors, when describing cartilage, to call the whole of the structure of which I have just given you a sketch (fig. 2, a—d) a cartilage-corpuscle, and in consequence of this having been viewed as analogous to the cells in other parts of animals, difficulties have arisen by which the knowledge of the true state of the case has been exceedingly obscured. A carti- lage-corpuscle, namely, is not, as a whole, a cell, but the external layer, the capsule, is the product of a later development (secretion, excretion). In young cartilage it is very thin, whilst the cell also is generally smaller. If we trace the development still farther back, we find in cartilage, also, nothing but simple cells, iden- tical in structure with those which are seen in other animal tissues, and not yet possessing that external secreted layer. You see from this, gentlemen, that the comparison between animal and vegetable cells, which we certainly cannot avoid making, is in general inadmissible, because in most animal tissues no formed elements are found which can be considered as the full equivalents of vege- table cells in the old signification of the word ; and be- cause in particular, the cellulose membrane of vegetable cells does not correspond to the membrane of animal ones, and between this, as containing nitrogen, and the former, as destitute of it, no typical distinction is pre- sented. On the contrary, in both cases we meet with a Fig. 2. Fig. 2. Cartilage-cells as they occur at the margin of ossification in growing cartilage, quite analogous to vegetable cells (cf. the explanation to fig. 1). a—e. In a more advanced stage of development. d. Younger form. 3 34 LECTURE 1. body essentially of a nitrogenous nature, and, on the whole, similar in composition. The so-called membrane of the vegetable cell is only met with in a few animal tissues, as, for example, in cartilage ; the ordinary mem- brane of the animal cell corresponds, as I showed as far back as 1847, to the primordial utricle of the vegetable cell. It is only when we adhere to this view of the matter, when we separate from the cell all that has been added to it by an after-development, that we obtain a simple, homogeneous, extremely monotonous structure, recurring with extraordinary constancy in living organ- isms. But just this very constancy forms the best crite- terion of our having before us in this structure one of those really elementary bodies, to be built up of which is eminently characteristic of every living thing—without the pre-existence of which no living forms arise, and to which the continuance and the maintenance of life is intimately attached. Only since our idea of a cell has assumed this severe form—and I am somewhat proud of having always, in spite of the reproach of pedantry, firmly adhered to it—only since. that time can it be said that a simple form has been obtained which we can everywhere again expect to find, and which, though different in size and external shape, is yet always identical in its essential constituents. In such a simple cell we can distinguish dissimilar constituents, and it is important that we should accurately define their nature also. In the first place, we expect to find a nucleus within the cell; and with regard to this nucleus, which has usually a round or oval form, we know that, particularly in the case of young cells, it offers greater resistance to the action of chemical agents than do the external parts of the cell, and that, in spite of the greatest variations in the external form of the cell, it generally maintains its ‘IBIS 9oUR{sUT L19A0 UT Te[oNU oy, ‘WNT[eqe190 oy} MOIS ]]99 stoyZuen ‘a ‘puels onvydud] & Wouy []90 o7e][998 OBael yeYMowog ‘p ‘jessea Arey ~8Q ‘9 ‘onsst) eaTjOoUTOD Wo [Jao pedeys-arpuidg -g ‘a0 onedeH “~P *g ‘SIT aq} ‘uuemyog £q poaydeocoe pue ‘ueprepyog Aq eau {Sut qsiy oy} Ul paeMsoy ynd sea YOIA MOTA VY} 0} SUIPIOD “OV ‘][99 eq} ut yuomdozeaep jo veisep JOYysSIy Be Ye 0} sulaas ‘a1OJor19y} ‘YI pue ‘! sus0j Jopyo ‘pedoyeaep AT[NJ | UI 4I YIM yoot ATIeTNsea om ‘puey J9y}O oy} UD ~“UoOH -oojop podeoso yoX sv sey yt ‘syfeo Sunod jo rzequmnu eq -elopIsuoo B ul ‘pue { aytstber oyntosqe ue oq 07 srvodde fl JY} SNpOsponuU oy JO pres oq youuRd 41 ‘WHIOF [BIA Jo uoysenb oY} 0} pxeSo1 WTA ‘smpoaonu paT[eo-os oy3— FIPS} UIPIIA oinjonsys JayjouR sesopoue APuURsu0D ATA ‘sqj90 pedojeaop AjayaTduroo ut ‘usin syt Ul ‘sneponu ey, "UIOF yuURJsUOD ATIvOT TOA @ SUIVIUIVUA snepoNuU oy} ‘1aMod [RIIA YLA poMopud [TIS SJUSMGTA SB sAVYE S][od se SuoT sv ‘osopo B 07 4YSNoIG U9eq JOU sey [[20 oY} Jo afl] oy} sv Suor sv ‘yey pres oq Avu y1‘AT[VIOUeK) + “oUOSIepuN sey UoMeTO oY} YoryA sosuvyo retnoed uodn yuepuedep pure ‘suondaoxe ores Ayouledyxe are osoyy ynq { souvrvodde aenSur 10 07e][O}8 % SvYy OsTe sneponu oy} yorym ut ‘ASopoyjed pue Lurojeue aATJeIVdWOD Ul SpRJ JO salIes sfoyM oy} ynoYSnosyy poleqyVos ol] YOTYM ‘sesvo poze[Ost poopul oie oso, ‘paesueyoun punoy AYWeysu0O ysour oy} st Yor qred qeyy ‘sodeys [[@ Jo sq[eo ut ‘A[Surpsoooe st snoponu yy, “wA0y gE ‘NOILVRYOLTIGO ATU dO AYOAHL '6 LECTURE I. ‘onnection between the three coexistent cell-constituents vas long thought to be on this wise: that the nucleolus vas the first to shew itself in the development of tissues, xy separating out of a formative fluid (d/astema, cyto- dastema), that it quickly attained a certain size, that then ine granules were precipitated out of the blastema and ettled around it, and that about these there condensed tmembrane. That in this way a nucleus was completed, ibout which new matter gradually gathered, and in due ime produced a little membrane (the celebrated watch- Fre. 4, glass form, fig. 4, d’). This descrip- tion of the first development of cells _ out of free blastema, according to : ey: which the nucleus was regarded as 5 “—¢°* preceding the formation of the cell, and playing the part of a real cell- ormer (cytoblast), is the one which is usually concisely lesignated by the name of the cell-theory (more accu- ‘ately, theory of free cell-formation),—a theory of deve- opment which has now been almost entirely abandoned, ind in support of the correctness of which not one sin- sle fact can with certainty be adduced. With respect to the nucleolus, all that we can for the present regard as sertain, is, that where we have to deal with large and ‘ully developed cells, we almost constantly see a nucleo- us in them ; but that, on the contrary, in the case of nany young cells it is wanting. You will hereafter be made acquainted with a series to. Fig. 4. From Schleiden, ‘ Grundzuge der wiss. Botanik,’ I, fig. 1. ‘ Contents of he embryo-sac of Vicia faba soon after impregnation. In the clear fluid, con- isting of gum and sugar, granules of protein-compounds are seen swimming about 2), among which a few larger ones are strikingly conspicuous. Around these lat- 2r the former are seen conglomerated into the form of a small disc (6, c). Around ther discs a clear, sharply defined border may be distinguished, which gradually 2cedes farther and farther from the disc (the cytoblast), and, finally, can be dis- netly recognised to be a young cell (d, e).” IMPORT OF THE NUCLEUS AND CELL-CONTENTS. 37 of facts in the history of pathological and physiological development, which render it in a high degree probable that the nucleus plays an extremely | important part within the cell—a part, I will here at once remark, less connected with the function and specific office of the cell, than with its maintenance and multiplication as a living part. The specific (in a narrower sense, animal) function is most distinctly manifested in muscles, nerves, and gland-cells; the peculiar actions of which—con- traction, sensation, and secretion—appear to be con- nected in no direct manner with the nuclei. But that, whilst fulfilling all its functions, the element remains an element, that it is not annihilated nor destroyed by its continual activity—this seems essentially to depend upon the action of the nucleus. All those cellular formations which lose their nucleus, have a more transitory existence; they perish, they disap- pear, they die away or break up. A human blood cor- puscle, for example, is a cell without a nucleus ; it pos- sesses an external membrane and red contents; but herewith the tale of its constituents, so far as we can make them out, is told, and whatever has been recounted concerning a nucleus in blood-cells, has had its founda- tion in delusive appearances, which certainly very easily can be, and frequently are, occasioned by the production of little irregularities upon the surface (Fig. 52). We should not be able to say, therefore, that blood-corpuscles were cells, if we did not know that there is a certain period during which human blood-corpuscles also have nuclei; the period, namely, embraced by the first months of intra-uterine life. Then circulate also in the human body nucleated blood-cells, like those which we see in frogs, birds, and fish throughout the whole of their lives. In mammalia, however, this is restricted to a cer- tain period of their development, so that at a later stage 3 LECTURE I. ae red blood-cells no longer exhibit all the characteris- es of a cell, but have lost an important constituent in qeir composition. But we are also all agreed upon ais point, that the blood is one of those changeable onstituents of the body, whose cellular elements possess o durability, and with regard to which everybody ssumes that they perish, and are replaced by new ones, rhich in their turn are doomed to annihilation, and verywhere (like the uppermost cells in the cuticle, in rhich we also can discover no nuclei, as soon as they egin to desquamate) have already reached a stage in neir development, when they no longer require that urability in their more intimate composition for which ve must regard the nucleus as the guarantee. On the other hand, notwithstanding the manifold inves- igations to which the tissues are at present subjected, re are acquainted with no part which grows or multi- lies, either in a physiological or pathological manner, in rhich nucleated elements cannot invariably be demon- trated as the starting-points of the change, and in which he first decisive alterations which display themselves, do ot involve the nucleus itself, so that we often can deter- ine from its condition what would possibly have become f the elements. / You see from this description that, at least, two differ- nt things are of necessity required for the composition f a cellular element; the membrane, whether round, agged or stellate, and the nucleus, which from the out- et differs in chemical constitution from the mem- rane. Herewith, however, we are far from having numerated all the essential constituents of the cell, or, in addition to the nucleus, it is filled with a rela- ively greater or less quantity of contents, as is like- rise commonly, it seems, the nucleus itself, the contents f which are also wont to differ from those of the IMPORT OF THE NUCLEUS AND CELL-CONTENTS, 39 cell. Within the cell, for example, we see pigment, without the nucleus containing any. Within a smooth muscular fibre-cell, the contractile sub- stance is deposited, which appears to be the seat of the contractile force of mus- cle; the nucleus, however, remains a nucleus. The cell may develop itself into a nerve-fibre, but the nucleus remains, lying on the outside of the medullary [white"] substance, a constant constituent. Hence it follows, that the special peculiar- ities which individual cells exhibit in particular places, under particular circum- stances, are in general dependent upon the varying properties of the cell-contents, and that it is not the constituents which we have hitherto considered (membrane and nucleus), but the contents (or else the masses jof matter deposited without the cell, zntercellular), which give rise to the functional (physiological) dif- ferences of tissues. For us it is essential to know ithat in the most various tissues these constituents, which, in some measure, represent the cell in its abstract form, the nucleus and membrane, recur with great con- stancy, and that by their combination a simple element is obtained, which, throughout the whole series of living vegetable and animal forms, however different they may be externally, however much their internal composition may be subjected to change, presents us with a structure Fia. Fig. 5. a. Pigment-cell from the choroid membrane of the eye. 6. Smooth mus- cular fibre-cell from the intestines. c. Portion of a nerve-fibre with a double con- tour, axis-cylinder, medullary sheath and parietal, nucleolated nucleus. ? All words included in square brackets have been inserted by the Translator, and are intended to be explanatory. 0 LECTURE I. f quite a peculiar conformation, as a definite basis for ll the phenomena of life. According to my ideas, this is the only possible start- ig-point for all biological doctrines. If a definite cor- espondence in elementary form pervades the whole series f all living things, and if in this series something else vhich might be placed in the stead of the cell be in vain ought for, then must every more highly developed rganism, whether vegetable or animal, necessarily, bove all, be regarded as a progressive total, made up of wrger or smaller number of similar or dissimilar cells. ‘ust as a tree constitutes a mass arranged in a definite aanner, in which, in every single part, in the leaves as a the root, in the trunk as in the blossom, cells are dis- overed to be the ultimate elements, so is it also with he forms of animal life. very | animal presents-ttself_as : sum of vital unities, every one of which manifests all he characteristics of life. The characteristics and unity f life cannot be limited to any one particular spot in a lighly developed organism (for example, to the brain of nan), but are to be found only in the definite, constantly ‘ecurring structure, which every individual element dis- lays. Hence it follows that the structural composition of a body of considerable size, a so-called individual, ilways represents a kind of social arrangement of parts, in arrangement of a social kind, in which a number of ndividual existences are mutually dependent, but in much a way, that every element has its own special wction, and, even though it derive its stimulus to activity rom other parts, yet alone effects the actual performance of its duties. I have therefore considered it necessary, and I believe you will derive benefit from the conception, to portion out the body into cell-territories (Zellenterritorien). I say territories, because we find in the organization of CELL-TERRITORIES AND INTERCELLULAR SUBSTANCE. 41 animals a peculiarity which in vegetables is scarcely at all to be witnessed, namely, the development of large masses of so-called intercellular substance. Whilst vege- table cells are usually in immediate contact with one another by their external secreted layers, although in such a manner that the old boundaries can still always Fig 6. be distinguished, we find in animal tissues that this species of arrangement is the more rare one. In the often very abundant mass of matter which lies between the cells (¢ntermediate, intercellular substance), we are seldom able to perceive at a glance, how far a given part of it belongs to one or another cell ; it presents the aspect of a homogeneous intermediate substance. According to Schwann, the intercellular substance was he cytoblastema, destined for the development of new cells. This I do not consider to be correct, but, on the contrary, I have, by means of a series of pathological ‘observations, arrived at the conclusion that the intercel- lular substance is dependent in a certain definite manner upon the cells, and that it is necessary to draw bounda- Fig. 6. Cartilage from the epiphysis of the lower end of the humerus of a, child. The object was treated first with chromate of potash, and then with aceticacid. In the homogeneous mass (intercellular substance) are seen, at a, cartilage-cavities (Knorpelhohlen) with walls still thin (capsules), from which the cartilage-cells, pro- vided with a nucleus and nucleolus, are separated by a distinct limiting membrane. b. Capsules (cavities) with two cells produced by the division of previously simple ones. c. Division of the capsules following the division of the cells. d. Separa- tion of the divided capsules by the deposition between them of intercellular sub- stance—Growth of cartilage. 42 LECTURE I. ries in it also, so that certain districts belong to one cell, and certain others to another. Yow will see how sharply these boundaries are defined by pathological processes (Fig. 129), and how direct evidence is afforded, that any given district of intercellular substance is ruled over by the cell, which lies in the middle of it and exercises influence upon the neighbouring parts. It must now be evident to you, I think, what I under- stand by the territories of cells. But there are simple tissues which are composed entirely of cells, cell lying close to cell. In these there can be no difficulty with regard to the boundaries of the individual cells, yet it is necessary that I should call your attention to the fact that, in this case, too, every individual cell may run its own peculiar course, may undergo its own peculiar changes, without the fate of the cell lying next it being necessarily linked with its own. In other tissues, on the contrary, in which we find intermediate substance, every cell, in addition to its own contents, has the superin- tendence of a certain quantity of matter external to it, and this shares in its changes, nay, is frequently affected even earlier than the interior of the cell, which is ren- dered more secure by its situation than the external intercellular matter. Finally, there is a third series of tissues, in which the elements are more intimately con- nected with one another. A stellate cell, for example, may anastomose with a similar one, and in this way a reticular arrangement may be produced, similar to that which we see in capillary vessels and other analogous structures. In this case it might be supposed that the whole series was ruled by something which lay who | knows how far off; but upon more accurate investiga-— tion, it turns out that even in this chainwork of cells a \ certain independence of the individual members prevails, \ and that this independence evinces itself by single cells t CELLULAR PATHOLOGY. 43 undergoing, in consequence of certain external or internal influences, certain changes confined to their own limits, and not necessarily participated in by the cells immedi- ately adjoining. That which I have now laid before you will be suffi- cient to show you in what way I consider it necessary to trace pathological facts to their origin in known histolo- gical elements; why, for example, I am not satisfied with talking about an action of the vessels, or an action of the nerves, but why I consider it necessary to bestow attention upon the great number of minute parts which really constitute the chief mass of the substance of the body, as well as upon the vessels and nerves. It is not enough that, as has for a long time been the case, the muscles should be singled out as being the only active elements; within the great remainder, which is generally regarded as an inert mass, there is in addition an enor- mous number of active parts to be met with. Amid the development which medicine has undergone up to the present time, we find the dispute between the humoral and solidistic schools of olden times still main- tained. The humoral schools have generally had the greatest success, because they have offered the most con- venient explanation, and, in fact, the most plausible interpretation of morbid processes. We may say that nearly all successful practical, and noted hospital, physi- cians have had more or less humoro-pathological tenden- cies ; aye, and these have become so popular, that it is extremely difficult for any physician to free himself from them. The solido-pathological views have been rather the hobby of speculative inquirers, and have had their origin not so much in the immediate requirements of pathology, as in physiological and philosophical, and even in religious speculations. They have been forced to do violence to facts, both in anatomy and physiology, 44 LECTURE I. and have therefore never become very widely diffused. According to my notions, the basis of both doctrines is an incomplete one; I do not say a false one, because it is really only false in its exclusiveness ; it must be reduced within certain limits, and we must remember that, besides vessels and blood, besides nerves and ner- vous centres, other things exist, which are not a mere theatre (Substrat) for the action of the nerves and blood, upon which these play their pranks.. Now, if it be demanded of medical men that they give their earnest consideration to these things also; if, on the other hand, it be required that, even among those who maintain the humoral and neuro-pathological doc- trines, attention at last be paid to the fact, that the blood is composed of many single, independent parts, and that the nervous system is made up of many active individual constituents—this is, indeed, a requirement which at the first glance certainly offers several difficulties. But if you will call to mind that for years, not only in lectures, but also at the bedside, the activity of the capillaries was talked about—an activity which no one has ever seen, and which has only been assumed to exist in com- pliance with certain theories—you will not find it unrea- sonable, that things which are really to be seen, nay are, not unfrequently, after practice, accessible even to the unaided eye, should likewise be admitted into the sphere of medical knowledge and thought. Nerves have not only been talked about where they had never been demonstrated ; their existence has been simply assumed, even in parts in which, after the most careful investiga- tions, no trace of them could be discovered, and activity has been attributed to them in parts where they abso- lutely do not penetrate. It is therefore certainly not unreasonable to demand, that the greater part of the body be no longer entirely ignored; and if no longer GROWTH OF PLANTS. 45 ignored, that we no longer content ourselves with merely regarding the nerves as so many wholes, as a simple, indivisible apparatus, or the blood as a merely fluid ma- terial, but that we also recognise the presence within the blood and within the nervous system of the enormous mass of minute centres of action. In conclusion, I have still some preparations to ex- plain, and will begin with a very common object (Fig. 7). It has been taken from the tuber of a potato, at a spot where you can view in its” pefection the structure of a vegetable cell, where the tuber, namely, is begin- ning to put forth a new shoot, and there is, consequently, a probability of young cells being found, at least, if we suppose that all growth con- sists in the development of new cells. In the interior of the tuber all the cells are, as is well known, stuffed full with granules of starch; in the young shoot, on the other hand, the starch is used up, in proportion to the growth, and the cell is again exhibited in its more simple form. In a transverse section of a young sprout near its exit from the tuber, about four different layers may be dis- tinguished—the cortical layer, next a layer of larger, then a layer of smaller, cells, and lastly, quite on the inside, a second layer of larger cells. Here we see nothing but regular structures ; thick capsules of hex- Fig. 7. From the cortical layer of a tuber of solanum tuberosum, after treatment with iodine and sulphuric acid. a. Flat cortical cells, surrounded by their capsule (cell-wall, membrane). 6. Larger, four-sided cells of the same kind from the cam- bium; the real cell (primordial utricle), shrunken and wrinkled, within the capsule. c. Cells with starch-granules lying within the primordial utricle. 46 LECTURE I. agonal form, and within them one or two nuclei (Fig. 1), Towards the cortex (corky layer) the cells are four-sided, and the farther one proceeds outwards, the flatter do they become ; still, nuclei may be distinctly recognised in them also. Wherever the so-called cells come in con- tact, a boundary line may be recognised between them; then comes the thick layer of cellulose, in which fine streaks may be observed; and in the interior of the capsular cavity you see a compound mass, in which a nucleus and nucleolus may be easily distinguished, and after the application of reagents the primordial utricle also makes its appearance as a plicated, wrinkled mem- brane. This is the perfect form of a vegetable cell. In the neighbouring cells lie a few larger, dimly lustrous, laminated bodies, the remains of starch (Fig. 7,c). The next object is of importance in my eyes, because I shall afterwards have to refer to it when instituting a com- parison with new formations in animals. It is a longi- tudinal section of a young lilac bud, developed by the warm days we have had this month (February). In the bud a number of young leaves have already begun to develop themselves, each composed of numerous young cells. In these, the youngest parts, the external layers, are composed of tolerably regular layers of cells, which have a rather flat, four-sided appearance, whilst in the internal layers the cells are more elongated, and ina few parts spiral vessels show themselves. Especially would I call your attention to the little out-growths (leaf-hairs—Blatthaare), which protrude everywhere along the border, and very much resemble certain ani- ' mal excrescences, é. g., in the villi of the chorion, where they mark the spots at which young, secondary villi will shoot out. In our preparation, you see the little club-shaped protuberances, which are repeated at cer- + GROWTH OF PLANTS. AT tain intervals and are connected internally with the rows of cells in the cambium. They are structures in which the more delicate forms of cells can best be distinguished, and, at the same time the peculiar mode of growth be discovered. This growth is effected thus: Fig. 8. a division takes place in some of the cells, and a transverse septum is formed ; the newly-formed parts con- «a@ tinue to grow as indepen- dent elements, and gradu- ally increase in size. Not unfrequently divisions take place also longitudinally, so 3% that the parts become thicker © (Fig. 8, ¢c). Every protu- berance is therefore origi- nally a single cell, which, by continual subdivison in a transverse direction (Fig. 8, a, 6), pushes its divisions for- wards, and then, when occa- sion offers, spreads out also in a lateral direction. In this way the hairs shoot out, and this is in general the mode of growth, not only in vegetables, but also in the physiological and pathologi- cal formations of the animal body. hS a XS F5) SES WSS = S Wass LN SIS firm ISAS IS a= foe Gates oe 8 | (ee e A ee aS SISSY JE SIIRS SISS/NIS IIR WEIL SSNS Fig. 8. Longitudinal section of a young February-shoot from the branch of a syringa. A. The cortical layer and cambium ; beneath a layer of very flat cells are seen larger, four-sided, nucleated ones, from which, by successive transverse divi- sion, little hairs (a) shoot out, which grow longer and longer (4), and, by division in a longitudinal direction (c), thicker. JB. The vascular layer, with spiral vessels. C. Simple, four-sided, oblong, cortical cells.—Growth of Plants. 48 LECTURE I. In the following preparation—a piece of costal carti- lage, in a state of morbid growth—changes are evident even to the naked eye, namely, little protuberances upon the surface of the cartilage. Cor- responding to these the microscope shows a proliferation of cartilage- cells, and we find the same forms as in the vegetable cells; large ' groups of cellular elements, each of which has proceeded from a single previously existing cell, arranged in several rows, and dif- fering from proliferating vegetable cells only in this—that there is intercellular substance between the individual groups. In the cells we can as before distinguish the external capsule, which, indeed, in the case of many cells, is com- posed of two, three, or more layers, and within them only does the real cell come with its membrane, contents, nucleus, and nucleolus. In the following object you see the young ova of a frog, before the secretion of the yolk-granules has begun. The very large ovum (Hizelle) (Fig. 10, C) contains a nucleus likewise very large, in which a number of little vesicles are dispersed—and tolerably thick, opaque con- tents, beginning, at a certain spot, to become granular and brown. Around the cell may be remarked the rela- tively thin, connective tissue of the Graafian vesicle, with a hardly visible layer of epithelium. In the neigh- Fig. 9. ees = Fig. 9. Proliferation of cartilage; from the costal cartilage of an adult. Large groups of cartilage-cells within a common envelope (wrongly so-called parent- cells), produced from single cells by successive subdivisions. At the edge, one of these groups has been cut through, and in it is seen a cartilage-cell invested by a number of capsular layers (external secreted masses). 300 diameters. LARGE AND SMALL ANIMAL CELLS. 49 bourhood are lying several smaller ova, which show the gradual progress of their growth. Fig. 10. As a contrast to these gigantic cells, I place before you an object from the bed-side ; cells from fresh catarrhal sputa. You see cells in com- parison very small, which with a higher power, prove to be of a perfectly globular shape, and, in which, after the addition of water and re- agents, a membrane, nuclei, and, when fresh, | cloudy contents can clearly be distinguished. Most of Fie. 11. Fig. 10. Young ova from the ovary of afrog. .4. Avery young ovum. B, A larger one. (C. A still larger one, with commencing secretion of brown granules at one pole (e), and shrunken condition of the vitelline membrane from the imbi- bition of water. a. Membrane of the follicle. 6. Vitelline membrane. c. Mem- brane of the nucleus. d. Nucleolus. S. Ovary. 150 diameters. Fig. 11. Cells from from fresh catarrhal sputa. -d. Pus-corpuscles. a. Quite fresh. 6. When treated with acetic acid. Within the membrane the contents have cleared up, and three little nuclei are seen. ZB. Mucus-corpuscles. a, A sim- ple one. 6. Containing pigment granules. 300 diameters. 4 50 LECTURE I. the small cells belong, according to the prevailing termi- nology, to the category of pus-corpuscles ; the larger ones, which we may designate mucus-corpuscles or ca- tarrhal cells, are partly filled with fat or greyish-black pigment, in the form of granules. These structures, however small their size, possess all the typical peculiarities of the large ones ; all the charac- ters of a cell displayed by the large ones again present themselves in them. But this is, in my opinion, the most essential point—that, whether we compare large or small, pathological or physiological, cells, we always find this correspondence between them. BHO? U Be LI. FEBRUARY 17, 1858. PHYSIOLOGICAL TISSUES. Falsity of the view that tissues and fibres are made up of globules (elementary granules)—The investment theory (Umhullungstheorie)—Equivocal [spontane- ous] generation of cells—The law of continuous development. General classification of the tissues—The three categories of General Histology— Special tissues—Organs and systems, or apparatuses. The EpiraettaL Tissurs—Squamous, cylindrical, and transitional epithelium— Epidermis and rete Malpighii—Nails, and their diseases—Crystalline lens— Pigment—Gland-cells. The Connective Tissuzrs—The theories of Schwann, Henle, and Reichert—My theory—Connective tissue as intercellular substance—Cartilage (hyaline, fibro- and reticular)—Mucous tissue—Adipose tissue—-Anastomosis of cells; juice- conveying system of tubes or canals, In my first lecture, gentlemen, I laid before you the ‘general points to be noted with regard to the nature and origin of cells and their constituents. Allow me now to preface our further considerations with a review of the animal tissues in general, and this both in their physio- logical and pathological relations. The most important obstacles which, until quite recently, existed in this quarter, were by no means chiefly of a pathological nature. I am convinced that pathological conditions would have been mastered with far less difficulty if it had not, until quite lately, been utterly impossible to give a simple and comprehensive sketch of the physiological tissues. The old views, 61 52 LECTURE II. which have in part come down to us from the last cen- tury, have exercised such a preponderating influence upon that part of histology which is, in a pathologi- cal point of view, the most important, that not even yet has unanimity been arrived at, and you will therefore be coustrained, after you have inspected the prepara- tions I shall lay before you, to come to your own con- clusions as to how far that which I have to communicate to you is founded upon real observation. If youread the ‘ Hlementa Physiologise’ of Haller, you will find, where the elements of the body are treated of, the most prominent position in the whole work assigned to fibres, the very characteristic expression being there made use of, that the fibre (fibra) is to the physiologist what the line is to the geometrician. This conception was soon still further expanded, and the doctrine that fibres serve as the groundwork of nearly all the parts of the body, and that the most various tissues are reducible to fibres as their ultimate constituents, was longest maintained in the case of the very tissue in which, as it has turned out, the pathological difficulties were the greatest—in the so-called celluiar tissue. In the course of the last ten years of the last century there arose, however, a certain degree of reaction against ' this fibre-theory, and in the school of natural philoso- fe a ee phers another element soon attained to honour, though it had its origin in far more speculative views than the former, namely, the globule. Whilst some still clung to their fibres, others, as in more recent times Milne Edwards, thought fit to go so far as to suppose the fibres, in their turn, to be made up of globules ranged in lines, This view was in part attributable to optical illusions in microscopical observation. The objection- able method which prevailed during the whole of the last and a part of the present century—of making obser- ELEMENTARY FIBRES AND GLOBULES. 53 vations (with but indifferent instruments) in the full glare of the sun—caused a certain amount of dispersion of light in nearly all microscopical objects, and the impression communicated to the observer was, that he saw nothing else than globules. On the other hand, however, this view corresponded with the ideas common amongst natural philosophers as to the ‘primary origin of everything endowed with form. ~~ These globules (granules, molecules) have, curiously enough, maintained their ground, even in iedcen histo- logy, and there are but few histological works which do not begin with the consideration of elementary granules. Tn a few instances, these views as to the globular nature of elementary parts have, even not very long ago, ac- quired such ascendancy, that the composition, both of the primary tissues in the embryo and | also of the later ones, was based upon them. A f ¢ cell was considered to be produced by the globules arranging themselves in a spherical form, so as to constitute a membrane, within which other globules remained, and formed the contents. In this way did even Baumgirtner and Arnold contend against the cell theory. This view has, in a certain manner, found support even in the history of development—in the so-called investment-theory (Umbhiillun gstheorie)—a doctrine which for a time occupied a very promi- nent position. The upholders of this theory imagined, that origi- a, o4 nally a number of elementary 2o%e globules existed scattered through Fia. 12. Fig. 12. Diagram of the globular theory. a. Fibre composed of elementary granules (molecular granules) drawn up in a line. 8. Cell with nucleus and spheri- cally arranged granules. Fig. 18. Diagram of the investment- (cluster-) theory. a. Separate elementary 54 LECTURE II. a fluid, but that, under certain circumstances, they gathered together, not in the form of vesicular mem- branes, but so as to constitute a compact heap, a globe (mass, cluster—Kliimpchen), and that this globe was the starting point of all further development, a membrane being formed outside and a nucleus inside, by the diffe- rentiation of the mass, by apposition, or intussusception. At the present time, neither fibres, nor globules, nor elementary granules, can be looked upon as histological starting-points. As long as living elements were con- ceived to be produced out of parts previously destitute of shape, such as formative fluids, or matters (plastic matter, blastema, cytoblastema), any one of the above views could of course be entertained, but it is in this very particular that the revolution which the last few years have brought with them has been the most marked. Even in pathology we can now go so far as to establish, as a general principle, that no development of any kind begins de novo, and consequently as to reject the theory of equivocal [spontaneous] generation just as much in the history of the development of individual parts as we do in that of entire organisms. Just as little as we can now admit that a tenia can arise out of saburral mucus, or that out of the residue of the decomposition of animal or vegetable matter an infusorial animalcule, a fungus, or an alga, can be formed, equally little are we disposed to concede either in physiological or pathologi- cal histology, that a new cell can build itself up out of any non-cellular substance. Where a cell arises, there a cell must have previously existed (omnis cellula e cellula), just as an animal can spring only from an animal, a plant only from a plant. In this manner, although there granules. 6, Heap of granules (cluster). ¢. Granule-cell, with membrane and nucleus, LAW OF CONTINUOUS DEVELOPMENT. 55 are still a few spots in the body where absolute demon- stration has not yet been afforded, the principle is nevertheless established, that in the whole series of living things, whether they be entire plants or animal organisms, or essential constituents of the same, an eternal law of continuous development prevails. There is no discontinuity of development of such a kind that a new generation can of itself give rise to a new series of developmental forms. No developed tissues can be traced back either to any large or small simple element, unless it be unto a cell. In what manner this continuous proliferation of cells (Zellenwucherung), for so we may designate the process, is carried on, we will consider hereafter ; to-day, my especial object only was to deter you from assuming as the groundwork of any views you might éntertain with regard to the composition of the tissues, these theories of simple fibres or simple globules (elementary fibres or elementary globules).— If it be wished to classify the normal tissues, a very simple point of view, founded upon marked characteris- tics, offers itself, upon which their division into three categories may be based. We either have tissues which consist exclusively of cells, where cell lies close to cell—in fact, cellular tissue in the modern sense of the word—or we find tissues, in which one cell is regularly separated from the other by a certain amount of intermediate matter (intercellular substance), and, therefore, a kind of uniting medium exists, which, while it visibly connects the individual elements, yet holds them separate. To this class belong the tissues which are now-a-days generally comprehended under the name of connective tissues (Gewebe der Bin- desubstanz), and of which what was formerly universally called cellular tissue constitutes the chief portion. Finally, there is a third group of tissues, in which the 56 LECTURE Il. cells have attained specific, higher forms of development, by means of which their constitution has acquired a type entirely peculiar ; indeed, in part so peculhar, as to appertain exclusively to the animal economy. These are the tissues which are really characteristic of animals, although a few among them exhibit transitions of vege- table forms. To this class belong the nervous and muscular systems, the vessels and the blood. Herewith is the list of tissues concluded. You must now proceed to consider, in what respect, in this summary of the result of histological researches, a contrast is afforded to what was formerly, chiefly in imitation of Bichat, regarded as constituting a tissue. Bichat’s tissues would, for the most part, not so much represent what we now regard as the subjects of General Histology, as what we must rather designate’as be- longing to Special Histology. For, if we regard the tissues in the light they were formerly regarded ; if we, for example, separate tendons, bones, and faciz, from one another, we then obtain an extraordinary variety of categories (Bichat had twenty-one), but there are not quite as many simple forms of tissue to correspond to them. In accordance with modern notions, the whole domain of anatomy should first be divided into the categories of General Histology (¢isswes properly so called). Special Histology, then, takes up the instances, in which a com- bination of tissues, sometimes very different, into a single whole (organ) takes place. Thus we speak, for example, of osseous tissue; but this tissue, the tela ossea of general histology, does not of itself form bone, for no bone consists entirely of tela ossea, but it has necessarily superadded at least periosteum and vessels. Nay, and from this simple conception of a bone, every bone of considerable size, for example, a long bone EPITHELIAL FORMATIONS. 57 differs ; for that is a real organ, in which we can distin- guish at least four different tissues. We have in it the tela ossea properly so called, the cartilaginous layer, the stratum of connective tissue belonging to the periosteum, and the peculiar medullary tissue. These several parts again are exceedingly heterogeneous in their nature, inasmuch as, for example, vessels and nerves enter into the composition of the marrow, the periosteum, etc. All these must be taken together to constitute the entire organism of a bone. Before we come, therefore, to systems or apparatuses, properly so called, the special subject of descriptive anatomy, a long series of grada- tions must be traversed, and in discussions we must always begin by having a clear idea of what the question is. When bone and osseous tissue are confounded to- gether, the extremest confusion is occasioned, and so also when it is sought to identify nervous with cerebral matter. The brain contains many things which are not of a nervous nature, and its physiological and pathologi- cal conditions cannot be comprehended if they are regarded as occurring in an aggregation of purely ner- vous parts, and no consideration is paid to the membranes, the interstitial substance, and the vessels, as well as the nerves. If, now, we consider the first of the classes into which we have divided General Histology, namely, the simple cellular tissues, a little more attentively, we find that those of which we can best obtain a general idea are unquestionably the epithelial formations, such as we meet with in the epidermis and the rete Malpighii, upon the external surface of the body, and in the cylindrical and ‘scaly epithelium of mucous and serous membranes. Their general plan is, that cell lies close to cell, so that in the most favorable specimens, as in plants, four- or six-sided cells lie in immediate apposition one to the 58 LECTURE Ii. other, and nothing at all is found between them. The same is the case in many places with the scaly or pave- ment-epithelium (Fig. 16). These forms are evidently in a great measure due to pressure. For all the elements of acellular tissue to possess perfect regularity of form, it is requisite that they should all grow in a perfectly uni- form manner, and simultaneously. If their development takes place under circumstances such that less resistance is offered in one direction, it then may come to pass that, as in the case of columnar or cylindrical epithelium, : the cells will shoot out in this one direction and become - very long, whilst in the other direction they remain very narrow. But even one of these cells, when seen in transverse section, will pre- ent an hex agonal shape, and if we look down upon the free surface of cylindri- cal epithelium, we see in it, too, regularly polygonal forms (Fig. 14, 4). Contrasting with these, singularly irregular forms are met with in places where the cells shoot up in an irregu- lar manner, and accordingly they are found with remark- able constancy on the surface of the urinary passages, in their whole extent from the calyces of the kidneys down to the urethra. In all these parts it is very common to meet with instances in which a cell is round at one end, whilst at the other it terminates in a point, or where it exhibits the appearance of a somewhat thick spindle, or is Fig. 14. Columnar or cylindrical epithelium from the gall-bladder. a. Four con- tiguous cells seen in profile, each with a nucleus and nucleolus, their contents, slightly marked with longitudinal striae; along the free (upper) edge, a thickish border, marked with fine, radiated lines. 6. Similar cells, with their free (upper, outer) surface seen obliquely, so as to show the hexagonal form of a transverse section, and their thick border. ¢. Cells altered by imbibition, somewhat swollen up and with the upper border split into fibrils. s EPIDERMIS. 59 slightly rounded on one side and excavated on the other, or where a, cell is so thrust in between others as to assume a clubbed or jagged form. But in these cases also the one cell always corresponds with the other in form, and it is not any peculiarity in the cell which gives rise to its shape, but the way in which it lies, its relations to the neighbouring cells, and its having to adapt itself to the arrangement of the parts next to it. In the direction of the least resistance the cells acquire points, jaggs and projections of the most manifold descrip- tion. As they did not well admit of classification, Henle gave them the name, which has since been adopted, of transitional epithelium, to express their gradual transi- tion into distinct scaly and cylindrical epithelium. Some- times, however, this is not the case, and another name for them might just as well have been adopted. On account of the importance of the subject, I will just add a few words with regard to the cuticle (epider- mis). In this it fortunately happens that, what is not the case in many mucous membranes, many layers of cells lie one above the other, and that the young layers (the rete Malpightt [mucosum]) can easily and con- veniently be separated from the older ones (the eprder- mis proper). Fig. 15. Fig. 15. Transitional epithelium from the urinary bladder. a. A large cell, with excavations along its border, into which more delicate club- and spindle-shaped cells fit. }. The same; the larger cell with two nuclei. c¢. A larger, irregularly angular cell, with four nuclei, d. A similar cell, with two nuclei and nine depres- sions, as seen from above, corresponding to the excavations of the border. (Comp. ‘ Archiv. fir path. Anat. und Phys.,’ vol iii, plate i., fig. 8.) 60 LECTURE II. ‘ On examining a perpendicular section of the surface of the skin, we for the most part see externally a very dense stratum, of variable thickness, which at the first glance is discovered to consist of nothing but flattened cells, that, when viewed edgeways, look like lines. They might -be taken for fibres, piled up one above the other, and with slight differences of level making up the the whole external layer. Beneath these layers we find, differing in thickness and substance, the so-called rete Malpighii, and next to this, in a downward direction, the papille of the skin. If, now, we examine the boundary between the epidermis and the rete, the result we obtain by nearly every method of examination is, 2 SEES 2s = S SSS SSS SS —S SsSS 5S SSS SSS SSS Sass x = SS —= SSS = SSS SSS = SSS ; oT PAY Fig. 16. Perpendicular section through the surface of the skin of a toe, treated ith acetic acid. P. P, Extremities of cut papills, in each of which a vascular loop, NAILS. 6] that to the innermost layer of the epidermis, very closely and almost abruptly, there succeed cells, which at first are also flattened, but in a less degree, and within which very distinct nuclei may be distinguished. These tole- rably large cells mark the transition from the oldest layers of the rete Malpighii to the youngest of the epi- dermis. This is the point from which proceeds the re- generation of the epidermis, in itself an inert mass,which is gradually removed from the surface. And here is also generally the boundary, at which pathological pro- cesses set in. The farther we advance inwards, the smaller do the cells become ; the last of them standing in the form of little cylinders upon the surface of the papille (Fig. 16 7, 7). On the whole, the relations of the individual parts throughout the whole surface of the skin are everywhere the same, however manifold the peculiarities of detail may be, which the individual layers offer in respect to thickness, position, firmness, and connection. A section of a nail, for example, which in its external appearance certainly widely differs from ordinary epidermis, pre- sents, nevertheless, on the whole, the same conformation, and has only one essentially distinctive feature, that, namely, in it two different epidermoidal structures are thrust, the one over the other, and thus a complication arises, which, if not duly attended to, may lead to the assumption of certain specific differences between it and other parts df the epidermis, whilst it really consists only in a peculiar change in the position of certain layers of and near it little spindle-shaped, connective-tissue corpuscles, displaying at the base a reticulated arrangement, may be observed; to the left, a bulging out of the pa- pille, corresponding to a tactile corpuscle, no longer visible, and situated at a deeper level. A. R. The rete Malpighii; immediately around the papilla a very dense layer of small, cylindrical cells (7, 7); more externally, polygonal cells, gra- dually increasing in size. #. Epidermis, consisting of flat and more closely packed layers of cells. S S. Duct of a sweat gland passing through. 300 diameters. 62 LECTURE Mi. the epidermis with regard to one another. The extremely dense and hard scales, which constitute the uppermost part, the so-called body of the nail (Nagelblatt), may, by different methods, be restored to forms in which they present the ordinary appearances of cells, and this is best seen after treatment with an alkali, when every scale swells up into a large, broadly oval, cell. In the uppermost layers of the epidermis the cells be- come everywhere flatter, and towards the external surface no more nuclei at all can be discovered in them. Still there is no original difference between the epidermis and the rete Malpighii; the latter is only the matrix of the epidermis, or indeed its youngest layer, inasmuch as from it there is a constant apposition of new parts tak- ing place, which gradually become flatter and flatter, and move upward as fast as the scales on the outside disap-. pear through friction of the surface, washing, or rubbing. But between the lowest layer of the rete and the sur- face of the cutis vera there are no intervening layers ; there is no amorphous fluid or blastema to be found there in which the cells could be generated, but they lie in direct contact with the papille of connective tissue of the cutis. There is therefore nowhere any space here, as there was thought to be even a short time ago, into which fluid transudes from the papillee and the vessels contained therein, in order that new cells may arise and develop themselves out of it. Ofsucha fluid there is absolutely nothing discernible, but throughout the whole series of the layers of cells of the rete and epidermis the same relations exist that we are familiar with in the bark of a tree. The cortical layer of a potato (Fig. 7) exhibits in a similar manner, externally, corky, epider- moidal cells, and underneath, as in the rete Malpighii, a layer of nucleated cells, the cambium, constituting the ‘matrix for the subsequent growth of the cortex. NAILS, 63 Very much the same is the case with the nails. On examining the section of a nail, made transversely to the long axis of the finger, we see virtually the same struc- ture as in ordinary skin, only every single indentation of the inferior surface does not correspond to a conical prolongation of the cutis, or papilla, but to a ridge which runs along the entire length of the bed of the nail, and may be compared with the ridges which are to be seen upon the palmar surface of the fingers. Upon these ridges of the bed of the nail are dwarfish, stunted papille, and upon them rests the rather cylindrically shaped youngest layer of the rete Malpighii; then follow cells continually increasing in size, until at last the really hard substance comes, which corresponds to the epi- dermis. Nevertheless—to discuss the subject at once, seeing that I shall not again have occasion to mention it—the structure of the nails has been difficult to make out, because they were conceived to be a simple formation. Nearly all the discussions, therefore, which have taken place, have turned upon the question where the matrix of the nail was, and whether the growth of the latter took place from the whole surface or from the little fold into which it is received behind. If we consider the nail with respect to its proper firm substance, its compact body (Nagelblatt), this only grows from behind, and is pushed forwards over the surface of the so-called bed of the nail (Nagelbett), but this in its turn also produces a definite quantity of cellular elements, which are to be regarded as the equivalents of an epidermic layer. On making a section through the middle of a nail, we come, most externally, to the layer of nail which has grown from behind, next to the substance which has been secreted by the bed of the nail, then to the rete Malpi- ghii, and lastly to the ridges upon which the nail rests. ¢ 54 LECTURB JI. Thus the nail lies in a certain measure loose, ard can easily move forwards, pushing itself over a moveable substratum, while it is kept in place by the ridges with which its bed is beset. When a section is made trans. versely through a nail, we see, as already mentioned, essentially the same appearance presented as that offered by the skin, only that a long ridge corresponds to every single papilla seen in ordinary sections of the skin ; the undermost part of the nail has slight indentations cor- responding to these ridges, so that, while gliding along over them, it can execute lateral movements only within certain limits. In this manner, the body of the nail which grows from behind moves forwards over a cushion: of loose epidermic substance (Fig. 17, @) in grooves which are provided by the ridges and furrows of the bed of the nail. The uppermost part of the nail, if examined when fresh, is composed of so dense a substance that it is scarcely possible to distinguish individual cells in it’ without applying reagents, and at many points an appearance is presented like that which we see in car- tilage. But by treating it with potash, we can convince ourselves that this substance is composed of nothing but epidermis-cells. From this mode of development you will see how easily intelligible distinctions may be drawn between the different diseases of the nails. There are diseases of the bed of the nail which do not affect the growth of its body, but may give rise to changes in its position. When there is a very abun- lant development of cells in the bed of the nail, the body may be pushed upwards (Fig. 17, 0); nay, it sometimes happens that the nail, instead of growing horizontally,, shoots perpendicularly upwards, the space underneath being filled with a thick accumulation of the loose cushiony substance (Polstermasse) (Fig. 17, c). Thus suppuration may take place in the bed of the nail with- CRYSTALLINE LENS 65 out the development of its body being thereby impeded. The most singular changes occur in small pox. When a pock forms upon the bed of the nail, there is nothing to be seen but a yellowish, somewhat uneven, spot ; but if, on the other hand, it is developed upon the fold, then its traces are left in the shape of a circularly depressed, and, as it were, excavated spot in the body of the nail as it gradually advances, a proof of a loss of substance pre- cisely similar to that which takes place in the epidermis. I will not to-day, gentlemen, enter more particularly into the spe- cial history of the formation of epi- dermis and epithelium, although it is of great importance for the right comprehension of many pathological pro- cesses, but content myself with calling your attention to the fact, that, under particular circumstances epithelial cells may undergo a series of transformations, through which they become extremely unlike what they originally were, and gradually assume appearances which render it impossible for those who are unacquainted with the history of their development to realize their original epidermic nature. The greatest abnormity of the kind is met with in the crystalline lens of the eye, which 1s originally a mere Fie. 17. Fig. 17. Diagrammatic representation of a longitudinal section ofa nail. a. The normal condition ; a gently curved, horizontal nail, implanted in its fold, and sepa- rated from its bed by a thin cushion. }. A more markedly curved and somewhat thicker nail, with great thickening of the cushion, and much increased curvation of the bed, the fold being shorter and wider. ce. Onychogryphosis; the nail, short and thick, reared up at a considerable angle, the fold short and wide, the bed fur- rowed on its surface, the cushion very thick and composed of layers of loose cells, piled up one above the other. 5 686 LECTURE II. accumulation of epidermis. It has its origin, as is well known, in a saccular involution of the external skin. At first its connection with the external parts continues to be maintained by means of a delicate membrane, the membrana capsulo-pupillaris; afterwards this atrophies and leaves the lens isolated in the interior of the eye. The fibres of the lens are therefore, as C. Vogt. has shown, nothing more than epidermoidal cells which have been developed in a peculiar manner, and their regene- ration, after the extraction of a cataract for example, is only possible as long as there still remains epithelium in the capsule to undertake the new formation, and to represent, as it were, a thin layer of rete Malpighii. This reproduces the lens in the same way that the ordi- nary rete Malpighii of the external surface does the cuticle. Amongst the other changes of epithelial struc- tures we shall in due time revert to the peculiar pig- ment cells that are produced in the most different parts by the direct transformation of epidermic cells, the con- tents of which either become coloured by imbibition, or have pigment engendered in them by a (metabolic) transposition of their elements. With the history of epithelial elements properly so called is immediately connected that of a peculiar class of structures which play a very important part in the accomplishment of the functions of an animal, namely the glands. The really active elements of these organs are essentially of an epithelial nature. One of Remak’s greatest merits consists in his having shown that in the normal development of the embryo the outer and inner of the well-known three layers of the germinal mem- brane chiefly produce epithelial structures, from a gra- dual proliferation of the elements of which glandular structures arise. Other observers, for example, Kolliker, had indeed before him made similar observations, but by GLANDS. 67 Remak was first established the law that the formation of glands in general must be regarded as consequent upon a direct process of proliferation on the part of epithelial structures. Previously large quantities of cytoblastema had been conceived to exist, in which, spontaneously, glandular substance took its rise ; but, with the exception of the lymphatic glands, and perhaps those belonging to the sexual organs, their mode of origin is everywhere this—that at a certain point, in a manner very similar to that which I described to you in the fore- going lecture, when speaking of the excrescences of plants, an epithelial cell begins to divide, and goes on dividing again and again, until by degrees a little process composed of cells grows inwards, and, spreading out laterally, gives rise to the development of a gland, which thus straightway consitutes a body continuous with lay- ers of cells originally external. Thus arise the glands of the surface of the body (the sudoriferous and sebaceous glands of the skin and the mammary gland), and thus also arise the internal glands of the digestive tract (the stomach glands and liver.) The most simple forms which glands can present do not occur at all in man. In infe- rior animals, however, uni-cellular glands have recently been discovered. ,The glands of the human body are invariably made up of a number of elements, which can, however, ultimately be traced back to a nearly simple type. Besides, in our own glands, in consequence of their size and complicated structure, other necessary constituents generally enter into their composition, so that, regarded as organs, they certainly do not consist of gland-cells only. But all parties are now pretty well agreed that the gland-cells are the really essential cle- ments, just as the primitive bundles are in muscle, and that the specific action of a gland is dependent upon the properties and peculiar arrangement of these elements. 68 LECTURE II. Generally speaking, therefore, glands consist of accu- mulations of cells, which usually form open canals. With Fie. 18. .the exception of the glands, whose functions are uncer- tain, such as the thyroid body and supra-renal capsules, there are in the human body only the ovaries which form an exception to this rule, inasmuch as their follicles are only open at times; yet they too must be open when the specific secretion of the ova has to take place. In most glands there is found indeed besides a certain quan- tity of transuded fluid, but this only constitutes the vehicle which floats off either the cells themselves, or their specific products. Suppose, for example, that in one of the ducts of the testicle a cell, in which there is a production of spermatozoa, becomes detached, then there transudes at the same time a certain quantity of fluid, which carries them away; but what makes the semen, semen, and constitutes the specific character of the action Fig. 18. A. Development of sweat-glands by means of the proliferation of the cells of the rete Malpighii in an inward direction. e. Epidermis. +. Rete Malpighii. g g- Solid process, constituting the first rudiments of a gland. After Kolliker. B. Portion of the duct of the sweat-gland ina state of complete development. tt. Tunica propria. ee. Layers of epithelium. THEORIES RESPECTING CONNECTIVE TISSUE. 69 is the peculiar power of the cell; the mere transuda- tion from vessels is no doubt a means of conveyance onwards, but does not constitute the specific action of the gland nor the real secretion. In an analogous man- ner, in all the glands of which we can follow the action in all its details with precision, the essential peculi- arities of their energy are derived from the development and transformation of epithelial cells. The second histological group is formed by the con- nective tissues (Gewebe der Bindesubstanz). This is the subject in which I take the most interest, because it was here that my own observations, which have led to the result.to which I directed your attention at the begin- ning of these lectures, originated. The alterations which I have succeeded in introducing in the views of histolo- gists with regard to the whole group have, at the same time, enabled me to give a certain degree of roundness and completeness to the cellular theory. Previously, connective tissue had nearly universally been regarded as essentially composed of fibres. On examining loose connective tissue in different re- gions, as, for example, beneath the corium, in the pia mater, subserous and submucous cellular tissue, we find wavy bundles of fibres, the so-called wavy connective tis- sue (Fig. 19, A). This wavy character, which is inter- rupted at certain intervals, so as to give rise to a kind of fasciculation, could, it was thought, with the less hesi- tation be attributed to the presence of separate fibres, because at the end of each bundle isolated filaments could in reality be seen to protrude. In spite of this, however, an attack was made upon this very hypothesis, somewhat more than ten years ago, and has proved of very great importance, though in a manner different to to that which was intended. Reichert endeavoured, namely, to show that the fibres were only an optical "0 LECTURE II. illusion produced by folds, and that connective tissue in all parts formed a homogeneous mass, endowed with a great tendency to the formation of folds. Fig. 19. Schwann had, in reference to the formation of con- nective tissue, assumed that there originally existed spin- dle-shaped cells, the caudate corpuscles (geschwiinzte Kérperchen) (fibro-plastic corpuscles of Lebert), which afterwards became so famous ; and that out of these cells fasciculi of connective tissue were directly developed by the splitting up of the body of the cell into distinct fi- brils, whilst the nucleus remained as such (Fig. 19, 8). Henle, on the other hand, thought the only conclusion his observations would warrant was, that there were originally no cells at all, but that nuclei only were formed in the blastema at certain intervals ; whilst the Fig. 19. A. Bundle of common, wavy, connective tissue (intercellular substance), splitting at its end into fine fibrils. B. Diagram of the development of connective tissue according to Schwann. a. Spindle-shaped cell (caudate corpuscle, fibro-plastic corpuscle of Lebert), with nu- cleus and nucleolus. 6. Cleavage of the body of the cell into fibrils. C. Diagram of the development of connective tissue, according to Henle, a. Hyaline matrix (blastema), with nucleolated nuclei regularly distributed through it. 8. Fibrillation of the blastema (direct formation of fibrils), and transformation of the nuclei into nucleus-fibres. THEORIES RESPECTING CONNECTIVE TISSUE. Th fibres, which afterwards appeared, were produced by a direct fibrillation of the blastema; and that, whilst the intermediate substance was thus being differentiated into fibres, the nuclei gradually became elongated, so as at length to run into one another, and thus give rise to peculiar longitudinal fibres, nucleus-fibres (Kernfasern) (Fig. 19, C). Reichert took an extremely important step in opposition to these views. He showed, namely, that originally there were only cells, and those in great abundance, between which intercellular substance was deposited. But the membrane of the cells became, he thought, at a certain period, blended with the intercel- lular tissue, and then a stage was reached analogous to that described by Henle, in which there no longer ex- isted any boundary between the original cells and the intermediate substance. And, finally, he imagined that the nuclei, too, entirely disappeared in some instances, whilst they were preserved in others. On the other hand, he positively denied the occurrence of the spindle- shaped cells of Schwann, and declared all such, as well as the caudate and jagged cells, to be just as much artificial products as the fibres, which were said to be seen in the intervening substance, were a false interpre- tation of an optical image. Now, my own investigations have shown, that both Schwann’s and Reichert’s observations, up to a certain point, have some foundation in truth. That, in the first place, in opposition to Reichert, spindle-shaped and stel, late cells indisputably do exist (Fig. 20) ; and secondly, in opposition to Schwann, and with Reichert, that a direct splitting up of the cells into fibres does not take place, but that on the contrary, what is afterwards pre- sented to our sight as connective tissue has really taken the place of the previously homogeneous intercellular substance. 1 have found, moreover, that Reichert, 72 LECTURE II. Henle, and Schwann, were wrong in maintaining that ultimately at best only nuclei or nucleus-fibres remained ; Fie. 20. and that, on the contrary, in most cases the cells them- selves preserve their integrity. The connective tissue of a later period is therefore not distinguished in its general structure and disposition in any respect from that of an earlier date. There is not an embryonic con- nective tissue with spindle-shaped cells and a perfectly developed one without them, but the cells remain the same, although they are often not easy to see. Essentially, therefore, this whole series of lower tis- sues may be reduced to one simple plan. Usually, the greater part of the tissue is composed of intercellular substance, in which, at certain intervals, cells lie imbed- ded, which in their turn present the most manifold forms. But these tissues cannot be distinguished by one’s con- Fig. 20. Connective tissue from the embryo of a pig, after long-continued boil- ing. Large spindle-shaped cells (connective-tissue corpuscles (Bindegewebskorper- chen)), some isolated, some still imbedded in the basis-substance, and anastomosing one with the other. Large nuclei, with their membrane detached ; cell-contents in some cases shrunken. 350 diameters. FORMATION OF CONNECTIVE TISSUE. %3 taining only round, another’s, on the contrary, only caudate or stellate, cells. but in all connective tissues Fie. 21. round, long and angular cells may occur. The simplest case is where round cells lie at certain intervals, and intercellular substance appears between them. This is the form which we see most beautifully shown in hyaline cartilage, as in that lining the joints, for example, in which the intercellular matter is perfectly homogeneous, and we see nothing but a substance which, though, per- haps, slightly granulated here and there, is on the whole quite as clear as water, so that as long as we do not see the edges of the preparation, doubt may arise as to whe- ther anything at all exists between the cells. This substance is characteristic of hyaline cartilage. Now we find that, under certain circumstances, the round cells became even in cartilage transformed into oblong Fig. 21, Diagram of the development of connective-tissue, according to my inves- tigations, .A. Earliest stage. Hyaline basis- (intercellular) substance, with largish cells (connective-tissue corpuscles); the latter drawn up in rows at regular intervals; at first separated, spindle-shaped, and simple; at a later period anastomosing and branched. B. More advanced stage; at a, the basis-substance which has become striated (fibrillated), presents a fasciculated appearance on account of the cells imbedded in it in rows, the cells becoming narrower and smaller; at 5, the striation of the basis-substance has disappeared under the influence of acetic acid, and the fine and long anastomosing fibre-cells (connective-tissue corpuscles), still retaining their nuclei, are seen. 4 LECTURE IL. spindle-shaped ones, as, for example, with great regula- rity in the immediate neighbourhood of the articular surfaces. The nearer, in the Fie, 22, examination of articular car- tilage, we approach to the free surface (Fig. 22, a,) the smaller do the cells become ; and, at last, nothing more is seen but small, flatly lenti- cular bodies, the substance intervening between which sometimes presents a slightly striated appearance. Here, therefore, without the tis- sue’s having ceased to be cartilage, a new type displays itself, which we much more regularly meet with in pure connective tissue, and hence the idea might easily arise that articular cartilage is invested with a special mem- brane. This is, however, not the case, for there is no synovial membrane spread over the cartilage, but its boundary towards the cavity of the joint is everywhere formed of cartilage itself. The synovial membrane only begins where the cartilage ceases—at the edge of the bone. On the other hand, we see that at certain points the cartilage passes directly into forms in which the cells become stellate, and the way is paved for their final anastomosis ; ultimately, spots are met with at which it is no longer possible to say where the one cell ends and the other begins, inasmuch as they communicate so directly one with another that it is impossible to detect a line of separation between their membranes. When Fig, 22. Perpendicular section through the growing cartilage of a patella. a. The articular surface, with spindle-shaped cells (cartilage-corpuscles) disposed in layers parallel to it, 0. Incipient proliferation of the cells. ¢. Advanced proliferation; large, roundish groups—within the enlarged capsules a continually increasing num- ber of round cells. 50 diameters. CARTILAGE—MUCOUS TISSUE. 5 such a case occurs, the cartilage, which up to that time had remained hyaline and homogeneous, becomes hete- rogeneous and striated, and has long since been called fibro-cartilage. From these forms a third has been distinguished, the so-called reticular [yellow or spongy] cartilage, as seen in the ear and nose, in which the cells are round, but encircled by a peculiar kind of thick, stiff fibres, whose mode of production has not yet been thoroughly made out, but they are, perhaps, derived from the metamor- phosis of the intercellular substance. Under these different types, presented by cartilage in its different localities, all the different aspects which the other connective tissues offer are included. There is also true connective tissue with round, long, and stellate cells. Just in the same manner we find, for example, in the peculiar tissue which I have named mucous tissue (Schleimgewebe), round cells in a hyaline, or spindle- shaped ones in a striated, or reticular ones in a meshy, basis-substance. The only criterion we possess for dis- tinguishing them consists in the determination of the chemical constitution of the intercellular substance. Every tissue is called connective tissue whose _basis- substance yields gelatine when boiled ; the intercellular substance of cartilage produces chondrine ; mucous tis- sue, on expression, a substance, mucin, precipitable by acetic acid, and insoluble in an excess of it, though dis- solving in muriatic acid when added in considerable quantity. Besides these, a few solitary points of difference in regard to peculiarity of form and contents may be pre- sented by individual cells at some later period of their existence. What we concisely designate fat is a tissue which is intimately connected with those of which we have been treating, and is distinguished from the rest by "6 LECTURE II. the fact that some of the cells enlarge and become stuffed full of fat, the nucleus being thereby thrust to one side. In itself, however, the structure of adipose tissue is pre- cisely the same as that of connective tissue, and, under certain circumstances, the fat may so completely disap- pear that the adipose tissue is once more reduced to the state of simple, gelatinous connective, or mucous tissue, Amongst these different species of connective tissue the most important for our present pathological views, are, generally speaking, those in which a reticular ar- rangement of the cells exists, or, in other words, in which they anastomose with one another. Wherever, namely, such anastomoses take place, wherever one cell is con- nected with another, it may with some degree of cer- tainty be demonstrated that these anastomoses constitute a peculiar system of tubes or canals which must be classed with the great canalicular system of the body, and which particularly, forming as they do a supplement to the blood- and lymphatic vessels, must be regarded as a new acquisition to our knowledge, and as in some sort filling up the vacancy left by the old vasa serosa which do not exist. This reticular arrangement is possible in cartilage, connective tissue, bone and mucous tissue in the most different parts; but in all cases those tissucs which possess anastomoses of this description may be distinguished from those whose elements are isolated, by the greater energy with which they are capable of con- ducting different morbid processes. ie BE WS Bo FEBRUARY 20, 1858. PHYSIOLOGICAL AND PATHOLOGICAL TISSUES. The higher animal tissues: muscles, nerves, vessels, blood. Muscles—Striped and smooth—Atrophy of—The contractile substance and con+ tractility in general—Cutis anserina and arrectores pili. Vessels—Capillaries—Contractile vessels—Nerves. Pathological tissues (Neoplasms), and their classification—Import of vascularity— Doctrine of specific elements—Physiological types (reproduction)—Heterology (heterotopy), heterochrony (heterometry), and malignity—Hypertrophy and hyperplasy—Degeneration—Criteria for prognosis, Law of continuity—Histological substitution and equivalents—Physiological and pathological substitution. In my last lecture I portrayed to you the first two groups of tissues, the one embracing epithelium or epi- dermis, and the other the different kinds of connective tissue. What still remains forms a somewhat heteroge- neous group, the individual members of which do not, indeed, in the degree that is the case with epithelium and connective tissue, bear a real relationship to one another, yet, on the whole, present a certain correspon- dence, in that they constitute the higher animal struc- tures, and are distinguished by their specific mode of development from the less highly organized epithelial and connective tissues. Moreover, most of them appear under the form of connected, more or less tubular, struc- tures. If a comparison be instituted between muscles, nerves, and vessels, the idea very readily suggests itself qT 78 LECTURE III. that we have in all three structures to deal with real tubes, filled with now more, now less, moveable contents, But this notion, however well it may accord with a superficial view of the matter, does not express the whole truth, inasmuch as we cannot compare the con- tents of the different tubes. The blood which is contained in the vessels, cannot, at least at present, be regarded as analogous to the axis- cylinder, or the medullary [white] substance of a nerve- tube, or to the contractile substance of a primitive mus- cular fasciculus (Muskelprimitivbtindel [muscular fibre}). I must, indeed, here remark, that the original develop- ment of all the structures which may be included in this group is still a subject of great controversy, and that the view maintaining the simply cellular structure of most of these elements is by no means completely estab- lished. This much, however, appears to be certain, that, at any rate in foetal parts, the blood-corpuscles are just as much cells as the individual constituents of the walls of the vessels within which the blood flows ; and that the vessel cannot be designated as a tube which invests the blood-corpuscles, as the cell-membrane does its contents. It is therefore necessary in the case of the vessels to draw a line between their contents and proper walls, and to repudiate the seeming resemblance between the vessels, and the nerves and muscular fibres. Again, if we wished to adopt the mode of origin of the several tissues as the basis of our classification, we should, in accordance with prevailing views, have to associate the lymphatic glands also with the blood, and might be rather reminded of a connection such as we have seen to exist in the relations between the epidermis and the rete mucosum. But here I must once more impress upon you that the lymphatic glands are distinguished from glands properly so called, not only by their not THE HIGHER ANIMAL TISSUES. "9 possessing any excretory duct in the ordinary sense of the word, but also because from the mode of their deve- lopment they by no means occupy the same position as ordinary glands, but are on the contrary at every period of their existence nearly allied to the connective tissues, and that, therefore, the temptation would rather be to class them with the tissues which we see produced by the transformation of the connective tissues. Yet this would at the present moment be still rather a ven- turous undertaking. Amongst all the forms of which we have here to treat, the elements of muscle have generally been regarded as the most simple. If we examine an ordinary red muscle (I do not say a voluntary one, inasmuch as in the heart also we meet with fibres of the Fie. 28. same form) we find it to be essen- tially composed of a number of cylinders, for the most part of equal thickness (primitive fasci- culi [fibres]), which on a trans- verse section are seen to have a cylindrical form, and on which we at once perceive the well-known transverse striz, that is, broad lines which generally run transversely through the fasci- culus with a somewhat wavy outline, and are almost as broad as the intervals that separate them. In addition to this transverse striation we also see, especially when certain modes of preparation have been adopted, strize fol- Fig. 23. A group of primitive muscular fasciculi [fibres]. @. The natural appear- ance of a fresh primitive fasciculus, with its transverse strie (bands or discs). b. A fasciculus gently acted upon by acetic acid; the nuclei stand out distinctly, and in one of them two nucleoli are visible, whilst in another the division is complete. c. A fibre acted upon more strongly by acetic acid; the contents are swollen up at the end, so as to protrude from the sheath (sarcolemma). d. Fatty atrophy. 300 diameters. 80 LECTURE IIL. lowing a longitudinal direction, and these, indeed, in some preparations preponderate to such a degree, that the muscular fasciculus appears to be striated almost exclu- sively in this direction. If now we add acetic acid, there are forthwith disclosed immediately beneath the sheath, and now and then also more towards the centre, nuclei which are tolerably large, and mostly contain large nucle- oli in greater or less number. In this manner, therefore, after we have cleared up the internal substance by the application of acetic acid, we again obtain an appearance which reminds us of the original cell-form ; and there has been the greater tendency to regard the whole of a primitive fasciculus as having sprung from a single cell, because according to the view which was formerly entertained, the individual primitive fasciculi of every muscle were thought to extend from the point of origin to that of insertion, and were therefore held to be as long as the muscle itself. This latter supposition has, however, been shaken by investigations which were set on foot in Vienna, under Briicke’s direction by Rollet, for he demonstrated that in the course of muscles the ends of primitive fasciculi are to be seen running into points, so that a primitive muscular fasci- culus would comport itself like a large fibre-cell (Fig. 105, A). These ends fit one into the other, and, accord- ing to this, the length of a primitive fasciculus would by no means correspond to the whole extent of the muscle. On the other hand, I must remark, that observations have been made in different quarters quite recently, which are rather of a nature to throw doubts upon the uni-cellular nature of these elements. Leydig regards them as rather containing a series of cells of a smaller kind, between which the contractile substance is lodged, his idea being based upon the circumstance that every. nucleus (Figs. 23, 6, c; 24, B) is enclosed in a special TRANSVERSELY STRIATED MUSCLES. 81 elongated cavity. In discussions respecting these ulti- mate elements of muscle, extremely difficult relations are involved, and I for my own part must confess that, however much I am inclined to admit the uni-cellular nature of the primitive fasciculi, I am still too familiar with the peculiar appearances in their interior not to be obliged to allow that another view may beadvanced. For the present, however, we must bear in mind that we have to do with a structure in which an external mem- branous sheath (sarcolem- ma) and contents are to be distinguished. In the latter, acetic acid causes nuclei to show themselves, and, when they (the contents) are in their natural condition, the peculiar transverse and longitudinal striation may be recognised in them. This Fig. 24. Muscular elements from the heart of a puerperal woman. A. Peculiar spindle-shaped cells precisely like the fibre-cells of the pulp of the spleen, probably belonging to the sarcolemma and set free in teasing out the preparation. a. Cres- centically curved cell, somewhat flat at one end, viewed on its surface. 6. A similar one, seen in profile, with flat nucleus. c, d. Cells, the nuclei of which lie in wu hernial protrusion of the membrane. e¢. A similar cell, viewed on its sur- face, with its nucleus, es it were, lying upon it. ZB. A primitive fasciculus, without its sheath (sarcolemma), with distinct longitudinal fibrils and large, roundish nuclei, of which one contains two nucleoli (incipient partition). C. A primitive fasciculus, which has been teased asunder and slightly cleared up by acetic acid; besides a divided nucleus, fine, awl-shaped, nucleus-like bodies are seen imbedded between: the longitudinal fibrils. 300 diameters. 1 This cavity Leydig supposes to be lined by a membrane, and therefore really to constitute a cell (connective-tissue corpuscle). The nuclei of every primitive fasciculus would, therefore, according to this view, be the nuclei of connective- tissue corpuscles, and the contractile substance, lying between these, would be equivalent to the intercellular substance of ordinary connective tissue. The nuclei here alluded to are the ordinary nuclei of muscle, as seen in the figs. quoted above and must not be confounded with the awl-shaped bodies represented in fig. 24, C, lying between the fibrils ; for, though these bodies look like nuclei, they are really, according to Leydig, portions of the divided processes of some of his connective- tissue corpuscles.—From a US. note by the Author. 6 82 LECTURE III. striation is altogether internal and not external. The membrane in itself is perfectly smooth and even; the transverse striation belongs to the contents, which, when seen in a mass, form the red substance of the muscle. Now it is this substance which has the property of contractility indubitably inherent in it, and even varies in appearance according to its state of contraction, be- coming broader when contracted, whilst the intervals between the individual transverse bands become some- what narrower, so that a change in the arrangement of its minutest constituents takes place, and this, as seems probable from the investigations of Briicke, not merely in the case of its physical molecules, but also in that of its visible anatomical constituents. Briicke, namely, by examining muscle by polarized light, has discovered different optical properties in the individual layers of substance—in those which compose the transverse strie and those which form the intervening mass. On the adoption of certain methods of preparation, every pri- mitive muscular fasciculus appears to be made up of plates or discs of a different nature, piled up one above another, and these in their turn to be entirely composed of minute granules (Bowman’s sarcous elements). In reality, however, the contents of a primaitive fasciculus consist of a certain number of fine, longitudinal fibrils, every one of which contains minute granules correspond- ing in position to the transverse striee or apparent discs of the primitive fasciculus, and held together by a pale, intervening substance. Now, since a considerable num- ber of primitive fibrils lie in apposition side by side, there arises, in consequence of the symmetrical position of the little granules, this very appearance of discs which really do not exist. In proportion to the activity of the muscle these parts assume an altered position with re- gard to one another ; during contraction the granules SMOOTH MUSCLES, 83 are approximated, whilst the intervening substance be- comes shorter and, at the same time, broader. Compared with this, the structure of the smooth, or- ganic, or, although this is a less expressive term, invo- luntary muscular fibres, appears much more simple. On examining any part of those organs in which smooth muscular fibres are contained, we find in the majority of cases, first of all, just as was the case with the transversely striated muscles, little fasciculi—as, for example, in the muscular coat of the urinary bladder. Within these fasciculi, upon further investigation, a series of distinct elements can be distinguished, of which a certain num- ber, six, ten, twenty, or more, are held together by a common connective substance. According to the notion which universally prevailed -until quite recently, every one of these elements was analogous to the primitive fasciculus of striped muscle. For as soon as we succeed | in separating these fasciculi of smooth muscle into their more minute constituents, we find their ultimate ele- ments to consist of long, spindle-shaped cells, which usually contain a nucleus in their centre (Fig. 5, 0). According to the view on the contrary, which, especially in consequence of the impul- sion given by Leydig’s investigations, has quite lately Fig. 25. Smooth muscular fibres from the parietes of the urinary bladder. A. Fasciculus still coherent, out of which at a, a single isolated fibre-cells protrude, whilst at 6 their simple divided ends appear. B. A similar fasciculus after being treated with acetic acid, whereby the long and narrow nuclei have become evident. a, and 6, as above. 300 diameters. 84. LECTURE III. begun to be mooted in various quarters, we should have to regard the bundle, in which a whole series of ‘fibre- cells is contained, rather as analogous to a transversely striated primitive fasciculus. Until, however, this point has been satisfactorily settled, I consider it advisable and more in accordance with known facts to regard each fibre-cell as the equivalent of a primitive fasciculus, Should, however, any change of opinion shortly occur, you will now at any rate be prepared for it. In one of these spindle-shaped or fibre-cells it is diffi- cult to distinguish anything particular. In very large cells of this kind, and with a high magnifying power, we can certainly frequently distinguish a fine longitudinal striation (Fig. 5, 5), so that it looks as if here, too, fibrils of some sort were disposed lengthways in the interior, whilst ordinarily no trace of any transverse strie is per- ceptible. Yet the pale, smooth muscles exhibit, chemi- cally speaking, a pretty close agreement with the trans- versely striped ones, since a similar substance (the so-called Syntonian of Lehmann) can, by the help of di- luted hydrochloric acid, be extracted from both; and one of the most characteristic substances which is met with in red muscles, namely Creatine, is met with also, according to the investigations of G. Siegmund, in the smooth muscular fibres of the uterus. One of the preparations of red muscle which I have placed before you exhibits an appearance which is also pathologically interesting ; among the fasciculi, namely, is one which presents the condition of the so-called pro- gressive (fatty) atrophy. The degenerated fasciculus is smaller and narrower, and at the same time little fat-globules are seen arranged in rows between the lon- gitudinal fibrils (Fig 23, d). Atrophy in muscles is chiefly characterized by a diminution in the diameter of the primitive fasciculi affected ; in fatty atrophy the CONTRACTILITY. 85 more palpable change is added, that little rows of fat- globules appear in the interior of the primitive fascicu- lus, during the accumulation of which the proper con- tractile substance decreases in bulk. The more fat there is, the less contractile substance ; or, in other words, the muscle becomes less capable of performing its func- tions in proportion as the normul contents of its fibres diminish. Pathological experience, therefore, also de- signates as the seat of the contractile power a definite substance, the occurrence of which, as especially the im- portant investigations of Kélliker have taught us, is con- nected with certain histological elements. Whilst for- merly many other things besides the substance of muscle, as for example, certain forms of connective tissue, were assumed to be contractile, lately the whole theory of contractility in the human body has been withdrawn within the limits of that substance, and observers have succeeded in tracing back nearly all the pecuhar pheno- mena of motion to the existence of minute parts of a really muscular nature. Thus, in the human skin there lie little muscles about as large as the smallest fascicult in the parietes of the urinarybladder, bundles consisting of diminutive fibre-cells, which run from the base of the hair-follicles towards the surface of the skin, and, when they contract, approximate the two. The result of this is naturally that the skin becomes uneven, and we get what is called a goose-skin. This singular phenomenon, which was previously regarded as inexplicable, has been simply explained by the demonstration of these purely microscopical muscles, the arrectores pilorum. So also we now know that the greater part of the muscular layers in vessels is composed of elements of this kind, and that the phenomena of contraction exhi- bited by the vessels must be referred solely and exclu- sively to the action of muscular fibres, which are con- 86 LECTURE III. tained in them in the form of circular or longitudinal layers. A small vein or a small artery can contract only in proportion to the quantity of muscle with which it is provided, and they are only distinguished by the circum- stance that either the longitudinal or the transverse mus- cular layers are the more strongly developed. I have called your attention to this point because you can see from it, how a simple anatomical discovery may supply the most important information with regard to Fig. 26. Small artery from the base of the cerebrum after the application of acetic acid. A. Small trunk; B and @, larger branches; D and Z, branches of the smallest size (capillary arteries). a, a. External coat, with nuclei, which run in the direction of the length of the vessel, and are seen first in a double and afterwards in a single layer, with a striated basis-substance ; at D and E the coat is reduced to a single layer, with longitudinal nuclei, which here and there have been replaced by masses of fat-granules (fatty degeneration). 6, 6. Middle coat (circular fibrous, or muscular, coat), with long, cylindrical nuclei, which run transversely around the vessel, and at its borders (where they look as though they had been cut across) present the appearance of round bodies; at D and Z transverse nuclei of the middle coat becoming continually scarcer. c, ¢. Internal coat, at D and # with longitudi- nal nuclei. 300 diameters. VESSELS. 87 physiological facts, which are widely separated from one another, and how the demonstration of definite morpho- logical elements may at once most essentially contribute to the elucidation of functions, which, without any such data, would be utterly incomprehensible. I will omit to speak here of the more intimate struc- ture of the nervous system, because I shall have occasion hereafter to consider it in a more connected form, else this would be the subject which would most suitably come next, seeing that there exist many points of resem- blance in the structure of muscular and nerve-fibres. But in the nervous system we find, in addition, nerve- cells (Ganglienzellen), which connect the individual fibres with one another, and must be regarded as the most important storehouses for all nervous energy. Concerning the structure of the vascular system also I will not here treat in detail, but will only say as much as is necessary to give a cursory view of the matter. A capillary vessel is a simple tube (Fig. 3, c), in which we have, with the aid of our present appliances, hitherto only been able to discover a simple membrane, beset at intervals with flattened nuclei, which, when seen in the middle of the surface of the vessel, present the same ap- pearance as in the elements of muscle, only that they usu- ally lie more at the sides, and therefore frequently have an awl-shaped appearance, from their sharp border alone being perceived. It is this, the most simple class of vessels, which we now-a-days solely and exclusively cali capillaries, and with regard to them we cannot say that they become wider or narrower by means of any action of their own, but at most that their elasticity renders a certain degree of contraction possible. Nowhere are there to be witnessed in them genuine processes of con- traction or relaxation succeeding it. The discussions which formerly took place with regard to the contracti- 88 LECTURE III. lity of the capillaries really had reference to small arte- ries and veins, the calibre of which grows narrower through the contraction of their muscular coats, or wider upon the occurrence of relaxation in consequence of the pressure of the blood. This is one of the first facts, and an important one it is, which have resulted from the more accurate histological knowledge of the smaller and larger vessels, and it shows us that we cannot speak of the general properties of vessels, inasmuch as the capil- laries differ essentially in structure from the small arte- ries and veins. These are composite structures, partak- ing of the nature of organs, whilst a capillary vessel is rather a simple histological element. Now that we have, gentlemen, completed a very general survey of the physiological tissues, the question arises, how the pathological ones in their turn comport themselves. By pathological tissues, of course, those only can be meant which really constitute is pelea new formations, and not physiological parts which have “simply _ undergone alteration in consequence of some _ deviation from the normal processes_of nutrition. “We SSE et have in them to deal with genuine neoplasms, with . the additional matter furnished by the growth of new tissues in the course of pathological processes, and the question ‘is, whether the general types which we have established | for the physiological tissues will also be found to hold _ good in the case of the pathological ones. ‘To this I un- . reservedly reply, yes ; and however much I herein differ from many of my living contemporaries, however posi- tively the peculiar (specific) nature of many pathological tissues has been insisted upon during the last few years, I will nevertheless endeavour in the course of these lec- tures to furnish you with proofs that every pathological structure has a physiological prototype, and that no form of morbid growth arises which canuot in its ele- CLASSIFICATION OF NEOPLASMS. 89 ments be traced back to some model which had _pre- viously maintained an independent existence in the economy. The classification of pathological new formations, of genuine neoplasms, was formerly by most observers attempted to be based upon their different degrees of vascularity. If you examine the different treatises which appeared upon this subject up to the time of the cell- theory, you will find that the question of organization was always decided by that of vascularity. Every part which contained vessels was regarded as organized, and every part as unorganized which was destitute of ves- sels. But this, according to present notions, is an incorrect view of the matter, inasmuch as we have also physiological tissues without vessels, as for example, cartilage. = But at a time when the more minute elements of tissues were at most only known as globules, and when very different virtues were attributed to these globules, it was quite excusable that everything should be referred to the vessels, particularly after the comparison John Hunter made between pathological new formations and the development of the chick in the egg, when he endea- voured to show that, just as the punctum saliens in the hen’s egg constitutes the first phenomenon of life, the vessels also where the first things to show themselves in pathological formations. You no doubt still remember how several ‘‘parasitical” new formations were de- scribed by Rust and Kluge as provided with an inde- pendent vascular system, which without having any connection with the old vessels, developed itself quite independently, as is the case in the chick. Many attempts had indeed been made even before this to refer the apparently so irregular forms of new formations to physiological paradigms, and herein essential service 90 LECTURE III. has been rendered by natural philosophers. At the time when theromorphism played a conspicuous part, and many analogies were discovered between pathological processes and the normal states of inferior animals, com- parisons also began to be instituted between new for- mations and familiar parts of the body. Thus, Johann Friedr. Meckel, the younger, spoke of mammary and pancreatic sarcoma. What has very recently beén described in Paris as heteradenia (Heteradenie), or a heterologous formation of glandular substance, was in the school of the natural philosophers a pretty generally accepted fact. Since the study of embryology has been prosecuted in a more histological manner, the conviction has gradually more and more been acquired, that most new formations contain parts which correspond to some physiological tissue, and in the micrographical schools of the west a _ certain number of observers have come to the conclusion, Athat in the whole series of new formations there is only one particular structure which is specifically different fom natural formations, namely cancer. With regard to this, the most important points urged are, that it differs altogether from every other tissue, and that it contains elements su? generzs, whilst, singularly enough, a second formation, between which and cancerous tissue the older writers were wont to draw parallels, namely tubercle, has—although to it too nothing strictly analo- gous could be discovered—been much neglected, owing to its having been regarded as an incomplete and some- what crude product, and as a structure which had never become properly organized. Yet, upon a more careful examination of cancer or tubercle, we snall find that everything depends upon our searching for that stage in their development, in which they are exhibited in their perfect form. We must not examine at too early a CLASSIFICATION OF NEOPLASMS. 91 period, when their development is incomplete, nor yet at too late a one, when it has proceeded beyond its highest point. If we restrict our observations to the time when development is really at its height, a phy- siological type may be found for every pathological formation, and it is just as possible to discover such types for the elements of cancer as to find them, for example, for pus, which, if it be sought to maintain the specific nature of certain formations, is just as much entitled to be regarded as something peculiar as cancer, Both of them stand upon precisely the same footing in this respect, and when the older writers spoke of cancer- pus they were in a certain measure right, inasmuch as cancer-juice is only distinguished from pus by the higher degree of development to which its individual elements have attained. A classification of pathological structures also may be made upon exactly the same plan as that which we have already ventured upon in the case of the physiological tissues. In the first place, there are also among these structures some which, like the epithelial ones, are essen- tially composed of cellular elements, without the addition of anything else of consequence. In the second place, we meet with tissues which are allied to those called connective, inasmuch as in addition to the cells a certain quantity of intercellular substance is present. In the third and last place come those formations which are akin to the more highly organized structures, blood, muscles, nerves, etc. Now, a point to which I must at once direct your attention is, that in pathological forma- tions those elements the more frequently exist, and the more decidedly prevail, which do not represent the higher grades of really animal development, and that, therefore, on the whole, those elements are most rarely umitated which belong to the more highly organized, and 39 LECTURE III. especially, to the muscular and nervous, systems. Still, these formations are by no means excluded; we find pathological new formations of every description, no matter to what tissue they may be analogous, provided it possesses distinctive features. It is only with regard to their frequency and importance that a difference prevails, and this is of such a naturé that the great majority of pathological productions contain cells analogous to epi- thelial cells, or to the corpuscles of the connective tissues, and that of those structures which we have included in the last class of normal tissues, the vessels and parts which may be compared with lymph and lymphatic glands are the most frequently met with as new formations, whilst real blood, muscles, and nerves, are the most seldom found as such. But, if we ultimately arrive at such a simple view of the matter, the question of course arises, what becomes of the doctrine of the heterology of morbid products, to the upholding of which we have long been accustomed, and to which the most simple reflection almost inevita- bly conducts us. Hereunto I can return no other an- swer than that there is no other kind of heterology in morbid structures than the abnormal manner in which they arise, and that this abnormity consists either in the production of a structure at a point where it has no business, or at a time when it ought not to be produced,: or to an extent which is at variance with the typical formation of the body. So then, to speak with greater precision, there is either a Heterotopia, an aberratio loci, or an aberratio temporis, a Heterochronia, or lastly, a mere variation in quantity, Heterometria, But we must be very careful not to connect this kind of heterology in the more extended sense of the word with the notion of malignity. Heterology is a term that, in its histolo- gical meaning may be applied to a large proportion of HYPERTROPHY AND HYPERPLASY. 93 pathological new formations, which, as far as the prog- nosis is concerned, may unquestionably be called benig- nant ; itis not rare for a new formation to occur at a point where it is certainly entirely misplaced, but at the same time does not occasion any considerable mischief. A lump of fat may very likely arise in a place where we should expect no fat, as, for example, in the submucous tissue of the small intestines, but, let the worst come to the worst, the result is only a polypus, which protrudes on the inner surface of the bowel, and may become tolerably large without giving rise to any symptoms of disease. If we consider the structures which are called heterologous in the more restricted sense of the word, with reference, namely, to the points at which they arise, they may be easily separated from the homo- logous ones (homeeoplastic ones of Lobstein), by their deviating from the type of the part in which they arise. When a fatty tumour arises in fatty tissue, or a connec- tive tissue (fibrous) tumour Bindegewebs-Geschwulst) in connectiye tissue, the type followed in the formation of the new structure is homologous to the type followed in the formation of the old one. All such formations are, as usually designated, included under the term hyper- trophy, or under that of hyperplasia, if we adopt the name I have proposed for the sake of more accurate dis- tinction. Hypertrophy, according to the meaning which I attach to the word, designates those cases in which the individual elements af a structure take up a considerable amount of matter, and thereby become larger ; and in consequence of the simultaneous enlargement of a num- ber of elements, at last the whole of an organ may be- come swollen. When a muscle becomes thicker, all its primitive fasciculi become thicker. A liver may become hypertrophied simply in consequence of a considerable 94. LECTURE III. enlargement of its individual cells. In this case there is real hypertrophy without, properly speaking, any new formation. Essentially different from this process are the cases in which an enlargement takes place in consequence of an ecrease in the number of the elements. A liver, namely, may also become enlarged by a very abundant development of a series of small cells in the place of the ordinary ones. Thus, when simply hyper- trophied, we see the panniculus adiposus of the skin swell up in consequence of every single fat-cell’s absorbing a larger quantity of fat than usual, and when this takes place in thousands upon thousands, nay, we may say, in hundreds of thousands and millions of cells, the re- sult is very obvious and strikes the eye (polysarcia). but itis just as possible for new cells to form in addi- tion to the old ones, and for an increase of size to take place without any enlargement of the individual cells. Fig. 27. Diagrams of hepatic cells. -A. Their simple physiological appearance. B. Hypertrophy: a, simple; 8, with accumulation of fat (fatty degeneration, fatty liver). ©. Hyperplasy (numerical or adjunctive hypertrophy). a. Cell with nucleus and divided nucleolus. 4, Divided nuclei. ¢, ¢. Divided cells. DEGENERATIVE NEW FORMATIONS. 95 These are essentially different processes, and may be styled semple and numerical hypertrophy. Hyperplastic processes (numerical hypertrophy) in all cases produce a tissue similar to that of the original part ; hyperplasia of the liver gives rise to new hepatic cells ; that of a nerve to new nerve-substance ; that of the skin to a fresh production of the elements of the skin. A heteroplastic process, on the contrary, engen- ders histological elements which correspond, indeed, to natural forms, elements, for example, resembling in structure those peculiar to glands, nerve-substance, the connective and epithelial tissues, but these elements do not arise in consequence of a simple increase in the number of such as previously existed, but in conse- quence of a change in the original type of the parent tissue. When cerebral matter forms in the ovary, it does not arise out of pre-existing cerebral matter, nor through any act of simple cell-proliferation ; when epi- dermis springs up in the muscular substance of the heart, however much it may correspond to that on the external surface of the skin, it is, notwithstanding, a heteroplastic structure. When we find hairs quite natu- ral in structure in the substance of the brain, however great the correspondence they exhibit with the hairs of the external surface, they will nevertheless be hetero- plastic hairs. In like manner we see cartilaginous tis- sue arise, without the existence of any essential differ- ence between it and ordinary, familiar cartilage, as, for example, an enchondromata. Still, an enchondroma is a heteroplastic tumour, even when occurring in bone, for perfect bone has no longer any cartilage in the parts where the enchondroma forms, and the term cartilage of bone (Knochenknorpel), as a designation for the organic basis of bone, is nothing but aterm. It is either from osseous or medullary tissue that the enchondroma 96 LECTURE III. springs, and at the very point where real cartilage ex- ists, for example, at the articular ends of the bone, no cartilaginous tumours, in the ordinary sense of the word, arise. It is not, therefore, with an hypertrophy of pre- existing cartilage that we have here to deal, but with a genuine new formation, which begins with a change in the local histological type. According to this manner of viewing the subject which is essentially different from that previously current, no attention is therefore paid, in considering the question of the heterologous nature of a new formation. to the composition of the structure as such, but only to the relations which subsist between it and the parent soil from which it springs. Heterology, in this sense, designates the difference of development in the new, as contrasted with the old, tissue, or, as we are wont to say, a degeneration, a deviation from the typical conformation. This is, as you will see, also really the most important point upon which we can ground our prognosis. We find tumours, which present the most striking resem- blance to the most familiar physiological tissues, An epidermic [epithelial] tumour (Epidermis- Geschwulst) may, as I have already pointed out, in its elementary structure entirely correspond to ordinary epidermis, but in spite of this it is not always a benignant tumour of merely local import, which may be traced to a merely hyperplastic increase in pre-existing tissues, for it some- times arises in the midst of parts which are far from containing epidermis or epithelium, as, for example, in the interior of lymphatic glands, or in that of thick layers of connective tissue, which are at a distance from any surface, and even in bone. In these cases the for- mation of epidermis is certainly quite as heterologous as it is possible to conceive anything to be. But practical. experience has shown us that it was altogether incorreet.. REPRODUCTION OF PHYSIOLOGICAL TISSUES. 94 to conclude from the mere correspondence of the patho- logical tissue with a physiological one, that the case would continue to follow a benignant course. It has been, as I must remark with particular empha. sis, one of the greatest, and at the same time best-founded, reproaches which have been levelled against the most recent micrographical doctrines, that, regarding the sub- ject from the certainly excusable point of view, namely, the correspondence between many normal and abnormal structures, they have declared every pathological new formation to be innocuous which exhibits a reproduction of pre-existing and familiar tissues of the body. If what I have communicated to you as my view be correct, namely, that throughout the whole range of pathological growths no structure of an absolutely new form is to be ‘found, but that we everywhere meet with structures hich may in one way or another be regarded as the eproduction of physiological tissues, then this point of view falls to the ground. In support of my view, I can at least adduce the fact that I have, in all disputes con- cerning the innocent or malignant nature of definite forms of tumours, up to the present time always proved to be in the right. Before we quit the consideration of General Histology, I would invite your attention for a few moments to a few points of primary importance which obtrude them- selves upon us on nearly every occasion. Whilst, namely, the animal tissues were being studied in their affinities to one another, questions relating to these affinities were at different times stumbled upon, which gave rise to generalizations that were more of a physiological cha- racter. When Reichert undertook to collect the connective tissues into one larger group, he set out with this position chiefly, that the demonstration of the continuity of tis- 7 98 LECTURE III. sues must be regarded as a decisive proof of their inti- mate relationship. That as soon as one part could be made out to be continuously (by union, not mere juxtaposition) connected with another, both “must be regarded as parts of a common whole. In this manner he sought to prove that cartilage, periosteum, bone, tendons, fascias, etc., really formed a continuous mass, a kind of basis-tissue (Grundgewebe) for the body, a connective sub- stance, which had only experienced certain changes in these different localities, without their being, however, of such a nature as to destroy the character of the tis- sue as such. This so-called law of continuity soon suf- fered the most violent shocks, and quite recently such a terrible breach has been made in it, that it can scarcely any longer be possible to derive therefrom any general criterion for the determination of the nature of a tissue. On the other hand, namely, new facts have been con- tinually brought forward in support of the continuity ot such histological elements as, according to Reichert, would be separated ¢oto celo from one another, as, for example, of epithelial and connective tissue ; and there has been a continually increasing mass of evidence in support of the assertion that cylindrical epithelium is capable of becoming elongated into fibres, which in the shape of filaments anastomose with connective-tissue corpuscles. Nay, it has been quite recently asserted by a whole series of observers that these superficial cells are pro- longed inwardly, and then enter into direct connection with nerve-fibres. With regard to this last point, I must confess that I am not yet convinced of the correct- ness of the representation ; but with respect to the for- mer one, that is a matter which will probably end in the demonstration of the real continuity of the elements. It would seem, therefore, that it is even now no longer possible to mark out the exact limits which divide every HISTOLOGICAL EQUIVALENTS AND SUBSTITUTIONS. 99 kind of epithelium from every kind of connective tissue, but only where scaly epithelium is met with, whilst the limits are doubtful wherever cylindrical epithelium exists. Just in the same manner elsewhere also do the bound- ary lines become obliterated. Whilst formerly the lim- its which separate the elements of muscle from those of tendon were considered to be most distinctly defined, extremely decisive proofs have in this case also been afforded, and first by Hyde Salter and Huxley, that fibres proceed from connective-tissue corpuscles, which whilst pursuing their course in an inward direction, all at once assume the character of transversely striped muscle. So, then, in the case of connective tissue, it would seem there exists a continuous connection between the ele- ments of the surface and the more highly developed ones of the deeper parts. Now if, on the other hand, it has turned out to be very probable that the corpuscles of connective tissue have definite relations to the vascular system, we are, as you see, almost justified in regarding this tissue as a kind of neutral ground for parts to meet upon (indifferenter Samelpunkt), as a peculiar arrange- ment for their intimate connection, an arrangement which, though certainly not exercising any great influence upon the higher functions of the animal, is yet of great importance as far as its nutrition is concerned. n the place of the law of continuity, therefore, we must necessarily put something else. And here, I think, the doctrine which has the strongset claims to our atten- tion is that of histological substitution. In the case of all tissues of alike nature it is quite possible, even whilst confining our attention to what occurs physiologi- cally in the various classes of animals. to find one tissue at a certain fixed point of the body replaced by an analo- gous one belonging to the same group, OT, in other words, by an histological equivalent. A spot invested with cylindrical, may acquire scaly, 100 LECTURE III. epithelium. A surface upon which cilia were originally seen, may afterwards be found to have ordinary epithe- lium. Thus, on the surface of the ventricles of the brain we meet at first with ciliated, and at a later period with simple scaly, epithelium. Thus, too, we see the mucous membrane of the uterus usually covered with ciliated epithelium, but during pregnancy we find the layer of ciliated cylinders replaced by one of squamous epithe. lium. Thus, also, in places where soft epithelium ordi- narily is found, epidermis may, under particular circum- stances, be generated, as, for example, in the prolapsed vagina. Thus, again, in the sclerotic coat of the eyes of fish, cartilage is found, whilst in man this tunic con- sists of dense connective tissue ; in many animals bone is found in parts of the skin, where in man there is only connective tissue; but in man, too, in many places where there was original cartilage, osseous tissue is afterwards discovered. But the most striking instances of such substitutions are met with in muscles. One animal has transversely striped muscular fibres in the same place that another has smooth ones. ’~ Jn diseased conditions pathological substitutions occur, | in which a given tissue is replaced by another ; but even when this new tissue is produced from the previously _ existing one, the new formation may deviate more or | less from the original type. There is therefore a great chasm between physiological and pathological substitu- | tion, or at least, between the physiological and certain forms of the pathological one. Physiologically, the substitution is constantly effected by the introduction of another tissue of the same group (homology) ; pathologically, very frequently by the agency of a tissue belonging to another (heterology). To this we must reduce the whole doctrine of the specific elements of pathology which have played so conspicuous a part in the last twenty years. LECTURE IV. FEBRUARY 24, 18658. NUTRITION AND ITS CHANNELS, Action of the vessels—Relations between vessels and tissues—Liver—Brain—Mus cular coat of the stomach—Cartilage—Bone. Dependence of tissues upon vessels—Metastases—Vascular territories [Gefiissterri torien] (vascular unities)—Conveyance of nutriment in the juice-conveying canals (Saftkandle) of the tissues—Bone—Teeth—Fibro-cartilage—Cornea— Semilunar cartilages. Accorpine to the ideas usually entertained with re- gard to nutrition, the vessels are regarded as the canals by means of which not only the interchange of material (Stoffverkehr) is accomplished, but upon the assistance of which, sometimes actively and sometimes passively afforded, reliance is placed whenever it is required to control an individual part in its interchange of material. The regulating principle in the process of nutrition was long designated by an expression which has even crept into the language of the present day, namely, the ‘‘action of the vessels,” as if they were endowed with a special power of actively influencing the condition of the neighbouring histological constituents, As I pointed out to you the last time, when upon the subject of muscular fibres (p. 85), we can now-a-days only speak of action in the vessels as far as muscular fibres are present in them, and the vessels are thus 101 102 LECTURE IV, a enabled by the contraction of these fibres to grow narrower or shorter. This narrowing of their channel may have the effect of impeding transudation of fluids, whilst, on the contrary, in the case of the relaxation or paralysis of the muscular fibres, the widening of the vessel may favour such transudation. Let us admit this for the pre- sent, but allow me, before proceeding farther, to enter somewhat into the analysis of the mass of tissue which lies around the vessels, and is generally conceived to be of a very simple and uncomplicated nature. If we select parts where the vessels lie very closely packed, and there is perhaps nearly as much vessel as tissue, as, for example, the /iver, in which this condition really does occur (for a liver, when its vessels are full, contains nearly as large a volume of vessels as it does of proper hepatic substance), we see that the interstices which are left between the vessels are filled with quite a small number of cells. If we examine a single acinus of the liver by itself, we find, when a very lucky transverse section has been obtained, in its centre the eo vena centralis or intralobula- ris, which runs into the hepa- tic vein, at the periphery branches of the portal vein, which send capillary twigs in- to the interior. These at once form a network, which at first has long, but after- wards more regularly shaped, meshes, and extends in the direction of the central (or hepatic) vein, and at last terminates in it. The blood, therefore, after it has en- Fig. 28. Section from the periphery of the liver of a rabbit; the vessels com- pletely injected. 11 diameters. CAPILLARY VESSELS OF THE LIVER. 103 tered by the interlobular (or portal) vein, flows through the capillary network into the intralobular vein, whence, by means of the hepatic veins, it is conducted back again to the heart. Now, in the case of an injected liver, this network is seen to be so close that what interstices there are left seem almost to occupy less room than the ves- sels themselves. We can thus easily imagine how the older anatomists, such as Ruysch, came to be led by their injections to the supposition that nearly everything in the body was made up of vessels, and that the differ- ent organs were only distinguished by differences in the arrangement of their vessels. But just the opposite to what is observed in an injected preparation does the proportion between vessel and tissue appear to be in an ordinary specimen from a liver. In this the vessels are scarcely perceptible. A similar network is indeed seen, but it is the network formed by the hepatic-cells (Fig. 27), which, closely crowded, one against the other, fill up all the inter-spaces of the vessels. It is plain, there- fore, that the capillary and hepatic-cell networks are interwoven in the most intricate manner, so that cells belonging to the parenchyma of the liver everywhere lie in almost immediate contact with the walls of the vessels, there being at most a fine layer between the cells and the walls, concerning which it is still a matter of dispute amongst histologists whether it is to be regarded as a peculiar coat, constituting the finest gall-ducts, or only as a very small quantity of connective tissue accom- panying the vessels. \ In this extremely simple case, a tolerably simple rela- tion may certainly be assumed to exist between the ves- sels and the cells; it may be conceived that the blood which flows through the vessels may, in proportion to the degree in which they are contracted or dilated, and to its own quantity, exercise a direct influence upon the 104 LECTURE IV. adjoining cells. It might indeed be objected, with re- gard to the conditions of nutrition, that we have here to deal with quite a peculiar arrangement of the vessels, which are essentially of a venous nature, as being com- posed of ramifications of the portal and hepatic veins, but the hepatic artery also enters into the formation of this capillary network, so that the blood in it cannot be resolved into its individual arterial and venous consti- tuents. Injections from each of the vessels named ulti- mately find their way into the same capillary network. In most parts, however, the relations do not present such a simple form as in the liver ; considerable inter- spaces often separate the individual cells, and no incon- siderable quantities of these elements are enclosed in every capillary mesh. I show you here a second object derived from a fresh human brain—from a lunatic who died with his cerebrum ina highly hyperemic state. Fig. 29, The section has been made through the corpus striatum, which was of a deep red colour. You have a good view Fig. 29. Natural injection of the corpus striatum of a lunatic. a, a. Gaps desti- tute of vessels, and corresponding to the strands of nervous fibres which traverse the ganglion. 80 diameters. MUSCULAR COAT OF THE STOMACH. 105 of the naturally injected vessels ; and the width of the individual meshes of the capillary network may be clearly seen. The section has been carried transversely through the corpus striatum, and at certain intervals large, roundish spots may be distinguished, which ap- pear dark by transmitted light (Fig. 29, a, a, a), but by reflected light and to the naked eye look white, and are formed by transverse sections of the nervous fibres which run in long strands towards the spinal marrow. The vessels scarcely penetrate into them. The rest of the mass, on the other hand, consists of the proper grey substance of the corpus striatum, within which a vascu- lar network with very fine meshes is distributed, the grey substance of the nervous centres being everywhere, both in their interior and in their cortical substance, dis- tinguished from the white by its greater vascularity. A few large vessels are observable in the object, giving off branches, the ramifications of which continually dimi- nish in size, until at last they terminate in capillary net- works with very fine meshes. Still, however close this network may be, every element of the substance of the brain by no means comes into immediate contact with a capillary vessel. The third object is a very slightly magnified injected preparation from the mus- Fre. 30. cular coat of the stomach, » in which, with a high power, the direction of the muscu- lar fibres is indicated by & fine longitudinal striz ; here the vessels form tolerably regular networks, connect- § ed with one another by~ Fig. 30. Injected preparation from the muscular coat of the stomach of a rabbit, magnified 11 diameters, 106 LECTURE IV. transverse anastomoses, and splitting up into smaller and smaller vessels, which form fine networks within the tissue, so that the whole of it is by this means map- ped out into a series of irregularly four-sided divisions. To each of the ultimate intervascular spaces is allotted a certain number of muscular elements, so that the ves- sels are in some parts in contact with the muscular fibres, whilst in others they lie at a greater distance from them. If we go on in this way examining the structure of the different organs and tissues, we pass from such as, when injected, seem to consist almost entirely of vessels, in time to those which contain scarcely any, and at last to such as really have none at all. This is most strikingly the case with the connective tissues, and the most im- portant amongst these are bone and cartilage. Perfectly developed cartilage has no longer any vessels at all; perfectly developed bone certainly contains vessels, but in a very variable degree. That perfectly developed cartilage contains no vessels, you will not, I suppose, call upon me to convince you by any additional, special proofs, inasmuch as you have seen various prepara- tions of cartilage, in which not a trace of them was to be observed. (Figs. 6, 9, 22.) I now place before you a piece of young cartilage, because you can see in it what the arrangement of the vessels in cartilage is at an earlier period. It is a section from the calcaneum of a new-born child, and in it the vessels run up from the already-formed central osseous mass into the cartilage which still remains. The preparation shows along the outermost surface of the cartilage the transition from it into the perichondrium, whilst the lower part of the sec- tion is taken from the border of the already-formed bone. From this part large vessels are seen running up and terminating in the middle of the cartilage by VESSELS IN CARTILAGE. 107 the formation of loops and plexuses, as it were a tree of villi (Zottenbaum) in the cartilage, and very much resembling a villus of the chorion of the ovum. In fact, the vessels mount up into the cartilage from the nutrient artery of the bone, but only to a certain height. There they form real loops, and at length break up into a fine Fig. 81. plexus of capillaries, out of which veins are ultimately formed, and run out again pretty near the spot where the artery entered. But the whole of the rest of the mass consists of non-vascular cartilage, the corpuscles of which, with a low power, look like fine points. Thus there is a whole host of cartilage-corpuscles lying be- tween the terminal loops and the external surface, and the whole of this layer is therefore dependent for its Fig. 81. Section of cartilage from the caleaneum of a new-born child. ©. The cartilage, with its cells indicated by fine points. P. Perichondrium and adjoining fibrous tissue. a. Inferior border very near to the line of junction between the cartilage and the bone, with the vascular loops ascending from the nutrient artery. 6, 6. Vessels which make their way through the perichondrium in the direction of the cartilage. 11 diameters. 108 LECTURE IV. nutrition upon the juice which exudes from the terminal loops and permeates the tissue, though to a trifling ex- tent also upon the materials which the scanty vessels of the perichondrium convey to it. The vessels which spring from the nutrient artery mark in all bones, at a tolerably early period, pretty exactly the limits to which the ossification subsequently proceeds, whilst the rem- nants of the cartilage which remain bordering upon the joint never contain vessels. With regard to the bones themselves, the disposition of their blood-vessels is in itself tolerably simple, but at the same time very characteristic. If we examine the compact substance, we can usually, even with the naked eye, distinguish upon its surface small openings throygh which vessels enter from the periosteum. With a mode- Fig. 32. Longitudinal section from the cortex of a sclerotic tibia. a, a. Medullary (vascular [Haversian]) canals, between them the bone-corpuscles for the most part parallel; but at 6 (in transverse section) concentrically arranged. 80 diameters. BONE-CORPUSCLES. 109 rately high power we discover that these vessels (Fig. 32, 2) immediately beneath the surface form a network with somewhat long’ meshes, or a series of tubes anasto- mosing with one another and, generally speaking, run- ning longitudinally, for though they sometimes take a somewhat more oblique course inwardly, they still essentially maintain a longitudinal direction. Between these meshes there remain comparatively wide inter- spaces, within which, precisely as we before saw the cartilage cells, we here see the bone-corpuscles, and indeed also in a longitudinal direction, parallel to the surface. If the same part be examined in transverse section, we of course see, where the longitudinal canals were previously observed, nothing but their transverse sections here and there united by oblique communica- tions! Between them lies the proper osseous tissue, deposited in lamellar layers, some of them parallel to Fie. 383. the surface, some concentrically arranged around the vessels. In the deeper layers of the compact substance Fig. 38. Section of bone. a. Transverse section of medullary (vascular [Haver- sian]) canal, around which the concentric lamella, J, lie with bone-corpuscles and anastomosing canaliculi. 1+. Lamelle divided longitudinally and parallel. 4. Irre- gular arrangement in the oldest layers of bone. vw. Vascularcanal. 280 diameters. 110 LECTURE IV. this concentric arrangement around the vessels con- stantly prevails. Between these more lamellated parts is left a small quantity of osseous substance (Fig. 33, 2) which does not present the same structure, but is arranged upon another, and independent, plan. Upon more accurate examina- tion it is seen to be formed of little columns, which are generally perpendicular to the long axis of the bone, but sometimes curve round, and so become parallel to the long axis. These are the remains of the spicula first formed during the growth of the bone in thickness, and are therefore of older date. As in the sections which are obtained by grinding down bone, the vessels themselves cannot for the most part any longer be distinguished, the cavities [Haversian canals] (Fig. 32, a, 33, a, v,) in which they run have been named medullary canals, improperly, inasmuch as Fig. 34. Bone-corpuscles from a morbid formation of bone in the dura mater of the brain. Their branching and anastomosing prolongations (canaliculi) are seen, as well us minute spots upon their walls, marking the funnel-shaped commence ments of the canaliculi, 600 diameters, VASCULAR CANALS OF BONES. 111 thexe is usually no marrow contained in these narrow channels ; they should properly be called vascular canals ; still the other term is so universally received, that it is even employed in cases where the wall of the vessel is in immediate contact with the internal surface of the cavity. Immediately surrounding these canals we see a series of peculiar structures; oblong or roundish bodies which usually appear black when the object is not fully brought into focus, and are provided with jaggs or processes. They used to be called bone-corpuscles, and their pro- cesses bone-canals (canaliculi ossei); and as the view was originally entertained that the calcareous matter was really deposited in them, and that the dark appear- ance which they usually present when viewed by trans- mitted light resulted from the presence of this matter, the canals were also termed canaliculi chalicophori, a name which has now been altogether abandoned, because convincing proofs have been obtained that, so far from being contained in them, the lime is, on the contrary, diffused throughout the homogeneous basis-substance which lies between them. As soon as this discovery was made, that, namely, the distribution of the lime in the osseous tissue took place in a manner just the reverse of thatin which it had been supposed it did, the other extreme was immediately run into, and for the name of bone-corpuscles that of bone- cavities (lacunze) was substituted, and it was assumed that bone contained nothing but a series of empty cavi- ties and canals, which were indeed penetrated by a fluid, but still were really nothing more than fissures in the bone. Some few observers indeed actually called them bone fissures NowI have endeavoured to demon- strate in various manners that they are real corpuscles, and not mere cavities in a dense basis-tissue, but struc- tures provided with special walls and boundaries of their 112 LECTURE IV. own, which separate them from the intermediate sub- stance. For by the help of chemical reagents (concen. trated mineral acids, and particularly hydrochloric acid) we are enabled, by dissolving the basis-substance, namely, to disengage the corpuscles from it. In this way we furnish, I think, the most complete demonstration that they are really independent structures. Besides, a nucleus may be distinguished within these bodies ; and, even without entering into the history of their develop- ment, we discover that here too we have once more to deal with cellular elements of a stellate form. Bone therefore exhibits in its composition a tissue, containing, in an apparently altogether homogeneous basis-substance, peculiar, stellate bone-cells distributed in a very regular manner. The intervals which exist between every two of the vessels in bone are often very considerable ; whole sys- tems of lamella, beset with numerous bone-corpuscles, thrust themselves in between the medullary canal. Here it is certainly difficult to conceive the nutrition of so complicated an apparatus to depend upon the action of vessels some of them so remote, and especially so, to un- derstand how every individual particle of this extensive compound mass can manage to maintain a special rela- tion of nutrition to» the vessels. For experience shows us that every single bone-corpuscle really possesses con- ditions of nutrition peculiar to itself, I have laid these details before you, in order to point out to you the gradual transition which takes place from the vascular and abundantly vascular, to the scantily vascular and non-vascular parts. If we would form a simple conception of the conditions of nutrition, I think we must lay it down asa logical principle, that what- ., ever is enunciated with regard to the nutrition of very vascular parts, must also hold good for that of scantily DEPENDENCE OF TISSUES UPON THE VESSELS. 113 and non-vascular parts; and that, if the nutrition of individual parts is considered to be directly dependent upon the vessels or the blood, it must at all events be demonstrated that all the elements which stand in im- mediate connection with one and the same vessel, and are assigned to a single vessel for their support, present conditions of life essentially similar. In the case of bone it would be necessary to show that every system of lamellae which has only one vessel for its nutrition, always exhibits a similar state of nutrition. For if that vessel, or the blood which circulates in it, be the active agent concerned in the nutrition, the utmost that can be admitted is, that one part of the elements may be more, another less, subjected to their influence ; but still it must essentially be a common and similar influence which they experience. That this is no unreasonable requirement, that a certain dependency of definite terri- tories of tissue upon definite vessels must undoubtedly be admitted, the most beautiful illustrations are afforded us in the doctrine of metastases, in the study of the changes which are effected by the occlusion of single capillary vessels, and with which we have become ac- quainted from the history of capillary embolia. In such cases, in fact, we see that a whole portion of tissue, as far as its immediate connection with a vessel extends, in its pathological relations also constitutes a whole—a vas- cular unity. But this vascular unity to a finer appre- hension still appears a compound, and it is not sufficient to split up the body into vessel-territories (Gefissterri- torien) alone, but within them a further division must be made into cell-territories (Zellenterritorien). - This view has, I think, been essentially furthered by our having discovered, as I lately pointed out to you (p. 76), the existence of a special system of anastomosing ele- ments in the connective-tissues, and by our having is 8 114 LECTURE IV. this manner filled the place of the vasa serosa (which the older writers imagined as a complement to the capilla- ries for these ultimate purposes of nutrition) with some- thing definite, by means of which the circulation of nu- tritive juices is rendered possible in parts which are in themselves poor in vessels. To keep to bone, we should Fie. 35. scarcely be justified in assuming the existence of vasa serosa in it. The hard basis-substance is throughout Fig. 85. Section of an osseous plate from the arachnoid of the cerebrum, but quite normal in its structure. A branching vascular (medullary) canal is seen with canaliculi opening into it, and leading to the bone corpuscles. 350 diameters, NUTRITION OF BONE. 115 uniformly filled with calcareous salts, so uniformly indeed, that no interval can be perceived between the indivi- dual calcareous particles. Though some few writers have assumed that little granules can be distinguished in it, this is an error. The only differentiation which can be seen is caused by the prolongation into the basis-sub- stance of the canaliculi, which all ultimately lead back to the bodies of the bone-cells (bone-corpuscles) and in their turn give out branches. The peripheral extremi- ties of these little branches or processes extend right up to the surface of the vascular (medullary) canal. They are therefore inserted exactly where the membrane of the vessel begins (Fig. 35), for they can be distinctly perceived as very minute orifices upon the wall of the canal. Now since the different bone-corpuscles are in their turn distinctly connected with one another, means are afforded by which a certain quantity of juice taken up from the surface of the vascular canal is not diffused throughout the whole mass of tissue, but confined to these delicate, continuous, and specially provided chan- nels, and forced to move onwards in canals which are inaccessible to injections from the vessel. For a time it was believed that the canaliculi could be injected from the vessel, but this is only possible when the vascular canal has become empty by maceration. This’ is a condition precisely similar to what we observe in the ¢eeth, in which the canaliculi can be in- jected from the pulp-cavity when empty. If a solution of carmine be injected into this cavity, the dental canali- culi are displayed in the form of numerous tubules run- ning up to the surface side by side in a radiated manner. The substance of the teeth also forms a tolerably broad layer of non-vascular material. Vessels are found no- where but in the pulp-cavity, in proceeding from which outwards we find nothing but the proper substance of 116 LECTURE IV. the tooth (dentine) with its system of tubes, which ex- tend nearly up to the surface, and in the root of the tooth are directly continuous with a layer of real bony substance (cement) the corpuscles of which are seated upon the. ends of the tubes. A provision for the con- veyance of the juices similar to that which in bone ori- ginates in the marrow, here takes its rise in the pulp, whence the nutritive fluid can be conveyed up to the surface by the means of tubes. These systems of tubes which are found in such a very marked form in bone and the teeth, are to be seen with far less distinctness in the soft structures, and it is chiefly for this reason, I imagine, that the analogy which exists between the soft connective tissues and the hard texture of bone has rot been clearly comprehended. These sys- tems are most distinctly seen in parts which are more of a cartilaginous nature, as, for example, in fibro-cartilage. But it is a fact of great significance that we find a series of transitional forms between cartilage and the other connective tissues, in which the same conditions are con- stantly repeated. In the first place, parts which chemi- cally belong to the class of cartilages, for example, the cornea, which yields chondrine when boiled, although nobody regards it as real cartilage. But more striking is the arrangement in those parts in which the external appearance speaks in favour of a cartilaginous nature, but the chemical properties do not correspond, as for example, in the semi-lunar cartilages (Bandscheiben) of the knee-joint, which are interposed between the femur and tibia for the purpose of protecting the articular cartilages from too violent contact. These parts, which even now are generally described as cartilage, yield no chondrine on boiling, but gelatine ; and yet, in this hard connective tissue, we meet with the same system of anas- tomosing corpuscles that prevails in the cornea and in CANALS IN THE SEMI-LUNAR CARTILAGES. 117 fibro-cartilage, and it is displayed with unusual distinct- ness and clearness. Vessels are almost entirely wanting in these cartilages, but in ex- change they contain a system of tubes of rare beauty. On making a section, we see that the whole is in the first place mapped out into large divi sions, exactly like a tendon ; these are subdivided into smaller ones, and these are pervaded by a fine, stellate | system of tubes, or, if youk will, of cells, inasmuch as the notion of a tube and that of a cell here quite coincide. The networks of cells which here * form the system of tubes, terminate externally in the septa bounding the individual divisions, and we here see in close proximity considerable collections of spindle-shaped cells. In these cartilages, too, the whole mass of tissue is only connected by its exterior with the circulatory system ; everything that penetrates into the interior must pass by a very circuitous route through a system of canals with numerous anastomoses, and the nutrition of the in- ternal parts is altogether dependent upon this mode of conveyance. The semi-lunar cartilages are structures of considerable extent and great density, and as they are entirely dependent for their nutrition upon this ultimate, minute system of cells, we have in them, much more Fig. 36, Fig. 86. Section from the semi-lunar cartilage of the knee-joint of achild. a. Bands of fibres, with spindle-shaped, parallel and anastomosing cells (seen in longi- tudinal section). 4. Cells, forming a network, with broad, branching, and anasto- mosing canaliculi (seen in transverse section). Treated with acetic acid. 350 diameters. 118 LECTURE IV. than in cartilage, to deal with such an arrangement for the supply of nutritive juices, as cannot be under the direct control of the vessels. __ For the sake of elucidation, I will merely add that the ultimate elements are seen to consist of very delicate ‘cells, which are prolonged into fine filaments, that in their turn ramify, and look, when cut across, like small points in which a clear centre can be recognised. The filaments can ultimately be very distinctly traced back to the common cell just asin bone. They are extremely fine tubes which are intimately connected with one an- other, only that here they are in certain spots collected into large groups, by means of which the conveyance of the nutritive juice is principally effected, and that the intercellular substance in no instance becomes infiltrated with lime, but always preserves its character as connec- tive tissue. I BG TU Ee OV, FEBRUARY 27, 1858. NUTRITION, AND CONVEYANOE OF THE NUTRITIVE JUICES. Tendons—Cornea—Umbilical cord, &: Elastic tissue—Corium. Loose connective tissue—Tunica dartos, Importance of cells in the special distribution of the nutritive juices, ALLow me, gentlemen, as a supplement to what we saw and discussed in the preceding lecture, to lay before you a few more preparations in illustration of that pecu- liar species of nutritive arrangement which we have already seen to exist in various tissues, and which, I hope, will appear to you of very great importance in pathological processes also. You will remember that the last object of our con- sideration was a ligamentous disc (Bandscheibe), as it occurs in its most marked form in the knee-joint in the so-called semi-lunar cartilages, which are really no car- tilages at all. On the contrary, they possess the qualities of a flat tendon, and the individual structural relations which we found in them, are repeated throughout the whole of the transverse section of a tendon. We have to-day a series of objects from the tendo Achillis, both of the adult and the child, displaying the different stages of its development ; and as this is, more- 119 120 LECTURE V. over a tendon which is of importance in more than one way in an operative point of view, I may, I am sure, be excused for speaking a little more at length concern- ing it. On the surface of a tendon we see, as you well know, with the naked eye, a series of parallel, whitish striz which run pretty close to one another in a longitudinal direction, and give rise to the characteristic glossy ap- pearance. In a microscopical longitudinal section these strie lie farther apart, so that the tendon presents a Fie. 37. somewhat fasciculated appearance and looks less homo- geneous than on the surface. This becomes much more evident in a transverse section, in which a series of Fig. 37. Transverse section from the tendo Achillis of an adult. From the sheath of the tendon, septa are seen at a, 6, and c, running inwardly, and uniting into a network so as to form the boundaries of the primary and secondary fasciculi. The larger ones (a and 6) generally contain vessels, the smaller ones (c) do not. Within the secondary fasciculi is seen the delicate network formed by the tendon-corpus- cles (reticulating cells—Netzzellen), or the intermediate system of juige-conveying , canals (Saftkanalsystem). 80 diameters, TENDONS. 121 smaller and larger divisions (bundles, fasciculi) are offered to the view. On magnifying the object, an internal arrangement is shown almost exactly corresponding to that which we have observed in the semi-lunar cartilages. Externally, the tendon is invested in its whole circumference by a fibrous mass, in which the vessels are contained, that are entwined around the tendon. From these at different points vessels proceed into the interior, where they are to be seen in the larger partitions which separate the fasciculi (Fig. 37, a); but into the interior of the fasci- culi themselves no trace of a vessel enters, any more than it does into the interior of the semi-lunar cartilages ; there, on the contrary, we again meet with the network of cells we have been talking about, or, in other words, the peculiar system of juice-conveying canals of which we lately considered the import in bone. Tendons may therefore in the first place be divided into larger (primary) bundles, and these in their turn into a certain number of smaller (secondary) fasciculi, which are separated by broadish bands of a fibrous sub- stance containing vessels and fibre-cells, so that a trans- verse section of a tendon presents a meshed appearance. From this intervening substance, which must not, how- ever, be regarded as a tissue of a peculiar description, there pass into the interior of the fasciculi stellate cells (tendon-corpuscles) which anastomose with another and establish a communication between the external vascular, and the internal non-vascular, parts of the fasciculi. This relation is, of course, much more evident in the tendons of children than in those of adults. The older the parts become, namely, the larger and finer do the processes of the cells in general become, so that in many sections we do not meet with the real bodies of the cells, but only see minute speck , which, by altering the focus, 122 LECTURE Y. may be traced into filaments—or point-like orifices. The individual cells, therefore, come to be more widely Fie. 38. separated, and it becomes more and more difficult to obtain a view of the whole of a cell at once. Besides, we must first obtain a clear notion of the relation be- tween a longitudinal and a transverse section. Where, namely, in a longitudinal section, there are spindle- shaped cells, in a transverse section will be seen stellate ones, and to the network of cells displayed in the trans- verse section corresponds the regular succession of spindle-shaped corpuscles, arranged in rows which we see in a longitudiual section, entirely in correspondence with the plan which we have shown to be followed in connective tissue. The cells, therefore, are here also only apparently simply spindle-shaped, when an exactly longitudinal section is examined; but if it has been Fig. 88. Transverse section from the interior of the tendo Achillis of a new-born, child. a. The intervening mass which separates the secondary fasciculi (corres ponding to Fig. 37, c), and entirely composed of densely aggregated spindle-shaped cells. Directly anastomosing with these, we see on both sides at 6, 6, reticulating and spindle-shaped cells running into the interior of the fasciculi. 3800 diameters. TENDONS—THEIR NUTRITION. 123 made a little obliquely, the lateral processes are per- ceived, by means of which the cells of one row commu- nicate with those of another. Fig. 89. Up to the present moment the progress of the growth of tendons after birth has not been made the subject of a regular investigation, and it is unknown whether any further multiplication of the cells takes place in them ; this much, however, is certain, that the cells in many places afterwards become much elongated, and the inter- vals between the individual nuclei extremely great. The actual structural relations, however, do not thereby experience any change ; the original cells also continue members of the great system of tubes, which in the per- fectly developed tendon pervades the whole tissue. Fig. 89. Longitudinal section from the interior of the tendo Achillis of a new- born child, a, a, a. Intervening bands. 46, b. Fasciculi. In both we see spindle- shaped, nucleated cells, partially anastomosing, with an inter-cellular substance slightly striated in a longitudinal direction, the cells being more crowded in the bands, and less numerous in the fasciculi. c. Section of an interstitial blood-vesseL. 260 diameters. 124 LECTURE V. Hence we see how, although the tendon contains nu vessels in its most internal parts, and, as may be ob- served in every case of tenotomy, receives but little blood by the external vessels of its sheath, and by the internal vessels of the septa between the larger fasciculi, it is possible, notwithstanding, for a uniform nutrition of the parts to take place. This we cannot imagine to be effected in any other way than by the distribution of nutritive juices in a regular manner throughout the entire substance of the tendon by means of special canals distinguishable from the vessels. The natural divisions of the tendon are, however, nearly entirely symmetrical, so that an equally large quantity of intercellular sub- stance falls to the share of every cellular element, and as the cell-networks in the interior can be directly traced into the dense bundles of cells of the septa, and these in their turn up to the vessels (Figs. 37, 38), we may, I think, unhesitatingly regard these reticulating cells as the channels for the transmission of this inter- mediate current of nutritive juice, which has no commu- nication by means of orifices with the general circu- lation. You have here a fresh instance in support of my view with regard to cell-territories. I would parcel out the whole tendon, not into primary and secondary fasciculi, but rather into certain series of cells connected in a reti- form manner ; to each series, moreover, I would assign a certain district of tissue, so that in a longitudinal sec- tion, for example, about half of each band of basis-sub- stance would belong to one, the other half to another series of cells. What is, therefore, regarded as consti- tuting the proper fasciculi of the tendon, would, accord- ing to this view, have really to be split up, and the ten- don portioned out into a great number of nutritive districts (Ernihrungs-Territorien), CORNEA—UMBILICAL CORD. 125 This is the condition which we everywhere find recur- ring in these tissues, and upon it will at the same time be found to depend, as I hope you will convince your- selves by direct observation, the size of the districts invaded by disease; every disease which essentially depends upon a disturbance in the internal disposition of the tissues is always made up of the sum of the separate changes occurring in such territories. But at the same time the pictures which are here offered to us afford a really zsthetical enjoyment through the delicacy of this arrangement, and I cannot deny that, as often as I look at a section of tendon, it is with a peculiar feeling of satisfaction that I contemplate these reticular arrange- ments, which effect a union between the exterior and the interior, and, excepting in bone, can in no structure be demonstrated with greater distinctness and clearness than in tendons. Considering the structure of the cornea and the dispo- sition of its parts, it would be most convenient, gentie- men, to proceed at once to the consideration of its his- tory, still I prefer reverting to it hereafter, inasmuch as itis at the same time the most suitable object for the demonstration of pathological changes. I will therefore only observe here, that in the same way that tendons have their peripheral system of vessels, and that their internal parts are nourished by a delicate juice-convey- ing system of tubes, so also in the cornea only the most minute vessels extend a few lines over its border, so that the central parts are completely destitute of vessels, as indeed they were obliged to be, in order to allow of the sransparency of the tissue. I should like, on the other hand, in connection with the foregoing tissues, to speak of one which has gene- rally met with but little special preference in histology, but is perhaps more likely to have some interest in your 126 LECTURE V. eyes, I mean the umbilical cord. Its substance (the so- called jelly (gelatina) of Wharton*) is also formed by one of those tissues which certainly contain vessels, but yet really possess none. The vessels which are trans- mitted through the umbilical cord, do not immediately contribute to its nourishment, at least not in the sense in which we speak of nutrient vessels in other parts. For when we speak of nutrient vessels, we always mean ves- sels which have capillaries in the parts which are to be nourished. The thoracic-aorta is not the nutrient ves- sel of the thorax, any more than the abdominal aorta, or the vena cava, is that of the abdominal viscera. We should expect, therefore, in the case of the umbilical cord to find umbilical capillaries in addition to the two umbilical arteries and the umbilical vein. But these arteries and this vein run their course to the placenta, without giving off a single small vessel, and it is only when they have reached that body that they begin to ramify. The only capillary vessels which are found in the whole length of the umbilical cord of a somewhat developed foetus do not extend more than about four or five lines (in rare instances a little farther), beyond the abdominal walls into that part of the cord which remains after birth, The Fig. 40. Fig. 40. The abdominal end of the umbilical cord of a nearly full-grown foetus, injected. .A. The abdominal wall. B. The permanent part of the cord with a congeries of injected vessels along its border. (. Its deciduous portion with the convolutions of the umbilical vessels. »v. The limits of the capillaries. * Lympheductus, vel gelatina, que eorum vices gerit, alterum succum albumini ovorum similorem abducit (a placenta) ad funiculum umbilicalem. (Thom. Whart. Adenographia, Amsteledami, 1659, p. 283.) THE UMBILICAL CORD. 127 farther up this vascular part extends, the greater the development of the navel. When the vascular layer is prolonged bat a very short distance the navel is greatly depressed ; when it reaches a long way up, a prominent navel is the result. The capillaries mark the limits of the permanent tissue ; the deciduous portion of the cord has no vessels of its own. This condition, which seems to be of great importance as regards the theory of nutrition, can be very easily seen with the naked eye in injected foetuses of five months and upwards, and in new-born children. The vascular layer terminates by a nearly straight line. Preparations of this sort do not, to be sure, furnish absolute proof, for there might happen to be a few minute vessels proceeding farther up, but invisible to the naked eye. But I formerly made this very point the subject of special investigation, and although I in- jected a number of umbilical cords, some from the arte- ries, and others from the veins, I never succeeded in discovering a single collateral vessel, however minute, that passed the limits of the persistent layer. The whole of the deciduous portion of the umbilical cord, that long portion which lies between its cutaneous end and its ter- mination in the placenta, is entirely destitute of capilla- ries, and there really exist no other vessels in it than the three large trunks. Now these are all of them re- markable for the great thickness of their walls, which, as we have really only known since the investigations of Kolliker, are enormously rich in muscular fibres. In a transverse section of the umbilical cord it may be observed, that the thick middle coat of the vessels is entirely composed ot smooth muscular fibres, lying in immediate contact one with the other, and in such abun- dance as is scarcely to be seen in any completely developed vessel. This peculiarity explains the extra- 128 LECTURE V. ordinary great contractility of the umbilical vessels which can be so readily seen in action on a large scal when mechanical stimuli are applied, when the vessel are divided with scissors or are pinched, or after th employment of electrical stimuli. Sometimes, upon thi application of external stimuli, they even contract t such a degree that their canal is entirely closed, and thu after birth, even without the application of a ligature as when, for example, the umbilical cord has been torr asunder, the bleeding may stop of itself. The thicknes of the walls of these vessels is, therefore, easily compre- hensible, for in addition to the muscular coat, which is of itself so thick, there is an internal, and, though it is certainly not very strongly developed, an external coat: and only after this do we come to the gelatinous, jelly- like tissue (mucous tissue (Schleimgewebe) ) of the umbili- cal cord. Through these layersf therefore, nutrition would have to take place, if the umbilical vessels were the nutrient vessels of the cord. Now 1 certainly can- Fig. 41. Fig. 41. Transverse section through a part of the umbilical cord. On the left is seen the section of an umbilical artery, with a very thick muscular coat, and to this, as one proceeds outwards, succeeds the gradually widening network of cells of the mucous tissue of the cord. 80 diameters. THE MUCOUS TISSUE OF THE UMBILICAL CORD. 129 not say with certainty whence the tissue of the umbilical cord derives its nourishment ; perhaps it receives nutri- tive matter from the liquor amnii, nor am I inclined to deny the possibility of nutriments passing through the walls of the vessels, or of the onward conveyance of nutritive materials from the small capillaries of the per- sistent portion. In any case, however, a large extent of tissue lies at a distance from all vessels and from the surface, and is nourished and supported without the pre- sence of any minute system of blood-vessels in it. Fora long space of time, indeed, no one troubled himself any further about this tissue, because it was designated by the name of jelly, and thereby summarily ejected from the number of the tissues and thrust into the ambiguous group of mere accumulations of organic materials. I was the first to show that it is really a well-constructed tissue of a typical form, and that what constitutes the ielly in the more restricted sense of the term, is the expressible part of the intercellular substance, after the removal of which there remains a tissue containing a delicate network of anastomosing cellular elements, simi- lar to that which we have seen to exist in tendons and other parts. A section through the external layers of the umbilical cord exhibits a structure bearing great resemblance to the external layers of the cornea ; first, an epidermoidal stratum, beneath it a somewhat denser dermoid layer, and then the Whartonian jelly, which corresponds in texture to the subcutaneous cellular tissue, and is in some sort equivalent to it. This has a pecu- liarly interesting bearing upon the tissues of a more advanced period, inasmuch as, by thus ranking the jelly with subcutaneous tissue, we at the same time establish its very close relationship to the vitreous body, which is the only remnant of tissue that, as far as I have until now been able to make out, persists in man in this con- 9 130 LECTURE V. dition of jelly. It is the last remnant of the embryonic subcutaneous tissue which in the development of the eye is inverted with the lens (which was originally epidermis, p. 38). The proper substance of the umbilical cord consists of a reticulated tissue, the meshes of which contain mucus (mucin) and a few roundish cells, whilst its trabeculz are composed of a striated fibrous substance. In this lie stellate corpuscles, and when a good preparation has been obtained by treatment with acetic acid, a symme- trical network of cells is brought to view, which splits up the mass into such regular divisions, that by means of the anastomoses which subsist between these cells throughout the whole of the umbilical cord, a uniform Fia. 42, distribution of the nutritive juices throughout the whole of its substance is in this instance also rendered possible. Fig. 42. Transverse section of the mucous tissue of the umbilical cord, exhibiting the network formed by the stellate corpuscles, after the application of acetic acid and glycerine. 300 diameters. CONNECTIVE (CELLULAR) TISSUE. 131 I have up to the present time, gentlemen, brought to your notice a series of tissues all of which agree in con- taining either very few capillary vessels, or none at all. In all these cases the conclusion to be drawn seems to be very simple—that, namely, the peculiar cellular, canali- cular arrangement which they possess serves for the cir- culation of juices. It might, however, be supposed that this was an exceptional property, appertaining only to the non- or scantily-vascular and, generally speaking, hard, parts ; and I must therefore add a few words con- cerning the soft textures which possess a similar struc- ture. All the tissues which we have hitherto considered, belong, in accordance with the classification which I have already given you, to the series of connective tissues ; fibro-cartilage, fibrous or tendinous tissue, mucous tissue, bone and the teeth, must one and all be considered as belonging to the same class. But to the same category belongs also the whole mass of what has usually been included under the name of cellular tissue (Zellgewebe), and for which the name proposed by Johannes Miiller, connective tissue (Bindegewebe) is the most appropriate ; that substance, which fills up the interstices in the most different organs, sometimes in greater, sometimes in less, quantity—which renders the gliding of parts one upon the other possible, and formerly was imagined to enclose considerable spaces (cells in an inexact sense of the word), filled with a gaseous vapor or with moisture. Of this kind is the peculiar interstitial, or connective, tissue, such as we meet with in the interior of the larger muscles between the several primitive fasciculi and in a still larger quantity between the several parcels, or bundles, of primitive fasciculi. Numerous arteries, veins, and capillaries lie in it; and the arrangements for its nutrition are the most favorable that can be imagined. Notwithstanding this, however, there exists in it also, in 132 LECTURE V. addition to its blood-vessels, a more delicate system of nutrient channels, precisely similar to that with which we have just become acquainted ; only that, wherever it is specially required, in particular parts a peculiar change takes place in the cells, the place of the simple cell-networks and -fibres being gradually occupied by a more compact structure, which originates in a direct transformation of them, namely, the so-called elastic tissue. A few months after I had made known my first obser- vations concerning the eystems of tubes existing in the connective tissues, Donders published his concerning the transformation of the cells of connective, into the ele- ments of elastic, tissue—a discovery which has essen- tially contributed to the completion of the history of connective tissue. If this tissue, namely, be examined at points where it is liable to be much stretched, and where consequently it must be endowed with great power of resistance, the elastic fibres will be found arranged and distributed in it in the same way that the cells and Fia, 43. Fig. 43. Elastic networks and fibres from the subcutaneous tissue of the abdomen ofa woman. a, a. Large elastic bodies (cell-bodies), with numerous anastomosing processes. 6,%, Dense elastic bands of fibres, on the border of larger meshes. ¢,¢ Moderately thick fibres, spirally coiled up at the end. d, d. Finer elastic fibres, at« with more minute spiral coils, 300 diameters, FIBRES OF ELASTIC TISSUE. 133 cell-tubules of connective tissue usually are, and the transformation of these latter into the former can gradu- ally be traced with such distinctness, that there remains no doubt, that even the coarser elastic fibres directly result from a chemical change and condensation of the walls of the cells themselves. Where originally there lay a cell, provided with a delicate membrane and elongated processes, there we see the membrane gradu- ally increasing in thickness and refracting the light more strongly, whilst the proper cell-contents continually decrease and finally disappear. The whole structure becomes in this way more homogeneous, and to a certain extent sclerotic, and acquires an incredible power of resisting the influence of reagents, so that it is only after long-continued action that even the strongest caustic substances are able to destroy it, whilst it com- pletely resists the caustic alkalies and acids in the degree of concentration usually employed in microscopi- cal investigations. The farther this change advances, the more does the elasticity of the parts increase, and in sections we usually find these fibres not straight or elongated, but tortuous, curled up, spirally coiled, or forming little zigzags (Fig. 43, c, e). These are the elements which in virtue of their great elasticity cause retraction in those parts in which they are found in con- siderable quantity, as, for example, in the arteries. The fine elastic fibres, which are those that possess the greatest extensibility, are usually distinguished from the broader ones which certainly do not present themselves in tortuous forms. As far as regards their origin, how- ever, there seems to be no difference between the two kinds ; both are derived from connective-tissue cells, and their subsequent arrangement is only a reproduction of the original plan. In the place of a tissue, consisting of a basis-substance and anastomosing, reticulated cells, 134 LECTURE V. there afterwards arises a tissue with its basis-substance mapped out by large elastic networks with extremely compact and tough fibres. It has not up to the present time positively been determined, whether in the course of this transformation the condensation (sclerosis) of the walls of the cells pro- ceeds to such a pitch as entirely to obliterate their cavity, and thus completely destroy their powers of conduction, or whether a small cavity remains in their interior. In transverse sections of fine elastic fibres, it looks as if the latter were the case, and there is therefore ground for the supposition, that in the trans- formation of the corpuscles of connective tissue into elastic fibres, nothing more than a condensation and thickening, and at the same time a chemical metamor- phosis of the membrane, takes place, but that ultimately, however, a very small portion of the cell-cavity remains. What sort of a substance it is that constitutes the elastic parts, has not been determined, because it is not possible to accomplish their solution by any means; with a part of the products of the decomposition of this tissue we are, indeed, acquainted, but nothing further is known concerning its chemical constitution. But from this no decision can be arrived at with respect either to its com- position, or position in a chemical point of view with regard to other tissues. This kind of transformation prevails to an extraordi- nary extent in the skin, especially in the deeper layers of the corium proper, and to it is chiefly owing the extraordinary resistance of this tissue which we so gratefully acknowledge when daily testing it in the soles of our shoes. For the firmness of the individual layers of the skin depends essentially upon the greater or less quantity of elastic fibres contained in them.. The most superficial part of the corium immediately beneath the ve ELASTIC TISSUE OF THE SKIN- 135 rete mucosum is formed by the papillary portion (Papil- larkérper), by which we are to understand not only the papillz themselves, but also a continuous layer of cori- aceous substance running along horizontally beneath them ; it is under this that the coarse elastic networks begin, whilst only fine elastic fibres, and these in a fasci- cular form, ascend into the papille themselves, at the base of which they begin to form fine and close-meshed networks (Figs. 16, P, P; 83, A.e; D,c). These latter are connected inferiorly with the very thick and coarse elastic network which pervades the middle and toughest portion of the skin, the corzwm proper ; below this comes a more coarsely meshed network within the less firm, but nevertheless very soltd, undermost layer of the cutis, which passes inferiorly into the adipose or subcutaneous tissue. In the places where such a transformation into elastic tissue has taken place, there are trequently scarcely any distinct cells to be found. This is the case not merely in the skin, but also especially in certain parts of the middle coat of arteries, and particularly in the aorta. Here the network of elastic fibres attains such a prepon- derance, that it is only with great care that minute cellu- lar elements can here and there be detected. In the skin, on the other hand, in addition to the elastic fibres, a somewhat greater number of small corpuscles are found, which have retained their cellular nature, though they are certainly so extremely minute that they must be specially sought for. They generally lie in the inter- stices of the large-meshed networks, where they either form a system with perfect anastomoses and small meshes, or else appear in the shape of more isolated, roundish bodies, in consequence of the individual cells not being very distinctly connected with one another. This is especially the case in the papillary portion of the 136 LECTURE V. skin, which both in its continuous layer and in the papille contains nucleated cells, in direct contrast with the corium proper, which at the same time is less vascu- lar. Buta far greater number of vessels was certainly needed in the former part, inasmuch as they have at the same time to furnish nutritive material for the whole Fie. 44. stratum of cuticle which lies above the papille ; never- theless, however, there is left only a small quantity of juice at the disposition of the papillae as such. Every papille, therefore corresponds to a certain (vascular) district of the superjacent cuticle, whilst on the other hand it is itself resolved into as many elementary (histo- logical) districts as there are elements (cells) in it. In the scrotum the subcutaneous tissue (the dartos) presents peculiar interest, from the fact of its being par- ticularly rich in vessels and nerves, quite in accordance with the peculiar import of the part; and besides from its possessing an enormous quantity of muscular tissue, consisting, in fact, of those little cutaneous muscles, which I lately described to you (p. 58). These are the really active elements of the contractile tunica dartos. In this very part in which formerly a contractile connec- tive substance was considered to exist. the quantity of the little cutaneous muscles is extremely large, and the Fig. 44. Vertical section from an injected preparation of the skin. . Epider- mis. R. Rete mucosum. /P. Papille of the skin, with their ascending and descending vessels ( loops). C. Cutis. 11 diameters. THE DARTOS. 137 rug of the scrotum are produced solely and exclusively by the contraction of these minute fasciculi, which, espe- cially after they have been coloured with carmine, can very easily be distinguished from the connective tissue. Fie, 45, They are of pretty nearly the same breadth, broader for the most part than the bundles of connective tissue ; and in them the individual elements are arranged in the shape of long, smooth fibre-cells. Every muscular fasci- culus, after it has been treated with acetic acid, presents at regular intervals those peculiar, long, frequently Fig. 45. Section from the tunica dartos of the scrotum. Side by side and paral- lel are seen, an artery (a), a vein (v), and a nerve (x); the first two with small branches. On the right and left of them organic muscular fasciculi (m, m), and in the interspaces soft connective tissue (c, c), with large anastomosing cells and fine elastic fibres. 300 diameters, 1388 LECTURE V. staff-shaped nuclei, and between them is seen a delicate division of the substance into separate cells, the contents of which have a slightly granular appearance. These are the wrinklers of the scrotum (corrugatores scrott), Besides, we also find in the extremely soft membrane a certain number of fine elastic elements, and in greater quantity the ordinary, soft, wavy connective tissue, with a great number of relatively voluminous, spindle-shaped and reticulated, granular, nucleated, cells. These persistent cells of connective tissue had pre- viously been totally overlooked, its fibrils having been regarded as its real elements. If, namely, the individual constituents of connective tissue be separated from one another, little bundles are obtained of a wavy form and streaky, fibrillar appearance. According to Reichert, indeed, this appearance is merely due to the formation of folds, an idea which ought not perhaps to be admitted to the extent in which it was advanced, but which has not been altogether refuted, inasmuch as a complete iso- lation of the fibrils can never be effected excepting by artificial means. At all events a homogeneous basis- substance, which holds the fasciculi together, must be assumed to exist in addition to the fibrils. This, how- ever, is a question of subordinate importance. On the other hand, it is extremely important to know, that wherever this lax tissue is met with, whether beneath the cutis, in the interspaces of muscle, or in serous mem- branes, it is pervaded by cells which for the most part anastomose (so as in longitudinal sections to form paral- lel rows, in transverse ones networks), and separate the bundles of connective tissue from one another, in much the same way that the corpuscles of bone separate its different lamella. In addition, the most manifold vascular connections are everywhere met with ; indeed, the ves- sels are so numerous, that a special nutrient canalicular THE DARTOS, 139 system in the tissue might even appear altogether unue- cessary. But this tissue also, however favourably its capillary channels may be disposed, stands in need of an arrangement of such a nature as to render a special dis- tribution of the nutritive juices to the separate cellular dis- tricts possible. It is only when we conceive the absorp- tion of nutritive matter to be a consequence of the activity (attraction) of the elements of the tissue them- selves, that we are able to comprehend how it is that the individual districts are not exposed every moment to an inundation on the part of the blood, but the proffered material is, on the contrary, taken up into the parts only in accordance with the requirements of the moment, and is conveyed to the individual districts in such a quantity, that in general at least, as long as any possibility of its maintenance exists, one part cannot be essentially de- -frauded by the others. LECTURE Vi. MARCH 3, 1858, NUTRITION AND CIROULATION. Arteries—Capillaries—Continuity of their membrane—Its porosity—Hsmorrhag by transudation (per diapedesin) —Veins—Vessels during pregnancy. Properties of the walls of vessels: 1. Contractility—Rhythmical movement—Active or irritative byperemia- Ischamia—Counter irritants. 2. Elasticity and its importance as regards the rapidity and uniformity of th current of blood—Dilatation of the vessels. 3. Permeability—Diffusion—Specific affinities—Relations between the suppl of blood and nutrition—Glandular secretion (liver)—Specific action of th elements of the tissues. Dyscrasia—Its transitory character and local origin—Dyscrasia of drunkards- Hemorrhagic diathesis—Sy philis. I HAVE endeavoured, gentlemen, in the last two lectures to present to you a somewhat detailed picture of th more delicate arrangements which prevail in the bod: for the conveyance of the different currents of nutritiv juices, and particularly for the conveyance of those cur rents in which the juices themselves are more hidde: from observation. Allow me to-day to pass on to th consideration of the larger channels and nobler juices which, according to prevailing opinion, stand more in th foreground. The distribution of the blood takes place, as is we known, within the vessels in the following manner: Th arteries divide into finer and finer branches, and whils 140 ARTERIES. 141 they thus divide, the character of their walls gradually undergoes such alterations, that at last minute canals, the so-called capillary vessels, appear, provided with a membrane as simple as any that is ever met with in the body. The histological appearances which present them- selves in these different vessels are as follows: On isolating an artery we find that its walls are rela- tively very thick, and in those arteries which can be fol- lowed with the naked eye, not only the well-known three coats are distinguished with the help of the micro- scope, but in addition to these, a fine epithelial layer, which invests the internal surface and is not wont to be included in the class of structures usually termed coats The internal and external coats are essentially forma- tions of connective tissue, which in the larger arteries display a continually increasing quantity of elastic fibres ; between them lies the relatively thick middle, or circu- lar-fibre, coat, which, as being the seat of the muscular fibres, constitutes what may be almost termed the most important component of the arterial walls. These mus- cular fibres are found in the greatest abundance in the middle-sized and smaller arteries, whilst in the very large ones, and especially in the aorta, elastic layers form the predominant constituent even of the circular-fibre coat. In small arteries, on microscopical examination, there may be easily observed within this coat (Comp. Figs. 26, 6, 6; 45, @) little transverse striations, corres- ponding to the individual fibre-cells, and encircling the vessel in such dense array that we find fibre-cell by the side of fibre-cell without any interruption. The thick- ness of this layer can be readily estimated in conse- quence of the well-marked limits set to it upon the in- and out-side by the longitudinal-fibre coats; the only deceptive appearance is presented by certain round bodies, which are to be seen here and there in the sub- 142 LECTURE VI. stance of the circular-fibre coat, but only at the border of the vessel (Figs. 26, 6, 0; 46 ,m, m), and which look like round cells or nuclei scattered through the tissue. These are fibre-cells seen in apparent transverse section. The layer formed by the middle coat may be most distinctly seen, however, after the addition of acetic acid, which causes the appearance of a great number of oblong nuclei. It is this layer which, generally speaking, confers upon the arteries their specific character, and distinguishes them most clearly from the veins. There are, indeed, numerous veins in the body which possess considerable layers of muscular tissue—for example, the superficial cutaneous veins ; still, in the case of the smaller vessels, the occurrence of a distinctly marked circular-fibre coat Fig. 46. is so peculiarly characteristic of arterial vessels, that, wherever we meet with such a structure, we are at once inclined to assume the vessel to be arterial. These vessels, which must be included among the Fig. 46. A minute artery from the sheath of the tendon of one of the extensors of a hand just amputated. a, a. External coat. m, m. Middle coat, with well developed muscular layer. i, 7. Internal coat, partly with longitudinal folds, partly with longitudinal nuclei, in the side-branch brought well into view in consequence of the two external coats having been torn away. 3800 diameters. ARTERIES AND CAPILLARIES. 143 larger ones, although even when full of blood they only appear to the naked eye like red filaments, pass gradually into smaller ones, and with a power magnifying three hundred diameters, we see them breaking up into branches, into which, even when they are very small, the three coats are at first continued. It is only in the smallest branches that the muscular coat finally disap- pears, the intervals between the individual transverse fibres becoming wider and wider, and the internal coat (the nuclei of which lie in a longitudinal direction and cross those of the middle coat at right angles (Fig. 26, D, E,)), at the same time appearing more and more distinctly through it. The external coat also may be followed for a short distance farther (being in many places, as in the brain, rendered more evident by the in- terspersion of pigment or fat, Fig. 26, D, £), till at last it alsc becomes lost to view, and only a simple capillary remains (Fig. 3, c). The general supposition, therefore, is that the proper capillary membrane most nearly cor- responds to the internal coat of the larger vessels, and it is usually considered that the more complete a vessel becomes, the greater is the number of the coats which develop themselves around it. The real developmental relations which these parts bear to one another have, however, been by no means accurately determined. Within the true capillary region there is nothing further worthy of notice in the vessels than the nuclei I have previously mentioned, which correspond to the longitudinal axis of the vessel, and are so imbedded in its membrane, that it is impossible to discover any traces of a surrounding cell-wall. The capillary membrane is seen to be quite uniform, absolutely homogeneous and continuous (Fig. 3, c). Whilst even as lately as twenty years ago, it was a matter of discussion whether there did not exist vessels which were destitute of true walls, 144 LECTURE VI. and were nothing more than channellings or excava- tions in the parenchyma of organs, as well as whether vessels could not be produced by the formation of new tracks in communication with the old channels by the forcing asunder of the neighboring parenchyma ; there can, at the present time, be no longer any doubt as to the vascular system’s being everywhere continuously closed by membranes. In these it is not possible to descry any porosity Even the minute pores, which have recently been observed in different parts, have not, up to the present time, met with their counterparts in the capillary membrane, and when the porosity of this membrane is spoken of, the expression can only be admitted in a physical sense, as applying to invisible, really molecular interstices. A film of collodion is not more homogeneous, nor more continuous, than the mem- brane of a capillary. A series of possibilities, which used to be admitted, as that, for example, the continuity of the capillary membrane did not exist at certain points, simply fall to the ground. A ‘‘transudation” or dia- pedesis of the blood through the walls of vessels without the occurrence of any rupture cannot for an instant be admitted ; and although we cannot in every individual case point out the exact site of the rupture, it: is, not- withstanding, quite inconceivable that the blood with its corpuscles should be able to pass through the walls in any other way than through a hole in them. This is such a very natural deduction from ascertained histolo- gical facts, that all discussion upon the point is impos- sible. After the capillaries have pursued their course for a time, small veins begin gradually to form out of them, and generally run back in the neighbourhood of the arte- ries (Fig. 45, v). In them the characteristic circular- fibre coat of the arteries is in general wanting, or at least SMALL VEINS. 145 it is very much less developed. In its place we find in the middle coat of the larger veins toughish layers, which are not characterized so much by the absence of muscu- lar elements as by the greater abundance of elastic ele- ments which run in a longitudinal direction and are found in greater or less quantity in different localities. Fig. 47. In an inward direction there follow next the softer and more delicate layers of connective tissue of the internal: Fie. 48. Fig. 47. A. Epithelium from the femoral artery (‘ Archiv f. path. Anat.,’ vol. iii.,, figs. 9and 12, p. 596). a. Division of nucleus. B. Epithelium from veins of considerable size. a, a, Largish, granular, round, uni-nuclear cells (colourless blood-corpuscles?) 4, 6. Oblong and spindle- shaped cells, with divided nuclei and nucleoli. ¢. Large, flat cells, with two nuclei, of which each has three nucleoli, and is in process of division. d. Coherent epithe- lium, with the nuclei in a state of progressive division, one cell having six nuclei. 320 diameters. Fig. 48. Epithelium from the vessels of the kidney. A. Flat, spindle-shaped cells with longitudinal folds and large nuclei from a new-born child. B. Ribbon- like, nearly homogeneous, plate of epithelium with longitudinal nuclei from an adult. 350 diameters. : 10 146 LECTURE VI. coat, and lying on this is found, in the last place, a flat, extremely translucent layer of epithelium, which is very prone to protrude out of the cut end of the vessel, and gives the impression of spindle-shaped cells, so that it may easily be mistaken for spindle-shaped muscular cells, The smallest veins likewise possess this epithelium, but, with this exception, are, properly speaking, entirely com- posed of connective tissue provided with longitudinal nuclei (Fig. 45, v). These relations undergo no essential change even when the individual constituents of the vascular system expe- rience the most extreme enlargement. This is best seen in pregnancy, in which not merely in the uterus, but also in the vagina, the Fallopian tubes, the ovaries, and the ligaments of the uturus, both the large and small arteries and veins, as well as the capillaries, exhibit a very high degree of dilatation, so that the rest of the tissue, in spite of its having likewise in no inconsiderable degree become enlarged, is thereby virtually thrust into the back- ground. Nevertheless, however, parts of this puerperal sexual apparatus are extremely well adapted for display- ing the relation between the histological elements and the vascular (arterial) districts. In the fimbrie of the Fallopian tubes, for example, every plexus or loop formed towards the borders by the greatly dilated capil- laries encloses a certain number of large connectivé tis- sue cells, of which only a few lie in immediate contact with the vessels. In the ale vespertilionum we find, moreover, very beautifully displayed, a condition which is of frequent occurrence in the appendages of the gene- rative organs, and similar to what we lately considered in the scrotum; the vessels, namely, are accompanied by flat bundles of smooth muscle in considerable quan- tity which do not belong to them, but only follow the course of the vessels, and in part receive the vessels MUSCULAR ELEMENTS. 147 into them. This is an extremely important feature, in- asmuch as the contraction of these ligaments, in which muscular tissue is not generally considered to exist, is by no means solely to be ascribed to the blood-vessels, as James Traer only a short time ago endeavoured to establish ; on the contrary, we find thickish, flat bundles of muscle which run through the middle of the liga- ments, and during menstrual excitement enable contrac- tions to take place, similar to those which we can follow with such great distinctness in external portions of the genital passages. If now the question be raised how far the individual elements of the vessels are of importance in the body, it is at once evident that the contractile elements play the most important part in the coarser processes of the cir- sulation, whilst the elastic constituents come next, and the simply permeable, homogeneous membranes last. Let us first consider the import of the muscular elements, and more particularly in those vessels which are chiefly provided with them, namely the arteries. When an artery is acted upon by any influence which causes a contraction of its muscular tissue, it must of course become narrower, inasmuch as the contractile cells lie in rings around the vessel ; this contraction may under certain circumstances proceed until the canal is almost entirely obliterated, and the natural consequence then is that less blood penetrates into the corresponding part of the body. When, therefore, an artery is in any way exposed to a pathological irritant, or when it is excited by some physiological stimulus, its proper action cannot be displayed in any other way than by its becom- ing narrower. Now, indeed, that the muscular elements of the walls of the vessels have become known, the old doctrine might again be taken up, that, namely, the vessels, 148 LECTURE VI. like the heart, originated a kind of rhythmical pulsating movement, which was capable of directly furthering the onward movement of the blood, so that an arterial hyper- zmia would be the result of an increased pulsation in the vessels. We are indeed acquainted with one isolated fact which is a proof that a real rhythmical movement does take place in the arterial walls; and this was first observed by Schiff in the ears of rabbits. Its rhythm, however, does not at all correspond with that of the well-known arterial pulsation ; the only counterpart to it exists in the movements which had previously been observed by Wharton Jones in the veins of the wings of bats, and proceed in an extremely slow and quiet manner. I have studied these phenomena in bats, and convinced myself that the rhythm coincindes neither with the cardiac nor the respiratory movements ; it is quite a peculiar, but comparatively not very forcible, movement, and takes place after tolerably long pauses, longer ones than are observed in the case of the circulation and shorter than those which occur in respiration. In the ears of rabbits, also, the contractions of the arteries are far slower than the cardiac and respiratory movements. After excluding these phenomena, which manifestly ought not to be explained in such a way as to support the old view of the local occurrence of pulsation, the essential fact remains, that the muscular fibres of a ves- sel contract upon the application of every stimulus which sets them in action, but that this contraction is not pro- pagated in a peristaltic manner, but is confined to the spot irritated, or, at most, extends a little beyond, and continues for a certain length of time at this spot. The more muscular the vessel is, the more lasting and forcible is the contraction and the greater is the obstruction experienced by the current of blood. The smaller the CONTRACTION OF ARTERIES. 149 vessels, the more rapidly, on the contrary, do we see the contraction succeeded by a dilatation, which, however, is not in its turn followed by a contraction, as it would have to be to constitute a pulsation, but persists for a longer or shorter time. This dilatation is not of an. active, but of a passive nature, and results from the pressure of the blood upon the wall of the vessel which has become fatigued and opposes less resistance. If we now proceed to examine the phenomena which Fig. 49. Irregular contraction of small vessels from the web of a frog’s foot after the application of stimuli. Copied from Wharton Jones. 150 LECTURE VI. are usually grouped together under the title of active hyperemia, there can be no doubt but that the mus- cular tissue of the arteries is generally essentially con- cerned therein. We very commonly find we have to _ deal with processes in which the muscular fibres of the vessels have really been stimulated, and the contraction is succeeded by a state of relaxation, such as scarcely ever occurs in an equally marked manner in the rest of the muscles—a state which is manifestly the expression of a kind of fatigue and exhaustion, and is the longer persistent, the more energetic the stimulus which was applied. In small vessels with few muscular fibres, therefore, it often seems as if the stimuli really induced no contraction, in consequence of the extreme rapidity with which a state of relaxation is seen to set in, con- tinuing for a considerable time, and allowing of an in- creased influx of blood. This same condition of relaxation we can experiment- ally most easily produce by cutting the nerves supplying the vessels of a part, whilst the contraction can be effected to a very great extent by submitting these nerves to a very energetic stimulus. That our acquaint- ance with this kind of contraction is of so late a date, is explained by the fact that the stimuli applied to the nerves must be very powerful, and that, as Claude Ber- nard has shown, only strong electric currents are suffi- cient for the purpose. On the other hand, the condi- tions which ensue upon the section of the nerves are in most parts so complicated, that the dilatation escaped observation, until the lucky spot was discovered also by Bernard, and by the scction of the sympathetic nerves in the neck a reliable and convenient field for observa- tion was thrown open to experiment. We obtain therefore the important fact that, whether the widening of the vessel, or, in other words, the ACTIVE HYPERAZMIA. ° 151 relaxation of its muscular fibres, be produced directly by a paralysis of the nerve or an interruption of the nervous influence, or whether it be the indirect result of a previous stimulation, giving rise to exhaustion—that, I say, in every case we have to deal with a kind of paralysis of the walls of the vessel,.and that the process is incorrectly designated active hyperamia, inasmuch as the condition of the vessels in it is always a completely passive one. All that has been built up upon this assumed activity of the vessels, is, if not exactly built upon sand, still of an extremely ambiguous nature, and all the conclusions that have besides been drawn with regard to the important influence which the activity of the vessels was supposed to have upon the conditions of nutrition of the parts themselves, fall at the same time to the ground. When an artery is really in action, it gives rise to no hypersemia ; the more powerfully it acts, the more does it occasion aneemia, or, as I have designated it, eschemia, and the less or greater degree of activity in the artery determines the greater or less quantity of blood which in a unit of time can stream into a given part. The more active the vessel, the less the supply of blood. If, then, we have to deal with an hyperemia the result of irrita- tion, the most important point, therapeutically, is just this: to place the vessels in such a state of activity as will enable them to offer resistance to the onward rush of blood. This we can accomplish by means of what is called counter-irritation, a higher degree of irritation in an already irritated part, stimulating the fatigued mus- cular fibres of the vessel to persistent contraction, and thereby diminishing the supply of blood and leading the way to a regulation of the disturbance. In the very cases in which reaction, that is, regulatory activity, is most called for, the chief point is to overcome that state 152 ; LECTURE VI. of passiveness which maintains the (so-called active) hyperemia. If we now pass from the muscular to the elastec con- stituents of the vessels, we meet with a property which is of very great importance, on the one hand in the veins, the activity of which is in many cases to be wholly referred to their elastic elements, on the other hand, in the arteries, and particularly in the aorta and its larger branches. In these the elasticity of the walls has the effect of compensating for the loss which the pressure of the blood experiences from the systolic dilatation of the vessels, and of converting the uneven current produced by the jerking movements of the heart into an even one. If the walls of the vessels were not elastic, the stream of the blood would unquestionably be rendered very much slower, and at the same time, pulsation would take place throughout the whole extent of the vascular apparatus as fur as the capillaries, for the same jerking movement which is communicated to the blood at the commencement of the aortic system would continue even into the smallest ramifications. But every observation we make in living animals teaches us that within the capillaries the stream is a continuous one. This equable onward movement is effected by the elasticity of the walls of the arteries, in virtue of which they return the impulse which they receive from the in-rushing blood with the same force, and by this means maintain a regu- lar onflow of the blood during the time occupied by the following diastole of the heart. If the elasticity of the vessel be considerably dimin- ished, without its becoming stiff and immoveable (from calcareous incrustations) in the same degree, the dilata- tion, which it undergoes from the pressure of the blood, is not again compensated; the vessel remains in a ELASTICITY OF THE COATS OF VESSELS. 153 dilated condition, and thus are gradually produced the well-known forms of ecstasts, such as we are familiar with in the arteries under the name of aneurysms, and in the veins under that of varices. In these processes, we have not so much, as has been represented of late, to deal with primary disease of the inner coat, as with changes which are situatéd in the elastic and muscular middle coat. If therefore it is the muscular elements of the arteries that have the most important influence upon the quan- tity of blood to be distributed, and the mode of its dis- tribution, in the several organs, and the elastic elements that are chiefly concerned in the production of a rapid and equable stream, they nevertheless exercise only an indirect influence upon the nutrition of the parts which lie outside the vessels themselves, and in this matter, we are obliged to betake ourselves, as a last resource, to the simple, homogeneous membrane of the capillaries, without which indeed not even the constituents of the walls of the larger vessels provided with vasa vasorum would be able to maintain themselves for any lengthened period. The difficulty which here presents itself has, as you know, during the last ten years, been chiefly got over by the assumption of the existence of dzffusive currents (endosmosis and exosmosis) between the contents of the vessels and the fluid in the tissues ; and by regarding the capillary wall as a more or less indifferent membrane, forming merely a partition between two fluids, which enter into a reciprocal relation with one another ; while the nature of this relation would be essentially deter- mined by the state of concentration they are in and their themical composition, so that, according as the internal or the external fluid was the more concentrated, the dif- fusive stream would run inwardly or outwardly, and, 154 LECTURE V.. according to the chemical peculiarities of the individual juices, certain modifications would arise in these currents, Generally speaking, however, the chemical side of this question has been but little regarded. It cannot be denied that there are certain facts which cannot well be explained in any other manner, especially in cases where essential alterations have taken place in the state of concentration of the juices, for example, in that form of cataract which Kunde has artificially pro- duced in frogs by the introduction of salt into their intes- tinal canal or subcutaneous cellular tissue. But in pro- portion as, after a physical study of the phenomena of diffusion, the conviction has been acquired that the mem- brane which separates the fluids is not an indifferent substance, but that its nature exercises a directly con- trolling influence upon the permeating powers of the fluids, it becomes impossible that a like influence should be denied the capillary membrane. We must not, how- ever, go so far, as to ascribe to this membrane all the peculiarities observable in the interchange of material, and so explain how it happens, that certain matters which enter into the composition of the blood are not distributed in equal proportion to every part, but leave the vessels at some points in greater, at others in less, quantity, and at others not at all. These peculiarities depend, manifestly, on the one hand, upon the differ- ent degrees of pressure to which the column of blood is subjected in certain parts, and, on the other, upon spe- cial preperties of the tissues ; and we are irresistibly com- pelled, both by the consideration of simply pathological, and particularly by that of pharmaco-dynamical, pheno- mena to admit that there are certain affinities existing between definite tissues and definite substances, which must be referred to peculiarities of chemical constitution, in virtue of which certain parts are enabled in a greater INFLUENCE OF THE VESSELS UPON NUTRITION. 155 degree than others to attract certain substances from the neighbouring blood. If we consider the possibility of such attraction with a little more attention, it is peculiarly interesting to ob- serve the behaviour of parts, which are at a certain dis- tance from the vessel. If we apply a definite stimulus, for example, a chemical substance, a small quantity of an alkali I will suppose, directly to any part, we see that this shortly afterwards takes up more nutritive matter, so that even in a few hours its size becomes considerably increased, and that, whilst before we were perhaps scarcely able to distinguish anything in its interior, we now find an abundant, relatively opaque material within it, in no wise composed of alkali which had made its way in, but essentially containing substances of an albuminous nature. Observation shows that the process in all vas- cular parts begins with hyperemia, so that the idea rea- dily presents itself that the hyperaemia is the essential and determining cause. But if we investigate the matter more minutely, we find it difficult to understand how the blood, which is in the hyperemic vessels, can contrive only to act just upon the irritated part, whilst other parts lying in the immediate vicinity are not affected in the same manner. In all cases in which the vessels are the immediate originators of disturbances which take place in a tissue, these are most marked in the immediate neighbourhood of the vessels and in the district which they supply (vascular (or vessel-) territory). If we introduce an irritating, as, for example, a decomposing body into a blood-vessel, a fact that has been established by me upon a large scale when tracing out the history of em- bolia, we by no means see that the parts at a distance from the vessel are the principal seats ‘of active change, but that this is in the first instance manifested in the wall of the vessel itself and then in the adjoining histological 156 LECTURE VI. elements. But if we apply the stimulus directly to the tissue, the central point of the disturbance will always continue to be that at which the stimulus produced its effect, just the same whether there are vessels in the neighbourhood or not. We shall hereafter have occasion to return to this sub- ject, and my only object here was to lay this fact before you in its general features, and thus repel the ordinary conclusion, which is as convenient as it is fallacious, that hyperemia (in itself passive) exercises a directly regulat- ing influence upon the nutrition of tissues. If a special proof were still required in order to com- plete the refutation of this assumption, which in an ana- tomical point of view is utterly untenable, we find a most apposite argument in the experiment above men- tioned of the section of the sympathetic. In an animal the sympathetic may be divided in the neck ; thereupon a state of hypersemia ensues in the whole of that half of the head, the ears become dark red, the vessels greatly dilated, the conjunctiva and nasal mucous membrane turgidly injected. This may continue for days, weeks, or months, without the least appreciable nutritive dis- turbance necessarily arising therefrom; the parts, although gorged with blood, are yet, as far at least as we are at present able to judge of this, in the same state of nutrition as before. If we apply stimuli sufficient to produce inflammation to these parts, the only thing that we remark is, that the inflammation runs its course more quickly, without exhibiting either in itself or in the na- ture of its products anything essentially unusual. The greater or less quantity of blood, therefore, which fiows through a part is not to be regarded as the only cause of the changes in its nutrition. There is, I sup- pose, no doubt that, when a part, which is in a state of irritation, receives more blood than usual, it is also able INFLUENCE OF THE VESSELS UPON NUTRITION 157 to attract a larger quantity of material from the blood with greater readiness than it otherwise would have done, or than it would be able to do, if the vessels were ina state of contraction or less filled with blood. If, therefore, it were to be objected to my view that in such conditions the most favorable effects are often produced by local abstractions of blood, this would be no proof of its incorrectness. If we cut off or diminish the supply of nutritive matter, we must, of course, prevent the part from absorbing more than its wont, but, vice versd, we cannot by offering it a larger quantity of nutritive mate- rial straightway compel it to take up more than it did ; these are two entirely independent cases. However apt one may be to conclude (and however much I may be disposed to allow, that at the first glance there is some- thing very plausible in such a conclusion) that, from the favourable effect which the cutting off of the supply of blood has in putting a stop to a process which arose from an increase of it, the process depended upon this increased supply, yet 1 am of opinion that the practical fact can- not be interpreted in this way. It is not so much an increase of quantity, either in the blood as a whole or in that portion of it contained in an individual part, which is required in order that a like increase should forthwith take place in the nutrition of that part, or of the whole body, as that, in my opinion, particular conditions should Obtain in the tissues (irritation) altering the nature ot their attraction for the constituents of the blood, or that particular matters should be present in the blood (specific substances), upon which definite parts of the tissues are able to exercise a particular attraction. If you apply this doctrine to the humoro-pathological conception of the processes, you will be able to deduce from it that Iam far from contesting the correctness of the humoral explanations in general, and that I rather 158 LECTURE VI. cherish the “conviction that particular substances which ' find their way into the blood are able to induce particu- lar changes in individual parts of the body by their be- ing taken up into them in virtue of the specific attraction of individual parts for individual substances. We know, for example, that a number of substances are introduced into the body which possess special affinities for the ner- vous system, and that among this number again there are some which stand in a closer connection with certain very definite parts of the nervous system, as for instance with the brain, the spinal cord or sympathetic ganglia, and others again with particular parts of the brain, spi- nal cord, etc. On the other hand, we see that certain materials have some special relation to definite secreting organs ; that they penetrate and pervade them by a kind of elective affinity ; that they are excreted by them; and that, when there is a too abundant supply of such materials, a state of irritation is produced in these or- gans. But an essential condition in all these cases is, _ that the parts which are believed to have a particular elective affinity for particular matters, should really exist, for a kidney which loses its epithelium is thereby de- prived of its secreting power. Another condition is that the parts should possess a relation of affinity, for neither a diseased, nor a dead, kidney has any longer the affinity for particular substances which the gland, when living and healthy, possessed. The power of attracting and transforming definite substances can be maintained at most for a short time in an organ, which no longer con- tinues in a really living condition. We are therefore, in the end, always compelled to regard the individual ele- ments as the active agents in these attractions. An hepatic cell can attract certain substances from the blood which flows through the nearest capil'ary vessel, but it must in the first place exist, and in the next be in the SPECIFIU AFFINITIES—LIVER. 159 ejoyment of its special properties, in order to exercise this attraction. If the living element become altered, if a disease set in which causes changes in its molecular, physical, or chemical peculiarities, then its power of ex- arcising this special attraction will at the same time also be impaired. Let us consider this example with still greater atten- tion. The hepatic cells are almost in direct contact with the walls of the capillaries, from which they are only sepa- rated by a thin layer of delicate connective tissue. If now we were to imagine that the peculiar property pos- sessed by the liver of secreting bile, merely consisted in a particular disposition of the vessels of the organ, we should indeed in no wise be justified in doing so. Simi- lar networks of vessels, in a great measure of a venous nature, are found in several other places, for example, in the lungs. But the peculiarity of the secretion of bile manifestly depends upon the liver-cells, and only so long as the blood flows past in the immediate neighbourhood of the hepatic cells, does the particular attraction of mat- ter continue which characterizes the action of the liver. When the blood contains free fat, we see that after a time the hepatic cells take it up in minute particles, and that if the supply continues, the fat becomes more abun- dant and is gradually separated in the form of largish drops within the hepatic cells (Fig. 27, B, 6). That which we see in the case of fat in a more palpable form, we must conceive to occur in the case of many other substances in a state of more minute division. Thus for the due performance of secretion it will always be essen- tial that the cells exist in a certain, special condition ; if they become diseased, if a condition be developed in them connected with some important chemical change in their contents, for example, an atrophy, ultimately caus- ing the destruction of the parts, then the power pos- 160 LECTURE VI. sessed by the organ of forming bile will at the same time continually become more limited. We cannot conceive a liver without liver-cells ; they are, as far as we know, the really active elements, since even in cases in which the supply of blood has become limited owing to obstruc- tion in the portal vein, the hepatic cells are able to pro- duce bile, although perhaps not in the same quantity. This fact derives peculiar value from its occurrence in the liver, because the matters which constitute the bile do not, as is well known, exist pre-formed in the blood, and we must therefore suppose the constituents of the bile to arise not by a process of simple secretion, but by — one of actual formation in the liver. This question has, as you are aware, recently become invested with a still greater degree of interest in consequence of the observa- tion of Bernard that the property of producing sugar is also inherent in these elements, whereby the blood is supplied upon so gigantic a scale with a substance which has the most decided influence upon the internal meta- morphic processes and upon the production of heat. If, therefore, we speak of the action of the liver, we can, both in regard to the formation of sugar as well as that of bile, mean nothing but the action of its individual ele- ments (cells), an action which consists in their attracting matters from the passing current of blood, in their effect- ing within their cavity a transmutation of these matters, and returning them in this transmuted form either to the blood, or yielding them up to the bile-ducts in the shape of bile. Now I demand for cellular pathology nothing more than that this view, which must be admitted to be true in the case of the large secreting organs, be extended also to the smaller organs and smaller elements ; and that, for example, an epidermis-cell, a lens-fibre or a cartilage-cell be, to a certain extent, admitted to possess the power of THE NOBLER JUICES. 161 deriving from the vessels nearest to them (not always indeed directly, but often by transmission from a dis. tance), in accordance with their several special require- ments, certain quantities of material; and again that, after they have taken this material up, they be held to be capable of subjecting it to further changes within themselves, and this in such a manner that they either derive therefrom new matter for their own development; or that the substances accumulate in their interior, with- out their reaping any immediate benefit from it; or finally that, after this imbibition of material, even decay may arise in their structure and their dissolution ensue. At all events it seems necessary to me that great promi- nence should be assigned to this specific action of the ele- ments of tissues, in opposition to the specific action of the vessels, and that in studying local processes we should principally devote ourselves to the investigation of pro- cesses of this nature. It will now, I think, be most suitable for us next to enter a little more in detail upon the consideration of the facts which form the basis of the humoro-pathologi- cal system—upon the study of the so-called nobler jutces. If the blood be considered in its normal influence upon nutrition, the most important point is not its movement, nor the greater or less afflux of it, but its intimate com- position. When the quantity of blood is great, but its composition does not correspond to the natural require- ments of the parts, nutrition may suffer ; when the quan- tity is small, nutrition may proceed in a comparatively very favourable manner, if every single particle of the blood contain its ingredients mixed in the most favorable proportions. If the blood be considered as a whole in contradistinc- tion to other parts, the most dangerous thing we can do 11 162 LECTURE VI. is to assume what has at all times created the greatest confusion, namely, that we have in it to deal with a fluid in itself independent, but upon which the great mass of tissues more or less depend. The greater number of the humoro-pathological doctrines are based upon the sup- position, that certain changes which have taken place in the blood are more or less persistent ; and just in the very instance where these doctrines have practically ex- ercised the greatest influence, in the theory, namely, of chronic dyscrasie, it is usually conceived that the change is continuous, and that by inheritance peculiar altera- tions in the blood may be transmitted from generation to generation, and be perpetuated. This is, I think, the fundamental mistake of the humo- ralists, the real hinge upon which their errors turn. Not that I doubt at all that a change in the composition of the blood may pertinaciously continue, or that it may propagate itself from generation to generation, but I do not believe that it can be propagated in the blood itself and there persist, and that the blood is the real seat of the dyscrasia. My cellulo-pathological views differ from the humoro- pathological ones essentially in this, that I do-not regard the blood as a permanent tissue, in itself independent, regenerating and propagating itself out of itself, but as in a state of constant dependence upon other parts. We need only apply the same conclusions which are univer- sally admitted to be true as regards the dependence of the blood upon the absorption of new nutritive matters from the stomach, to the tissues of the body themselves also. When the drunkard’s dyscrasia is spoken of, no- body of course imagines that every one who has once been drunk labours under a permanent alcoholic dyscra- sia, but the common opinion is, that, when continually fresh quantities of alcohol are ingested, continually fresh THEORY OF DYSCRASIA—ITS LOCAL ORIGIN. 163 changes also declare themselves in the blood, so that its altered state must continue as long as the supply of fresh noxious matters takes place, or as, in consequence of a previous supply, individual organs remain in a diseased condition. Ifno more alcohol be ingested, if the organs which had been injured by the previous indulgence in it be restored to their normal condition, there is no doubt but that the dyscrasia will therewith terminate. This ex- _ ample, applied to the history of all the remaining dyscra- _ siz, elucidates in a very simple manner the proposition, - that every dyscrasia ts dependent upon a permanent supply of noxious ingredients from certain sources. As a con- tinual ingestion of injurious articles of food is capable of producing a permanently faulty composition of the blood, in like manner persistent disease in a definite organ is able to furnish the blood with a continual supply of mor- bid materials. The essential point, therefore, is to search for the local origins of the different dyscrasiz, to discover the definite tissues or organs from which this derangement in the constitution of the blood proceeds. Now Iam quite willing to confess that it has not in many cases hitherto been possible to find out these tissues or organs. In many cases, however, success has been obtained, although it cannot be said in every instance in what way the blood has become changed. Thus we have that remarkable condition, which may very well be referred to a dyscra- sia, the scorbutic condition, purpura, and the petechial dyserasia. In vain will you look around for decisive in- formation as to the nature of this dyscrasia, and as to the kind of change experienced by the blood when purpura or scurvy show themselves. What has been found by one has been contradicted by another, and it has even been shown that sometimes no change had taken place in the proportions of the grosser constituents of the 164 LECTURE JI. blood. There remains in this case, therefore, a quad ig- notum, and you will, I am sure, deem it excusable, if we are unable to say whence a dyscrasia proceeds, of which we are altogether unacquainted with the nature. How- ever, the knowledge of the nature of the change in the blood does not involve an insight into the requisite con- ditions for the dyscrasia, and just as little is the reverse the case. In the case of the hemorrhagic diathesis, also, it must at all events be regarded as an important step in advance, that we are in a number of instances able to point to a definite organ as its source, as, for example, to the spleen or liver. The chief point now is to deter- mine what influence the spleen or the liver exercises upon the special composition of the blood. If we were acquainted with the nature of the changes effected in the blood by the influence of these organs, it might not perhaps be difficult from our knowledge of the dis- eased organ also at once to infer what kind of change the blood would experience. But it is nevertheless an important fact that we have got beyond the mere study of the changes in the blood, and have been able to ascer- tain that there are definite organs in which the dyscrasia has its root. In conformity herewith we must conclude that, if there is a syphilitic dyscrasia in which a virulent sub- stance circulates in the blood, this cannot be perma- nently present there, but that its existence must be due to the persistence of local depots (Heerde), whence new quantities of noxious matter are continually being intro- duced into the blood. By following this track we arrive at the conclusion which we have already mentioned, and which is of extreme importance in a practical point of view, that, namely, every permanent change which takes place in the condition of the circulating juices, must be derived from definite points in the body, from individual LOCAL ORIGIN OF DYSCRASIA. 165 organs or tissues ; and this fact, moreover, is educed, that certain organs and tissues exercise a more marked influence upon the composition of the blood than others ; that some bear a necessary relation to this fluid, others only an accidental one. LEHCTUBE VIL. MARCH 6, 1858. THE BLOOD. Fibrine—Its fibrille—Compared with mucus, and connective tissue—Hamogeneous condition. . Red blood-corpuscles—Their nucleus and contents—Changes of form—Blood-crys- tals (Hematoidine, Hemine, Hematocrystalline). Colourless blood-corpuscles—Numerical proportion—Structure—Compared with pus- corpuscles—Their viscosity and agglutination—Specific gravity—Crusta granu- losa—Diagnosis between pus-, and colourless blood-corpuscles. { inTEND to lay before you to-day, gentlemen, some further particulars with regard to the history of the blood. I concluded my last lecture by impressing upon you the necessity of localizing the different dyscrasie ; em- ploying the term localize, not in its ordinary sense, as the dyscrasize have heretofore been considered as local- ized, but rather in a genetical meaning, in accordance with which we constantly refer the dyscrasia to a pre- existing local affection, and regard some one tissue as __ the source of the persistent changes in the blood. If now we consider the different dyscrasie with regard to their importance and their source, two great categories of dyscrasic conditions may at the very outset be distin- guished, according namely as the morphological elements of the blood become changed, or the deviation is more of a chemical one, and seated in the fluid constituents. Among these latter, it is the fibrine, which. in conse- 166 FIBRINE. 167 quence of its coagulability, first, and that very soon after the blood has been removed from the living body, assumes a visible form, and which for this reason hag frequently passed for a morphological constituent of the blood. This notion concerning it has of late been maintained in many quarters, and has indeed always had a traditional existence in medicine, inasmuch as from ancient times fibrine was constantly brought forward in addition to the red constituents of the blood as a special element,'and it was the custom to estimate the quality of the blood, not only from the number of the blood- corpuscles, but frequently in a much more positive man- ner from the amount of fibrine. This dissociation of fibrine from the other fluid consti- tuents of the blood is, to a certain extent, of real value, because fibrine, like the blood-corpuscles, is quite a peculiar substance, and so exclusively confined to the blood and the most closely allied juices, that it really may be viewed as connected rather with the blood-cor- puscles than with the mere fluids which circulate as serum. If we consider the blood in its really specific constituents, in those, by means of which it becomes blood, and is distinguished from other fluids, it cannot be denied that, on the one hand, the corpuscles with their hematine, and, on the other, the fibrine of the liquor sanguinis are the elements in which the specific differences must be sought for. If now we next proceed to consider these constituents a little more closely, the morphological description of fibrine is comparatively rapidly made. On examining it, as it appears in blood-coagula, it is nearly always found in the form described by Malpighi, the fibrillar. Its fibres generally form extremely fine interlacements, delicate networks, in which they usually cross and join one another in a somewhat tortuous form. The greatest 168 - LECTURE VII. variations exhibited by these fibres when forming out of the blood have reference to their size and breadth; these are peculiarities con- cerning which it has not hitherto been possible to form any certain judgment. I meet with these variations pretty frequently, but without being in a position to assign the causes which determine them. The extremely fine and delicate fibres are those usually met with; but sometimes we find far broader, and almost ribbon-like fibres, which are much smoother, but in other respects, cross and interlace in pretty nearly the same manner. Essentially, therefore, there is always present in a clot a network composed of fibres, in the meshes of which the blood-corpuscles are enclosed. If a drop of blood be allowed to coagulate, fine filaments of fibrine can be seen everywhere shooting up between the blood-corpuscles. With regard to the nature of these fibres, we may observe that there are only two other kinds which, his- tologically speaking, bear at all a near resemblance to them. The one kind occurs in a substance which, singularly enough, effects an approximation between the most ancient, perfectly antique, craseological ideas and the modern ones, namely in mucus. In the old Hippo- cratical system of medicine the whole mass of fibrine is, as is well known, included under the terms phlegma, mucus, and when we compare mucus with fibrine, we are obliged to confess that there does indeed exist a great similarity between them in the form they assume upon coagulation. In a similar manner to fibrine, Fig. 50. Coagulated fibrine from human blood. a, Fine, 6, coarser and broader fibrils. c, Red and colourless blood-corpuscles enclosed in the coagulum. 280 diameters. FIBRINE, MUCUS AND CONNECTIVE TISSUE. 169 mucus also forms into fibres, which frequently become isolated and then coalesce, so as to give rise to certain figures. The other substance which belongs here is the intercellular, or, if you will, the gelatine-yielding sub- stance of connective tissue, the collagen (gluten of earlier writers). The fibrils of connective tissue only differ in that they are not usually reticulated, but run a parallel course, whilst in other respects they resemble those of fibrine in a high degree. The intercellular substance of connective tissue presents another point of resemblance with fibrine in the great analogy of its behaviour with reagents. When we expose it to the action of diluted acids, especially the ordinary vegetable acids, or also weak mineral acids, the fibres swell up and disappear before our eyes, so that we are no longer able to say where they are. The mass swells up, every interspace: disappears, and it looks as if the whole were composed: of a perfectly homogeneous substance. If we slowly wash it and again remove the acid, a fibrous tissue may, if the action have not been too violent, once more be obtained, after which the previous condition can be pro- duced afresh, and changed again at pleasure. This behaviour has hitherto remained unexplained, and for this very reason Reichert’s view, which I have already mentioned, that the substance of connective tissue, is really homogeneous and the fibres are only an artificial product, or an optical delusion, has something alluring in it. In fibrine, however, the individual fibres can, much more distinctly than is the case with connective tissue, be so completely isolated, that I cannot help saying that I regard the separation into single fibres as really taking place, and not merely as an artificial one, or as a delusion on the part of the observer. But it is very interesting to observe that this fibrillar stage of fibrine is invariably preceded by a homogeneous 170 LECTURE VIL. one, just as connective tissue originally wears the form of a homogeneous intercellular substance (mucus) from which fibres are only by degrees, if I may so express myself, excreted, or, to employ the usual term, differen- tiated. So fibrine, too, which is first of all gelatinous, becomes differentiated into a fibrillar mass. And indeed in the case of inorganic substances also we find certain analogous appearances. From deposits of calcareous salts or silicic acid, which were originally perfectly gela- tinous and amorphous, solid granules and crystals are gradually separated. The name fibrils may therefore still be retained to designate the usual form in which fibrine presents itself, but at the same time it must be borne in mind, that this substance originally existed in a homogeneous, amor- phous, gelatinous condition, and can again be reduced to it. This reduction can not only be effected artificially, but takes place also naturally in the body itself, so that where we have previously found fibrils, we may after- wards meet with the fibrine in a homogeneous condi- tion, as, for example, in the vessels, where aneurysmal coagula, and others, are gradually converted into a homogeneous mass of cartilaginous density. Now, with reference to the second portion of the blood, the blood-corpuscles, 1 may express myself briefly, as they are well-known elements. I have already remarked that nearly all the histologists of the present se es time are agreed that the co- a - loured corpuscles of the blood ®2© 4b @o 2 ®6o0 cA ©-6@ of man and the higher mam- G og ©® nalia contain no nuclei, but ©) that they are simple vesicles, Fig. 51. Nucleated blood-corpuscles from a human foetus, six weeks old. a. Homogeneous cells varying in size, with simple, relatively large nuclei, of which RED BLOOD-CORPUSCLES AND THEIR CONTENTS. 171 concerning the cellular nature cf which doubts might be permitted, if we did not happen to know that, at certain periods of the development of the embryo, they do contain nuclei. An ordinary red blood-corpuscle must therefore be considered as composed of a closed mem- brane, containing a tolerably tough mass, which is the seat of the colour. Now, in man the blood-corpuscles are, as is well known, flat, disc- or plate- ‘ i ; Fig. 52. shaped bodies, with a central depression wee on each ‘surface, and, when regular in’ ie 038 : : ahs im 2°42 form, constitute, as it were, a ring, in the is aoe centre of which the colour is fainter from f the diminished thickness. The contents are generally somewhat summarily regarded as consisting of hama- tine, or the colouring matter of the blood. They are, however, unquestionably very complex, and what is called heematine forms merely a part of them ; how great a part it has not been hitherto possible to determine. Whatever other matters are contained within the blood- corpuscle belong entirely to its chemistry. Certain changes produced by the action of external media con- stitute all that can be seen of them. We observe that the blood-corpuscles, according as they imbibe oxygen, or contain carbonic acid, appear light or dark, whilst they alter their form a little. We know, further, that a few are slightly granular, but the greater number more homogeneous; at * a colourless corpuscle. 6. Cells with extremely small, but well defined nuclei, and distinctly red contents. c¢. After the addition of acetic acid the nuclei are seen in some instances shrivelled and jagged, in several, double; at * a granular corpuscle, 280 diameters. Fig. 52. Human blood-corpuscles from an adult. a, An ordinary disc-shaped, red blood-corpuscle; 6, a colourless one; c, red corpuscles seen in profile, and standing upon their rims. d. Red corpuscles arranged in the form of rouleaux of money. e. Red corpuscles which have become irregular in outline, and shrivelled through loss of water (exosmosis). . Shrivelled red corpuscles, with tuberculated margins, and a projection, like that produced by a nucleus, upon the flat surface of the disc. g. A still more shrivelled state. h. The highest degree of shrivelling (melanic corpuscles), Magnified 280 diameters. 172 LECTURE VII. by the action of chemical fluids, certain quantities of water are abstracted from the corpuscles, and that they then shrivel up and experience peculiar changes in form, which might very easily give rise to errors. These are not unimportant conditions, and I will therefore now add a few words concerning them. When a blood-corpuscle is exposed to a loss of water by the action of a strongly concentrated liquid upon it, the first thing we observe is that, as fast as fluid exudes, little prominences arise on the surface of the corpuscle, at first very much scattered, sometimes at the border, sometimes more towards the middle, and in the latter case, occasionally bearing a deceptive resemblance to a nucleus (Fig. 52, e, f). This has been the source of the erroneous assumption of nuclei, which have been so much described. If a blocd-corpuscle be watched for a considerable time whilst under the action of concentrated media, more and more protuberances are seen to arise, and the surface of the corpuscle becomes less in diameter. At the same time, little folds and knobs form with con- tinually increasing distinctness on the surface, and the cell becomes jagged, stellate, and angular (Fig. 52, g). Jagged bodies of this sort are to be seen every moment on examining blood which has been for some time ex- posed to the air. Even mere evaporation will produce this change. We can effect it with great rapidity by altering the composition of the serum by the addition of salt or sugar. If the abstraction of water continue, the corpuscle grows smaller still, and ultimately becomes smooth again, and at the same time globular (Fig. 52, h), or even perfectly spherical, whilst its colour appears much more intense, and the contained mass assumes quite a deep blackish-red hue. Hence we are able to draw the not uninteresting conclusion, that this exos- mosis consists essentially in a withdrawal of water, dur- EFFECTS OF FLUIDS UPON THE RED CORPUSCLES. 173 ing which perhaps one or more other matters pass out. as, for example, salt, but the essential constituents remain behind. The hematine does not follow the water ; the membrane of the blood-corpuscles keeps it back, so that when a large quantity of fluid is lost, the heematine in the interior must of course become propor- tionately increased in density. The reverse is the case when we employ diluted fluids. The more diluted the fluid, the more does the blood-cor- puscles enlarge ; it swells up and becomes paler. Or treating blood-corpuscles, which have become smaller from the action of concentrated fluids, with water, we see them pass back from the globular into the angular form, and from this into the discoidal one ; after which they continually become more and more globular, often assume very peculiar shapes, and again grow paler. This process may, if the dilution of the blood be effected with great precaution, be continued until the blood-cor- puscles scarcely seem to retain a trace of colour, though they still remain visible. In ordinary cases, when much liquid is added at once, such a violent revolution is pro- duced in the economy of the blood-corpuscle, that an escape of the hematine immediately ensues. We then obtain a red solution, in which the colouring matter is free and dissolved in the fluid. I call your attention to this peculiarity, because it is continually occurring in the course of investigations, and because it explains one of the most important phenomena in the formation of pathological deposits of pigment, in which we meet with a precisely similar escape of hematine from the blood- corpuscles (Fig. 54, a). The expression generally made use of under such circumstances is, that the blood- corpuscles are dissolved, but it has long been a well- known fact that, as was first shown by Carl Heinrich Schultz, although there apparently no longer exist any LT LECTURE VII. cells, yet their membranes may, by means of an aqueous solution of iodine, again .be rendered visible, whence it is evident that it was only the high degree of distension and the extraordinary thinness of the membranes which prevented the corpuscles from being seen. Indeed, very violent action on the part of substances chemically dif- ferent is required, in order to effect a real destruction of the blood-corpuscles. If, immediately after they have been treated with a very concentrated solution of salt, water be added in large quantity, we may succeed in bringing things to such a pass that the contents of the corpuscles are abstracted without their swelling up, and their membranes remain behind visible. This was the reason why Denis and Lecanu asserted that the blood- corpuscles contained fibrine ; for they believed that, by treating them first with salt and then with water, they were able to demonstrate its presence in them. This so- called fibrine is, however, as I have shown, nothing more than the membranes of the blood-corpuscles ; real fibrine is not contained in them, although their walls are certainly composed of a substance which has more or less affinity to albuminous matters, and may, when obtained in large masses, present appearances reminding one of fibrine. Now with regard to the substances contained in the blood-corpuscles, they happen quite recently to have become invested with great interest in consequence of the more morphological products which have been observed to arise out of them, and which have produced a kind of revolution in the whole theory of the nature of organic matters. I refer here to the peculiar forms of coloured crystals. which can, under certain circumstances, be obtained from the colouring matter of the blood, and which have acquired not only on their own account great chemical, but also very considerable practical, interest. HAMATOIDINE. 175 We have already become acquainted with three different kinds of crystals, of which hematine seems to be the common origin. To the first form, with which I at one time busied myself much, I have given the name of Hematoidine. This is one of the most frequent of metamorphic products, and is spontaneously formed in the body out of hama- tine, and that indeed often in such large quantities that its excretion can be perceived with the naked eye. This substance in its perfect form presents itself in the shape of oblique rhombic columns, and is of a beatiful yellow- ish-red, or frequently, when in thicker pieces, deep ruby- red, colour, and forms one of the most beauti- ful crystals we are acquainted with. In little plates too it is not uncommonly met with, and op frequently bears a considerable resemblance @ &d to the crystalline forms of uric acid. In the majority of cases the crystals are very small, not merely microscopical, but even somewhat difficult of observation with the microscope. A man must either be a very keen observer, or provided with special prepara- tory knowledge, else he will frequently discover in the spots where the hematoidine is lying nothing more than little streaks, or an apparently shapeless mass. But, upon more accurate inspection, the streaks resolve themselves into minute rhombic columns, the mass into an aggregation of crystals. This substance may be con- sidered as the regular, typical, ultimate form into which heematine is converted in any part of the body where large masses of blood continue to lie for any length of time. An apoplectic effusion in the brain, for example, cannot be repaired by any other process than by a large portion of the blood undergoing this form of crystalliza- Fig. 53. Fig. 53. Crystals of Hamatoidine in different forms (Comp. ‘ Archiv. f. path. Anat.,’ vol. i, p. 391, plate iii, fig. 11), Magnified 300 diameters. 176 LECTURE VII. tion, and if we afterwards find a coloured cicatrix at the spot, we may feel perfectly assured that the colour is dependent upon the presence of hematoidine. When a young woman menstruates, and the cavity of the Graafian vesicle, from which the ovum has been ex- truded, becomes filled with coagulated blood, the hama- tine is gradually converted into hematoidine, and we afterwards find at the spot where the ovum had lain, the beautiful deep-red colour of the hamatoidine crystals, which remain as the last memorials of this episode. In this manner we can count the number of apoplectic attacks, or calculate how often a young girl has menstru- ated. Every extravasation may leave behind its little con- tingent of hematoidine crystals, and these, once formed, remain in the interior of the organ, in the shape of compact bodies endowed with the greatest powers of resistance. With respect to the peculiarities of hamatoidine, it has, in a theoretical point of view, another special claim to Fig. 54. Pigment from an apoplectic cicatrix in the brain (‘ Archiv,’ vol. i, pp. 401, 454, plate ili, fig. 7). a. Blood-corpuscles which have become granular and are in process of decolorization. 6. Cells from the neuroglia, some of them pro- vided with granular and crystalline pigment. c. Pigment-granules. d. Crystals of Hematoidine. /. Obliterated vessel with its former channel filled with granular and crystalline red pigment, 300 diameters. HAMINE. 177 our interest, from its presenting to us a series of proper- ties, which render it conspicuous as the only substance in the body, at least, that we are as yet acquainted with, which is allied to the colouring matter of the bile (Chole- pyrrhine). By the direct action of mineral acids, or after previous treatment and preparation by means of alkalies, the same, or precisely similar, colour-tests are obtained, which are yielded by the colouring matter of the bile when treated with mineral acids, and it seems also from other facts, that we have here a body before us, which is very intimately connected with the colouring matter of the bile. This circumstance derives its especial interest from its being supposed, for other reasons also, that the coloured constituents of the bile are products of the de- composition of the red colouring matter of the blood. In the interior of extravasations there really does arise a yellowish red substance which may be designated as a newly formed kind of biliary colouring matter. The second kind of crystals which arise out of hema- tine was discovered later; they are very similar to the preceding ones, but differ from them in that they do not occur as a spontaneous product in the body, but must be artificially produced. They are more of a dark brownish Fia@. 55. ony: 42 90-7 > colour and usually form flat rhombic plates with more acute angles ; they are in an extraordinary degree capa- ble of resisting tests, and also do not, when acted upon p Fig. 55. Crystals of Hemine, artificially procured from human blood. 300 dia- meters. 12 178 LECTURE VII. by the mineral acids, exhibit the peculiar play of colours afforded by hematoidine. This second kind of crystals has received the name of Hemine from their discoverer Teichmann. Quite recently Teichmann has himself be- gun to entertain doubts as to whether it is not really a sort of hematine. These forms do not present as yet the slightest pathological interest, but, on the other hand, they have proved of very great importance in forensic medicine on account of their having been recently em- ployed as one of the surest tests for the examination of blood-stains. I myself have been in a position to make experiments of this sort in forensic cases. For this pur- pose the best mode of proceeding is to mix dried blood in as compact a form as possible with dry, crystallized, powdered common salt, and then to add to this mixture glacial acetic acid, and evaporate at a boiling heat. When this has been done, crystals of heemine are found where the blood-corpuscles or the substance previously lay, in which the presence of hematine was doubtful. This is a reaction which must be ranked among the most certain and reliable ones with which we are acquainted. There is no other substance in which we know such a transformation to take place, but hematine. This test is extremely important, because it is applicable in the case of extremely minute quantities, only they must not be spread over too large a surface. It would therefore not be easy of application in a case where we had to deal with a cloth which had been dipped into a thin, watery, fluid coloured with blood. Yet I was able, in the case of a murdered man, on the sleeve of whose coat blood had spurted, and where some of the drops were only a line in diameter, from these minute specks to produce innumerable crystals of hamine, though of course micro- scopical ones. In cases in which the ordinary chemical tests would necessarily absolutely fail on account of the HAMATO-CRYSTALLINE. 179 smallness of the quantity, we are still able to obtain hemine. When the massof blood is so very small, the size of the crystals is certainly also extremely minute, and we then find, asin the case of hamatoidine, small needles of an intensely brown colour and provided with acute angles. The third substance which belongs to this series, is the so-called Hamato-crystalline, a substance about the dis- covery of which the learned still dispute, for the simple reason that it was found out piecemeal. The first obser- vation concerning it was made by Reichert in extrava- sations in the uterus of the guinea-pig, in a preparation which, I think, had already lain for some little time in spirits. This observation of his acquired especial signifi- cance because he showed that these crystals in certain respects behaved like organic substances, inasmuch as they became larger through the action of certain agencies, and smaller through that of others, without any change of form, a phenomenon which, up to that time, had not been known to take place in crystals. Afterwards these crystals were again discovered by K@lliker, but Funke, Kunde, and especially Lehmann, have examined them more closely. The result has been that they are very different in different classes of animals, but hitherto it has not been possible to discover any definite reason for their existence, or to obtain any insight into the nature of the substance itself. In man the crystals are tolerably large. At first it was believed that they only occurred in the blood of certain organs, but it has since turned out that they occur everywhere, though they are obtained with greater readiness in certain morbid conditions. In a few very rare cases it happens that they are found already formed in the blood of the dead bodies of animals. These crystals are very easily destructible ; both when they dry up and when they become moist, or are brought into vontact with any fluid medium, they perish, and they are 180 LECTURE VIL. therefore only observed in certain transitional stages, which must be exactly hit upon, in the destruction of blood-corpuscles. The well-developed forms in man are perfectly rectangular bodies ; but very frequently they are extremely small, and nothing is seen but simple spicules which shoot up into the object at certain spots in large masses. There is besides this peculiarity about them, that they retain the property which hematine itself has of becoming bright red with oxygen and dark red with carbonic acid. It is still, however, a frequent subject of discussion whether their whole substance is composed of colouring matter, or whether in this case also the crystals are really colourless and merely impreg- nated with pigment ; this much, however, may be regarded as certain, that the colour has something very character- istic about it, and that the existence of a close connec- tion between it and the ordinary colouring matter of the blood cannot be doubted. If we now revert to the natural morphological ele- ments of the blood, we meet with the colourless corpus- cles as its third constituent. They are present in compa- ratively small quantity in the blood of a healthy man. To three hundred red corpuscles we reckon about one colourless one. As they generally present themselves in the blood, they are spherical corpuscies, which are some- times a little larger, sometimes a little smaller than, or of the same size as, ordinary red blood-corpuscles, from which er Bo. @ “e© ob they are, however, strikingly g© ‘O® 62 @z distinguished by the want of all ae) ee colour and by their perfectly spherical form. In a drop of blood which has become quiet, the red cor- Fia. 56. Fig. 56. Colourless blood-corpuscles from a vein of the pia-mater of a lunatic. A. Examined when fresh ; a in their natural fluid, 6 in water. B. After the addi- COLOURLESS BLOOD-CORPUSCLES. 181 puscles are usually found aggregated in rows, presenting the familiar form of rouleaux of money, with their flat discs one against the other (Fig. 52, d) ; in the interspaces may be observed here and there one of these pale, spheri- cal bodies, in which in the first instance, when the blood is quite fresh, nothing more can be distinguished than an occasionally slightly granular-looking surface. Jf water be added, the colourless corpuscles are seen to swell up, and in proportion as they absorb the water, a membrane first becomes distinct ; then granular contents gradually come into view with more and more clearness, and at last some indication is perceived of the presence of one or several nuclei. The apparently homogeneous globule is gradu- ally transformed into a structure with delicate walls, and often so fragile, that when water is incautiously added, the external parts begin to fall to pieces, and in the in- terior a somewhat granular mass displays itself, which becomes looser and looser, and discloses within it a nu- cleus generally in process of division, or several nuclei. These may be made to display themselves with much greater rapidity, by treating the object with acetic acid, which renders the membrane translucent, dissolves the nebulous contents, and causes the nucleus to coagulate and shrivel up. The nuclei then are seen to be dark bo- dies with sharply defined outlines, and one or more in number according to circumstances. In short, we ob- tain in this way in the majority of cases the view of an object which presents the peculiar appearance that one of our confréres now present, Dr. Giiterbock, first pro- claimed to be the special characteristic of pus-corpuscles. The question concerning the resemblance or want of re- tion of acetic acid: a—c, cells with a single, granular nucleus, which becomes pro- gressively larger, and is finally provided with a nucleolus. d. Simple division of the nuclei, ¢. A more advanced stage of the division. #—h. Gradual division of thc nuclei into three parts, i—z, Four and more nuclei. 280 diameters, 182 LECTURE VII. semblance between the colourless cells of the blood and pus-corpuscles still continues to occupy the attention of observers, and it will probably still require a number of years before the views entertained with regard to the connection between the colourless corpuscles and pyzemia have been rendered so clear that relapses on one side or the other will not now and then recur. There is namely this source of error, that upon examining a num- ber of persons, in the blood of several among them cor- puscles will be found which have only a single nucleus, and that a very large one and not unfrequently provided with a nucleolus, whilst in the blood of others no corpus- cles will be seen which do not contain several nuclei. Now, since these latter bear a great resemblance to pus- corpuscles, those observers, who had previously chanced to meet with nothing but uni-nuclear corpuscles in nor- mal blood, cannot be blamed for believing, in another case in which they see multi-nuclear ones, that they have something essentially different before them, namely, pus- corpuscles in the blood, and that the case is one of pyx- mia. But, strange to say, the corpuscles with one nu- cleus form the exception, and you may look for a long time without finding blood in which all the cells have only one nucleus. Oddly enough to-day, while occu- pied in preparing the microscopical objects, I stumbled upon a specimen of blood, in which scarcely : anything but cells with one nucleus are to be @®©® met with, and these in extremely large num- 50% 9b ber ; it was taken from a man who died of smallpox, and in whom a very highly remark- able acute hyperplasia of the bronchial glands existed. Now, one might be inclined to believe that these are Fig. 57. Fig. 57. Colourless blood-corpuscles in variolous leucocytosis. a. Free or naked nuclei. 6, 5. Colourless cells with small, simple nuclei. c¢. Larger, colourless cells, with large nuclei and nucleoli. 300 diameters. PROPERTIES OF COLOURLESS BLOOD-CORPUSCLES. 182 eu different qualities of blood. But in opposition to such an idea it must be remarked, that, although in the cases in which the one or the other kind of corpuscles exist in large quantities, we have to deal with a pathological phe- nomenon, yet that, when we do not find such large quantities, we have before us only an earlier or a later stage of the development of the elements. For one and the same blood-corpuscle may, in the course of its life, have one or several nuclei, the one belonging to an earlier, the several to a later, stage of its existence. You must always bear in mind, that the change is seen to take place in the same individual in a short time, in- deed often in the course of a few hours, so that in blood which had previously only contained one sort, after- wards quite a different one may be found—a proof of the rapidity of the change to which these bodies are sub- jected. Allow me, gentlemen, to add a few words with regard to the more palpable relations which the individual con- stituents of the blood present towards one another. It is, as you well know, generally assumed that of the mor- phological constituents only two are accessible to the grosser perception of the naked eye, namely, the red corpuscles in the clot, and the masses of fibrine, which under certain circumstances form a buffy coat, but that, on the other hand, the colourless cells are not to be per- ceived by the unaided sight. This isa notion which I consider myself bound to correct. The colourless cor- puscles, whenever they are present in considerable num- bers, become very distinctly manifest to the more prac- tised eye during the separation of the constituents of the blood, and especially when the coagulation is accompanied by movement; and they then exhibit a peculiarity, with which it is as well that one should be acquainted when one is required to pass judgment upon specimens de- 184 LECTURE VII. rived from post-mortem examinations, and the ignorance of which has led to great errors. The colourless cor- puscles possess namely, as was brought to light in the discussion which Herr Ascherson, now here present, had some time ago with E. H. Weber, the peculiar property —— of being sticky, so that they A readily adhere to one another, and under certain circumstances of b also cling fast to other parts, 4 when the red corpuscles do not is present this phenomenon. This tendency to adhere to other 3 parts is particularly evident when several of the corpyscles are at the same time placed in a position which enables them to stick together. Thus, in blood in which there is an actual increase in the number of colourless cells, it is extremely common for agglutinations to take place among them, as soon as the pressure, under which the blood flows, is diminished ; in every vessel, in which the stream becomes slower, and the pressure weaker, an agglutination of the corpuscles may take place. The adhesiveness (viscosity) of the colourless blood- corpuscles produces besides this effect, that, as has been shown by Herr Ascherson, when the blood is flowing as usual through the capillary vessels, the colourless cor- puscles generally float rather more slowly than the red, and that, whilst these move along more in the centre of the vessel in a continuous stream, a comparatively large vacuity is left at the circumference, within which the Fig. 58. A. Fibrine clot from the pulmonary artery, and corresponding to its terminal branches; at a, a beset with largish patches, composed of heaps of white cells; at 6, b, 6 with specks of an analogous nature. Natural size. B. A portion of one of these specks or heaps, composed of thickly crowded, colourless blood-corpuscles. Magnified 280 diameters. AGGLUTINATION OF COLOURLESS BLOOD-CORPUSCLES. 185 colourless corpuscles move, and that indeed often with such constancy, that Weber came to the conclusion that every capillary lay within a lymphatic vessel, in the inside of which the colourless blood- or lymph-corpuscles floated. But there cannot be the least doubt but that the canals in question are single ones, in which the colourless corpuscles float along closer to the walls than the red ones ; and it ig in this peripheral space that, whilst the corpuscles move on, we see one here and there stick fast for a moment, then tear itself away and again move on slowly, so that the name of the slug- gish layer (triige Schicht), applied to this part of the stream, has been universally adopted. These two peculiarities, first, that, when the current becomes weaker, the corpuscles here and there cling to the walls of the vessel, and in some measure adhere to them, and, secondly, that they gather together and become conglomerated into largish masses, combine to produce this effect, that, when there exists a large number of colourless corpuscles in the blood, and death occurs, as it does in ordinary cases, after a gradual weakening of the propelling force, the colourless cor- puscles collect in vessels of every description, into small heaps, and generally lie upon the outside of the later formed blood-clot. If, for example, we pull out of the pulmonary artery the generally very tough clot of blood which fills it, minute granules will perchance be found upon its surface (Fig. 58, A), little beads of a white colour, which look like specks of pus, or are connected several of them toge- ther in the form of a string of pearls. This appearance Fig. 59. Capillary vessel from the web of a frog’s foot. 7». The central stream of red corpuscles. 7, 2, 2. The sluggish, peripheral layer of the stream with the colourless corpuscles. Magnified 280 diameters. 186 LECTURE VII. most frequently presents itself at those points where the number of the bodies is normally the largest, namely in the interval between the orifice of the thoracic duct, and the capillaries of the lungs. The naked eye can with tolerable ease detect in these clots the greater or less quantity of colourless corpuscles. Under circumstances inducing the presence of a very large number of them, whole heaps of them may be seen, investing different parts of the coagulum like a sheath, and if one of these heaps be placed under the microscope, many thousands of colourless corpuscles are seen crowded together. If the coagulation of the blood takes place, when it is more at rest, another appearance is presented with great distinctness, as may be seen in the vessels used to receive the blood after venesection. When the fibrine does not coagulate very quickly, as is the case in inflammatory blood, the blood-corpuscles begin, in consequence of their greater specific gravity, to sink through the fluid. This subsidence proceeds, as is well known, to such a pitch, that, after the fibrine has been removed by stir- ring, the serum becomes perfectly clear, in consequence of the corpuscles’ falling to the bottom. On defibrinating blood rich in colourless corpuscles, and allowing it to stand, a double sediment forms, a red and a white one. The red one constitutes the deeper, the white one the more superficial stratum, and the latter looks exactly as if a layer of pus were lying upon the blood. When the blood has not been deprived of its fibrine, yet coagulates slowly, the subsidence of the corpuscles does not take place so completely, but only the highest part of the liquor sanguinis becomes free from corpuscles ; and when after this the fibrine coagulates, we obtain the well-known crusta phlogistica, the buffy coat, and on looking for the colourless corpuscles, we find them forming a separate layer at the lower border of the buffy coat. This pecu- RED, WHITE AND COLOURLESS BLOOD-CORPUSCLES. 187 larity is simply explained by the different specific gravity of the two kinds of blood-corpuscles. The colourless - ones are always light, poor in solid matter and very deli- cate in structure, whilst the red ones are as heavy as lead in comparison, owing to their richness in hematine. They therefore reach the bottom with comparatively great rapidity, whilst the colourless ones are still engaged in falling. If two bodies of different specific gravities be allowed to fall from a sufficient height in the open air, the lighter one will, you know, in a similar manner, reach the ground after the other, owing to the resistance of the air. In the coagulation which takes place in blood derived from venesection, this white clot does not usually form a continuous, but an interrupted, layer, composed of little heaps or nodules adhering to the under side of the buffy coat. Hence Piorry, who was the first to observe this appearance, but completely mis- interpreted it, seeing that he referred it to an inflamma- tion of the blood itself (Haemitis) and established the doctrine of Pyzemia, upon it, termed this form of buffy coat crusta granulosa. It really consists of nothing more than large accumulations of colourless corpuscles. Under all circumstances this layer resembles pus in appearance, and since, as we have already seen, the colourless blood-cells individually are constituted like pus-corpuscles, you see that we are liable not only in the case of a healthy person to take colourless blood-cells for Fie. 60. Fig. 60. Diagram of a bleeding-glass with coagulated hyperinotic blood. a. The level of the liquor sanguinis. c. The cup-shaped buffy coat. 7. The layer of lymph (Cruor lymphaticus, Crusta granulosa), with the granular and mulberry-like accumu- lations of colourless corpuscles. 1. The red clot. 188 . LECTURE VIL : pus-corpuscles, but still more so in pathological condi- tions when the blood or other parts are full of these ele- ments. You can imagine how apt the question is to present itself, which has already been seriously raised by Addison and Zimmermann, whether pus-corpuscles are not merely extravasated colourless blood-cells, or vice versa, whether the colourless blood-cells found within the vessels are not pus-corpuscles which have been ad- mitted into them from the exterior. We are here called upon for the first time to make the practical application of the principles which I laid down with regard to the specific nature and heterology of elements (p. 92.) A pus-corpuscle can be distinguished from a colourless blood-cell by nothing else than its mode of origin. If you do not know whence it has come, you cannot say what it is; you may conceive the greatest doubt as to whether you are to regard a body of the kind as a pus- or a colourless blood-corpuscle. In every case of the sort the points to be considered are, where the body belongs to, and where its home is. If this prove to be external to the blood, you may safely conclude that it is pus; but if this is not the case, you have to do with blood-cells. GeO RE Yi. MARCH 10, 1858. BLOOD AND LYMPH. Change and replacement of the constituents of the blood—ibrine—Lymph and ita coagulation—Lymphatic exudation—Fibrinogenous substance—Formation ot the buffy coat—Lymphatic blood, hyperinosis, phlogistic crasis—Local forma- tion of fibrine—Transudation of fibrine—Formation of fibrine in the blood. Colourless blood-corpuscles (lymph-corpuscles)—Their increase in hyperinosis and hypinosis (Erysipelas, pseudo-erysipelas, typhoid fever)—Leucocytosis and leukeemia—Splenic and lymphatic leukemia. The spleen and lymphatie glands as blood-making organs—Structure of lymphatic glands. Tue last time, gentlemen, I introduced to your notice the individual morphological elements of the blood, and endeavored to portray their special peculiarities. Allow me to begin to-day with a few words concerning their origin. From the facts which have been ascertained with regard to the first development of the elements of the blood, important conclusions may be drawn respecting the nature of the changes which take place in the mass of the blood in deceased conditions. Formerly the blood was regarded more as a juice shut up by itself, which was indeed to a certain extent connected with the parts external to it, but yet was in itself endowed with real durability, and it was assumed that it could retain pecu- 189 190 LECTURE VIII. liar properties for lengthened periods, nay, that these might cling to it for many years. Of course it was im- possible at the same time to entertain the opinion, that the constituents of the blood were of a perishable nature, and that new elements were added to it, to replace the old ones. For the durability of a part as such presupposes either that all its individual particles are durable, or that these individual particles are continually producing fresh ones within the part which bear impressed upon them all the peculiarities of the old ones. In the case of the blood, therefore, one would have to assume that its con- stituents really did subsist for years, and could for years present the same changes, or one would have to imagine that the blood transmitted something from one particle to another, and that from a parent blood-cell to its pro- geny something hereditary was handed down. Of these possibilities the former has, I believe, at the present time been pretty generally discarded. No one, I think, now imagines that the individual constituents of the blood last on for years. On the other hand, the possibility that the corpuscles of the blood are renewed by propagation, and that certain peculiarities which are introduced into the blood at a certain time, are transmitted from cor- puscle to corpuscle, cannot straightway be rejected. But the only phenomena pointing to such a propagation of the blood, concerning which we possess any positive information, belong to an early period of embryonic life. There it appears from observations which were only the other day again confirmed by Remak, the existing blood- corpuscles undergo direct division, the process being that in a corpuscle which during the early stages of its deve- lopment had displayed itself as a nucleated cell, first of all a partition of the nucleus takes place (Fig. 51, c) ; and that then the whole cell becomes constricted in the middle, and gradually is really seen to pass into a state ORIGIN OF BLOOD-CORPUSCLES—LrMPH. 191 of complete division. At this early period it is therefore certainly allowable to regard a blood-corpuscle as en- dowed with qualities which are propagated from the first series of cells to the second, and from this to the third, and so on. In the blood of a fully developed human being, nay even in that of a foetus in the later months of pregnancy, these phenomena of partition are no longer known, and not a single one of the facts which can be adduced from the history of development speaks in favour of an increase of the cellular elements taking place in fully developed blood by means of direct division, or any other formative process taking its rise in the blood itself. As long as the possibility was regarded as demonstrated, that cells might arise out of simple cytoblastema by means of the direct precipitation of different substances, so long was it pos- sible to conceive new precipitates as forming in the liquor sanguinis from which cells were produced. But this view also has been abandoned. All the morphological elements of the blood, whatever may be their nature, are at present considered to be derived from sources external to the blood. On all hands recourse is had to organs which do not communicate with the blood directly, but rather by the means of intermediate channels. The principal organs which here come into play are the lymphatic glands. Lymph is the fluid which, whilst it conveys certain substances to the blood which come from the tissues, at the same time brings along with it the corpuscular elements out of which the blood-cells con- tinually recruit their numbers. With regard to two of the constituents of the blood, there can, I think, be scarcely any doubt but that this is the view which is perfectly warranted, I mean with regard to the fibrine and the colourless corpuscles. As for the fibrine, the properties of which I brought to your 192 LECTURE VIII. notice last time, it is a very essential and important fact that the fibrine which circulates in lymph differs in cer- tain respects from that contained in the blood, which we see on examining different extravasations, or blood drawn from a vein. The fibrine of lymph has this special pecu- liarity, that under ordinary circumstances it coagulates within the lymphatic vessel neither during life nor after death, whilst blood in many instances coagulates even during life, and regularly does so after death, so that coagulative power is attributed to blood as being one of its regular properties. In the lymphatics of a dead ani- mal or human corpse, no coagulated lymph is met with, yet the coagulation takes place directly the lymph is brought into contact with the air, or has changes imparted to it by some diseased organ. The explanation of this peculiarity has been attempted in very different ways. For my own part I must still adhere to the view that there is, properly speaking, no perfectly developed fibrine contained in lymph, but that it becomes perfect either by contact with the atmosphe- ric air, or in abnormal conditions by the introduction into it of altered matters. Normal lymph contains a substance which is very readily converted into fibrine, and is, when it has once coagulated, scarcely to be distinguished from fibrine, but which, as long as it continues to circulate with the ordinary stream of lymph, cannot be regarded as really perfect fibrine. This is a substance, of which I had demonstrated the presence in various exwdations, especially in pleuritic fluids, long before my attention had been drawn to its occurrence in lymph. In many forms of pleurisy the exudation long remains fluid, and a number of years ago a peculiar case came under my notice, in which on puncturiug the thorax a liquid was evacuated which was perfectly clear and fluid, but in a short time after its evacuation had its whole FIBRINE OF LYMPH. 1938 mass pervaded by a coagulum, as is often enough the case with fluids from the abdominal cavity. After I had removed this coagulum from the liquid by stirring it, in order to convince myself of its identity with ordinary fibrine, the next day a fresh coagulum displayed itself, and this took place also on the following days. This co- agulative power lasted fourteen days, although the ope- ration had been performed in the midst of the heat of summer. This therefore was a phenomenon essentially differing from the ordinary coagulation of the blood, and somewhat difficult to explain upon the supposition that real fibrine existed completely developed in the fluid, but it seemed to indicate that it was only under the influ- ence of the atmospheric air that the fibrine was produced from a substance which must indeed have been nearly related to fibrine, but yet could not be real fibrine. I therefore propose to give it the distinctive name of fibri- nogenous substance, and when I afterwards had come to the conclusion that it was the same substance which we find in lymph, I was enabled to extend my view so as to include the proposition, that in lymph also fibrine is not contained in a perfect form. This same substance, which is distinguished from ordi- nary fibrine by its requiring to be a longer or shorter time in contact with atmospheric air before it can become coagulable, is also found under certain circumstances in the blood of the peripheral veins, so that even by an ordinary venesection performed on the arm blood may be obtained, distinguished from ordinary blood by the slowness of its coagulation. Polli named this coagula- tive substance brady-fibrine. Such cases occur especially in inflammatory diseases of the respiratory organs, and most frequently give rise to the formation of a buffy coat (crusta pleuritica, crusta phlogistica). You all know that the ordinary crusta phlogistica forms in the blood of 13 194 LECTURE VIII. pneumonia or pleurisy the more readily the greater the wateriness of the liquor sanguinis, and the poorer the blood is in solid constituents, but it is an essential requisite that the tibrine should coagulate slowly. If the duration of the process be noted watch in hand, the conviction will soon be acquired that a very much longer time passes than is requisite for ordinary coagulation. From this frequent phenomenon, as it is met with in the ordinary formation of a crust upon the surface of inflamed blood, gradual transitions are observed to a greatly increased prolongation of the period during which fluidity is re- tained. The most extreme instance of this kind as yet known occurred in a case observed by Polli. In a vigorous man, suffering from pneumonia, who came under treatment in the summer, at a time which does not offer the external conditions most favourable to slowness of coagulation, the blood, which flowed from the opened vein, took a week before it began to coagulate, and not until the end of a fortnight was the coagulation complete. In this case, too, occurred the other phenomenon which J had ob- served in the pleuritic exudations, namely, that decom- position (putrefaction) took place in the blood at an unusally late period in proportion to this lateness of coagulation. Now since phenomena of this kind are observed to occur with especial .frequency in chest affections, a fre- quency so especial indeed that the buffy coat was long since designated Crusta pleuritica, there would seem to be some grounds for inferring from this, that the function of respiration has a definite influence upon the occur- rence or non-occurrence of the fibrinogenous substance in the blood. At all events, the peculiarity possessed by the lymph is under certain circumstances transmitted to the blood, so that either the whole of the blood partakes FIBRINE REGARDED AS A LOCAL PRODUCTION. 195 of it, and that in a higher degree, the greater the disturb- ance under which the respiration labours; or, in addi- tion to the ordinary, quickly coagulating matter, a second which coagulates more slowly is found. It frequently happens, namely, that two sorts of coagulation subsist side by side in the same blood, one early and the other late, especially in the cases in which direct analysis shows an increase of fibrine, a hyperinosis. These hyperinotic conditions appear therefore to indicate that in them an increased supply of lymphatic fluid is introduced into the blood, and that the matters which are afterwards found in the blood are not the products of an internal fransfor- mation of its constituents, and that therefore the ori- ginal source of the fibrine must not be sought for in the blood itself, but in those parts from which the lymphatic vessels convey the increased supply of fibrine. In explanation of these phenomena, I have ventured to advance the hypothesis, somewhat bold perhaps, though I consider it perfectly able to sustain discussion, namely, that fibrine generally, wherever tt occurs in the body exter- nal to the blood, is not to be regarded as an excretion from the blood, but as a local production ; and I have endea- vored to introduce an important change in the views en- tertained with regard to the so-called phlogistic crasis in relation to its localization. Whilst it had previously been the custom to regard the altered composition of the blood in inflammation as a condition existing from the very outset, and especially denoted by a primary increase in the fibrine, I on the contrary have shown the crasis to be an occurrence dependent upon the local inflammation. Certain organs and tissues have inherent in them in a higher degree the power of producing fibrine and of fa- vouring the occurrence of large quantities of fibrme in the blood, whilst other organs are by far less adapted for its production. 196 LECTURE VIIL I have, moreover, pointed out the fact, that those or vans which with especial frequency exhibit this peculiar combination of a so-called phlogistic state of the blooa with a local inflammation are generally abundantly pro- vided with lymphatic vessels and connected with large masses of lymphatic glands, whilst all those organs which either contain very few lymphatics, or in which these vessels are scarcely known to exist, do not exercise any influence worth naming upon the amount of fibrine in the blood. Former observers had already remarked that there were inflammations occurring in very import- ant organs, as for example, in the brain, in which the phlogistic crasis was, properly speaking, not at all met with. Now it is precisely in the brain that we have scarcely any evidence of the existence of lymphatics. In those cases, on the contrary, in which the composition of the blood is earliest altered, namely, in diseases of the respiratory organs, we find an unusually abundant net- work of lymphatics. Not merely the lungs are pervaded by, and covered with, them, but the pleura also has ex- tremely numerous connections with the lymphatic sys- _ tem, and the bronchial glands constitute almost the great- est accumulations of lymphatic-gland substance possessed by an organ in the whole body. On the other hand, we are acquainted with no fact which shows it to be possible that, in consequence of a simple increase of the pressure of the blood, or of a simple change in the conditions which influence its cir- culation, an exudation of fibrinous fluids could in any organ take place into its parenchyma, or upon its sur- face, from the blood. It is certainly generally imagined that, when the current of the blood attains a certain strength, fibrine begins to appear in the exudation, but this has never been proved by experiment. Nobody has ever been able, by the production of a mere change i LOCAL FORMATION OF FIBRINE, 197 the force of the current of the blood, to induce the fibrine to transude directly as it is wont to do in certain inflammatory processes; for this some irritation is always required. The greatest obstructions may be in- duced in the circulation, exudations of serous fluids may be experimentally produced upon the largest scale, but that peculiar fibrinous exudation which the irritation of certain tissues provokes with so much ease, never ensues upon these occasions. That the fibrine in the blood itself is produced by a transformation of the albumen, is a chemical theory, which has no other evidence in its favour than the fact that albumen and fibrine have a strong chemical resem- blance, and that, on comparing the questionable formula for fibrine with the equally questionable one for albu- men, it is very easy to imagine how, by the abstraction of a couple of atoms, the transition from albumen to fibrine might be effected. But our being able in this manner to deduce one of the formule from the other does not afford the slightest proof that an analogous transformation occurs in the blood. It may possibly take place in the body, but even then it would at any rate be more probable that it was accomplished in the tissues, and that from them the fibrine was conveyed away into the blood by means of the lymph. This is, however, the more doubtful, because rational formule for the chemical composition of albumen and fibrine have not yet been determined, and the incredibly high atomic numbers in the empirical formule point to a very com- plex grouping of the atoms. Let us therefore hold fast the well-ascertained fact that fibrine can only be made to exude upon any surface by the occurrence of some irritation, that is, local change, in addition to the disturbance in the circulation. This local change, however, is, as results from experi- 198 LECTURE VIII. ment, alone sufficient to cause the exudation of fibrine, even when no obstruction arises in the circulation. Such obstruction is not therefore in any way needed in order that the production of fibrine may commence at any given point. On the contrary, we see that the cause of the greatest differences in the nature of exudations is to be found in the special constitution of the irritated parts. On the simple application of an irritating substance to the surface of the skin, there arises, when the irritation, whether chemical or mechanical in its nature, is only slight in degree, a vesicle, a serous exudation. If the irritation is more violent, a liquid exudes, which in the vesicle appears quite fluid, but coagulates after its eva- cuation. If the fluid from a blister raised by a cantha- rides-plaster be received into a watch-glass and exposed to the air, a coagulum forms, showing that there is fibrinogenous substance in the fluid. But we sometimes meet with conditions of the body, in which an external stimulus is sufficient for the production of blisters con- taining a fluid which directly coagulates. I had, last winter, a patient in my wards, whose feet had remained -n a state of anzesthesia ever since they had been frozen, and I employed as a remedy, amongst other things, local baths containing aqua regia. After a certain num- ber of these baths, blisters, which varied in diameter up to two inches, and were found, when opened, to be filled with large, jelly-like masses of coagulum, formed upon every occasion on the anesthetic part of the soles of the feet. In other persons probably ordinary blisters would have formed, containing a fluid, which would not have coagulated until after its evacuation. Such a difference manifestly depends upon a difference, not in the com- position of the blood, but in the disposition of the part affected. The difference between that form of pleurisy, which from its very commencement furnishes coagulable LOCAL FORMATION OF FIBRINE. 199 and coagulating fluids, and that in which the exudation is coagulable, but not coagulating, certainly points to peculiarities in the local irritation. I do not think therefore that we are entitled to con- clude that in a person who has an excess of fibrine in his blood, there is on that account also a greater tendency to fibrinous transudation ; on the contrary, I should rather expect that in a patient who produces at a certain point a large quantity of fibrine-forming substance, much of it would pass from that point into the lymph and finally into the blood. The exudation may therefore in such cases be regarded as the surplus of the fibrine formed in loco, for the removal of which the lymphatic circulation did not suffice. As long as the current of lymph does suffice, all the foreign matters which are formed in the irritated part are conveyed into the blood ; but, as soon as the local production becomes excessive, the products accumulate, and in addition to the hyperinosis, a local accumulation of fibrinous exudation will also take place. On account of the shortness of the time which is allotted to us, we cannot follow up this subject in its whole . extent, but still I hope that you will at least completely grasp the fundamental idea which has guided me. Here, too, we have another example of that dependence of a dyscrasia upon a local disease to which I but a short time ago called your attention as being the most impor- tant result of all our investigations concerning the blood. Now it is a very remarkable fact, and one which adds weight to this very view of mine, that it is very rarely that a considerable increase of fibrine takes place without a simultaneous increase in the colourless blood-corpuscles, and that therefore the two essential constituents which we find in the lymph we again meet with in the blood. In every case of hyperinosis we may rely upon discover- ing an increase in the colourless corpuscles, or, in other 200 LECTURE VIII. words, every irritation of a part, which is abundantly provided with lymphatics, and freely connected with lymphatic glands, occasions also the introduction of large numbers of colourless cells (lymph-corpuscles) into the blood. This fact is especially interesting, inasmuch as you will perceive from it, that not only organs richly pro- vided with lymphatic vessels can occasion this increase, but that certain processes also are more calculated than others to lead to the introduction of considerable quantities of these elements into the blood, namely all those which are early conjoined with serious disease in the lymphatic system. If you compare an erysipelatous, or a diffuse phlegmonous (according to Rust pseudo-erysipelatous), inflammation in its effects upon the blood with a simple superficial inflammation of the skin, such as occurs in the course of the ordinary acute exanthemata, or after trau- matic or chemical irritation, you will at once see how great the difference is. Every erysipelatous or diffuse phlegmonous inflammation has the peculiarity of early _ affecting the lymphatic vessels and producing swellings in the lymphatic glands. In such a case we may feel assured that an increase in the number of the colourless- corpuscles is taking place. Further, we find the signifi- cant fact, that there are certain processes which simul- taneously cause an increase of fibrine and colourless cor- puscles, and others again which only occasion an increased production of the latter. To this latter category belong the whole series of simple diffuse inflammations of the skin, in which also no considerable formation of fibrine takes place in the diseased parts. On the other hand, a number of conditions belong to it, which with regard to the quantity of fibrine may be designated as hypinoti- cal, all the processes namely which belong to the typhoid class, and agree in producing considerable swelling now LEUCOCYTOSIS AND LEUKAM,A. 901 of one, and now of another, kind in the lymphatic glands, but do not produce any local exudation of fibrine. Thus typhoid fever causes these changes not only in the spleen, but also in the mesenteric glands. ‘The condition in which the increased proportion of colourless corpuscles in the blood appears to be depend- ent upon an affection of the lymphatic glands, I have de- signated by the name of Leucocytosis. Now you know that another matter has long been the subject of my stu- dies, the affection named by me Leukemia, and our next business must be to determine how far genuine leuka- mia differs from these leucocytotical conditions. In the very first cases of leukeemia which came before me, a very essential property was discovered to exist, namely, that there was no essential variation in the proportion of fbrine in the blood. Afterwards it was found out that the proportion of fibrine might, according to the parti- cular circumstances of the case, be greater or less than, or the same as, usual, but that a continually augmenting imcrease of the colourless blood-corpuscles invariably took place ; and that the coincidence of this increase with a diminution in the number of the coloured (red) corpus- cles became more and more marked, so that as a final result a condition was attained, in which the number of the colourless corpuscles was almost equal to that of the red ones, and striking phenomena were displayed, even when the coarser modes of observation were employed. Whilst in ordinary blood we can seldom count more than one colourless corpuscle to about three hundred coloured ones, there are cases of leukeemia in which the increase of the colourless ones reaches such a height, that to every three red corpuscles there is one colourless one, or even two; or in which indeed the greater numbers are in favour of the colourless corpuscles. In dead bodies the increase in the colourless corpus- 202 LECTURE VIII. cles generally appears more considerable than it really is, from reasons which I but a short time ago pointed out to you (p. 184); for these corpuscles possess extraordi- nary adhesiveness and accumulate in considerable masses wherever there is a retardation in the stream of blood, so that in the dead body the greatest number is always found in the right heart. Once, before I left Berlin, this singular case occurred to me, that, when I punctured the right auricle, the physician who had treated the case cried out, astonished, ‘‘ Why, there’s an abscess there !” So like pus did the blood appear. This puriform condi- tion of the blood does not indeed pervade the entire cir- culating stream ; the whole of the blood never looks like pus, because a comparatively large number of red cor- puscles always continues to exist ; stillit sometimes hap- pens that blood flowing from a vein even during life exhibits whitish streaks, and that, when the fibrine has been removed by stirring, and the defibrinated blood is allowed to stand,a voluntary separation at once takes place, the whole of the blood-corpuscles, red and colour- less, gradually sinking to the bottom of the vessel, and there forming a double sediment, a lower red stratum, covered by an upper, white and puriform one. This is explained by the difference in the specific gravity of the two kinds of corpuscles and the time they take to sink (p. 186). In this way too we are enabled very readily to distinguish leukemic from chylous (lipemic) blood in which a milky appearance of the liquor sanguinis is produced by the admixture of fat, for, if the fibrine be removed, after some time there forms not a white sediment, but a cream-like layer on the surface. In the histories of all the known cases of leukemia we only find it once as yet recorded that the patient, after he had been for some time the subject of medical treat- ment, left the hospital considerably improved in health. LEUKAEMIA, 903 In all the other cases the result was death. I do not wish by any means to infer from this that the disease in question is absolutely incurable ; I hope on the contrary that for it too remedies will at length be discovered ; but it is certainly a very important fact that we have in it, much, as in the progressive atrophy of muscles, to deal with conditions, which, when abandoned to themselves, or subjected to any one of the hitherto known methods of treatment, continually grow worse and ultimately lead to death. These cases possess, in addition, the remark- able peculiarity that, usually towards the close of life, a genuine hemorrhagic diathesis is developed and heemor- rhages ensue, which occur with especial frequency in the nasal cavity (under the form of exhausting epistaxis) but may also, under certain circumstances, take place in other parts of the body, as for example on a very large scale in the form of apoplectic clots in the brain, or of melzena in the intestinal canal. Now, upon investigating whence this curious change in the blood takes its origin, we find in the great majority of cases that it is a certain, definite organ which presents itself over and over again with convincing constancy as the one essentially diseased, an organ which frequently, even at the outset of the malady, forms the chief object of the complaints and distress of the patients, namely, the spleen. In addition, a number of lymphatic glands are very frequently diseased, but the affection of the spleen stands in the foreground. Only in a few cases have I found the change in the spleen the less and that in the lymphatic glands the more prominent, and in these, matters had proceeded to such a pitch, that lymphatic glands, at other times scarcely observable, had developed themselves into lumps the size of walnuts, and that indeed in some few places there appeared to be scarcely anything else than glandular substance. Of the 904 LECTURE VIII. glands which lie between the inguinal and lumbar glands we are wont to hear but little, nor have they indeed even a suitable name. Some of them lie in the course of the iliac vessels, and some in the real pelvis. But in two of these cases of leukeemia I found them so enlarged that the whole cavity of the pelvis proper was, as at were, stuffed full of glandular substance, between which the rectum and the bladder only just dipped in. I have therefore distingushed two forms of leukeemia, namely, the ordinary splenic, and the lymphatic, form, which are certainly not unfrequently combined. The distinction rests not only upon the circumstance, that in the one case the spleen, in the other the lymphatic glands, constitute the starting point of the disease, but also upon the fact that the characteristic morphological elements which are found in the blood are not precisely similar. Whilst namely in the splenic forms these elements are generally comparatively large and perfectly developed cells with one or more nuclei, and in many cases bear a particularly great resemblance to the cells of the spleen, we notice in the well-marked lymphatic forms that the cells are small, the nuclei large in proportion and single, usually sharply defined, with~dark outlines and somewhat granular, whilst the cell-wall is frequently in such close apposition to them that an interval can scarcely be de- monstrated. In many instances it looks as if perfectly free nuclei were contained in the blood. In these (the lymphatic) cases, therefore, it seems that the enlarge- ment of the glands alone, which is accompanied in its progress by a real increase in the number of their ele- ments (hyperplasia), also conveys a larger number of cel- lular elements into the lymph and through this into the blood, and that, just in proportion to the predominance of these elements, the formation of the red cells suffers obstruction. This is in a few words the history of these HYPERINOSIS, LEUCOCYTOSIS AND LEUK MIA. 905 processes. Leukzemia is thus a sort of permanent, pro- gressive leucocytosis, whilst this on the other hand in its simple forms constitutes a transitory process, connected with fluctuating conditions in certain organs. You see therefore that there are at least three different conditions here, bordering one upon the other : hyperino- sis, leucocytosis and leukemia, between which and the lymphatic fluids there exists an intimate connection. The one series, that namely which is distinguished by an increase in the quantity of fibrine, is rather to be referred to the accidental condition of the organs from which the lymphatic fluids are derived, whilst those states which are induced by an increase in the number of cellular ele- ments are rather regulated by the condition of the glands through which these fluids have flowed. These facts can hardly, I think, be interpreted in any other manner than by supposing that the spleen and lymphatic glands are really intimately concerned in the development of the blood. This has become still more probable since we have succeeded in obtaining chemical evidence also in support of it. Herr Scherer upon two occasions ex- amined leukemic blood which I had submitted to him, in order to compare it with the matters he had discovered in the spleen, and the result was that hypoxanthine, leucine, uric, lactic, and formic, acid, were found there. In one case of leukemia a liver which I had kept for several days became entirely covered with granules of tyrosine ; in another, leucine and tyrosine crystallized in large masses out of the contents of the intestines. In short, everything points to an increased action in the spleen, which normally contains these substances in con- siderable quantity. A good many years elapsed (after 1845) during which I found myself pretty nearly alone in my views. It has only been by degrees and indeed, as I am sorry to be 206 LECTURE VIII. obliged to confess, in consequence rather of physiological than pathological considerations, that people have come round to these ideas of mine, and only gradually have their minds proved accessible to the notion, that in the ordinary course of things the lymphatic glands and the spleen are really immediately concerned in the produc- tion of the formed elements of the blood ; and that in particular the corpuscular constituents of this fluid are really descendants of the cellular bodies of the lymphatic glands and the spleen which have been set free in their interior and conveyed into the current of the blood. And let this serve as an introduction to the consideration of the question of the origin of the blood-corpuscles themselves. You will probably recollect, gentlemen, from the time of your studies, that the lymphatic glands used to be regarded as coils of lymphatic vessels. The afferent lymphatics may, as is well known, even with the naked eye be seen breaking up into smaller branches, disappear- ing within the glands, and finally again emerging from them. From the results of the mercurial injections which even in the last century were made with such great care, the only inference to be drawn appeared to be, that the afferent lymphatic vessel formed a number of convolutions, which interlaced in various ways and were finally continued into the efferent vessel, so that the gland was composed of nothing else than the thickly crowded coils of the afferent vessels. The whole atten- tion of modern histologists has been directed to the task of confirming this tortuous transit of the lymphatic ves- sels through the gland, but after many years of labour spent in vain, the attempt was at length abandoned. At the present moment there is, I should suppose, scarcely an histologist who believes in the perfect conti- nuity of the lymphatic vessels throughout the gland, but STRUCTURE OF LYMPHATIC GLANDS. 907 Kolliker’s view is generally adopted, that the lymphatic glands interrupt the current of the lymph, the afferent vessel resolving itself into the parenchyma of the gland and reconstituting itself out of it. This condition we cannot well compare with anything else than a kind of filtering apparatus, something like our ordinary sand or charcoal filters. When a gland is cut across, a structure is frequently brought to view resembling that of a kidney. At those points where the afferent vessels break up, a firmer sub- stance is seen to lie, half surrounded by which a kind of hilus marks the spot at which the lymphatic vessels again forsake the gland. Here there is found a reticular tissue with an often distinctly areolar or cavernous structure, into which, besides the efferent lymphatic vessels, blood- vessels also enter on their way into the proper substance of the gland. Kélliker has accordingly distinguished a cortical and a medullary substance ; but the so-called medullary substance scarcely retains the character of glandular tissue. This is found chiefly in the cortical substance, which is of greater or less thickness, and it is therefore best to call the medullary substance simply the hilus, since afferent and efferent vessels lie there in close contact, just as in the hilus of the kidneys the ureters and veins emerge, whilst the arteries enter. The essential part of the gland is therefore the periphery, the often kidney-like cortical substance. In this can be distinguished, whenever the gland is at all well developed (and in some cases of pathological en- largement it is extremely distinct) even with the naked eye, little, roundish, white or grey granules lying side by side. When the part is moderately well filled with blood, around each granule may be pretty nearly always discerned a red circle of vessels. These granules have long been called (follicles, but it was doubtful 208 LECTURE VIII. whether they were distinct formations or mere convolu- tions of the lymphatic vessel protruding on the surface. Upon more delicate microscopical examination, the proper (glandu- lar) substance of the follicles can easily be distinguished from the fibrous meshwork (stroma) which bounds them on all sides, and is externally continuous with the connective tissue of the capsule. The internal substance is chiefly composed of little cellular ele- ments, which lie pretty loosely, being merely enclosed in a fine network of star-shaped, often nu- cleated trabecule. If we attempt to search for the lymphatic vessels in the cortical substance, but very little can be discovered of them in the stroma, and if a gland be injected, the injection penetrates right into the middle of the follicles. If a mesenteric gland be examined during chylification, that is perhaps three or four hours after a meal at which fat has been taken in abundance, its whole substance appears white and per- fectly milky, and on examining individual parts of it microscopically, the minute fat-drops of the chyle may be detected every where lying between the cellular ele- ments of the follicles. It seems, therefore, that the cur- rent of lymph forces its way between these elements, and Fie. 61. Fig. 61. Sections through the cortical substance of human mesenteric glands. A. View of the whole cortical substance slightly magnified: P, investing adipose tissue and capsule, through which blood-vessels v, », v enter. F, F, F. Follicles of the gland, into which the blood-vessels in part plunge, at i, ¢ the interstitial tissue separating the follicles (stroma). B. More highly magnified (280 times). C. The tissue of the capsule with paral- lel fibrils. a, a. The reticulum, partly empty, partly filled with the nucleated con- tents. The whole corresponds to the outer part of a follicle. STRUCTURE OF LYMPHATIC GLANDS. 209 that no really free channel for it exists, seeing that the lements le crowded together like the particles in a sharcoal filter, so that the lymph trickles out again on the other side in a more or less purified state. The fol- icles should accordingly be regarded as spaces filled with cellular clements but variously intersected by a trabecu- ar network, and thus they can no longer be held to be sonvolutions or dilatations of the lymphatics, but must ye viewed as interposing themselves in the course of these vessels after they have broken up into a series of ramifications continually increasing in minuteness. Of the minute elements contained in the follicles, the sells of the parenchyma, some appear to become separated Fie. 62. B + A é d a2, cu S20 G2e” “a a® FOP and afterwards to mingle with the blood as colourless blood- or lymph-corpuscles. The more the glands be- come enlarged, the more numerous are the cellular ele- ments which pass into the blood, and the larger and more perfectly developed are the individual colourless cells of the blood wont to be. The same condition seems to prevail in the spleen. Originally we all imagined that the veins were the chan- Fig. 62. Lymph-corpuscles from the interior of the follicles of a lymphatic gland. A. As usually seen; a, free nuclei, with and without nucleoli, simple and divided. 3. Cells with smaller and larger nuclei, which are closely invested by the cell-wall. B. Enlarged cells from a hyperplastic bronchial gland in a case of variolous pneu- monia (comp. in Fig. 57 the colourless blood-corpuscles from the same source). a. Largish cells with granules, and single nuclei. 6. Club-shaped cells. c. Larger cells with larger nuclei and nucleoli. d. Division of nuclei. . Club-shaped cells in close apposition (cell-division?). C. Cells with an endogenous brood. 300 diameters. 14 210 LECTURE VIII. nels by which the colourless corpuscles were conveyed away from the spleen; but in this instance also I have come to the conclusion that their removal is in all proba- bility effected by means of the lymphatic vessels. LECTURE IX. MARCH 13, 1858. PYAIMIA AND LEUCOCYTOSIS. Comparison between colourless blood- and pus-corpuscles—Physiological re-absorp tion of pus; incomplete (inspissation, cheesy transformation), and complete (fatty metamorphosis, or milky transformation). Intravasation of pus. us in the lymphatic vessels—Retention of matters in the lymphatic glands—Me- chanical separation (filtration)—Coloration by tattooing—Chemical separation (attraction): Cancer, Syphilis—Ivritation of lymphatic glands, and its relation to leucocytosis. Digestive and puerperal (physiological) leucocytosis—Pathological leucocytosis (Scrofulosis, typhoid fever, cancer, erysipelas). Lymphoid apparatuses: solitary and Peyerian follicles in the intestines—Tonsils and follicles of the tongue—Thymus—Spleen. ‘omplete rejection of pyzemia as a dyscrasia susceptible of demonstration morpho- logically. . In a practical point of view the question of pyemia forcibly intrudes itself upon us in connection with the changes which we have last considered, and as this must still be reckoned among the most controvertible of sub- jects, you will, I hope, allow me to enter a little more particularly into its details. What is to be understood by pyemia? It has gene- rally been conceived to be a condition, in which tke blood contains pus, and as pus is essentially characterized by its morphological constituents, what is meant of course is, that pus-corpuscles are to be seen in the blood. Now that we have found out, however, that the colour- 211 219 LECTURE IX. less corpuscles of the blood as they usually appear and are to be observed in people in the best state of health, resemble pus-corpuscles in every respect (p. 180), one essential point in the question is thus at the very outset got rid of. In order, however, to render the subject to some extent perspicuous, it is necessary to enter into the _ consideration of the different points of view which are here involved a little more in detail. Colourless blood-cells are so like pus-corpuscles as easily to be mistaken for them, so that if in any specimen we meet with such elements, we can never say with certainty off-hand whether we have to deal with colourless blood-, or pus-corpuscles. Formerly, and to some extent even up to our own times, the view was very generally enter- tained that the constituents of pus pre-existed in the blood ; that pus was only a kind of secretion from the blood, in somewhat the same way that urine is ; and that it could also like a simple fluid return into the blood. This view explains, you see, the conception which has been so long preserved in the doctrine of the so called physiological reabsorption of pus. It was imagined that the pus might be again taken ap into the blood from the different points at which it had been deposited, and that a favourable turn was thereby effected in the disease, inasmuch as the reabsorbed pus was thus at last removed from the body. The tale went that in the case of a patient with pus in the cavity of the pleura the disease might terminate in the evacuation of purulent urine or purulent feeces, without the pus having previously made its way directly from the pleura into the urinary passages or the intestinal canal. It is therefore admitted to be possible that pus may be reabsorbed and conveyed away in substance. Afterwards, when the doc- trine of pyeemia had more and more gained ground, these cases were distinguished by the name of physiological re- REABSORPTION OF PUS. 213 bsorption of pus, from that which was considered to be rathological, and the only question that remained was, a what way the first process with its favourable and the econd with its malignant issue could be accounted for. “his matter finds its simple solution in the fact that pus is pus ws never reabsorbed. There is no form, by which yus in substance can disappear by the way of reabsorp- ion ; it is always the fluid part of the pus which is taken ip, and therefore what is called the reabsorption of pus nay be referred to the two following possibilities. In the first case, the pus with its corpuscles is at the ime of the reabsorption still more or less intact. Then he pus becomes of course thicker in proportion as the luid disappears. This constitutes the long known ¢hick- ning (inspissation) of pus, whereby is produced what the ‘rench term ‘‘ pus concret,” which consists of a thick nass, containing the pus-corpuscles in a shrivelled con- lition, when not only the fluid between the pus-corpus- les (pus-serum) but a part also of that present in them 1as disappeared. Fig. 63. A. Pus-corpuscles, a fresh, 6 after the addifion of a little water, c—e fter treatment with acetic acid, the contents cleared up, the nuclei which were in wocess of division, or already divided, visible, at ¢ with a slight depression on heir surface. B. Nuclei of pus-corpuscles in gonorrhcea; a simple nucleus with iucleoli, 6 incipient division, with depressions* on the surface of the nuclei, ¢ pro- sressive bi-partition, d tri-partition. (C. Pus-corpuscles in their natural position vith regard to one another. 500 diameters. * By many held to be nucleoli, 214 LECTURE IX. Pus consists essentially of cells, which in their ordinary condition lie close to one another (Fig. 63, C, and be- tween which a small quantity of intercellular fluid (pus- serum) exists. Within the pus-corpuscles themselves lies a substance which is likewise provided with a great quan- tity of water ; for nearly every specimen of pus, although it may look very thick when fresh, contains such a large amount of water that it loses a great deal more by eva- poration than a corresponding quantity of blood. The latter only gives the impression of being more watery: because it contains a great deal of free (intercellular), but relatively little intracellular, fluid, whilst in pus on the contrary there is a greater quantity of water in the cells, and less without them. When then reabsorption takes place, the greatest part of the intercellular fluid first dis- appears, and the pus-corpuscles draw nearer to one an- other ; soon, however, a part of the fluid from the cells themselves also vanishes, and in propor- tion as this is the case, they become @ 6. & aa smaller, more irregular, angular, and un- @ poo even, they assume the most singular ‘ ® forms, lie closely pressed together, re- ses fract the light more strongly on account of their containing a greater quantity of solid matter, and present a more homogeneous appear- ance. This kind of inspissation is by no means so rare a pro- cess as it is often assumed to be, but on the contrary of extremely frequent occurrence, and almost even more important than frequent. This is namely one of the pro- cesses which lead to the formation of the much discussed Fig. 64. Inspissated, cheesy pus. u. Shrivelled pus-corpuscles, diminished in size, somewhat distorted, and looking more homogeneous and solid than usual. b. Similar corpuscles with fat granules. ¢. Their natural position with regard to one another. 300 diameters. INSPISSAT ION (TUBERCULIZATION) OF PUS. 915 cheesy products which have recently been all included under the term tubercle, and concerning which it has been shown, especially by Reinhardt, that they must to a very considerable extent really be referred to pus as their origin, and therefore be regarded as inflammatory products. Hereafter, we shall see that these observa- tions have been employed for the deduction of false con- clusions concerning tubercle itself; but that by inspissa- tion inflammatory products can be converted into things which are called tubercles, is indubitable. It is precisely in the history of pulmonary tuberculosis that this opera- tion plays a very prominent part. You have only to imagine shrivelled-up cells like these inclosed within the alveoli of the lungs and undergoing inspissation of their contents in one alveolus after another, and you will at length obtain a cheesy hepatization such as is usually described under the name of tubercular injfiltration.. This imperfect reabsorption, in which only the fluid constituents are reabsorbed, leaves the mass of solid con- stituents lying in the part as a caput mortuum, as a mass deprived of vitality and no longer capable of life. This is the kind of inspissation which we see occur on a large scale in the case of imperfect reabsorption of pleuritic exudations, when very large layers of a crumbling sub- stance remain behind in the sac of the pleura; and also round about the vertebral column in caries of the verte- Fie. 65. Gio 2B so £ d Be (i 4 p ED er & 4 q © Fig. 65. Inspissated hemorrhagic pus from a case of empyema, some of it in pro- cess of disintegration. a. The natural mass, containing granular débris, shrivelled pus- and blood-corpuscles. 6, The same mass treated with water; a few granular, decolorized blood-corpuscles have become evident, cand d. After the addition of acetic acid, 300 diameters, and at d 520. 216 LECTURE IX. bre (Spondylarthocace), cold abscesses, etc. In all these cases the reabsorption is at an end as soon as the fluid has disappeared. Herein consists the evil import of these processes. For the solid parts which are not reabsorbed, either remain lying in the part as such, or they may afterwards soften, in which case, however, they do not usually undergo reabsorption, but for the most part give rise to ulceration. At all events what is reab- sorbed is not pus, but a simple fluid composed in great part of water, a few salts, and a very small quantity of albuminous matter, and there can be no question but that we have here presented to us one of the most incom- plete forms of reabsorption. The second form of purulent reabsorption is that which constitutes the most favourable case, when the pus really disappears and no essential part of it need remain be- hind. But here too the pus is not reabsorbed as pus, but first undergoes a fatty metamorphosis ; every single cell sets fatty particles free within it, breaks up and at last nothing further remains than fatty granules and inter- vening fluid. Then therefore there exist no longer either cells or pus; and their place is occupied by an emulsive mass, a kind of milk, composed of water, some albuminous mat- ter and fat, and in which even sugar has on various occa- sions been demonstrated, whereby a still greater analogy with real milk is brought about. It is this pathological milk which afterwards comes to be reabsorbed—once more therefore not pus, but fat, water, and salts. These are the processes which may be denominated ‘ physiolo- Fig. 66. Pus engaged in retrograde fatty metamorphosis (fatty degeneration), a. Commencement of the change. 0. Fat-granule cells with nuclei still distinct. ce. Granule-globule (inflammatory globule). d. Disintegration of the globule. ¢ Emulsion, milky débris. 350 diameters, PUS IN THE LYMPHATIC VESSELS. O17 gical reabsorption of pus ;” a reabsorption, in which pus is not reabsorbed as such, but either only its fluid consti- tuents, or its solid ones after they have been considerably altered by an internal transformation. There is however certainly one case in which pus in substance may become the object, not exactly of a reab- sorption, but at any rate of an intravasation, and where this intravasated pus may circulate within the vessels ; I mean the case in which a vessel receives a wound or is perforated and pus passes through the opening into its interior. An abscess may lie close to a vein, burst through the walls, and evacuate its contents into the ves- sel. Still more easily can such a transit be effected in lymphatic vessels which run into open abscesses. The only question therefore is how far we are entitled to con- sider this case as a frequent one. As far as the veins are concerned, the possibility of such an occurrence has been for the last twenty years confined within somewhat nar- row limits, and the notion of the reabsorption of pus in substance through the medium of the veins has been more and more abandoned; but about its taking place by means of the lymphatics people still pretty fre- quently talk, and indeed they have frequently occasion, to do so. But it is almost a matter of indifference whether the pus really finds its way into lymphatic vessels from the outside, or, whether, as others assume to be the case, it owes its origin to inflammation in the lymphatic vessels ; ultimately, the question is always this, how far a lymph- atic vessel filled with pus is capable of effecting an eva~ cuation of its contents into the circulating stream of blood, and producing a genuine pyemia. The possibility of such an occurrence must as a rule be denied, and in- deed for a very simple reason. All the lymphatic ves- sels which are in a condition to take up pus in this way 218 LECTURE IX. are peripheral ones, whether they arise from external or internal parts, and only after a somewhat lengthened course do they gradually reach the blood-vessels. In all, interruptions are formed by the lymphatic glands, and since we know that the lymphatic vessels do not pass through the glands as wide, tortuous, and interlacing canals (p. 208), but that, after they have broken up into fine branches, they enter into spaces which are filled with cellular elements, it is manifest, that no pus-corpuscle can pass a gland. This is a very important point of view which curiously enough is generally overlooked, although it meets with the best possible confirmation in the daily experience of the practical physician. In proof of the inevitable ob- struction to the passage of solid particles through the lymphatic glands, a very pretty experiment is afforded by a custom prevalent amongst the lower classes of our population, the well-known practice of tattooing the arms and occasionally other parts. When a workman or a soldier has a number of punctures made upon his arm, and arranged so as to represent letters, signs, or figures, nearly always, in consequence of the great number of punctures, some of the superficial lymphatic vessels are injured. It could not indeed well happen otherwise than that, when whole regions of skin are circumscribed by the pricks of a needle, at least some few lymphatic ves- sels should be hit upon. Afterwards a substance is rub- bed in which is insoluble in the fluids of the body, such as cinnabar, gunpowder, or the like, and which, remain- ing in the parts, causes a permanent coloration of them. But in the rubbing in a certain number of the particles find their way into lymphatic vessels, are carried along in spite of their heaviness by the current of lymph, and reach the nearest lymphatic glands, where they are sepa- rated by filtration. We never find that any particles are DEPOSITS IN LYMPHATIC GLANDS AFTER TATTOOING. 919 conveyed beyond the lymphatic glands and make their way to more distant points, or that they deposit them- selves in any way in the parenchyma of internal organs. No, the mass always settles in the nearest group of glands. On examining the infiltrated glands it is easy to convince oneself that the size of the deposited particles is less than that even of the smallest pus-corpuscle. Fie, 67. TED YY pl Ly py : yy Ps In the object which I place before you (Fig. 67) the spot has accidentally been hit upon, at which the lymphatic vessel enters into the gland, and whence, enclosed within the trabecule of connective tissue which are prolonged from the capsules between the follicles, it proceeds in a spiral form, and finally breaks up into its branches. Where these pass into the neighbouring follicles, which are here Fig. 67. Section through the cortical substance of an axiMlary gland from an arm, the skin of which had been tattooed. A large lymphatic vessel is seen entering from the cortical substance, gently winding and breaking up into fine branches. Round about are follicles, for the most part filled witn connective tissue. The dark, finely granular mass represents the deposit of cinnapar. 80 diameters. 220 LECTURE IX. indeed in great part filled with connective tissue, they have poured out the whole mass of cinnabar, so that in part it still lies within the intervening trabecule, but yet in part has penetrated into the follicles themselves. The preparation comes from the arm of a soldier who had the figures rubbed in in 1809, so that the mass has remained nearly fifty years in the same place. None of it has penetrated farther than this spot; even the next layer of follicles does not contain any. The particles are however so small, and the majority of them so minute in com- parison with the cells of the gland, that they cannot at all be compared to pus- corpuscles. Now when such molecules as these are un- able to pass, when such extremely minute particles cause an obstruction, it would be somewhat bold to imagine that pus-corpuscles, which are relatively large, could effect a passage. This arrangement, gentlemen, by means of which the free current of fluid is interrupted in the lymphatic glands, and the coarser particles are retained there in quite a mechanical manner, admits, as may readily be conceived, of no other kind of reabsorption from the pe- riphery through the medium of the lymphatic vessels than that of simple fluids. We should indeed be mistaken, if we were to consider the whole action of the lymphatic glands to consist merely in their being interposed like filters between the different portions of the lymphatic ves- sels. They have manifestly another part to play, inas- much as the substance of the glands indubitably takes up Fia. 68. Fig. 68. Reticulum of an axillary gland filled with cinnabar, from an arm which had been tattooed (Fig. 67). wu. Part of an inter-follicular trabecula with a lymph- atic vessel; 6 one of its larger branches entering into a follicle; e, ¢ the anasto- mosing, nucleated networks of the reticulum; the dark granules are particles of cinnabar. 300 diameters. LYMPHATIC GLANDS IN CANCER AND SYPHILIS. 991 into itself certain ingredients from the fluid mass of the lymph, retains them, and thereby also alters the chemi- cal constitution of the fluid, so that it quits the gland all the more altered because it must at the same time. be assumed that the gland yields up certain constituents to the lymph, which did not previously exist in it. I will not here enter into minute details, since the his- tory of every malignant tumour affords the best examples in support of this position. When an axillary gland be- comes cancerous, after previous cancerous disease of the mamma, and when during a long period only the axil- lary gland remains diseased without the group of glands next in succession or any other organs becoming affected with cancer, we can account for this upon no other sup- position than that the gland collects the hurtful ingredi- ents absorbed from the breast, and thereby for a time affords protection to the body, but at length proves insuf- ficient, nay, perhaps at a later period itself becomes a new source of independent infection to the body, inas- much as a further propagation of the poisonous matter may take place from the diseased parts of the gland. Equally instructive examples are afforded by the his- tory of syphilis, in which a bubo may for a time become the depository of the poison, so that the rest of the eco- nomy is affected in a comparatively trifling degree. As Ricord has shown, it is precisely in the interior of the real substance of the gland that the virulent matter is found, whilst the pus at the circumference of the bubo is free from it; only so far as the parts come into contact with the lymph conveyed from the diseased part, do they absorb the virulent matter. If we apply these facts to the reabsorption of pus, we are not, even in the case when it has really made its way into lymphatic vessels, at all entitled to conclude that as an immediate consequence of this irruption the blood be- 929 . LECTURE IX. comes infected with the constituents of pus ; on the con- trary a retention of the pus-corpuscles will probably take place within the glands, and even the fluids which suc- ceed in passing them, will during that passage lose a great part of their noxious properties. Secondary glan- dular swellings show themselves in various forms after peripheral infection. How can they be explained other- wise than upon the supposition, that every contaminat- ing (miasmatic) substance, which is to be regarded as essentially foreign or, if | may so express myself, hostile, to the body, by penetrating into the substance of the gland, produces in it a state of more or less marked irri- tation which very frequently increases to a real inflam- mation of the gland? I shall hereafter revert to the sub- ject of irritation and enter a little more fully into the con- sideration of the meaning which should be attached to it, and I will therefore here only make this remark, that according to my investigations the irritation of a gland consists in its falling into a state in which there is an increased formation of cells in it—its follicles becoming enlarged, and after a time exhibiting a much greater number of cells than before. In proportion to the extent of these processes we then see the colourless elements of the blood also increase. Every considerable irritation of a gland is followed by an increase in the proportion of lymph-corpuscles in the blood, and every process there- fore which is accompanied by glandular irritation, will also have the effect of supplying the blood with larger quantities of colourless blood-corpuscles, or, in other words, of producing a leucocytotic condition. If then the opinion be entertained that pus has been absorbed, and that pus is the cause of the disturbances which have de- clared themselves, nothing is easier than to demonstrate the presence of cells in the blood which have the appear- ance of pus-corpuscles and are often present in such large LEUCOCYTOSIS CONFOUNDED WITH PY_.EMIA. 998 quantities as to form accumulations (Fig. 58) which may be seen, in the dead body, with the naked eye, looking like minute spots of pus; or as to constitute large, con- tinuous or granular layers on the inferior surface of the buffy coat of blood taken from a vein (Fig. 60). Appa- rently the proof is as plausible as possible. The observer starts with the supposition that pus has found its way into the blood ; he examines the blood and really discovers elements, having all the appearance of pus-corpuscles, and in very great numbers. Even if it be admitted that colourless blood-cells may look like pus-corpuscles, still the conclusion which has been repeatedly arrived at in cases of pysmia, is very seductive, namely, that on ac- count of the great multitude, they cannot possibly be colourless blood-, but must be pus-corpuscles. This was the conclusion arrived at years ago by Bouchut on the occasion of an epidemic of puerperal fever which he then took to be pysemia, but has very recently, founding his Opinion upon the same observations, declared to have been acute leukemia. It is moreover the same conclu- sion which Bennett came to in the much-discussed matter of priority between us, when he observed a case of in- dubitable leukemia some months before I saw my first case, and inferred from the presence of colourless corpus- cles in larger numbers than in any instance upon record, that it was a case of ‘“‘suppuration of the blood.” This conclusion of his indeed was not original, but was based upon the hemitis of Piorry of which I lately spoke (p. 187), this physician having conceived the blood itself to become inflamed and engender pus, a state which was afterwards denominated spontaneous pyemia by the Vienna school. Now all these errors proceeded from the circumstance that such an enormously great number of colourless cor- puscles were found in the blood. Now-a-days their 224 LECTURE IX. occurrence can be just as simply explained according to our theory of hematopoiesis, as it previously seemed explicable only according to that of pyaemia. Irritation of the lymphatic glands explains without any difficulty the increase in the colourless, pus-like cells in the blood, and that too in all cases—not only in those where pyemia was expected to be found, but also in those where it was not expected, but where the blood, not- withstanding, exhibited the same quantity of colourless corpuscles as in genuine pye#mia answering to our clinical notions of the disease. Thus it has been shown that every meal produces a certain state of irritation in the mesenteric glands, inas- much as the constituents of the chyle which are conveyed to these bodies, act as a physiological stimulus to them. The milk which we drink, the fatty matters in our soups, the various kinds of fat distributed in a state of minute division throughout the more solid articles of our food, find their way in the form of extremely minute globules into the lacteals and diffuse themselves there just like the cinnabar in the glands; but the smallest of the fatty molecules after a time force their way through the gland. For such minute bodies therefore there still exists a real permeability in the channels of the gland, but even they are for a time retained, and it always takes a long time before the mesenteric glands after a meal again become entirely free from fat, and the propulsion of this sub- stance through them is manifestly effected by a propor- tionately strong pressure. At the same time we observe an enlargement of the gland, and likewise after every meal an increase in the number of colourless corpuscles in the blood—a physiological leucocytosis, but no pyzemia. In proportion as pregnancy advances, as the lymphatic vessels in the uterus dilate, and the interchange of mate- rial in the organ increases with the development of the PHYSIOLOGICAL ANP PaTHOLOGICAL LEUCOCYTOSIS. 995 foetus, the lymphatic glands in the inguinal and lumbar regions become considerably enlarged, and that some- times to such an extent, that, if we were to find them in a similar state at any other time, we should regard them as inflamed. This enlargement conveys into the blood an increased quantity of fresh particles of a cellular na- ture, and thus from month to month the number of colourless corpuscles augments. At the time of birth we may see in the defibrinated blood of nearly every puerperal woman, whether suffering from pyzemia or not, the colourless corpuscles forming a pus-like sediment. This too is a physiological form which is far from being a pyemic one. But if care be taken to select a puerperal woman, offering symptoms of disease which correspond with those usually presented by pyzemia, nothing is easier than to find these numerous colourless multi-nuclear cells, which are precisely such as are supposed to corroborate the presence of pyemia. These are fallacious conclu- sions which result from imperfect knowledge of the nor- mal conditions of life and development. As long as we are exclusively bent upon proving the presence of pye- mia, all this may have the appearance of being a great and new occurrence, and we may, when we examine the blood of a woman in child-bed, consider ourselves justi- fied in concluding that she has pyemia even before its symptoms declare themselves. But we may examine when we will, we shall always find some traces of leuco- cytosis, just as it has already long been known that it is very common for a buffy coat to form in the case of preg- nant women, because their blood generally has conveyed into it a larger quantity than usual of a more slowly con- tracting fibrine (hyperinosis). This is accounted for by the increased nutrition of the uterus, and by the changes, so nearly allied to inflammatory processes, which are go- ing on in the uterine system, and are associated with a 15 296 LECTURE IX. certain amount of irritation in the lymphatic glands im- mediately in connection with it. If we proceed a step farther and consider pathological cases, we meet with these leucocytotic conditions in the whole of that series of diseases which are complicated with glandular irritation, and in which the irritation does not lead to a destruction of the glandular substance. During the progress of an attack of scrofula, in which, if the disease run a somewhat unfavourable course, the glands are destroyed, either by ulceration, or cheesy thickening, calcification, etc., an increased introduction of corpuscles into the blood can only take place as long as the irritated gland is still in some degree capable of per- forming its functions, or still continues to exist ; as soon however as the gland is withered or destroyed, the for- mation of lymph-cells likewise ceases and with it the leu- cocytosis. In all cases, on the other hand, in which a more acute form of disturbance prevails, connected with inflammatory tumefaction of the glands, an increase in the colourless corpuscles always takes place in the blood. So it is in typhoid fever, in which we observe such ex- tensive medullary (markige) swellings of the abdominal glands ; so it is in cancer patients, when irritation of the lymphatic glands manifests itself; so, lastly is it in the eourse of the processes which come under the denomina- tion of malignant erysipelas and are so early wont to be accompanied by glandular swellings. Such is the mean- ing of this increase in the colourless elements which ulti- mately always refers us to an increased development of lymph-corpuscles within the irritated glands. It is now of importance that I should point out to you, that at present our conceptions concerning lymphatic glands are much more comprehensive than they were a short time ago. The most recent histological investiga- tions have shown that. in addition to the ordinary well- LYMPHOID ORGANS. 224 known lymphatic glands, which are of a certain size, a great number of smaller apparatuses exist in the body which possess precisely the same structure, but do not exhibit such a complex arrangement as we find in a lymphatic gland. To this class belong above all the /fol- licles of the intestines, both the solitary and the Peyerian. A Peyer’s patch is nothing more than a lymphatic gland spread out as it were upon the surface ; the individual follicles of the patch, just as the solitary follicles of the digestive tract, correspond to the individual follicles of a lymphatic gland, only that the former, in man at least, are disposed in a single layer, the latter in several. The solitary and Peyerian glands have therefore nothing at all in common with the ordinary glands which pour their secretions into the intestinal canal ; on the contrary, they rather hold the position, and manifestly also fulfil the functions, of lymphatic glands. To the same category belong in all probability also the analogous apparatuses which we find grouped to- gether in such large masses in the upper part of the digestive tract, where they form the ¢onsizs and the folli- cles of the root of the tongue. Whilst in the intestine the follicles lie spread out on an even surface, in these parts the surface is inverted and the individual follicles lie around the involuted membrane. To the same category belongs moreover the thymus gland, which in its interior exhibits no other differences of structure excepting that the aggregation of the folli- cles reaches a still higher degree than in the lymphatic glands. Whilst in most of the lymphatic glands we have a hilus, where there are no follicles, this ceases to be the case in the thymus gland which has no hilus. Finally, to the same class belongs also a very essential constituent of the spleen, namely, the Malpighian or white bodies, which in different persons are distributed in just 298 LECTURE IX. as different numbers throughout the parenchyma of the spleen, as the solitary and Peyerian follicles in the intes- tine. In a section through the spleen we see the trabe- cule radiating from the hilus towards the capsule and enclosing certain districts of glandular substance, within which the red spleen pulp lies, interrupted here and thera by a sometimes greater, sometimes less, number of white bodies (follicles) of larger or smaller size, single or in groups, and sometimes almost clustered. The structure of these follicles agrees exactly with that of the follicles of lymphatic glands. We may therefore regard this whole series of appara- tuses as nearly equivalent to the lymphatic glands pro- perly so called, and a swelling of the spleen will, under certain circumstances, furnish just as abundant a supply of colourless blood-corpuscles, as is the case when a lymphatic gland enlarges. This possibility explains how it is that, for example, in cholera, where the change in the solitary glands and Peyer’s patches forms the chief part of the disease, and where the swelling of the other lymphatic glands is much less marked, we meet at an extremely early period with a considerable increase in the colourless corpuscles. Hereby is explained moreover why, in such cases of pneumonia as are connected with great swelling of the bronchial glands, an increase in the number of colourless blood-corpuscles likewise takes place, which is generally wanting in those forms of pneu- monia which are not connected with such swelling. The more the irritation extends from the lung to the lymph- atic glands, the more abundantly noxious fluids are con- veyed from the lung to the glands—the more manifestly does the blood undergo this change. Upon examining these different pathological processes m this manner one by one, it is really impossible to dis- cover anything at all, which in a morphological point of REFUTATION OF A MORPHOLOGICAL PYMIA. 929 view, could even in a remote degree justify the assump- tion of a condition such as might be called pyemia. In the extremely rare cases, in which pus breaks through into veins, purulent ingredients may, without doubt, be conveyed into the blood, but in such instances the intro- duction of pus occurs for the most part but once. The abscess empties itself, and if it be large, an extravasation of blood is more apt to ensue than the establishment of a persistent pyzemia. Perhaps we shall at some future time succeed, in the course of such a process, in discover- ing pus-corpuscles with well-defined characters in the blood ; at present, however, the matter stands thus, that it can most positively be maintained that nobody has hith- erto succeeded in demonstrating, by arguments capable of supporting even gentle criticism, the existence of a morphological pyemia. This name therefore must, as designating a definite change in the blood, be entirely abandoned. LHOG?TU RH Xx. MARCH 17, 1858. METASTATICAL DYSCRASLA. Pyzmia and phlebitis—Thrombosis—Puriform softening of thrombi—True ard false phlebitis—Purulent cysts of the heart. Embolia—Import of prolonged thrombi—Pulmonary metastases—Crumbling away of the emboli—Varying character of the metastases—Endocarditis and capillary embolia—Latent pyemia. Infectant fluids—Diseases of the lymphatic apparatuses and secreting organs— Chemical substances in the blood; salts of silver—Arthritis—Calcareous metas- tases—Diffuse metastatic processes—Ichorrhamia—Pyemia asa collective name. Chemical dyscrasia#—Malignant tumours, especially cancer—Diffusion by means of contagious parenchymatous juices. GENTLEMEN,—I was interrupted the last time in my description of pyzmia by the termination of the lecture, just as I was about to discuss the nature of the connection between this disease and certain affections of the vessels. As soon as it was found necessary to abandon the ori- ginal view, in accordance with which the mass of pus which was believed to be seen in a vein, was considered to have made its way in (been absorbed) through an opening in its walls, or through its yawning extremity, recourse was had to the doctrine of phlebitis, which is still the one most current. It was imagined that the pus which was regarded as the really noxious matter, was furnished as a product of secretion by the wall of the 230 PHLEBITIS. 93% vessel (John. Hunter). This doctrine, however, presented some difficulty, because it was soon pretty generally ‘ allowed that a primary purulent inflammation of the veins did not occur, but that, as was first distinctly shown by Cruveilhier, at the commencement a clot of blood is always present. Cruveilhier himself was so greatly sur-. prised at this observation of his, that he connected a the- ory with it which was beyond all medical comprehension. He concluded namely from the impossibility of explain- ing why inflammations of the veins began with coagula- tion of the blood, that inflammation in every case what- ever consisted in a coagulation of the blood. The impos- sibility of explaining phlebitis seemed to him to be got over by raising coagulation into a general law, and by referring every inflammation to a phlebitis on a small scale (capillary phlebitis). Cruveilhier was the more in- duced to assert this in consequence of his entertaining similar views with regard to other morbid processes, and believing that cysts, tubercles, cancer, and in short all important processes, accompanied by changes susceptible of anatomical demonstration, really ran their course within special, minute veins imagined by him. This man- ner of thinking, however, continued so entirely alien to that of the great majority of learned and unlearned phy- sicians, that the separate conclusions propounded by Cru- veilhier, which were adopted in medical science in part as drawn up by him, were altogether misunderstood. Cruveilhier was right in this point, as indeed has since been more and more acknowledged, namely, that the so- called pus in the veins in the first instance never lies against the wall of the vein, but always first appears in the centre of the previously existing clot of blood which marks the outset of the process. He imagined that the pus was secreted from the wall of the vessel, but that it did not remain there, but by means of “‘ capillary attrac- 932 LECTURE X. tion” made its way to the centre of the clot. This was a very singular theory, which can only be approxima- tively comprehended by assuming, as it was still the cus- tom to do in Cruveilhier’s time, pus to be a simple fluid. But apart from these extremely obscure interpretations, the fact remains constant, against which even now no argument can be advanced, that before a trace of inflammation is visible, we find a clot, and that shortly afterwards in the middle of this clot a mass dis- plays itself, which differs in ap- pearance from the clot, whilst on the other hand it exhibits a greater or less resemblance to pus. With this observation as my starting point, I have endea- voured to clear up the doctrine of phlebitis, as far as lies in my power, by substituting for the mysticism which pervaded Cru- veilhier’s interpretation, merely a statement of the real facts. We do not know that inflammation as such has any necessary connection with coagula ; on the contrary, it has turned out that the doctrine of stasis rests upon manifold misinterpretations. Inflammation may un- questionably exist when the current of blood within the vessels of the affected part is perfectly free and unob- structed. If we therefore leave inflammation on one side and confine our attention simply to the coagulation Fig. 69. Fig. 69. Thrombosis of the saphenous vein. S. Saphenous vein. Z Thrombus: v, v’ thrombi seated on the valves (valvular) in process of softening, and connected by more recent and thinner portions of coagulum. C. Prolongation of the plug, projecting beyond the mouth of the vessel into the femoral vein C’. PURIFORM SOFTENING OF THROMBI. 933 of the blood, to the formation of the clot (thrombus), it seems most convenient to comprehend the whole of this process under the term Thrombosis. I have proposed to substitute this term for the different names, phlebitis, ar- teritis, etc., inasmuch as the affection essentially consists in a real coagulation of the blood at a certain fixed spot. Upon investigating the history of these thrombi, we find that the puriform mass which is met with in their interior does not originate in the wall, but is produced by a direct transformation of the central layers of the clots themselves, a transformation indeed which is of a chemical nature, and during which, with a result similar to that which can be artificially obtained by the slow digestion of coagulated fibrine, the fibrine breaks up into a finely granular substance and the whole mass becomes converted into débris. This is a kind of softening and retrograde metamorphosis of the organic substance, in the course of which from the very commencement a num- ber of extremely minute particles become visible ; the large threads of fibrine crumble into pieces, these again into smaller ones, and so on until after a certain time has elapsed the chief part of the mass is found to be composed of small, fine, pale granules (Fig. 70, A). In cases in which the fibrine is comparatively very pure, we frequently see scarcely anything else than these granules. Fie. 70. Fig. 70. Puriform mass of débris from softened thrombi. A. The granules seen in disintegrating fibrine, varying in size, and pale. B. The colourless blood-cor- puscles set free by the softening, some of them in process of retrograde metamor- phosis; «, with multiple nuclei, 6, with simple, angular nuclei and a few fat-gra- nules, c, non-nucleated (pyoid) corpuscles, in a state of fatty metamorphosis. C. Red blood-corpuscles undergoing decolorization and disorganization, 350 diame- ters. 234 LECTURE X. You see, gentlemen, the microscope solves the difficul- ties in a very simple manner, by demonstrating that this mass, which looks like pus, is not pus. For we under- stand by pus a fluid essentially provided with cellular elements. Just as little as we can imagine blood with- out blood-corpuscles, just as little can pus exist without pus corpuscles. But when, as in the present instance, we find a fluid which is nothing more than a mass per- vaded by granules, this may indeed, as far as external appearance goes, look like pus, but never ought to be regarded as real pus. Jt is a puriform, but not a puru- lent substance. But now we frequently see that in addition to these gra- nules a certain proportion of other structures show them- selves, for example, really cellular elements (Fig. 70, B), which are round (spherical), or angular, present one, two, or more nuclei, frequently lie tolerably close to one an- other, and in reality exhibit a great similarity to pus- corpuscles, the distinction at most being that very often fat-granules occur in them, indicating that a process of disintegration is going on. Whilst therefore in individual cases there can, on account of the often very greatly pre- ponderating mass of débris, exist no doubt as to what the observer has before him, in others considerable doubts may exist as to whether real pus is not present. These doubts cannot be removed in any other way than by an examination into the history of the development of the puriform mass. Now that we have already seen that colourless blood- and pus-corpuscles perfectly agree with one another in form, so that it is impossible to draw a real distinction between them, the question which sug- gests itself in cases where we find round, colourless cells in a clot of blood, whether these cells are colourless blood- or pus-corpuscles, can only be decided by deter- mining whether the corpuscles were present in the DISAPPEARANCE OF RED CORPUSCLES IN THROMBI. 935 thrombus from its very commencement, or only sprang up in it afterwards, or found their way into it in some other manner. Now upon accurately following up the different stages of the process, the very positive result is obtained that the corpuscles pre-exist, and that they do not arise within the clot, and are not forced into it. Even when quite recent thrombi are examined, the corpuscles are found in many places heaped up in great masses, so that, when the fibrine breaks up, they are set free in such numbers, that the débris are nearly as rich in cells as pus. It is with this process just as when water which is tho- roughly impregnated with solid particles is frozen and then exposed to a higher temperature ; when the ice melts the enclosed particles must of course again come to light. To this view of the matter one objection may be raised, to wit, that we do not see the red blood-corpuscles set free in a similar manner. The red corpuscles, however, perish very early ; they are soon seen to grow pale ; they lose a portion of their colouring matter and become smaller, whilst numerous dark granules appear at their circumference (Figs. 54, a; 70, C), and in the majority of cases they entirely disappear, nothing but these gra- nules at last remaining. Still there are also cases in which the red corpuscles retain their integrity within the softening mass. As a rule they certainly perish, and it is precisely upon this that depends the peculiarity of the transformation, by means of which a yellowish white fluid arises bearing the external appearance of pus. And for it too an explanation may be found without any par- ticular difficulty, if it be borne in mind how very trifling is the power possessed by the red blood-corpuscles of resisting the most various reagents. If to a drop of blood you add a drop of water, you see the red corpus- 236 LECTURE X. cles disappear before your eyes while the colourless ones remain behind. That therefore, which according to the ordinary nomen- clature is called suppurative phlebitis, is neither suppu- rative, nor yet phlebitis, but a process which begins with a coagulation, with the formation of a thrombus in the blood, and afterwards presents a stage in which the thrombi soften, so that the whole history of the process is contained in the history of the thrombus. But here I must impress upon you that I do not, as has been said of me in different quarters, deny the possibility of a real phlebitis, and that I have not in any way discovered that there is no such thing as phlebitis. No/ phlebitis cer- tainly does exist. But it is an inflammation which really affects the walls, and not the contents of a vessel. In the larger vessels the most different layers of their walls may become inflamed and enter upon every possible phase of inflammation, and yet all the while their chan- nel remain entirely unaltered. In accordance with the views generally entertained the internal coat of the ves- sels was thought to be like a serous membrane, and as this readily furnishes fibrinous exudations or purulent masses, the same was supposed to be the case with the internal coat. Concerning this point a series of investi- gations was years ago set on foot, and I too have occu- pied myself at various times with it, but hitherto no ex- perimenter, who carefully prevented the blood from streaming into the vessels, has succeeded in producing an exudation, which was deposited in their cavity. On the contrary, when the wall is inflamed, the ‘‘exuded mat- ter” (Exsudatmasse) passes into the wall, which becomes thicker, cloudy, and subsequently begins to suppurate. Nay, even abscesses may form, which cause the wall to bulge on both sides like a variolous pustule, without any coagulation of the blood ensuing in the cavity of the ves- PURULENT CYSTS IN THE HEART. 937 sel. At other times, certainly, phlebitis, properly so called (and in like manner arteritis and endocarditis), is the cause of thrombosis, in consequence of the formation of inequalities, elevations, depressions, and even ulcera- tions upon the inner wall which favour the production of the thrombus. Still, wherever phlebitis, in the usual sense of the word, takes place, the alteration in the coat of the vessel is almost always a secondary one, and in- deed occurs at a comparatively late period. The process runs its course in such a way that the most recent parts of the thrombus always consist of the blood which has most lately coagulated. The softening, the partial liquefaction, generally commences in the centre, in the oldest layers, so that, when the thrombus hag -attained .a certain size, there exists in the midst of it a cavity of larger or smaller dimensions, which gradually enlarges and keeps approaching more and more closely to the wall of the vessel. But in general this cavity is shut off in an upward and downward direction by means of a more recent and tougher portion of the clot which, after the manner of a cap, takes care that, as Cruveilhier expresses himself, the ‘‘ pus” remains sequestered, and all contact between the débris and the circulating blood is prevented. Only sideways does the softening ' extend until it at last reaches the wall of the vessel itself ; this becomes altered, it begins to grow thicker and at the same time cloudy, and ultimately even suppuration takes place within the walls. The same thing which we have hitherto considered in the veins occurs also in the heart. In the right ventricle especially we not unfrequently see what are called puru- lent cysts between the trabecule of its wall. They pro- ject into the cavity like small rounded knobs, and form little pouches which, when cut open, contain a soft pulp that may present a completely pus-like appearance. 2388 LECTURE X. People have plagued themselves to an indefinite extent about these purulent cysts and invented all possible the- ories to account for them, until at length the simple fact came out, that their contents are frequently nothing more than a finely granular pulp of an albuminous sub- stance, which does not offer even the slightest resem- blance in its more intimate structure to pus. This was so far tranquillizing, as there is no observation as yet on record of the death of any patient from pyaemia who had sacs of this description even in pretty considerable num- ber, but it ought to have struck those who are so much in- clined to establish a connection between peripheral throm- boses, which are however just the same thing, and pyzemia. For the question naturally arises how far particular disturbances that can be designated by the name of pye- mia may, in consequence of the softening of the thrombi, be evoked in the body. To this in the first place we may answer that secondary disturbances certainly are very frequently occasioned, but not so much by the immediate introduction of the softened masses as fast as they be- come liquid into the blood, as by the detachment of lar- ger or smaller fragments from the end of the softening thrombus which are carried along by the current of blood and driven into remote vessels. This gives rise to the very frequent process upon which I have bestowed the name of E'mbolha. This is an occurrence which we can here only briefly touch upon. In the peripheral veins the danger pro- ceeds chiefly from the small branches. By no means rarely do these become quite filled with masses of coagu- lum. As long however as the thrombus is confined to the branch itself, so long the body is not exposed to any particular danger ; the worst that can happen is that, in consequence of a peri- or meso-phlebitis,* an abscess * See the Author’s “ Gesammelte Abhandl.,” p. 484. EMBOLIA—PROLONGED THROMBI AND THEIR IMPORT. 9389 may form and open externally. Only the greater num- ber of the thrombi in the small branches do not content themselves with advancing up to the level of the main trunk, but pretty constantly new masses of coagulum de- posit themselves from the blood upon the end of the thrombus layer after layer, the thrombus is prolonged beyond the mouth of the branch into the trunk in the direction of the current of the blood, shoots out in the form of a thick cylinder farther and farther, and becomes continually larger and larger. Soon this prolonged thrombus (Fig. 71, ¢) no longer bears any proportion to the original (autochthonous) thrombus (Fig. 71, ¢), from which it proceeded. The prolonged thrombus may have the thickness of a thumb, the original one that of a knit- ting-needle. From a lumbar vein, for example, a plug may extend into the vena cava as thick as the last pha- lanx of the thumb. Fie. 71. It is these prolonged plugs that constitute the source of real danger ; it is in them that ensues the crumbling away which leads to secondary occlusions in remote ves- sels. They are the parts from which larger or smaller Fig. 71. Autochthonous and prolonged thrombi. ¢, ¢’. Smallish, varicose, lateral branches (circumflex veins of the thigh), filled with autochthonous thrombi which project beyond the orifices into the trunk of the femoral vein. ¢. Prolonged thrombus produced by concentrically apposed deposits from the blood. ¢’. Pro- longed thrombus, as it appears after fragments (emboli) have become detached from it. 240 LECTURE X. particles are torn away by the blood as it streams by (Fig. 71, 2’). Through the vessel originally occluded no blood at all flows ; in it the circulation is entirely interrupted : but in the larger trunk through which the blood still con- tinues its course, and into which only at intervals the thrombus-plugs project, the stream of blood may detach minute particles, hurry them away with it, and wedge them tightly into the nearest system of arteries or capil- laries. Thus we see, that as a rule all the thrombi at the pe- riphery of the body produce secondary obstructions and metastatic deposits in the lungs. I long entertained doubts whether I ought to consider the metastatic inflam- mations of the lungs one and all as embolical, because it is very difficult to examine the vessels in the small me- tastatic deposits, but I am continually becoming more and more convinced of the necessity of regarding this mode of origin as the rule. When a considerable num- ber of cases are compared statistically, the result ob- tained is that every time metastatic deposits occur, thrombosis is also present in certain vessels. Quite re- cently, for example, we have had a tolerably severe epidemic of puerperal fever, and in this it was found that, however manifold the forms the disease assumed, yet all those cases which were accompanied by metas- tases in the lungs, were also attended with thrombosis in the region of the pelvis or in the lower extremities, whilst in the inflammations of lymphatic vessels the pulmonary metastases were wanting. Such statistical results carry with them a certain amount of compulsory conviction, even where strict anatomical proof is wanting. Into the pulmonary artery the introduced fragments of thrombus of course penetrate to different depths accord- ing to their size. Usually a fragment of the kind sticks DIFFERENT VARIETIES OF METASTATIC DEPOSITS. 941 fast where a division of the vessel takes place (Fig. 72, £), because the diverging vessels are too small to admit it. In the case of very large fragments even the principal trunks of the pulmonary artery are blocked up, and instantaneous asphyxia ensues ; other fragments again penetrate into the most minute arteries and there give rise to very minute, and sometimes miliary inflammations of the parenchyma. In explanation of these small and often very numerous deposits, I must mention a conjecture which only occurred to me whilst engaged in my more recent observations, but which I do not scruple to declare to be a necessary inference. I believe namely that, when a considerable fragment of a thrombus becomes wedged at a certain point in an artery, it may in its turn crumble away through the onward pressure of the blood, and thus the minute particles to which this crumbling of the lar- ger plug gives rise be conveyed into the small branches into which the vessel breaks up. Thus alone does it seem to me that the fact can be explained, that in the district supplied by an artery of considerable size a num- ber of little deposits of the same sort are often found. This whole series of cases has nothing whatever to do with the question, whether there is pus in the blood or not. We have in them to deal with bodies of quite a different nature, with fragments of coagula in a more or less altered condition, and according as this alteration has assumed this or that character, the nature of the pro- Fie. 72. Fig. 72. Embolia of the pulmonary artery. P. Moderately large branch of the pulmonary artery. . The embolus, astride upon the angle (spur—Sporn), formed by the division of the artery. ¢, ¢’, The capsulating (secondary) thrombus: ¢, the portion in front of the embolus reaching to the next highest collateral vessel ¢; t', the portion behind the embolus, in a great measure filling up the diverging branches r, 7’, and ultimately terminating in the form of a cone. 16 249 LECTURE X. cesses which arise in consequence of the obstruction may also be very different. If, for example, a gangrenous softening has taken place at the original site of the coa- gulum, the metastatic deposit will also assume a gangre- nous character, just as this would be the case if gangre- nous matter were inoculated. So, vice versd, it also happens that the secondary disturbances, like those at the spot whence the fragments were detached, run a very favourable course, the embolus like the thrombus becom- ing converted into pigment and connective tissue, and at the same time growing smaller. This group of processes must be separated from those ordinarily occurring in pyzemia all the more, because the same processes are also met with on the other side of the Fie. 73, lungs in the regions belonging to the left side of the cir- culation, where they often run the same course and pre- Fig. 73. Ulcerative endocarditis affecting the mitral valve. a. The free, smooth surface of the mitral valve, beneath which the connective-tissue-corpuscles are en- larged and clouded, whilst the intervening tissue is denser than usual. 6. A con- siderable hilly swelling caused by increasing enlargement and cloudiness of the tis- sue. v. A swollen part which has already begun to softenand break up. d, d. The tissue at the lower part of the valves which is stil but little altered, with numerous corpuscles, the results of proliferation. e, e. The commencement of the enlarge- ment, cloudiness, and proliferation of the corpuscles. 80 diameters. CAPILLARY EMBOLIA. 943 sent the same results, but are still less dependent upon an original phlebitis. Thus, for example, endocarditis by no means seldom forms the starting point of such me- tastases. Ulceration takes place in one of the valves of the heart, not by means of the formation of pus, but in consequence of an acute or chronic softening ; crumbling fragments of the surface of the valve are borne away by the stream of blood and reach with it far distant points. The kind of obstruction which these masses produce is altogether similar to that which the thrombi in the veins give rise to, but they present a different chemical consti- tution. Their minuteness also and their friability favour their penetration into the smallest vessels in a high de- gree. Therefore we do not so very unfrequently find the obstructing mass in minute microscopical vessels Fie, 74. Fie. 75. Fig. 74—75. Capillary embolia in the tufts (penicilli) of the splenic artery after endocarditis (Cf. Gesainmelte Abhandlungen zur wiss. Medicin. 1856, p. 716). 44. Vessels of a tuft magnified 10 times, in order to show the position of the oc- cluding emboli in the arterial district. 75. An artery filled a little before its divi- sion, and in the branches into which it next divides, with fragments of the finely granular embolic mass (Cf. Fig. 73, ¢). 300 diameters. 944 LECTURE X. which are no longer to be followed with the naked eye, and in them it usually extends as far down as a point of division and somewhat beyond. This mass constantly presents a finely granular appearance, and does not con- sist of the coarse débris that we find in the veins, but of a very fine, yet at the same time dense, granular matter ; chemically, it possesses the extremely convenient quality for examination of being remarkably resistant to the ordi- nary tests, and thus readily distinguished from other mat- ters. This is capillary embolia properly so called, one of the most important forms of metastasis, which frequently gives rise to minute deposits in the kidney, the spleen, and the substance of the heart itself; in certain cases occasions sudden occlusions in the vessels of the eye or brain, and according to circumstancs produces metastatic deposits or sudden functional disturbances (amaurosis, apoplexy). Here too one can clearly convince oneself that in recent cases the wall of the vessel is quite unal- tered at the seat of the affection ; nay here indeed the doctrine of phlebitis would no longer suffice, since these are not vessels which possess vasa vasorum, and concern- ing which it might be assumed that a secretion proceeded from the wall inwards. In these cases it is impossible to regard the occluding mass in any other light than as one primarily existing in the vessel, and in no wise depend- ent upon the condition of its wall. Perhaps this description has convinced you, gentlemen, that two essential errors have existed in the doctrine of pyzmia ; the one, that people thought they had found pus-corpuscles in the blood, when only colourless blood- corpuscles were really present ; the second, that they thought they had found pus in vessels in which nothing more than the products of the softening of fibrine existed. Yet we have ascertained that this last class of cases cer- tainly furnishes the most important source of genuine METASTASES DUE TO INFECTANT MATTERS, 945 metastatic deposits. But in my opinion, the history of the processes which have been called pyamia is not con- fined to these conditions. When the process runs its course free from all complication, so that from the origi- nal seat of the disease (thrombosis in a vein, endocarditis, etc.), only solid masses in an undecomposed state are de- tached and cause obstructions, the real process is in many cases brought to notice only in consequence of the metastasis. There are cases which run their course so latently that all the earlier stages of the affection are en- tirely overlooked, and that the first rigors which declare themselves announce that the development of the meta- static processes has already set in. Usually, however, another condition must be taken into consideration, which is not directly accessible either to the coarser or more delicate modes of anatomical investigation ; I mean certain fluids, which in themselves bear no immediate and necessary relation to pus as such, but manifestly differ very much from one another in their nature and origin. Whilst I was engaged in the consideration of the changes which lymph undergoes, I pointed out to you (p. 220), that fluids which were taken up by lymphatic vessels were not only freed in the filters of the lymphatic glands from corpuscular elements, but were also in part attracted and retained by the substance of the glands, so as to display some activity within them. Similar effects appear to take place also elsewhere than in the glands. Where the reabsorption was primarily effected by the veins, this must, of course, always be the case. There is namely a series of peculiar phenomena which pervade all infectious processes as a constant element. These are on the one hand the changes which the lymphatic and lymphoid glands may undergo not so much at the seat of the primary affection as rather in the body gene- rally, and on the other hand the changes which the 246 LECTURE X. secreting organs offer, through which the matters have to be excreted. It was for some time believed that tumefaction of the spleen was characteristic of typhoid fever, inasmuch as it formed a parallel to the swellings of the mesenteric glands occurring in that disease. But more accurate observation has shown that a great number of feverish conditions which follow a more or less typhoid course, and affect the nervous system in such a manner that a state of depression is brought about in its most important central organs, set in with swelling of the spleen. The spleen is a remarkably sensitive organ, which swells not only in intermittent and typhoid fever, but also in most other processes in which noxious, infectant matters have been freely taken up into the blood. No doubt the spleen must always be considered in its near relationship to the lymphatic system, but its diseases in addition usu- ally bear a very direct relation to analogous diseases of the important glands in its vicinity, especially the liver and the kidneys. In most cases of infection do these three organs exhibit corresponding enlargement con- nected with real changes in their interior ; but since these changes do not, even on microscopical examination, ap- parently present anything remarkable, the attention of the observer is chiefly attracted by the result which is obvious to the naked eye, namely, the great swelling. On careful comparison, however, a good deal is disco- vered, so that we can affirm with certainty that the gland- cells quickly become changed, and that disturbances early show themselves in the elements by means of which ° the secretion is to be accomplished. I shall revert to this subject hereafter. Allow me now, in elucidation of these conditions, in the first place to advert to one or two more obvious examples which are accessible to direct observation. DEPOSITION OF SILVER IN THE TISSUES, DAT We know that when any one takes salts of silver, they penetrate into the different tissues of his body ; and if we do not employ them in a really corrosive and destructive manner, the silver penetrates into the elements of the tissues in a state of combination, the nature ofjwhich has not yet been satisfactorily made out, and, when it has been made use of long enough, produces a change of colour at the point of application. A patient who had in Dr. Von Graefe’s out-patient room on the 10th No- vember received a solution of nitrate of silver as a lotion, very conscientiously employed the remedy up to the pre- sent time (17th March) ; the result of which was that his conjunctiva assumed an intensely brown, nearly black appearance. The examination of a piece cut out of it showed that silver had been taken up into the paren- chyma, and indeed in such a manner that the whole of the connective tissue had a slightly yellowish brown hue upon the surface, whilst in the deeper parts the deposi- tion had only taken place in the fine elastic fibres of the connective tissue, the intervening parts, the proper basis- substance, being perfectly free. But deposits of an en- tirely similar nature take place also in more remote organs. Our collection contains a very rare preparation from the kidneys of a person who on account of epilepsy had long taken nitrate of silver internally. Init may be seen the Malpighian bodies, in which the real secretion takes place, a blackish blue colouring of the whole of the membrane of the coils of the vessels, limited to this part "in the cortex, and appearing again, in a similar, though less marked form, only in the intertubular stroma of the medullary substance. In the whole kidney, therefore, besides the parts which constitute the real seat of their secretion, those only are altered which correspond to the ultimate system of capillaries in the medullary substance. 248 LECTURE X. Of the well-known discoloration of the skin by silver T need not speak here. : Another instance is afforded us by gout. If we exa- mine the concretions (tophi) in the joints of a gouty per- son, we find they are composed of very delicate, needle- shaped, crystalline deposits of all possible sizes, and con- sisting of urate of soda, with at most here and there a pus- or blood-corpuscle lying between them. We have here therefore also, as when silver has been employed, to deal with a material substance which is usually ex- creted by the kidneys, and that indeed not rarely in such large quantities, that deposits form even within the kid- ney itself and large crystals of urate of soda accumulate, especially in the uriniferous tubules of the medullary portion, so as sometimes to lead even to an occlusion of the tubules. If, however, this secretion does not pro- ceed in a regular manner, the immediate result is an ac- cumulation of urates in the blood, as has been shown in a very able manner by Garrod. Then at last deposits begin to form at other points, not throughout the whole body, nor uniformly in all parts, but at certain definite points and in accordance with certain rules. Here we have to do with very different forms of meta- stasis from those with which we became acquainted whilst considering the nature of embolia. That the changes which ensue in the substance of the kidney, in consequence of the absorption of silver from the stomach, accord with what has in pathology since times of old been termed metastasis is unquestionable. This consists in a transferrence of matter from one spot to another, so that the same substance which had previously been pre- sent in the first comes and lodges in the second, and the secreting organ takes up minute particles of the matter into its own tissue. This is what we find coasiantly METASTASIS. 9249 recurring in the history of all metastatic deposits of this kind, in which only matters in solution and not particles of a visible and mechanical nature are present in the blood. The urate of soda cannot be directly seen in the blood of the gouty person, unless it have previously been col- lected by the help of chemical processes ; and just as lit- tle the salts of silver. I have moreover described a new form of metastasis which is certainly more rare but yet belongs to the same category. When calcareous salts are reabsorbed from the bones in large quantity, the bone-earth is generally ex- creted by the kidneys, likewise in large quantity, so that sediments form in the urine, the knowledge of which has straggled down to us in the history of osteomalacia [mollities ossium], from the notorious Mme. Supiot in the last century. But this regular excretion of the cal- careous salts is not unfrequently impaired by disturb- ances in the functions of the kidneys, in the same way as in arthritis the excretion of urate of soda; then there also arise metastatic deposits of bone-earth, but at other points, namely the lungs and the stomach. Considerable portions of the lungs sometimes become calcified without any injury to the permeability of the respiratory pas- sages ; the diseased parts look like fine bathing sponge. The mucous membrane of the stomach becomes filled in like manner with calcareous salts, so that it feels like a rasp and grates under the knife without the glands of the stomach becoming directly implicated ; they are merely imbedded in a stiffened mass, and possibly even thus secretion might take place from them. To these kinds of metastasis in which definite sub- stances, though not in a palpable form, but in solution, find their way into the mass of the blood, careful atten- tion must at all events be paid when we endeavour to unravel the complex mass of conditions which are com- 250 LECTURE X. prehended under the term pyzmia. I see at least no other possible way of explaining certain more diffuse processes, which do not present themselves in the form of the ordi- nary circumscribed metastatic deposits. To this class be- longs that metastatic pleurisy which develops itself with- out any metastatic abscesses in the lungs—that seemingly rheumatic articular affection, in which no distinct deposit is found in the joints—that diffuse gangrenous inflamma- tion of the subcutaneous connective tissue which cannot well be accounted for unless we suppose a more chemical mode of infection. Here we have, as may be seen in cases of variolous and cadaveric infection, to deal with a transferrence of corrupted, ichorous juices into the body ; and we must admit the existence of a dyscrasia (ichorous infection) in which this ichorous substance which has made its way into the body, displays its effects in an acute form in the organs which have a special predi- lection for such matters. Now it may: possibly happen that in the course of the same case of illness the three different changes which we have considered may coexist. An increase in the num- ber of the colourless corpuscles (leucocytosis) may take place to such an extent as to tempt one to believe in the presence of a morphological pyemia. This will at all events always be the case when the process has been con- nected with extensive irritation of the lymphatic glands. The formation of thrombi, moreover, and embolia with metastatic deposits may occur. And finally there may at the same time be taking place an absorption of icho- rous or putrid juices (ichorrhzemia, septhemia). These three different conditions may present themselves as com- plications one of the other, but do not necessarily coin- cide. If it be wished therefore to retain the term pye- mia, let it be reserved for such complications as these, only we must not seek for a common central point in a ICHORRH.EMIA—CANCEROUS DYSCRASIA. 951 purulent infection of the blood, but the term must be re- garded as a collective name for several processes dissimi- lar in their nature. IT hope, gentlemen, that what I have now imparted to you will be sufficient to put you in possession of the chief bearings of the subject. Of course no real demonstra< tion can be afforded without reference to distinct cases. You will, however, yourselves have sufficient opportunity for testing the exactitude of this description of mine, and I shall be glad if you find that important data have thereby also been furnished, by which clearer conceptions with regard to the really practical, and especially the therapeutical, questions arising out of the subject, may be obtained. 5 Now that we have become acquainted not only with corporeal particles, but also with certain chemical sub- stances as the originators of dyscrasia, lasting for a lon- ger or shorter time according as the supply of these par- ticles and substances continues for a longer or shorter pe- riod, we may briefly revert to the question, whether, in addition to these forms, a kind of dyscrasia can be shown to exist in which the blood is the permanent seat of definite changes. We must answer this question in the negative. The more marked a really demonstrable contamination of the blood with certain matters is, the more manifest is the relatively acute course of the process. Just the very forms* in which medical men are most apt to con- sole themselves—especially for the shortcomings of the therapeutical results, with the reflection that they have to do with the deeply rooted and incurable chronic dys- crasia—just these forms depend, I imagine, least of all upon an original change in the blood ; for these are pre- * Tubercle, cancer, purpura, syphilis, etc. 252 LECTURE X. cisely the cases, in the majority of which extensive alte- rations are discovered in certain organs or in individual parts. I cannot assert that investigation has in this mat- ter in any way been pushed to its utmost limits, I can only say that every resource afforded by microscopical or chemical analysis has hitherto been fruitlessly em- ployed in investigating the part played by the blood in these processes ; and that, on the other hand, we are in most of them able to demonstrate important changes in larger or smaller groups of the ultimate constituents of organs ; and that on the whole the probability that the dyscrasia should in these instances also be regarded as secondary, and as derived from definite points in organs, becomes stronger every day. I shall have to examine this question a little more closely when I come to con- sider the theory of the propagation of malignant tumours, in the case of which recourse is, you know, so often had to the supposition that the malignancy has its root in the blood which gives rise to the local affections. And yet it is precisely in the course of these processes that it is comparatively most easy to show the mode of propaga- tion, both in the immediate neighbourhood of the dis- eased part, and in remote organs ; and it is in them we find, that there is one circumstance which especially favours the extension of such processes, namely the abundance of parenchymatous juices in the pathological formation. The drier a new formation is, the less in general are its powers of infecting, both nearer and more distant parts. ‘T'he mode of propagation itself commonly DIFFUSION BY MEANS OF CONTAGIOUS JUICES. 952. instance encroach upon the walls of the veins, so that they become really cancerous, and after a certain time the cancer either grows directly through the walls into the vessel and there continues its course, or a thrombus forms at the point, which invests the cancerous plug in a greater or less degree and into which the mass of can- cer grows. Here, therefore, we see a diffusion of the disease may possibly take place in two different manners, but the diffusion of corpuscular elements only in one, when, namely, an irruption ensues into the veins. An absorption of cancer-cells by means of the lymphatics cannot indeed in itself be ranked amongst impossibilities but at all events this much is certain, that no propaga- tion of the disease can take place until the lymphatic glands have in their turn undergone a complete cancer- ous transformation, and similar masses of cancer push on their growth from them into their efferent vessels. In no case can a peripheral lymphatic vessel sweep along into the blood the cells of the cancer so simply as it does the fluid parts ; this is only conceivable and possible in the case of the veins. But even in that case there is not the slightest probability that noxious matters are fre- quently diffused by their means, and for the simple rea- son that the metastases of cancer very frequently do not correspond with those with which we have become ac- quainted as occurring in embolia. The usual form of metastatic diffusion in cancer follows rather the direction of the secreting organs. The lungs, as is well known, are much more rarely invaded by cancerous disease than the liver, not only after gastric and uterine, but also after mammary cancer which would necessarily rather produce cancer in the lungs, if it were anything corpuscular which was conveyed away, became stagnant and gave rise to a new eruption of the disease. The manner in which the metastatic diffusion takes place seems, on the contrary, 954 LECTURE X. to render it probable that the transferrence takes place by means of certain fluids, and that these possess the power of producing an infection which disposes different parts to a reproduction of a mass of the same nature as the one which originally existed. We need only imagine a process similar to that which we see upon a large scale in small pox. The pus of small pox when directly ino- culated does indeed induce the disease, but the conta- gium™ is also volatile, and a person may have pustules over his skin after merely breathing air of a certain cha- racter. A similar state of things seems to prevail in cases, in which, in the course of heteroplastic processes, dyscrasize occur which do not burst out afresh at points which, according to the direction of the current of blood or lymph, would be most directly exposed to them, but at remote spots. As the salts of silver do not deposit themselves in the lungs, but pass through them to be precipitated only when they reach the kidneys or the skin, so an ichorous juice may pass from a cancerous tumour through the lungs without producing any change in them, and yet at a more remote point, as for example in the bones of a far distant part, excite changes of a malignant nature. * «. e, Contagious matter.—Zransl. LECTURE XI. MARCH 27, 1858, PIGMENTARY ELEMENTS IN THE BLOOD. NERVES. Melanemia—lIts relation to melanotic tumours and colorations of the spleen, Red blood-corpuscles—Origin—Melanic forms—Chlorosis—Paralysis of the respira- tory substance—Toxicemia. The nervous system—lIts pretended unity. Nerve-fibres—Peripheral nerves: their fasciculi, primitive fibres, and perineurium —Axis-cylinder (electrical substance)—Medullary substance (Myeline)—Non- medullated and medullated fibres—Transition from the one kind to the other: hypertrophy of the optic nerve—Different breadth of the fibres—Their termina- tions—Pacinian and tactile bodies. GrnTLEMEN,—I have still some observations to make to you in reference to the changes of the blood, more for the sake of completeness than because I am able to offer to you in doing so any decisive points of view. In the first place I wish to mention one other condi- tion which has recently been a great deal talked about, and might, when occasion offered, present increased in- terest to you, the so-called melanemia. This is a condi- tion most nearly connected with leukemia, inasmuch we have in it to deal with elements, which, like the colour- less corpuscles in leukemia, make their way from defi- nite organs into the blood and circulate with it. The number of recorded observations concerning this matter is already tolerably large, indeed I might almost say, 255 256 LECTURE XI. larger than perhaps is necessary, for it seems indeed that here and there mistakes have slipped in, which should, I think, be again removed from the history of the affection. But unquestionably there is a state iv which coloured elements are met with in the blood that do not belong to it. Isolated observations in support of this fact have already for a considerable length of time* been upon record, and indeed first occur in the history of melanotic tumours, concerning which it has frequently been de- clared that in their neighbourhood minute black particles are met with in the vessels, and the opinion put forward that from this source the melanotic dyscrasia arose. But this is not quite the condition which is meant when me- lanzemia is now-a-days spoken of. In the last ten years not a single observation has been made known which in any way adds to our knowledge concerning the passage of the particles of melanotic tumours into the blood. The first observation concerning that class of diseases ‘which in a narrower sense of the word is designated me- laneemia, was made by Heinrich Meckel in the case of a lunatic a short time after I had published my description of leukemia. Meckel found that here too the spleen was enlarged in a very considerable degree and pervaded by black pigment, and he therefore ascribed the change in the blood to an absorption of coloured particles from the spleen. The next observation I made myself (and that too in a class of cases which afterwards proved very fruit- ful) in the case of an ague-patient, who had long been afflicted with a considerable enlargement of the spleen ; for I found in the blood of his heart cells containing pig- ment. Meckel had only observed free granules and * Dr. Stiebel, sen., of Frankfort-on-the-Maine, calls my attention to the fact that he had already in a review of Schénlein’s Clinical Lectures (in Haser’s ‘ Archiv’), mentioned the occurr..nce of pigment-cells in the blood. Note to the Second Edition. MELAN AMIA, OB flakes (Schollen) containing pigment. The cells which I discovered in many respects bore a resemblance to colour- less blood-corpuscles ; they were spherical, but frequently also rather oblong, nucleated cells, within which a greater or less number of large black granules were to be seen. In this case also the occurrence of a large black spleen was again verified. Since that time attention has been cofitinually more and more drawn to these conditions by Meckel himself and by a number of other observers in Ger- many, and last of all by Frerichs, and in Italy by Tigri. Tigri has not scrupled *| to designate the disease mlza nera, from the blackness of the spleen in it, whilst according to the view of Meckel which has been ex- panded by Frerichs, it is rather one of the more severe forms of intermittent fever which is to be explained in this way. It has been attempted to explain the serious import of" these affections by supposing that the elements, which find their way into the blood, accumulate at certain points in the more minute capillary districts, and there produce stagnation and destruction. This was especially held to be the case in the capillaries of the brain, in which they were said to attach themselves after the man- ner of emboli to the points of division, and so occasion sometimes capillary apoplexies, sometimes the comatose and apoplectic forms of severe intermittent fever. Fre- richs has added a new and important kind of obstruction, namely, that of the minute hepatic vessels, which is said ultimately to give rise to atrophy of the parenchyma of the liver. Fig. 76. Melanemia. Blood from the right heart (Cf. ‘Archiv f. pathol. Anate- mie und Physiologie,’ vol. ii., fig. 8, p. 594). Colourless cells of various shapes filled with black, and in part angular, pigment-granules. 300 diameters. 17 258 LECTURE XI. If all this be the case, there would seem to exist an extremely important series of conditions directly depend- ent upon the dyscrasia. Unfortunately I can myself say but little concerning the matter, inasmuch as I have not since my first case again been in a position to observe anything similar. I cannot therefore form a decided opinion with regard to the value of the relations which have been laid down with respect to the connection of the secondary changes with the contamination of the blood. I only wish to remark that all the facts with which we are acquainted concerning these conditions, in dicate that the contamination of the blood has its rise in a definite organ, and that this organ, asin the case of the colourless blood-corpuscles, is generally the spleen. In the course of my description of the blood I have hitherto scarcely made any mention of the changes which take place in the red corpuscles, not by any means be- cause I regarded them as unimportant constituents of that fluid, but because as yet remarkably little is known concerning their changes. The whole history of the red blood-corpuscles is still invested with a mysterious obscu- rity, inasmuch as no positive information has even at the present time been obtained with regard to the origin of these elements. We only know this much with certainty, as I have already (p. 190) had occasion to remark, that a part of the original corpuscular elements of the blood proceed just as directly from the embryonic formative cells of the ovum, as all the other tissues which build themselves up out of them. We know, moreover, that in the first months of the existence even of the human embryo, divisions take place in the cells, whereby an increase in the number of them’present in the blood itself is produced. But after this time all is obscure, and this obscurity indeed corresponds pretty RED BLOOD-CORPUSCLES—THEIR ORIGIN. 259 exactly with the period at which the corpuscles in the blood of man and the mammalia cease to exhibit nuclei. We can only say that we are acquainted with no fact whatever which speaks in favour of a further independ- ent development, or of a cell-division, in the blood, but that everything points to the probability of a supply from without. The only hypothesis which has in more recent times been advanced with regard to the independ- ent development of the blood-corpuscles in the blood itself, is that of G. Zimmermann,* who assumed that there were little vesicles present in the blood, which gra- dually grew by intussusception whilst circulating with it, and ultimately constituted the real blood-corpuscles. Now little corpuscles certainly do occur in the blood (Fig. 52, h), only, when they are more accurately examined, a peculiarity reveals itself which is unknown in young embryonic forms, namely that they oppose an extraordi- nary degree of resistance to the most different agencies. In their ordinary state they are of a beautiful dark red, the colour being very intense and frequently nearly black ; if they are treated with water or acids which dis- solve the ordinary red corpuscles with ease, it is observed that the little bodies require a very much longer time before they disappear. Upon adding a large quantity of water to a drop of blood, they will be seen to remain for a considerable time after the other corpuscles have dis- appeared. This peculiarity accords best with what occurs in the changes which take place in the blood, when it is 2 * Zimmermann has recently (‘ Archiv f. path. Anat. und Phys.,’ vol. xviii, pp. 221-242) given us a more explicit statement of his views, and from it we gather that he considers the blood-corpuscles to originate in small, colourless vesicles which are introduced from the chyle into the blood and may be seen in it when its fluidity has been preserved by means of salts. But probably these vesicles are only artificial products, similar to those described nearly ten years ago by Harting (*Nederl. Lancet,’ 1851, 3d ser., 1st Jaarg., p. 224).—From a MS. Note by the Author. 260 LECTURE XI. extravasated or remains for a long time stagnant within the vessels. Such changes undoubtedly lead to a de- struction of the corpuscles, so that in the case of the cir- culating blood also the conclusion may with great proba- bility be drawn, that the bodies in question are not young forms, engaged in development, but on the contrary old ones in process of decay. I agree therefore essen- tially with Karl Heinrich Schultz’s view, who has de- scribed these bodies under the name of melanic (mela- nése) blood-corpuscles, and regards them as the precur- sors of the moulting of the blood (Blutmauserung)—pre- paring for the really excrementitious transformations. There are certain conditions in which the number of these corpuscles becomes extremely large. In very healthy individuals very few of them are found, only in the blood of the vena porte Schultz believes he has always observed a considerable number. It is certain, however, that there are diseased conditions in which their number becomes so large, that a greater or smaller quan- tity of them is met with in nearly every drop of blood. These conditions cannot however as yet be classed in de- finite categories, because but little attention has been excited with regard to them. They are found in slight forms of intermittent fever, in cyanosis after cardiac dis- ease, in typhoid-fever patients, in the fever accompany- ing ichorous infection after operations, and in the course of epidemic disorders, still always in such diseases as are accompanied by a rapid exhaustion of the mass of blood and give rise to cachectic and anemic states. This is one of the processes in which clinical observation also might lead to the conclusion that an abundant destruction was going on in-the constituents of the blood within the ves- sels. In addition to these changes we have precise know- ledge concerning another class distinguished by quantita- CHLOROSIS. 261 tive changes in the number of the corpuscles. These conditions, of which Chlorosis is the principal represen- tative, offer a certain resemblance to those which are accompanied by an increase in the number of the colour- less blood-corpuscles, to leukemia in a narrower sense of the word and the merely leucocytotic states. Chlo- rosis is distinguished from leukemia by the circumstance that the entire number of the corpuscles is smaller. Whilst in leukemia colourless corpuscles in some sort take the place of the red ones and a real diminution in the number of the cellular elements in the blood is not produced, in chlorosis the elements of both kinds become less numerous, without the occurrence of any definite disturbance in the numerical relation existing between the coloured and colourless corpuscles. This points to a generally diminished formation, and, if we may conclude (as I certainly think one can at the present moment scarcely help doing), that the red corpuscles also are brought to the blood from the spleen and lymphatic glands, all this would indicate that in chlorosis a dimin- ished formation takes place in the blood-glands. Leukee- mia is of course much more easily explained, inasmuch as in it we find representatives of the whole mass of cel- lular elements and can imagine that a part of them, instead of being transformed into red corpuscles, are pursuing their development as colourless ones. In the history of chlorosis, on the contrary, much obscurity still prevails, since we cannot positively demonstrate the ex- istence of a primary affection of the blood-glands. Ana- tomical observations indicate that the foundations of the chlorotic ailment are very early laid ; for the aorta and the larger arteries are usually, and the heart and sexual organs frequently, found imperfectly developed, facts which lead us to infer that the disposition is either con- genital or formed in early youth. 262 LECTURE XI. A third series of conditions may here too be men- tioned, which, however, do not affect the form of the blood-corpuscles, that, namely, in which the internal con- stitution of these elements has undergone changes, with- out the production of any definite morphological effect. Here we have essentially to deal with functional disturb- ances which are probably connected with more subtle changes in the composition of the blood, changes in the proper respiratory substance (respiratorische Substanz). For just as in muscles we find the substance of the pri- mitive fasciculus, the compact mass of syntonine, to be the contractile substance, so in the contents of the red corpuscles do we recognize the presence ofthe really active, respiratory substance. This under certain cir- cumstances undergoes changes which render it incapable of continuing its functions, a kind of paralysis, if you will. That something of the kind has occurred we see from the fact that the corpuscles are no longer capable of absorbing oxygen, as may be directly proved by expe- riment. That molecular changes in the composition of the blood are here really at work, we find satisfactory evidence in the action of poisonous substances which, even in extremely minute quantity, so change the hema- tine that it is thrown into a kind of paralysis. To these substances belong a part of the volatile compounds of hydrogen, for example, arseniuretted and cyanuretted hydrogen, and further, according to Hoppe’s investiga- tions, carbonic oxide, of all of which comparatively very small quantities are sufficient to diminish the respiratory power of the corpuscles. Analogous conditions have already long since been observed by many in the course of typhoid fevers, in which the capability of taking up oxygen decreases in proportion as the disease assumes a severe and acute character. Microscopically, however, with the exception of a few melanic corpuscles, scarcely THE NERVOUS SYSTEM. 263 anything is to be seen; chemical experiment and the coarse perception of the naked eye in this instance alone discover the occurrence of peculiar changes. It may therefore be said that in this quarter really the most has yet to be done. We have rather presumptive evidence than facts. If now we briefly sum up what I have laid before you concerning the blood, we see, either that certain sub- stances find their way into it, which exercise an injurious influence upon its cellular elements and render them in- capable of performing their functions; or that from a definite point, either from sources external to the body, or from some organ, matters are conveyed into it, which thence exercise an injurious influence upon other organs ; or finally that its constituents are not replaced and rege- nerated in a regular manner. Nowhere in this whole series do we find any one condition, indicating that defi- nite changes once set on foot in the blood itself can be permanently maintained, in other words that a perma- nent dyscrasia is possible, unless new agencies derived from a definite source are continually brought to bear upon the blood. This is the reason why I began by call- ing your attention to this point of view, which I conceive to be of extreme importance in practice also, namely, that in all forms of dyscrasiz the chief point is to search for their local origin. Let us now proceed to the consideration of another subject which comes next in historical importance, namely the structure and arrangement of the nervous system. The great mass of the nervous system consists of fibrous constituents. It is to them that nearly all the finer physiological discoveries, which the last fifteen years have brought with them, have reference, whilst the remaining portion of the nervous system, in quantity 264 LECTURE XI. much smaller, namely, the grey, or ganglionic, substance, has hitherto opposed difficulties even to histological in- vestigation which are still far from being overcome, so that the experimental examination of this substance has scarcely been able to be taken in hand. It is indeed often maintained that a great deal is now known about the nervous system, but our knowledge is for the most part confined to the white substance, the fibrous portion, whilst we are unfortunately obliged to confess that, both in an anatomical, but more especially in a physiological point of view, we are still involved in the greatest uncer- tainties with regard to the grey substance, which, as far as its functions are concerned, manifestly holds a much higher position. As soon as we consider the question of the influence exercised by the nervous system in the different pro- cesses of life, anatomically, a single glance suffices to show, that the point of view which neuro-pathologists have been accustomed to set out with, is a very erroneous one. For they fancied they saw in the nervous system an un- usually simple whole, from the unity of which resulted the unity of the body in general, of the whole organism. But even though one has nothing but very rough anato- mical ideas concerning the nerves, still one ought not to shut one’s eyes to the fact that this unity is in a very sorry plight, and that even the scalpel demonstrates the nervous system to be an apparatus composed of an ex- tremely large number of parts of relatively equal value without any single discoverable central point. The more accurately we make our histological investigations, the more do the elements multiply, and the ultimate compo- sition of the nervous system proves to be disposed upon a plan analogous to that which has been followed in all the other parts of the body. An infinite quantity of cellular elements manifest themselves side by side, more THE NERVOUS SYSTEM—PERINEURIUM. 2658 or less autonomous, and in a great measure independent of one another. If in the first instance we exclude the ganglionic sub- ' stance and confine ourselves simply to the fibrous matter, we have on the one hand the real (peripheral) nerves in the narrower sense of the word, and on the other the large accumulations of white medullary substance, of which the greater part of the cerebrum, cerebellum, and the columns of the spinal marrow is composed. The fibres of these different parts are indeed on the whole similarly constructed, but disclose in their intimate structure such numerous, and in part, such considerable differences, that there are spots, with regard to which even at this very moment we cannot say with certainty whether the ele- ments we have before us are really nerves, or belong to an altogether different kind of fibres. The greatest cer- tainty has been acquired with regard to the structure of the ordinary peripheral nerves ; in them the following can generally be distinguished with tolerable facility. Allthe nerves which can be followed with the naked eye contain a certain number of subdivisions, or fasci- culi, which afterwards separate in the form of branches or twigs. On tracing out these individual twigs which keep continually dividing, we find that the nerve under nearly all circumstances retains a fascicular arrangement until nearly its ultimate divisions, so that every fascicu- lus in its turn comprises a greater or less number of so- called primitive fibres. The term, primitive fibre, which is here employed, was originally selected, because a nerve-fasciculus was regarded as analogous to the primi- tive fasciculus of a muscle. This notion afterwards be- came almost obsolete, and Robin was the first who in more recent times again directed attention to the sub- stance which holds the fasciculus together and which he called perinewrium. It consists of very dense connective 266 LECTURE XI. tissue, which upon the addition of acetic acid, it seen to contain small nuclei, and is different from the looser con- nective tissue which in its turn holds the fasciculi to- gether and constitutes the so- called neurilemma. When we use the term nerve-fibre alone in its histo- logical sense, we always mean the primitive fibres, and not the fasciculi which to the naked eye look like fibres. These ultimate fibres in their turn possess, one and all, a special external membrane, which, when it has been entirely freed from its contents—a matter certainly very difficult to accomplish, but sometimes occurring sponta- neously in pathological conditions, as for example in cer- . tain states of atrophy—displays nuclei upon its walls (Fig. 5, c). Within these membranous tubes lie the pro- per nerve-contents, which in ordinary nerves may again be divided into constituents of two descriptions. These can scarcely be distinguished apart in a nerve which is quite fresh ; but in a short time after it has perished or been cut out, or after the action of any medium upon it, they at once separate very distinctly from one another, one of the constituents undergoing a rapid change which has generally been termed coagulation, and by means of which it is marked off from the other constituent (Fig. 78). When this has taken place there is distinctly seen in the interior of the nerve-fibre, the so-called axis-cylin- Fie. 77. Fig. 77, Transverse section through one of the trunks of the brachial plexus. 2, 4. Neurilemma, from which one thicker partition /’ and finer prolongations, indi- cated by light-coloured lines, run through the nerve and divide it into small fasci- culi. These exhibit the dark, punctated, transverse sections of the primitive fibres, and between them is seen the perineurium. 80 diameters, NERVE-FIBRES—AXIS-CYLINDER—MEDULLARY SHEATH. 267 der (the primitive band of Remak), a very fine, delicate, pale structure ; and round about it a tolerably firm, dark mass, here and there run- ning together, the nerve-me- a dulla or medullary sheath [white substance of Schwann] ; this fills up the space between the axis-cylinder and the external membrane. But the nerve- tube is generally so tightly filed with its contents that, when viewed in the ordinary way, scarcely anything is seen of the separate constituents, the axis cylinder being always with difficulty visible within the medullary substance. Hence the fact may be accounted for, that its very existence was disputed for years and the view proclaimed by many, that it was also an appearance due to coagulation, produced by a separation of the ori- ginally homogeneous contents into an internal and exter- nal mass. This view is however unquestionably incor- rect: every mode of examination at last discloses this primitive band ; even in transverse sections of nerves the axis-cylinder is very distinctly seen in the interior, with the medulla round about it. It is the so-called nerve-medulla which gives the nerve- fibres in general their white appearance ; wherever the nerves contain this constituent, they look white; Fig. 78. Grey and white nerve-fibres. A. A grey, gelatinous nerve-fasciculus from the root of the mesentery, after the addition of acetic acid. 2B. A broad white primitive fibre from the crural nerve: a the axis-cylinder laid bare, 2, 0 a varicose state of the fibre with its medullary sheath ; at the end at m, m the medullary mat- ter(myeline) protruding in convoluted forms. @. A fine, white primitive fibre from the brain, with its axis-cylinder protruding. 3800 diameters. 268 LECTURE XI. wherever it is wanting, they appear translucent and grey. There are therefore nerves which are akin in colour to ganglionic matter, are comparatively transparent and possess a more clear and gelatinous appearance than the others ; and they have thence been called grey or gela- tinous nerves (Fig. 78, A). Between the grey and white nerve-substance therefore there does not exist the differ- ence that the one is ganglionic and the other fibrous, but only this, that the one contains medulla and the other does not. In general the absence of medulla in a nerve stamps it as one of a lower and more imperfect kind, whilst the presence of this substance announces a more abundant nutrition and a higher development in the part. Not long ago I made an observation in which a direct illustration of the practical importance of these two con- ditions was displayed in a very unexpected manner, the usually translucent grey nerve substance having been trans- formed into an opaque and white matter, namely in the retina. I found namely entire- ly by accident one day, in the eyes of aman in whom I was looking for changes of quite another kind—round about the papilla of the optic nerve, where the uniformly trans- lucent retina is ordinarily seen—a number of whitish, Fie. 79. Fig. 79. Medullary hypertrophy of the optic nerve within the eye (Cf. ‘ Archiv f. pathologische Anatomie und Physiologie,’ vol. x., p. 190). A. The posterior half of the globe of the eye, seen from before ; from the papilla of the optic nerve pro- ceed in four directions radiating striw of white fibres. 2B. Fibres from, this optic nerve in the retina, magnified 300 times: u, a pale, ordinary, slightly varicose fibre, 6, one with a gradually thickening medullary sheath, c, a similar one with its axis- cylinder protruding. MEDULLATED AND NON-MEDULLATED NERVES. 969 radiating strie like those which one sometimes meets with upon a small scale in dogs, and pretty constantly in rabbits in different directions. The microscopical exa- mination showed that, like as in these animals, medullated fibres had developed themselves in the retina, and that its fibrous layer had become thicker and opaque in con- sequence of the assumption of medullary substance. On examining the individual fibres I found, on tracing them from the fore and middle parts of the retina backwards towards the papilla, that they gradually increased in breadth, and at the same time displayed, at first in an almost imperceptible, but afterwards in a very striking manner, an investing layer of medulla. This is a kind of transformation, therefore, which essentially impairs the functions of the retina, for this delicate membrane becomes thereby more and more impervious to light, in- asmuch as the white substance does not suffer the rays of light to pass through. The same change occurs in nerves during their deve- lopment. A young nerve is a delicate, tubular structure, provided with nuclei at certain intervals and containing a pale grey substance. The medulla does not appear until afterwards, and then the nerve becomes broader and the axis-cylinder becomes distinctly defined. Itmay be said therefore that the medullary sheath is not an absolutely necessary constituent of a nerve, but is added to it only when it has arrived at a certain stage in its development. Hence it follows that this substance, which was for- merly regarded as the essential constituent of a nerve, according to present views plays a subordinate part. Those only who do not even now admit the existence of the axis-cylinder, regard the white substance of course not only as the greatly predominating constituent, but ‘also as the really active element of the nerve-contents. 270 LECTURE XI. Now it is very remarkable that this same substance is one which most extensively prevails in the animal body. I had, curiously enough, in the first instance in the exami- nation of lungs come across forms which presented very similar qualities to those which we observe in the me- dulla of the nerves. Although this was very surprising, yet I did not really think there was an actual correspond- ence, until I was gradually led by a series of further ob- servations which accumulated in the course of several years, to examine a number of tissues chemically. The result showed, that there scarcely exists a tissue rich in cells in which this substance does not occur in large quantity ; still it is only in the nerve-fibre that we ob- serve the peculiarity, that the substance separates as such, whilst in all other cellular parts it is contained in a finely divided state in the interior of the cells, and is only set free when the contents undergo a chemical change, or are subjected to the action of chemical reagents. From blood-cells, from pus-cor- puscles, from the epithelial cells of the most various glan- dular parts, from the interior of the spleen and similar glands unprovided with excretory ducts, this substance can in every case be obtained by extraction. It is the same substance which forms the principal constituent of the yellow mass of yolk in the hen’s egg, whence its taste and peculiarities, especially its peculiar tenacity and vis- cidity which are employed for the higher technical pur- poses of the kitchen, are familiar to every one. It is this substance, for which I have proposed the name of medul- Fie. 80. Fig. 80. Drops of medullary matter (myeline—according te Gobley, lecithine). A. Differently shaped drops from the medullary sheath of cerebral nerves, after they have become swollen up with water. 3B. Drops from decomposing epithelium from the gall-bladder in their natural fluid. 800 diameters, AXIS-CYLINDER (ELECTRICAL SUBSTANCE). o71 lary matter (Markstoff), or myeline, that in extremely large quantity fills up the interval between the axis- cylinder and the sheath in primitive nerve-fibres. If the nutrition of a nerve suffer disturbance, this sub- stance diminishes in quantity and indeed may under cer- tain circumstances totally disappear, so that a white nerve may be again reduced to the condition of a grey or gelatinous one. This constitutes grey atrophy, or gelatinous degeneration, in which the nerve-fibre in itself continues to exist, and only the peculiar accumulation of medullary matter has been affected. Herein you may seek for an explanation of the circumstance, that in many cases where, in accordance with the results of anatomical investigation, it was formerly thought one might expect to find a part completely incapable of fulfilling its func- tions, proof has been afforded by means of clinical obser- vation, aided by electricity, that the nerve is still capa- ble of performing its functions, although in a less degree than normal. Hence too it is manifest that the medulla cannot be the constituent in which lie vested the func- tions of the nerve as such. To the same conclusion phy- sical investigations also have generally led, and at the present time therefore the axis-cylinder is pretty gene- rally looked upon as the really essential constituent of the nerve, which is also present in pale nerves, whilst in white ones it can only be distinctly isolated by the sepa- ration of the investing medullary sheath. The axis-cylin- der would therefore seem to be the real electrical sub- stance of natural philosophers, and we may certainly admit the hypothesis which has been advanced, that the medullary sheath rather serves as an isolating mass, which confines the electricity within the nerve itself, and allows its discharge to take place only at the non-medullatea extremities of the fibres. The peculiar nature of the medullary matter most fre 272 LECTURE XI. quently displays itself in this way, that when a nerve is torn across or cut (Fig. 78, m, m), the medulla usually protrudes from it, presenting, especially after it has been acted upon by water, a peculiar striated appearance (Fig. 80, A). It takes up water namely, which is a proof that it is not a neutral fatty substance in the ordinary sense of the term, but can at most, on account of its great power of swelling up, be compared to certain saponace- ous compounds. The longer the action of the water lasts, the longer are the masses which protrude from the nerve. They have a peculiar, ribbon-like appearance, keep con- tinually acquiring new streaks and layers, and give rise to the most singular shapes. Frequently also fragments become detached and swim about, forming peculiar, stra- tified bodies, which in recent times have been confounded with corpora amylacea, but are distinguished from them in the most positive manner by their chemical reactions. With regard to the histological varieties of nerves amongst themselves, investigation shows that in different parts more or less highly deve- loped forms greatly predominate. On the one hand, namely, the nerves are essentially distin- guished by the breadth of their primitive fibres, on the other hand, by the presence of medulla. We have very broad, middle-sized and small white fibres, and in like manner broad and fine grey fibres. A very considerable size is generally speaking but seldom attained by the grey ones, because the size of a nerve depends more upon the greater or less quan- tity of medulla it contains than upon the volume of the axis-cylinder, but still variations present themselves Fig. 81. Broad and narrow nerve-fibres from the crural nerve with the medullary substance irregularly swollen up. 800 diameters. VARIETIES OF NERVE FIBRES, 975 everywhere, so that some nerves are coarser and others finer. Generally, we may say, that the primitive fibres usu- ally become finer in the terminal portions of nerves, and that the ultimate ramifications of these latter are wont to contain comparatively the finest fibres ; still this is not an absolute rule. In the optic nerve we commonly find from the very moment of its entrance into the eye only very narrow, pale fibres (Fig. 79, a), whilst the tactile nerves of the skin present quite up to their terminations comparatively broad and dark bordered fibres (Fig. 83). It has not yet been found possible to arrive at any cer- tain opinion with regard to the import of the different kinds of fibres from their breadth and the proportion of medulla they contain. Fora time it was believed that a distinction of this sort could be established between them, namely, that the broad fibres were to be regarded as derived from the real cerebro-spinal parts, the fine ones as parts of the sympathetic; but this is not found to be borne out by facts, and all that can be said is, that the ordinary peripheral nerves certainly are abundantly provided with broad fibres, whilst the sympathetic nerves contain a comparatively larger portion of fine ones. In many places, as for example in the abdomen, grey, broad fibres predominate (Fig. 78, A), with regard to the ner- vous nature of which doubts are still entertained by some. For the present, therefore, no definite conclu- sions can be drawn as to any difference in the functions of a nerve from its mere structure, although it can scarcely be doubted that such differences must exist, and that a broad fibre must exhibit other properties, even if only quantitatively different, than a fine one, a medul- lated fibre others than a non-medullated one. However concerning all this nothing is at present known with cer- tainty ; and since it has been demonstrated by more 18 a74 LECTURE XI. delicate physical investigations that the nerves, which had been previously assumed only to conduct in the one or the other direction, possess the power of conduction in both directions, I should not, I think, be justified in here advancing any hypotheses with regard to their cen- tripetal or centrifugal conduction. The great difference, gentlemen, which is to be re- marked in regard to the functions of individual nerves, cannot as yet be referred so much to any difference of structure in them, as to the peculiarity of the structures with which the nerve is connected. Thus on the one hand the special function of the central organ from which the nerve proceeds, and on the other, the special nature of its distal termination, afford a clue to its own specific functions. With reference to the terminations which the nerves present at their peripheral extremities, histology has, I should say, in the course of the last few years celebrated its most brilliant triumphs. Previously it was, as you well know, a matter of dispute whether the nerves ended in loops or in plexuses, or whether their terminations were free, and the one or the other opinion was held with equal exclusiveness. Now, we have examples of most of these modes of termination, but the fewest of that form which was for a time regarded as the regular one, namely the termination in loops. The most manifest form of termination, though the one whose functions are, singularly enough, even now the least known, is that in the so-called Pacinzan or Vaterian* bodies—organs, concerning the import of which we are still unable to make any statement. They are found in man comparatively most marked in the adipose tissue of the ends of the fingers, but also in tolerably large * Vater was professor at Wittenberg, and died in 1751. PACINIAN BODIES. 275 numbers at the root of the mesentery ; most distinctly and readily, however, in the mesentery of the cat, in which they extend a considerable distance up, whilst in the human body they are situated only at the root of the mesentery, where the duodenum comes in contact with the pancreas in the neighborhood of the solar plexus. Moreover they pre- sent great variations in different indi- viduals. Some have very few, others a great number, of them, and it is very possible that certain individual pecu- larities result therefrom. Thus I have, for example, on several occasions found a great number of these bodies in lunatics, though I do not wish at present to lay any great stress upon this discovery. A Pacinian body, as seen with the naked eye, is of a whitish colour, usu- ally oval and somewhat pointed at one end, from a line to a line and a half (1—1#’”’) long, and firmly attached to a nerve in such a way that a single primitive fibre passes into each body. It presents a comparatively large num- ber of elliptical and concentrical layers, which at the upper end are in pretty close contact, but at the other are separated by a wider interval, and en- close in their interior an oblong space generally some- Fie. 82. Fig. 82. Vaterian or Pacinian body from the subcutaneous adipose tissue of the end ofa finger. S. The peduncle, consisting of a dark-bordered, medullated pri- nitive nerve-fibre z, and the thick perineurium p, p provided with longitudinal nuclei. @. The body itself with the concentric layers of the perineurium which is swollen out into a bulbous shape—and the central cavity, within which the pale axis-cylinder is seen running along and terminating in a free extremity. 150 diameters. 276 LECTURE XI. of what more pointed towards the upper end. Within these layers nuclei can be distinctly seen disposed in regular order, and on following the layers towards the stem of the nerve, they are there observed finally to pass into the perineurium which is in this part very thick. They may therefore be regarded as gigantic developments of the perineurium, which however only enclose a single nerve-fibre. Now on tracing the nerve-fibre itself we observe that its medullated portion usually extends only up to the beginning of the body, when the medulla dis- appears and the axis-cylinder is seen continuing its course alone. Itthen runs on through the central cavity, and terminates at no great distance from the upper end generally simply, yet often in a little bulbous swelling* and in the mesentery very frequently in a spiral coil. In rare cases it happens that the nerve divides and seve- ral branches pass into the body. But in every case we seem to have before us a mode of termination. What these bodies signify, what office they perform, whether they have anything to do with the function of seusation, or whether their province is to develop any one of the properties of the nervous centres, we are as yet entirely ignorant. A certain degree of resemblance to these structures is exhibited by the tactile bodies which have been recently so much the subject of discussion. When the skin and more especially the sensitive part of it is microscopically examined, two sorts of papillee, as was first discovered by Meissner and Rud. Wagner, are distinguished, the one narrower, the other broader, though certainly interme- diate forms are met with (Fig. 83). In the narrow ones we constantly find a simple, in broader ones of the same class a branching, vascular loop, but no nerve. This * Quite recently Jacubowitsch has, as he thinks, discovered a ganglion cell in this part.—J£S. Note uf Author. TACTILE BODIES. 277 point is so far of importance, that we have, by means of these observations, been made acquainted with a new nerveless structure. In the other kind of papilla we very frequently find no vessels at all, but on the other hand nerves, and those peculiar structures which have been designated tactile bodies. A tactile body manifests itself as an oblong-oval struc- ture, tolerably distinctly marked off from the remainder of the papilla, and has, with some degree of boldness in- deed, been compared by Wagner to a fir-cone. It is generally rounded off at the upper and lower end, and does not exhibit a longitudinal striation, as the Pacinian bodies do, but on the contrary transverse nuclei. Now a nerve runs up to every one of these bodies, and from every one of them a nerve returns, or more correctly, we usually see two nervous filaments, generally pretty Fig. 83. Fig. 83. Nervous and vascular papilla from the skin of the end of a finger, after the separation of the epidermis and rete Malpighii. .A. Nervous papilla with a tac- tile body, up to which ascend two primitive nerve-fibres n; at the base of the pa- pilla fine elastic networks e, from which fine fibres radiate, between and on which connective-tissue-corpuscles are to be seen. B, C, D. Vascular papille, with, at C, simple, at B and D, branching vascular loops, and in addition fine elastic fibres and connective-tissue-corpuscles ; p. the papillary body running its horizontal course, at c fine stellate cells belonging to the cutis proper. 8v0 diameters, 278 LECTURE XI. \ close to one another, which can be readily traced up to the side or base of the body. After this point their course is very doubtful, and in different cases the condi- tions vary so much that we have not yet succeeded in making out with certainty the relation of the nerves to these bodies. In many cases, namely, the nerve is very distinctly seen to ascend and also to entwine itself around the body. Sometimes it seems as if the body really lay in a nervous loop, and thus the possibility of a more concentrated action on the part of external agen- cies upon the surface of the nerve was provided for. At other times again it looks as if the nerve came to a ter- mination much sooner, and buried itself in the body. Some have assumed, with Meissner, that the body itself belongs to the nerve which resolves itself into it. This I do not hold to be correct, and the only point which seems to me to be doubtful is, whether the nerve ends in the body or forms a loop around it. Apart from anatomical and physiological considera- tions, this example is of great value in the interpreta- tion of pathological phenomena, because we here find two complete contrasts in parts which in.themselves are quite analogous ; for, on the one hand, we have nerve- less but vascular, on the other, non-vascular, papilla. yet provided with nerves. The peculiar relations which the layers of the rete mucosum and epidermis bear to the two kinds of papilla, do not appear to present any essential differences. They are nourished just as perfectly over the one sort as over the other, and seem to be just as little provided with nerves over the one as over the other. These are facts which indicate a certain independence in individual parts and furnish distinct evidence that parts of considerable size and even richly provided with nerves can subsist, maintain their existence and perform TACTILE BODIES. ye!) their functions without vessels, and that on the other hand parts which relatively contain numerous vessels, can ~ absolutely dispense with nerves without incurring any disturbance in the state of their nutrition. LECTURE XII. MARCH 31, 1858. THE NERVOUS SYSTEM. Peripberal terminations of the nerves—Nerves of special sense—The skin and the distinction of vessel-, nerve-, and cell-territories in it—Olfactory mucous mem- brane—Retina—Division of nerve-fibres—The electrical organ of tishes—Mus- cles—Further consideration of nerve-territories—Norvous plexuses with gan- glioniform enlargements—Intestines—Errors of the neuro-pathologists. The great nervous centres—Grey substance—Ganglion- [nerve-] cells containing pigment—Varieties of ganglion-cells; sympathetic cells in the spinal marrow , and brain, motor and sensitive cells. Multipolar (polyclonous) ganglion-cells— Different nature of the processes of ganglion-cells, I return, gentlemen, to-day once more to the skin. The difference which exists between the individual pa- pille of the skin seems to me so important theoretically, that I think I must claim your special attention to it. In the greater number of the papille we see, as I mentioned to you the last time, a single or, when the papilla is very large, a branched, vascular loop. The majority of these vascular papille have no nerves; others again which contain tactile bodies, no vessels. If we imagine the vessels and tactile bodies removed, there remains only a very small quantity of substance in the papilla, but within it there still are morphological elements, and it is easy to convince oneself that connective tissue with its corpus- cles (which latter after injection are very easily distin- 280 NERVES OF SPECIAL SENSE. 281 guished from the vessels), is in immediate contact with the cells of the rete mucosum (Fig. 83). The case is espe- cially favourable when, in consequence of any disease, as for example small-pox, a slight tumefaction of the whole ° thickness of the skin in the parts affected has taken place, and the corpuscles are a little larger than they normally are. In ordinary papille it is somewhat more difficult to discover these elements, still upon closer examination they may be seen everywhere, even by the side of the tactile bodies. Thus, even in the finest of these prolongations of the cutis, it is not an amorphous mass which is found, bear- ing a constant relation to the vessels and nerves ; on the contrary this mass of connective tissue always manifests itself as the one thing invariably present in the structure, as the real fundamental constituent of the different (vas- cular and nervous) papille, and the individual papillze do not acquire a different character until in the one case vessel, in the other nerves, are added to this funda- mental substance. We certainly know little concerning the special rela- tions which the vascular papille bear to the functions of the skin, still it can scarcely be doubted that an import- ant relation must exist, and that as soon as we are better able to separate the different offices of the skin, greater importance will be attached to the vascular papille also. This much however we can even now say, that it is incor- rect to imagine that a special nervous branch exists in every anatomical division of the skin: just as physiolo- gical experiments* show that considerable sensitive dis- tricts exist in the skin, so also more minute histological in- vestigation teaches us that there is a relatively scanty ter- mination of nerves upon the surface. If therefore we think fit to divide the skin into definite territories, those * The allusion is to Weber’s experiments with compasses.—TZrans. 289 LECTURE XII appertaining to the nerves will, as a matter of course, be larger than those belonging to the vessels. But every vessel territory (papilla) also which is marked out by a ‘single capillary loop is divided mto a series of smaller (cell-) territories, all of which certainly lie along the banks of the same vessel, but still have an independent existence, each of them being provided with a special cel- lular element. In this manner it is very easy to explain how within a papilla a single (cell-) territory may become diseased. Suppose, for example, that such a territory swells up, in- creases in size, and continually keeps shooting farther and farther upwards, then arborescent ramifications may Fie. 84, arise (accuminate [spitzes] condyloma*) without the whole papilla’s being affected in a like manner. The Fig. 84. The fundamental substance (connective tissue) of an acuminate condy- loma of the penis with freely budding and branching papilla, after the epidermis and the rete mucosum have been completely detached. 12 diameters. * The Germans speak of condylomata data and acuminata. The condyloma latum is invariably of syphilitic origin, and is identical with the plaque muqueuse of the French, who never use the term condylome in this sense. Condyloma acuminatum, on the contrary (by the French termed simply condylome), is not syphilitic in its nature, but frequently occurs in gonorrhea, though it is also met with independently of this disease.—From a MS. Note by the Author. VESSEL-, NERVE-, AND CELL-TERRITORIES. 283 vessel does not shoot up until later and forces its way into the branches when they have already attained a cer- tain size. It is not the vessel which pushes out the parts by its development, but the first signs of development always show themselves in the connective tissue of the papilla. The study of the conditions of the skin therefore affords special interest to those who wish to devote them- selves to the critical examination of the doctrines held concerning general pathology. And first with regard to the neuro-pathological views, it is quite inconceivable how a nerve which lies in the middle of a whole group of nerveless parts, can contrive to force a single papilla from among this group, with which it has not the slightest connection, into a state of pathological activity in which the remaining papille of the same nerve-territory take no share. Just as difficult is it, in the diseases of non- vascular papille, to find an explanation which shall accord with the views of a humoro-pathologist. Even when ina vascular papilla the different cell-territories attain different states, these would not admit of a ready explanation, if we were to regard the whole process of nutrition in a papilla as directly dependent upon the general condition of the vessel which supplies it. Similar considerations might be entered upon with regard to all points of the body. Still we have in the skin a particularly favourable example for demonstrating how very incorrect it is to regard all vessels as subject to a particular nervous influence. There are a number of vessels which are entirely removed from the influence of all nerves, and, if we still confine our attention to the skin, the influence which a nerve is in a condition to exercise, is limited to this, that the afferent artery, which supplies a whole series of papillae in common (Fig. 44) may by its means be brought into an altered condition, so that a contraction or dilatation, and in correspondence 984 LECTURE XII. with these states a diminished or increased supply of blood to a considerable district, takes place. If now we return from this digression to our real sub- ject, you will recollect that I had described to you my ignorance concerning the real mode of termination which the nerves have in the tactile bodies. Whether the nerve ultimately forms a loop, or in any manner directly terminates in the internal substance of the body, is not, I think, as yet absolutely decided. If now we consider other instances of the terminations of nerves, nowhere does any probability manifest itself that they really do form loops. In every case in which more certain knowledge has been acquired, the proba- bility has on the contrary always become greater, that the nerves either terminate in a large plexus or recticular expansion ; or that they end in special apparatuses, con- cerning which it is still doubtful whether they are pecu- liar processes of a particular shape, into which the nerves shoot out at their extremities, or whether they consti- tute peculiar parts, non-nervous in their nature, to which the nerves attach themselves. This latter mode of ter- mination is, it would appear, characteristic of most of the higher organs of sense, but in no single instance, in con- sequence of the extreme difficulty which the investigation of these parts presents, have any views been proposed which have met with universal assent. Notwithstanding the numerous investigations into the structure of the retina and cochlea, the mucous membrane of the nose and mouth, that have been made in the course of the last few years, it must be confessed that the ultimate points of histological detail have not as yet been altogether satisfactorily settled. In nearly all cases there remain two possible ways in which the nerves may terminate. According to some their terminations are connected with special structures which, according to the language RETINA. 285 hitherto employed, cannot be regarded as being of a ner- vous nature, but are peculiar appendages of the nerves, though they are certainly stated by other observers to be directly connected with nerve-fibres, as for example in the nasal mucous membrane. This namely is regu- larly clothed with cylindrical epithelium, which is plen- tifully provided with cilia and forms several layers, lying one above the other, so that there are several rows of cells covering one another. In these, according to seve- ral recent observers, cells are met with, which terminate in a somewhat long filament, and do not, like other epi- thelial cells, end upon the surface, but run in an inward direction, so as to become directly continuous with the ends of the nerves. According to others, particularly Max. Schultze, on the contrary, and this view seems tc be the more correct one, peculiar filiform ends of nerves force their way out between the epithelium. The objects of smell would therefore according to both views really come directly in contact with the structures forming the terminations of the nerves. Similar epithelium-like strue- tures have recently been described as occurring also in the mucous membrane of the tongue, seated upon pecu- liar papille, which appear to possess a pre-eminently nervous character. These structures moreover might lay claim to a certain resemblance with the ultimate terminations which we find in the case of the optic nerve in the retina, and in that of the auditory nerve especially in the cochlea—termina- tions, which may in the latter case, as far as their exter- nal shape is concerned, be compared to long-tailed epi- thelial cells, whilst those in the retina constitute struc- tures of peculiar delicacy. In the reténa namely the optic nerve, after its entrance into the interior of the globe of the eye, spreads out in such a way, that its fibrous elements run along on the anterior side of the retina, that 286 LECTURE XII. side, namely, which is turned towards the vitreous body (Fig. 85, 7) ; posteriorly, there follows a stratum of vary- ing thickness, which belongs to the retina indeed, but in no wise proceeds from the direct expansion of the optic nerve. In this layer we see, where it borders upon the layer of pigment-cells of the choroid coat, and in imme- diate contact with these cells, a peculiar stratum which has been subjected to a strange destiny, inasmuch as it was for a considerable time transplanted to the anterior Fig. 85. side of the retina—the famous bacillar layer (layer of rods—Stibchenschicht [membrana Jacobi]) (Fig. 85, s). This layer, which belongs to the most easily injured parts of the eye, and for this reason in many instances escaped the notice of earlier observers, consists, when viewed in profile, of a very large quantity of closely Fig. 85. A. Vertical section through the whole thickness of the retina, after it had been hardened in chromic acid. J. Membrana limitans, with the ascending, supporting fibres. jf. Fibrous layer of the optic nerve. g- Layer of ganglion-cells. n. Grey, finely granular layer, with the radiating fibres passing through it. &. In- ternal (anterior) granular layer. é. Intermediate, or intergranular, layer. ik’, Ex- ternal (posterior) granular layer. s. Layer of rods and cones, 300 diameters B, C (after H. Miller), Isolated radiating fibres. RETINA. 987 packed little rods, arranged in a radiated form, and be- tween which at certain intervals appear broader, conical bodies. When the retina is viewed from behind, 7. e., from the choroid coat, we see regularly arranged between these cones fine points which correspond to the ends of the little rods, Now that which intervenes between this bacillar layer and the proper expansion of the optic nerve, is likewise a very complex affair, in which a series of layers follow- ing one another in regular succession can be distin- guished. Immediately in front of the bacillar layer comes a comparatively thick stratum, which appears to be nearly entirely made up of coarse granules, the so- called external granular layer (Fig. 85, %’). Then comes a thinner layer which generally presents a tolerably amorphous appearance, the inter-granular layer (Fig. 85, 2). Then we again have coarsish granules (the inter- nal granular layer) ; these bodies in both layers having much the appearance of nuclei (Fig. 85, &). Next fol- lows a second layer of a more uniform, finely granular or finely striated appearance, and of a more greyish hue (Fig. 85, 2), and then only the tolerably thick stratum of the optic nerve, which in its turn is bounded by a membrane, the membrana limitans (Fig. 85, 7), which is in close apposition to the vitreous body. Within this last layer we see, besides the fibres of the optic nerve, and situated behind them, a number of largish cells, which have the appearance of nerve-cells (Fig. 85, g). This extremely complex structure in a membrane which at first sight is so simple and so delicate, readily accounts for its being extremely difficult to ascertain with : cer- tainty all the relations of its individual parts. It was one of the most important advances towards the know- ledge of these relations which was made by the discovery of Heinrich Miiller, that namely from behind, from the 288 LECTURE XII. bacillar layer into the most anterior layers, a series of rows of fine fibres could be traced (radiating fibres, also called Miillerian fibres), which both receive the granules, and support the cones and rods (Fig. 85, B, C). This very complicated apparatus is placed as nearly as possible perpendicularly to the course of the fibres of the optic nerve. The greatest difficulty which exists with regard to the anatomical connection of the parts, is to determine whether the radiating fibres, either by bending directly round, or by a lateral anastomosis, become continuous with the optic or ganglionic fibres, and are thus them- selves nervous, or whether only an intimate apposition takes place, and so the nerves bear no other relation to the radiating fibres than those of proximity. A tactile body may also, you know, be either regarded as a body formed by a swelling of the nerve itself, or as a special structure up to which the nerve only proceeds or into which it enters. This question (of the connections of the radiating fibres) has not yet been definitively settled. At one time the probability became rather stronger that direct communications existed, at another that nothing more than a mere apposition took place. It can, how- ever, even now no longer be doubted, that this appara-- tus is essential to the perception of light, and that the optic nerve might exist with all its parts without in any way possessing the power of receiving impressions of light, if it were not connected with this apparatus. It is well known that just that point in the background of the eye, where there are only optic fibres and no such appa- ratus, is the only one which does not receive impressions of light (the blind spot). In order therefore that the light may be rendered at all capable of acting upon the optic nerve, it unquestionably requires to be collected by means of this apparatus of fibres, and it is therefore an extremely interesting question for delicate physical THE PLEXIFORM DISTRIBUTION. 989 researches, whether the nerve itself receives at its ex- treme ends the vibrations of the waves of light, or whether another part exists, the oscillations of which act upon the optic nerve and produce a peculiar excitation in it. At all events there do ascend from the mem- brana limitans slightly curved fibres (Fig. 85, 7), proba- bly connective tissue with its corpuscles, which afford a kind of stay or support to the whole apparatus (support- ing fibres [Stiitzfasern]), and are not, I should suppose, freely connected with the rest of it. We have, gentlemen, by the consideration of these re- lations brought out the fact, that the specific energy of individual nerves does not so much depend upon the pe- culiarity of the internal structure of their fibres as such, but that a great deal must be attributed to the special terminal arrangement, with which the nerve is connected, either directly or by contact, and from which the different nerves of sense de- oe rive their peculiar powers. If for exam- ple we examine a transverse section of the optic nerve external to the eye, it offers no peculiarities as compared with other nerves, which could at all account for this particular nerve’s being better able to conduct light than other nerves, whilst on the other hand the peculiar manner in which its extreme ends are ‘distributed sufficiently explains the un- usually great sensitiveness of the retina to light. With regard to the terminations of nerves, there is still one mode to be men- tioned ; the plexiform distribution. This Fig. 86. Division of a primitive nerve-fibre at ¢, where we find a constriction; 2’, b” branches. u. Another fibre, crossing the former one. 300 diameters, 19 290 LECTURE XIL is a point to which more recent researches have been principally directed by Rudolph Wagner, inasmuch as this inquirer instituted investigations into the distribu- tion of the nerves in the electrical organ of fishes, and in so doing gave the chief impulse to the doctrine of the ramification of nerve-fibres. Up to that time nerves had been regarded as continuous, single tubes, which re- mained single throughout the whole of their course from a nervous centre to their termination. At present we know that nerves are distributed like vessels. Now see- ing that nerve-fibres directly divide, usually dichoto- mously, and their branches again divide and subdivide, extremely abundant ramifications may in this way in time arise, the import of which is extremely different, according as the nerve is motor or sensitive, and either collects impressions from, or diffuses motor impulses Zo, a considerable extent of surface. A truly marvellous instance has lately come to our knowledge in the electri- cal nerve of the electrical silurus (malapterurus), which has become so celebrated by the interesting experiments of Dubois-Reymond. Here Bilharz has shown that the nerve which supplies the electrical organ is in the first in- stance only a single microscopical primitive fibre, which keeps continually dividing until it finally resolves itself into an enormously great number of ramifications which spread themselves out upon the electrical organ. Here therefore the nervous influence must all at once diffuse itself from one point over the whole extent of the elec- trical plates. In man we are still in want of distinct evidence with regard to this question, because the immense distances, over which individual nerves extend, render it almost impossible to follow any single given primitive fibres from their central origin to their extreme peripheral ter- mination, But it is not at all improbable that in man NERVOUS PLEXUSES. 291 too analogous arrangements exist in some organs. although perhaps not such striking ones. If we compare the size of the nervous trunks in certain parts with the total number of operations which are effected in an organ, for example, in a gland, it can scarcely appear doubtful that at least analogous arrangements exist there also. This mode of distribution offers peculiar interest in this respect, that many parts which are separated by intervals of space are thereby connected with one an- other. The electrical organ is composed of a number of plates, but not every plate is supplied with nerves pro- ceeding from the centre and intended only for it. The silurus does not set one or other of its plates in motion, but is obliged to set the whole of them in motion ; it is quite unable to divide the action. It can increase or diminish the intensity, but must always call the whole into operation. If in like manner we consider the ar- rangements which prevail in certain muscles, we find there is no evidence to justify us in assuming that every portion of a muscle receives special, independent nerve- fibres. On the contrary, a special division of nervous action in muscles only exists to a very limited extent, as we know from our experience in our own bodies. The neuro-pathological doctrines would lead us to infer that the will, or the soul, or the brain is able by means of spe- cial fibres to act upon every single part, but in reality this is by no means the case, for the nervous centres have mostly only one single path by which they can communicate with a certain number of similar elemext- ary apparatuses. Now with regard to nervous plexuses, we are at the pre- sent time acquainted with most extensive arrangements of the kind in man, in the submucous tissue of the intes- tines, where the relations have recently been more closely investigated, in the first instance by Meissner and after- 292 LECTURE XIL wards by Billroth. The submucous layer of the intes- tines is therefore, as Willis long ago declared it to be, a Fig. 87. 740 VPI VOWAN Ho Gap? Pea os 2 80 B OSS 995g Ip of of ys ogee § wo = JF_ 0 WS ys H | a 8 OPSSQ RY e Fah AN Si g Qo & Wefed ws Yo? Q nervous tunic. On following up the afferent nerves, they are seen, after having divided, at last to break up into real networks ; these in new-born infants present at cer- tain points very large nodules, from which the nerve- fibres spread out into interlacements, so that a certain resemblance is thereby produced to a network of capil- laries. To what extent such arrangements prevail in the body generally has not yet been determined ; for these facts also are almost entirely new, and have only recently attracted the attention of observers, but probably the Fig. 87. Nervous plexus from the submucous tissue of the intestinal canal of a child, from a preparation of Herr Billroth’s. x, n,n. Nerves which unite to form a network, and exhibit at their points of junction glanglioniform swellings abounding in nuclei. 0, 2. Vessels, and in the intervals nuclei belonging to the connective tissue. Magnified 180 diameters. NERVE-PLEXUSES—INTESTINES, 293 number of these nervous membranes will eventually be augmented. In order, however, to avoid any misunder- standing, I must at once add that these plexiform expan- sions are by no means simple, but that the large nodules I have mentioned have the appearance of ganglions, so that we have here in some sort new nervous centres pre senting themselves, and affording the possibility of a reinforcement of, or obstruction to, the original impulses. For the functions of the part this arrangement is mani- festly of great importance, for we should not well be able to explain the peristaltic movements of the intestinal canal, if some contrivance did not exist by which stimuli, that in the first instance were conveyed only to one spot in the canal, could be transferred from network to net- work and from part to part. The modes of distribution of nerves, with which we were till recently acquainted, were not sufficient to afford anything approaching an ex- planation of the nature of peristaltic action, whilst these investigations of Meissner’s have at once furnished us with a most suitable groundwork for an interpretation of it. So much concerning the general forms which are, as far as we know at present, assumed by the peripheral terminations of the nerves. On the whole, these results correspond but little with the opinions which were formerly entertained, and with the hypotheses still advanced by the neuro-pathologists. The views of a neuro-pathologist of pure water amount, as is well known, to this, that a nervous centre is able, by means of nerve-fibres, to produce particular effects upon all, even the smallest, particles of the territory un- der its sway. Ifa mass of cancer or pus is to spring up in any little spot in the body, or merely a simple dis~ turbance of nutrition to ensue, the neuro-pathologist re- quires a special arrangement, by means of which the nervous centre is enabled to have its influence conveyed 294 LECTURE XII. into even the most minute districts of the periphery, and some route along which the messengers can travel who have been appointed to bear the order to the remutest points of the organism. Actual experience teaches us nothing of the kind. At those very spots where we know such an extremely complicated arrangement of the terminal apparatuses to exist, as I have described to you in the organs of sense, the nerves have no connection with the nutrition of the parts, and especially no demon- strable influence upon the elementary structures. In nearly all other places, either whole surfaces, or parts of organs are supplied with nerves in a uniform manner, or from these surfaces and parts of organs collective impres- sions are conveyed to the centres. In many parts con- cerning which we can certainly demonstrate that nervous influence is exercised upon them, as for example in mid- dle-sized and small vessels, we do not yet at all know to what extent their individual constituents receive special nerve-fibres. So bad are the anatomical foundations of the neuro-pathological doctrines. There still remains for us, gentlemen, now that we have discussed the terminal arrangements of the periphe- ral nerves, to consider the important series of nervous centres, or in a more restricted sense of the term, gangli- ome apparatuses. As I lately remarked to you, we find these predominating in those parts of the nervous centres in which there is grey matter. Still the mere grey hue of a part is not decisive proof of its ganglionic nature ; and in particular we must not suppose that the ganglion- cells are at all essentially concerned in the production of sthe grey colour, seeing that we find grey matter in many places where ganglion-cells do not exist. Thus, the most external layer of the cortex of the cerebrum does not contain any well-marked ganglion-cells, although it looks NERVOUS CENTRES—GANGLION-CELLS. 995 grey ; but we find there a translucent connective sub- stance, pervaded by a large number of delicate vessels, and assuming, in proportion as these are more or less full, at one time more a reddish grey, at another more a whitish grey hue. On the other hand it frequently hap- pens that, where there are ganglion-cells, the substance really does not look grey, but has a positive colour vary- ing between brownish yellow and blackish brown. Thus we find spots in the brain, which have long been known by the names of substantia nigra, fusca, etc., in which the black or brown colour, which we perceive with the naked eye, is dependent upon the ganglion-cells, which form really coloured points. This coloration appears only in the course of years. The older an individual becomes, the more conspicuously do the colours show themselves ; still under certain cir- cumstances pathological processes also seem to accelerate their manifestation. Thus in the ganglia of the sympa- thetic it is a striking phenomenon, that certain morbid processes, for example, typhoid fever, appear to exercise a powerful influence in producing an early deposit of pig- ment. Since the pigment however constitutes a rela- tively foreign mass in the internal economy of the gan- glion-cells, and is not, as far as we know, subservient to their proper functions, but has all the characters of an inert accidental deposit, it may really be quite possible that these conditions should be regarded as a kind of premature senescence in the ganglia. In these cases we discern in the ganglion-cells (Fig. 88, a) in addition to the very distinct, large nucleus with its large, bright nucleo- lus, the contents properly so-called, which consist of a finely granular substance, and at a certain spot enclose the pigment which is generally deposited excentrically, but sometimes around the nucleus. Under certain cir- cuxnstances this deposit increases to such an extent that 296 LECTURE XII. a great part of the cell is filled up with it. The more abundant it is, the darker does the whole spot appear to the naked eye. Formerly it was imagined that the majority of ganglion- cells were merely round bodies, but the conviction has been gradually gaining strength, that this form is an artificial one, and that the real state of the case is rather, that processes strike out from the cell in various directions, and ultimately become continuous with nerves or other ganglion-cells. These processes are in the first instance pale, and even where their transition into ordinary, darkly-contoured nerve-fibres can be traced, they are observed (but generally not until a cer- tain distance from the ganglion-cell) to become thicker and gradually to provide themselves with a medullary sheath. This circumstance which was formerly unknown explains how it was, that during so long a period so much obscurity prevailed with regard to these conditions. In the first part of their course, therefore, the processes of the glanglion-cells, especially in the brain and spinal marrow, are not nerves in the ordinary meaning of the word, but pale fibres which frequently bear scarcely any resemblance to the non-medullated fibres I have already described to you, and have rather the appearance of pale axis-cylinders (Fig. 88, a, 0). It was long believed that essential differences existed between the ganglion-cells according as they belonged to one or other of the three principal divisions of the Fie. 88. Fig. 88. Elements from the Gasserian ganglion. u. Ganglion-cell with nucleated sheath, which is prolonged around the efferent nerve-process; in the interior, the large, clear nucleus with its nucleolus, and round about it an accumulation of pig- ment. 8. Isolated ganglion-cell with a pale process proceeding up to it. c. Deli- cate nerve-fibre with pale axis-cylinder. 300 diameters. GANGLION-CELLS IN THE SPINAL CORD. 297 nervous system, and therefore especially between the cells of the sympathetic and those of the brain and spinal marrow. But in this point also the contrary has proved to be the case, especially since Jacubowitsch has brought to our knowledge the new fact, of the correctness of which I have fully convinced myself, namely, that struc- tures which are perfectly analogous to the ordinary gan- glion-cells of the sympathetic, also occur in the middle of the spinal marrow and several parts which are consi- dered to belong to the brain. It may therefore be said, that cells belonging to the sympathetic nerve, concerning which it has already long been known that a great part of its fibres have their origin in the spinal marrow, are really also met with in the spinal marrow, and that in this respect also the cord does not form a simple and neces- sary contrast to the main trunk of the sympathetic. If we examine the spinal marrow, which affords the clearest representation of the plan of a true nervous cen- tre in the narrowest meaning of the word, a little more closely, we everywhere find in its grey substance (the horns), and indeed in nearly every transverse section, different kinds of ganglion-cells. Jacubowitsch has, and I believe him to be in the main correct, distinguished three different forms, of which he calls the one motor, the second sensitive, and the third sympathetic. These lie generally in separate groups. T shall revert to this subject when I come to speak more at length concerning the spinal marrow; here I only wish to speak about the different forms of ganglion- cells. The so-called unipolar forms, are, in proportion as the examinations are conducted with more care, con- tinually becoming more and more rare. In the great nervous centres most of the cells possess at least two pro- cesses, and very many are multipolar or, more accurately, 298 LECTURE XII. Fie. 89. MOTOR, SENSITIVE AND SYMPATHETIC CELLS. 999 many-branched (polyclonous).* A multipolar cell is a body with a large nucleus, granular ‘contents and, if it be particularly large, a spot of pigment, and is provided with processes running in different directions. These processes often divide into twigs and thus commences the condition of which I have already spoken (p. 290), that whole masses of filaments or fibres proceed from one point—a condition which indicates, that, in the first in- stance indeed according to circumstances, one path or another can be made use of, but that, when once a path has been chosen leading in the direction of the periphery, the impulse must be propagated in a relatively equable manner throughout the whole series of ramifications. These multipolar forms (Fig. 89, A) are mostly compara- tively large, and lie accumulated in those parts which are subservient to the motor functions! and they there- fore may be briefly designated motor cells. Those forms which correspond to the sensitive spots (Fig. 89, B) are usually smaller and do not present such an extraordinary luxuriance of ramification as the larger ones. A large portion of them possess only three, or perhaps, four branches. Those which Jacubowitsch has called sympathetic are, on the other hand again, larger, but have still fewer branches and are distinguished by a greater roundness of shape. These are differences which are certainly not so decided, as to enable us already at once to determine in every single case from the appear- ance of a ganglion-cell to which category it belongs ; but still, if we consider the individual groups, they are so Fig. 89. Ganglion-cells from the great nervous centres; A, B, C from the spinal cord, from preparations belonging to Herr Gerlach, D from the cortex of the cere- brum. A. Large, many-rayed cell (multipolar, polyclonous) from the anterior horns (motor cell). B. Smaller cells with three large processes, from the posterior horns (sensitive cells). @. Two-rayed (bipolar, diclonous), more rounded cell, from the neighbourhood of the posterior commissure (sympathetic cell). 800 dia weters. * KAov, wre, a shoot, twig.—TR 300 LECTURE XII. striking, as to incite the observer to reflection upon the different qualities of these groups. In the course of time probably further distinctions, perhaps even in the internal economy of these cells, will be detected, but at present nothing more can be stated concerning them. This is a very great and lamentable void in our knowledge, and a void which we now particularly feel, because this is just the place where we should have to discuss the pacific action of these different elements. But it must not be overlooked that these conditions are among the most difficult which are ever submitted to anatomical investigation, and that one’s endeavors to produce specimens of a character to convince one’s own eyes alone, nearly always fail, because it is scarcely possible to succeed in effecting a real isola- tion of the cells with all their processes and connections, and because, on account of the extraordinary fragility of these bodies, one is nearly always compelled to trace them out in hardened sections. When sections are made of structures which to a great extent are composed of fibres and in which these run in a longitudinal, a transverse, or an oblique direction, so that an interlacement is always presented to the view, it depends of course entirely upon a happy chance whether in a section the course of a sin- gle fibre can be followed up over a large space with a certain degree of distinctness. This difficulty can certainly be lessened by making the sections in all possible direc- tions and thus increasing the probability of at last stum- bling upon the direction followed by the divisions of a branch, but even then the obstacles still remain so great that one can hardly expect, ever to be able to take in at one view the whole of the ramifications and connections of a cell belonging to the great nervous centres, that is provided with at all a large number of branches. In this respect also the electrical organ of fishes has PROCESSES OF THE GANGLION-CELLS, 301 become a particularly interesting subject for investiga- tion, inasmuch as the one fibre which supplies the organ has been traced back by Bilharz to a single central gan- ghon-cell, which is so large that it can be dissected out with the naked eye. This ganglion-cell has also delicate offsets in other directions, but it has not hitherto been possible to determine their ultimate relations any more than we are able to obtain a definite notion of the minute anatomy of the human brain, and especially to discover, to what extent connections take place there between the different cells. By the investigations which have been instituted into the structure of the spinal cord, it has been shown to be extremely probable, that all the processes of the individual ganglion-cells do not become continn- ous with nerve-fibres, but that a part of them run to other ganglion-cells and thus establish a communication between the cells. Moreover at certain points, espe- cially in several parts of the surface of the drain, still finer processes are found, which proceed from ganglion- cells and are connected with peculiar, quite characteris- tic apparatuses (bacillar layer of the cerebellum and cere- brum), which offer the greatest resemblance to those in the retina, those extremely delicate, vibratory arrange- ments of the radiating fibres. The processes of the ganglion cells might therefore, I think, be divided into three categories ; genuine nerve- processes, ganglion-processes, and those of which the im- port is entirely unknown and which, it would seem, are connected with peculiar and altogether specific appara- tuses, concerning which it is for the present uncertain, whether they are to be regarded as the terminations of the nerves, or only as structures placed in apposition to them. LECTUBEH ATT. APRIL 3, 1858. SPINAL CORD AND BRAIN. The spinal cord—White and grey matter—Central canal—Groups of ganglion-celle -—White columns and commissures, The medulla oblongata and the brain—Its granular and bacillar layer. The spinal cord of the petromyzon and its non-medullated fibres. The intermediate substance (interstitial tissue) —Ependyma ventriculoram—Neuro- glia—Corpora amylacea, Tue last time, gentlemen, I laid before you the results of the most recent observations concerning the nature and distribution of the ganglion-cells in the great nervous centres ; allow me now to dwell a moment upon that organ which serves as a type in the development of the vertebratee, and is at the same time the one whose struc- ture we can best take in at one view, namely, the spinal cord. The spinal cord presents, as is well known, and can with ease be seen by the naked eye in any transverse section, in different parts of its course, a different amount of white matter, though nearly everywhere the white matter predominates over the grey. This appears in transverse sections in the form of the well-known horns, which are distinctly marked off from the pure white of the rest of the mass by their sometimes pale grey, some- 802 SPINAL CORD—GREY MATTER—CENTRAL CANAL. 8038 times reddish grey colour. Wherever then the substance appears white to the naked eye, it is essentially composed of real, medullated nerve-fibres, in which only here and there a few ganglion-cells are imbedded ; and indeed a large proportion of these fibres are of considerable breadth, so that the quantity of medullary matter is at certain points extremely large. The grey matter of the horns is the real seat of the ganglion-cells, but here too the grey colour is by no means to be entirely ascribed to the accumulation of ganglion-cells ; on the contrary, they never, as you will afterwards see, form more than a small portion of this matter, and the grey hue is chiefly due to there generally being in these parts no separation of that opaque, strongly refractive substance (myeline, medullary matter) which fills the white nerves. It is in the centre of the grey substance that, as Still- ing, especially, has shown, the central canal (canalis spi- nalis) actually exists, which had previously been so com- monly supposed to be present, and had also frequently been described as of constant occurrence, but-of which nevertheless no one had ever previously been able to furnish a regular demonstration. In the case of the old observers, as for example Portal, their investigations were in every instance confined to a few pathological speci- mens, from which they derived all the information they possessed upon the subject, and from which they inferred in a somewhat arbitrary manner that the presence of a canal was the rule. This sentral canal is so minute that extremely success- ful sections are required in order that it may clearly be perceived by the naked eye. Usually nothing more than a rounded grey spot can be detected, which is distin- guished from the surrounding parts by its somewhat greater density. It is by microscopical examination 304 LECTURE XIII. alone that we can detect in this spot the transverse section of the canal in the shape of a minute hole (Fig. 90, ¢, ¢), which, like nearly all the free surfaces of the body, is in- vested with a layer of epithelium. . It has now taken up its stand as a really regular, constant and persistent ca- nal. It is continued throughout the whole extent of the spinal marrow from the filum terminale, where it cannot at all times be very distinctly demonstrated, up to the fourth ventricle, where the orifice by which it opens into the so-called sinus rhomboidalis* is situated im the gela- tinous substance of the calamus scriptorius. Here it may Fig. 90. The half of a transverse section from the cervical part of the spinal mar- row. fa. Anterior fissure; fp, posterior fissure. ec. Central canal with the central thread of ependyma. ca. Anterior commissure with nerve-fibres crossing one another; cp, posterior commissure. a. Anterior roots; rp, posterior ones. gm. Accumulation of motor cells in the anterior horns; gs, sensitive cells of the posterior horns ; gs’, sympathetic cells. The black, dotted mass represents a trans- verse section of the white substance of the cord (the nerve-fibres belonging to the anterior, lateral and posterior columns) and its lobular divisions, 12 diameters. * A name given to the floor of the fourth ventricle. WHITE MATTER OF THE SPINAL CORD. 805 in the first instance be traced as a direct continuation from the floor of the fourth ventricle into a minute fun- nel-shaped fissure or line. As for the ganglion-cells, they are generally found in the largest number in the anterior and lateral parts of the anterior horns. It is at this spot that we chiefly meet with the large many-rayed corpuscles which we consi- dered the last time—corpuscles, which have in great part been traced into efferent nerves of the anterior root, and therefore give origin to motor nerves. An analogous, but less distinctly grouped accumulation is found in the direction of the posterior horns, but there the cells are rather the small, many-rayed ones, such as those I lately described to you ; they are connected with the fibres which run into the posterior root, and are therefore probably subservient to the functions of sensa- tion. Besides, there is generally a third, sometimes more closely aggregated, at others more scattered, group of cells to be seen, which in their whole conformation re- mind us of the familiar cell-forms we meet with in the ganglia (Figs. 89, C; 90, gs’). Their special position in the spinal marrow is certainly not so clearly defined as that of the other parts; perhaps they should be regarded as the origin of the sympathetic roots which run from the spinal marrow to the main trunk of the sympathetic, but this is as yet by no means clearly made out. In the white substance of the anterior, lateral and pos- terior columns are found the medullated nerve-fibres, which in general follow an ascending or descending course, so that in transverse sections of the spinal mar- row we scarcely gain sight of anything else than trans- verse sections of the nerve-fibres. Under the microscope therefore we generally see dark points, every one of which corresponds to a nerve-fibre. The whole mass of fibres constituting the columns of the spinal cord is, from 20 306 LECTURE XIII. within outwardly, split up into a series of groups or seg- ments chiefly following a radiating arrangement, or in some sort into wedge-shapes lobules, in consequence of a sometimes smaller, sometimes larger quantity of connec- tive tissue with vessels pushing its way in between the separate divisions, which are of a fascicular nature like those of the peripheral nerves. This connective tissue is directly connected with the more abundant mass of it present in the grey matter. Now with regard to the nerve-fibres themselves, it is probable that a certain num- ber of them proceed throughout the whole length of the spinal marrow, but it ought certainly not to be assumed that they are all derived from the brain; a probably considerable portion no doubt have their origin in the ganglion-cells of the spinal marrow itself, and then bend round into the anterior or posterior columns. Besides, the conviction has more and more gained ground, that, botly between the two halves of the spinal marrow and between the separate groups of ganglion-cells, direct communications, commassures, exist—fibres passing across from one cell to another and from one side to the other, some so as to cross with those of the opposite side (ante- rior commissure), and some so as to run in a straight and parallel direction (posterior commissure). With the help of these anatomical observations a no- tion, though indeed as yet a very unsatisfactory one, can be formed of the routes along which the different pro- cesses are carried on within the nervous centres. Every special function possesses its special elementary, cellular organs; every mode of conduction finds paths distinctly traced out for it. In general too, well-defined peculiari- ties in the structure of the individual nervous centres correspond to the differences of function, and particularly the posterior horns become gradually more and more strongly developed as we ascend ; and in proportion as BACILLAR LAYER OF CEREBRUM AND CEREBELLUM. 807 this development proceeds, we see the medulla oblongata, the cerebellum and cerebrum, coming into view, whilst the motor parts withdraw more and more into the back- ground and ultimately almost entirely disappear. All nervous centres, the lowest as well as the most highly developed, are disposed upon an analogous plan ; the only thing which, at least as yet, can be regarded as an especially characteristic peculiarity of the encephalon, is the circumstance, to which I called your attention in the last lecture, namely, that in the cerebrum and cerebel- lum processes from ganglion-cells are connected with par- ticularly complicated apparatuses, which most resemble Fig. 91. Fig. 91. Diagrammatic representation of the disposition of the nerves in the cor- tex of the cerebellum, after Gerlach (‘ Mikroscopische Studien,’ plate L, fig. 3), A. White matter, 3B, OC, grey matter, B, granular layer, C, cellular layer. 308 LECTURE XIII. the granular and bacillar layers of the retina (Fig. 91) which I have brought before your notice. For here too we find branched, almost arborescent filaments, which bear upon them minute granules, often in several rows, and attach themselves to the ganglion-cells in a manner essentially differing from, and much more delicate than that observed in the case of the proper nerve-processes. This kind of ganglion-cells may very likely stand in some close connection with the psychical functions, but at pre- sent we have no accurate information upon the subject, and it will, I expect, still be a long time before anything positive can be made out about it, seeing that parts which are much more accessible to investigation, like the retina, present the very greatest difficulties to those who seek to discover the functions of the individual segments. The conformation which we have found to exist in the spinal marrow of man is essentially the same throughout the whole series of vertebrate animals, only that in man it is generally more complicated, and exhibits a greater abundance both of nerve-fibres and ganglionic matter. I Fie. 92. iia Sek as ae pa id Fig. 92. Transverse section through the spinal marrow of Petromyzon fiuviatilis. F. Anterior fissure, #'’, posterior fissure, c, central canal with epithelium, gm, large many-rayed ganglion-cells with processes in the direction of the anterior roots, gp, smaller, many-rayed cells with processes running to the posterior roots, gs, large, roundish cells in the neighbourhood of the posterior commissure (sympatbetic cells). 2, n. Transverse sections of the large, pale nerve-fibres (Millerian fibres), n’, gaps out of which the large nerves have gallen; n', gaps belonging to smaller Abres, Besides, the cut ends of numerous finer and coarser fibres, ey . SPINAL MARROW OF THE LAMPREY. 809 have brought you for comparison a section from the spi- nal marrow of one of the lowest of the vertebrate, namely the lamprey (petromyzon). In this animal the spinal marrow forms a very small, flat band which has some- what of a depression on the surface, and at first sight looks like a realligament. On making a transverse sec- tion of it, it is found to contain the same parts that we see in man, but all only in a rudimentary form. What in ourselves we call grey matter, is also found there on both sides in the shape of a flattened oblong lobe which contains a few scattered ganglion-cells, but only very few, so that perhaps only four or five are met with on each side of the transverse section. In the centre a cen- tral canal can likewise be detected, and that too lined with an epithelial layer similar to that which occurs in man. Below and in front of it generally lie a number of largish, round cavities, which correspond to unusually large, non-medullated nerve-fibres (Fig. 98, @), which were first seen by Joh. Miiller. Farther outwards lie a few other thick fibres, but greatly exceeding these in num- ber a large quantity of very fine fibres which give the transverse section a very diversified, regularly dotted ap- pearance. Among the ganglion-cells three different kinds can here also be distinguished. Towards the outside of the grey matter lie many-rayed cells, larger anteriorly, smaller and more simple posteriorly. More internally and posteriorly on the other hand we find larger, more rounded, seemingly diclonous (bipolar) cells, comparable to the sympathetic forms. These cells communicate across the middle-line ,by means of real fibres, and be- sides we find processes which run out from the spinal marrow forwards and backwards and form the anterior and posterior roots. This is the simplest plan we have, displaying these relations ; it is the general type of the anatomical structure of these parts. 310 LECTURE XIII. A circumstance worthy of particular observation here is that in the petromyzon, in the whole substance of the spinal marrow, no medullary matter exists in an isolated form, as is the case in man; we only find simple, pale fibres, which Stannius has without hesitation pronounced to be naked axis-cylinders. But without taking into account the fact that some of them have an enormous diameter, we find upon more accurate examination, as in the case of the gelatinous grey fibres in man, a membrane very clearly seen in transverse sections, especially after it has been coloured with carmine—and in the centre a finely granular matter, so that they seem rather to correspond to entire nerve-fibres. Hitherto, gentlemen, in considering the nervous sys- tem, I have only spoken of the really nervous parts of it. But if we would study the nervous system in its real rela- tions in the body, it is extremely important to have a knowledge of that substance also which lies between the proper nervous parts, holds them together and gives the whole its form in a greater or less degree. It is by no means very long ago since the existence of such interstitial masses of tissue was really only conceded in the case of peripheral nerves, and since the neurilemma was only traced back as far as the membranes of the spi- nal cord and brain, such an enveloping tissue being at most allowed to exist within the ganglia and in the sym- pathetic. In the nervous centres properly so called, and Fig. 93. Pale fibres from the spinal marrow of Petromyzon fluviatilis, 4. Broad, narrow, and extremely fine fibres. B. Transverse sections of broad fibres with a dis- tinct membrane and granular centre. 300 diameters, LINING MEMBRANE OF THE CEREBRAL VENTRICLES. 811 especially in the brain, this interstitial matter of ours was regarded as essentially nervous, for a substance of the kind appeared a natural desideratum, as long as a direct transferrence of impulses from fibre to fibre was admitted to take place, as long therefore as the necessity for a real continuity of conduction within the nerves them- selves was not recognized. Thus in the brain a finely granular substance was spoken of as existing, which in- sinuated itself between the fibres, and though it certainly did not establish a complete connection between them, inasmuch as it occasioned a certain difficulty in the trans- ferrence of impulses, yet nevertheless seemed to render a certain amount of conduction possible, so that when the impulse reached a certain degree of intensity, a direct transferrence from fibre to fibre could take place. This substance is however unquestionably not of a ner- vous nature, and if inquiry be made as to the relation which exists between it and the familiar groups of physi- ological tissues, it is impossible to doubt but that the substance in question is a kind of connective tissue ; and therefore an equivalent of that tissue with which we be- came acquainted in the shape of perineurium (p. 265). But the appearance of this substance is certainly very dif- ferent from that of what we call perineurium or neurilem- ma. These are comparatively firm, and often indeed hard and tough tissues, whilst the substance in question is ex- tremely soft and fragile, so that it is only with very great difficulty that we can succeed in making out its structure. I first had my attention directed to its peculiarities in investigations which I many years ago (1846) instituted into the nature of the so-called ining membrane of the cerebral ventricles (Ependyma). At that time the view was generally held, which had been put forward first by Purkinje and Valentin, and afterwards especially by Henle, that a real lining membrane did not exist in the 312 LECTURE XII. ventricles of the brain, but only an epithelial covering, ihe epithelial cells directly resting upon the surface of the horizontally disposed nerve-fibres. This epithelial layer was what Purkinje called ependyma ventriculo- rum.* This assumption, it is true, was never shared in by pathologists. Pathological observation held on its course pretty unconcernedly by the side of these histolo- gical assertions. However, it appeared desirable that some understanding should be come to on the subject, since in a merely epithelial ependyma an inflammation would scarcely take place, like that which is wont to be attributed to serous membranes. The result of my in- vestigations was, that there certainly does exist a layer beneath the epithelium of the ventricles, which in many parts has quite the character of connective tissue, but in other places possesses great softness, so that it is ex- tremely difficult to give a description of its appearance. Every, even the slightest, traction of the part alters its appearance, and a substance now granular, now striated, now reticulated, now of any other form, is seen. At first I thought I had succeeded in showing that a tissue analogous to connective tissue did actually exist in this part, and that the presence of a membrane could be demonstrated. But, the more I occupied myself with the examination of it, the more did I become convinced that a real boundary between this membrane and the deeper layers of tissue did not exist, and that a mem- brane could only be spoken of improperly, inasmuch as the notion of a membrane involves the supposition that it is more or less different from the parts beneath it, and constitutes a separable object. Now in the present * This term kas had its signification extended by the Author, who takes it to include the whole of the layer (connective tissue as well as epithelium), which resta upon the nerve-fibres and is interposed between them and the cavity of the ventri- cles.—From a MS. Note by the Author. EPENDYMA OF THE VENTRICLES OF THE BRAIN. 313 instance a separation of a rough kind may certainly not unfrequently be effected, but a more delicate kind of separation is altogether impossible. When the surface of any section of the ventricular wall is examined with a tolerably high power, the first thing noticed on the sur- face is an epithelium, sometimes in a better, sometimes in a worse state of preservation (Fig. 94, EZ). In the most favourable cases we find cylindrical epithelium with cilia, extending throughout the whole extent of the cavity of the spinal marrow (central canal) and of that of the brain (ventricles). Beneath this layer follows a sometimes more, sometimes less pure layer of a structure resembling connective tissue, which at first sight cer- tainly appears to be separated by a sharp outline from Fie. 94, Fig. 94. Ependyma ventriculorum and neuro-glia from the floor of the fourth cerebral ventricle. 2, Epithelium, W, nerve-fibres. Between them the free portion of the neuro-glia with numerous connective-tissue-corpuscles and nuclei, at v a ves- sel. In addition, numerous corpora amylacea, which are moreover represented separately at ca. 300 diameters, 314 LECTURE XIII. the deeper parts, for even with the naked eye, and espe- cially after the addition of acetic acid, an external grey and translucent layer is very distinctly seen, whilst the deeper layer looks white. This white appearance is due to the presence of medullated nerve-fibres which first occur singly, then continually become more numerous and closely aggregated, and as a rule run parallel to the surface. Thus it may certainly appear as if a particular membrane existed here, which could be separated from the uppermost nerve-fibres. But now, if we compare the substance which advances to the surface with that which lies between the nerve-fibres, no essential diffe- rence presents itself; on the contrary, it turns out that the superficial layer is nothing more than an extension upwards, beyond the nervous elements, of a portion of the interstitial tissue which is everywhere present be- tween them, but in this layer alone is seen in all its purity. The connection therefore is a continuous one. You see from this description that it was a very idle dispute, when it was discussed for years, whether the membrane which clothed the ventricles was a continua- tion of the arachnoid or pia mater, or was a special mem- brane. There is, strictly speaking, no membrane at all present, but it is the surface of the brain itself which directly meets the eye. In the case of articular cartilage also we must call it idle to dispute what kind of mem- brane invests the cartilage, since the cartilage itself ad- vances right up to the free surface of the joint. Neither is there any prolongation from the arachnoid or the pia mater to the surface of the ventricle ; the last processes which these membranes send inwardly are the choroid plexuses and the tela chorioides [velum interpositum]. Beyond these there is no serous covering found investing the internal surface of the ventricles of the brain. For this reason the conditions of the cerebral cavities cannot. NEURO-GLIA -ITS CELLULAR ELEMENTS. 818 be exactly compared with those of ordinary serous sacs, In the tela chorioides or the plexuses, a series of pheno- mena may certainly manifest themselves, which are pa- rallel to the diseases of other serous parts, but this can never take place in the same manner on the ventricular surface of the brain. This peculiarity of the membrane, namely, that it be- comes continuous with the interstitial matter, the real cement, which binds the nervous elements together, and that in all its properties it constitutes a tissue different from the other forms of connective tissue, has induced me to give it a new name, that of newro-gha™* (nerve- cement). The view that the substance in question be- longs to the class of connective tissues has recently been admitted on nearly all sides, but with regard to the ex- tent to which any isolated structures that occur in it are to be considered as belonging to this substance, opinions are still divided. Even when I instituted my first spe- cial investigations into the structure of the ependyma of the brain and spinal cord, it turned out that certain stel- late cells which are met with in the middle of the spinal marrow (in the wall of the central canal, the existence of which was afterwards more accurately demonstrated, namely, in what I called the central thread of ependyma), and which up to that time had been regarded as nerve- cells, unquestionably belonged to the neuro-glia. After- wards, and especially by the Dorpat school with Bidder at its head, a series of investigations were published, in which a great number of cells in the spinal marrow were set down as belonging to this connective tissue. Bidder himself was ultimately led to regard all the cells which are found in the posterior half of the spinal marrow, and therefore those sympathetic and sensitive cells also which you have just seen, as connective-tissue-corpuscles. On * ydia, glue—Tr. 316 LECTURE XIII. the other hand, Jacubowitsch has utterly denied the oc- currence of the cellular elements of connective tissue in any part of the brain or spinal cord, and has asserted that the interstitial tissue, which by him too, indeed, is regarded as connective tissue, is an altogether amorphous, finely granular or reticulated matter, which nowhere contains a single corpuscular element. Between these extremes, I think, we are perfectly justified by experi- ence in steering a middle course. There can, according to my firm conviction, be no doubt but that the larger cells which pervade the posterior horns of the spinal mar- row are nerve-cells ; but, on the other hand, it must be maintained with equal positiveness, that, where neuro- glia is met with, it also contains a certain number of cel- lular elements. Immediately beneath the surface of the cerebral ventricles we commonly meet with spindle- shaped cells lying parallel to it, just like those which are found in other kinds of connective tissue ; these become larger under certain circumstances, and, in oblique sec- tions, often display themselves in the form of stellate cells (Fig. 94). A substance altogether similar in structure to that, with which we have already become fa- miliar in connective tissue—especially & b ie as far as its cells are concerned—is also 0 Gg ® found between the nerve-fibres of the cD 6® cerebrum ; only the cells are so soft and fragile, that generally nothing but nu- clei can be perceived, scattered at certain intervals throughout the mass. On making a careful search, how- ever, even in fresh (not artificially hardened) specimens, soft cellular bodies of a roundish or lenticular form can Fig. 95. Elements of the neuro-glia from the white substance of the cerebral hemispheres of a human subject. a. Free nuclei with nucleoli, 5, nuclei with the granular remnants of the cellular parenchyma broken up in making the preparation, c, perfect cells. 800 diameters. Fie. 95. PERINEURIUM AND NEURO-GLIA. 317 be detected, which possess finely granular contents and large granulated nuclei with nucleoli, and lie, certainly in no very great number, between the nervous elements. At certain spots it has indeed been hitherto impossible to draw a well-defined boundary-line between the two tissues, and especially so at the surface of the cerebel- lum and cerebrum, between the granules which I have already (p. 307) described to you as connected with large ganglion-cells, and the nuclei of the connective tissue. Wherever the parts are seen severed from their connec- tions, it is not easy to make the distinction, and a posi- tive decision is only possible as long as the parts are viewed in their natural position. Now it is certainly of considerable importance to know that in all nervous parts, in addition to the real nervous elements, a second tissue exists, which is allied to the large group of formations, which pervade the whole body, and with which we have in the previous lectures become acquainted under the name of connective tissues. In considering the pathological or physiological conditions of the brain or spinal marrow, the first point is always to determine how far the tissue which is affected, attacked or irritated, is nervous in its nature, or merely an inter- stitial substance. We thus obtain at the very outset the important criterion for the interpretation of morbid pro- cesses, that the affections of the brain and spinal marrow may sometimes be rather interstitial, at others rather parenchymatous, and experience shows us that this very interstitial tissue of the brain and spinal marrow is one of the most frequent seats of morbid change, as for ex- ample, of fatty degeneration. Within the neuro-glia run the vessels, which are therefore nearly everywhere separated from the nervous substance by a slender intervening layer, and are not in immediate contact with it. The neuro-glia extends in 318 LECTURE XIII. the peculiarly soft form, which it presents in the great nervous centres and particularly in the brain, only to those parts which must be regarded as direct prolonga- tions of the cerebral substance, namely to the higher nerves of sense. The olfactory and auditory nerves also contain interstitial substance of the same character, whilst in all the rest, and even in the optic nerve itself, an in- creasing mass of a tougher tissue displays itself, which assumes quite the character of perineurium. Perineurium and neuro-glia are therefore equivalent parts, the only difference being that the one is of a soft, medullary, fragile nature, whilst the other is akin to the well-known fibrous tissues. The neurilemma stands in the same relation to the perineurium that the membranes of the brain and spinal ‘cord do to the neuro-glia. Wherever neuro-glia exists, a very singular peculiarity presents itself which it has as yet been impossible to explain either chemically or physically, namely, that in every such case those peculiar bodies may be met with, which even in their structure remind one of granules of vegetable starch, whilst in their chemical reactions they altogether correspond to them—the much discussed cor- pora amylacea (Fig. 94, ca). They are found to the greatest extent and in the greatest numbers in the epen- dyma of the ventricles and spinal canal, and are the more abundant the greater the thickness of the ependyma. In many places but very few of them are found, whilst in others again: their numbers increase so greatly, that the whole thickness of the ependyma is filled with them to such a degree, that it looks as if a pavement were be- fore one. They display themselves, however, strangely enough, in pathological conditions also, frequently in great numbers, when, in consequence of some disturb- ing cause, the quantity of neuro-glia becomes increased in proportion to that of nervous substance, as for CORPORA AMYLACEA. 3819 example after atrophic processes. In tabes dorsalis, as one used to say, or the atrophy of single columns of the cord, as we now usually interpret the old expression, we find, in proportion as the atrophy progresses, and the nerves in certain directions perish—cuneiform segments, in which the substance up to that time white becomes from without inwards grey and translucent—there being apparently a production of grey matter. This degene- ration is most frequent in the posterior columns, gene- rally in the immediate vicinity of the posterior fissure, and here it may go on, and generally does go on, in such a manner that the wedge penetrates deeper and deeper and at the same time increases in width. In these parts then the whole substance of the medullated fibres gradu- ally disappears, and distinct nerves are no longer disco- verable—the whole spot generally consisting of neuro-glia with an enormous accumulation of corpora amylacea. Nowhere in the body has there as yet been found any- thing completely analogous to structures of this sort, ex- cepting, as I have said, in those parts which appear to be direct protrusions of the cerebral substance, namely in the higher organs of sense, in the case of which origi- nally a certain quantity of central nervous matter entered into the sensorial capsules (Sinneskapseln) of the embryo. In the cochlea too, and the retina, bodies occur, which Fig. 96. Section of the spinal marrow in partial (lobular), grey or gelatinous atro- phy (degeneration). f. Posterior longitudinal fissure, s, s posterior, m, m anterior nerve-roots, communicating with the grey substance of the horns. In J a slighter, in Ba more marked degree of atrophy, which is shown in the posterior columns around the central fissure 7, and in the lateral columns at J. Natural size. 320 LECTURE XIII. are allied to the corpora amylacea, although the chemi« cal tests have as yet only proved successful in the case of those found in the internal ear. When these bodies are isolated, they exhibit in every respect such a complete analogy to vegetable starch that, long before I succeeded in discovering the analogy in chemical reaction, Purkinje had already introduced the term corpora amylacea on account of the morphological resemblance. You are no doubt aware, that the chemi- cal correspondence has in many quarters been doubted ; the late Heinrich Meckel especially had great doubts upon the subject, and supposed them to have a greater affinity to cholesterine. In more recent times, however, the matter has been investigated even by professed botanists, and every one who has bestowed close atten- tion upon it, has as yet acquired the same conviction which I published as my own. Niigeli pronounces these bodies to be really and truly starch. Morphologically, they present themselves either as per- fectly circular bodies with regular, concentric layers, or their centre is a little on one side; or we find twin bodies ; or again the bodies are more homogeneous, pale, with a dim lustre, like fatty substances. When they are cautiously treated with a dilute solution of iodine, they assume a pale bluish, or greyish blue colour, though a great deal certainly depends upon the proper degree of concentration of the test. If afterwards we very cau- tiously add sulphuric acid, we obtain, when the proper effect is produced, a beautiful blue, which is best shown by allowing the reagent to act very slowly. When sul- phuric acid acts violently upon them, a violet tint, which speedily becomes brownish red or blackish, is obtained, presenting a most decided contrast to the neighbouring parts, which become yellow or at most yellowish brown. GEO TT be xT, APRIL 7, 1858. ACTIVITY AND IRRITABILITY OF CELLULAR ELEMENTS, DIFFERENT FORMS OF IRRITATION. Life of individual parts—The unity of the neurists—Consciousness—Activity of individual parts—Excitability (irritability) as a general criterion of life—Mean. ing of irritation—Partial death—Necrosis. Function, nutrition, and formation, as general forms of vital activity—Difference of irritability according to the different forms of activity. Functional irritability—-Nerves, muscles, ciliated epithelium, glands—Fatigue and functional restitution—Stimuli—Their specific relations—Muscular irritability. Nutritive irritability—Maintenance and destruction of elements--Inflammation— Cloudy swelling—Kidney (morbus Brightii) and cartilage—Neuro-pathological doctrines—Skin, cornea—The humoro-pathological doctrines—Parenchymatous exudation, and parenchymatous inflammation. Formative irritation—Multiplication of nucleoli and nuclei by division—Multi- nuclear cells; medullary cells and myeloid tumours—-Comparison between for- mative muscular irritation and muscular growth—Multiplication (new forma- mation) of cells by division-—-The humoro- and neuro-pathological doctrines. Inflammatory irritation as « compound phenomenon--Neuro-paralytical inflamma- tion (Vagus, Trigeminus). I HAVE given you, gentlemen, a somewhat lengthy sketch of the histological arrangements of the body, in order to make the inference plain to you, which in my opinion must be the starting point of all future conside- yations that are instituted concerning life and vital ac- tivity—that, namely, in all parts of the body a splitting’ up into a number of small centres takes place, and that nowhere, as far as our experience extends, does a single 21 821 3822 LECTURE XIV. central point susceptible of anatomical demonstration exist, from which the operations of the body are carried on in a perceptible manner. And even if we appeal to the experience which every one daily stores up around him, we shall find that this is the only view which con- cedes life to the individual parts of an organism, or allows it to the plant—the only view which enables us to institute a comparison both between the collective life of the developed animal and the individual life of its smallest parts; and also between the life of a plant as a whole and the life of the individual pgrts of a plant. The opposite view which at this very moment is mani- festing itself with a certain degree of energy—that namely, which beholds in the nervous system the real central point of life—is met by this extremely great difficulty, that, in the very same apparatus, in which it places its unity, it again finds the same splitting up inte an infinite number of separate centres, which is pre- sented by the rest of the body; and that in no part of the whole nervous system it can show the real central point, from which, as from a seat of government, man- dates are issued to all quarters. It may seem very convenient to say that the nervous system constitutes the real unity of the body, inasmuch as there is certainly no other system which enjoys such a complete dissemination throughout the most various peripheral and internal organs. But even this wide dis- semination and the numerous connections which exist between the individual parts of the nervous system, are by no means calculated to show it to be the centre of all organic actions. We have found in the nervous system definite little cellular elements which serve as centres of motion, but we do not find any single ganglion-cell in which alone all movement in the end originates. The THE UNITY OF THE NEURISTS—CONSCIOUSNESS. 823 most various individual motory apparatuses are connected with the most various individual motory ganglion-cells, Sensations are certainly collected in definite ganglion- cells, still among them too we do not find any single cell which can in any way be designated the centre of all sensation, but we again meet with a great number of very minute centres. ° All the operations which have their source in the nervous system, and there certainly are a very great number of them, do not allow us to recognise a unity anywhere else than in our own consciousness ; an ana- tomical or physiological unity has at least as yet been nowhere demonstrable. If we really were to set down the nervous system with its numerous separate centres as the central point of all organic actions, even then the thing actually sought for, a real unity, would not have been obtained. If a clear idea is formed of the difficulties which stand in the way of such a unity, it can scarcely be doubted, but that we are continually led astray by the spiritual phenomena displayed in our own persons, in the interpretation of organic processes. Feeling ourselves to be something simple and indivisible, we always start with the presumption that everything else must be regulated by this indivisible principle. But if we trace the development of any given plant from its first germ up to the highest point in its evolu- tion, we meet with a series of processes altogether analogous, without our being able to entertain the suppo- sition for a moment, that such a unity exists in it, as we are led by our consciousness to suppose exists in us. Nobody has been able to detect a nervous system in plants ; in no case has it been discovered that the whole of the fully developed plant was governed from a single point. All the vegetable physiology of the present day is based upon the investigation of the activity of cells, and if a 324 LECTURE XIV. violent opposition is still made to the introduction of the same principle also into the animal economy, there is, I think, no other difficulty in the way but the one, that as- thetical and moral scruples cannot be overcome. It cannot of course here be our business either to refute these scruples or to point out how they might be reconciled with the views I advocate. I have only to show in how great a degree the pathological processes which especially interest us, in all cases conduct us back to the same cellular principle, and how much they are in every case opposed to that notion of a single con- trolling principle, which is sought to be established by the neuro-pathologists. This opinion of mine has after all really nothing’ new or uncommon in it. If for thou- sands of years the life of the individual parts of the body has been talked about, if the position is admitted, that in diseased conditions the death of individual parts, necrosis or gangrene in them may take place, whilst the whole still continues to exist—the inference is, that something of our way of thinking had long been ex- pressed in the views held by the world in general: only people had not formed very clear notions upon the subject. If we speak of the life of the individual parts of a body, we must also know in what way life manifests itself, and whereby it is essentially characterized. This characteristic we find in activity, an activity indeed, in which there is displayed by every single part, whilst it contributes its contingent, according to its peculiarities, to the general activity of the body—something identical with the life of the other parts ; for else we should be in no way justified in regarding life as something in every case similar, and derivable from some common origin. This vital activity is, as far at least as we are able to judge, nowhere, in no part whatever, carried on by means of any cause allotted to it from the very begin- IRRITABILITY. 325 ning, and entirely confined to it, but we everywhere see that a certain een is necessary for its avons “Tike aa Beaton ‘The irritability of a part, therefore, ‘appears to us the criterion, by which we can judge “whether it is alive or not. Whether, for example, a nerve be alive or dead, we cannot immediately deter- mine by an anatomical examination of it, conducted either microscopically or macroscopically. In the out- ward appearance, in the more obvious structural ar- rangements, which we are able to decipher by the aid of our auxiliaries, we rarely find sufficient to enable us to come to a decision upon a point such as this. Whether a muscle is alive or dead, we are but little able to judge, inasmuch as we find its structure still preserved in parts which perished years ago. I found in a foetus, which, in a case of extra-uterine pregnancy, had lain thirty years in the body of its mother, the structure of the muscles as intact as if it had just been born at its full time. Czermak examined parts of mummies, and found in them a number of tissues which were in a state of such perfect preservation, that the conclusion might very well have been come to, that the parts had been taken from a living body. Our notion of the death, decease, or necrosis of a part, is based upon nothing more or less than this, that whilst its form is preserved, and indeed in spite of it, we can no longer detect any irritability in it. This has been most clearly shown quite recently in the course of some investigations into the more hidden properties of nerves. Now that, by the investigations of Dubois-Reymond, activity has been shown to exist in nerves even when in a so-called state of repose, and that it has been discovered, that in a nerve, even when seemingly at rest, electrical pro- cesses are continually going on, and that it constantly 326 LECTURE XIV. produces an effect upon the magnetic needle—now we are able, by means of this physical experiment, with certainty to judge when a nerve is dead, for, as soon as death has stepped in, those qualities cease, which are in- separably connected with the life of the nerve. This peculiarity which we find in some parts exhibited in such a marked degree and so evidently demonstrable, becomes less and less apparent, the more lowly the or- ganization of the part, and our criteria are least to be depended upon in the case of the class of connective tissues ; for we are, indeed, really frequently much puz- zled to decide whether a part composed of one of them is still alive or has already perished. If now we proceed with our analysis of what is to be included in the notion of excitability, we at once dis- cover, that the different actions which can be provoked by the influence of any external agency, are essentially of three kinds; and I consider it of great importance that you should pay particular attention to this point, as it will greatly assist you in the classification of patholo- gical conditions, and because it is not wont to be set forth with particular distinctness. When, namely, a given action is called into play, we have to deal with a manifestation either of the function, the nutrition, or the formation of a part. It certainly cannot be denied that at certain points the boundaries between these different processes disappear, and that between the nutritive and formative processes and also between the functional and nutritive ones, there are tran- sitional stages ; still, when they are typically performed, there is a very marked difference between them; and the internal changes which the individual excited part undergoes, according as it only performs its functions, or is subjected to a special nutrition, or becomes the seat of special formative processes, exhibit considerable dif- FUNCTIONS OF CELLS—CELL-CONTENTS, 827 ferences. The result of an excitation, or if you will, an irritation, may, according to circumstances, be either a merely functional process; or the effect may be that a more or less increased nutrition of the part is induced without there necessarily being any excitation of its func- tions ; or a formative process may set in, giving rise to a greater or less number of new elements. These differ- ences manifest themselves with greater or less distinct- ness in proportion as the individual tissues of the body are more or less capable of responding to the one or other kind of excitation. When, namely, we speak of the functions of parts—in the case of a considerable num- ber of tissues the real functions shrink into a very small compass ; we are on the whole able to say but very little concerning the real functions, in the higher sense of the word, of nearly all the connective tissues, and of the great majority of epithelial cells. We are no doubt able to say what their use under particular circum- stances is, still they always rather appear to be rela- tively inert masses, which scarcely perform any real functions in the ordinary meaning of the word, but rather serve as supports to the body, or as coverings to the different surfaces, or, in other localities, according to circumstances, act as media of union, intervention, or separation. The case is different, on the other hand, with those parts, which, owing to the peculiar nature of their inter- nal arrangement, are liable to a more rapid change, such as the nerves, muscles, and muscular organs, glands and a few other structures, as, for example, among the epithelia, ciliated epithelium. In all these tissues, which are subservient to important functions, we find that these functions are chiefly due to very delicate changes of arrangement, or if you wish it expressed in more precise terms, to minute changes of place, in the minute 328 LECTURE XIV. particles of the internal matter, the cell-contents. In these cases therefore it is not so much the real cell in its pure form which decides the question, as the specific matters with which it is provided internally ; the chief agent is not so much the membrane or the nucleus of the cell, as the contents. It is these which, when exposed to cer- tain influences, become comparatively rapidly changed, without our being always able morphologically to de- tect any trace of a change in the arrangement of the contained particles. The utmost that we can observe in the shape of a palpable result is a real locomotion of small, visible particles, but we cannot push our analysis to such an extent, as to enable us to form any opinion as to the internal cause, in virtue of which this locomo- tion is effected by the ultimate particles which compose the cell-contents. When an excitation takes. place in a nerve, we now know that a change in its electrical state is connected with it, a change which, from all that is known to us concerning electrical excitation in other bodies, must of necessity be referred to a change in the position which the individual molecules assume to one another. If we conceive pn the axis-cylinder to be made up of elec- SELES trical molecules, we can easily imagine @@GBEGS that every two of these molecules take up an altered position with regard to one another at the moment the stimulus is applied. Of these processes we see nothing. The axis-cylinder looks just as usual. If we watch a muscle during its contrac- tion, we remark, it is true, that the intervals which sepa- rate the individual so-called discs (p. 82) become shorter ; and as we now know that the substance of the mus- Fig. 97. Fig. 97. Ideal diagram of the condition of the molecules of a nerve when it is at rest (in a peripolar state, 4), or in an electrotonic (dipolar) state, B. From Lud- wig, ‘ Physiolog.,’ I, p. 103. FUNCTIONAL IRRITABILITY. 829 cle consists of a series of minute fibrils, which in their turn contain little granules at certain intervals corres- ponding to these discs, we conclude therefrom with some degree of assurance that really local changes take place in the minutest elements, though they cannot be further referred to any visible or directly recognizable cause. We cannot perceive any definite chemical change, or any alteration in the state of nutrition of the parts ; we only see a displacement, a dislocation of the parti- cles, which, however, probably depends upon some slight chemical change in the molecules composing them. In the case of ciliated epithelium you see how the fine cilia, which are seated upon the surface of the cells, move inacertain direction, and in this direction exercise a locomotory effect upon the little particles which come near to them. If we isolate the individual cells, we see that every one of them has at its upper end a bor- der of a certain thickness, from which little hair- shaped prolongations run oft. These all move in such a way that a cilium which, whilst quiet, stands quite upright, bends forwards and then throws itself back- wards. But we are unable to perceive any changes within the individual cilia, by means of which the move- ment is effected. Just the same is the case with gland-cells, con- cerning which we cannot entertain the least doubt that they produce a definite locomotory effect. For since Ludwig has shown in his researches on the salivary glands, that the pressure of the outward current of saliva is greater than that of the inward stream of blood, the only conclusion that is left us is, that the gland-cells exercise a definite motor influence upon the fluid; and that the secretion is driven out with a definite force, which is not due to the pressure of tne blood, or any special muscular action, but to the specific energy of the 330 LECTURE XIV. cells as such. Still we are just as little able to discern in a gland cell, whilst performing its functions, that its constituent particles are engaged in any peculiar material process, as we were in the case of the nerves, or ciliated epithelium. These facts derive great support from the circumstance that we are able to perceive, that the functional activity of individual parts does experience a certain amount of impairment, if it is continued for too long a time. In all parts certain states of fatigue manifest themselves, states, during which the part is no longer able to origi- nate the same amount of movement, that up to that time could be perceived in it. But, in order that they may again become competent to perform their functions, these parts by no means always require a new supply of nutriment, a fresh absorption of nutritive material ; rest alone is sufficient to enable them to resume their activity in a short space of time. A nerve, which has been cut out of the body, and used for experiment, after a cer- tain lapse of time becomes incapable of discharging its functions ; but if it be allowed to repose under favour- able circumstances, which prevent it from drying up, it gradually regains its powers. This restitution of func- tonal power (functional restitution), which takes place without any proper nutritive action, and in all proba- bility depends upon the circumstance, that the mole- cules which had quitted their usual position gradually revert to it—we can produce in, different parts by means of certain stimuli. According to the views of the neuro-pathologists these stimuli would only act upon the nerves, and through the medium of the nerves upon the other parts; but with reference to this very point we have some facts which cannot well be explained in any other way than by the assumption, that an in- fluence is really exercised upon the parts themselves. FUNCTIONAL IRRITATION. 331 If we take a single ciliated cell, and, after entirely isolating it from the body, allow it to swim about, and wait until a state of complete repose has declared itself, we can again call forth the peculiar movements of its cilia by adding a small quantity of potash or soda to the fluid, a quantity not large enough to produce corro- sive effects upon the cell, but sufficient, upon penetra- tion into it, to induce a certain change in its contents. A peculiarly interesting fact, however, is that the num- ber of substances which will act, as stimuli, upon ciliated epithelium, is limited to these two. This explains how it happened that Purkinje and Valentin (who, it is well known, first made experiments, and those upon a very extensive scale, upon ciliary movement), although they experimented with a very large number of substances, at last, after they had tried all sorts of things—mechan- ical, chemical and electrical stimuli-—came to the con- clusion that there was no stimulus whatever, which could provoke the ciliary movement. I had the good fortune incidentally to stumble upon the peculiar fact, that potash and soda are such stimuli. Here we cer- tainly cannot call in any nervous influence to our aid, and such influence appears to be the less admissible for the reason that, in accordance with the well-known ex- periments, the ciliary movement is maintained in the dead body at atime when other parts have already be- gun to putrefy. The ciliated epithelium of the frontal sinuses and the trachea is found in human corpses in a state of perfect excitability thirty-six to forty-eight hours after death, when every trace of irritability has long vanished from the remainder of the body. Much the same is the case with all other excitable parts. We see nearly everywhere that certain excitants act more readily than others, and that many are totally incapable of producing any particular effect. Nearly 332 LECTURE XIV. everywhere do we find specific relations or affinities to exist. If we cast our eyes upon the glands, it is a well- known fact that there are specific substances, by which we are enabled to act upon one gland, and not upon another ; to rouse the specific energy of one gland, whilst all the rest remain unaffected. In the case of glands it is certainly much more difficult to exclude the influence of the nerves, than in that of ciliated epithe- lium, still certain experiments are recorded, in which, after the section of all the nerves, say of the liver (G. Harting), it was found possible, by means of the injection of irritating substances into the blood (these being such as experience had shown to bear some inti- mate relation to the organ), to provoke an increased secretion in the organ. The discussion of this subject has, as you no doubt are well aware, recently chiefly become centred in the question of the irritability of muscle, a question which has proved so difficult for the very reason that the pos- session of irritability was restricted by Haller with great exclusiveness to muscle. Haller with the greatest ob- stinacy combated the opinion that any other part was irritable ; and curiously enough he even contested the irritability of parts, which, as the minuter investigations of later observers have shown, contain muscular ele- ments, as for example, the middle coat of the vessels. Indeed, he made use of tolerably energetic expressions when repudiating the excitability of the vessels, which even then was maintained by others. I have already informed you that there are large tracts in the vascular system (for example, in the umbilical vessels of the foe- tus, where they are particularly well marked) in which enormous accumulations of muscular fibres are found, but not a trace of any nerves. Here irritability exists ina high degree ; we can produce contractions of the NUTRITIVE IRRITABILITY. 333 muscles mechanically, chemically and electrically. Just the samé is the case with many other, small vessels, which by no means exhibit nerve-fibres in all their parts. In them too we can at every single point where muscles exist, at once provoke contraction. The solution of this question has recently, as is well known, been particularly promoted by the fact that, by the employment of certain poisons, especially the woo- rara poison, observers have succeeded in paralyzing the nerves right down to their extreme terminations, or at least as far as these were accessible to the experiment ; and this in such a manner, that the objection cannot well be raised, that the excitability of the extreme ter- minations of the nerves contained in the muscle is pre- served. The paralysis produced by the woorara poison is completely confined to the nerves, whilst the muscles just as completely retain their irritability. Whilst the most violent electrical currents were made to act upon the nerve in vain, without the production of the least movement, the slightest mechanical, chemical or electri- cal stimuli are sufficient to throw the muscle experi- mented upon into a state of excitation. I have mentioned these facts to you, in order that I might not be thought to treat the different divisions of my subject too unequally. The question of function, however, interests us less here. Nevertheless, you will be able to gather from what I have communicated to you, that now-a-days it can no longer be said with any show of reason that the nerves alone are irritable parts, but that we are irresistibly led to consider functional irritabi- lity, at least, as a property belonging to whole series of organs. Far less known, gentlemen, is that clearly demonstra- ble series of processes in which nutritive irritability mani- fests itself—that power possessed by individual parts of 334 LECTURE XIV. taking up, when excited by definite stimuli, more or less matter and transforming it. This constitutes at the same time the first step in the most important processes which we have to follow into the domain of pathologico-anato- mical facts. A part, which nourishes itself, can in doing so either limit itself to a mere maintenance of its existence, or it may, as is especially seen in pathological cases, take up into itself a larger quantity of nutritive material than is wont to happen in the ordinary course of things. If we investigate these processes of absorption more closely, we always find that, as I have already had occasion to re- mark to you, the number of histological elements remains the same before and after the occurrence of the excita- tion ; and we thus distinguish simple hypertrophies from the hyperplastic conditions, to which, in their external effects, they often bear so great a resemblance (p. 94, Fig. 27, B). Itis, however, of extreme importance for the attainment of correct pathological notions, that we should know that a part, which in virtue of some inhe- rent power, takes up a large quantity of material, need not on that account necessarily fall into a permanent condition of enlargement, but that on the contrary, under these very circumstances there often arises subsequently in its internal economy a disturbance which imperils the persistence of the part and becomes the proximate cause of its destruction. There are, as we know from experi- ence, certain limits to the enlargement of every tissue, within which it is able to maintain a regular existence ; if these limits be exceeded, and especially, if suddenly, we always see that obstacles spring up impeding the fur- ther life of the part, and that when the process runs a particularly acute course, a weakening of the part sets in, proceeding to a complete destruction of it. Processes of this kind form a part of that domain which CLOUDY SWELLING. 335 in ordinary life is assigned to inflammation. A number of inflammatory processes on their first appearance really exhibit nothing more than an increased assumption of material into the interior of the cells, entirely resembling what we find in simple hypertrophy. If, for example, we consider the history of Bright’s disease in its ordinary course, we constantly find, that the very first thing which can be detected in a kidney affected with this disease, consists in this, that in the interior of the uriniferous tu- bules whilst still quite intact, the individual epithelial cells which are, as is well known, even in their normal state tolerably large, become still larger. These epithe- lial cells which fill up the tubules are not only large, but at the same time also present a very cloudy appearance, inasmuch as a larger quantity of material than usual has everywhere been taken up into the cells. The entire uriniferous tubule is thereby rendered broader, and appears even to the naked eye as a convoluted, whitish, opaque body. If we isolate the indi- vidual cells, which is somewhat difficult, as the cohesion of the particles compos- ing them has usually begun to suffer, we find in them a granular mass apparently containing nothing else than the granules which are normally present in the interior of the cells, but which accumulate in greater numbers the greater the energy with which the process is carried on, so that even the nucleus gradually grows indistinct. This is the condition of cloudy swelling (triibe Schwellung), as it is met with in many irritated parts, as an expression Fie. 98, Fig. 98. Convoluted urinary tubule from the cortex of the kidney in morbus Brightii. «. Tolerably normal epithelium, 6, state of cloudy swelling, c, com- mencing fatty metamorphosis and disintegration. At 6 and c increased breadth of the tubule. 300 diameters. 336 LECTURE XIV. of the irritation which attends many forms of what is called inflammation. From these processes backwards to the phenomena of simple hypertrophy we find no recog. nizable boundaries at all. We cannot at once say, when we meet with a part enlarged in this way, and contain- ing a greater amount of matter than usual, whether it will retain its life or perish ; and therefore it is extremely difficult in very many cases, when nothing at all is known concerning the process through which such a change has been produced, to distinguish simple hypertrophy from those forms of inflammatory processes which are essen- tially accompanied by an increased absorption of nutri- tive material. In these processes too it is scarcely possible to refuse the individual elements, when incited by a stimulus directly applied to them, the power of taking up an increased quantity of material ; at least it is opposed to all the results of experience, to assume that such an in- creased absorption must be due to a special innervation. If we select a part which, in accordance with all observa- tion, is entirely destitute of nerves, as for example, the surface of an articular cartilage, we can, as was shown many years ago by the beautiful experiments of Redfern, produce altogether similar effects by means of direct stimuli. In precisely the same way, there are not un- frequently observed, in chronic diseases of cartilage, no- dular elevations of the surface ; and upon examining such spots microscopically we find the same thing that I showed you in a former lecture in a costal cartilage (p. 48, Fig. 9), namely, that the cells which at other times are very delicate, small, lenticular bodies, increase in size, swell up into large, round corpuscles, and in pro- portion as they take up more matter, enlarge in all direc- tions, so that at last the whole spot forms a little protu- berance above the surface. Now in articular cartilage DIRECT IRRITATION OF TISSUES. 337 uo nerves at all are found; the terminal ramifications of those nearest to it are at best situated in the medulla of the bone immediately adjoining, and that, perhaps, is separated from the irritated spot of the surface by an in- tact, intervening layer of cartilaginous tissue one or two lines in thickness. Now it would indeed be contrary to all experience to conceive that a nerve could from the medulla of the bone exercise a special action upon the cells of the surface of the cartilage, which were the seat of irritation, without a simultaneous affection of the cells lying between the nerve and the irritated spot. If we draw a thread through a cartilage, so that merely a trau- matic irritation is produced, we see that all the cells which lie close to the thread become enlarged through an increased absorption of material. The irritation pro- duced by the thread extends only to a certain distance into the cartilage, whilst the more remote cells remain altogether unaffected. Such observations cannot be ex- plained otherwise than by assuming that the stimulus really acts upon the parts to which it is applied; it is impossible to conclude that it is conducted to the nerve by any channel perhaps more in accordance with the neuro-pathological doctrine, and then only by: reflex action conveyed back again to the parts. There certainly are but few tissues in the body which are so completely destitute of nerves as cartilage, but even when we observe what happens in the parts most abundantly supplied with nerves, we find in every case, that the extent of the irritation, or to speak more accu- rately, the extent of the irritated area, by no means cor- responds to the size of any particular nerve-territory, but that in a tissue in other respects normal the size of the affected area essentially corresponds to that of the local irritation. If we make the experiment with the thread, upon the skin, a whole series of nerve-territories are 22 338 LECTURE XIV. intersected by it. Still the whole of the territories be- longing to the nerves which lie along the thread, ire not thrown into the same morbid condition, but the nutritive irritation is limited to the immediate vicinity of the thread. No surgeon expects in operations of the kind, that all the nerve-territories traversed by the thread, will become diseased in their whole extent. Great com- plaints would have to be raised against nature, if every ligature, every seton were to exercise an irritating influ- ence, beyond the limits of the parts with which it is in immediate contact, upon the whole extent of the nerve- districts which it passes through. Thus we see in a tis- sue in which what takes place in such a case can be very clearly traced, namely in the cornea, that in parts of it to which no vessels extend, there are certainly still nerves which possess a reticular arrangement, and leave larger and smaller districts of tissue between them altogether devoid of nerves. Nowif we apply any stimulus directly to the cornea, as for example, a red hot needle, or lunar caustic, the district which is thereby set in morbid action by no means corresponds to the distribution of any nerve. It once happened to me with a rabbit that the cautery lighted precisely upon a nervous filament, but the mor- bid action remained confined to the immediate vicinity of this spot, and by no means spread over the whole dis- trict appertaining to the nerve. It is therefore utterly impossible, even if observations, like those on cartilage which I have laid before you, are not allowed to have any weight, not to admit that the phenomena of irritation in parts supplied with nerves are in no respect different from those which occur in nerveless parts, and that the immediate effects essentially depend upon the enlargement and tumefac: tion of the surrounding elements, so that when there are many of them, a visible swelling of the whole part is PARENCHYMATOUS KERATITIS. $39 the result. This is what you observe when a ligature is anywhere drawn through the skin. If on the following day the immediate vicinity of the thread be examined, an active enlargement of the cellular elements is found, quite irrespective of the distribution of vessels and nerves in the part. There is, as you see, an essential difference between what I here lay down and the opinions which have gene- rally been advanced with regard to the proximate causes of these swellings. According to the old maxim: ubi stimulus, ibi affluxus, it was generally conceived that the first thing which took place was an increased afflux of blood (which was itself referred by the neuro-patho- logists to the excitation of sensitive nerves), and then that the immediate consequence of the increased afflux was an increased excretion of fluid from the blood, constituting the exudation which filled the part. In the first timid attempts which I made to alter this conception, I employed the expression parenchymatous* exudation, retaining the term exudation, out of deference to prevailing opinion. I had, namely, convinced my- self that in many places where a swelling had occurred, there was absolutely nothing else to be seen than tissue. In a tissue which consisted of cells, I could, after the swelling (exudation) had taken place, still see nothing * The term Parenchyma was first employed by Erasistratus of Alexandria to de« signate the mass of tissue which lies between. the vessels of a part, and in his opinion fo:med a kind of affusion from them. Thus Galen says (Isagoge s. Introductio, cap. xi.): ‘‘ Cerebrum ex nullo principali vase compositum esse videtur Erasistrato, eoque nurrimenti parenchyma, i. c., affusio, ipsi esse videtur.” In the same way tie word is used by Vesalius (De humani corp. fabrica, lib. V., cap. 7) and by Thom. Bartholin (Anatome, lib. I., cap. 14), for the proper substance of the liver, lying external to, or between, the vessels. It therefore essentially denotes the tissue of which an organ is constituted. In a narrower sense those constituents of an organ which are peculiar to it, and give it its specific character, may be distin. guished as its proper parenchyma, in contra-distinction to its merely interstitial tissue. In my book the term has been used in both of these senses.—From a MS. Note by the Author 340 LECTURE XIV. but cells; in tissues composed of cells and intercellular substance, nothing but cells and intercellular substance ; the individual elements indeed were larger, fuller and filled with a quantity of matter with which they ought not to have been filled, but there was no exudation in the manner in which it had been imagined to exist, namely free, or in the interstices of the tissue. All the matter was contained in the elements of the tissues themselves. This was what I intended to express by the term, parenchymatous exudation, and hence the name, parenchymatous inflammation, is derived—a name which was, indeed, used in former times, but in quite another sense from that I meant—and which is now more generally employed than is perhaps desirable. It is, however, at all events important that you should draw a distinct line of demarcation between this form of irritation as a general standard and the other forms (especially the formative one), inasmuch as in it only the constituent elements of a tissue already existing in the body take up a larger quantity of material, and besides these enlarged elements nothing else is present. I will immediately send round a preparation to you, in which you will see a very characteristic example of such an inflammation. It is almost the most striking example which for a long time has come before me. It is a specimen from a case of so-called Keratitis, from one of Herr von Graefe’s patients, in whom, after vio- lent, diffuse phlegmonous inflammation of the extremi- ties, an extremely rapid inflammatory opacity of the cornea took place. When the cornea was put into my hands, it seemed to me as if it were opaque and swollen in its whole thickness. The vessels of the borders were very full of blood. But when I made a section through the part, it at once became evident, even with a low power, that the opacity extended by no means uni- PARENCHYMATOUS KERATITIS. 341 formly throughout the whole cornea, but was limited to a definite portion of the tissue. This portion is so characteristic in reference to the different explanations possible, that the case, I think, presents especial inter- est theoretically. It turned out namely that the opacity began in the immediate proximity of the posterior surface and at the circumference of the cornea, close to the membrane of Descemet [posterior elastic lamina of Bowman] at the point where the iris is attached. Thence the opacity, assuming almost the shape of a flight of steps, mounted up into the cornea till within a certain distance of the external surface. Then it proceeded at the same level, till it descended upon the other side again in a similar manner. Thus an opaque bow was formed throughout the whole substance of the cornea, without reaching the external (anterior) surface and without encroaching upon the central parts of the posterior surface. If we wi : imagine the nutrition of the cornea to proceed from the aqueous humour, the opacity did not assume the form Fig. 99, Parenchymatous keratitis. .4, A, Anterior (external), B, B, posterior (internal) side of the cornea. @, @. The clouded zone with enlarged cornea-cor- puscles, 18 diameters. 342 LECTURE XIV. that might have been looked for, for then we should rather have expected that the hindermost layer would be the first to undergo the change. If any influence from without had been here in operation, the opacity must have been seated in the most anterior layers ; if again the opacity were one which essentially proceeded from the vessels, we might, inasmuch as they chiefly lie along the border and nearer to the anterior surface, have expected to find the principal disease there. Finally, if the changes had their origin in the nerves, we should have found the opacity spread in the form of a network on the surface—and not a bow of this kind. The substance of the cornea consists, you know, ac- cording to general opinion, of lamellz (plates) which run in a more or less parallel direction through the Fie. 100. cornea. Now if this opinion be the correct one, we should have to deal with a process which, whilst advanc- 4 Fig. 100. Perpendicular section of the cornea of the ox, for the purpose of showing the form and anastomoses of its cells (corpuscles). Here and there are seen the cut ends of some of the processes of the cells, looking like fibres or points. 500 diameters. From His, ‘Wurzb, Verhandl,’ IV., plate IV., fig. I. STRUCTURE OF THE CORNEA. 343 ing €., lamella to lamella, each time moved a little farther on. Only the cornea is not composed of perfect lamelle, but of layers, which certainly are on the whole placed one against the other in a lamellar form, but yet are connected with one another ; they do not lie any how, more or less firmly or loosely upon one another, but there exist direct connections between them. It is therefore rather a large coherent mass, which is interrupted in certain directions by cellular ele- ments, just as is the case in the very different tissues which we have already specially considered. A vertical section discloses spindle-shaped cells which anastomose with one another, but at the same time also possess lateral processes; and in consequence of their being regularly imbedded in the basis substance, this lamellar, foliated or plate-like arrangement of the whole tissue is produced. When viewed upon the surface, in horizontal section, they show themselves in the form of many-rayed, stellate but very flat cells, which may be compared to bone-corpuscles. Fie. 101, If now in this case of ours we follow the process with a higher power, we discover, what may easily be shown Fig. 101. Horizontal section of the cornea, parallel to the surface and showing the stellate, flat corpuscles, with their anastomosirg processes. [From His, loc. cit., fig. II. 344 LECTURE XIV. to be the case in every form of keratitis, that the change is essentially seated in the corpuscles or cells of the cor- nea, and that in proportion as we approach the clouded spot either from without or within, the little narrow cells continually become larger and more cloudy. At last we find them presenting almost the appearance of sacculated canals or tubes. Whilst this enlargement of the elements, this acute hypertrophy, if you will, is going on, the con- tents of the cells are at the same time becoming more cloudy, and it is this cloudiness of the contents which in its turn occasions the opacity of the whole coat, for the proper basis-substance appears to be altogether unaf- Fie. 102. fected. This cloudiness of the contents is in part occa- sioned by particles which are of a fatty nature, so that the process seems to have begun to assume the character of a degenerative disease. I should have had no hesita- tion in believing that a destruction of the cornea had here Fig. 102. Parenchymatous keratitis (ef. Fig. 99), seen with a higher power. At A the cornea-corpuscles in a nearly normal condition, at B enlarged, at Cand D still more enlarged, and at the same time clouded 350 diameters, NUTRITIVE AND FORMATIVE IRRITATION. 845 really set in, but Herr v. Graefe assures me that, from what he has seen, such conditions may, when the disease runs a favourable course, terminate in resolution. And there is really nothing at all in the matter at variance with this possibility ; for, since the cells still exist and the only thing required is that their changed contents be get rid of, a complete restitution may no doubt take place. Now just this doctrine of a semply nutritive restitutional power is of very great importance practically. In such a case as this, where nothing has taken place excepting that the cells, without ceasing to display their activity, have accumulated in their cavities a larger quantity of material than usual, everything is prepared for the pro- cess which we call reabsorption ; the cells can transform a certain quantity of the material and convert it into soluble substances, and the material in this form may dis- appear in the very same way in which it came. The structure in the main remains the same all the while nothing foreign has thrust itself in between the parts the tissue presents throughout its original constituents. From the phenomena of this nutritive irritation direct transitions to incipient formative changes are often seen. If namely, we follow up the higher degrees of irritation which take place in a part, we find that the cellular ele- ments, shortly after they have experienced the nutritive enlargement, exhibit further changes which begin in the interior of the nuclei, generally in such a manner that the nucleoli become unusually large, in many cases some- what oblong, and sometimes staff-shaped. Then as the next stage we usually see that the nucleoli become con- stricted in the middle, and assume the form of a finger- biscuit (Bisquit), and a little later two nucleoli are found. This division of the nucleoli is an indication of the impend- ing division of the nucleus itself, and the next stage is, 346 LECTURE XIV. that about such a divided nucleolus the finger-biscuit-like constriction, and afterwards the real division, of the nu- Fie. 103. cleus takes place, as we have already seen in colourless blood- and pus-corpuscles (Figs. 11, 4, 0; 56, 63). Here we manifestly have to deal with something essentially different from what we had before. In the simple hy- pertrophy consequent upon nutritive irritation, the nu- cleus may remain quite intact ; here, on the other hand, we frequently see that the contents display a relatively slight amount of change, the utmost being that the cells become larger, whence we infer that a quantity of new material has been taken up into them. In many cases the changes are limited to this series of transformations, of which the division of the nucleus must be regarded as the conclusion. This may be repeated, so that three, four or more nuclei arise (Fig. 15, 8, ¢, d). Thus it comes to pass that we sometimes find cells—not merely in pathological conditions, but also not unfre- quently where the development is altogether normal— which contain twenty to thirty nuclei or more. Recently in the marrow of bones, especially in young children, cells have been observed, where the entire structure is Fig. 108. Cells from a melanotic tumour of the parotid gland extirpated in 1851 by Herr Textor. A. Free cells with division of the nucleoliand nuclei. 2B. Net- work of connective tissue-corpuscles with division of their nuclei. 300 diameters. DIVISION OF NUCLEOLI. 347 full of nuclei, which often attain the size of the whole original cell. Such formations occur in many tumours in Fig. 104. such large quantities, that in England a particular species is thereby distinguished, and on the proposal of Paget a myeloid tumour (medullary swelling) has been received into the classification. This formation is not, however, confined to the medulla of the bones, but occasionally occurs in nearly all situations. Muscle, upon irritation, exhibits precisely similar forms. Whilst transversely striated muscles are generally pro- vided with nuclei at certain intervals, though in no great abundance, we find, on examining a muscle in the neigh- bourhood of an irritated part, as for example, a wound, a corroded or ulcerated surface, that a multiplication of the nuclei is going on in it; we see nuclei with two nu- cleoli; then come constricted, and then divided, nuclei (Comp. Figs. 23, b,c; 24, B,C), and so it goes on, until we find in different places whole groups of nuclei lying side by side, in which the divisions have taken place to a large extent, or else whole rows of them, one behind the other. In the most marked cases of this sort the num- ber of nuclei increases to such a degree, that at first sight we can scarcely believe we are looking at muscles ; and that fragments of the primitive fasciculi offer the greatest Fig. 104. Cells from the marrow of bones. u. Small cells with single and divided nuclei. 6, 6. Large, many-nucleated cells. 350 diameters. From Kolliker, ‘ Mikr. Anat.,’ I., p. 364, fig. 113, 348 LECTURK XIV. resemblance to those plaques @ plusieurs noyaux which Robin has described in the marrow of bones. This is something quite peculiar which looks extremely like the commencement of a real new- formation, only that new-forma- tions in the ordinary sense of the word are not limited to sin- gle cell-constituents. Besides we must bear in mind this very important fact, that exactly the same limitation takes place in the earliest embryonic development of muscle, in the course of the first growth of the primitive muscular fasciculi. For this is the manner in which muscle originally grows. Ifa growing muscle be watched, the same division of the nuclei is wit- nessed, and after groups and rows of nuclei have arisen in it, they are, in the course of growth, gradually thrust farther and farther asunder by the continual increase of the intermediate sarcous sub- stance. Nowalthough a growth in length has not as yet been demonstrated with certainty in a pathologically irri- tated muscle—I say demonstrated, because there really is a probability that something of the kind may yet be proved to be the case—we must still hold the perfect analogy of morbid irritative processes with the natural ones of growth to be a well-ascertained fact. For the formative act of real growth begins with a multiplication Fie. 105. 7 jie Fig. 105. Division of nuclei in primitive muscular fasciculi from the immediate neighbourhood of a cancerous tumour in the thigh. At A a primitive fasciculus, the transverse striation of which is not represented all the way down, with its na- tural, spindle-shaped extremity f, and incipient multiplication of the nuclei. 2B. Strongly marked proliferation of nuclei. 300 diameters, NEW FORMATION OF CELLS. 349 of the centres, inasmuch as the nuclei must, as was long since shown by John Goodsir, be regarded as the central organs of the cells. If now, gentlemen, we advance a step further in these processes, we come to the new formation of the cells them- selves. After the multiplication of the nuclei has taken place, the cell may certainly, as we have seen, continue to subsist as a coherent structure ; still the rule is, that even after the first division of the nuclei, the cells themselves undergo division, and that after some time two cells are found lying closely side by side, separated by a more or less straight partition, and each provided with a nucleus of its own (Fig. 6, 0, 6). This is the natural, regular manner in which the real multiplication of cellular ele- ments takes place. Then, the two cells may separate, if the tissue is one which possesses intercellular substance (Fig. 6, c, d) ; or may remain lying close to one another, in the case of a tissue simply composed of cells (Fig. 27, C’). This series of processes, which in their subsequent course lead to a continually proceeding division of the Fie. 106. cells, and to the production of large groups of cells from single ones (Figs. 9, 22), occurs in the adult body just as unquestionably as the result of a direct irritation of the tissues, as the class we spoke of before. If, for example, we follow up a little farther the case which we before considered, of the production of a simple mechanical irritation by drawing a thread through the parts, we usu- Fig. 106. Cells from the central substance of an intervertebral cartilage of an adult. Intra-capsular multiplication of cells. 300 diameters. 350 LECTURE XIV. ally observe that the swelling is not simply limited to the enlargement of the existing cells, but that they divide and multiply. Round about a thread, which we draw through the skin, a number of young cells generally show themselves as early as the second day. The same change may be brought about by the application of a chemical stimulus. If, for example, caustics be applied to the sur- face of a part, the first thing that happens is that the cells swell up and then, when the process follows a regu- lar course, divide, and begin to proliferate more or less abundantly. Here too we have still to deal with actions which do not exhibit the slightest difference in the real mode of their accomplishment, whether the part be pro- vided with nerves, or destitute of them, whether it con- tain vessels or not. Accordingly, we cannot say that any part of these processes appears to be necessarily dependent upon ner- vous or vascular influence, but, on the contrary, we are in all these cases referred to the parts themselves. The relation of the vessels is not by any means to be ex- plained in the way in which it is ordinarily done; the absorption of matter into the interior of the cells is un- questionably an act of the cells themselves, for we are as yet acquainted with no method enabling us to pro- duce this kind of proliferation in the body, by any mode of experimentation, through the medium of an agency primarily affecting either the nerves or the vessels. The circulation may be heightened in the parts as far as it is possible to heighten it, without the production of such an increased nutrition of the parts as to give rise to any swelling or multiplication of the elements themselves. Those very experiments too upon the section of the sympathetic nerve which I have already mentioned, have, as is well known, proved (I myself have very fre- quently performed this experiment and watched its NEURO-PARALYTICAL INFLAMMATION. 351 effects with this especial object) that an increased afflux of blood may last for weeks—an afflux of blood accompanied by a marked elevation of temperature and corresponding redness, as great, both of them, as we ever meet with in inflammations—without the produc- tion of the least enlargement in the cells of the part, or the excitation of any process of proliferation in them. Irritation of the nerves may be combined therewith. But when the tissues themselves are not irritated, when the irritation is not made to act upon the parts them- selves, either by the direct application of the irritating matters, or by their introduction into the blood, the occurrence of these changes cannot be relied upon. This is a most important argument, from which I draw the conclusion that these active processes have their foundation in the special action of the elementary parts, an action which does not depend upon an increased afflux of blood or any excitation of the nerves, but which is certainly promoted by them, though it can also continue entirely independent of them, and manifests itself with just as great distinctness in a paralyzed and nerveless part. In support of these positions I will only add that more recent observations have gradually done away with the whole class of the so-called neuro-paralytical inflammations. The two nerves with which we are almost exclusively concerned in the discussion of inflam- matory phenomena, are the pneumogastric and the fifth pair, after the section of which, in one case, pneumonia, in the other, those celebrated changes in the eyeball have been observed to declare themselves. These ob- servations have now been explained in this way, that inflammations certainly may come on after such sections, but that the real interpretation to be put upon them is, 852 LECTURE XIV. that they manifest themselves in spite of the section.* With regard to the pneumogastric it was, as is well known, long since shown by Traube that the paralysis of the rima glottidis, whereby the entrance of the buc- cal fluids into the air-passages is facilitated, is the principal source of the inflammation ; besides, the more accurate interpretation of the pathological specimens has determined, that a great part of what had been called pneumonia, was really nothing more than atelec- tasis with hyperemia of the lungs; actual pneumonia may with certainty be avoided, if the possibility of the penetration of foreign bodies into the bronchi is cut off. The same.has been ascertained to be the case with the inflammations coming on after the section of the fifth pair, and indeed by means of a very simple experiment. After a number of attempts of the most varied kind had been made for the purpose of removing the different disturbing influences affecting the eye that was deprived of its sensibility, a very simple method was at last dis- covered in Utrecht for providing the eye with a substi- tute for its sensitive apparatus; for Snellen sewed be- fore the eyes of animals, in which he had cut the fifth pair, their still sensitive ears. From that time the ani- mals had no more attacks of inflammation, inasmuch as on the one hand a direct protection was afforded to the eye, and on the other the animals were preserved by the presence of a sensitive covering from all traumatic influences. As soon as sensation was re-established, not in the eye itself, but only before the eye, what was really nothing more than a traumatic inflammation was got rid of.+ * For if, as the neuro-pathologists assume, irritation produces inflammation through the medium of the nerves, then, when the nerves are cut, all inflammation ought to be impossible. + In the text the influence of the section of nerves is perhaps not described with NEURO-PARALYTICAL INFLAMMATION. 858 We can therefore now say, there is no form of dis- turbauce of this kind known which can be traced to the abolition of the action of a nerve. A part may be para- lyzed without becoming inflamed ; it may be anasthetic without becoming exposed to this danger. There is always required in addition some special irritation, either of a mechanical or chemical nature, and proceeding either from without or from the blood, in order to pro- duce the peculiar liability. In this manner therefore we have, as you see, a series of connecting links between facts eminently pathological and the most common processes of physiological life facts of which the special import can, however, only be understood and defined, when the distinctions are made to which I called your attention at the commencement of the lecture, that is, when the different kinds of irrita- tion are separated according to their functional, nutritive sufficient minuteness, According to the author’s views, of which a more detailed account may be found in his: Handbuch der spec. Pathologie und Ther. Erlangen, 1854 (Vol. I., pp. 31, 50, 80, 276, 314, 319), the section and paralysis of nerves certainly exercise some influence upon the nutrition of the tissues, although per- haps only an indirect one. The states arising from such causes he has classed together under the name of Neurotic Atrophy. Parts which have in this way suffered derangement in their nutrition, and as a consequence have become weak- ened, are less capable of controlling the disorders by which they are attacked, and accordingly simple irritation in them readily becomes aggravated into inflammation (asthenic inflammation). But in these cases the inflammation is always the conse- quence of some special irritation, never the direct result of the section of the nerves, Still, as in the case of the fifth pair and the pneumogastric, such section may be the cause of irritants’ (foreign bodies and other agents) more readily acting upon the anesthetic or paralyzed parts. Cl. Bernard has recently declared that the section or irritation of nerves in weakened parts produces effects which cannot be elicited in healthy ones. We have therefore here to deal with a very complicated state of things. The change in the nerve is generally succeeded by a disturbance in the function or circulation of the part, or in both, and when the part is already weakened (z. ¢, altered in its nutrition) this disturbance may prove a source of irritation to it, and thus the effects be produced which Bernard ascribes to other causes. In quite a similar manner we see that, even when the nervous supply is in its normal state, purely mechanical disturbances in the circulation act upon weak- ened parts as morbid irritants—From a MS, Note by the Author. 23 354. LECTURE XIV. or formative nature. If they are jumbled together, as they have been by the neurists, and especially, if the formative and nutritive processes are not kept apart, then it is impossible to arrive at any simple explanation of the phenomena. Those states of irritation which we witness in the course of the severer forms of disease—the really inflammatory kinds of «irritation—never in any case admit of a simple explanation. In inflammation we find side by side all the forms of irritation of which I have given you an analysis. Indeed, we very frequently see, that when the organ itself is made up of different parts, one part of the tissue undergoes functional or nutritive, another formative changes. If we consider what happens in a muscle, a chemical or traumatic stimulus will perhaps in the first instance produce a functional irritation of the primitive fasciculi ; the mus- cle contracts, but then nutritive disturbances declare themselves. On the other hand in the interstitial con- nective tissue, which binds the individual fasciculi of the muscle together, real new-formations are readily pro- duced, commonly pus. Here we have to dem with a formative irritation, whilst the inflamed primitive fasci- culus commonly produces no pus, any more than it does new muscular substance ; on the contrary we most fre- quently see, when the irritation has attained a certain height, degenerative processes set in. In this manner the three forms of irritation may be distinguished in one part. Of course there may be in addition also an irri- tation of the nerves, but this has, at least if we do not take function into account, no connection of cause and effect with the processes going on in the tissue proper, but is nothing more than a collateral effect of the original disturbance. This must, in my opinion, be regarded as the most important result derived from é INFLAMMATORY IRRITATION. 855 the facts of Special Histology, and it is all the more certain because it can be tested both by experiment and by physiological and pathological experience. Soon, I will show you how in the study of inflamma- tory processes a clearer apprehension of their nature may hereby be obtained. LECTURE XV. APRIL 10, 1858. PASSIVE PROCESSES. FATTY DEGENERATION. Passive processes in their two chief tendencies to degeneration; Necrobiosis (soft ening and disintegration) and induration. Fatty degeneration—Histological history of fat in the animal body; fat as a com: ponent of the tissues, as a transitory infiltration, and as a necrobiotic matter, Adipose tissue—Polysarcia—Fatty tumours—lInterstitial formation of fat—Fatty degeneration of muscles. Fatty infiltration—Intestines ; structure and functions of the villi—Reabsorption and retention of the chyle—Liver; intermediate interchange of matter by means of the biliary ducts. Fatty liver. Fatty metamorphosis—Glands; secretion of sebaceous matter and milk (colostrum) —Granule-cells and granule-globules—Inflammatory globules—Arteries; fatty usure and atheroma in them—Fatty débris. WE have, gentlemen, hitherto nearly always spoken of the actions of cells and the processes which manifest themselves in them, when, in consequence of any exter- nal influence, they give signs of their vitality. There take place in the body, however, also a tolerably large number of passive processes, in which, as far at least as can be demonstrated, there is no particular activity dis- played by the cells. Allow me therefore, before we proceed farther in the description of the active processes, to speak a little more in detail concerning these passive processes. For the history of the affections of cells, as they are exhibited to us in our patients, is generally 856 DEGENERATION. 857 composed of processes, which belong, some of them, rather to the active class, and some of them, rather to the passive one; and the obvious results are in many cases apparently so similar in both classes, that the ulti- mate changes which we meet with, after the continuance of the process for a certain time, may very nearly be the same. Here particularly it was for a time, very difficult to define the boundaries, and a great part of the confusion which marked early microscopical efforts, was occasioned by the extraordinary difficulty there was in separating active and passive disturbances. Passive disturbances I call those changes in cellular elements, whereby they at once either merely lose a por- tion of their activity, or are so completely destroyed, that a loss of substance, a diminution in the sum total of the constituents of the body is produced. Both series of pas- sive processes, taken together, viz., those which are in the first instance marked by an essential diminution of power, and those which terminate in a complete destruction of the parts, constitute the chief part of the domain of what is called degeneration, although—a point that we must hereafter consider more closely—a great part of what must be called degeneration must be transferred to the series of active processes, It makes of course an extremely great difference whe- ther a vital element continues to subsist as such, or whe- ther it entirely and completely perishes: whether at the conclusion of the process, it still exists, even though in a condition of much diminished functional power, or whe- ther itis altogether destroyed. And here we have the important practical distinction, that in the one series of processes there is a possibility of a repair of the cells, whilst in the other direct repair is impossible, and a rege- neration can only take place by means of a substitution of new cells from the neighbourhood. For when a cell 358 LECTURE XV. has perished, it is of course impossible for any further development to originate in it. This latter category, where the cells are destroyed during the course of the process, I proposed a few years ago to designate by a term which has been employed to express disease generally by K. H. Schultz, viz., Necro- biosis.* For we have, namely, always here to deal with a gradual decay and death, a dissolution, we might almost say, a necrosis. But the idea of necrosis really does not offer any analogy to these processes, inasmnch as in ne- crosis we conceive the mortified part to be preserved more or less in its external form. Here on the contrary the part vanishes, so that we can no longer perceive it in its previous form. We have no necrosed fragment at the end of the process, no mortification of the ordinary kind, but a mass in which absolutely nothing of the pre- viously existing tissues is preserved. The necrobiotic pro- cesses, which must be completely separated from necrosis, are in general attended by softening as their ultimate re- sult. This commences with a friability of the parts ; they lose their coherence, at last really liquefy, and more or less moveable, pulpy or fluid products take their place. We might therefore without more ado name this whole series of necrobiotic processes softenings, if a number of them did not run their course, without the malacia’s ever be- coming apparent to the naked eye. As soon, namely, as a process of this sort sets in in a compound organ, as for example, a muscle, a palpable myo-malacia is cer- tainly produced when all the muscular elements at a given point are at once affected ; but it happens far more ‘requently that, in the course of a muscle, only a compa- ratively small number of primitive fasciculi are affected, * Necrobiosis is death brought on by (altered) life—a spontaneous wearing out of living parts—the destruction and annihilation consequent upon life—natural as opposed to violent death (mortification.)—From a £8. Note by the Author. FATTY DEGENERATION. 359 whilst the others remain almost intact. Then indeed a softening really does occur, but such a minute one, that it is altogether imperceptible to the naked eye and can only be demonstrated microscopically. In this case we generally make use of the expression, atrophy of muscle, although the process which has attacked the individual primitive fasciculi, does not in any way differ in its na- ture from the processes which we at other times term softening of muscle. This is the reason, why the term softening, which must be reserved for coarse pathological anatomy, cannot sim- ply be applied to histological processes, and why it is better to say necrobiosis, when we have to do with these more delicate processes. The common feature of all the varieties of the necrobiotic process is, you know, that the affected part at the close of the process is destroyed, nay annihilated. A second class of passive processes is formed by the simply degenerative forms, in which, at the conclusion of the process, the affected part is in some condition or other less fitting it for action, and has generally become more rigid. This group might therefore be termed hardenings (tndurations) and thus a group be formed distinguishable even externally from the necrobiotic processes. Only the term induration also would easily be misunderstood, inasmuch as in this class likewise many conditions occur, in which the hardness of the organ on the whole at least does not become more considerable, but only isolated, very minute parts undergo change, so that no very strik- ing effects are apparent to the sense of touch. Allow me now to hold up to you as types a few of the processes belonging to this class, which are of the great- est importance in a directly practical point of view. Among the necrobiotic processes the one which is un- 360 LECTURE XV. questionably the most widely spread and the most im- portant in the course of all cellular disturbances, is fatty metamorphosis, or as it has also long been wont to be called, fatty degeneration. This process is attended by a continually increasing accumulation of fat in different organs. Even the old notion of fatty degeneration in- volved the idea of a continually increasing change of such a nature that pure fat at last took the place of whole parts of organs. It has turned out, however, that this old notion, which is even now retained by many in the language of pathology, includes a great number of com- pletely different processes, and that errors would inevit- ably be committed if it were sought to interpret the whole ° group from a pathogenical point of view, in a simple manner. The history of fat in its relation to the tissues may, gene- rally speaking, be considered under three aspects. We find namely one class of tissues in the body, which serve as physiological reservoirs for fat, and in which the fat is contained as a kind of necessary appurtenance, without however their own permanency being in any way en- dangered by its presence. On the contrary, we are actu- ally accustomed to estimate the well-being of an indivi- dual by the amount of fat contained in certain tissues, and to regard the degree of fulness presented by the in- dividual fat-cells as a criterion of the successful progress of the interchange of matter generally. This forms there- fore a complete contrast to the necrobiotic processes, in which the part, in consequence of the accumulation of fat, really altogether ceases to exist. A second series of tissues do not constitute regular re- servoirs for fat, on the contrary fat is found in them only at certain times and transitorily, for after a short time it again disappears from them, without their being on that account left in an altered state. This is the case in the PHYSIOLOGICAL FATTY METAMORPHOSIS. 361 ordinary absorption of fat from the intesti: al canal. When we drink milk, we expect in accordance with old experience that it will gradually pass from the intestines into the lacteals, and thence be conveyed into the blood ; we know that the passage of digested matters from the intestines into the lacteals takes place through the epithe- lium and the villi, and that some hours after a meal the epithelium and the villiare full of fat. Now, with respect to such a fat-containing villus or epithelial cell, we take for granted that in the natural course of events it will at last yield up its fat, and after some time again become perfectly free from it. This is fatty infiltration of a purely transitory character. Finally, we have a third series of processes, namely, those which lead to necrobiosis and which have of late frequently been regarded as peculiarly pathological ones. But, as it has been shown to be the case in all other con- ditions that pathological processes are not specific ones, but, on the contrary, that others analogous to them exist in normal life, so also the conviction has been acquired that this necrobiotic development of fat is an entirely regular and typical process in certain parts of the body, nay that it is even met with in very obvious forms in physiological life. The most important types of this pro- cess we find on the one hand in the secretion of milk, the sebaceous matter of the skin, the cerumen of the ears, etc., and on the other in the formation of the- corpus lu- teum in the ovaries. In all these parts a development of fat takes place precisely in the same manner that we meet with it in the nocrobiotic fatty metamorphosis occurring from morbid causes, and in what we call seba- ceous matter, milk or colostrum we have formations ana logous to the pathological masses of fat which constitute fatty softening. If in any person milk is manufactured in the brain instead of in the mammary gland, this con- 362 LECTURE XV. stitutes one form of cerebral softening ; the product may morphologically exactly correspond with what in the mammary gland would have been quite normal. The great difference, however, is this, that, whilst in the mammary gland the cells which perish are replaced by a succession of new cells, the disintegration of elements in an organ which is not arranged so as to furnish such a succession, leads toa permanent loss of substance. The same process which in one organ yields the happiest, nay the sweetest, results, brings along with it in another, painful lesions. If then you picture to yourselves these three different physiological types, we have in the first case an accumu- lation of fat in the cells in such a way, that at the close of the process every single cell is entirely full of it. This yields us the type of the so-called adipose cellular tissue, or simply, ad¢pose tissue, as it occurs in such large masses especially in the subcutaneous tissue, where it on the one hand gives rise to beauty, particularly in the female figure, and on the other to the pathological conditions of obesity or polysarcia. Fat-cells always possess a mem- brane and fatty contents, but the fat so completely fills up the interior, and the membrane is so extremely thin, delicate and tense, that usually nothing else is seen than Fie. 107. Fig. 107. Adipose cellular tissue from the panniculus [adiposus.] A. Ordinary subcutaneous tissue, with fat-cells, some interstitial tissue, and at 4 vascular loops; a, an isolated fat-cell with membrane, nucleus and nucleolus. B. Atrophic fat in phthisis, 300 diameters. ADIPOSE TISSUE—FATTY DEGENERATION OF MUSCLES. 363 the drop of fat, and thus it was, until very recently, still a matter of discussion whether the fat-cells really were cells. Itis in reality very difficult to come to a distinct decision upon the subject, but supporting testimony of a very beautiful character is supplied in the course of natu- ral processes. When a person becomes thinner, the fat gradually disappears, the membrane loses somewhat of its tension, is no longer so thin and delicate, and thus becomes more clearly manifest, being sometimes distinctly separated from the drop of fat, and even provided with a recognizable nucleus (Fig. 107, A, a). We have here therefore a real, complete cell with nucleus and mem- brane, though the contents have been almost entirely sup- planted by the fat it has taken up. This so-called adi- pose cellular tissue is a form of connective tissue (p. 76), and when it undergoes retrogressive metamorphosis, it is clearly seen to be reduced to connective or mucous tis- sue, for between the cells a small quantity of intercellu- lar substance again becomes apparent (Fig. 107, A, d, B). This species of adipose tissue it is, gentlemen, which under certain circumstances not only gives rise to poly- sarcia and obesity, from continually increasing quantities of connective tissue becoming involved in this accumu- lation of fat, but is also the foundation of all anomalous fatty structures, for example, of lipomata. The differ- ent forms of these structures, and particularly real fatty tumours, are distinguished from one another only by the greater or less quantity of interstitial connective tissue, which the tumour contains, and upon which their greater or less consistence depends. It is the same form of accumulation of fat which we see appear in morbid conditions in a series of cases which, in compli- ance with old tradition, are still called fatty degenera- tion ; and it is indeed particularly the fatty degeneration of muscles which in many instances presents nothing 364 LECTURE XV. else than a more or less advanced development of adi- pose cellular tissue between the primitive muscular fasciculi. It is a similar process to that which we meet with in the fattening of animals, and which is often exhibited in simply fattened muscles m the human body, Fat-cells insinuate themselves between the primitive muscular fasciculi, and lie of course in stripes in the direction of the muscular fibres, which may remain unchanged. The development in this case has its origin in the interstitial tissue of the muscle. At the com- mencement of the development, and when it proceeds with very great regularity, it may happen, that single rows of fat-cells lying one behind the other al- ternate with the rows of muscu- lar elements. In this case, where the primitive fasciculi are forced asunder, and the circu- lation in the muscle is generally disturbed in consequence of the abundant development of fat, so that the flesh becomes pale—it looks to the naked eye as if there no longer existed any muscular tissue whatever. If, for example, in an inferior ex- tremity, which in consequence of an anchylosis of the knee has remained unexercised, the gastrocnemii are examined, we find nothing but a yellowish mass exhi- biting scarcely any strize and without any appearance of flesh, but upon a more minute examination it is dis- covered, that the primitive muscular fasciculi still pass, essentially unaltered, through the fat. In this case the fat forms an impediment to the use of the muscle, but the primitive fasciculi still exist and are to a certain Fie. 108. Fig. 108. Interstitial growth of fat in muscle (fattening). //. Rows of intersti- tial fat-cells ; mm, m, m, primitive muscular fasciculi. 500 diameters. TRANSITORY FATTY JNFILTRATION. 865 extent capable of action. This process therefore is essentially different from necrobiosis, where the muscu- lar fibres as such completely perish. Here we have a purely interstitial formation of adipose tissue, ordinary connective tissue becoming converted into adipose tissue, and the term, fatty degeneration, which is so very liable to be misunderstood, should be avoided. This form occurs pretty frequently, especially in the heart, and may, when it attains a great extent, produce considerable derangement in the motor power of the muscular substance of this organ, but in pathological importance it stands far below real fatty metamorphosis, although this again in its outwardly visible results much resembles it. The hearts described by the cld anato- mists as fatty were in a great measure only hearts infil- - trated with fat; on the other hand, what is meant at the present day when genuine fatty degeneration (meta- morphosis) of the heart is spoken of, is not this obesity of the heart, this interlarding of its fibres with fat-cells, but rather a real transformation of its substance, going on in the interior of the fibres (Fig. 23). In the latter case the fat lies im, in the former between the primitive fasciculi. The second series of processes consists in the transi- tory accumulation of fat in certain organs, as we meet with it in a typical form in digestion. When a fatty substance has been eaten, and has passed into the state of emulsion, we find that, when it has reached the upper end of the jejunum, and to some extent even in the duodenum, the villi of the mucous membrane be-- come whitish, clouded and thick, and more minute examination shows, that they are filled with extremely minute granules, much-more minute than can be pro- duced by any artificial emulsion. These granules, which are found even in the chyme, come in the first 366 LECTURE XV. instance into contact with the cylindrical epithelium with which every single intestinal villus is invested. On the surface of every epithelial cell we find, as was first discovered by Kélliker, a peculiar border which, when the cell is seen in profile, exhibits minute and fine striae ; when viewed from above, and seen upon the surface, the cell appears hexagonal and, as it were, dotted over with a number of minute points (Comp. the epithelium . of the gall-bladder, Fig. 14, and also Fig. 109, A). Kolliker has put forward the conjecture, that these fine strie and dots correspond to minute pore-canals, and that the absorption of the fat is effected by its minute particles being taken up through these minute pores upon the surface of the epithelial cells. But the object is one which is accessible only to the highest powers of our optical instruments, and it has therefore hitherto been impossible to obtain perfectly clear notions as to whether the striz really correspond to fine canals. or Fie. 109. Fig. 109. Intestinal villi, showing the absorption of fat. A. Normal human intestinal villus from the jejunum; at « the cylindrical epithelium in part still investing it with the delicate border and nuclei; ¢, the central lacteal vessel ; v, ¥, blood-vessels ; in the rest of the parenchyma the nuclei of the connective and muscular tissue. 2B. Villus in a state of contraction, from a dog. @. Human intestinal villus during the absorption of chyle, D, in a case of retention of chyle; at the apex a large fat-drop, emerging from a crystalline envelope. 280 diameters. ery ABSORPTION OF FAT IN THE INTESTINES. 367 whether, as Briicke supposes, the truth is rather that the whole of this upper border is composed of little rods or pillars resembling cilia. I must confess that my own investigations also have rather disposed me to adopt this latter opinion, especially as comparative his- tology shows us real ciliated epithelium to be the equi- valent structure in the same parts. At all events this much is certain, that, a short time after digestion has taken place, the fat no longer lies only outside, but is found also inside, the cells, and first at their outer end; then it gradually advances farther and farther inwards in the cells, and indeed so distinctly in rows, that it might easily give rise to the impression, that fine canals ran throughout the whole length of the cells themselves (Fig. 109, C, a). But this too is a question which will not, I think, with our present optical instruments, be so very speedily settled. At any rate, the plain fact re- mains, that the fat passes through the cells, and this indeed in such a way, that at first only their outer end is filled with it, then a time comes when they are quite full of fat, then a little later the outer part again be- comes entirely free from it, whilst the inner still con- tains a little, until at last all the fat entirely vanishes from the cells. In this manner its gradual progress may be followed from hour to hour. After the fat has ad- vanced as far as the inner extremity of the cells, it begins to pass into the so-called parenchyma of the villus (Fig. 109, C). Whether the epithelial cells have an orifice below, and whether, as has been quite re- cently maintained by Heidennain junior, they are con- nected with extremely minute canals formed by the con- nective-tissue-corpuscles, is not quite decided, though it is very probable. It is extremely difficult to come to any definite conclusions with regard to these extremely minute arrangements of the substance of tissues. In 368 LECTURE XV. the interior of the villi we generally find the network of blood-vessels a little below the surface (Fig. 109 A, v, v), whilst in its axis there is a tolerably wide cana- licular cavity with a blunt extremity, the commence- ment of the lacteal vessel, as far as it can at present be determined with certainty (Fig. 109, A, c). At the periphery of the villi Briicke has discovered a layer of muscular fibres, which is of great importance in diges- tion, inasmuch as by its help an approximation of the apex of the villus to its base, a shortening is effected, as may very readily be seen. Upon cutting off villi from the intestine of an animal just killed, they may be seen under the microscope to contract, become wrinkled, thicker and shorter (Fig. 109, B); thereby a pressure from without inwards is manifestly produced, which promotes the onward movement of the juices. So far the matter is tolerably clear, only what sort of a structure the rest of the parenchyma has, it is ex- tremely difficult to see. Upon the outer side of the muscular layer, smallish nuclei are seen, which, as I poimted out many years ago, are now and then pretty distinctly enclosed in fine, cellular elements. But whether these parenchymatcus cells anastomose with one another so as to form a special network, I am unable to say. During the process of absorption it looks as if the fat which keeps penetrating farther and farther into the interior of the villi, filled up the whole parenchyma.* At last it reaches the central lacteal, and there the regular current of chyle begins. The whole process therefore presupposes an emulsive condition of the fat, which penetrates through the parts * T have quite recently convinced myself by the examination of transverse sec: tions of villi, filled with chyle, in man, that the fat does not lie scattered in tho parenchyma, but forms deposits in the interior of special minute cavities (cells ?).-- Note to the Second Edition. RETENTION OF CHYLE. 369 oO everywhere in a state of extremely minute division ; in the regular course of events the particles are so ex- tremely minute, thatif the chyle is examined when fresh and still warm, scarcely a trace of the solid particles can be detected in it. But every disturbance which occurs in the process of absorption, and impedes the onward movement of the fatty particles, causes them to run together; larger granules separate in the tissues, drops appear which continually increase in volume, until at length they attain quite a large size. These are found even in the epithelial cells or within the tissue of the villi, and indeed it sometimes happens that the ends of the lacteals grow wider, and swell out into a bulbous form from the great accumulations of fat, so as to be recognized even by the naked eye. Nowhere have they been so frequently witnessed in a striking form, as in cholera, and a good description of these appearances as occurring in this disease was published as far back as 1837 by Bohn. They indicate nothing more than an obstruction to the current of lymph in consequence of the disturbances in the respiration and circulation (Fig. 109, D). Since attacks of cholera are well known to occur with preponderating frequency during digestion and are attended by greatly impeded respiration, which makes itself felt throughout the whole venous system, they must of course also react upon the stream of chyle. Thus the enormous accumulation (retention) of fat in the villi is explained. This is therefore, if you will, a pathological condition, but it only depends upon a tran- sitory obstruction, and we have every reason to suppose that, when the current again becomes free, these large drops of fat ‘are gradually removed. But here we set foot upon other domains, where the boundaries of patho- logy can only be traced with great difficulty, and this is particularly the case with the liver. 24 370 LECTURE XV. It has been known from of old that the vei is the organ, which is by far the most liable to fall intc a state of fatty degeneration, and the knowledge of this state has long been derived from popular experimeit. The history of the patés de foie gras proves this in the most agreeable manner, although M. Lereboullet of Strasburg maintains that the fatty livers of geese are physiological ones, essentially different from the pathological ones which are not eaten, but only observed. However, I must confess that I have hitherto been unable to discover the difference between physiological and pathological fatty livers ; on the contrary, I believe that it is only by ad- mitting the identity of the two that correct notions with regard to the pathological fatty liver can be obtained. We are namely acquainted with a fact which was like- wise first observed by Kolliker, that in sucking animals, a few hours after digestion has taken place, a kind of fatty liver is a constant physiological occurrence. When of the same litter of animals some are made to fast, while others are allowed to suck, those which have sucked have a fatty liver a few hours afterwards, whilst the others have not. The fatty liver appears quite pale, though certainly not so white as a goose’s liver. This observation led me to examine the question of the rela- tion of the fat to the liver a little more minutely, and 1 cer- tainly think we may positively conclude that there does exist a close connection between the physiological and pathological forms. I found, namely, that a short time after the hepatic cells display this repletion with fat, a similar condition is found in the course of the biliary ducts, and that both in them and in the gall-bladder the epithelium presents the same appearances which we have witnessed in the intestinal epi- thelium during the absorption of fat. You only require therefore to invert the picture we just now considered FATTY LIVER. 8371 (Fig. 109) ; instead of a villus, invested externally with epithelial cells, imagine a canal clothed on the inside with epithelium. The delicate cylindrical epithelium in the gall-bladder has the same striated border as that in the intestine (Fig. 14), and the fat is seen in the same way to penetrate into it from without, to pursue its course down- wards and after a time to pass into the wall of the gall- bladder. The same qnay be said of the biliary passages (duct. biliferi, hepat., cystic., choledoch.), which are also provided with cylindrical epithelium of a similar struc- ture. I have watched the same process also in young sucking animals after digestion, and there it is easy to convince oneself that the fat, which for a time is con- tained in the hepatic cells, is manifestly excreted from them into the biliary ducts, but that in the course of these ducts the fat is reabsorbed and thus a second time returns into the circulation. Such an intermediate interchange of matter as this, where the fat passes from the intestine into the blood, from the blood into the liver, from the liver into the bile, and thence again into the lymphatics, or into the capilla- ries which conduct the blood back to the hepatic veins and to the heart, presupposes of course, Just as absorption in the intestines does, that the conveyance back again must take place under favourable circumstances ; if any dis- turbing cause arises, a retention will of course ensue, and the place of the fine granules will gradually be occupied by large drops. But this is the mode of proceeding as it can really be traced in the fatty liver. Upon studying a fatty liver, it is generally seen that the fat is first deposited in that zone of the acini which is immediately contiguous to the capillaries into which the branches of the portal vein break up (Fig, 110. ¢, c). When sections of the organ are carefully examined with the naked eye, it looks in many parts as if one had an 372 , LECTURE XV. oak-leaf with its ribs and indentations before one ; the ramifications of the branches of the portal vein correspond to the ribs, the fatty zone to the sub- stance of the leaf. The more abun- dant the infiltration, the broader does the fatty zone become, and there are cases in which the fat fills the whole of the acini up *he central (intralobu- lar) hepatic vein (Fig. 110, 2) and every single cell is crammed full of fat. In rare cases it certainly happens, that we find just the reverse, and that the fat lies around the central vein ; these are cases which are probably to be explained by supposing that the fat is already in process of excre- tion and only the last cells still retain a little of it. Only we must take care not to confound with this condition a kind of fatty, necrobiotic atrophy which occurs particu- larly in chronic cyanosis.* If now we consider the process in detail, we find that the manner in which the hepatic cells fill themselves, en- tirely corresponds to that, in which an epithelial cell in the intestine becomes filled with fat. At first we find fat-granules widely scattered, and indeed very small. They become more numerous, more closely aggregated, and after a time larger; at the same time the cells be- Fig. 110. The adjoining halves of two hepatic acini. p. A branch of the portal vein with braches p’ p”, corresponding to the interlobular veins. h, h. Transverse sections of the intralobular, or hepatic, vein. a. The pigment zone, 6 the amyloid zone, c the fat zone. 20 diameters. * Cyanosis (chronic) is here used to express the general venous congestion which is consequent upon chronic affections of the lungs and heart. ‘‘Since (as the Au- thor says ina MS. note) it has become known that cyanosis, even when produced by congenital malformation of the heart, does not arise from a commingling of arterial and venous blood, but from an obstruction to the venous circulation, it has seemed reasonable to designate every more general hyperemia, due to such ob- struction, by the same term.” ‘‘ Acute cyanosis,” he adds, ‘“ occurs in acute affec- tions of the lungs, as for example, in pertussis.” —Tr. FATTY LIVER. 373 come larger, swell up, and larger and smaller drops of fat are found in them (Fig. 27, B, 6), until, when filled to the utmost, they present the same appearance as those of adipose tissue ; scarcely any membrane, and scarcely ever a nucleus is seen, nevertheless they both still con- tinue to exist. This is the condition which is called fatty liver, in the proper sense of the word. In it too we have what we found to be the case in adi- pose tissue—a persistence of the cells. There is no such thing as a fatty liver in which the cells have ceased to exist ; these constituents of the organs always exist, only they are almost entirely filled with drops of fat instead of with their ordinary contents. It can scarcely be doubted but that even in this condition they still contain a certain amount of matter capable of performing its functions. For in many animals, as for example the cod-fish from which liver-oil is obtained, the functions of the organ are still performed, however large the quantity of oil contained in the cells. In man too, even in the most advanced stage of fatty liver, we still find bile in the gall-bladder. So far therefore these conditions can in no respect be compared to the necrobiotic conditions, which are found in the course of fatty degeneration in so many other parts, and in which the elements perish. In fatty degeneration, in the ordinary sense of the word, we find, in the later stages of the affection, somewhere or other, friable, softened places, where the fat is contained in free drops—in some sort fatty abscesses. It is therefore a fact of extreme importance, and one which I consider to afford very decided indications for the correct apprecia- tion of this form [fatty liver], that in it there is always a persistence of the histological constituents, and that, how- ever much these constituents may become filled with foreign substances, they still continue to exist as celis. Hence it follows, that a fatty condition of the liver may 374 LECTURE XV. be removed, that it is curable, without any particular regenerative processes being required for the cure. The only requisite is, that the causes of the retention be re- moved, and the hepatic cells be freed from fat. It is true we have no positive information respecting either the one or the other of these points. We are not acquainted with the states which lead to the retention of the fat, nor with the conditions under which it can again be expelled. However, now that we have got so far, it will probably also be possible to make out the remaining facts. For it is conceivable, for example, that simply the elasticity of the histological elements is of importance ; that when the cell walls become relaxed, they may readily admit a quantity of matter, and tolerate its presence in them, whilst, if they are very elastic, a removal, an expression of their contents, may be more likely to ensue. The state of the circulation also is certainly of importance, and the frequent occurrence of fatty liver in chronic affec- tions of the lungs and heart is certainly in no small de- gree to be ascribed to the increased pressure to which the venous blood is subjected. What I was particularly anxious, gentlemen, to render evident to you, was the great difference which this kind of fatty degeneration presents from that which we have previously considered. Whilst there we saw arise be- tween the proper specific constituents of the organ—fat- cells which belonged to the connective tissue, here it is the specific gland cells themselves which are the seat of the fat. On the other hand, you must take into consider- ation the great difference from the necrobiotic processes of fatty degeneration, in which the cells as such disap- pear. We have now, gentlemen, to consider this third series of fatty conditions a little more closely, those, I mean, which are attended by a destruction of the elements, and FORMATION OF SEBACEOUS MATTER. 875 of which we have set up the secretion of milk and seba- ceous matter as the true types. That these two secre- tions are analogous to one another, is simply explained by the circumstance that the mammary gland is really nothing more than an enormously developed and pecu- liarly formed accumulation of cutaneous (sebaceous) glands. In their development both classes are perfectly analogous. Both are produced, by means of a progres- sive proliferation, from the internal layers of the epider- mis (p. 68, Fig. 18, A). .To the same category also be- long the ceruminous glands of the ear, and the large glands of the axilla. In all these cases the fat, which constitutes the chief constituent of milk, at least as far as its external appearance is concerned, and which furnishes the sebaceous secretion, originates in the interior of epithelial cells which gradually perish and set the fat free, whilst scarcely a trace of the cells is preserved. The se- baceous glands are generally seated on the sides of the hair-follicles at some depth below the surface ; we there find a series of mi- nute lobules, into which a prolon- gation of the rete mucosum is un- interruptedly continued. The cells of this become more numerous and larger, so as to fill the gland-sacs with a nearly solid matter. Then the fat begins to be Fig. 111. Hair-follicle with sebaceous glands from the skin. ¢. The hair, 6 its bulb, ¢, e, the layers of cells dipping down from the epidermis into the hair-follicle. gg. Sebaceous glands in the act of secreting sebaceous matter ; at 7, the secretion mounting up by the side of the hair and accumulating. 280 diameters, 376 LECTURE XV. secreted into their interior, at first in small particles, which soon become larger, and after a short time the individual cells can no longer be distinctly perceived, but only conglomerations of large drops, which rise up out of the gland into the hair-follicle. If we unravel the gland so as to form a flat surface, its layers of cells would have the appearance of epidermis, only that the oldest cells do not become horny, but are destroyed by fatty metamorphosis. The secretion is a purely epi- thelial one, like the seminal secretion. This process furnishes us at the same time with an , accurate representation of the formation of milk. You need only imagine the ducts much lengthened, and the terminal acini greatly developed; the process remains essentially the same: the cells multiply abundantly ; the multiplied cells undergo fatty degeneration, and ulti- mately there remains scarcely any material traces of these cells excepting the drops of fat. The closest re- semblance to the manner in which the secretion of seba- ceous matter ordinarily takes place, is presented by the earliest period of lactation when the so-called colostrum is yielded. A colostrum-corpuscle (Fig. 112, C’) is the still coherent globule which results from the fatty de- generation of an epithelial cell. The formation of colos- Fig. 112. Fig. 112. Mammary gland during lactation, and milk. .A. Lobule of the mam- mary gland, with milk issuing out of it. B. Milk globules. @. Colostrum, a, a dis- tinct fat-granule cell, d, the same with evanescent nucleus. 280 diameters. COLOSTRUM- AND MILK-CORPUSCLES. 377 trum and sebaceous matter differs in this respect only, that the fat-granules remain smaller in the former case, and that whilst large drops very soon show themselves im sebaceous matter, in colostrum the last cells which are observed, usually contain only minute fat-granules, very densely aggregated, whereby the whole cell ac- quires a somewhat brownish appearance, although the fat has no actual colour. This is the granular corpuscle (corps granuleux) of Donné. Foi the discovery of this gradual transformation of cellular bodies into fat-granule masses we are indebted to Reinhardt. Still he shrank from extending this important discovery of the formation of colostrum to the history of milk in general, for the reason, that, during the later periods of lactation properly so-called, granulated bodies are no longer met with. It is, how- ever, unquestionable, that between the earlier formation of colostrum-corpuscles and the later one of milk, there is no other difference than this, that in the formation of colostrum the process goes on more slowly, and that the cells maintain their cohesion longer, whilst in the secre- tion of milk the process is acute and the cells more speedily perish. Perfectly developed colostrum con- tains an extremely large number of granulated cor- puscles, milk nothing more than a number of compara- tively large and small drops of fat, mixed up together, the so-called mulk-corpuscles (Fig. 112, B), which are nothing more than drops of fat, and like the majority of the drops of fat that occur in the animal body are sur- rounded by a delicate, albuminous membrane, called by Ascherson the haptogenic* membrane (haptogenmem- bran). But the individual drops (milk-corpuscles) cor- respond to the drops which we find in the secretion of * J. e., produced by contact.—TRansL. 378 LECTURE XV. sebaceous matter ; they are produced by the « alescence of the minute granules which appear in the secretion of colostrum. Now that we have seen these types of physiological transformation, gentlemen, the description of the patho- logical changes no longer offers any difficulty. With the exception of very few structures, as for example, red blood-corpuscles and the nerve-fibres in the great nervous centres, nearly all other cellular parts may under certain circumstances undergo a similar metamor- phosis, which displays itself in a precisely similar man- ner, that is, isolated, extremely minute globules of fat appear in the cell-contents, become more abundant, and gradually fill up the cell-cavity, without, however, run- ning together into such large drops, as is the case in fatty infiltration and in the adipose-tissue formations. Usually, the development of the fat-granules first de- clares itself at some distance from the nucleus; very seldom does it begin at the nucleus. This is the cell which has long been called the granule-cell. Then comes a stage, in which the nucleus and membrane are indeed still to be seen, but the fat-granules lie as close to one another as in colostrum corpuscles ; only at the spot where the nucleus lay, there is still a little gap (Fig. 66, 0). From this stage there is but a short step to the complete destruction of the cell. For a cell never remains for any length of time in the state of a granule-cell, but as soon as it has once entered into this stage, the nucleus generally disappears at once, and ultimately the membrane also, probably by a species of solution. Then we have the simple granule-globule, or as it was formerly called, «nflammatory globule [exudation- corpuscle], which Gluge first described under this name (Fig, 66, @). Gluge in this made one of those mistakes which not GRANULE-CELLS—G LOBULES, 379 unfrequently marked the early periods of microscopy. He saw, when examining a kidney, bodies of this sort in the interior of a canal, which he took for a blood- vessel ; this happening at a time when the doctrine of stasis was most in vogue, he imagined he had before him a vessel with stagnating contents which were disin- tegrating, and generating inflammatory globules. Un- fortunately the blood-vessel was a uriniferous tubule ; what he took to be parts of disintegrating blood-corpu- scles, was fat; and what he called inflammatory glo- bules, fatty degenerated renal epithelium. One might easily have spared oneself this error in the history of stasis, but atethat time there were few people who knew what was the appearance of uriniferous tubules and how they might be distinguished from vessels, and thus some time elapsed before this theory of inflammation was put down. At present we call the body a granule-globule and regard it as the first distinct proof of degeneration, when the cell no longer retains its existence as a cell, but merely its former shape remains, after the parts which really constitute a cell, namely the membrane and the nucleus, have completely passed away. After this, in accordance with external circumstances, either a com- plete destruction of the parts ensues, or they may still persist, coherent. If, namely, we have to deal with very soft parts, in which much fluid or juice has been present all along, the granules fall asunder. The medium which bound them together and enabled them to retain the globular fortt, namely, a remnant of the old cell- contents, is gradually dissolved. The globule breaks up into a crumbling mass, which is often still somewhat co- herent in places, but from which one drop of fat after another is detached, so that the correspondence with milk is very beautifully displayed. 380 LECTURE XV. This is the manner in which the disintegration of nearly all parts takes place, which essentially consist of cells and naturally contain a good deal of fluid, as for example pus among familiar pathological products (p. 216, Fig. 66). If, on the contrary, the parts are in themselves somewhat more rigid, so that movement in and displacement of, the fatty mass takes place with less facility, the fat remains in the form of the previous cell. Of this we meet with an example in the fatty degenera- tion of the walls of arteries. In the aorta, the carotids and the cerebral arteries, changes of the inner coat are often seen with the naked eye of such a nature, that small, whitish spots of a rounded or angular form, occasionally running one into the other, project somewhat above the surface. If an incision is made at these spots, it is found that they are quite superficial, that they lie in the innermost layer of the internal coat and must not be confounded with the really atheromatous condition. If such-.a spot be cut out, it is found that a fatty degeneration of the connective-tissue-corpuscles of the innermost coat has taken place; and since they are branched cells, we do not here have granule-cells in their ordinary rounded form, but often very long, fine bodies, which here and there swell up into the form of a spindle or star, and in which the fat-granules lie heaped up like strings of pearls, whilst between there still remains intermediate substance quite intact. It is the cellular elements of the connective tissue which in these cases undergo the change in their totality. Afterwards the intermediate substance also softens, the cellular fat-granule masses fall asunder, and the current of blood carries away the particles of fat with it. In this way a number of un- even places are produced upon the surface of the vessel, which swell up as long as the process continues, after- FATTY METAMORPHOSIS. 381 wards become worn away (usurirt), and acquire a slightly velvety appearance, without there being any ulceration Fie. 113, in the proper sense of the word. This is a particular form of fatty usure which occurs in many parts, as for example in articular cartilages, and even on the surface of mucous membranes, for example, that of the stomach (Fox). But at no time does the matter accumulate in such abundance as is the case in abcesses which have undergone fatty degeneration. If, on the other hand, a similar process commences beneath the surface, as in the atheromatous process, the fatty degeneration then proceeds from below upwards, and the surface is not reached until the last. By softening, the so-called athe- romatous deposit (Heerd*) is produced, which contains a softened mass resembling the contents of atheromata [sebaceous,} or epidermic, cysts] of the skin, in which Fig. 113. Fatty degeneration of cerebral arteries. A. Fatty metamorphosis of the muscular cells of the circular-fibre coat. £2. Formation of fat-granule cells in the connective-tissue-corpuscles of the internal coat. 300 diameters. ~ Heerd (hearth) in the sense in which it is here employed, has no precise equiva- lent in English, although it exactly corresponds to the French foyer. ‘‘ It denotes,” says the Author, ‘‘ the spot, where the fire of the disease burns, but expresses at the same time that this spot is a limited one.” I have therefore translated it by various words, such as deposit, dépdt, seat (of the disease), collection, patch (atheromatous), focus, &¢.—TRansL. + These cysts are wrongly called sebaceous, inasmuch as they are essentially epidermic, and are generally derived, not from the sebaceous glands, but from the hair-follicles. The atheromatous matter is in these cases chiefly composed of degene- rated and disintegrated epithelium.—From a MS. Note by the Author. 389 LECTURE XV. the mixture of sebaceous matter and epidermis pro- duces a pultaceous mass. What we find in the arteries is a mixture of fatty débris with softened intermediate substance ; and, since the fatty mass is shut off, a kind of enclosed deposit results—as it were an abscess. It is only after the softening has proceeded to some extent that the surface gives way, and matters issue from the cavity into the vessel, whilst others proceed from the blood into the cavity. In this manner destruction, demolition, ulceration is produced, and ultimately the atheromatous ulcer, a species of ulcer very nearly allied to the ordinary forms of ul- ceration, but indebted for its origin to fatty metamor- phosis alone. It is a product of the [atheromatous] deposit, but it no longer contains any formed elementary parts. Cholestearine indeed may still be set free, but we have really and truly to deal with a destructive and ultimately ulcerative process. It is only in those parts, in which, as in the mammary and sebaceous glands, there is a succession of new cells, that the process of fatty metamorphosis can continue for any length of time without leading to such an annihilating result. But, even in these instances, the different cells affected ulti- mately perish and break up, as in the really fatty de- generation. LEO U Eh Xx ¥ L. APRIL 14, 1858. A MORE PRECISE ACCOUNT OF FATTY METAMORPHOSIS. Fatty degeneration of muscles—Fatty metamorphosis of the substance of the heart —Formation of fat in the muscles in distortions. Corpus luteum of the ovary—Fatty metamorphosis of pulmonary epithelium—Yel low softening of the brain—Arcus senilis. Optical properties of fattily degenerated tissues—Renal epithelium in Bright’s dis- ease—Successive stages (cloudy swelling, fatty metamorphosis, fatty detritus [débris], atrophy)—Inflammatory globules—Similarity of the result in inflam- matory and non-inflammatory changes. Atheromatous process in arteries—Its relation to ossification—Inflammatory cha- racter of the process; its analogy with endocarditis—Formation of the athe- romatous deposit—A ppearance of cholestearine—Arterio-sclerosis—Endoarte- ritis—Calcification and ossification of arteries. Mixed, activo-passive processes. To-pay, gentlemen, I have sent round afew specimens of fatty degenerations, in part to serve as a supplement to what you saw at the last lecture. One or two of these preparations are intended to dis- play the fatty degeneration of the substance of the heart. You will observe that, even with the naked eye, certain changes can be recognized in the heart, namely, a disco- loration of its whole substance (which no longer presents the red hue of muscle, but wears a pale yellow tint), and besides peculiar spots on the papillary muscles. If you examine these more closely, you will perceive, in the direction of the primitive fasciculi, short, yellowish 883 384 LECTURE XVI. streaks which communicate so as almost to present a plexiform arrangement, and pervade the substance of the papillary muscles, whilst they offer a striking contrast to the reddish colour of proper muscular substance. This is the perfect form of genuine fatty metamosphoris of the real muscular substance of the heart, which differs most essentially from obesity of the heart, in which this organ becomes extremely fat and adipose tissue here and there so infiltrates its walls, that scarcely any muscle is to be perceived. Be- tween the two conditions there always remains the notable diffe- rence, that in the former case whole portions of active substance’ are interrupted by parts which are manifestly no longer capable of action. I have besides brought you another specimen of mus- cle we obtained yesterday at the suggestion of our con- frtre Berend. A body, namely, with posterior (angular) and lateral curvature (Kypho-Skoliose) was brought for post-mortem examination, and, when we examined the muscles at the point of curvature, we found the longissi- mus dorsi at the spot where it passed over the projec- tion, converted into quite a flat, thin, pale yellowish mass. At one point the muscle has, with the exception of a membranous layer, entirely disappeared, its red hue has altogether vanished ; towards the lower part the muscle also presents an abnormal appearance, but there it is composed of alternate longitudinal red and yellow streaks. This is the form exhibited by most fattily de- generated muscles which we find in distortions of the * Fig. 114. Fatty degeneration of the muscular substance of the heart in its dif- ferent stages. 300 diameters. Fie. 114. FATTY DEGENERATION OF MUSCLES. 885 limbs, as for example, in the different kinds of club-foot. In these it generally turns out, that, in the parts corres- ponding to the yellow streaks, there is not only a real transformation of the muscular substance, but that an in- terstitial development of adipose tissue has also nearly constantly taken place there, so that it lies in rows be- tween the primitive muscular fasciculi, and thereby pro- duces a striation which looks yellowish to the naked eye, and is due to an arrangement very similar to that which gives rise to the red striation of genuine muscular tissue.* This is precisely how matters stood in the case I spoke of recently (p. 364, Fig. 108), where we found a row of fat-cells between every two primitive fasciculi ; the yel- low that you saw there, was not altered muscle, but a mass of fat which had grown in between the muscular fibres. But in addition to such interstitial adipose tissue there is in the case now before us a parenchymatous de- generation in the same muscle ; the substance of the mus- cle is also really in a state of fatty degeneration. The degenerated fibres are, however, only to be seen with the naked eye in the lower parts of the muscle, whilst the portion which lay in immediate contact with the greatest projection of the thorax and had been subjected to the greatest tension, to the naked eye presents no trace of muscular tissue. Under the microscope, how- ever, we even there find isolated muscular fibres lying close to one another and still distinctly transversely stri- ated, and others plentifully filled with fat. You see, therefore, that these are two different conditions ; the one form, where the muscle is interrupted in the course of its primitive fasciculi by degenerated places, and where * For, aseach row of fat-cells lies between two primitive fasciculi (Fig. 108), the fat (like the substance of the fasciculi, the cyntonine) has a layer of sarcolemma upon each side of it, so that, if the syntonine atrophies, the fat appears to have taken ity place and to lie wéthén the primitive fasciculi, and many well known au- thors have taken this to be the case.—From a MS. Note by the Author. 25 386 LECTURE XVI. therefore the same primitive fasciculus, is, as it pursues its course, now in a state of degeneration, now preserved in all its integrity ; the other form in which the disease sweeps along the primitive fasciculus, and this undergoes the change in its whole extent at once, and where there- fore normal and degenerated fasciculi lie side by side, and may alternate with one another, Here is another specimen from a young female (who died shortly after menstruation in consequence of a burn) in which you will find a very beautiful corpus luteum in the ovary. I lay it before you because you will be able to see, from it, how obviously fatty metamorphosis may display itself to the unaided eye. The incision into the ovary has been made perpendicularly to the surface, at a point where a little prominence and slight rent upon the surface mark the place at which the ovule has emerged (Fig. 115, B). From the point in the tunica albuginea where the follicle has burst, the very broad, yellowish Fie. 115. white layer (Fig. 115, A, 4), from which the body derives its name, is seen running around a red mass. It is this Fig. 115. Formation of corpora lutea in the human ovary. A. Section of an ovary: a, a follicle recently burst and filled with coagulated blood (extravasation, thrombus), and around it the thin yellow layer; 6, a follicle, which had burst at an earlier period, already corrugated, and provided with a diminished thrombus and thickened wall; ¢, d a still more advanced stage of retrogressive metamorphosis. B. External surface of the ovary, with the fresh rent caused by the bursting of the follicle, from the cavity of which the thrombus is seen peeping out. Natural size. FATTY METAMORPHOSIS OF PULMONARY EPITHELIUM. 3887 layer which, in a puerperal corpus luteum, is of very great breadth and has a rather reddish yellow tint; ina menstrual corpus luteum it is narrower, and very dis- tinctly separated on the inner: side from the freshly ex- travasated contents which have filled up the follicle emp- tied by the extrusion of the ovule. This internal red mass consists entirely of thrombus, or blood-clot. The external layer essentially consists of fattily degenerated cells, and the yellow colour which it bears is occasioned by the refraction produced by the numerous minute par- ticles of fat. This is not a real colour, but a phenome- non of interference. - A similar change you see in a lung which we took to- day out of the body of a man who, after caries of the in- ternal ear, had a thrombosis of the transverse sinus with gangrenous metamorphosis, and, in consequence, gan- grene of the lung. The cells we have here to deal with were not taken, however, from the actual seat of the gan- grene itself, but from a condensed spot in the neighbour- hood, where a very abundant accumulation of masses of proliferating epithelium (catarrhal pneumonia) had taken place. In this case you can see the difference between fat-granule-cells (Fig. 66), and other forms of granule- cells, very prettily shown. For in these masses of epi- thelium which have filled up the alveoli of the lung, you find extremely numerous pigment-cells, such as in cases like this are brought up in great quantity in the sputa, which are indebted to them for the well-known smoky grey spots (Fig. 11, 6). At first sight it is difficult to make a distinction between fat-granule-, and pigment- cells, inasmuch as in both cases apparently the same image is offered to our view. In the one case the cells appear as brownish yellow corpuscles, although their indi- vidual particles have no positive colour ; in the other, on the contrary, they contain unquestionable, grey, brown, 388 LECTURE XVI. or black, pigment. The diagnosis of ordinary granule- cells, by which fat-granule-cells are always meant, is, however, very important, because in other parts also, as for example, in the brain, we find both sorts of granule- cells, those containing fat and those containing pigment, side by side ; and even when the affection is limited to very small spots in this organ, it is very important* for the interpretation of the objects found to know whether they belong to the one or the other class. For in the brain also the accumulation of a number of minute par- ticles of fat may on the whole, through the multiplication of the refracting points, occasion an intense yellow colour. The different proportion of fat and the degree of its divi- sion produce a greater number of varieties of colour which at last manifest themselves very distinctly to the naked eye, so that the more minute and the more closely ag- gregated the fatty particles are, the more marked is the production of a pure yellow or brownish-yellow hue even to the naked eye. What we call yellow softening of the brain is also really nothing more than a form of fatty de- generation, where the yellow appearance of the affected spot is owing to the accumulation of finely granular fat. As soon as this is removed, the colour also disappears, although the fat thus extracted is by no means of so deep a hue as the spot whence it was derived. The refraction of light between the extremely minute particles is the chief cause of this phenomenon of colour. It is self-evident that at every point, where the fatty degeneration attains a high pitch, great opacity will always present itself. A transparent part becomes opaque when it undergoes fatty degeneration ; this we see, for example, in the cornea, the fatty clouding of which may become so marked in arcus senilis, that an en- * Eor the pigment would point to apoplexy, the fat to softening FATTY DEGENERATION OF RENAL EPITHELIUM. 889 tirely opaque zone is thereby produced. Even in places, where the parts were originally not transparent, but only translucent, a complete opacity may be seen to de- clare itself in proportion as the process of fatty degene- ration progresses. Consider, for example, a kidney in the stage of fatty degeneration. I show you here a preparation which does not present the ordinary granular atrophy of Bright’s disease, but a more chronic and smooth form. The convoluted uriniferous tubules of the cortex are very much enlarged, and the whole of its epithelium is in a state of fatty degeneration, so that within the tu- bules there is really nothing else to be seen than a densely crowded mass of fat-granules. If however microscopical sections are very carefully prepared, the fat-granules are in the first instance still seen collected in isolated groups (as granule-cells or granule-globules, Fig. 98) ; but upon slight pressure the mass disperses in such a way, that the whole uriniferous tubule is uni- formly filled with finely emulsive contents. Even with the naked eye you can distinctly recognize the change ; and as soon as one has become accustomed to discri- minate with some degree of accuracy between these less obvious conditions, there is not the slightest diffi- culty in discovering from the aspect of such a part the presence of a change in the renal epithelium, and that indeed of this particular kind, for there is no other form of change which could be compared to it. If you examine the surface of the kidney you will perceive that over the rather greyish, transculent ground, upon which the Stellule Verheynii* stand out, small opaque spots are scatterred in the most varied manner, most of them forming not real points, but usually small segments of an arc. These will always be found to be parts of \ * The stellate veins, —TRaNsL, 390 LECTURE XVI. the convolutions of uriniferous tubules wlich have mounted up to the surface. These yellowish, opaque- looking convolutions correspond to fattily degenerated uriniferous tubules, or to speak more accurately, to uriniferous tubules filled with fattily degenerated epithe- lium. If a section be compared with the surface, the same markings are very distinctly seen to run through the whole of the cortex, from the periphery down to the upper borders of the medullary cones, and to invest the individual cones formed by the tubuli recti which are prolonged into the cortical substance—at pretty regular intervals. If sections are made in such a case in the neighbour- hood of the surface and parallel to it, we readily obtain a view embracing the fattily degenerated tubules by the side of more normal ones, and of unaffected glomeruli. With a lower power and by transmitted light, we see close to the Malpighian bodies which appear as large, light, globular structures, the convolutions of the de- generated uriniferous tubules interlacing in various ways, and the convoluted tubules distinguished by their opaque, shaded appearance from the straight ones, which are lighter and more translucent. I will here call your attention to the circumstance, that in all fatty parts, where, by reflected light and as we usually view objects with the naked eye, we see whitish, yellowish, or brownish-yellow parts—by transmitted light, as generally employed for microscopes, and espe- cially with the higher powers, either black, or brownish black, or at least very dark parts, surrounded by sharply-defined shadows, appear. A granule-globule which, when lying together with several others, pro- duces a spot white and opaque to the naked eye, will, when viewed by transmitted light, display a nearly black appearance. ‘ GENUINE FATTY METAMORPHOSIS. 391 We have now compared a series of examples of fatty degeneration, and may henceforth confine ourselves to the consideration of genuine fatty metamorphosis, in which the normal structure of the part is ultimately destroyed, and the place of the histological elements is gradually occupied by a purely emulsive mass, or, more concisely, fatty debris. It makes no difference whether it is a pus-cell, a connective-tissue-corpuscle, a nerve- or muscular fibre, or a vessel which experiences the change ; the result is always the same; namely, milky débris. an amorphous accumulation of fatty particles in a more or less highly albuminous fluid. But though we hold to the agreement of all cases of fatty metamorphosis in this respect, it by no means, however, follows that the importance of this change as a morbid process is in every case the same. This you may at once infer from the circumstance, that, whilst I have introduced this process to your notice in the category of purely passive disturbances, one of the very structures which we most frequently find in it, the granule-globule, has been re- garded as a specific element of inflammation. For years an inflammatory globule [exudation corpuscle] was looked upon as an essential phenomenon in the process of inflammation, and in fact, the frequency with which cells in a state of fatty degeneration are found in inflamed parts, affords sufficient proof, that in the course of inflammatory processes, which it is impossible we should ever regard as simply passive processes, such transformations must take place. It is therefore very essential to find a means of distinguishing between the two classes. This offers indeed in particular cases very great difficulties, and according to my conviction the only possible method by which clear notions upon the subject can be obtained, consists in examining whether the condition of fatty degeneration is a primary or se- 392 LECTURE XVI. condary one, whether it sets in as soon as the distur. bance can be perceived, or whether it does not occur until some other perceptible disturbance has gone before. Secondary fatty degeneration, or that in which this peculiar transformation occurs only in the second place, generally succeeds to a first and active stage; a whole series of those processes which we do not scruple to call inflammations run their course in such a way, that a fatty metamorphosis sets in as the second or third ana- tomical stage of the change. Here therefore the fatty degeneration does not arise as a direct result of the irritation of the part, but where we have the opportu- nity of more accurately tracing the history of the changes, it nearly always turns out, that the stage of fatty degeneration has been preceded by another stage, namely that of cloudy swelling, in which the parts enlarge and increase in extent and density, in conse- quence of their absorbing a large quantity of matter into themselves. Absorbing 1 say advisedly, because I hold it to be untrue that the part is in any way forced by external influences to take up this matter, or that it is inundated with exudation proceeding from the vessels, for the same phenomena present themselves also in parts which have no vessels. It is only when the ac- cumulation has attained such dimensions, that the natural constitution of the part is thereby endangered, that a fatty disintegration is set up in the interior of the elements. Thus we may designate fatty degenera- tion of the renal epithelium as a stage of Bright’s dis- ease (or as I say, parenchymatous nephritis), which has been preceded by a stage of hyperemia and swelling, in which every epithelial cell accumulated a large quantity of cloudy matter in itself, without there having been originally a trace of a drop of fat observable. Thus we see that a muscle under the influence of INFLAMMATORY FATTY DEGENERATION, 893 agencies which it is universally conceded produce in- flanmation, as for example after wounds, and chemical corrosions, swells up, that its primitive fasciculi become broader and more clouded, and that as a second stage the same fatty degeneration commences in them, which at other times we see primarily arise. It may therefore certainly, when quite general terms are used, be said, that there does exist an inflammatory form of fatty degeneration ; still, strictly speaking, this inflammatory form is never anything more than a later stage, a termination, which announces the commencing disintegration of the structure of the tissue, when the part is no longer in a condition to continue a separate existence, but is to such an extent abandoned to the play of the chemical forces of its constituent parts, that the next result is its really complete dissolution. Now inflammatory conditions of this kind are of very great importance, because in all parts whose essential ele- ments become changed in this manner, no immediate restitution is possible. When inflammation takes place in a muscle and in its course the primitive muscu- lar fasciculi fall into a state of fatty degeneration, as a rule they also perish, and we afterwards find a loss of substance in the muscle at the spot where the degenera- tion took place. The kidney, whose epithelium has passed into a state of fatty degeneration, nearly always shrivels up, and the result is a permanent atrophy. In exceptional cases something perhaps occurs, which reminds us of a regeneration of the epithelium, but usually a collapse of the entire structure ensues. The same thing is witnessed in the brain in yellow softening, no matter how it may have been caused. Whether there have been inflammation or not, a va- cuity is formed, which is never again filled up with nervous matter. Perhaps a simple fluid may replace 394. LECTURE XVI. the wanting tissues, but as to any repri duction of a new, functionally active part, that must ever be out of the question. Herein you must seek the explanation of the circum- stance, that conditions apparently very similar, and which from a_pathologico-anatomical point of view might be declared to be identical, in a clinical point of view lie widely apart, and that the same forms of changes are met with in analogous parts, without, how- ever the whole process, to which they belong, being the same. When a muscle falls into a state of simple fatty degeneration, its primitive muscular fasciculi may have just the same appearance as if inflammation or perma- nent tension had acted upon it. Myocarditis generates forms of fatty degeneration in the substance of the heart altogether analogous to those due to excessive dilatation of the cardiac cavities. When one of these, for example, either through some obstruction to the current of the blood, or from insufficiency of the valves, is per- manently much dilated, fatty degeneration of the muscu- lar tissue constantly manifests itself in the part which has been most stretched. This form, morphologically speaking, completely resembles the early stages of my- ocarditis, and in many cases it is utterly impossible to say with certainty in what way the process may have arisen. I have, in order to clear up to some extent these difli- culties, as they are presented by an important, frequent and at the same time much misunderstood process, pre- pared a series of specimens exhibiting really atheromatous conditions of the arteries. For it is particularly in the case of these conditions that the confusion, which has pre- vailed with regard to the interpretation of the change, has perhaps been the greatest. At no period in the course of this century has a com- ATHEROMATOUS AFFECTION OF ARTERIES. 895 plete understanding ever been come to as to what was to be understood by the expression atheromatous change in a vessel. Some have taken the term in a wider, others in a narrower sense, but still it has perhaps been taken in too wide a sense by all. When, namely, the anato- mists of the last century applied the name of atheroma to a definite change in the coats of arteries, they of course had in their minds a condition similar to that of the skin, to which ever since the days of ancient Greece, the name of atheroma, grit-follicle, (Griitzbalg) [sebace- ous or epidermic cyst], had been assigned. It is self- evident, therefore, that the idea of atheroma presupposes a closed sack. Nobody ever called anything in the skin an atheroma that lay open and uncovered. It was there- fore a curious misapprehension when people recently be- gan to call changes in the vessels atheromata, which were not seated below the surface and shut off from the sur- rounding parts, but belonged to the surface. Thus it has come to pass that, instead of an enclosed deposit being, in accordance with the original meaning of the term, called atheromatous, a change has frequently been so termed which commences quite at the surface of the in- ternal arterial coat. When the matter began to be exa- mined more minutely, and fatty particles (Fig.113) were found at very different points in the walls of the vessels, both when atheroma was, and was not, present—when at last the conviction was obtained, that the process of fatty degeneration was always the same and was identi- eal with the atheromatous change, it became the custom to unite all the forms of the fatty degeneration of arte- ries under the designation atheroma. Gradually, peo- ple even came to speak of an atheromatous change in vessels, that only possessed a single coat, for in them too we meet with fatty processes. At all times there have moreover been observers who 396 LECTURE XVI. regarded the ossification of vessels as a change belonging to the same category as atheroma. Haller and Crell be- lieved that the ossification proceeded from the athero- matous matter, and that this was a juice which, like that exuding under the periosteum of bone, was capable of generating plates of bone out of itself. Afterwards it was recognized that atheromasia and ossification were two parallel processes, which, however, might be referred to a common origin. Now it would, I think, have been logical, if in the next place an understanding had been come to as to what this origin was, from which the athe- romatous change and the ossification proceeded. But, instead of this, the track of fatty degeneration was pur- sued, and thus the atheromatous process was extended to a number of vessels, in which, on account of the thin- ness and the simple structure of their walls, the forma- tion of any dépdt, which could really be compared to-an atheromatous cyst of the skin, was altogether impossible. The state of the matter here also is more or less very simply this, that two processes must be distinguished in the vessels, which are very analogous in their ultimate results ; first, the semple fatty metamorphosis, which sets in without any discoverable preliminary stage, and in which the existing histological elements pass directly into astate of fatty degeneration and are destroyed, so that a larger or smaller proportion of the constituents of the walls of the vessel perishes; and, in the next place, a second series of changes, in which we can distinguish @ stage of irritation preceding the fatty metamorphosis, comparable to the stage of swelling, cloudiness, and en- largement which we see in other inflamed parts. I have therefore felt no hesitation in siding with the old view in this matter, and in admitting an inflammation of the in- ner arterial coat to be the starting point of the so-called atheromatous degeneration ; and I have moreover en- THE ATHEROMATOUS PROCESS. 397 deavoured to show that this kind of inflammatory affec- tion of the arterial coat, is in point of fact exactly the same as what is universally termed endocarditis, when it occurs in the parietes of the heart. There is no other difference between the two processes than that the one more frequently runs an acute, the other a chronic, course. By the establishment of this distinction between the different processes which occur in the arteries, the differ- ence of the course they pursue is at once accounted for. Last time I laid an artery before you, on the inner sur- face of which you saw little whitish patches, which were due to simple fatty transformation. To-day you see very extensive patches in the aorta, in which the atheromatous change has taken place. But, as is wont to be the case in changes of this kind, in addition to the specific trans- formation attendant upon the chronic inflammatory pro- cesses going on in the deeper parts, you find on the sur- face also a simply fatty change, so that we have the two processes occurring together. If now we examine athe- romasia a little more minutely, for example in the aorta, where the process is the most common, the first thing we see present itself at the spot where the irritation has taken place, isa swelling of larger or smaller size and not unfre- quently so large as to form a really hump-like projection (Buckel) above the level of the internal surface. These projections are distinguished from the neighbouring parts by their translucent, cornea-like appearance. In their deeper parts they look more opaque. When the change has lasted for a certain time, the first further metamor- phoses do not show themselves at the surface, but just where the internal comes into contact with the middle coat as has been very well described by the old writers. How often have they distinctly contended that the internal coat could be stripped off over the affected spot! 398 LECTURE XVI. Hence arose the description of Haller, that the pultace- ous, atheromatous mass lay in a close cavity, as it were a little cystic tumour between the internal and middle coat. The only mistake was, that the tumour was re- garded as a distinct body separable from the coats of the vessels. It is rather the internal coat itself which without any well defined limits passes into a state of degeneration within the prominent spot. The farther this degeneration advances, the more distinctly does an enclosed collec- tion arise out of the destruction of the deepest layers of the internal coat ; and at last it may be that the swelling fluctuates, and that upon cutting into it the pultaceous matter is evacuated, like the pus, when an abscess is cut into. Now if the mass be examined which is present at Fie. 116, Fig. 116. Vertical section through the walls of the aorta at a sclerotic part in which atheromatous matter is already in the course of formation. m m'. Middle coat, ¢ 7’ 2”, internal coat. At s the highest point of the sclerotic part where it pro- jects into the cavity of the vessel, i the innermost layer of the internal coat running over the whole dépét, ’ the proliferating, sclerosing layer, preparing for fatty dege- neration, 2” the layer immediately adjoining the middle coat which has already un- dergone fatty degeneration, and at e, e, is in process of direct softening. ATHEROMATOUS DEPOSITS IN ARTERIES. 899 the close of this process, numerous plates of cholestea- rine are seen, which display themselves even to the naked eye as glistening lamelle ; large rhombic tablets, which lie together in large numbers, side by side, or covering one another, and altogether produce a glittering reflec- tion. In addition to these plates, we find under the microscope black-looking granule-globules, in which the individual fat-granules are at first very minute. These globules are often present in very large quantity ; some of Eid, 117, them are seen, breaking up, and falling to pieces, parti- cles of them swimming about, as in milk. Besides these there are amorphous _frag- ments of tissue of larger or smaller size which still cohere, and are rather due to the soft- ening of the rest of the sub- stance of the tissue which has not undergone fatty degeneration ; and in them heaps of granules are here and there imbedded. Jt is these three constituents together, the cholestearine, the granule- cells and fat-granules, and finally the large lumps of half- softened substance, which give the atheromatous matter its pultaceous character, and really produce a certain degree of resemblance to the contents of a pultaceous [sebace- ous, epidermic] cyst (Griitzbeutel) of the skin. With regard to the cholestearine, it is by no means a specific product, appertaining to this kind of fatty transforma- Fig. 117. The pultaceous atheromatous matter from a patch in the aorta. aa’. Fluid fat, the product of the fatty metamorphosis of the cells of the internal coat (qa), which become transformed into granule-globules (u’ a’), then disintegrate and set free large and small drops of oil (fatty débris). 6. Amorphous, granularly-wrinkled flakes of tissue softened and swollen by imbibition. ¢, ¢’. Crystals of cholestea- rine; ¢ large rhombic plates; c, c’ fine rhombic needles. 300 diameters, 400 LECTURE XVI. tion alone. On the contrary, we see in every case, where fatty products remain stagnant for a considerable time within a closed cavity in which but. little inter- change of matter can go on, that the fat sets free cho- lestearine. All the masses of fat which we meet with in the body contain a certain quantity of cholestearine in combination. As to whether the cholestearine which — is set free had already previously existed, or whether a real new formation of it takes place in the parts, not a word can as yet be said, inasmuch as no chemical fact has, it is well known, been made out, which throws any light upon the manner in which the formation of cholestearine is effected, or upon the substances, out of. — which cholestearine may be formed. This much, how- ever, we must hold fast, that cholestearine is a product set free at a late period from stagnating, and, particularly, from fatty matters. I may take this opportunity to mention the reaction of cholestearine with iodine and sulphuric acid, which has recently become important, and is similar to that which we have already (p. 31) considered when speak- ing of the cellulose of plants. When, namely, iodine alone is added to cholestearine, no change is seen any more than in cellulose, under similar circumstances ; but when, on the other hand, sulphuric acid is applied to the iodized mass of cholestearine, its plates become coloured and assume, particularly at first, a brilliant indigo-blue tint, which gradually passes into a yellowish brown, until the cholestearine is converted into a brown- ish drop. Sulphuric acid alone produces a fatty-looking substance which is neither cholestearine, nor any special combination of cholestearine and sulphuric acid, but a product of the decomposition of the former. Sulphuric acid alone also produces very beautiful phenomena of colour with cholestearine. FORMATION OF ATHEROMA IN ARTERIES. 401 If now, gentlemen, we trace the development of the atheromatous condition a little further back, we come— anteriorly to the period when the pultaceous matter is found in the seat of the atheroma—across a stage, where nothing more is found than fatty degeneration in its ordinary form of granule-cells, and we distinctly con- vince ourselves, that the process in this stage absolutely differs in no respect from that which in the case of the heart and kidney we have just declared to constitute the stage of fatty metamorphosis. At this period, imme- diately before the formation of the dépdt, the state of matters, as seen with a high power, is about as follows. On making a section we see the fatty cells which are interspersed through the tissue becoming larger towards the middle and lying more closely together, but gene- Fig. 118. rally bearing the form of cells; but, as we proceed from within outwards they become smaller and less numerous. All these cells are filled with small, fatty granules which strongly reflect the light. Hereby is produced what looks to the eye in a section like a whitish spot. Between these fatty corpuscles runs a meshed Fig. 118. Vertical section from a sclerotic plate in the aorta (internal coat, inner surface) in process of fatty degeneration; ¢, the innermost part of the coat with round nuclei, isolated, and in groups of several (divided). A. The layer of en- larging cells; networks are seen with spindle-shaped cells which enclose sections of cells resembling those of cartilage. p. Proliferating layer; division of the nuclei and cells. a, a’. The layer which is becoming atheromatous; a, the com- mencement of the process, a’, the advanced stage of fatty degeneration. 300 diameters. 402 LECTURE XVI. basis-substance, the really fibrous stroma of the internal coat, which we plainly see continued towards the exte- rior into the normal internal coat. This fact, that we are able to acquire the direct conviction that the fibrous layer which lies over the dépdt, is continued into the fibrous layer of the neighbouring normal portions of the internal coat, is one of especial value in the interpretation of these processes. In this manner the view which was for a considerable time defended by Rokitansky also, that the affection consists in a deposit upon the internal coat, is refuted. In a vertical section it is distinctly seen that the most external layers run in a curve over the whole swelling and return into the internal coat, and the old writers were quite right when they said—speak- ing of a stage in which the formation of the athero- matous dépét had already made considerable progress— that the internal coat over the whole of the dépdt could be stripped off in a piece. On the other hand, however, we can convince ourselves, that the inferior layers of the internal coat run directly into the dépét, and that their continuity has been broken by their degeneration, so that we have not to deal either with an interjacent deposit (between the internal and middle coat), as the old writers supposed, but the whole of what we have before us is degenerated internal coat. In some particularly violent cases the softening mani- fests itself even in the arteries not as the consequence of a really fatty process, but as a direct product of inflammation. Whilst at the circumference a fatty softening takes place, in the centre of the seat of change a yellowish cloudy appearance is seen to arise, where- upon the substance almost immediately softens and dis- integrates, and a mass of coarse, crumbling fragments is found (Fig. 116, e, e) which fills the centre of the athe- romatous dépdt. SCLEROSIS AND OSSIFICATION OF ARTERIES, 403 In the last place, it is a question where the seat of the fatty degeneration really is. Here too again (as in the cornea) it may be imagined that the fat is deposited in spaces intervening between the lamellew ; and even now there are still a small number of histologists who will not admit, that connective tissue contains only cells, and no empty spaces. But if a section through one of these (atheromatous) patches be examined from below upwards, it is seen that the same structure which pre- sents itself in the fatty parts, shows itself also in the merely horny or half cartilaginous layers. Bands of fibres, in the intersections of which small lenticular cavities appear, are found there as they are also in the normal condition of the internal coat; but in the cavities and in the bands of fibres lie cellular elements (Fig. 118). The enlargement which the part undergoes in consequence of the process and which we call sclerosis, depends upon this; the cellular elements of the coat increase in size and a multiplication of their nuclei takes place, so that spaces are not unfrequently found in which whole heaps of nuclei are lying. This is the mode in which the process sets in. In many cases division occurs in the cells, and a great number of young cells are met with. These afterwards become the seat of the fatty degeneration (Fig. 118, a, a’), and then really perish. Thus we have here an active process, which really produces new tissues, but then hurries on to destruction in consequence of its own development. But one who knows that the fatty degeneration is here only a termination, and that the process is really a formative one, inasmuch as it begins with a proliferation —he can readily imagine the possibility of another ter- mination, namely ossefication. For here we have really to do with an ossification, and not merely, as has re- cently been maintained, with a mere calcification ; the 404. LECTURE XVI. plates, which pervade the inner wall of the vessel, are real plates of bone. Since they form out of the same sclerotic substance from which in other cases the fatty mass arises, and since a real tissue can only arise out of a pre-existing one, it follows of course that, when the process terminates in fatty metamorphosis, we cannot assume this to consist in a simple dissemination of fatty particles which has taken place in whatever interspaces we like to fix upon. The essential difference which exists in a large vessel, as for example, the aorta, between this process [athe- roma] and simple fatty degeneration is therefore this, that in the latter a very slight swelling arises on the surface of the internal coat, a swelling, which at once disappears if the superficial layers be removed by a horizontal section, and beneath which there still remains a portion of the coat unaltered. In the other case, on the contrary, we have in the extreme stage a dépét which lies deep beneath the comparatively normal sur- face, afterwards bursts, discharges its contents and forms the atheromatous ulcer. This commences as a small hole in the internal coat, through which the thick, viscous contents of the atheromatous dépdt are squeezed out on to the surface in the form of a plug; gradually more and more of these contents is evacuated and carried away by the stream of blood, until at last there remains a larger or smaller ulcer which may extend as far as the middle coat, and indeed not unfrequently involves it. We have therefore always to deal with serious disease of the vessel leading to just as destruc- tive results, as we see in the course of other violent inflammatory processes. You need only apply these observations to the history of endocarditis, and you will have a correct notion of all that goes on there also. In the valves of the heart also we find simple fatty ENDOCARDIAL EXCRESCENCES. 405 degeneration taking place both at the surface and deep beneath it. The process generally pursues its course so latently that no disturbance is perceptible during life, nor are we able, in the present state of our knowledge, to name any very obvious anatomical change as being the subsequent result of it. On the other hand, what we call endocarditis, what can be demonstrated to arise in the course of rheumatism, and may indubitably ap-: pear as a sort of equivalent to the rheumatism of the peripheral parts, begins with a swelling of the deceased spot zse/f. There is, namely, no exudation, but the cellular elements take up a greater quantity of material, and the spot becomes uneven and rugged. Then we see, when the process runs its course somewhat slowly, Fie. 119 either that an excrescence, a condyloma arises, or that the swelling assumes a more mammillated form, and af- terwards becomes the seat of a calcification which may produce real bone. If the process runs a more acute course, the result is either fatty degeneration or soften- ing. The latter gives rise to the ulcerative forms, in which the valves crumble to pieces, drop off, and em- Fig. 119. Condylomatous excrescences of the mitral valve; simple, granular swellings (granulations) and larger prominences (vegetations), some villous, others branched and putting forth secondary buds; in all elastic fibres running upwards, 40 diameters. 406 LECTURE XVi. bolical deposits are produced in remote parts (Fig. 73, p- 242).* Only in this manner, by observing, namely, the earli- est stages of the changes, is it possible to form certain and practically useful opinions with regard to pathologi- cal processes. Never ought one, basing one’s opinion ‘apon the difference of the processes in a clinical point of view, to allow oneself to be induced to regard their ultimate products as necessarily different. The most violent inflammatory processes which run their course in quite a short time, may have the same terminations as those which, in other cases, are brought about more slowly. It is not my intention to go through the series of the different passive disturbances which may possibly arise in the later stages of irritative conditions, in detail. Else we should be able to discover analogous instances in the history of nearly all degenerative atrophies. In all cases we must discriminate between the conditions in which a part becomes directly the seat of such a retro- erade metamorphosis, and those in which it previously underwent an active change. The description which I have given you of the fatty processes directly applies to the class of calczfications. If it be wished to discriminate between ossification and calcification, it is not sufficient to keep the ultimate re- sult in one’s eye. ack arya ta hs PERSE Wee SE ais) i i pete at heh re ea ee ee Se ¥ eect ike eae