enoanrr an - a 4,4 5 . *. z " ? - ry" . - - « ++) i?izs it me 9 oy | : ye: gh ‘ Li - Ps e\% ee! + +25 - : uf ‘ ? oe i 7A at be csi « . = +, 4/9 STE hy ? *. ty ba Soc tes, *+ - 6 e.° ° . ; , «7? ® . $91 i 7 7 ‘ - a! =a . oT - ,/@ * si %) H - ‘; e -* J » > -- ey i« ; * . iby St ry ae”, ; ° 1 * "9 ; - ° * ~ : t . ‘ * %, EE <7 ; °¢ \ Ho ; ‘ a =i) i " >. * - " % + - r r + * . * : e? + "> ; pare if 4 ad > rei ey . - ~ oe ts bi . 47 “1 ef 4 e ‘ a ir retht ty e ey’ * r , * . , ba - Te “ve LY * * . ate ia oLe ‘ ; . = +e! 4 « é °°? i “7 . > «,2.9 *. ’ : . ° f ° Pivejsteats iy » Beery ty Sf > fiiga ict P74 big Book SiG Cepprignee COPYRIGHT DEPOSIT: inet BOOK COMPARATIVE GENERAL PATHOLOGY FOR Practitioners and Students of Veterinary Medicine BY PROFESSOR DR: TH. KITT OF MUNICH Authorized Translation BY DR. WILLIAM W. CADBURY Assistant Demonstrator of Pathology in the University of Pennsylvania Edited with Notes and Additional Illustrations BY DR: ALLENS, SMITH Professor of Pathology in the University of Pennsylvania Illustrated with Four Colored Plates and One Hundred and Thirty-one Text Illustrations CHICAGO W.T. KBENER & CO. 1906 LIBRARY of CONGRESS Two Geples Received OCT 31 1906 | Copyrighted, 1906 By W. T. KgENER PREFACE TO GERMAN EDITION _ The introduction of students of veterinary medicine to the Study of pathology, because of the lack up to the present time of a German text book of general pathology adapted to diseases of animals, has depended chiefly upon works written for the practitioner of human medicine; the lectures of instructors in vet- erinary medicine and students’ notes, made with more or less accuracy, supplying the necessary additions and explanations. Only one work, the Text Book of General Pathological Anat- omy by Birch-Hirschfeld, has been amended from the standpoint of our special branch of medicine, by the addition of veterinary- medical paragraphs from the facile pen of Johne, so as to seem adapted for students in veterinary schools; but it is confined to pathological anatomy, and the physiological and etiological fea- tures, the manifestation of functional impairments, pathogenesis, etc., require further reference to special works. As an introduction atid foundation for appreciation of the practice of veterinary medicine, to be studied and put into applica- tion in the latter portions of the college curriculum, after com- pletion of the courses in anatomy, physiology and the natural sciences, the student should be given a general idea of the mean- ing of disease, the xtiology of diseases, of the make-up of our medical knowledge and of the principles of classification, as well as a general familiarity with the alterations in structure and func- tion met in disease. It is for this reason that lectures on general pathology are provided, introductory to the special applied branches of study. The need of a work concisely comprehending such features has determined me to undertake the task of pre- paring a condensed outline of the fundamental facts of pathology with special adaptations to the requirements of veterinarians. Of course, it has been necessary to make use of much material from works intended for the student of human medicine, and I am - vividly reminded of the old sentence in the Latin grammar—*‘‘Plinius 1V Preface to German Edition. nullum librum legit, ex quo non excerpserit.” I therefore ac- knowledge at the otitset and at various places in the text, that I have freely employed in the preparation of the following text- book the works of Ribbert, Perls, Krehl, Durk, Samuel, Thoma, Birsch-Hirschfeld, Johne, Uhle and Wagner, as it is in fact prac- tically impossible to write an authoritative work on general pathology without dependence upon other authors. The scientific development of veterinary medicine depends primarily upon the same principles which obtain in human med- icine. The propositions and methods of research which were originally employed in the study of human pathology, are for us, — too, ftindamentals for the appreciation and investigation of the nature of the animal’ diseases. Every new advance in human — medicine in the fields of anatomy, physiology, the use of the micro- scope, technique of clinical study, surgical and therapeutic meth- ods, bacteriological and practical hygiene, has been. of advantage to comparative medicine, and, mutatis mutandis, has found an application in veterinary practice, and has pointed out the way for advanced work in our own branch. There has been much as- sistance afforded, too, in the fact that many of the discoveries of value to human medicine have been made from experimental studies upon animals, and the principles of general pathology par- ticularly have been fundamentally proven by comparative study of the anatomy and physiology of animals; both branches of med- icine, therefore, drawing from the same sources and having a common field of work. | Apart from these considerations, however, the representatives of veterinary medicine have, by. their independent achievements, built up the pillars and walls of their own scientific temple, with such multiplicity of specialized purposes and requirements that the method and practice of veterinary medical instruction have come to have a peculiar character of their own. Consideration of these requirements is attempted in this volume. 3 It is well known to every teacher who is required to act as an examiner, how difficult it often is for thé candidates in an examination to express what they well know and how, no matter how clearly the questions may be presented, or what statements are made suggesting a proper answer, this or that really capable student finds himself forced to struggle with words and is handi- capped in expressing his ideas. In order to lessen these diffi- culties for students, I have endeavored to frame my definitions . Preface to German Edition, — Vv ,’ concisely, to present the positive facts in as clear and as brief a manner as possible, and to limit to what is absolutely essential the incomplete, uncertain and controversial points of ‘study, the elaborate discussion of which is usually confusing and tends to weary the student. Of course, important objections and ques- tioned points in theories have been noticed, lest the student be led to mere memorization and superficial study, and in order that he may be stimulated to think. I believe that the work will be found useful to the practising veterinarian as well, as a general presenta- tion of the most recent position of the science. I have omitted description of the individual types of animal parasites and bacteria and taken up only in this connection their bearings upon general pathology. The scope of the work wceuld otherwise have been too large; and full details upon these sub- jects may be found in the part devoted to special pathology (Lehrbuch der pathol. Anatomie der Haustiere. I1. Aufl. Igor. F, Enke, Stuttgart) and in my Lehrbuch der Bakterienkunde und pathol. Mikroskopie (IV. Aufl. M. Perles, Wien, 1903). The subject of malformations is also treated of at the beginning of the special section just mentioned, and a repetition is therefore super- fluous. The publisher has presented the volume in an excellence of style which places me under special obligation to him. Numerous new illustrations are included, prepared by the ar- tistic hand of K. Dirr; some of the cuts I have borrowed from the works of authors cited in the text. For a number of photo- graphs I must thank for their kindness the veterinary physicians Dr. Jakob and Dr. W. Ernst, the latter of whom, a skillful micro- scopist and bacteriologist, has been engaged for a number of years in my institution and has aided me in a most valuable man- ner in carrying on investigations bearing upon my studies. Munich. ‘FER oK ie PREFACE TO AMERICAN EDITION The work of translating and preparing for publication the following edition of Kitt’s General Pathology has been a pleasure, because of the real value of the work and because both editor and translator have believed the labor a service to the profession. As Professor Kitt states in the preface to the German edition, it is ‘practically the only work devoted to a discussion of general pathology from the standpoint of the veterinarian; and the need of such a work has long been manifest to every teacher of pathol- ogy in charge of students of veterinary medicine: The impres- sions given by any book upon pathology, even the best, which has been framed primarily for use in connection with human medicine, are often unfortunate from the inaptness of the descriptions of lesions for the needs of men studying comparative medicine. It is undoubtedly true that the general processes of disease are funda- mentally the same in whatever subject they occur; but the varieties of appearances of one and the same type of lesion in different species may well be sufficiently marked to make the descriptions based upon the changes met in any given animal confusing and perhaps inadequate for students, whose experience in the earlier years is anything but extensive. The differences, for example, in the appearances of a tuberculous caseated area in man, in the cow, hog, horse, or in carnivora, well illustrate the point in mind; or the differences in bulk and in other character- istics of various tumors as met in man and in the large domestic animals serve as an example. The adaptation of the present volume to the needs of students who, as Professor Kitt points out, have had to accept, as a rule, the descriptions of lesions as seen in man and then amend them by notes from lectures, has strongly appealed to us as instructors of veterinary students, and will find, we believe, an equal appreciation from others whose work has fallen in similar lines. The book reflects well the tendency of modern pathological Vill Preface to American Edition. teaching to devote considerable effort to direct the thought of the reader along lines of pathological physiology, to make the student reason for himself from given anatomical data and appearances as to the necessary functional faults and failures which would follow. Pathological anatomy is, of course, fundamental and finds its place on every page; but the author has had in mind the application of pathology to the living diseased animal, and the anatomical descriptions and discussions serve as a basis for explanation of the development of the processes and the func- tional faults the diseased animal must necessarily manifest. The chapters on disturbances of the circulatory, respiratory and other functions are, of course, brief, but they are by no means super- ficial and indicate well the lines of necessary study for the prac- ticing physician and are stimulative to thought on the part of the student. The value of such a work is-not confined to the veterinarian ; the intimate relations comparative pathology bears to the study of human medicine and the need that experimentalists should be in the best possible position to appreciate the reactions peculiar to various species of experiment animals require of pathologists broader and broader powers of recognition. Much of the criticism against animal experimentation has its only force in that in the hands of men unfamiliar with the animals utilized, both in their normal life and in their pathological reactions, the best results are not obtained, at least not. appreciated, by such workers in return for the sacrifice entailed. The best is accomplished, other things being equal, by men whose training comprehends a broad biological and physiological experience and who are familiar with the peculiarities of physiological reaction and anatomical changes to be met in the animals employed under the operation of given pathogenic influences. Such works as the present volume, intro- ductory to the fuller Special Pathology in the companion volumes of the German edition, have therefore a proper place on the shelves of every pathologist, whether his work deals with human or with comparative problems as its major field. In presenting the book to our English-speaking colleagues and students, the editor and translator have endeavored to follow closely Professor Kitt’s language, although no attempt to be abso- lutely literal in the translation has been made. Doubtless the effort to translate the German idiom to its English equivalent has often failed; and we both appreciate the fact that unwittingly the Preface to American Edition. ix verbiage of the translation has sometimes, in the endeavor to keep close to the original, come to be somewhat complicated for English text. The editorial notes, which are always enclosed in special brackets ([ |), have purposely been kept within brief limits, because of our realization of the sufficiency of the work for the introductory purposes for which it is intended by the author, and because of a desire to keep the size of the book near the limits of the original edition. We feel that for use at the hands of graduate physicians the book as it stands meets the purpose for which it was written; for student purposes, as a handbook as well as a general text, it would perhaps have been regarded as an advantage to have added descriptive matter to the tables of the vegetable and animal parasitic organisms and to have ex- panded the text somewhat in connection with minute anatomy, thus giving it a fuller adaptation to laboratory studies. A num- ber of illustrations have been generously added by the publishers with this latter view in mind. These illustrations, made by the well-known artist, Louis Schmidt, include figures 63, 82, 86, 80, Be eiGr. 102 103, 104, TIr and 125; and it is thought that the book, with such additions, will find a fuller place as an aid to the student in the laboratory of pathological histology. The publishers have not spared expense to make this work possible in the translated form, and by their interest have, we feel, placed the profession under obligations. For ourselves the venture is in no sense a financial one, and if others will find, as we hope, that our efforts have aided in pressing forward the general good for both veterinary and human medicine, our com- pensation will be ample. ALLEN J. SMITH. Witrt1rAM W. Capsury. September, 1906. - PARDEE Or CONTENTS LT BELTED, 8 gee 000 le Aa a eg ea Definition of Pathology; Conceptions of Disease; Pro- cesses of Disease. Ree BUDE ALU OLOGY oO ojos eel eA boc wasn b's ie bs ae apes Meee eiomes Loward: DISCASC.. 220552 b. doen cis ce eee dee see. Predisposition and Immunity; Defensive Mechanisms of the Body. Seuernical and Inherited Disease. ..... 26. ...0.5. 002s sane ees Placental, Intrauterine Origin of Disease; Germinal Variation; Germinative Predisposition; Hereditary Conditions. eee pEALOn ya JOISCUTDATICES loc) youve. c's sin» aapeherateoe Qe as emeecomvie Mt ItCiiOnale AUCLEVIbYiac. cor «. 0 x «os eve caue areca res retirees TG CIC OS osrsls, oy Ae, hale Pepe Suess es, 3 uc eee ee “ULL IN OSES, NSS ale a aad Pot Se eR Mreetiied | | VCCUCICS, 20/2 fey e ca Sto ++ 63.02 eee ee Mechanical and Traumatic ABENCIES. .... «Jake Coe ee eee dOle DONIC A SENTS ry on bo 50 cc... Sa wl ona ee Pmcwome Or Lnbectious Agents... ....... csv oe cee Mee Me CASTLE, Maids ss aye wie s basse «ss nS CR Geurse and Termination of Disease..............0.eecuavcee Symptoms, Diagnosis, Natural and Artificial Means of Recovery, Death. Srenlatory Disturbances.............-.--...ssreee. Rete ones isampances Ot, Cardiac. Fticlency: . Aman Civ oe eae Local Variations in Amount of Blood in a part (Hy- PeeOUNEL, See NTLNUUL TED ip wni'a’ gy, Deavre:'n sn cay via ON eaang a: ON Ogee Me 10 16 30 xii Table of Contents. PAGE Hemorrhage: 2 see eee, 2 alo 119 Dropsy .and »CMidenina terse Se ved tis Occlusion of Blood Vessels (Thrombosis and Embo- lism). ; 2.1 See eee oe ee ee 2 Alterations of the Blood (Plethora, the Anzmias, ~ Leukzertiia ) Sere kone Gee rn 156 Disturbances of Metabolism, Retrograde Changes and Necrotic Processes. oy peat ee ets aes ee 165 Disturbances of Heat Regulation, Overheating, Fever. 165 IN@CEOSI SI ain oe eee rer ee ns ooh gon Sen . ae Al ropliyetae pte erte 49x ton 2 pen 2. rr 185 Clouds, SS wellie. (2) Sepa d hs oe ae eo 190 The Wathy :s... .e a 205 Pigmentation. 34.220. een. BGS oe 209 Calcitheation and Concrement Formation. ....72.395ee 216 Processes of Repair and New Formation...:..:.... 25eee fo ae Regeneration... 6.2.24" evel si. s ante de Soe 222 Transplantation......20..222) . J 2. 22 ee 251 Elypetirophy. ; 2. an. ets oo. Dee 254 Inflammation: o........... 2.4. 3 ee 258 Tuberculosis: >. 5.3. . ..<.: 2 ee 291 “Glanderse aye Per rr ke: - iene ROD ActinNOMYyCOSISS! 2 2...... os. : he eee re 318 Botryoniycosiss.5.0 ..0..4:. (42. eee ‘i. ae 324 Tumors “(Autoblastomata). .:.-5225 =a. ee 225 Fibroma (p. 341)—Lipoma (p. 346)—Myxoma (p. 349)—Chondroma (p. 350)—Osteoma (p. 353)— Myoma (p. 356)—Neuroma, Glioma (p. 358)—Hem- angioma, Lymphangioma (p. 362)—Sarcoma (p. 365) —Lymphoma (p. 372)—Melanoma (p. 377)—Endo-, Peri-thelioma, Cholesteoma (p. 380)—Papilloma (p. 383 )—Adenoma (p. 388)—Cancers (p. 394)—Epithe- lial Cysts, Dermoid Cysts (p. 415)—Adenocystoma (p. 418)—Odontoma (p. 419)—Teratoma, Embryoma (p. AY), Table of Contents. Mimctional Disturbances. . 62.0. cb. Oe ee ee el ee ee. Nervous Disturbances; Disturbances of Motion....... AD oes pivcre WSU DATICES egg co 3% iy onde ae eas coe nespinastory « Disturbamees(. ho... eel. EASE Rent Disturbances,or- Urinary, excretion. «2. es do Disturbances of tier Mayrord Binction.{.2., 5252.4. - Dicrumpamcesworermes semial, Eunction 2.5.05 04... 2. COMP Ieee taster ae? (SL lelse els eller ee ee) (elk eo: aie) @1.e! a..6° e je: je) 8 © «: «) @ © je: ©. 0) @ 1s, © 64.0) \e te). « Ne Fad AT. — * is — - ia ~ INTRODUCTION Pathology (76 rdéos, suffering; 6 dJyos, science) may be defined as the natural Iustory of diseases, or as the scientific study of diseases. The terms “disease,” “disordered” and “morbid” are employed to indicate the existence of disturbances of the physio- logical activity of the organs; that is, the presence of some devia- tion from the anatomical and chemical relations of the body- constituents which exceeds the limits of physiological variation and which calls forth such disturbances. In ordinary life we designate as “‘health” a state of the body in which the vital manifestations (nutrition, metabolism, motility, sen- sation, psychical activity) are carried on in harmony; and it is as- sumed in addition that the various organs.are of normal structure, and that the individual experiences a feeling of well-being. On the other hand the term “disease” carries with it a conception opposed to this so-called health, that of an irregularity of function and of impairment of efficiency of the organs and systems of organs, accompanied as a rule by a feeling of discomfort: The distinctions between these two conceptions merge, however, and are lost when we consider the infinite gradations between health and disease, and as we are required to employ the terms, either empirically or scientifically, in a narrower or broader sense. There might exist, for example, an organ of distinctly faulty structure in an individual without causing any appreciable disturbance of the general health, as a malformed kidney, or a curvature of the spine. One of two paired organs, as a lobe of the thyroid or one of the kidneys, may be anatomically so altered and incapable of function as to merit being considered diseased; nevertheless the individual may feel well and live many years. Moreover in healthy bodies there may now and again be evinced deviations from the normal vital manifestations which may simulate morbid disturbances, but which are not felt or regarded as such because of their brief dura- tion, because they are soon corrected by the protective and regu- lating mechanism of the body, or are at most expressions of such 2 Introduction. adjustments; for example, after marching there may be a brief elevation of body temperature even to fever heat. In considering a body corpulent from fat deposit, one may be at a loss to indicate whether the corpulence is but a normal condition, or whether a really morbid State of obesity has commenced; and, at least in the popular mind, intoxication from alcohol is certainly not to be con- sidered as a disease although in the stricter interpretation we are forced to look upon it as a departure from the state of health. Besides the term Disease, therefore, general convenience of speech requires the use of such terms as Sickness, Indisposition, Feeble Health, Defect, Fault or Damage, and limits the employ- ment of “disease” to such conditions in which the structural and functional disturbances go so far as to hinder the more important vital processes, to cause pain and to impair in an essential manner the vital phenomena of the organism as a whole. By the expressions “feeble health,” “debility” (¢mbecillitas) is to be understood a diminished power of bodily resistance to pathogenic influences ; “sickness” or “indisposition” is used when there is a subjective feeling of impaired health and where but minor grades of disease actually exist. “Defects,” “damages” and “faults” are conditions in which certain parts of the body appear structurally abnormal and do not properly functionate; conditions in which the derangements have come to a definite standstill, and only under special conditions are likely to give rise to further morbid manifestations. Should these be congenital, arising in the period of feetal life, they are spoken of as Malformations, Congenital Defects, Developmental Faults, Vitia Congenita; if acquired after birth as sequels of dis- ease (wholly or partly removed), or if the results of mechanical in- fluences, as Acquired Deformities, Mutilations, or Vitia Acquisita. In its proper meaning the term Disease has no reference to any entity or thing, but to more or less complicated processes and con- ditions which are evidences of disturbances of the physiological constitution and activity of the body; this applying to the individual cells as well as to the whole group of cells making up the organism. Diseases are therefore to be distinguished as diseases of the cells or structural elements of the organs, as diseases of the tissues, of organs, of systems, and of the individual or organism as a whole. [Inasmuch as life is but an expression of a harmony of structural and functional relation between the cellular constituents of the body: among themselves and of the maintenance of efficient adaptability to the bodily environment, disease should be thought of as being made Nature of Disease. 3 up of any change of structure or modification of function which may impair this harmony and adaptability to cellular or bodily surroundings. And individual diseases may then be ,understood as including special groups of such modifications of structure and function, these groups varying in the isolated affections in type, distribution and number.]| The processes which go to make up a disease are not fundamentally different from the physiological processes, are not features foreign to the operation and structure of the healthy body, but are to be directly referred to these; the only difference being that in disease they manifest themselves in a site, at a time or in a degree other than in the normal state of the body. Pathological processes may therefore, as by Virchow, be con- sidered as heterotopic, heterochronic and heterometric physiologi- cal processes (érepos, another; 6 réros, place; xpdvos, time; yérpov, amount). As an illustration: a hemorrhage into the ovary, caused by the bursting of a follicle and ovulation, is normal, but a hemorrhage into the brain is abnormal; unconsciousness in sleep is normal, but at an unusual time and in pronounced degree, as in swooning, is pathological. Almost invariably physiological ana- logies are to be found, in comparison with which the alterations of disease are manifestly but quantitative variations or variations of place and time. The gastric mucous membrane, when the stomach is full and engorged during the process of digestion, is very full of blood and red; in another part of the body, as the conjunctival mucous membrane, this same redness and congestion would be pathological. The endometrium normally sheds epithelial cells and leucocytes in the lochial secretion in considerable numbers after the removal of the placenta ; were this not merely temporary but of per- manent duration the condition would constitute a pathological one, a catarrh. In the tumors or pathological new growths, which are apparently so foreign to the general organism, there are to be found only the same tissue elements as belong to the normal body, which however possess a power of growth which is abnormal. Even the phenomena of death have their physiological counterpart, as in the mummification of the umbilical cord. | The various pathological processes may be classed as follows: (1) Anatomical-pathological processes (gross pathological-ana- tomical or pathological-histological): Here are included all changes of structure or lesions whether of the gross organs or of the tissues and cells, as lesions of continuity of the skin and musculature (wounds), changes in consistence (as cerebral soften- 4 . Introduction. ing or induration of the liver), occupation of spaces and formation of false membranes by fibrinous material (pleurisy, croup), micro- scopic changes in the cells (karyolysis, fatty infiltration). (2) Chemico-pathological processes: Quantitative and qualitative changes of the chemical constituents of the animal organism and its parts (metabolic faults), as the presence of bile in the blood, albu- men in the urine, uric acid in the joints or abnormal proportion of water in the blood. [Here might well be included, too, the ex- cessive formation or uric acid or its salts, of the faulty carbohy- drate changes of diabetes, the development of faulty types of albumen in the blood and within the cells, the toxic changes of urzemia and other intoxications, those essentially chemical processes which underlie in an important degree the changes produced by infections, as well as a wide group of more or less indefinite meta- bolic diseases.] - (3) Functional-pathological or symptomatic disturbances (some- times spoken of as dynamic disturbances): These are faults in the nicety of balance of the various physiological activities of the or- ganism, as the occurrence of convulsions, pain, unconsciousness, labored breathing, diarrhoea or dribbling urine. Functional dis- turbances are usually caused by structural and metabolic faults. Commonly the.latter are primary, as in physiological life the effi- ciency, growth and development of the organs are dependent upon the chemical processes of nutrition and metabolism. Our knowl- edge of the morphological and chemical basis of functional de- rangements is, however, incomplete. Consideration, description and investigation of pathological variations may therefore be divided into (a) Pathological Morphology or Anatomy, (b) Pathological Chemistry and (c) Symptomatology, together with (d) considerations of the influences under which dis- eases develop, and the actual causes of disease (Aetiology: airéa, cause). In the origin of disease some cause is apt to act so as to bring about material changes, chemical and physical, pathological lesions (ledere, to injure) of the component elements and organs, as well as the counteraction or pathological reaction on the part of these same elements and organs, both of which manifest them- selves by functional disturbances (symptoms or signs of disease). That phase of pathology which seeks to explain the development of lesions and symptoms constitutes Pathogenesis (¥# yéveou, de- velopment, beginning); that which concerns the observation of the chronological succession of disease-events, the onset, course Divisions of Pathology. 5 and termination of disease, is known as Nosology (% vés0s, sick- ness). The object of pathology is primarily the acquisition of knowl- edge of the laws which govern pathological changes (Pathognomy, from yyvécxw, to become acquainted with) ; in addition, to point how and why certain lesions and reactions must follow certain causes. Dealing in its broadest sense with life under abnormal con- ditions, pathology presents itself as Pathological Physiology; and moreover provides a scientific basis for the prevention and cure of disease, and thus the foundation of rational Prophylaxis — (apo- guidcow, to prevent or guard against something) and Therapy ) Oepareta, therapeutics, from deparetw, to attend, to heal). For convenience in instruction pathology is separated into two divisions: General Pathology and Special Pathology. This is done with the purpose of facilitating a systematic presentation of the wide scope of the study; general pathology dealing with the ele- mentary pathological processes and their causes without reference to their site in the body, and being thus introductory to special pathology, in which the various individual phenomena of morbid change in the different organs and systems find expression. With the healthy living individual as its starting point, and basing its comparisons upon the average normal structure and ordinary physiological functions of the organism, pathology is dependent upon anatomy, physiology, chemistry and physics as its guides. A clear understanding or comprehension of its processes is impossible without a thorough knowledge of the organization of the animal body; a knowledge which includes the external configuration, the internal structure, the vital phenomena of health and the functions of each of the different organs. Chemistry and physics are essential for such a comprehension, both in their own immediate relations and, too, in connection with zoology and botany bearing upon the interpretation of disease causes. It is possible that one without this knowledge, a layman, may recognize various common morbid conditions (as wounds, fractures of bones, catarrhs, blisters, etc.), may name them correctly, and even treat them correctly on the basis of traditional information empirically acquired; and by frequent ob- servance of such conditions may accumulate a fair amount of skill in their diagnosis and treatment. This is known as empirical knowl- edge. But to be able to scientifically interpret the complex picture presented by disease, to understand the whole trend of the process, its signs, its inception, and its recovery, and moreover to practice a 6 Introduction. rational method of treatment, is possible only to those who have become versed in these basic branches of learning. Only unpre- judiced observation of nature and careful scientific study based upon anatomy and physiology, can give such insight. “To attempt to guess by speculation what is hard to learn even by thorough investigation has failed in this as in every other field of natural philosophy.” (Samuel.) “The enigmas of disease are far too complex, the intermingling of forces in the higher forms of life are far too involved, that thought alone should successfully recog- nize such threads, not even to mention their absolute demonstra- tion. The pages of general pathology are filled with the vanity of such attempts.” (Samuel.) . Our knowledge of disease is primarily obtained from observa- tion of the external appearances of diseased human beings and ani- mals, from accumulation of experience with the external manifesta- tions of disease (clinical observation). As long as autopsies were not permitted upon the bodies of the dead, diseases received con- sideration only from such external features; and there existed only a symptomatic classification of disease. It was customary to speak of jaundice, dropsy, ardent fevers, nervous fever, etc., as diseases, and to endeavor to explain by clever theories and all sorts of base- less ideas the origin of internal affections, whose cause and location were for the most part unknown. They were regarded as mysteri- ous occurrences, for which evil spirits or the influence of the stars on the lower world shouid be held responsible; and knowledge of pathology and the art of healing as well had to be groped for in darkness. Nothing beyond those morbid conditions caused by wounds, by gross external violence, or such affections of the skin or mucous surfaces which were patent to the eye, was dealt with in a less confused manner. In many lines the physicians of antiquity, who sought to deter- mine the nature of disease by dissection of human and animal cadavers, gained astonishing experience, practical skill and an ac- quaintance with the subjects, as is manifest from the clever experi- ments and methodical investigations of these early thinkers. But in the centuries of the Middle Ages, so barren of medical advance- ment, even long after the founding of the universities (which oc- casionally did succeed in making isolated discoveries of value in connection with physiology) medical science became stationary and fixed, hemmed in between philosophical systems on the one hand and all manner of outgrowths from a purely speculative and Sources of Pathology. 7 hypothesis-building science on the other. The learned doctors, with their schools of practically nothing more than mere dogma, who had no acquaintance with the structure and vital functions of the body save what could be gained from its exterior, knew little more than the charlatans of their times. Veterinary medicine was prac- ticed by butchers, farriers and grooms, whose information and practical knowledge were based upon the doctrines, conceptions and recipes handed down from former generations. At the present time clinical observation is no longer limited to the mere detection of the external signs of disease, but seeks an explanation for them, searches for evidence of the internal morbid processes and for the precise location and for the causes of disease, calling to its aid every means of anatomical and physiological in- vestigation and contributing materially to the complete develop- mental history of disease. In point of time the real development of pathological science corresponds with the period when first the study of the exact loca- tion of disease was begun with the aid of the dissecting scalpel and the microscope. Morbid anatomy came to be recognized as the foundation stone of scientific medicine, and remains the most im- portant landmark in experimental studies. It was recognized that definite symptoms are related with certain structural alterations, that it is possible to make inferences as to the altered state and structure of the organs from given disturbances of function, and that the symptomatology of a case may thus furnish a basis for the anatomical diagnosis and the anatomical conception of the dis- ease in hand. Many of the alterations of disease are of such a character that the position, shape, consistence, color, weight and contents of the parts affected are strikingly different from the characteristics in health, and even the unaided eye sees at once why symptoms must have been induced; and from the study of such evidence afforded by the dead bodies of diseased human beings and animals there has been accumulated a large amount of data ana statistics toward the establishment of a clear insight into the develop- ment, cause and termination of disease. Visceral anatomy along with visceral physiology has taught us what we know of the prin- ciples governing the action of the heart, the circulation of the blood, atmospheric interchange in the lungs, the functions of the digestive and urogenital tracts, and no little part of the pathology of the sensory organs; and it is quite possible for one to draw conclusions from given anatomical changes how the mechanism of the grosser 8 Introduction. parts of the body is interfered with, fails or becomes irregular, as in case of cardiac obstruction, obstruction of the blood vessels or intestinal canal by clots of blood or foreign bodies, or how in- testinal displacement or unusual taxing of the organs must or may lead to disturbances. The entire group of physiolegical methods of investigation are of value in the solution of pathological problems; physics and chemistry aid in explanation and find the most varied application in their study. There has been developed in pathology along the lines of its special studies a series of prac- tical methods of animal experimentation, known as Experimental Pathology, affording accurate information in many of the problems of pathogenesis and supplying valuable demonstrations of the cor- rectness of our best established observations and conclusions. One may at will, by operative procedure upon living animals, by ligation or occlusion of blood vessels or ducts of glands, produce and imitate mechanical changes of various types; and it is quite possible by killing the experiment animal at any time to note precisely the anatomical changes and progress of the disease thus induced, from which the course of actual diseases of a corresponding type have come to be well appreciated. By operative removal of some organ or part of an organ, it is possible to obtain an idea as to the results which are likely to follow analogous disease processes in the same part, as in case of the thyroid gland, liver, kidney or adrenal. All our knowledge of regenerative growth of tissues, the healing of wounds, the union of fractured bones and of the general process of inflammation we owe directly to experimental studies on animals. By administering to animals various types of material of ap- parently poisonous character, it has been possible to study the action of a wide range of substances and to acquire the essential basis for diagnosis of the intoxications. The complete life history of the animal parasites, their development and multiplication in the human and animal body, and the diseases caused by them, have been worked out by means of animal experimentation in a really. classical man- ner; and the practical application of this knowledge in food exami- nation, in meat inspection and in other lines of prophylaxis against disease, are exceedingly numerous and have led to marked diminu- tion of such diseases as hydatids, trichinosis and mange. But above ~ all else animal experimentation has lifted the dark cloud which formerly obscured the nature of infectious diseases; and only from successful attempts in transmission by inoculation has it been pos- sible to explain and obtain precise knowledge as to the real nature Importance of Pathology. 9 of plagues and their development. As long as these methods were not employed superstition and fear dominated mankind whenever a pestilence appeared. To-day, with realization of the conditions essential for infection and the modes of transmission, medical acumen has determined the surest preventive measures for con- trolling and combatting these diseases; and even the worst epi- demics, as of plague and cholera, have largely lost their terrors. With confidence the work of extirpation is being carried forward, and medical science, crowned with success, has completely stamped out a number of these infections and is daily solving the difficulties | in the prevention and cure of such evils. To sympathetic persons it may indeed seem a serious thing that we be forced for our own advantage to make use of the sufferings of lower animals in order to avert such dangers from ourselves and to purchase by animal sacrifice the means of combatting con- tagion. But the instinct of self-preservation impels man, just as the necessity for food with any animal demands the death of other creatures. The slaughter of animals for sport is far worse, and productive of more pain to them; and many of the methods of kill- ing in the kitchen of the epicure are much less excusable than. any of the practices in the whole range of deplored animal inoculation, so unavoidable for the establishment of medical science. When it is realized that without the results obtainable by such work—Ex- perimental Pathology—millions of people must forever be threatened by early death from pestilence, as of old, when countless numbers were sufferers in these epidemics and were hurried off before their time and when destructive cattle plagues forced heavy burdens on the land, whole hecatombs of animals for which the experi- mentalist must account must appear but a trifling matter. Prohi- bition of animal experimentation, as is sought by unrestrained zoomania, would be equivalent to prohibiting the cure of the sick; since nature affords for many affections no means for restoration other than the blood of inoculated animals. Human education and the high ethical tone of medical science will certainly be sufficient security that experimental pathology in pursuit of its purposes will not lend itself to useless animal torment. HISTORY Ore PATHOLOGY Much of our experience and knowledge of the diseases of man and of the lower animals has come down to us from antiquity. The gift of observation and the faculty of reasoning, as well as his desire to restore impaired health, impelled primitive man to formu- late some kind of ideas regarding the origin and nature of disease. And as the grade of individual and popular intelligence advanced and as experience grew in value with its transmission from genera- tion to generation by traditions and records, so our conceptions of disease expanded and our knowledge advanced, or on the other hand mistaken ideas took deeper hold or false notions once discarded again came into prominence. History informs us that for some thousands of years there had been attained considerable skill in the art of healing among the Babylonians, Persians, Egyptians, Hindoos, Israelites, Greeks and Romans both among the priests and in the hands of a special class of physicians; and although religion and superstition, mysticism and philosophical speculation had much in- fluence over it, medicine really was possessed of a very notable fund of information. In the fourth and fifth centuries before Christ considerable work was done by physicians and naturalists like Alkmzon (B. C. 540), Hippocrates II, the son of Heraclides (B. C. 460-375) and Aristotle (B. C. 384-323) in the line of dissection of animals for inference to the supposedly similar structure of the human body, human cadavers being but rarely obtained for purposes of dissection. Dis- semination of the knowledge of medicine which existed was ad- vanced by the great schools of learning, like the Museum and Serapeum in Alexandria with their magnificent libraries (700,000 rolls of papyrus in the Museum and 300,000 in the Serapeum), and by the profuse literature of the Greeks and Romans. To some extent, doubtless, veterinary medicine shared in this, being practised both by the general physicians and by a special class of veterinarians, known as mulomedici, hippiatres (immos, horse; iarpds, physician), ktentatres (xrqvos, domestic animal ; tarpés, physician) and veterinarii; Early History. Il yet in a large measure it remained in its primitive condition in the hands of shepherds and farmers. At the beginning of our present era medicine was chiefly domi- nated by the teachings iormulated by Hippocrates and Aristotle in their general writings. The study of comparative natural science, instituted by Aristotle, laid the foundation of our knowledge of animal biology, of comparative anatomy and physi- ology; while Hippocrates and after him the physicians of his school established pathology. At that time it was held that there were in the animal and human body four cardinal humors, “blood, mucus, and yellow and black bile.’ It was taught that a proper relationship between these (crasis) insured health; and that dis- ease depended upon the occurrence of lack or excess of one or other, that is upon some modification of their relationship (dys- crasis). Next to the blood, the principal vital humor, Hippocra- tes placed mucus in order of importance, because it is often dis- charged in large quantities from the nose and was thought to come from the brain and to escape through the ethmoidal open- ings. Yellow bile was often seen in vomit; but black bile was entirely a product of the imagination and was supposed to arise in the spleen. The basis of vital phenomena was supposed to be the inspired air (pneuma, the breath of life), which was thought to contribute warmth to the body. In conformity with - the accepted theory of corruption of the humors, therapeutic measures were directed to a riddance from the system of the ma- ferial which had caused the “dyscrasia;’ and for this reason evacuants, diaphoretics, diuretics and venesection played an im- portant part in those times. The importance which Hippocrates ascribed to these fluids or humors led to the application by later generations of the name Humoral Pathology to this system. The solid structures of the body were not entirely disregarded, but only vague ideas prevailed in relation to them. There was a theory (Democrites) that the solid parts were made up of particles known as atoms, between which there were pores [for the passage of air and humors], that the width of these pores varied with the varying density of deposition of the atoms, and that by some such method the state of the body was regulated. ‘To this extent, therefore, there was a Solid Pathology, which, however, found but few adherents. Efforts toward such theoretical explanations found support particularly in the schools of philosophy; and tenacity of such views and the rigid 12 History of Pathology. adherence to authority, together with constant seeking after the keenest dialectic in argument, gave to one school of physicians of the day the character of “dogmatists ;’ while others discarded entirely speculative reasoning and called themselves “empiricists,” boasting that their methods of practice were based entirely on experience. They rejected the study of anatomy as superfluous; in which, however, the dogmatists, although essentially bookmen and theorists, made some progress. In the middle of the second century Claudius Galenus (born in Pergamon, Asia Minor, A. D. 131; educated in Smyrna, Corinth and Alexandria, and afterwards practicing his profession in Rome; died A. D. 206), noted both for his discoveries and as a prac- titioner, revolutionized medical science by his efforts to harmonize the prevailing theories with practical experience and thus give them a real value, and by his work in the establishment of ra- tional scientific methods through comparative anatomy and ex- periments upon living animals. Throughout the middle ages, even into the fifteenth century, the theories of Galen, whose discoveries were numerous and whose extensive writings contain much that is of descriptive value, were held in esteem and respect, par- ticularly his opinions upon anatomy and physiology. Through studies of this character at the hands of physicians -a close relationship developed between veterinary medicine and human medicine; but there were other influences which aided in the development of comparative pathology. Agriculturists, like Xenophon, Cato, Columella, and Virgil, and veterinary specialists who in Roman times attained an independent standing, and among whom should be mentioned Apsyrtos (circa 290-350, A. D.) and Publius Vegetius Renatus (circa 540, A. D.) as es- pecially distinguished, there were collected and recorded in litera- ture their experiences with various diseases, especially epidemic affections among animals. Although there is much useless em- piricism included in the dissertations of these writers, there are also no little excellence of observation and soundness of thought; and the works of the last-named author, like those of Galen, served for centuries as valuable sources of information. The general collapse of the sciences after the fall of the Roman Empire, during the time of migration of the European peoples and the period of the Middle Ages, resulted in a long stagnation in medicine. Practically all that is worth considering was the preservation of the writings of the ancients, for which we Middle Ages and Modern History. 13 are chiefly indebted to the monks, working as copyists in the monasteries. Technical medical skill made scarcely any note- worthy progress. With the founding of the universities in the thirteenth to fifteenth centuries, when a resumption of anatomical investigations gradually became possible, and with the discovery of the printing art, which stimulated the translation and wide dissemination of the works of Grecian and Roman authors, there began a new epoch. The luminous works of the human anato- mists like Vesalius, Failopius and Eustachius, the experimental researches of Servetus and Columbus Cesalpinus, and particularly William Harvey’s (1578-1658) discovery of the true conception of the circulation of the blood, led directly to the recognition of the errors in Galen’s system and to a reorganization of medical science.* As usual pathology again fell into error, ascribing, un- der the influence of prevailing views in natural science, the various processes of disease and their causation now to this, now to that physical or chemical factor. Speculative hypotheses took precedence of actual experiment, and attempts at proper explana- tion were quite lost in the fancies of the individuals. Some were followers of the “chemical school’ founded by Sylvius, and en- -deavored to explain every fault by chemical changes in the com- position of the body, as the introduction of “sharps” (Boer- . haave) ; others, the “neuropathologists,’ when the importance of the nervous system became recognized, laid stress upon the in- fluence of the nerves (William Cullen), or upon the effect of “stimuli” and the irritability of the tissues (the theory of ex- citability of Haller and Prown). Others, basing their views upon mechanics, believed the vital phenomena of morbid disturbances depended upon mechanical faults of relationship (“mechanical school,’ founded by Santoro, 1561-1635, Borelli, 1608-1677). Still others spoke of “vital spirits” circulating in the body, of “forces,” of the power of the “entities” (Paracelsus+), or made some injury to the immortal soul the ‘real principle of disease (G. E. Stahl, 1660-1734). These doctrines were denominated vital- ism and animism. Such ideas have found adherents even as late as within the nineteenth century, clothed usually in high-sounding foreign verbiage to make the greater impression. Along with these speculative theories, however, exact clinical *Compare Hichbaum, Geschichte der Heilkunde: Berlin, Pareys’ Verl., 1885. +Theophrastus Bombastus, whose proper name was Paracelsus, distinguished different forces, an ens astrale (power of the stars), an ens naturale, spirituale, veneni, etc., as factors in life and disease. 14 History of Pathology. observation, physiological experimentation and anatomical dissec- tion grew more and more toward a plane of real excellence, af- fording an increasing clearness of insight into the processes which obtain in both healthy and diseased bodies. The anatomical changes shown in necropsies directed attention to the topography of disease. Morgagni (1682-1771), a teacher of anatomy in Padua, in his work, “De Sedibus et Causis Morborum” (1761), outlined the first comprehensive and systematic exposition in this direction and came to be regarded as the founder of pathological anatomy. From efforts to correlate manifestations of disease of the various organs with the presence of anatomical changes, arose the school of Pathological-anatomical Diagnosis, to which is due the discovery of a number of valuable methods of diagnosis (per- cussion, thermometry, the microscope, chemical analysis), and which had as its founders men like Bichat, Pinel, Ceérvisart, Dupuytren, Auenbrigger, Laennec and Rokitansky. The advances in physiology inaugurated by Johannes Muller (1801-1858) and the cellular theory formulated by Th. Schwann, along with the development of microscopic anatomy, are respon- sible for an important change from the older conceptions of dis- ease, giving us as a basis for our ideas of morbid processes a cellular pathology, first proposed by Rudolph Virchow (1858), who referred the real seat of disease to the individual cells and the tissues, and regarded disease as depending upon the reaction of these to harmful influences. Although it is but about fifty years ago that Schonlein’s school looked on disease as some sort of living thing of extra-corporeal origin, entering the bodies of men and animals like a parasite and expelled by our therapeutic measures ; yet in the interim the study of 4tiology has developed the definite view that disease is but the manifestation of mor- phological, chemical and functional changes which are induced by the most varied harmful influences upon the cells and tissues, chemical or physical; and thus to-day, through uniform and ex- act methods of objective research, clear conceptions and. positive knowledge are in hand relative to most diseases. As far as comparative pathology is concerned, it too was com- pletely dormant from the fourth until the eighteenth century, at first because of the general depression in science, later because medical practitioners had but little interest in the diseases of ani- mals when human medicine was developing along these newer lines, but especially because of the aversion which men. came to Comparative Pathology. 15 & hold for even mere contact with the dead bodies of animals. Among the rare publications appearing in the middle ages there is only one large work on the anatomy of the horse (issued in 1598 by the Venetian senator, Carlo Ruini, but probably the product of some physician) which is at all worthy of note as showing any advance in knowledge. At the same time the nat- ural history of the domestic animals was considerably advanced by C. Gessner (1516-1565) and Aldrovandi (1522-1605). Prac- tice of veterinary medicine was relegated more and more to far- riers, executioners and butchers and naturally drifted into the crudest sort of empiricism. However, when .skill in riding and horses became more prized in the courts of princes and in war, there was a change for the better; and Italian, French and Ger- man masters of the stable (Pignatelli, Marx Fugger, Bohme, Winter von Adlersfliigel, Robertson, J. von Sind, Solleysel, Pluvi- nel, Lafosse) published a number of works upon the diseases of the horse. From the eighteenth century physicians once more be- gan to frequently pay attention to animal pathology; the necessi- ties arising from devastating epidemics among cattle, particularly cattle plague, stimulating the members of the medical faculties to endeavor to stamp out these diseases and to publish numerous articles upon investigations bearing in this direction (Ramazzini, Lancisi, Schroeck, Golike, Kamper, Sauvages, von Haller, Paulet). Ine the years from 1762-1790, in most of the [European] states, schools of veterinary medicine were established, the first being inaugurated by Bourgelat in Lyons and Alfort. With this step comparative medicine found a place in scientific institutions, later, after various changes in organization, assuming the rank of independent colleges or becoming incorporated with the universi- ties. The first teachers of veterinary medicine were for the most part physicians; and even to the present the progress of the sci- ence is in close sympathy and relation with human medicine. However, the men who in the nineteenth century have been edu- cated to the dignity of independent investigators and to a new standard as veterinarians, have broadened comparative medicine to a many sided field; and the results of their discoveries and their practical achievements have become of importance not only to the farming and cattle-raising industries, but to the general wel- fare of mankind as well when one takes into consideration the consumption of meat and the dangers of animal epidemics. PREDISPOSITION TOWARD DISEASS Any living being becomes affected by disease when no longer able to adapt itself to its environment and to the demands to which the functional ability of its cells and organs is subjected. As soon as such external influences exceed the limits of endur- ance, aS soon as they so affect the cells and organs as to induce alteration of function, they become causes of disease. There is really nothing upon which the anfmal body is dependent or with which it is related, but may on occasion cause the onset of disease—nutriment, air, light, temperature, the various animal and vegetable organisms about it, the varied accidents of nature, its own active and passive relations, as well as every physiological process going on in its economy; and the very same factors, which are generally essential for the maintenance of existence and the well-being of the individual, may become agencies of harm and noxious (nocere, to harm) influences productive of disease. Whether the individual should experience the harmful possi- bilities of such factors or not depends upon the imherited po- tentiality of the organism, the functional capabilities of its cells and tissues, and upon the efficiency of its protective and reg- ulative mechanism. Sensitiveness to noxious influences, known as Predisposition, and insensitiveness or insusceptibility, commonly spoken of under the terms Resistance or Immunity, are by nature widely different among different species and individuals and even among the different tissues in the same animal; and are subject to considerable variations and abnormalities. The polar bear, the Esquimau dog and the reindeer are accustomed to the cold of the north, but sicken in the,temperature of warmer climes; many ani- mals thoroughly adapted to the tropics, perish when transferred to cooler regions even though furnished with their usual food. Indi- vidual animals of the same species often manifest differences of susceptibility, as where in herds of cattle or even, as is often ob- served, in a number of cattle kept in the same stable, some path- Variations in Predisposition. 17 ogenic influence equally operative upon the whole group fails to produce its effect upon all, certain individuals resisting it suc- cessfully; or it is often noticed that here and there an animal sickens under conditions quite favorable for most of its species. The difference between different tissues in predisposition and im- munity may be seen in comparing the skin and mucous meim- branes. The surface of the skin, with its hard epithelial cover- ing, is much less sensitive to irritative substances than are the delicate mucous membranes; the mucous membrane of the stom- ach in the living animal is resistant to the action of acids, but that of the lower end of the intestinal. tract may be injured by the acid of the gastric juice. A number of poisons (snake venom, tetanus toxine) are en- tirely harmless when taken into the alimentary canal; aithough, if introduced by way of iesions of the skin into the tissues, they are extremely pathogenic. Especial interest attaches to the differences in predisposition and immunity toward the viruses of infectious diseases. In all infectious diseases we have to deal with poisonous materials caused by micro-organisms. These micro-organisms (muicro- phytes, vegetable microscopic organisms; mlicrozoa, animal micro- scopic organisms) gain entrance to the body by alimentation, or by the respiratory path, or through wounds, or may even actively penetrate the tissues should they be in close relation with the skin or mucous surfaces. Within the body structure they mul- tiply for a time and werk harm to the tissues chiefly by the specific poisons existing in their protoplasm (that is, in the bodies of the microbes) or by poisons elaborated by them, diffused in the tissues and taken up by the blood. In the contest waged with these microscopic ioreign invaders a twofold task is set for the animal body; it must in the first place destroy the microbes and at the same time must render their toxines inert. One ani- mal may accomplish this with ease; another with difficulty. Some species of animals are by nature uninfluenced by the toxine of an infection which is sure to produce disease in another species; thus cattle are immune to glanders, the horse to pulmonary tuberculosis, and chickens bear large doses of tetanus toxine with- out injury to health. Such absence of reaction to infections and their toxines in an animal species is spoken of as natural immunity. It is to be explained from one standpoint by the idea that the cells and tts- 18 Predisposition and Immunity. sues of the immune animal have no afinity, or but little affinity (chemical affinity), toward the toxines of the infection. The poisonous elements simply do not enter into combination with thein. For example, the nervous system of the turtle is absolutely immune to the toxines of diphtheria and tetanus, and these sub- stances may be injected into the animal entirely without effect. Yet the toxines thus introduced may remain in the bodies of the experiment animals for months without being rendered inert by the juices; and should the blood of such a turtle be injected into some susceptible animal it will act in the same manner upon the latter as would the toxine itself. From a-second point of view it is to be recognized that im- munity may depend upon the fact that some of the cells of the animal in question are able to take up and digest micro-organisms, and thus render them harmless (Phagocytosis). This power of seizing and ingesting small particles, organic and inorganic, or dead and living cells, is peculiar especially to the motile types of leucocytes (wandering cells, white blood cells), but is also possessed by giant cells, splenic and medullary cells, and even fixed connective tissue cells (as endothelium); and plays an important part in the economy of the body. Its significance has been pointed out especially by the ingenious investigations of Metschnikoff, Leber,and Bordet. These phagocytes act as scaven- gers, taking up and making away sometimes with blood debris, nuclear fragments, pigment, fat globules and all sorts of minute foreign particles with which they come in contact. The ingestion of such corpuscular elements is with them a simple process of feeding. The movemert and approach of the phagocytes may be induced by a number of stimuli, as warmth or an acid, acting upon their own tactile or chemical sensitiveness. In coming in contact with foreign particles they attempt to increase their surface of contact as much as possible [applying their protoplasm more and more about the surface of the particle, and thus eventually enveloping it in their own material]; and are at- tracted by various chemical substances (chemotaris). [It is but fair to add here that while the theory of chemotaxis, as a part of the general theory of “tropisms” or of blind automaton- like response of living things to external forces or attractions, finds wide adherence among medical men and biologists, there are nevertheless others who do not accept such a view, the latter finding reason to believe that the manifestations which the former Protective Substances. 19 school attribute solely to non-intelligent attraction from without are really due to an inherent power of a low intelligent char- acter of the organisms showing them. These latter would attribute even to individual cells as the phagocytes, a low but actual volitional power to either originate or refrain from efforts to approach the foreign particles referred to.] The proto- plasm of the phagocytes apparently can secrete digestive juices [there is reason to think that certain granules seen in leucocytes are of the nature of ferments], through the action of which they are able to assimilate nutritive matter and dissolve foreign bodies. In this latter manner, in part at least, it is possible that the virus of infectious diseases may be removed from the tissues. Nuttall first pointed out that in the blood plasma of healthy ani- mals there exist certain substances which are capable of dissolv- ing the body matter of bacteria, and of thus destroying them. These substances, called alexins by Buchner, and complements by Ehrlich (by others addiments and cytoses), are products of the cells, which are either given off by the living cells (Buchner) or are set free by cellular destruction (Metschnikoff); and are found in varying amount in the circulating blood of the indi- vidual animals. An excellent example of these substances is seen in the effect, discovered by Behring, of the serum of white rats upon the anthrax bacillus. If hundreds of thousands of anthrax germs are placed in some serum from a white rat (at 37° C.) it will be noticed after ten or fifteen minutes that the bacilli have become swollen and degenerated (granular), and after from four to seven hours that they have completely dis- appeared. Canine or ovine serum does not possess this power, but should a few drops of rats’ serum be added to sheep serum, the bactericidal action will immediately appear. The serum of the horse also has a strong bactericidal power. It must be clear that the cause of natural immunity cannot be attributed to the bactericidal action of the serum alone, for both rats and horses are susceptible to anthrax; it must be thought of, as already men- tioned, as dependent in part upon the lack of affinity of the living cells for the toxines of the infection, and in part upon their phagocytic power. Just as among different animal species and individuals there may be some one kind which is more highly resistant to poisons than the rest, so there may be met others exhibiting an excessive susceptibility to such 20 Predisposition and Immunity. influences. For example, cats are extremely sensitive to carbolic acid. It is well known that some persons possess so marked a susceptibility tc a number of substances and foods (as strawberries, mushrooms, crabs, lobsters, cocoa or alcohol) that after partaking of them they experience severe pain, vomiting and cutaneous eruptions, and in the same way are apt to be severely affected by certain medicaments (chloroform or mor- phine) ; they are influenced by such substances, as it were by poisons. Such extreme susceptibility is known as idiosyncrasy (tvs, - peculiar; ovyKpao.s, combination). As a rule, the predisposition or immunity of individuals is only a relative one; that is, it is variable and of moderate degree, may be increased or decreased, and is often only temporary. Racial or specific immunity may also be but relative. Rabbits are ordinarily immune to symptomatic anthrax, but now and again a rabbit is found to be susceptible to this disease upon inoculation. Goats, horses and cattle are strongly resistant to swine-erysipelas, but if large amounts of the virus are injected intravenously they may show severe symptoms. Young dogs are somewhat susceptible to anthrax; older dogs less so. Young sucking calves are very rarely affected by “black leg” and usually resist inoculation tolerably well; but as soon as they begin to eat vegetable food they become very susceptible to the disease in question. Thus age and food are seen to have an influence upon predisposition and immunity. How intimately connected the latter factor is may be inferred from the experiment, origi- nally performed by Feser and afterward confirmed by others, in which rats, 1f fed upon meat alone, are found asa faleweomme immune to anthrax, while if fed on bread they soon succumb to inoculation with the virus. . By experimentation it has been shown, moreover, that hunger is a predisposing cause, that bodily overexertion (overheated ani- mals), nutrition of restricted quality and excessive amount ( as a diet too rich in fat) may have such depressing influence that animals subjected to them readily succumb to injurious agencies which they would otherwise bear, and particularly become less resistant to infections. It is also true that certain. altered condt- tions of the tissues afford especially vulnerable points for the attack of pathogenic influences; for example, gastric catarrhs, by diminishing the production of hydrochloric acid, favor the deposition and pathogenic action of bacteria which are otherwise destroyed by the gastric juice. As a rule, previous disease leaves as a sequel an increased disposition, the formerly affected tissues Acquired Predisposition and Immunity. 2a showing a diminished resistive power for a long time (local pre- disposition; locus minoris resistentie), as, for example, mucous membranes after catarrhs. 7 Predisposition to disease and (a matter of extreme impor- tance) wmmunity agaist disease may be acquired. It is well known that recovery from certain infectious diseases is accom- panied by an insusceptibility to a repetition of the same affection. This immunity after previous attacks is at times only temporary, but a few weeks or months in duration, or it may extend over many years or for the entire lifetime. The alteration which has taken place in the condition of the body in such cases is chiefly a chemico-biological one, and although much remains enigmatical concerning it, some insight into the process has been obtained through experimental investigation. Besides the discoveries of Jenner and Pasteur, who gave to mankind facts and methods of the highest importance toward success in combating infections, by which it has become possible by artificial inoculation of an attenuated virus to produce a mild course of the infection and to obtain therefrom immunity from subséquent attacks of the same disease, there must also be recalled the important discovery that in the blood of man and animals, after attacks of infections, there appear certain substances which are of specific anti-toxic char- acter and are destructive to the virus, and that upon the produc- tion of these substances depend protection and recovery from these diseases. The tissues of the animal body react to irritants which gain access to them. Should a particle of dust or a gnat happen to lodge upon the conjunctiva, such a foreign body acts as a stimulant to the nerves of the mucous membrane, this inducing a free secretion of tears, which usually wash away or dissolve the object. In an analogous manner there is a reaction on the part of the tissues should a toxine or some pathogenic germ (virus, bacterium) come into contact with them, not in this case with a simple secretion to wash away the poison, but nevertheless re- straining the poison and giving origin to substances which are apparently actual antitoxines, or which are able to destroy and thus render harmless the germs of disease. The conditions un- derlying the production of such antagonistic or protective sub- stances, their mode of origin, manner of action and properties, are of extremely complex nature. The numerous experiments of such investigators as Behring, Ehrlich, Brieger, Kitasato, Wassermann, Buchner, Emmerich, Fodor, Nuttall, Nirssen, Bordet, Morgenroth 23 Predisposition and Immunity. and Sachs, have, however, brought forward facts hitherto unsus- pected and of the greatest interest in this connection, and have pointed out not merely theoretical hypotheses upon immunity, but also practical methods of extreme value in combating the in- fectious diseases. As already pointed out, there already pre-exist in the normal blood of every animal certain substances capable of dissolving foreign material which has in some way gained entrance, and, by entering into combination with resultant toxic matter, of render- ing it harmless. In some of the glands, as the thyroid and liver, neutralization of toxic matter and noxious metabolic products is being continually carried on; and when one considers the innu- merable reactions ,and interactions which are taking place in metabolism, resulting in the most varied types of secretory ma- terial with destructive and digestive properties, it is easy to think of the body and each of its cells as a chemical laboratory of manifold productive ability. In attempting an explanation of the mechanism involved in the production of these antibodies (antagonistic or protective substances), Ehrlich has proposed a brilliant, and, at first thought, a very convincing theory, the chief points of which are briefly included in the following. The hypothetical details of this theory have recently met such serious objection at the hands of Gruber that in a great measure it seems but doubtfully credible. The basic fact that antitoxines and protective substances are products of the cells and organs of the body is not endangered by this criticism, but the problem of how and where such substances are formed is renewed as a matter for further investigation. According to this view the cells of the body may be thought of as organisms which consist of a basis of protoplasm, which has as its vital center a nucleus (vital nucleus of Ehrlich) ; this protoplasmic unit may be fancied as being possessed about its periphery of armlike processes, the receptors or side-chains of Fhrlich. [It is to be understood here that the author refers to the protoplasmic molecules as the basis of this theory, each mole- cule being composed of a more or less complex group of atoms or of combinations of atoms. The vital center does not refer to the nucleus seen as a structural part of the cell, but to the struc- tural nucleus of such a complex molecule of its protoplasm. As is attempted in the graphic chemical formula of a complex or-— ganic molecule with the symbol C as its center, to indicate as Ehrlich’s Theory of Immunity, 2a “side-chains” the various atoms or groups of atoms linked about this nucleus, so in Ehrlich’s view the living proto- plasmic molecule may be thought of as having as its elemental or basic compound a vital nucleus about which are attached, and probably from which spring, a number of other atomic groups subsidiary to the center of the molecule and corresponding to the side-chains of the formula, but essential to the efficiency and integrity of the whole complex molecule, since they are its means of combination. These are the receptors or haptophores of the molecule. Every molecule possesses these haptophores in addition to its principal part, the centre or nucleus (in living protoplasmic molecules, the vital centre). Should these haptophores be lost in the living molecule, they are replaceable by others of like type because of the vital regenerative power of the molecule. | The receptors are the principal instruments of [molecular, or in other words] intracellular metabolism and provide nutri- tive substance to the cells through their ability to unite chemic- ally with such material. However, just as proper food elements may thus combine, so other albuminous bodies or materials chem- ically allied to foods become linked to or combined with the receptors, as material extracted from bacteria, various poisons of animal, bacterial and vegetable origin (toxines, venom of bees, spiders or snakes, diphtheria toxine, ricin, abrin, the substance of blood cells, spermatozoa and nervous tissue, and the milk albumen of different kinds of animals). Such union occurs be- cause these substances contain in their molecular composition certain groups of atoms, which, like similar atomic groups in foods, have an affinity (chemical affinity) for the atomic groups of the cellular protoplasm; these Ehrlich speaks of as their haptophore groups. [Thus both the protoplasmic molecules of the body cells are provided with haptophores or combining chains, and, too, all nutritive or harmful molecules which come in con- tact with them. Should there be affinity between the haptophores of the cellular protoplasm and those of the introduced molecules a combination will result.} With such combination — effected [the molecule and in proportionate degree the whole] cell comes under the influence of the substance chained to it. Should the latter possess properties actively harmful to the protoplasm, poisonous qualities (toxophore), the cellular protoplasm becomes more or less injured, and a pathological cellular lesion results. There may ensue complete death of the cell [protoplasm], 24 Predisposition and Immunity. or merely a condition of irritability or partial injury. If the injury be partial that part of the cell [protoplasmic molecule] which remains sound restores the defect. In this condition of irri- tability or stimulation there is a reaction on the part of the cellular protoplasm left with its vital centre intact to regenerate the receptors destroyed by the toxic influence. Following a law recognized by Weigert, regeneration in the cells of an organism is usually productive of more of the substance than originally ex- .isted at the site of loss; and so here the restoration is often SO active that an excessive number of receptors are supplied to replace those which have been destroyed. “Such an excess of receptors constitutes a useless ballast for the cells and the extra ones are thrown out into the blood and circulate therein” (Ehr- lich, Wechsberg). The presence of these free receptors in the blood, representing haptophores or chemically combining sub- stances, affords opportunity for materials which have gotten into the blood and which have chemical affinity for them, having come in contact, to enter into combination with the receptors. Thus held by these free receptors, such substances are prevented from involving the cellular protoplasm, and as a result the cells and the whole individual are protected from the disease. This power of molecular combination differs in the different cells of the same individual and in the cells of different species of individuals. One species may possess no cells containing the elements essential for combining with a certain toxine; th@re would then be absolutely no chemical affinity shown between the cellular molecules and the toxic molecules, and a priori the latter must be without effect. In such a case the toxine, perhaps in large quantities, may remain for weeks in the blood and general circulation without any harm resulting to the individual. Such instances are examples of natural immunity. On the other hand, an individual may possess a vast number of receptors not merely in the general body, but each cell, each corpuscle, for example, may contain a mass of material capable of combining with sub- stances of one or other kind. In classification of these receptors it is customary, following Ehrlich, to distinguish them as of EL tiolll, etc. orders The first order (uniceptors) includes receptors having only one haptophore group for poisons (toxines) and utilizing this for combination with such substances; they are called antitoxines. The presence and formation of antitoxines is illustrated by the Lysms. 25 immunity to toxines acquired after infectious disease. The tox- ines are allied to the albumens* and enter the blood in a state of solution; thus dissolved, they here enter into combination and are therefore inert before they gain access to the tissues, as the nerv-. ous tissues—the cells (bacteria) which give origin to the toxines being removed from the economy by phagocytosis (as tetanus or diphtheria bacilli). Another class of receptors [III order of Ehrlich] has the power of combining with foreign cellular elements and at the same time drawing into the combination the ferment-like alexines which naturally have pre-existed in the blood; these thus must possess two haptophore groups (a cytophile and a complementophile group), and for this reason are known’ as amboceptors. For this element which is the medium (amboceptor) of the chemical union (anchoring together) the following terms are also employed: desmon (sé =I bind), immune body, imtermediary body, copula, 1mmumisin, fixateur, sensitising body. The alexine is also known as:the complement, addiment and cytose. When by the combined action of these two elements the destruction and solution of foreign cellular elements (the toxine- producing animal and vegetable microorganisms themselves) are accomplished, the compound antibody [amboceptor and comple- eeGereis spoken of as a cytolysm (E. S. London).- The presence of the two elements allied to each other is shown by experiment. If one will heat a serum containing cytolysins to 56° C. the complemental element will be destroyed, and the serum will be found to have lost its cytolytic power, is inert. If, however, to this serum there be added another, ordinary serum, containing only complement and inert by itself, the cytolytic power is restored to the first, and it is said to have been reactivated. So, too, the desmon or amboceptor in the cytolysin may be removed by adding to serum cells for which it has affinity [and by centrifugation these may be thrown down; while the serum continues to contain the complement]. There are a number of cytolysins of different kinds, each exerting its influence as a rule upon only one certain kind of cell [this depending upon the peculiar affinity of the amboceptor in the cytolysin combination]; thus we recognize among many those which act upon red blood cells (hemolysins), upon sperma- *Poisons of other types, alkaloids, glucosides, saponines, which do not act by forming chemical combination do not cause the formation of antitoxines in the organism, (Hhrlich, H. Sachs.) 26 Predisposition and Immunity. tozoa (spermolysims), upon bacteria (bacteriolysins), upon white blood cells (leucolysins). Some dissolve several kinds of cells, as in the case of spermolysins, which destroy red blood cells as well as spermatozoa. From this it may be seen that in general cytolysins possess specificity of action. The appearance of cytolysins in the body of any given animal is occasioned by the introduction of cells of a different species of animal into the first. If human blood be injected in increasing amounts under the skin of a rabbit or into its peritoneum, the serum of the rabbit will acquire the power of dissolving the hu- man red blood cells, but not those of horses, cattle or guinea-pigs. If the spermatic fluid of guinea-pigs be introduced into rabbits, in the same way the serum of rabbits becomes solvent for the spermatozoa of guinea-pigs, but cannot influence the spermatozoa of another species of animal. If colon bacilli be injected into an animal a cytolysin will be developed destructive only to these microphytes, and in fact only to the particular strain of this bacterial group which was employed in the experiment. From the foregoing it should be realized that the principal feature in the production of immunity against foreign cellular elements is the formation of the amboceptor or desmon, and that this alone is a new product of the cells of the invaded body; the other element, the alexine, naturally pre-exists in every body, its. combination with the desmon form- ing the cytolysin. If, however, the necessary alexine be absent or present in insufficient amount, the cytolysin will not appear. In this latter way must be explained such occurrences as where, in spite of repeated introduction into an animal of some type of cells, the blood acquires no cytolytic power, but where on further addition of the serum (containing the required alex- ine) from another species of animal cytolytic activity is immediately produced. The sources of the amboceptors are apparently the bone- marrow, spleen, lymph glands and perhaps the subcutaneous con- nective tissues. In addition to the production of antitoxic and cytolytic sub- stances the body may engage along the same line of reaction in the formation of substances [II order of Ehrlich] which cause foreign cells to aggregate in masses (clumping, agglutina-_ tion), the so-called Agglutinins; and other substances which coagulate foreign types of albumens (Coagulins) and cause their precipitation (Precipitins). In illustration, if defibrinated human blood be injected into a rabbit there is developed in the blood of the latter a substance which will act on human blood to Post-Infectious Immunity. 27, cause a flocculent precipitate, but which will not (as a rule, and never if certain modes of application are employed) exhibit such precipitating qualities with any other type of blood. It is inter- esting in this connection to add that the serum of a rabbit so treated will also precipitate the blood of anthropoid apes, gorillas, orang-outangs and chimpanzees, thus indicating a relationship of these animals to man. Cytolysins and hzmolysins also serve to show the relationships existing between animals in the zoological system of classification. Inasmuch as this reaction is applicable as well with a solution of old and dried blood, the discovery (which as an outcome of research in the field of immunity is due particularly to Bordet, Ehrlich and Morgenroth) has acquired especial importance as a means of information concerning the source of blood stains in forensic medicine. Other albumens may also lead to the formation of specific antibodies in the animal organism, as milk albumen; thus by subcutaneous injection of goat’s milk into rabbits, horses or cows a serum may be obtained which will immediately cause a precipi- tate if it be added to goat’s milk. In the same way, by inocula- tion, coagulins may be obtained for cow’s milk. In the same way, too, in the course of an infectious disease a series of substances are produced in the human or ani- mal organism which render the infectious matter for the time harmless. Should the infectious products develop very rapidly, and by their poisonous properties cause serious protoplasmic changes in the body cells, the disturbance is apt not to be limited or checked, and in spite of any reactive-products which may be formed the function of the cells becomes altered and the animal dies. Should the [protoplasmic molecules of these] cells be only partly injured the body prevails over the disease, the molecular defects of the cells becoming regenerated. The surplus of anti- bodies, the result of this regenerative action, are after recovery found circulating in the blood, and in some instances may even pass into the milk. The amount of protective bodies or anti- bodies in the body-fluids varies according to the intensity of the reaction and the time elapsed after recovery from the infection, the greater part being used up during the course of the disease and the remaining gradually disappearing in metabolism; while with the removal of the stimulus the supply from the cells tends to cease. If, however, infectious and toxic material be again introduced into the system, stimulating and injuring the cellular 28 Predisposition and Immunity. protoplasm, the production of antibodies will be again induced, receptors being again formed. This form of immunity, produced through cellular activity following the introduction of the infec- tious agents, is known as ‘active immunization.” The discovery of the existence and production of specific antibodies in the serum, for which we are mainly indebted to the studies of Behring upon tetanus- and diphtheria-immunity, has led to extremely im- portant methods of prophylactic and therapeutic inoculation against a number of the infectious diseases. This becomes possible from the fact that the blood serum of an animal which has survived a certain infection and is highly immunized against it can be em- ployed by injection to produce in a second animal similar im- munity against the same disease. The production of the pro- tective material in the blood depends upon the introduction into the experiment animals, either intravenously or subcutaneously, of , gradually increasing amounts of the infectious material against which immunization is sought. The animals in this way become more and more highly immunized and their blood serum becomes correspondingly rich in antitoxine. By such a system of pro- gressive inoculation it is possible to attain a degree of concentra- tion in which a thimbleful of the serum contains more immuniz- ing material than would exist:in all the blood of the body after one single attack of the disease. The ability to produce such materials exists in the cells of all kinds of animals, both those susceptible to the disease in question and those naturally resistant to it. For example, by injecting the bacilli of swine-erysipelas, which in natural conditions are pathogenic only to the bristled kine, it is possible to induce the reaction also in sheep, goats, cattle and horses and produce in their blood immunizing substances ; and then, after withdrawal of the blood from animals‘thus pre- pared, to obtain from it a prophylactic and curative serum in suffi- cient quantity for use in hogs., The production of active im- munity in an individual requires some time, because the body cells must first form the protective substances; in other words, must first pass through the period of the disease, perhaps four to six weeks in duration. When, however, the prepared serum is intro- duced there is no such demand ‘placed on the body cells; the pro- tective substances, already formed, produced from the animal supplying the serum are introduced into the second animal. An immunity thus obtained is spoken of as “passive immunity.” It comes on immediately or in a few hours after the inoculation, Protective Immunization. 29 according to circumstances. As a definite cellular reaction in such a case does not occur at all, or at best only in a minor degree, and as the amount of protective antitoxic material intro- duced is gradually used up, destroyed or excreted , (urine) and no new antitoxine is afforded because of lack of proper reaction, such passive immunity passes away after a short time (seven to fourteen days). The recognition of this peculiarity has in practical application led to ,the coincident or successive employment of both methods of immunization in case of certain of the infectious diseases. Serum is first injected so as to induce a passive immunity in an animal, and living germs are next inoculated so as to transfer a passive into an active immunity; the previous introduction of the protective serum making the later inoculation with living microbes practically free from danger. CONGENITAL AND INHERITED DISEAS@s If there exist at time of birth in an individual actual disease, or peculiarities of predisposition or immunity which also char- acterized the parents or ancestors, such conditions are said to be congenital (innate), and in the latter instance mherited (heredi- tary) as well. The genesis of such an occurrence is by no means always the same, although in a measure it is apparently dependent upon conditions of the parents. During intrauterine life the embryo may experience injuries affecting its normal growth, causing deformity, interfering with the proper development of a limb or organ, or destroying some part already in stage of development. Such injuries are for the most part mechanical in type, as where atmniotic adhesions (or more rarely tumors of the uterus) by constriction or pressure of this or that part of the foetus (which in its movements might be entangled in the amnion) may compress, wound or otherwise injure it. Depending on the nature of such an injury, the embryo may in consequence present gross or trivial faults of one sort or another; these are spoken of as fetal or embryogenous anomalies, vitia congenita, developmental defects or monstrosities. Except when a uterine lesion is the cause of the deformation of the fcetus, the mother has no influence upon the production of anomalies in the offspring. There are a number of infectious diseases whose causative micro-organisms are capable of gaining access to the foetus indi- rectly through the placenta. In ,their multiplication in the pla- cental tissue they may, by growth, penetrate it and obtain entrance to the blood of ,the foetal side. Under such circumstances the newly born animal carries into the world with it the same disease from which the maternal parent was suffering during the term of her pregnancy; the acquirement is here placental. The most com- mon example ,of such a transmission is seen in congenital tuber- culosis in cattle, occurring only in case the cow has uterine tuber- culosis. The congenital pathological conditions of this type have Congenital Predisposition. 31 therefore an intrauterine mode of origin, which, if strictly inter- preted, is comparable to acquirement by an external influence, only that in this instance it operates within the womb. It is reasonable to believe that injurious metabolic products which pass through the placenta of a mother animal suffering from some febrile condition (especially metabolic and nutritive disturbances which react from the mother upon the embryo, affecting primarily the ovum, or in the father’s case affecting the spermatozoon in a similar manner) occasion morbid predisposi- tions, as diminished developmental energy, or perhaps a tendency to excessive growth (dwarfism, fcetal chondrodystrophy, gigan- tism), weak metabolic power, tendency to fatty degeneration or fatty deposition (ovogenic or spermatogenic predisposition, con- genital degenerative inheritance). | According to Weissmann and Ziegler, it is quite probable that often predisposition to disease and congenital pathological char- acteristics are due to germinal variations; that is, that when two unadapted sexual cells unite there may be developed to some de- gree new and perhaps even abnormal peculiarities in the embryo from the union of the two elements (amphimixis of the ovum and spermatozoon). Thus healthy, strongly-constituted parents may often be seen who sometimes beget offspring of feeble constitution, weak-minded or of other morbid tendency. The offspring is never entirely like either parent, and the various members of the same generation are never alike in bodily struc- ture and character. Only in case of twins, developing from one ovum or from one act of copulation, is there striking similarity of the bodily features. In the mingling of the maternal and paternal sexual elements two strains of hereditary tendency unite to pro- duce new germinal variations. Should there be thus produced new peculiarities of value to the individual, or which we care to preserve, type-characteristics (precocity), these are not regarded as pathological; but it is readily conceivable that the variations might but poorly fit the offspring for life and render it but feebly resistant to given pathogenic influences or show from the first abnormal constitution of its tissues. In such cases is presented a germinative or constitutional predisposition. A predisposition, no matter how developed, as well as ac- quired immunity, may be transmitted to the offspring, provided the individual is capable of begetting; yet not every tendency toward disease and not all the resistive powers of the parent are 32 Heredity. necessarily continued to succeeding generations. Only such con- ditions are transmitted as pre-existed in the germ, in the seg- mentation cells and the embryo, or those in which apparently the nature of the whole parental cellular stricture is altered, as germinal variations and so-called constitutional tendencies and diseases. i ‘ Injuries and diseases which do not involve the sexual cells, as all simple traumatic lesions of the body, give rise to no trans- mission. For example, the common custom of cropping the ears and tails of dogs has never led to the birth of a short-eared or stub-tailed dog or of such a breed (just as the practice of cir- cumcision, practiced for hundreds of years among various peo- ples, has never yet caused any congenital anomalies of the prepuce). If occasionally structural anomalies of this type are encountered careful investigation will show that some intrauterine mechanical fault is responsible for the defect in the foetus, as Bonnet has demonstrated in case of stump-tailed dogs that the caudal vertebre have been bent or deformed simply by intra- uterine pressure (amnion). This is also proved by the fact that the same anomaly occurs in cats (and in any other animals whose tails are unobjectionable to man and for the removal of which there is no occasion), showing that the habit of cropping can scarcely be held responsible. Non-transmissible conditions and those which are truly in- herited may very closely resemble each other in their anatomical features, and yet depend on entirely different causes; only the closest inquiry revealing the fundamental influences producing them. For example, supernumerary toes (polydactylism) may be an atavistic phenomenon, a family trait, or may occur in a foetus as a splitting of a digit because of amniotic adhesions; in the same way harelip (congenital fissure of the lip) may be caused by local amniotic trauma or may be an hereditary anomaly. * Heredity is best understood when it concerns chemical in- fluences. As indicated by Ribbert, it may be conceived that the whole body can suffer from the wide dissemination through it of some chemical substance and that, of course, under the circum- stances the germ cell is also reached by the same noxious ma- terial. If the organism survive such disturbance and become immune through the changes called forth by the chemical poison, the germ cell may also survive with the same immunizing changes. Should’ such a process befall both parents, both spermatozoon | Hereditary Disease. 32 and ovum are likely to be immune and the new cellular structure resulting from the copulation of these two (the embryo) will possess the same characteristic and transmit it again, because its own sexual cells are clearly the descendants of the rest of the group. In the same way a predisposition may be established and transmitted, because the chemical substance in some way weakens the germ cell and diminishes its resistive ability, and by the fusion of two similarly enfeebled sexual cells the progeny, as the product of both, partakes of their qualities. Similarly to such chemical influence as Ribbert suggests, any exaggeration or diminution of the body temperature must affect the germ cells. Inherited pathological conditions and properties of immunity need not necessarily manifest themselves in each successive gen- eration of posterity indefinitely; for the most part they are limited to a few generations and then disappear. But they may recur in later generations. If but one of the progenitors possess a certain predisposition and come in sexual union with a non- predisposed individual, the pathological condition will progress- ively diminish by half (Ribbert) because of its distribution in the two sexual cells; is proportionately corrected by the healthy cell of the copulation and by germinal variation; and grows weaker and weaker until it is no longer a factor in the posterity. Should the peculiarity reappear after several intervening genera- tions, it may be assumed that this occurs as a result of the union of two germ cells, each possessed beforehand of a disposition which was hitherto latent, but which from the summation of the characteristics of both parent cells has again become. sufficiently intensified to reappear as a pathological fault (Ribbert). Hence we distinguish: a direct heredity from father and mother to the off- spring; a latent heredity if the offspring of affected parents are spared but in the next or later generations the disease should appear, arising from a transmitted tendency; a collateral heredity, should the disease manifest itself in the side lines of the family group; an atavistic heredity, when the origin of the disease suggests a reversion to the family ancestry. In human medical practice the following are considered as diseases transmissible by heredity: Hzemophilia or haemorrhagic diathesis, color blindness or Daltonism (so named after the Englishman, Dalton, who was himself color-blind), lenticular Opacity or “gray cataract” (or cataract), near-sightedness or 34 Heredity. myopia, pigment-atrophy of the retina, polyuria (production of excessive amounts of urine), predisposition to mental diseases, to progressive muscular atrophy, to tumors, to obesity and to cer- tain malformations (dwarfism, polydactylism, harelip, etc.). The anomalous conditions mentioned are due, perhaps, to germinal variations, possibly first brought into active manifestation by the introduction of some external disturbing factor. (Vide Rib- bert, Lehrbuch der allgem. Pathologie. 1901.) What parts respectively are taken by heredity and by external influences in the development of congenital affections is im many instances difficult or even impossible to determine, as our knowl- edge of these matters is still deficient. This is particularly true regarding the so-called hereditary defects of the domestic animals. Among the diseases included in this category for the last century or more, some are surely not inherited and not transmissible but occur because of external influences; for example, intermittent ophthalmia, cataract, asthma, ringbone, frog-thrush. Others, as dumb-staggers [“blind-staggers’], hamoglobinzmia, curb, spavin, deficient hoof-formation, may be caused directly by external in- fluences, although it cannot be denied that inherited structural de- fects may indirectly favor their appearance.* As instances of direct inheritance and congenital origin may be mentioned many cases of goitre in animals. *Cf. Dieckerhoff, Ueber d. Erbfehler bei Zuchtpferden: Zeitschr. f. Veterinar- kunde, 1902, Feb., p. 53. Gavisis.OF DISEASE The influences which lead to bodily injury, to pathological lesions, and which are spoken of collectively as disease causes (cause morb1) may be arranged in a number of classes. There are influences against which the strongest and most resistive constitution is powerless and which inevitably induce disease in the animal coming under their action; such absolute pathogenic imfluences include ‘mechanical forces, intense thermic and electric agencies, mineral and vegetable poisons in their higher dosage and concentration, and, provided they can gain entrance to the intracorporeal structures, various animal para- sites, bacteria and [animal] microorganisms. Other harmful agencies are pathogenic only under special circumstances and are therefore only relatwe, depending, for example, on the quantity of the exciting agent, or upon special predisposi- tion of the subject or:upon the concurrence of several harmful influences (relative causes of disease). The occasion which brings a harmful influence in relation with the body or subjects the latter to such influence, is spoken of as the predisposing cause (causa proxima). ‘The principal factor in producing a lesion is known as the special, immediate or essential. cause of disease (causa essentialis); among these it should be understood that either external harmful agencies which have gained entrance into the body or which operate upon it from without, or some already existing tendency toward disease may be included. For example, pasturing upon some upland infested with anthrax affords the opportunity by which the anthrax bacillus as the essential cause of anthrax gains entrance to the body; an injury, the favoring condition for wound infection by the essential cause of tetanus. Anything which promotes the action of an injurious agent may be regarded as a contributary cause (causa au.ilians). Pathological influences may be divided into the following groups: 36 Causes of Disease. 1. Disturbances of Nutrition and Alimentation: Abnormal states of nutrition depending on irregularity in the water or nutri- tive elements afforded. | 2. Obstructions to Respiration: Interferences with oxygen convection. 3. Functional Disturbances: Depending upon fatigue, upon overexercise of the organs. 4. Thermic Influences: High or low temperatures. 5. Electric Agencies. 6. Mechanical or Traumatic Agencies. 7. Chemical or Toxic Agents: Poisons. 8. Microbic or Infectious Agents: Micro-organisms belong- ing to the protophytes and protozoa. g. Animal Parasites: Of the class of worms and arthropoda. Disturbances of Alimentation and Nutrition. Total deprivation of food without water supply (complete in- anition) leads, in case of the higher vertebrates, to rapid loss of body-weight, emaciation and death in the course of from one to four weeks. With absolute rest (as in case of imprisonment in a caved-in mine) an adult man may retain life without food and drink for about twenty. days; exertion hastens the end. Strong dogs have lived under similar conditions for thirty-six days; horses and cats should live for about four weeks with absolute rest. Guinea-pigs and rats die within three to nine days. Liberge states that a well-conditioned cow, which had wandered into an out of the way place and had remained there forty days without food and without opportunity for much exercise, picked up quickly on a milk diet and was in tolerable condition eight days after being set free. If water is obtainable abstinence from food can be endured without permanent harm by man and carniverous animals for from two to four weeks, and the fatal end may be postponed for a considerably longer period. A cat experimented on by Bidder, weighing two and one-half kilograms, died on the eighteenth day from starvation after having lost 1,197 grams (water consumed, 131.5 grams). Birds of prey (eagle) endure hunger and thirst for twenty to twenty-eight days; small birds only two to nine days. Mascagni has recorded a turkey’s having fasted for twenty- , nine days. In case of cold-blooded animals the requirement for food is so small that water-salamanders and turtles may live for ~_ Disturbances of Nutrition. 37 a year, snakes for six months and frogs for nine months, taking nothing but water. . When fasting an animal must furnish whatever energy 1s necessary for the maintenance of its proper temperature and for its organic functions (muscular activity and circulation) by the destruction of its body tissues, nourishment from external sources being impossible or insufficient. How the destruction of tissues, an actual self-combustion, takes place and how the vital organs live upon the less important structures, is well shown by the com- prehensive studies of E. Voit. Fat and glycogen are first sacri- ficed, and as long as these substances are present the albuminous elements are not subject to the destructive process, the muscular structures afterwards bearing the greatest part of the loss. Loss of weight and atrophy are most marked in the omentum and the fleshy parts (also the fat and glycogen stored in the liver), and fat animals succumb to starvation later than lean ones Accord- ing to Chossat, young, poorly nourished pigeons die after three days with a loss of one-third their body-weight ; plump ones after thirteen days, with a loss of half their weight. The heart shows the least loss in weight (its constant activity and functional stimu- lation hindering its atrophy) ; the central nervous system similarly loses but little, and the diminution in the red corpuscles is com- paratively unimportant. (Lipomata are unaffected in starvation; attempts to cause their removal by starvation have been un- successful—Samuel.) Death from starvation takes place after the development of great muscular weakness, with complete loss of power and deep stupor (Samuel). In the bodies of animals dead from this cause are to be noted muscular and glandular atrophy, passive congestion and degenerative changes, together with scanty contents of the small intestine and diminished lumen of the latter. Complete inhibition of water (as in feeding with material arti- ficially deprived of its water) acts quite as effectively as hunger, death taking place in from eight to twelve days. Animals, un- able to quench their thirst, refuse food, and the organism is unable to adequately supply the fluid secretions necessary for digestion. Death probably is due to the retention in the system of injurious metabolic products (with poisonous qualities), which cannot be flushed out. Actual drinking of water may very well be avoided by a number of animals (rabbits, guinea-pigs, cats or parrots) without injury to health, provided the food ingested contain water. 38 Causes of Disease. Diminution in the amount of food ingested, undernutrition (relative or incomplete inanition), is often met with in connection with diseases of the alimentary tract; its consequences are pre- cisely similar to those of total withdrawal of food, save that the progression of the case is slower. Usually the condition is ac- companied by a diminution of erythrocytes in the blood (imanition anemia), the alimentary disease producing wide disturbance through fluid-waste (diarrhcea) and other complications. Faulty composition of food causes partial starvation, the body suffering loss in its fat, albumen or carbohydrate should its nour- ishment lack or contain but an insufficient amount of one of these substances, or should the animal by preference and exclusively feed upon only one of these types of nutritive material. Impoverish- ment of the diet in such manner brings about emaciation and yhysical weakness. If lime should be deficient in the food and water supply the skeleton will fail of its most essential constituent, that which gives it its rigid strength, and the bones become soft. Respiratory Faults. All animals die by asphyxia* if their supply of oxygen be prevented. A wide range of factors may bring about a diminu- tion in the proportion of oxygen contained by the blood, asso- ciated as a rule with insufficient separation of the carbonic acid and its consequent high proportion in the blood. Primarily this may result from the insufficient access of atmospheric air to the respiratory organs, as by closure of the superior orifices [smoth- ering| or by obstruction of the respiratory tube [choking] and constriction of the latter (strangulation, compression of the larynx or trachea) by fluids and foreign bodies (the latter also by lodging in the pharynx and occluding the trachea), pres- sure upon the larynx and trachea by tumors, obstruction by tumors or swelling of the mucous membrane in the folds of the glottis or in the bronchial tubes, collections of blood, fluid or coagulated exudates in the lungs and bronchi. A second group of asphyxiating causes includes interference *The editor is here taking the liberty of using the word asphyxia as the general term, including smothering as meaning respiratory obstruction, operative at the respiratory orifices, mouth and nos¢c; choking, respiratory obstruction operative within the mouth, nasopharynx or esophagus (pressing on the larynx or trachea) ; strangulation, respiratory obstruction by constriction or pressure from without upon the larynx or throat generally; suffocation, respiratory obstruction by any type of cause operative below the level of the larynx, either within (as a suf- . focative gas) or without (as pressure upon the chest). In English this meaning is attached to asphyxia, although as Prof. Kitt indicates in the present section it really means pulseless; his own general term is “Hrstickung.” Respiratory Disturbances. 39 with the respiratory movements, as in case of rupture of the diaphragm, the principal muscle of respiration, in case of its immobility or when it is forced forward by flatulence, in case of marked pressure from without upon the chest walls (animals standing pressed together in railway cars), or in case of pressure upon the lungs by large fluid collections in the chest cavities. Failure of respiratory movement may also occur from nervous origin (pressure upon the brain, paralysis of the vagi, spasm of the bronchial muscles). Premature separation of the piacenta or compression of the umbilical cord in the maternal canal prevents oxygen convection to the feetus. Furthermore, passive congestion of the lungs, interference with the emptying of the pulmonary veins and hzmic changes in which the blood corpuscles. have lost their ability of taking up oxygen (carbon monoxide poisoning) render diffusion of the gases so difficult that the same result of lowering oxygenation arises, and the respiratory disturbance eventually advances to the stage of suffocation. ‘The presence of irrespirable gas and the reduction of oxygen in the air of an inclosed space (instead of 20.8 per cent., perhaps only 2 to 3 per cent.) act in a similar manner. In one or other of such a variety of ways asphyxia may be the termination of a number of diseases and is the commonest cause of death. It is usually accompanied by the symptoms of dyspnea (4% diorvoa, from mvéw, difficult breathing, shortness of breathing), labored respiratory movements (suffocative dyspneea), marked increase in the cardiac movements, spasmodic twitching of the general musculature and loss of consciousness,’Toward the close the respiratory movements become irregular, sometimes intermit and suddenly cease, the inspirations occasionally becoming very deep (terminal respiratory movement); and the spasms weaken the cardiac action (true asphyxia, actual pulselessness, from a privitive and 54 cdvyyués, the pulse). When the diminution in oxygen is gradual in its onset these symptoms appear less promi- nently; but as the tissues degenerate from the insufficient supply of oxygen (fatty degeneration of the heart, liver, kidneys) and as the respiratory nervous center loses its excitability, the patient dies from gradually increasing loss of consciousness and cardiac failure. According to the rapidity of onset of the fatal end and the causes of the asphyxia, the post-mortem findings present dif- ferent pictures. In addition to the local changes due to strangu- 4O Causes of Disease. lation, obstruction to the respiratory passages or the rest of the causes mentioned, the most common features of this mode of death are found in the tar-like, uncoagulated, dark condition of the blood (excessive presence of carbonic acid, deficient decarboni- zation) and in the presence of hemorrhages in the lung and pleura. Excessive Functional Stimulation. All organic- activity is accompanied by consumption of the essentially functionating material of the organs and by the formation of metabolic products. Both of these factors, especially the accumulation of the latter substances in the tissues of the organ, lead to a gradual reduction in efficiency, that is, to fatigue. This is normally corrected (restoration or reconstitution of the part) during the intervals of rest, when the accession of arterial blood replaces what has been lost and the lymph current sweeps out the waste products (fatigue waste). Should the various or- gans be required to continue their activity without intervals of rest for a long time, or should they suddenly be overstrained, or called into functional effort beyond their physiological ability, their parenchymatous substance may be so affected by the height- ened metabolism and so marked an accumulation take place of the waste products of fatigue (carbon dioxide, phosphoric acid, either free or combined as acid phosphates), that exhaustion or wearing out results, with complete abolition of functional ability. This condition is clearly pathological if tissue changes can de- velop in the process and make the loss of function permanent (fatty degeneration or cellular atrophy), or if the cessation of function, momentary though it be, can cause in the vital organs disturbances involving the general economy or the actual death of the individual. Coincidence of other contributing causes (the weakened stage in fevers, traumatism or thrombosis) favors the development of such functional lesions from overexertion, as seen especially in the heart, the general muscles and in the nervous system. General muscular fatigue and cardiac exhaustion may be the cause of death in overheated animals. Horses suffering from thrombosis of the abdominal aorta and its branches exhibit signs of functional disturbance of the muscles of the posterior limbs, even under moderate effort, because of their poor arterial supply and the accumulation of waste products from fatigue.. The heart Functional Stimulation; Thermal Influences. 41 fatigued by prolonged effort may lose its power of contraction to such a degree that it becomes abnormally distended by the pres- sure of the contained blood (cardiac dilatation, insufficiency of the heart), with ensuing disturbance of the circulation. Over- stimulation of the nervous system by sudden psychical shock is not only in man productive of serious results; fright palsy with cessation of cardiac action (paraplexis) has also been observed in the lower animals (fowls). A gradually and only moderately increasing demand upon the muscles and glands acts as a stimulus to their functional activity, provided proper nutrition be afforded the tissue, and results in fasc- tional hypertrophy, that is, in an increased growth of the cellular elements corresponding to the demand for work. This may be noted especially in tubular structures provided with muscular walls (smooth muscle), where there is gradually and spontane- ously developed an increasing competence for the work required of the muscle, as in the thickening of the muscular layers of the bladder in case of gradually narrowing stricture of the urethra (v. junctional hypertrophy). Thermic Influences. High temperature of the surrounding atmosphere (above the body temperature peculiar to the animal) may lead to failure of heat loss (heat stasis) and hyperthernua of the entire body with fatal termination by so-called heat-stroke. .This is frequently ob- served in hogs when crowded in railway cars. The condition is most easily induced if the dissipation of the body heat by evapora- tion is diminished, and at the same time heat production in- creased in the animal by prolonged muscular effort or by rich feeding. (It is known from experiments that warm-blooded ani- mals kept in well-ventilated warm chambers at 36 to 40° C. die, some in from one to three days, others in from ten to thirty days. The body temperature of such animals—rabbits—rises to 39 to 42° C.; they become dyspnoeic and there is increase in the frequency of the pulse; the hemoglobin of the blood is re- duced, and degenerative changes develop in the heart, the liver and kidneys.—Ziegler.) The cause of death is cardiac failure (heat rigidity) occasioned by the overheated blood, or may de- pend upon a thickening of the blood through excessive loss of fluid by sweating and respiration (fall of blood pressure, dimi- 42 Causes of Disease. nution in vascular tone). As anatomical changes are found red- dening of the skin (in hogs), failure of blood coagulation, dilata- tion of the right heart, venous hyperemia of the lungs, liver, kidneys and brain. The names insolation and sun-stroke are ap- plied to that form of heat-stroke which is caused by the influence of the direct- heat-ravys of the sun upon the body, particularly upon the head; it is thought to depend upon a paralytic dilatation of the vessels of the meninges and cortex of the brain, and the affection is accompanied by convulsions and marked symptoms of excitation (Birch-Hirschfeld). The influence of heat locally applied occasions lesions known as burns (combustio), of various grades according to the degree of temperature, the duration of application and the resist- ive powers of the tissues to heat. Burning may result from con- tact with solid, liquid or gaseous heated matter, or from direct action of a flame or radiant heat. Short exposure-to a tempera- ture of 40 to 50°, or longer exposure to 30 to 407 7G aaemone. ductive of an inflammatory reaction marked merely by dila- tation of the capillaries (hyperemia) and redness of the part (inflammatory burn, erythema, burn of the first degree or of mild degree). The process is only superficial, leading at most to desquamation of the epithelium. Exposure to heat of 60 to 80° C. (burn of the second or intermediate degree) is productive, in addition to the hyperemia, of rapid exudation of serous fluid from the dilated vessels beneath the epithelial layer, The cells of the stratum Malpighii are pressed apart by this, become swollen, are loosened from the papillary bodies, and the firm, horny portion of the epidermis is raised up to form a blister. Through minute fissures, easily made in this bleb, pyogenic bacteria may enter, the fluid contents through further exuda- tion [leucocytes] becoming turbid and purulent. Should the blister rupture the hyperemic papilla beneath are exposed, the repair of the epidermis starting from the epithelium at the mar- gins of the lesions or from remnants of the Malpighian cells which were not destroyed. In case of mucous membranes, which are devoid of the horny epithelial layer, blister formation is not likely to take place, the epithelial layer desquamating in shreds;. and the denuded surface is covered by a coagulating exudate, the so-called croupous or false membrane. ‘The more severe influ- ences. of ‘heat, above 80° C. (burns of the thrd degree), produce searing and charring (eschar formation); the burned — Thermic Influences. 43 tissue coagulates ; the blood within the capillaries is coagulated and stagnant, the tissue dying in consequence and being trans- formed into a brownish crust (or eschar). At the border of the actually involved and necrosed tissue inflammation ensues. Heal- ing follows by the separation of the charred material and the formation of scars, which are apt to be of a radiating, reticular appearance, and which by their contraction and shrinkage may cause considerable disfiguration. All these degrees of burning may coexist as the heat has happened to influence in a greater or less measure one or more places. In extensive burns of the skin (if as much as one-third of the body surface is involved) the subject is likely to die, even in case of burns of no more than the first or second degree. Death may take place within but a few hours after the occurrence of the accident with symptoms of impaired respiration, cardiac weakness and fall of the body temperature. In other cases the fatal end may take place after the course of a week, during which there may have been apparently favorable progress, pulmonary cedema and nephritis often developing in the meantime. Other cases pursue a course of some weeks’ duration before the lethal end. The explanation of the dangerous features and fatal termi- nation of such burns is to be sought'in part in functional dis- turbance of the skin in heat dissipation, fall of blood pressure, over- heating and inspissation of the blood (cardiac paralysis) and in part by the changes which the blood corpuscles undergo. Dif- ferent investigators (Salvioli, Maragliano, Castellino, Ponfick) have shown by experiment and observation upon. human cases, that after burns of the skin the red blood corpuscles, partly de- generate (broken into small particles) and partly without any apparent structural changes, are incapable of conveying oxygen, and give up their hemoglobin (partly changed into methzemoglobin) into the serum, whence it is excreted by the liver and kidneys; that, further, the formation of hyaline thrombi is apt to take place and that these alterations of the blood may be regarded as the cause of death. Low temperatures, which deprive the body of its proper warmth, may give rise to either local or general disturb- ances in warm-blooded animals. Sensitiveness to the power of withstanding cold varies very much in the different animal species. Fishes chilled to the freezing point may seem to be lifeless, their lymph frozen into solid ice; yet they may com- 4A Causes of Disease. pletely recover from such a condition. Frogs are said to remain viable for hours subjected to a temperature of -2.5° C., with the heart frozen solid (anabiosis). According to Koch, resuscitation is possible only by gradual thawing and providing only a part of the water present in the body has been actually frozen; in case of rapid thawing, violent diffusion currents appear between the water emerging from its crystalline form and the concentrated albuminous solutions of the bldod and tissues, which may destroy the tissues (Koch, Ziegler). Fibernating animals sleep but lightly with a blood temperature of 6° C., but soundly at 1.6° C.; their cardiac beats sink to eight to ten each minute; breathing is almost suspended, the movement of the lungs caused by the heart action alone carrying on the feeble gas diffusion in the lungs (Samuel). The hair and feathers (especially the winter pelt) of animals lessen the loss of heat by radiation and by convection of the [warm] ‘air from the surface of the body; in consequence of which animals are seen to endure with ease the ordinary cold, providing they are well nourished, move about freely and thus produce heat abundantly. [The loss of this protective element or the presence in the hair of much moisture favoring the ready convection of the heat from the body surface reduces tremen- dously the power of resistance to cold; and one finds the cattle in the prairies freezing to death in a rain at a temperature con- siderably above ice-forming temperature, although were the hair dry and capable of holding the layer of warmed air close to the skin the animals would have shown no signs of discomfort. |] If there be diminution of heat-production because of insufficient nutrition, and extreme cold, even well-pelted animals (hares and deer) and birds may be frozen to death. Death by freezing takes place by loss of sensibility of the nervous system, with fall of body temperature, diminution in the frequence of the cardiac and respiratory movement, cerebral anzmia, loss of muscular power and blood coagulation. The local action of cold, varying with duration of exposure and intensity, causes tissue changes of the same types as in burns (frosting, congelation). Primarily there results a constric- tion of the vessels of the part exposed (local anemia), after which, if the cold continue, the nerves and muscle tissue of the vessel walls become paralyzed and dilatation of the vessels ensues with increased blood content, this condition usually returning to Thermic Influences. 45 normal when the low temperature of the part is corrected. Tem- peratures below the freezing point are, however, likely to so disturb the vessel walls that inflammation of the tissue (swelling and redness of the skin, frostbite, chilblain) develops with or without the formation of blisters; or after especially long and severe exposure the blood and lymph circulation cease and the tissue dies as a result. The necrotic area may be separated from the normal by inflammatory reaction, or if it remain moist may undergo putrefaction through the influence of invading bacteria. The extremities.are the parts of the body most commonly sub- ject to freezing, but it is seen rather seldom among animals, for example, the scrotum in bulls (Bang), the paws in dogs, in horses the thick skin of the hoof, particularly the crown and pastern. Jewsejenko and Cadiot have recorded instances of necrosis from freezing of the deeper part of the foot in horses (in the Russo-Turkish and Franco-German wars, as well as in Algeria). e hadss By the term catching cold (chilling) is meant the pathogenic action of heat loss not sufficient to cause freezing, but produc- tive of functional disturbances and inflammation of nerves, muscles, joints and internal organs. The laity commonly and primarily for almost all affections attributes chilling as the cause; and even the physician often evades the question as to the origin of some malady with the vague phrase of the possibility of catch- ing cold, because of the obscurity of the etiology of the case. Many diseases formerly regarded as produced by exposure to cold are now recognized in the advanced state of etiological in- vestigation as infectious, although undoubtedly there is a group of affections in which chilling of large areas of the skin and mucous membranes may with confidence be held responsible as the causal agency. Such a relation is evident in cases where, after unusual exposure to cold (thorough soaking, strong draughts, falling into icy water, heat loss by radiation to some neighboring cold object as a stone wall) there immediately develop in the chilled parts pains, functional disturbances and symptoms of in- flammation, or where in a short time these phenomena without other demonstrable cause appear in the subjacent or more distant parts of the body. Cats almost invariably become sick if they become soaked by falling into the water, while flocks of sheep have been attacked by pleuro-pneumonia directly after wool washing if, while wet, they were left exposed to cold air. The 46 | Causes of Disease. occurrence of paroxysms of colic (dysperistalsis) in sweating horses after chilling of the surface cannot be denied. Rabbits and guinea pigs dipped into ice-cold water have been known to quickly sicken and die from pulmonary and renal inflammatory affections. As a further illustration it is well known that the peritoneum is very susceptible to the effects of lowered tempera- ture, and that in case of extrusion of the viscera or in operations involving the exposure of the peritoneal cavity there often arise, even at a temperature of 21° C., entirely from the chilling (under conditions of asepsis and in the absence of other causes), a gen- eral depression of temperature, attacks of colic, peritonitis and perhaps a fatal termination. Hofer has observed that chilling may affect even fishes, provided they be suddenly changed from a warm water to a cold; and that such chilling causes changes in the skin (desquamation and necrosis of the epithelium). Attempts to frame a theory explanatory of the real nature of chilling have as yet been unproductive of any definite informa- tion on the subject. If it be assumed that the blood in the cutaneous vessels is chilled, it remains unexplained why practi- cally only isolated parts of the body are affected, although the chilled blood flows on to other organs. Excretion of blood pig- ment in the urine: (hemoglobinuria) after exposure to cold might well be explained upon the idea of chill effects upon the blood causing destruction of the corpuscles, yet in such cases of hemoglobinuria there is usually a previously developed myositis and the red color of the urine is looked upon as a result of the liberation of muscle pigment and not as depending solely on blood destruction. The chilling of the skin causes extensive vas- cular constriction and the blood is forced from the surface and accumulates in the internal or more deeply lying parts of the body. Why in these cases the blood is not evenly distributed in the body, but collects in special localities, is an open question. Sudden exposure of a cutaneous or mucous surface to cold un- doubtedly causes an appreciable vascular tonic contraction, which may be ascribed to stimulation of the vaso-motor nerves. This vascular spasm is not limited to the area directly affected by the cold, but extends consensually or reflexly to adjacent or symmetri- cal, or distant vascular areas (Samuel). If, for example, one dip a hand into very cold water the other hand also becomes paler (Samuel), and probably everybody has had the experience that oc- Thermic Intiuences. 47 casionally a sudden chilling of the feet brings on directly a reflex sneezing and nasal catarrh. Rossbach has observed in experiments upon cats that by applying cold compresses over the abdomen vas- cular constriction passing over into vascular dilatation develops in the mucous membrane of the respiratory passages. There usu- ally succeeds upon the vascular constriction a relaxation of the vessel walls with which is associated a marked congestion (vid. Hyperemia). Such disturbances are,. of course, commonly cor- rected, the vascular constriction and internal congestion together with the vascular relaxation disappearing, and the chilling is realized but for a short time as a sense of cold or brief catarrhal affection by the subject. Why the same adjustment does not occur in all cases is not clear. We only know. as a fact that the chilling leaves in the skin itself practically no anatomical altera- tions, that the sensitiveness of the nerves, contractility of the vessel walls, the circulation and perspiration are entirely re- stored, while in the deeper structures the vascular spasm and the succeeding vascular dilatation are apt at times to be pro- longed. Sometimes, as further consequences, local engorge- ments, nutritive faults of the tissues, inflammatory exudates, ex- cessive mucous glandular secretion are to be seen; sometimes catching cold may manifest itself only by nervous symptoms, functional disturbances and sensations of pain and may abso- lutely fail to give any idea concerning the anatomical changes of the tissues. Affections which arise in consequence of catching cold are often but transient and are very apt to change their location in a system of tissues, appearing successively at different points along the larger nerves and in muscular regions and at different joints. For this reason they have been called rheumatic affections. [While it is true, as the author indicates, that the varied effects of chilling of the cutaneous surface are not susceptible of a simple explanation, there are certain probable influences which can scarcely be overlooked. The development of congest- ive states in some mucous membrane in connection with the more or less widespread vascular changes beginning in the skin may be held as offering favorable conditions for the more active growth and penetration of some microorganisms, which perhaps in the normal condition, although present, were unable to advan- tageously invade the membrane, and many of the catarrhs which follow refrigeration undoubtedly show clear evidence of such in- 48 Causes of Disease. fectious agencies. The old idea that by causing a more or less prolonged contraction of the cutaneous vessels the skin secretions are reduced or prevented and that in this way there tend to accumulate metabolic or other toxines in the tissues cannot be set aside. Such substances have been thought to perhaps possess irritant qualities which disturb the sensory nerves and muscle fibres and other structures, the rheumatic pains and stiffness sup- posedly arising in consequence. At least some weight is to be given to the readiness of disappearance of such symptoms when by warmth and exercise the general circulation is stimulated and skin secretion heightened, these toxines then perhaps finding more ready excretion from the body than could be afforded by the other excretory paths. |] Electrical Influences. Powerful electrical discharges upon the animal body induce paralysis of the nervous apparatus (especially of the respiratory centre), electrolytic destruction of the red Blood cells, local burns of the skim and laceration of the tissues. Death usually follows; but the paralysis and unconsciousness may, after shorter or longer duration, go on to recovery. The larger animals (cat- tle and horses in the stall or in the open) are especially liable to be struck by lightning (Frohner, Ziegenbein). Contact with live wires and completion of the circuit through the bodies of horses occasionally takes place when they step upon the contact points of an electric railway in the street pavements or on a broken overhead wire.* Horses have been killed by a current strength of 500 volts, 100 amperes (Puntigam, Mouquet, Blanch- ard) ; alternating currents of 160 volts are sufficient to kill dogs (Birch-Hirschfeld). According to Leblanc, horses are exceptionally susceptible to electricity. A horse was killed, for example, by a relatively light current which the owner passed through the bit in order to divert the attention of the animal while being shod. Anatomical changes may be entirely absent when death has been caused by electricity, or the hair may be found singed and the skin burned by the electric spark; and at the points of en- trance and exit of the lightning or current; as well as im the internal organs, the tissues may be lacerated, with which lesions *Birds sit on telegraph wires with impunity because they are not in contact with the earth. Electrical and Mechanical Influences. 49 hemorrhages of course occur. Along the entire course of the current tree-like, branching lines of ‘singeing (hyperemia and hemorrhages), the so-called lightning pictures, may be seen in the skin and intestines. In addition the blood is dark and un- coagulated, the muscles dark brownish-red, the endocardium stained by the altered blood, and the heart muscle at times the seat of hemorrhagic infarcts. Mechanical Influences. Pathological changes are very frequently produced by me- chanical force. These are either lesions of tissue cohesion, ruptures (breaks in continuity, lesio continu), or of compression, as the constriction of a hollow organ, condensation of tissues or displacement of organs. If this be caused by eternal forces or foreign bodies the process is spoken of as traumatism (trauma, 76 tpadua, lesion, lat. lesio), The active agent is either a dull (fall, blow, jolt, pressure, pull, friction) or a pointed or sharp (stab, incis- ing) solid body. . In the same way imternal mechanical disturbances may be caused by adhesions of the tissues, tumors and other pathological products producing constricting influences, or by excessive blood pressure, abnormal gas expansion or pressure by fluids; or may involve the functions of organs (displace- ment of actively motile stomach, intestine, uterus or, muscle). If the force gives rise to loss of continuity amounting to visible separation of the tissue the lesion is spoken of as a wound, hurt, teay (vulnus, trauma in restricted sense); if affect- ing dense structures (as bones, cartilage or teeth), as a break (fracture) ; if the tissue be destroyed by compression, as a crush, contusion or bruise. Displacements (dislocations) are met in joints, bones or muscles, as wrenching or luxations; in the intes- tines as ruptures (hernia), or twists (volvulus). The term stenosis is employed in connection with constriction and oblitera- tion of hollow organs; where the closure is caused by some fac- tor in the inside of the organ it is spoken of as an occlusion stenosis; where it is due to external pressure it is said to be a pressure stenosis, The results of mechanical injury are extremely numerous and vary with the size and character of the producing agent, as well as of the local lesion, and with the relative importance of wounded tissue to the general organism. A wound is often 50 Causes of Disease. complicated by other factors, as from the entrance of microbic or toxic agencies through the opening or breach made by the foreign body, with the result of further alteration of the tissues. The traumatic agent may be at the same time the conveyor of such substances, or may itself be a living parasite. Intense mechanical force may sometimes without any evident lesion, sometimes with manifest lesion, cause serious and perhaps fatal effects upon the nervous system. For example, this occurs in vio- tent concussion of the body (commotio from com-moveo), espe- cially if the vertebral column be directly affected (concussion of brain and spinal cord—the former causing the loss of conscious- ness, the latter bilateral palsies of the extremities, the bladder and rectum). What the precise anatomical changes are which in such instances take place in the central nervous system has as yet not been determined, autopsy usually showing nothing that is characteristic. Possibly the alterations are molecular. Death sometimes takes place suddenly, too, from blows upon the abdominal wall and viscera. Such instances are characterized by sudden loss of strength, fall in body temperature, cardiac fail- ure and diminution of nervous excitability. This condition is known as shock, traumatic stupor, collapse, traumatic reflex par- alysis. It is thought that the paralysis and cardiac failure in such cases is due to vagus irritation. Chemical Agents; Poisons. Substances which harm the animal body by their chemical ac- tion are known as potsons; the actual process of introduction of the poison and its action, as poisoning or intoxication. Probably nearly all chemical substances can, under proper conditions, act as poisons, or, in other words, have a deleterious influence upon the tissues; the mode and power of combination of the chemical and the amount and degree of concentration in which it is present in the body being important items. For example, a substance as essential for the body as sodium chloride will in large doses cause vomiting and fatal poisoning in dogs. The most poisonous substances, as hydrocyanic acid or nicotine, have absolutely no effect when given in the minute doses of the homeopaths. Changes in the relation of the atoms and solubility may transform a non-poisonous substance into a poisonous one and vice versa; of the two forms of phosphorus, only the white is Chemical Agents. 51 poisonous, the amorphous red form being harmless even in large quantities. A number of substances which are insoluble in water, and which have practically no effect when brought in contact with the skin or when introduced subcutaneously, are changed by the hydrochloric acid of the stomach so as to become serious poisons; for example, carbonate of barium is changed in the stomach into the soluble chloride of barium. On the other hand, there are substances which are apparently energetic poisons when in- troduced into the blood, but which are inert in the stomach be- cause they are completely neutralized by the albuminates of the gastric juice (Samuel). Many poisons belong to the mineral kingdom or are artifi- cially made from minerals, as arsenic, mercury, iodine, bromine, chlorine, lead, copper and others, and the various compounds of these substances (oxides, sulphides, chlorates, chlorides, etc.). The organic compounds, as alcohol, chloroform, hydrocyanic acid, cyanide of potassium, carbolic acid and picric acid, especially [include many poisons]. The vegetable kingdom (Samuel) affords many examples of poisons. There are whole families of plants whose genera and species possess some poisonous principle common to them all. In many plants certain parts may contain a poisonous substance, while the rest may be quite free from it and edible (as is well known in case of potato plants, solanum tuberosum, whose leaves, blossoms, seed and immature fruit contain the poisonous solanin, while the tubers are quite free from it). A number of plants are innocuous, slightly or seriously poisonous, depending upon ques- tions of climate, location, character of the soil and cultivation; the almond tree, for example, bears either sweet or bitter al- monds, according to the location. The most powerful poisons contained in the higher plants are the vegetable alkaloids (mor- mute, atropine, colchicine, digitaline, etc.). In case of the lower plants also, especially the bacteria, there are products, some of which are marvelously toxic, fatal to large animals in the most minute and scarcely appreciable amounts; these substances, analogous to the alkaloids and enzymes, or of albuminous nature, are embraced by the terms toxrines, toxalbumens, toxenzymes. (See also chapter on bacteria.) Among animals there are a number known to be able to elaborate poisonous secretions within special glands, especially the venomous snakes (vipera berus, the common adder of Ger- 52 Causes of Disease. many; vipera Redu and ammodytes in southern Europe, the dif- ferent species of crotalus (or rattlesnake) in America, possessing poison glands in connection with the teeth or jaws. Scorpions, the females and neuters among honey bees, wasps and bumble bees possess poison glands and a sting at the posterior end of the abdomen; toads and salamanders, wart-like skin glands; hairy caterpillars, many biting flies, gnats and gadflies, salivary glands. There are certain species of fish, like the barbel, whose sexual glands contain a poisonous fluid and whose fins are provided with a poisonous substance derived from the skin glands. It is not certain whether the occasional poisonous qualities of edible mussels, oysters and star fish depend on transient gland secre- tions (sexual seasons), upon the food of these animals, or whether they arise from bacterial changes of the animal after death. The changes caused by poisons are partly limited to certain localities, partly connected with general anatomical and physio- logical changes.* The poisons may be arranged for classification in four groups, according to their modes of action: (1) Corrosive, locally irri- tative poisons; (2) Parenchymatous poisons; (3) Hemic poisons; (4) Nerve and Cardiac poisons. Many do not confine their in- fluence to a simple type, but excite lesions and symptoms of mul- tiple character simultaneously. The corrosive and locally irritative poisons (caustica, irritan- tia) vary in their results with the dosage and concentration of application and with the character of the tissue with which they come in contact, ranging from simple hyperemia and inflammation to coagulation, eschar-formation and solution of the tissues. Such lesions depend upon special properties of the substances, as abstraction of water from the tissues, precipitation or solution of the albumens, formation of precipitates in mucus forming tis- sues, solution and decomposition of urea, conversion of fats and carbohydrates into acids, as well as production of a variety of chemical changes in the salines of the body or other destruction of the structure of the living protoplasm. Among these caustics and irritants (to the skin or mucous membranes by direct contact) are included the corrosive acids (sulphuric, nitric, hydrochloric, oxalic, osmic, acetic, carbolic,y etc.), the caustic compounds of the alkalies and alkaline earths (potassium and sodium hydrox- *The following is taken from the works of Samuel, Ziegler and Birch- Hirschfeld. 7Carbolic acid or phenol is really an alcohol. Chemical Agents. 53 ides, quicklime, barium chloride), the corrosive salts of the heavy metals (salts of antimony and mercury, zinc chloride, zinc sul- phate, chromate of potassium, etc.), the poison of the beetle Lytta vesicatoria, cantharidin, snake venom, the poison of the sting glands of bees, wasps and hornets, the salivary secretion of gadflies, stinging flies and mosquitoes, and the so-called acria or acrid medi- caments derived from a number of plants (croton oil, mezereum, etc.). A number of poisons, volatile or gaseous in form, may also cause dermal or mucous membrane irritation, especially to the lining of the respiratory tract during inhalation (irrespirable gases). Should these irritant and corrosive substances be ab- sorbed and be conveyed by the lymph paths into the blood and internal organs, they may cause, in addition to their local effects, associated disturbances of the heart and nervous system, the liver and kidneys. Substances inducing degenerations of these paren- chymatous organs may be spoken of as parenchymatous poisons, their effects depending chiefly upon alterations of tissue meta- bolism, regressive nutritive changes and formation of precipitates in the tissues. Among this group phosphorus belongs, capable of causing’ extensive fatty degeneration of tissues, especially the liver. Corrosive sublimate, chromic acid, cantharidin, which pro- duce marked changes in the renal parenchyma, are also irritants. The production of argyria, the impregnation of the tissues with minute black particles of silver after long continued administration of nitrate of silver, may be thought of as a similar process; and lead is an excellent example of parenchymatous poisons, producing, as it does, a wide range of disturbances, palsies, de- generations and both loca! and general pathological results. The so-called hemic poisons act principally by depriving the red blood corpuscles of their power to act as conveyors of oxy- gen, by inducing their disintegration, liberating and breaking up hemoglobin or causing thrombosis. Some in addition may cause lesions at the point of introduction, and perhaps directly influence the nervous system. Some of them are gases entering the blood through inhalation, others are in solution and are derived per- haps from the intestine or from wounds. ‘The best known blood poison is carbon monoxide, a constituent of illuminating gas, which enters into combination with hemoglobin to form carbon- oxyd-hemoglobin, and thus prevents absorption of oxygen by the blood and induces a tissue asphyxia. A characteristic feature of CO poisoning is the bright, cherry-red color of the blood. Sul- 54 Causes of Disease. phuretted hydrogen (in poisoning from the gas of manure pits) acts partly by paralyzing the nervous system, partly by forming sulphmethemoglobin, giving a greenish (almost cadaveric) tint to ' the blood. Hydrocyanic acid and cyanide of potassium also cause a rapid paralysis of the central nervous system, in addition to interfering with oxygenation of the blood cells and tissues (cyan- methemoglobin, bitter-almond odor in the organs). Potassium chlorate, nitrobenzole, potassium nitrate and amyl nitrite cause marked destruction of red corpuscles and transform hemoglobin » into methemoglobin, in which the oxygen is more firmly fixed than in the oxyhemoglobin. The blood, and of the organs in such instances the kidneys especially, take on a striking brown color. Extensive hzmocytolysis, with liberation and solution of the hemoglobin in the blood plasma, giving a blood-red color to the urine (hemoglobinuria), are caused by various toxines of fungous and bacterial origin (ptallin, helvellic acid), arsenu- retted hydrogen, anilin, nitrous acid (fumes), carbolic acid and other poisons. Coagulation of the blood and its sequels are seen in poisoning with ricin (from the seeds of castor oil plant) and abrin (from the seeds of abrus precatorius). Infectious Agencies. By the term infection (ificere, to put into, to inoculate, to taint) is meant the entrance into the system of a disease-pro- ducing microorganism capable of self-multiplication, a pathogenic microbe. Nature is richly supplied with microorganisms; which on the borders between the animal and vegetable kingdoms represent primitive forms of living matter, in their minuteness are visible only with the aid of the microscope and are recognizable as consisting of but single cells. According to their classification as plants or animals, they are spoken of as protophytes or pro- tozoa. ‘There are forms which are only visible with a magnifica- tion of 2,000 diameters, and even then as barely perceptible points without definable cellular characters; and there ‘are reasons for believing that still smaller organisms exist, invisible with our present optical instruments, but by no means unreal, being dem- onstrated as corpuscular entities by other methods, as by their detention in filtration or by inoculation (so-called invisible microbes). Infectious Agents. 55 Even in ancient times the idea prevailed that devastating epidemic diseases were caused by a living contagion (contagiwm vivum sive animatum). The nature of these contagions re- mained hidden, however, to the physicians of antiquity; and the impossibility of determination led, especially in the middle ages, to the wildest conjectures as to the nature and origin of epidemics. They were attributed to evil spirits, deemed punish- ments from on High, fancied the results of supermundane pow- ers, of influences of the stars; their origin was sought in con- ditions of the weather, in magnetic and meteorological processes, in putrid gases and in peculiarities of the soil; and the hidden factor was characterized as a constitutio epidemica or pestilens. It is only about fifty years that our conceptions as to the real nature of epidemics began to become clearer and an assured foundation became established by precise observation—when, with the aid of the microscope, it became possibie to demonstrate the existence of low vegetable organisms as foreign and invading elements in the diseased body and to determine the role which they play in the production of disease. In the last few decades this phase of science, stimulated and reorganized by the luminous work of Louis Pasteur and Robert Koch, improved by many technical aids and demonstrative methods, has fully disclosed the developmental history of many infectious diseases. Advances of tremendous significance for the whole of medical science, dis- coveries and experiences of the greatest consequence in the com- bating and cure of diseases, have been attained in this line of study. * The demonstration of the relation which a given microbe bears to a given disease has been especially facilitated by the success of artificial cultivation of microorganisms outside the body (in vitro, upon nutritive media) and of production at will at any time thereafter of the infectious disease by inoculation. Such experiments have been made not only in animals, but also in human beings many times; and anyone conversant with the subject can convince himself by combined cultural and inocula- tion experiments that certain microbes cause certain diseases. The objection that the microorganisms are not the cause but the accompaniment or product of the disease can easily be proved worthless. Of course there are microbes in the body which have nothing to do with disease, merely surface inhabitants of the integument and mucous membranes, able to penetrate into the 50 Causes of Disease. blood and internal organs only after death of the animal (mostly putrefactive organisms). Those parts of the human or animal bedy which are freely accessible are exposed to the entrance of bacteria as of anything else from the exterior. Many of these microorganisms find fa- vorable conditions for existence in the surface of the skin and mucous membranes, live and multiply there without doing harm, finding their nutrition in the secretions and refuse of such lo- calities. They come from the air where they exist in the dust, from food and drink, and, in fact, from any objects in which they exist and with which contact is had. In our alimentary tracts there are always millions of bacteria* and other fungi, in the stomachs of ruminants countless infusoria, all of which par- take of the nutrient fluid and aid by certain secretions of their own in the digestion of the food, but have no pathogenic action; they are our table guests (commensualists) and stand in a re- lation of symbiosis to us (living together for mutual profit). As long as these conditions are maintained and as long as they obtain their nutrition merely from the dead material they may be considered as harmless saprophytes (camps, decayed; bvrov, vegetable growth). Their harmlessness is explicable by the fact that these microorganisms are not in any way fitted for attack- ing the living substance of the animal body, and their metabolism gives rise to no products which might be toxic to the cells and tissues of the animal; or whatever toxines there may be are quickly neutralized by the body secretions. Besides, their increase is held in check by the various adjustment powers of the body. The protective epithelium of the skin and mucous membranes prevents their penetration into the tissues; they are expelled from the air passages by the activity of the cilia of the lining epithelium and from time to time by the expectoration of mucus; many are retarded in their growth by the acidity of the gastric juice and by the intestinal secretions, as well as by the bile; large numbers are expelled with the excrement from the in- testines; many dry up upon the surface of the body. Moreover, the various organs and cells, as the liver and phagocytes and the blood particularly, contain substances of antitoxic and microbici- *A stained smear preparation should be made from the surface of the gums, tongue or throat of a convenient cadaver as proof of the interesting flora existing there and as evidence of the wandering corpuscles in our cellular constitution. Vid. for fuller consideration Kitt, Bakterienkunde f. Tierdrzte, IV. Aufi. Wien, 1903. Infectious Agents. 57 dal power; and even though they have gained access into the blood, bacteria may by these agencies be rendered harmless. There must, therefore, be special conditions afforded before a microorganism can become the actual cause of infection. In’ the first place the microbe must possess peculiar toxic powers. All microbes carry on metabolic processes and elaborate a va- riety of chemical substances in the medium in which they exist. If among these products there be any which are harmful to ani- mal tissue, the possibility of toxic action exists. Since Brieger called attention to these substances and indicated their relation to disease occurrence, many of these microbic poisons have been proved to exist by various investigators and the process of infec- tion is recognized as invariably connnected with intoxication. In one class of microorganisms, the bacteria, poisons have been demonstrated which are apparently free, soluble secretory products of the bacterial cells, and which exhibit strong simi- larity to ferments. ‘These poisons are as yet not well defined from a chemical standpoint; they are quickly rendered inert by Beite@ heated (to 50° to’ 80° ©.) and are peculiar in that they do not manifest their activity at once, but require a certain period of incubation. They are, moreover, especially peculiar in their specificity and in the fact that when introduced into a susceptible animal there 1s invariably a specific antitoxine gener- ated. They are, therefore, not a homogeneous product of all bacteria, but differ among themselves from their origin and the particular kind of microbe, each as a special product of a special process. These poisons are collectively called toxines. According to Ehrlich’s theory, a toxine is a poison which possesses two specific groups of atoms, one of which, the /aptophore, anchors the toxic molecule: to the cellular protoplasm for which it has affinity; the second, or torophore group, doing the harm, supplying the real poisonous agent.‘ The toxines act then because they enter into chemical combination with the cells. (Vide Chapter on immunity, pp. 18 and 22.) The proof that a microorganism secretes a toxine and through it produces disease of the animal body is shown by the following: Many bacteria can be grown artificially upon nutritive culture media, as bouillon. If they secrete soluble toxines these will accumulate in the medium. If such a culture be passed through a filter impervious to bacteria, as a porcelain filter, the bacteria will be retained by the filter and the bouillon will pass through clear and quite free from bacteria. If there follow the injection 58 Causes of Disease. of such a germ-free filtrate (into a suitable animal) evidence of toxic action, especially a specific one, then we must be dealing with a dissolved toxine yielded by the bacteria. The best and simplest example of this is afforded by cultures of tetanus bacilli, the filtrate from which produces typical and characteristic te- tanus symptoms, the dry residue from the evaporation of the filtrate acting in the same manner. A second proof that the immediate agent of bacteria is their soluble toxine may be had by artificially removing the latter from the germs. If water be allowed to run for several hours through the residue of bacteria upon the filter they will be washed free of the toxines and can be inoculated in enormous amounts, by the millions, without giving rise to apparent harm (the inert bacterial cells being quickly destroyed by phagocytosis in the ani- mal body). Yet if these harmless bacteria be returned to a nutri- tive medium where they can again multiply, they produce poison anew, this collecting in the substance of the bacteria and in the fluid in such quantities that inoculation of even the smallest quantity, a very few of the bacteria, will produce fatal effects. The virulence of toxines is remarkable; a hundred-thousandth of a cubic centimeter of the filtrate of a tetanus culture is suffi- cent to kill small animals, and a ten-thousandth of a milligram of the dried substance will do the same; less than one milligram would cause tetanus convulsions in a human being. Such facts prove that some bacteria are provided with toxic agencies of frightfully dangerous power and explain why, when such causes of disease gain entrance into the human or animal body, they prove victorious in their conflict with the animal cells. Toxins do not act uniformly upon all animals. Intoxication oc- curs only when they enter into chemical combination, only in bodies whose cells possess substances (receptors) capable of union and having chemical affinity for the toxine. In bodies in which such receptors do not exist the toxine behaves as an indifferent substance. This explains why certain animals show a natural immunity against certain toxines and why the bacteria producing the latter are harmless to these animals, as chickens are insus- ceptible to tetanus toxine. There are some germs which produce no toxine separable by filtration as a secretion, but whose toxicity is occasioned by sub- stances enclosed in the body of the microbe and fixed there (endotoxines). Some of these substances are of albuminous na- = Infectious Agents. 50 ture (toxalbumen, mycoprotein, bacterial protem). They vary in their composition and modes of operation, some being peculiar to certain kinds of bacteria, others common to several forms. In general they act like albumens foreign to the animal, causing in- flammatory changes, necrosis of cells and tissues and exciting fe- brile reactions. The dead bodies of the bacteria act in the same way to some degree, their toxic substances being freed only by the death and maceration of the microorganisms. A number of bacteria produce pathological changes also by elaboration of: acids and gas-forming substances, as sulphuretted hydrogen. | In addition to their chemical action it should be said that mechanical disturbances may be occasioned by bacteria which, in their multiplication, produce masses, perhaps for example ob- structing the blood vessels. The sum total of the pathogenic properties of a microbe is spoken of as its virulence. According to the quality of toxine produced and the energy of growth of the microbe in the animal body, there may be recognized gradations and differences of in- tensity of virulence of the various genera, species, strains and individual microbes; their power of disease production corres- sponding with the same factors. Just as in artificial culture in a number of nutrient media a bacterium will either elabo- rate much toxine and grow rapidly or will produce but little toxine and grow slowly, according to the composition, reaction and temperature of the medium; so in different kinds of animals there is a variation in capability of growth and toxine production of a given microbe. In adaptation to the conditions of nutrition afforded in a given body microorganisms may in greater or less measure lose the power of growth exhibited in some other body, may be altered in their pathogenic power; this is spoken of as change of virulence by transmission. Such change may manifest itself either as an attenuation or as an intensification of virulence. The oldest known example of attenuation by transmission is seen in the change of virulence of the germ of smallpox; variola, which in man is severe and marked by pock eruption all over the body, produces in the cow merely a local and mild eruption. In the cow, moreover, even in the first generation, it is permanently so attenuated that after reinoculation in man it gives rise to only a benign local eruption (not a general one). Wide differences of virulence exist: between the different strains [growths of the 60 Causes of Disease. same organism from _ different sources] of the _ tubercle bacillus; those obtained by culture from the human body have become almost non-virulent for cattle by their adaptation to man, although some strains are readily transmissible. Avian tubercle bacilli are innocuous for mammals (except rabbits) and conversely it is difficult to infect chickens with human tuberculosis. How- ever, Nocard succeeded, by placing human tubercle bacilli, inclosed in collodion sacks containing bouillon, in the peritoneal cavity of chickens, in so adapting their growth to the avian body that there- after (in later generations of the culture) they became pathogenic for birds as well as men. In part, at least, the variability in the virulence of microbes of the same species must be recognized as a reason for the occurrence of either a comparatively mild or a severe course of an infectious disease (formerly called genius epizooticus) as well as for its self-limited termination. For example, mouth and foot disease in some of the epidemics which sweeps the country runs an unusually severe course with high mortality, although under ordinary circumstances it is not a fatal disease, recovery taking place in the course of two weeks. The investigations of Loeffler have shown that the virus of this plague, if inoculated from cow to cow, gradually loses its pathogenic powers, whereas if alternately transmitted from cow to swine in a long series the virulence is maintained or even increased. It is interesting, too, that pathogenic organisms may be influenced in artificial cul- ture outside the body so that their virulence may be either in- creased or diminished (change of virulence by artificial culture methods). Toussaint and Pasteur, who were the first to estab- lish this possibility, have demonstrated that anthrax bacilli, promptly fatal to cattle, sheep, rabbits and mice, may be so attenuated in virulence by artificial culture in bouillon at a tem- perature of 42° C. that they produce fatal effects only in mice. Similar facts have since been established in connection with a number of microorganisms capable of artificial cultivation, culmi- nating in efficient methods of prophylactic inoculation (Pasteur). This is easily understood when we realize that the attenuated germs give rise to but a mild attack of the infection when inocu- lated, which, however, leaves behind an immunity to the disease. On the other hand, an intensification of the virulence, even of microorganisms ordinarily without pathogenic influence, has been obtained by other cultural methods, as in nutrient media rich in Infectious Agents. 61 albumens and in the absence of oxygen (Wiener, Hueppe). From such considerations it may easily be appreciated that virulence is a very variable property.* It is also essential for the development of an infectious dis- ease that the infectious agent should be afforded a suitable path of entrance or atrium to the tissues. Mere contact with a micro- organism does not necessarily result in disease; there are often pathogenic microbes upon the surface of the skin and mucous membranes, the host in no wise suffering in consequence. The virulent germs of tetanus and of spreading gangrene are very fre- quently present in the intestinal canal of herbivora and omnivora, but without inducing pathological results as long as the mucous membrane is intact, their toxines being neutralized and destroyed by the digestive juices. So, too, pyogenic and putrefactive micro- organisms are found in large numbers in the intestinal contents and externally upon the skin in healthy human beings and animals, becoming pathogenic only in case of introduction into the lymph and blood through some tissue lesion. The ordinary places through which microorganisms gain ac- cess to the tissues are the external skin with its gland pores, the digestive and respiratory tracts, the conjunctival mucous sur- faces and the uro-genital passages. The protective epithelium of the skin and mucous membranes interferes with the penetration of most bacteria into the tissues and with their toxic action, partly because of the impenetrable barrier afforded (the horny epithelial layer), partly because the secretions of normal mucous membranes may wash off and destroy the microorganisms and dilute their toxines to such an extent that they are rendered inert or neutralized. This protective means is not an absolute one against some of the bacteria. Some may directly or by growth-extension penetrate the unaltered skin or mucous membranes; or, having gained entrance to sebaceous and sweat glands, especially the glandular ducts or lymph follicles (which are open upon the surface as in the pharynx and intestine), may be carried into the deeper structures by leucocytes (glandular or follicular infec- tion). Many microbes are provided with means of motility (flag- ella) and are thus able to penetrate into canals, or from a surface may find their way into slight depressions or inappreciable defects in the epithelium, where, after local increase, their toxic metabolic *See further Kitt, Bakterienkunde fur Tierdirete, M. Perle, publisher, Wien, 1903, 4th edition. 62 Causes of Disease. products naturally come to reach such a degree of accumulation (concentration) that further tissue change is caused and opportu- nity thus afforded for further penetration by the germs. In this manner rats may be infected by plague by merely dropping upon the unaltered conjunctiva the plague bacteria; and the trypansome of dourine (horse) invades the body by its own motile power through the mucous membrane; various bacteria, if they can gain entrance into a duct in the nipple of the mammary glands, may multiply luxuriantly in the milk and give origin to intense sup- purative inflammation. Microbes gain access to the digestive tract. along with food and drink or may be swallowed after being inhaled with dust. The special point of infection (so-called iutestinal or food in- fection) in this case is usually the lymph glands of the mouth and pharynx, or of the intestine; by the same route it is possible that the toxic products of microorganisms, themselves confined to the interior of the intestinal canal, may be absorbed through the blood and lymph channels. Microbes gain access to the respiratory tract by inhalation (inhalation infection) with dried dust particles or in the fine dis- charge coughed up by diseased animals and subsequently dried. They are in this case in part retained on the nasal mucous mem- brane, in part adhere to the pharyngeal surfaces and may thence pass into the lymph follicles and extend by route of the lymph- atics or be swallowed (giving rise indirectly to an alimentary infection), or they may be carried by the currents of air into the lungs directly. Infection of the urogenital mucous membrane usually takes place by transmission of the germs from one to another indi- vidual in the course of séxual congress (covtal infection). A most favorable opportunity for infection is afforded by wounds of the skin or mucous membrane (wound infection), affording access to the microbes into the lymph spaces and chan- nels of the connective tissue, to the subcutaneous and_ sub- mucous structures, favoring penetration into the peritoneal cavity and eventually into the blood. The wounds may be so small as to be inappreciable to the unaided eye, as some tiny abrasion of the epithelium; or it may be that before the disease actually appears there may intervene a considerable period of time, the wound perhaps long healed, so that the point of entrance is en- tirely lost (cryptogenetic infection; «kpiwrew, to conceal). This ff nfectious Agents. 63 latter is often the case when we are dealing with a follicular in- fection. The various pathogenic microbes do not possess uni- form powers of disease production, of multiplication and dissemi- nation, granted that they gain entrance by one or other of the points suggested. Some give rise to infection, no matter from what point they are introduced; that is, they are capable of Seumity irom various atria (tubercle baci!li). Others require introduction in certain situations in order that they may show pathogenic effects, a fixed point of access. For example, the te- tanus bacillus, as already indicated, can only be actively patho- genic from wounds; the germs of vaginal catarrh and epidemic abortion naturally (partly effective also in case of intra- vascular inoculations) involve only the genital mucous mem- igamies ss the bacteria of «mastitis invade the lactiferous ducts Gao etae bacteria of cali diarrhcea confine their activity to the stomach and intestines. These peculiarities probably depend upon the presence at the appropriate points of entrance of es- pecially favorable conditions for multiplication of the germs, other parts presenting certain interfering conditions. Many germs require some special underlying condition in order that they may live and multiply. For example, the piro- plasmata must get into the blood, because they can only obtain their sustenance under the conditions afforded by the living blood and die out in the body fluids. Other organisms, as the colon bacillus and vibrio of Metschnikoff, thrive best in the chyme and intestinal mucous membrane. | Doubtless the condition of the cells and juices of the body plays some part in the question of development of the infection. The biological and biochemical differences in cells and _ fluids, designated as tissue predisposition and tissue immunity, are indi- cated by the fact that a given species of animal is by nature com- pletely resistant to a certain microbe and its toxine, surely lethal for some other species, and by the varying rates with which dif- ferent tissues are involved, as where practically only one of the tissues offers resistance to the growth of the microbes (as the resistance of muscles to tuberculosis) or where but a single tissue is involved. Hence the question of development of an infectious disease depends not only upon the existence of a given essentially virulent microbe, but also upon the defensive powers of the body, upon the antitoxic and microbicidal properties of its organs and 64 Causes of Disease. upon the mechanical obstruction to the penetration of the germ into the tissues (vide pp. 18, 21). The interval between the entrance of the microbes into the subject and the manifestation of appreciable symptoms is spoken of as the period of incubation. ‘The length of this stage depends upon the vital peculiarities, the virulence and number of the microorganisms, and upon the site of the infection and the predisposing factors in the animal affected. Ii the @mierewes are capable of rapid multiplication and of generating large amounts of toxic material (as the bacteria of chicken-septiczemia, which rapidly increase in the circulating blood, or the colon bac- teria of mastitis which thrive luxuriantly in the milk of the udder) the period of incubation is usually of but a few hours’ duration. Microorganisms of slow growth, as tubercle bacilli and actinomycetes, induce functional disturbances only after the structural changes which they bring about have attained a certain grade of development, and of necessity extend their period of incubation over weeks and months. Before the symptoms are appreciable clinically extensive anatomical changes may in many cases have developed, whence it follows that a disease may be latent or occult in its period of incubation, although if the animal be slaughtered it is clearly seen to have been present for some time. For example, in the case of pleuro-pneumonia in cattle there are often found characteristic appearances of the pulmonary in- flammation in animals which have been slaughtered when appar- ently quite healthy; and in hogs affected with erysipelatous valvu- lar endocarditis of intense grade, the disease may be discovered only on slaughtering, the animals having shown in life no symptoms of a character to have suggested the existence of their disease. In rabies and tetanus, in which the virus causes symptoms only after it has become fixed in the cerebral nervous system [the toxine in case of the latter rather than the germ itself], the disease manifests itself the more rapidly the closer the point of infection to the brain: if the virus be ganec lated directly into the brain the incubation lasts but a few days, while in case of ordinary subcutaneous inoculation it may be prolonged to weeks, the virus being at first retained in the lymph glands. Cases of infection of human beings by the bites of rabid dogs manifest rabies in 8-14 days where the wounds are in the face, but when the hands or feet have been bitten the period of incubation lasts usually one or two months, and sometimes the Infectious Agents. 65 @isease does not appear for a year: The influence exerted by the virulence, the amount of toxine and the particular infec- tious germ upon the period of infection may be appreciated after introduction of tetanus toxine into mice; the symptoms of the disease, depending upon the dosage, appearing after varying inter- vals from 12 hours to 2—6 days. The dissemination and multiplication of pathogenic germs 1n the body exhibit a number of peculiarities. Some micro-organ- isms remain closely confined to the immediate vicinity of the point of infection, giving rise from this localized situation to toxic results in proportion to their own disintegration and to the ab- straction by the fluids of the body of their toxic substances. Thus they mav cause lesions only in the neighboving tissues or induce intense general disturbance after absorption. The tetanus bacillus, for example, does not grow free in the body (except in the uter- ine cavity, where, under anzrobic conditions, the organism can accumulate in large quantities after having once been introduced) ; in the course of a day or two after incculation it can no longer be found at the site of infection (wound), nor elsewhere in the body. It.disappears because of its disintegration and through the agency of the phagocytes. Its toxine, however, is absorbed and causes the ganglion cells to undergo necrobiotic changes. Often bacteria, as the pyogenic organisms, increase by multiplication at the site of infection, but are prevented from further extension by the defensive properties of the body. For the most part the germs are distribttted from the point of infection along the lymph channels, in part at least because the newly developed germs are produced about the borders of the focus, . are swept away in the lymph plasma or are taken up by the leuco- cytes and carried elsewhere. The local focus (local infection) en- larges directly into the surrounding regions. (regional infection) ; and the microbes, conveyed by way of the lymph channels, are car- ried deep into the tissues to the lymph glands, from one site to an- other, from one lymph gland ‘to another, tintil they finally reach the blood. They may also gain direct entrance imto the capillaries, veins and arteries from the point of infection (as in wounds or ulcers, or by direct extension by growth through the vessel walls) and be carried along with the blood current (embolic or hemato- genous infection). There thus are produced at a distance from the point of entrance or primary focus of infection new deposits of the infectious agents; and either new local areas of disease, 66 Causes of Disease. secondary metastatic foct of infection, are caused, or the micro- organisms are widely disseminated throughout the whole body (general infection, bacteriemia). As an illustration, streptococci of epidemic coryza in the horse gain access to the pharynx with the drinking water or with the inspired air; they here first give rise to a purulent catarrhal inflammation, penetrate by direct growth into the pharyngeal follicles, gradually make their way along the Eustachian tubes to the middle ear and here set up a similar puru- lent inflammation. Being carried away by the lymph current and by leucocytes, they give rise to abscess formation in the retro- pharyngeal lymph glands, and by going lower, in the cervical nodes ; and, too, they may be swallowed and infect the mesenteric lymph glands as they pass along the chyliferous tract. Passing from the lymph glands to finally reach the blood, they are disseminated by the latter generally throughout the body, and cause a variable num- ber of metastatic abscesses in such situations as the brain, lungs, liver and kidneys, eventually a septico-pyemia. In similar way infection of the umbilical vein in the new-born by pyogenic bacteria causes primarily a local abscess-formation at the umbilicus, fol- lowed by multiple venous-embolic abscesses in the liver, later in the lungs, the joints and elsewhere. It may happen that at the point of infection the local lesions are so slight as to be appreciable only by microscopic study, that the microbe passing from this point first lodges in the lymph glands or may perhaps even pass through several lymph-nodes without occasioning any disturbances, multiplying and manifesting its influences only after it has gained access to the blood and circulated in the body and become fixed in this or that position at a distance from the original site of entrance. The tubercle bacillus, for example, may be absorbed from the intestines with- out causing any alterations in them, but giving rise to caseation of the mesenteric lymph-nodes; or these may be traversed by it, the germ gaining access to the blood, and perhaps first deposited in the bone-marrow, where it gives origin to the primary tubercu- lous focus. The physiological movements and changes of position of the intestines and muscles aid in great measure the spread and dis- tribution of the invading and multiplying microorganisms; pyogenic microbes which have gained access to the peritoneal cavity are apt to be spread over the whole peritoneal sur- face by the peristaltic movement of the intestine, the resulting peri-. Infectious Agents. 67 tonitis as a consequence being generally a diffuse one. Tuber- cle bacilli having effected an entrance into the pleural or peri- cardial cavities multiply in the lymph and are actually rubbed into the whole serous surface by the movements of the heart and lungs. For this reason there usually occurs in these regions a disseminated, dense eruption of tubercles involving the whole pleura, pericardium and epicardium. So, too, currents in the secretory fluids on mucous surfaces are favorable to the dissemina- tion of microorganisms; and the covering of these surfaces permits migration and generalization, especially of the motile forms. Tubercle bacilli may thus reach the larynx in the bronchial secre- tions from cavities in the lungs, and if retained may occasion laryngeal ulceration; pyogenic bacteria from the pharynx may pass to the Eustachian tubes and middle ear in horses; and in case of infection of the milk ducts of the nipple the different kinds of bac- teria in the milk and milk passages advance into the parenchyma of the udder and give rise to mastitis. The pathogenic action of bacteria is, as already indicated, for the most part a toxic process, but also in some degree a mechan- tcal one; it is governed both by the properties and the quantity of the extremely varied metabolic products elaborated by the individual microbes, but is also dependent upon factors deter- mined by the place of infection and by the predisposition of the tissues. Local and general effects are distinguishable; first by the fact that at the original point of infection and at metastatic locali- ties anatomical lesions are originated (inflammations, degenera- tions, necroses, proliferations, depending upon the nature of the microbe, both in the sense of a mere foreign body and of the pecu- liarity of its constituent materials) ; and, second, by the develop- ment of general metabolic disturbances, especially fever, from the generalization of the infectious agents and their products. In each case the phenomena are expressions of tissue reaction to the noxious foreign microbe undergoing multiplication from time to time in the system (v. chapters on fever, limiting inflammation). Each kind of pathogenic microorganism manifests a fixed mode of action, determined by its manner of multiplication in the tis- sues and the particular nature of its toxic product (specific action), and therefore produces a specific disease. In case of other causes of disease there is no uniformity of action, but, on the contrary, a variability; or, better, it may be said that other or non-infectious diseases may occur in the same form from the 68 Causes of Disease. effect of a variety of agencies. A nasal catarrh may be caused by the inhalation of dust, irritant gases, chemical fluids, the influence of cold upon the external surface of the body, or from infection; cold may produce in one subject painful peristalsis (colic), in another muscular rheumatism, in a third a coryza, a pneumonia, an intestinal catarrh. In infectious diseases the body generally reacts with uniformity in a definite manner; the basic symptoms and lesions are invariably manifest, and it is possible to decide from the presence of certain signs of the disease that a definite type of infection exists. By specificity, therefore, we understand that each infectious disease is the result of fixed in- fectious agents and not of anything else. Anthrax is always caused by the anthrax bacillus, and never by any other microbe or noxious agency of any sort; glanders is caused by the glanders bacillus; smallpox by the smallpox contagium. There are, how- ever, some micro-organisms which, because of similarity of toxic properties and analogous modes of multiplication, give rise to the same anatomical tissue changes, so that clinically the same anatomical types of disease are produced by several kinds of germs (the groups of the pyogenic bacteria, the micro-organisms of septicemia, of moist gangrene and of mastitis). Such in- fectious diseases are said to be polybacterial. Variations in the duration of infectious diseases, modifications and degrees of anatomical changes, are proportioned in the sever- ity of the infection to the grade of virulence of the mucrobes, and are dependent as well upon the place of entrance of the infec- tion and the predisposition of the tissues. Just as a corrosive substance, an acid, depending upon whether it comes in contact with animal tissue in concentrated or dilute form, produces either an eschar, tissue necrosis, inflammation or mere hvperzmia, so a difference is appreciable in the action of microbes according as they are highly toxic or more or less attenuated. The importance of the factor exerted by the place of entrance of the infection is indicated by the studies of Arloing, Cornevin and Thomas upon the bacillus of symptomatic anthrax (“black leg’); this micro- organism, if inoculated into the muscles and subcutaneously, kills animals after intense symptoms; but if the inoculation be made into the trachea or intravenously there follows merely an abortive course, which, however, is succeeded by an immunity. Variations of susceptibility and resistive powers in different animal species and individuals to precisely the same-infectious agent may cause Infectious Agents. 69 marked variations in the clinical and anatomical picture of the same infectious disease. hus a certain strain of glanders bacilli has been known to cause in a horse a chronic glanders lasting over several years, but in guinea-pigs and field mice a very acute type of the disease; the bacillus of hog-erysipelas, pro- ducing in one hog an acute septicemia, to cause in a second a slight urticaria, in a third a chronic cardiac valvular affection. The influence of tissue resistance upon the disease picture is especially apparent when inoculations of the organisms of chicken- cholera of high grade of virulence are made into rabbits previously treated by serum injection. Rabbits which have not. been previ- ously subjected to serum injection succumb to hypodermic inocu- lation of but a small number of bacteria as early as from 12 to 24 hours, dying of severe acute septiczemia; those previously injected and then subjected to the same inoculation die only after 5 to 14 days, and then show extensive purulent phlegmons, purulent and fibrinous pleurisy and pericarditis, or merely an anemia as a re- sult of the prolonged infection. Recovery from an infectious disease usually leaves thereafter a certain degree of immunity (v. active immunity, p. 27). Sometimes several kinds of pathogenic organisms gain en- trance at the same time through one point of infection, the result- ant infection being thus a complicated one (mixed infection) ; or after the individual is attacked by one infection other types may invade (secondary mixed infection). The former condition is seen when the infective matter from the beginning contained sev- eral varieties of pathogenic germs, as where a wound is contami- nated with earth containing both spores of tetanus bacilli and pus bacteria, or where a cow’s nipple is soiled with filth and dung in which there are streptococci and colon bacilli. So, too, micro- organisms which have existed indefinitely upon the surface of some mucous membrane may, if occasion presents, penetrate into the tissues along with some other type of infection and combine with the latter in producing pathogenic effects ; thus, should there be pro- duced by some foreign body an injury to the tongue or pharynx of the cow, the various putrefactive organisms living as sapro- phytes in the mouth may occasion with pyogenic bacteria a mixed infection. The second form of mixed infection, the successive mvasion of a second or third pathogenic germ, may be noted where local changes from a primary infection bring about condi- tions which facilitate the access and growth of other microbes; as 70 Causes of Disease. when ulceration has occurred in the primary infection and the protective epithelium has been lost, or when in the course of a disease the bactericidal substances normally present in the fluids of the body have been exhausted and the resistance of the tissues reduced in consequence. Not infrequently such mixed infection is to be seen in hog-cholera, the micro-organisms of which cause necrotic and coagulative destructive changes in the intestinal mucous membrane and general wasting; there is thus prepared so suitable a culture medium for the sputum bacteria and necrosing bacilli present in the pharyngeal mucus and in the intestinal con- tents that these readily penetrate into the tissues and materially contribute to intensify the disease and hasten a fatal termination. Admixture with or contamination (association) of an infection by one or more other types of pathogenic microbes, each with its special properties, and the combined action of all, as a rule causes a severe course of the infectious disease and occasions unusual pathological processes (complications). The mere presence and microscopic recognition of several types of microbes in any focus of disease or in the tissues of the cadaver by no means warrant, without other knowledge, the assumption that there has existed a mixed infection; after the death of the animal great numbers of saprophytic organisms living on the surface of the mucous membranes wander into the organs, and necrotic or ulcerating foci in the lungs, intestine or skin are apt to harbor the same sort of organisms from the air or food (so-called symbiotic bacteria). The association of such essentially non- pathogenic germs, or, too, of pathogenic microbes with another pathogenic variety, may (as especially pointed by Leclainche-Vallée in studies on symptomatic anthrax) determine actual infection; for example, a symbiotic bacterium may prevent phagocytosis by a negative chemotactic power and thus produce conditions favoring the increase of the other infecting agent. This should not be interpreted as meaning that a given microorganism cannot alone cause its special disease, and that only when in association with other microbes can produce its effect; it merely applies to special conditions in which the specific infectious agent is attenuated or is situated in an unsuitable point for infection. All known pathogenic microorganisms are individually capable of giving origin to their peculiar infections, and each is the specific bearer of such infection. Those micro-organisms regarded as pathogenic may be classed in two groups: In the first group are microbes usually living in the external world, but inducing disease in the animal body if by accident they gain access to it (ectogenous infectious agents, facultative parasitic microbes). The diseases arising from this group affect individual animals here and there, or may attack a Infectious Agents. pe number, provided there be opportunity of convection from their habitat in the soil to the animal body with water, food, etc. They are essentially of telluwric origin, and it is customary to speak of Spontaneous disease or miasmatic (76 wlacya, from uatyw, to con- taminate) origin in this connection. In the second group are included microorganisms which, being exclusively adapted to the animal body from an indefinite period, live and thrive in it as their habitat (entogenous infectious agents, obligate parasitic microbes). Diseases occasioned by these do not appear as spon- taneous infections, but occur only when a human being or animal comes in contact with a previously infected individual or with desquamated or excretory material from such an individual in such manner that the infectious agent can pass to the former. Such instances are spoken of as contagious infectious diseases. {Among many there is to-day a strong tendency to deny the existence of pure miasmatic infections, and thus to regard the terms contagious and infectious as synonymous, such persons hold- ing that the so-called miasmatic diseases are caused by organisms which are essentially facultative parasites, and in more or less direct manner have come from previously diseased individuals. @he difference of view is by no.means a vital one, and the author’s recognition of their immediate derivation from a source other than a previously diseased individual is correct. In the sense that these facultative parasitic microbes once affecting an individual may be further transmitted, his division, however, be- comes unnecessary, since in this manner all infectious diseases are contagious. | A certain number of infectious maladies may be acquired in both ways; originating primarily from the soil, the microorgan- isms multiply in the animal body and then are transmitted from the diseased to other individuals (contagio-miasmatic diseases). The fact that some microorganisms thrive only in the animal body and die when in the external world is a phenomenon of adaptation. It may be assumed that all these obligate parasitic germs originally lived a free saprophytic life in nature, but having accidentally gained access to an animal body thrived therein and by rapid succession of generations usual to such low organisms acquired a special adaptation for the conditions thus afforded and lost their faculty of propagation outside. Changes in nutritional conditions are likely to cause changes in their metabolism, and the influence which invading microbes have 72 Causes of Disease. upon the tissues of the body depends in part upon their metabolic activity and metabolic products. From investigations of Wiener it has been shown conclusively that a type of bacteria common to the human intestine and regarded as entirely harmless in this situation and in the excreta, can by special nutritive influence be so transformed as to acquire highly toxic properties (the so-called colon bacilli, living as saprophytes in the colon). If fed ordina- rily to rats they give rise as a rule to no disturbances whatever, but if the colon bacilli have been cultivated for a few days under anzerobic conditions on a medium specially rich in albumen (eggs) they acquire an intense virulence, and if fed to rats produce a severe and almost invariably fatal enteritis. Although such transformation of a non-toxic saprophyte into a toxic pathogen cannot off-hand be accomplished with other micro-organisms, this isolated fact proves that it is possible for infections of a character new and unknown to us to arise from time to time; and as a matter of fact spontaneous infectious diseases do now and again appear which have not been previously observed and which are to be regarded as rarities. It is a pure accident when the special germs are brought into contact with the human and animal body; and it is further conditional upon special circumstances of nutri- tion whether the microbe possess virulent properties, as in case of the meat intoxications caused by various microorganisms, sausage poisoning, diarrhoea and vomiting and wound infections. Some infectious diseases are of very frequent occurrence because the agent is widely disseminated in nature or because opportunities for transmission to the animal body are often afforded. For in- stance, the tetanus bacillus exists in the soil in many localities, and wounds are often contaminated by dirt, the opportunity for tetanus infection being correspondingly common. Such wide- spread microorganisms and their infectious diseases are spoken of as ubiquitous. As the alpine rose and reindeer moss, palms and cacti flourish only within certain geographical limits, and as poisonous snakes and the different kinds of insects have their habitats only in certain parts of the earth; so certain microbes occur only in certain lands, where alone, too, the corresponding infectious diseases arise as spontaneous affections. Such districts are foci in which annually a certain number of cases are likely to occur, and it is said that the disease is established in such places (indigenous, endemic). Truly contagious diseases may also be endemic, provided in a certain district (irrespective of soil ‘ Infectious Agents. 73 conditions) there are always a number of animals suffering from the special infectious disease, so that others from these may in turn acquire the affection. When an infectious disease occurs in isolated cases here and there it is spoken of as a sporadic disease ; if many or great numbers of individuals are affected, it is spoken of as a plague, an epizootic (epidemic) ; if it extend over large areas, and if not merely one species, but many, are affected, it is called a panzootic (pandemic). Animal diseases transmissible to man may be spoken of as androzoonoses. | The separation of spontaneous from contagious infections, the recognition whether a microbe is miasmatic or purely contagious, is of importance in dealing with epidemic diseases; the purely contagious diseases can be eradicated by measures protecting the well from the diseased animals and their excrementitious matters. This has been demonstrated in the extirpation of cattle plague, pleuro-pneumonia and hydrophobia from districts in which for- merly they were rife. SUMMARY OF THE MOST IMPORTANT INFECTIOUS DISEASES AND THEIR AGENTS.* I. Bacteriaemias, Septicaemias. Bacillus avisepticus (Bact. avisepticum s. avicidum), septiczemia of birds and rabbits (chicken cholera). ’ Bac. pleurisepticus, sporadic and epidemic septicemia of all domestic animals (bac. bovisepticus, suisepticus), deer and cattle plagues, pasteurellosis bovis, Bac, anthracis; anthrax of domestic animals and man. Bac. wdematis maligni, spreading gangrene of domestic ani- mals and man. Bac. sarcophysematos bovis, symptomatic anthrax of cattle. Bac. gastromycosis cvis, bradsot of sheep. [Bradsot is a dis- ease of sheep in northern Europe, by many regarded as a form of symptomatic anthrax. | Bac. pestis tarandi, reindeer plague. Bac. rhusiopathi@ suis, swine erysipelas. Bac. suipestifer, hog cholera. Bac. pestis bubonice, human bubonic plague, transmissible to swine and rats. *Wor detailed description and technique of investigations, v. Kitt, Bakterien- kunde f. Tierdrete, 1V. Aufl., Wien, 1903. 74, Causes of Disease. II. Toxic Infections. Bacillus tetam, tetanus in all animals and man. Bac. botulinus, sausage poisoning in man. Bac. enteritidis, meat poisoning in man. Bac. dysenterie vitulorum, diarrhoea in calves. Vibrio Metschnikovi, vibrio cholera of chickens [microspira Metschnikovi, irregular]. III. Inflammatory and Pyogenic Organisms. Staphylococcus pyogenes aureus (albus, flavus, citreus), sup- puration of wounds, furunculosis. Streptococcus phiogogenes sive pyogenes (various forms), suppuration of wounds. Micrococcus tetragenus, umbilical suppuration in calves. Bacillus mallei, glanders in horses and man. Bac. lymphangitidis ulcerose, lymphangitis in horses. Saccharomyces farciuminosus, turunculosis in horses. Streptothrix farcini bovis, furunculosis in cattle [Nocard’s pseudotuberculous nodules in the skin and viscera of cattle]. Streptococcus equi, contagious coryza of the horse. Bacillus acneos equi, contagious pustular dermatitis of horse. Bacterium phlegmasie@ uberis (a number of varieties), mastitis in the cow. | Streptococcus mastitidis (a number of varieties), mastitis in cow. Micrococcus mastitidis gangre@nos@ ovis, mastitis of sheep. Bacillus pvelonephritidis bovis, nephritis of cow. Bac. pyocyaneus, purulent inflammations. Bac. coli communis (a number of varieties), various forms of cellulitis, mastitis, nephritis and enteritis. Botryomyces ascofornians, suppuration and granuloma forma- tion in horse. Cladothrix canis, various suppurations in the dog. IV. Diphtheritic Necroses. Bacillus necrophorus, traumatic necrosis, multiple coagulation necrosis of mucous membranes, liver and lungs in cow, horse and sheep. Bac. diphtherie columbarum, pigeon diphtheria. Infectious Agents. 75 Bac. diphtherie avium, chicken diphtheria. Bac. diphtherie honunis, diphtheria in man, exceptionally in cats and birds. V. Tuberculosis and Actinomycosis. Bacillus tuberculosis, tuberculosis of man and the lower ani- mals (varieties in birds and cold-blooded animals). Bac. bronchiolttidis vituli, cheesy pseudotuberculosis of the lungs in the cow. Bac. pseudotuberculosis ovis, in sheep. Actinomyces bovis, actinomycosis of cow (with varieties). Streptothrix capre, pseudotuberculosis of the goat. VI. Specific Diseases of the Sexual Organs. Bacillus abortivus vaccarum, epidemic abortion of cows. Micrococcus abortivus equi, epidemic abortion of mares. Streptococcus vaginalis vaccarum, contagious vaginitis of cows. (Trypanosoma equiperdum s, flagelose), dourine in horse. [Spirocheta pallida, syphilis in man?] VII. Pleuropneumonia. The infectious agent of contagious pleuropneumonia of the cow. VIII. Epidemic Diseases Caused by Ultramicroscopic Agents. Contagium of foot and mouth disease, in cattle, swine, sheep, and transmissible to man. Contagium of cattle plague. Contagium of smallpox in man, transmissible to cow, horse, rabbits. Contagium of sheep pox. Contagium of rabies of dog, transmissible to man and _ all mammals. Contagium of Lombardy chicken plague. IX. Diseases Due to Flagellata, Piroplasmata and Sporozoa. Trypanosoma Evansi, surra in domestic animals in India. ce Brucei, nagana in African animals. ’ da equiperdum, dourine in horse. “é 76 Causes of Disease. Trypanosoma Theileri, African cattle plague. [ is Gambiense, African sleeping sickness in man.| Plasmodium malarie equorum, African equine malaria. [Plasmodium of human malaria—tertian, quartan and dispar, duck, goose (intestine). Gnathostoma hispidum, hog (stomach). ce 88 Causes of Disease. 3—Pin Worms. Oxyuris vermicularis, dog, man (rectum). 2 curvula, mastigodes, horse (colon and rectum). ambigua, rabbit (czecum). 4—-Strongylus Worms. Eustrongylus gigas, dog, horse, cow {kidneys, peritoneum, heart, liver). Eustrongylus tubifex, duck (intestine). Strongylus armatus s. sclerostomum armatum, horse (intes- tine) ; peritoneum (larvze and embryos wander into the arteries, brain, testes); str. armatus has recently been subdivided by Sticker into three species: Scler. edentatum, bidentatum, quadri- dentatum. Strongylus tetracanthus (sclerost. tetr.), horse (large intes- tine). Strongylus contortus, ruminants (abomasum, small intestine). “I Ostertagi, cow, sheep, goat (abomasum). Curticci, cow, sheep (abomasum, small intestine). oncophorus, cow (abomasum, small intestine). Harkeri, cow (abomasum). retorteformis, ruminants, hare, rabbit (abomasum, sinall intestine). Strongylus filicollis, sheep (small intestine). radiatus, cow (small intestine). inflatus, cow (colon). Axel, ass (stomach). hypostomus, sheep, goat (intestine). filaria, sheep, goat, fallow deer, red deer (bronchi, 3 ae lungs). ~Strongylus paradoxus, hog, sheep (bronchi, lungs). 5) commutatus, sheep, goat, hare (lungs, bronchi). oe micrurus, cow, horse, red deer, fallow deer (bron- chi, lungs). | Strongylus Arnfieldu, horse (lungs). ; sagittatus, red deer (lungs). capillaris, goat, sheep, chamois (bronchi, lungs). dentatus, hog (large intestine). rubidus, hog (America). annulatus (Strong. s. Filaria tracheo-bronchialis), dog (air passages). Ammal Parasites. 89 Strongylus vasorum canis, dog (blood vessels). ‘i pussilus, cat (lungs). tenuissimus, horse (stomach). ‘i leporum, hare, rabbit (stomach), (America). 33 tenuis, goose (czecum). z nodularis, goose (pharynx). mS s. Syngamus trachealis, bronchialis, fowl, pheasant, horse, goose, duck, etc. (air passages). Dochmiuus trigonocephalus, dog, cat (intestine). ie stenocephalus, dog (intestine). tubeformis, cat (intestine). bovis s. CGtsophagostoma vesiculosum, cow (intes- 6 tine). (Esophagostoma columbianum, sheep, deer (intestine). Uncinaria cernua, sheep, goat (intestine). Ollulanus tricuspis, cat (stomach, embryos in the lung). Strongyloides intestinalis s. Anguillula stercoralis, man, fowl (intestine ). Anguilula vivipara, horse (colon). Rhabdonema longum, sheep, hog (intestine). 5—Whip Worms. Tricocephalus dispar, man, dog. oH afimis, ruminants (large intestine). crenatus, hog (large intestine). depressiusculus, dog (large intestine). | Trichosoma erophilum, cat (trachea, bronchi). felis catt, cat (urinary bladder). longicolle, fowls (cecum and rectum). annulatum, fowls (pharynx). contortum, duck (crop, pharynx). collare, fowls (intestine). iy tenuissimum and brevicolle, pigeon (small intes- 6c cc tine ). Trichina spiralis, hog, rat, man, all carnivora (intestine, em- bryos and undeveloped trichinella in muscle). 6—Filariae. Filaria papillosa s. equina, horse (peritoneum, pleura), ‘“ terebra, cow, deer (peritoneum, eye). go Causes of Disease. Filaria lacrymalis, horse, cow (conjunctival sac). ‘“ ammitis, dog (heart) (Asia [America] ). s. Spiroptera sanguinolenta, dog (stomach, aneurisms, ee pharynx). Filaria s. Spiroptera strongylina, hog (stomach). “ -s. Spiroptera megastoma and microstoma, horse (stom- ach); Gongylonema scutatum, sheep, cow, horse (pharynx) ; Gongylonema pulchrum, hog (pharynx, tongue). Filaria s. Onchocerca reticulata, horse (tendons, ligamentum nuche ). Filaria hemorrhagica, horse (skin). Dermofiliaria irritans, horse (skin). Filaria uncinata, goose (pharynx, crop, intestine). ~. nasa, tow (erep): s. Dispharagus spiralis, fowl (pharynx, crop). Tropidocera inflata, duck (crop). ce 7—Annelides. Hemopis sanguisuga, horse (pharynx). COURSE AND TERMINATION OF DISEASE; SYMPTOMATOLOGY; DIAGNOSIS The disturbances of function which indicate the existence of disease, as well as anatomical or chemical organic changes, are spoken of as the signs or symptoms of disease; the branch of study dealing with these as semeiology or symptomatology (76 onuetoyv from onuatvw, to denote; cup-rirrev, to happen with, that is, in connection with certain disease states) .* The art of concluding from symptoms the existence of definite morbid changes in the body, of determining the nature and loca- tion of disease, is known as Diagnosis or establishment of a diagnosis (4 didyvwors, differentiation or thorough knowledge; from yyvéccer, to recognize). Formerly when the anatomical and chemical faults which underlie disease were unknown it was deemed sufficient for the physician to merely appreciate the ex- ternal manifestations of disease, and such terms as dropsy, jaun- dice, fever and marasmus were used without attempt at nearer approach to the causes of these symptoms. Even to-day there may now and again be times when it is necessary to rest satisfied with no more than such a symptomatic diagnosis. However, as far as it is possible to conclude from symptoms that definite ana- tomical changes exist, or as far as such are directly manifest, we are accustomed in these days to make anatomical diagnoses; and as far as it is possible to determine the development of any affection, to make also an etiological diagnosis. The aim of modern diagnosis is the study of the disease from all three of these points of view and the appreciation of the condition of all the organs in their relation to each other, so as to permit of the recognition of how a given local condition must influence the rest of the organs of the body generally, *The principal features of this chapter have been in part adapted from Handbuch der allgem. Pathologie, Uhl und Wagner (Leipzig, 1876). g2 Symptomatology; Diagnosis. A purely symptomatic diagnosis is illustrated by such examples as the determination of varieties of convulsions, of palpitations, coughs; a symptomatic and anatomical diagnosis, by the recognition of a relation existing between jaundice and some hepatic affection; an zxtiological diag- nosis, by the conclusion that a jaundice depends upon the presence of some microorganisms in the liver and blood. [Very frequently diagnoses are classified as topographical, when indicating the location and extent of lesions, and as mnosologtcal, when indicating the nature of the process. No diagnosis can be regarded as complete unless embodying the recogni- tion of both location and nature oi an affection,.as well as oi its xtiology, in so iar as is possible. Incomplete, purely topographical diagnoses, as the declaration of “lung disease,’ “kidney disease,’ etc., are often made to serve the nonce, or by the careless as final; in the same way an incomplete, merely nosological diagnosis is often met with where it is said that an individual is the subject of “inflammation,” “congestion,’ “dropsy,* “fever,” “tuberculosis.” The full diagnosis should declare that the subject has an inflammation of the pericardium, if possible indicating the cause of the pericarditis; “tuberculous caseation of the lungs’ would embody all the desirable points of view.] Symptoms immediately referring to changes in a given part, as abnormality of color, increased size, hardness, softness or un- evenness of outline,; are spoken of as direct symptoms; those which do not depend upon the diseased organ entirely, but which perhaps may be appreciable in the products of such an organ or become manifest in other organs in relation with the diseased part, are known as indirect symptoms. ‘Thus a direct symptom of a lesion of one of the cardiac valves would be a cardiac mur- mur; an indirect symptom of pericarditis would be an cedema of the dewlap. There are certain symptoms called pathognomonic symptoms, which definitely indicate the existence of some particu- lar disease, as the rusty nasal discharge in pneumonia, locking of the jaws in tetanus, crepitus at the site of a fracture of bone; however, as a rule a single symptom does not suffice for a diag- nosis, but must be considered in its relations with a wider group of recognized features. Study of disease phenomena constitutes a large part of clinical pathology and pathological anatomy; the ability to recognize and to determine the importance of symptoms is one of the essentials of the medical art, and depends on the skill, experience, general knowledge and power of judgment of the individual conducting the examination of the subject. The majority of symptoms can be realized only by special methods of examination. He who has not acquired such methods cannot have a clear understanding about the morbid condition extant in the body of his patient, and is really groping about in the dark- Diagnosis. 93 ness. Eye, ear and sense of touch, partly unaided, partly aided by instruments of precision and special technical methods (em- ployment of reflecting mirrors for illumination, of instruments used in percussion and auscultation, of methods of mensuration, weighing, thermometry, microscopy or chemical tests) contribute to our power of appreciation of the signs of disease. With ex- memence it is possible that the examiner .at a single glance (diagnosis at a distance) may recognize some types of disease, some forms which manifest themselves by sharply marked ex- ternal features appreciable even at a hasty inspection. Other morbid conditions may be more or less correctly conjectured from the information given by some person from his observation of the patient (diagnosis from the anamnesis: dva-ppvicxw, to recollect). Both methods are open, however, to serious error if practiced alone, being based on incomplete data and imperfect in- vestigation; and although practical experience with quick per- ception of frequently observed facts may often arrive at the truth by such methods, only careful objective study will guaran- tee an absolutely certain diagnosis. In order to gain a compre- hensive idea of the pathological process presented, it is essential not only to consider the functional disturbances of one single part of the body, which is apparently the seat of the disease, but to systematically inquire into the condition of every part of the economy and every function. (For fuller discussion of these points the reader is referred to Friedberger-Frohner, Lehrbuch der klinischen Untersuchungs- methoden, or Moller, Klin. Diag. der dussern Krankheiten der Haustiere, F. Enke, publisher.) The art of diagnosis concerns itself, after the proper recog- nition of the symptoms manifested, with the condition of the organs, finally reaching a definite conclusion through processes of comparison of the features appreciated with the commonly ac- cepted pathology of known diseases. All possible affections are carefully considered, the symptoms presented by the subject con- trasted with those of each different known disease, and determina- tion of the affection attempted from the strongest features of correspondence. [In systematic study of a given case it is well to follow some routine of investigation. Thus commonly one takes into consider- ation such general features as the age, sex, race or species of the subject, the general surroundings and habits of life and features 94 Course of Disease. bearing on questions of heredity; subsequently the general pre- vious medical history of the subject, the anamnesis, is taken up, and a study of the known features of the present attack in its development. Thereafter is made a close and complete objective study of the subject, this including as thoroughly as possible the whole body, the condition of every organ by the methods of ordinary physical diagnosis and the more elaborate methods of clinical technology. Given such data one should be able by his patho- logical training to recognize the seat of the affection and the extent of its distribution in the body, the topographical diagnosis, and the nature of the affection, the nosological diagnosis. | The establishment of a diagnosis leads directly to prognosis and therapeutic application. By the term prognosis is meant the foretelling of the mode of development [the order of the events in the course, and the duration of the disease] and termina- tion (whether favorable, prognosis fausta; unfavorable, prognosis mfausta; or uncertain, prognosis anceps). The course and ter- mination of many diseases may be predicted with more or less certainty, inasmuch as examples of the affections are constantly occurring and an experienced physician is quite familiar with their development and modes of progress. The prognosis must, however, in a measure depend upon each individual case, its special constitutional peculiarities, the degree of general involve- ment of the body and the distribution of the disease-changes, the vital importance of the affected organ, the variations of the disease from its usual trend, the complications and the possibility of em- ploving proper remedial measures. Therapeutics (4 depareta, from Oeparedw, to serve or cure) or remedial treatment has to deal with efforts directed toward com- pensation for and removal of disease. Where it is possible by definitely conceived measures to remove the basic fault, the anatomical alterations and the causative influence underlying the morbid condition, therapy manifestly becomes rational or radical; where it is possible only to combat symptoms (pain, fever) it is said to be symptomatic treatment, which at best is but a tempo- rary means or measure of relief (palliative, from pallium, a cloak or protection). The duration and course of diseases depend closely upon their causes and upon the extent and nature of their basic structural alterations. Some diseases are sudden in their onset, last but a few minutes or hours, and terminate in the death of the individual Diagnosis. 95 or in a rapid disappearance of the various lesions. The former type includes such conditions as wounds, lacerations of external or internal parts or the effects of poisons which rapidly and com- pletely destroy the function of vital organs; the latter, character- ized by rapid recovery, is met in disturbances which are not fol- lowed by structural changes, as convulsions, anemic and hypere- mic states of the brain, of the skin and of mucous membranes. On the other hand, diseases may continue for weeks or months, or even years. They may begin suddenly or gradually and insidiously ; may manifest alternately intensity and diminution in the severity of their symptoms, fluctuations in the morbid processes (remis- sions and exacerbations); may invade suddenly: (paroxysmal; paroxysm, invasion) and present interruptions (imtermittent) in the course, sometimes ending with gradual improvement (lysis, resolution), sometimes in a rapid, abrupt change (crisis, decisive stage), leading to recovery or death. [By the course of the dis- ease is meant the order of manifestation of the various stages or events of the disease. It may be definite, regular or acute on the one hand, when its events proceed in orderly manner and come to a definite termination, or it may be mdefinite, wregular or chronic, when there is no fixed order of events and there is no set limita- tion. Among the different types of the regular course two major forms are recognized: (a) the continued course, where there is but little variation in the intensity of the symptoms from time to time, and (b) periodic courses, in which at certain definite times special events manifest themselves. Among the periodic courses are met, intermittent forms, in which there alternate periods of absence of symptoms, known as intermissions, with periods of presence of the symptoms in their intensity or paroxysms; remit- tent forms, in which there alternate periods of intensity of symp- toms, known as exacerbations, with periods of diminution in in- tensity, known as remissions; and recurrent forms in which there alternate comparatively long periods of absence of symptoms, the intermissions, with similarly prolonged periods of their presence, recurrences. The last form differs from the first in the length of the alternating periods. | Diseases of brief duration are called acute diseases; those of prolonged course, chronic. The former may last for a variable period, up to fourteen days, while the latter extend over a course of more than forty days; any instances falling between these durations may be classed as sub-acute affections, In case of 96 Course of Disease. diseases which ordinarily continue for a year or more, a shorten- ing of the course to a few months manifestly fixes such duration as an acute one, as in case of tuberculosis, glanders or rickets. [The terms acute and chronic have really a less limited signif- cance than the author here applies to them; they each have in one sense a reference to the length of the course, but in addition refer. perhaps without desirable clearness, to the possibility of recovery and the intensity of symptoms and the order of events in the course. In the matter of time it is scarcely possible to give any, fixed number of days, or even months, to the terms. Each dis- ease is a law unto itself, and only in the broadest way may we say that an acute course is one of brief duration. But in addi- tion, when we apply this term, we mean that whatever the actual duration, at any rate the disease will come to a definite limit; and, moreover, we expect the course to follow more or less closely a given order in the manifestation of its symptoms, and believe there is a chance of recovery. In case of chronic diseases again . we cannot set a fixed limit of days, months, or even years, which shall declare the course to be a chronic one (Thus, while alienists are inclined to set a limit of a year to cases of mania or melan- cholia, and to call all cases chronic if of longer duration, there really are no appreciable differences in many instances of even longer duration from their condition within the first few weeks of insanity.) Moreover, when a case is declared chronic, while there is no actual assertion to this effect, nevertheless there is a feeling of hopelessness as to the chance of recovery; the termina- tion looked for is rather death, and that at an indefinite time. No exact order of symptom presentation is expected in such chronic cases. Finally, while there are often exceptions to this point, in general the severity of the symptoms of an acute case is apt to be greater than in a chronic form of the same disease. | Diseases often show [especially those of an acute, regular or definite type of course] a succession of definite periods or stages in which certain phenomena appear, which are empiricaliy expected and whose development is awaited with the progression of the anatomical changes. These diseases are said to have a typical course. [A regular or definite course is well illustrated by the acute infectious fevers, in which the following periods may be recognized in the order named: (a) ifection (time of en- trance of the microbic cause), (b) imcubation (a period without symptoms, but during which the germs are multiplying in the Stages of Disease. 97 economy to sufficient number to excite their definite effects), (c) prodromes (a period of indefinite and usually slight symptoms, the first and as yet more or less obscure evidences of the presence of microbes in the system), (d) imvasion (the period of develop- ment of the specific syniptoms of the affection; this, if it occur rapidly, is said to be a frank invasion; if gradually, is called an imsidious imvasion), (e€) acme or fastigium (the period of fullest intensity of the disease), (f) occasionally an amphibolic stage (a period of uncertainty and marked variation, corresponding to the popular idea of crisis and used by the author above in this sense), (g) decline (period of disappearance of the disease; this, if it occur rapidly, is said to be “by crisis; if slowly, “by lysis”), (h) finally, not as a true stage of the disease, but a definite period before health is resumed, convalescence (period of repair and re- building of structures destroyed or impaired in the course of the affection, and of resumption of efficient function by the various parts of the body). If the cause of an acute disease be not a vital one the course includes, of the above stages, only those of invasion, acme, decline and convalescence. | However, in such well-known affections, as a result of special etiological factors or the accidental interference of external in- fluences, variations (irregularities) may occur, rendering the course an atypical one. In case the symptoms remain for a long time of uniform type and intensity, without appreciable ameliora- tion or increase, the disease is said to be stationary. Latent diseases are those which do not manifest themselves, either at all or in part, in certain phases of their development. This depends upon either the impossibility or difficulty of proper examination of the organs, which are the seat of the disease (as the pancreas or some parts of the lung), or upon the fact that the disease is so localized or has been so gradual in its development that the function of the organ has not been materially affected. Latency is often, therefore, only a temporary or transient feature, and it is often correct to speak of a latent stage and of a later manifested or open stage. Some diseases, cven though they be severe, remain latent because they are followed by adaptations (compensatory conditions) which entirely prevent their usual symptoms, as when a valvular lesion of the heart is followed by compensatory cardiac hypertrophy. When a disease is characterized merely by local symptoms and alterations it is known as a Jocal disease or disease of [this. or 98 Course of Disease. that| organ; if, however, a number of organs are involved and their functions interfered with, and if the general economy is ap- parently affected, the condition is spoken of as a general disease or a dissenunated (generalized) disease. {Examples of general disease are met with in such alterations as provoke general metabolic disturbances and abnormalities in the composition of the blood. Formerly the term constitutional disease or dyscrasia, de- composition of the blood, was used in this connection.) Funda- mentally there is no distinction in these terms, but as a rule the term dissenvination has special reference to a multiplication of local lesions, to an extension of the causes of the disease to a number of situations where new foci of the same type appear, or to a reaction of a functional disturbance of one organ upon the rest of the system. For example, a prolonged disturbance of the function of the kidneys will give rise to a disturbance in the cardiac action and retention of harmful products of metabolism; or, as in the case of tuberculosis, the infectious agencies pass from the original local fccus into the lymph and blood, extend by direct growth into the surrounding organs, and in various scat- tered foci in the body to which they have been conveyed; the dis- ease thus becoming disseminated and generalized. Some affec- tions, on the other hand, at first manifest general symptoms (fever), later, however, showing distinct evidence of their purely local type. Variations in the course of disease may also depend upon the predisposition characterizing the animal species in ques- tion, as, for example, is seen in case of glanders in field mice, an acute septicemic affection, in contrast to the same disease in horses, where it is usually a chronic local atfection, gradually ex- tending through the system. The local lesions which first arise from the operation of a pathogenic agency are known as primary lesions, those which fol- low as secondary. The action of such an agency may be confined to one locality, the lesions disappearing after its removal, as in- case of corrosion, heat action or traumatism. The generalization usually depends directly upon the spread of the pathogenic influ- ences through the body, and may therefore take place (1) by continuity and contiguity of the tissues (per continuitatem, per contiguitatem), (2) by the blood or lymphatic tissues (hematogen- ous, lymphogenous), and (3) as already referred to, the func- tional interdependence of one organ upon the others may, in case of disease at one point, lead to further change in other parts of the \ Extension of Disease; Termination of Disease. 99 system (sympathetic or consecutive lesions). By the term exten- sion by continuity is understood the progress of the pathological process upon the surfaces in continuity and along uninterrupted tissues in the immediate vicinity of the original focus, as along the mucous membrane of the nose to the frontal and maxillary sinuses, from.the pharynx to the Eustachian tubes and middle ears. Extension by contigwity occurs from one surface to that of an adjacent organ in contact with the first, as from the visceral pleura to the costal pleura, from the serous surface of the stomach to the liver. The explanation for such a mode of extension is mainly to be found in the fact that the pathogenic agent finds some particular opportunity for invading such adjacent tissues; thus bacteria may pass to an adjoining structure, be swept along by its fluids and spread widely. A suppurative or gangrenous focus in the lung may in some such manner gain access to the pleura; the latter may rupture and the microorganisms, spread over the entire pleural surface from the respiratory movements, may give rise to an extensive pleuritis. Hematogenous extension of a disease occurs when the pathogenic agents gain access to the blood; lymphogenous extension, when such influences, through the agency of the wandering cells, are mingled with the lymph (cf. embolism). Sympathetic disturbances in function are appar- Gaim part the result of sensory and motor reflex action, in part the result of primary changes, the efficiency of one organ depending upon the functional integrity of another, as a chronic hepatic cirrhosis induces cardiac hypertrophy and splenic cyanosis by the circulatory disturbances which it produces. Coincidence of diseases may occur entirely independently of any relation between the processes, or may depend upon some connec- tion; where this occurs complications are said to exist. Thus swine-erysipelas is often complicated by valvular endocarditis (the infectious germs invading the latter structures), or suppurative osteitis of the cranium may be complicated by a meningitis (through extension of the suppuration by contiguity to the meninges ). The termination of disease may result in one of three ways: I. Recovery, cure or restoration, complete re-establishment of the disturbed function and condition of the organ; 2. Incomplete recovery, with appearance of secondary affec- tions, persistence of sequels or defects; or 3. Death of the individual. 100 Termination of Disease. Termination in recovery is accomplished through the repara- tive powers natural to the economy. The body is possessed of a variety of regulative mechanisms, whereby the influence of harm- ful agencies is neutralized, the loss of chemical substances and tissues is repaired, and noxious materials are eliminated from the system. Such processes may in a compensatory fashion correct this or that fault, as by the discharge of toxic matter from the stomach or intestines, the removal of the products of fatigue from the muscles and nerves through the blood and lymph, the expul- sion of exudations from the lungs through expectoration. Many corpuscular disturbing factors (as bacteria, dead cells, hzemor- rhagic foci) are removed through the activitv of the living cells (phagocytes) and digested, the body being thus freed of such sub- stances. Other foreign bodies are encapsulated by a wall formed by the tissues of the organism for their own protection, and thus rendered harmless. Deficiency of nutritive material in the fluids and cells is corrected by the supply from the stomach and intes- tine; dead cells are replaced by new elements from existing forma- tive areas (as new blood cells from the bone-marrow). Tissue losses are repaired by processes of regeneration. And, too, the production of antibodies of most varied type is possible for the protection of the animal body. The therapeutic art is in no wise at variance with natural proc- esses of recovery, but, on the contrary, employs the various regu- lating and compensatory mechanisms of the body in order to bring about an adjustment of the disturbances, and attempts to induce conditions more favorable to a rapid adjustment than is possible when no influence is brought to bear upon the pathogenic agent; at the same time it attempts to restrain further. agencies which may retard the recovery. The practice of medicine missiles directed to guard against the extension of contagious diseases and particularly against the inception of disease, so that in this phase, too, the lofty power of science holds nature in check, which, with- out the aid and skilled intervention cf man. would threaten with annihilation, all too soon, the creatures of the earth. The signifi- cance and success of medical science is particularly impressed upon one when it is recalled how destructive epidemic diseases, which in times past carried off millions of animals and men, have in some instances been wholly eradicated, in other instances greatly diminished. By appreciation of the nature of a varied group of _ affections, there has come the discovery of efficient methods for Termination in Recovery; Death. IOI their cure and for prophylaxis against them. Of course, no rem- edy has been found for death, the inevitable end of development of all living beings, and the laws of nature can by no medica- ment, whatever its power, be broken. Yet the skillful use of the means of nature may hold off premature death and may assist the injured body to regain its health. Medical art can prevent fatal hemorrhages, it loosens adhesions, cuts away what is unfit, dilates narrow canals, has antidotes at its disposal, can procure rapid evacuation of the bowel or emesis, remove foreign objects from the body, relieve promptly nervous strain, alleviate pain directly, often correct irregularity of cardiac action, reduce dan- gerous temperatures and accomplish a multitude of services with- out which a given disease might well end unfavorably or be protracted over a tedious course. After recovery begins at the close of a general affection, there occurs a period, known as convalescence, the subject still evincing muscular weakness and marked sensitiveness to external influences. [During this period there are taking place various reparative and reconstructive processes in the economy, looking to the restoration of altered and destroyed elements, and, too, functional efficiency is being re-established, and all remaining factors of the previous disease are being finally eliminated from the system. ] Recovery is regarded as incomplete where, after a disease has run its course, there persist in the economy conditions preventing normal functional efficiency of the organs or where there is evi- dent some permanent impairment of tissue [sequele of disease]. As illustrative of this may be mentioned deformities of bones, cicatricial strictures of canals, kinks of the intestines, pericardial, pleural or other adhesions by bands of connective tissue result- ing from the previous disease, opacity of the normally transparent media of the eye, palsies of muscles and nerves, or the defects left after ulceration or burns. Termination of disease in death (exitus lethalis or letalis, from Jetum, death; from A7é forgetfulness, \avdévw to make forget- ful) occurs when the organs which subserve the most important and necessary processes of vitality suspend their function. Inas- much as continuance of life depends in an important measure upon the uninterrupted supply of blood containing oxygen to the medulla oblongata through the action of the heart, underlying which must be recognized the necessity for respiratory movements regu- lating the efficiency of the pulmonary surface in the intake of 102 Termination of Disease. oxygen and output of carbon dioxide, it is essential to accept as causes of death of primary importance, various lesions and func- tional disturbances of the hind brain, the heart and the lungs. These parts are therefore spoken of as the atria mortis. Inhibi- tion of their functions may be a direct result of chemical, me- chanical or electrical influences (as from poisons which destroy or paralyze the nerve cells, concussion, the action of lightening), or may indirectly follow a wide variety of factors interfering with tissue nutrition, metabolism and gaseous interchange (anx- mia, albuminous waste, closure of respiratory passages, elevation ot depression of body-temperature, reflex palsies). The more important modes, therefore, by which this or that disease may induce death, are: I. Cessation of cardiac action, caused by toxic or reflex nerv- ous paralysis of the cardiac ganglia, fatigue and degeneration of the cardiac muscle, cardiac rupture, complete obstruction to the escape of blood from the cardiac chambers (formerly known as exittus lethalis per syncopem, cvv-xérrev, to strike together). 2. Asphyxiation, from interference with intrapulmonary respiratory interchange of gases, obstruction of the lungs or upper respiratory passages, compression of these tubes, spasm or palsy of the respiratory muscles, diaphragmatic rupture (exitus lethalis per suffocationem). * 3. Medullary Paralysis, or paralysis of the respiratory centre in the medulla oblongata, from circulatory interference at the base of the brain, influence of toxic substances upon the nerve cells, concussion of the brain or reflex influences (exitus lethalis per apoplexiam, drordjccev, to strike down). 4. Hemorrhage, from rupture of important vessels, or ex- travasation of large amounts of blood into the somatic and visceral cavities. 5. Exhaustion, from inanition or consumption (diminished nutrition and exaggerated metabolism, accumulation of fatigue products and poisonous metabolites, auto-intoxication). These modes of death may, of course, complicate each other and may be mutually causative of each other (as when hzmor- rhage induces ischemia of the heart and coronary vessels, with the result of cardiac cessation and at the same time the symptoms of suffocation, due to an anemia of the medulla). Senile debility, more or less complicated by various diseases, is also to be re- garded as a cause of death (senile marasmus, from wapatver, to Ternunation in Death. ites or weaken), a natural and necessary termination for each individual cell and for the entire cellular complex. In the individual cell, as well as in all the tissues of the organism of higher animals, changes are continually proceeding which lead to the destruction of the living substance and sooner or later result in the death of the individual. The living multinucleated organism is continually losing cells by their death, the substance of which is eliminated from the economy with the excretory material or is broken up and re-employed by the system. From causes inherent in the organ- ism itself, but at present impossible of clear definition (vid. Ver- worn: Geschichte des Todes; Allgem. Physiologie) the power of multiplication ceases in the individual groups of cells and organs in varying rates in the different species of animals, and with vary- ing swiftness the characteristics of old age and of death become apparent. Perpetual youth, immortality in the sense of reproduc- tion, always renewing themselves, is possible only for the conju- gated sexual cells (propagation cells), while in case of the somatic elements (and those sexual cells failing of copulation) the vegetal force sooner or later disappears. Whenever the decay of cells of vital importance reaches the grade in which it distinctly interferes with the rest of the economy, the mutual relations of the various parts is disturbed, and death ensues, just as a clock stops when its wheels wear out or are broken. Transition from life to death may occur suddenly (mors subi- tanea) ; the animal falls from its standing position to the ground, becomes unconscious, and for a few moments at most is thrown into convulsions with groaning respirations. Such sudden termi- nation may be noted in death from lightening stroke, sun stroke, rupture of the heart, cerebral concussion, massive internal hzmor- rhages or cardiac and cerebral paralysis. In the majority of in- stances, however, death comes on gradually, with the manifesta- tion of characteristic phenomena which predict the termination of life, and which together constitute what is known as the death- agony (% aywrta, the struggle, death struggle). They include the signs of a progressive paralysis of the nervous and muscular sys- tems, together with those of the disease which causes death. Animals in the agonal state are unable to raise themselves from the ground, usually lie flat on one side, from time to time lifting the head and letting it fall heavily to the ground, with the feet rigidly extended and moved convulsively, at first violently, but gradually more and more weakly. Respiration is slowed and 104 Termination of Disease. labored, deep groaning respirations following at irregular inter- vals the ordinary shallow breathing. With the appearance of pul- monary oedema, rales, heard even at a distance, are produced by the fluid exudate beaten into a foam in the air passages (death rattle). Involuntary discharges occur from the bowel and blad- der, when paralysis of the sphincter muscles develops. The heart beats more rapidly, but the relaxed arteries are no longer able to propel the blood forward and the pulse in consequence, although quick, grows small and finally indistinguishable, and the skin is cool. The hair is bathed with a clammy sweat. The body tem- perature in the agonal period in diseases accompanied by loss of blood or inanition falls considerably below normal (hypothermia, to 36-35° C.), while in other types there may be an ante- mortem rise in temperature. Extinction of life means complete cessation of metabolism, of cellular growth and the existence of the individual; and death therefore manifests itself by complete termination of the functions of all parts of the body. ‘The last breath, naturally in the form of expiration, and the moment of complete cessation of the heart may ordinarily be looked upon as marking the actual end of life. However, the organs do not all perish at precisely the same moment; after the last breath the heart may flutter a few minutes; and after death from hemorrhage, peristaltic movements of the intestines may sometimes be ob- served for perhaps fifteen minutes; and similarly after death from electricity muscular contractions may be elicited as long as rigor mortis does not set in (one to three hours after death). The following are the characteristic signs of true somatic death: 1. Muscular rigidity (rigor mortis), sometimes setting in im- mediately after death, sometimes only after four to twenty hours later, and depending upon the coagulation of the muscle albumen. The muscles in this change become set, shortened and thickened, as in vital contractions; the extremities are rigid and either cannot be flexed or only with the application of considerable force, and the mouth cannot be opened by ordinary traction upon the lower jaw. After twenty-four hours, or perhaps later, the rigidity disappears [due to decomposition]. 2. Cadaveric fall of temperature (algor mortis) develops in from half an hour to twenty-four hours after death, varying with the surrounding temperature and the degree of metabolic activity prevailing at the time of the death agony. In some affections, as in tetanus, because of the important heat production caused by the Signs of Death. 105 muscular contractions and because after death heat dissipation falls on account of the cessation of the circulation in the peri- phery of the body, a post-lethal internal temperature rise, to perhaps 42-44° C., occurs, persisting a number of hours. 3. The eye in death: The eyelids of the cadaver are usually half open (rigidly) ; the ocular bulb is sunken and somewhat less tense than in life (evaporation of some of its fluids) ; the cornea becomes dull and opaque; the pupils are dilated. The ocular reflex movements upon touch are entirely absent. 4. Appearance of putrefaction: The bacteria in the digestive tract, producing all sorts of fermentative changes in the contents of the canal, shortly after the death of the tissues, penetrate the latter and cause their putrefaction. The gases, produced in large quantities from the fermentative processes, dilate the stomach and intestines, causing abdominal distension, sometimes to such a degree as-to force the lower bowel out of the anus, rupture the diaphragm and allow the intruding intestines to distend the chest. The advance of putrefaction may be noted in the colorless parts of the skin by greenish discolorations (sulphur compounds of hemoglobin), and also by the foul odors of cadaveric decomposi- tion. These changes cause the disappearance of the rigidity of the body and progress the more rapidly the warmer the surround- ing temperature. Measures which inhibit the growth of the putrefactive bacteria, preservation in alcohol or formaline (injection of the vessels with antiseptic or balsamic substances), refrigera- tion, drying, prevent putrefaction. With the advance of putre- faction all the organic matter of the body is broken up into ammoniacal compounds, carbonic acid and water, with the forma- tion of a great variety of by-products (putrefactive alkaloids, acids, gas-forming matter, etc.) until finally only the solid calcified bones remain. The name apparent death is applied to a condition in which all the vital functions are depressed to the 'owest possible degree, when only by great care in the examination of the seemingly dead body can there be detected feeble cardiac contractions and occa- sional faint respiratory movements, a condition accompanied by loss of consciousness and sensibility, and by reduction of the body temperature. In recently born animals this condition is seen com- paratively frequently, lasting perhaps for hours (asphy.ria neona- torum) ; in this connection it is perhaps due to a premature separa- tion of the placenta, aspiration of the amniotic fluid, compression of the umbilical cord, or to anemia. DISTURBANCES OF CIRCULATION Life and health are possible for the organs only if there be unimpaired circulation of a blood capable of supplying oxygen and nutrition to them. Disturbances of the circulation, as well as faults of the blood and lymph, in other words, deficiency in the provision and passage of good blood through the organs, endanger both life and health. | The normal heart possesses a notable adaptabilty to the varying demands upon its capacity for work; it accommodates itself im- mediately to the current of blood entering it by virtue of the elas- ticity of its walls; regulates the energy and rhythm of its contrac- tions in conformity to the amount of blood in its chambers, the general circulatory resistance and the demand for blood in the ac- tive or resting organs. This power of accommodation enables it, to a certain extent, to overcome and compensate for pathological dis- turbances affecting the hzmic circulation; under such circumstances there is said to take place a compensation for these disturbances. Where such conditions of resistance to the heart’s action are of slow development and permanent, a thickening of the myocar- dium is assumed in connection with the increased requirement for work, consisting essentially in an increase in the number and size of the muscular elements (cardiac hypertrophy). It may be said that even physiologically the size and muscular strength of the heart are adjustable to the demands made upon it in its function as a forcing-pump or as a suction pump. Certain animals, for example, which in the course of their lives perform especially intense muscular work, are likely to exhibit hearts larger in pro- portion to the body-weight than animals accustomed to but little muscular activity.* Pathological hypertrophy differs from this physiological form only in its cause, in the latter the excessive work being but a natural and customary condition in the life of the animal, in the former the result of abnormality of the vascular *See also Kitt, Lehrbuch der pathol. Anatomie d. Haustiere. II. Aufl. Cardiac Hypertrophy. 107 system, of excessive blood pressure and of unusual quantities of blood within the organ. Such “work-hypertrophy” of the gen- eral organ is met in connection with epicardial adhesion to the parietal pericardium, compression of the base of the heart from pleuritic adhesion, tumors or similar conditions, because in such cases the propulsive effort of the entire organ has a greater oppo- sition to overcome. Hypertrophy of one side of the heart is seen especially in case of valvular lesions. These valvular lesions involve irregularities in the closure of the orifices of the heart and its great vessels; they are of two types, either narrowing of the orifices from pro- liferative changes, bloods clots, etc. (stenosis), or incompleteness of closure of the orifices by the valves (valvular insuficiency). Stenosis at the aortic opening increases the work of the left ven- tricle in order that the blood may be forced through the narrowed orifice, and in proportion there ensues a work-hypertrophy of the left ventricular wall. Following stenosis at the origin of the pul- monary artery there occurs a work-hypertrophy of the right heart (sometimes dilatation after special preceding strain). Valvular insufficiency also leads to hypertrophy, because where the valves are incompletely closed there first occurs a tendency to stasis because of the back pressure of the blood (regurgitation), which is likely to induce ventricular or auricular dilatation, and therefore the heart is required to work the harder in order to propel the larger quantity of blood. Although the so-called compensatory hyper- trophy of the heart does in some measure contribute to the regula- tion of the blood distribution and is of some service, yet in reality it is only the expression of an increased blood-pressure in one of the ventricles or auricles or in the afferent or efferent vessels, and the compensation which it induces is only a relative one. As a matter of fact, the increase of pressure persists and the circulation does not become normal (Krehl). Even when the animal is at rest the continued heightened blood pressure causes the develop- ment of dilatation of the capillaries, pulmonary passive congestion and distension with consequent diminution in the pulmonary excur- sion, together with difficulty in breathing. The arteries show dis- tinct changes of the pulse, the vessels being unusually tense and distended; they eventually lose their elasticity and may rupture. A very large heart may in addition mechanically interfere with the lungs. ‘These consequences are still more evident if the indi- vidual exercises physically, the muscular exertion raising the blood 108 Disturbances of Circulation. pressure still higher. (Powerful muscular contractions force larger amounts of blood into the right heart; the ventricles become engorged and the hemic pressure rises.) Eventually the heart loses its force as a pathological hypertrophy is not, as might be sup- posed from the thickness of the walls, capable of indefinite response to increased functional demands, but on the contrary, is often unable to accomplish even the more moderate requirements made upon the strength of the heart. Perhaps the reason for this is tliat the influences which give rise to cardiac hypertrophy at the same time harm the myocardium in other respects. For example, valvular lesions, causing the heart to become hypertrophied in their train, are frequently caused by infectious substances. Such agencies may also cause a myocarditis ; and if the inflammation be protracted and of low grade, it causes considerable reduction in the efficiency of the muscle. Moreover, the conditions which cause pathological cardiac hypertrophy are typically not stationary, but on the con- trary the circulatory difficulties are apt to progress (the stenosed orifices are likely to become still more narrowed, thrombi which interfere with the vascular lumen become larger, capillary areas become contracted) ; and from such extra demands upon its ability the heart becomes fatigued. There must eventually, therefore, suc- | ceed upon compensatory hypertrophy a period of failure of com- pensation, a period of broken compensation. [There are numer- ous influences which combine to limit cardiac hypertrophy and to determine its eventual loss of compensatory power, and so certain and uniform are these results that it might well be declared a law that every pathological hypertrophy of the heart must necessarily reach a limit to its enlargement and must thereafter fail in its power of compensation and undergo degenerative changes. The limita- tions, aside from those set by the age of the muscle and its inher- ent power of increase, depend mainly upon the amount of proper blood which the coronary vessels are able to supply. In a great measure this is determined by the original size and construc- tion of these vessels, although doubtless there is a possibility of true hypertrophy in these so as to accommodate the growing needs of the enlarging organ; yet if the original cause of the hypertrophy were a widespread arteriosclerosis the coronary arteries would be extremely likely to have been involved. Even were this not true, the mechanical influence of a hypertrophied left ventricle upon the walls of these vessels in close functional and topograph- ical relation with the pumping action, and the similar influences Cardiac Failure. 109 of the aortic recoil after closure of the aortic valve, must favor the development of a local coronary sclerosis on account of the possibility of fibrillary injuries to the walls. Given an arterio- sclerosis there is every reason to expect an imperfection of the cor- onary circulation from the narrowing of the lumen and the in- creased rigidity of the tubes; and with the imperfection of circu- iation thus fixed upon the myocardium, its nutrition and ability to further enlarge are necessarily limited. The functional de- mands progressing, fatigue, degeneration and cardiac failure are the necessities of a not distant future. | Diminution of cardiac force is spoken of as cardiac failure, cardiac insufhciency. It follows various influences affecting the myocardium or its ganglia, among which as prominent examples may be mentioned excessive exertion or fatigue, numerous poisons and the analogous substances present in the system in the infectious diseases, diminution in the blood supply to the myocardium, in- flammations and degenerations of the muscle, excessive fatty de- posits of the heart, and atrophy of the myocardium. All patholog- ical changes which occasion cardiac insufficiency are followed by disturbances in the movement and distribution of the blood.