f
■>i.'
LIBRARY
OF THE
University of California.
Class
TEXT BOOK
OF
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 Patholog:>' in the Universitj' of Pennsylvania
Edited with Notes and Additional Illustrations
BY
DR. ALLEN J. SMITH
Professor of Pathology in the University of Pennsylvania
Illustrated with Four Colored Plates and One Hundred and
Thirty-one Text Illustrations
V" OF THE
UNIVERSITY
OF y CHICAGO
CAvro^^}^^ W. T. KEENER & CO.
1 906
.^^
*V\.,
<d'
ff
SEVERAL
Copyrighted, 1906
Bv W. T. Keener
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 setiological fea-
tures, the manifestation of functional impairments, pathogenesis,
etc., require further reference to special works.
As an introduction and 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 aetiology 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
iv Preface to German Edition.
nullum librum legit, ex quo noii excerpserit." I therefore ac-
knowledge at the outset 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, fundamentals 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, wdth
such multiplicity of specialized purposes and requirements that
the method and practice of veterinars' medical instruction have
come to have a peculiar character of their own. Consideration
of these requirements is attempted in this volume.
It is well known to every teacher who is required to act as
an examiner, how difficult it often is for the 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 mv definitions
Preface to German Edition. v
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 luere 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 v/ork would
otherwise have been too large; and full details upon these sub-
jects may be found in the part devoted to special pathology
{Lehrhuch der pathol. Anatomic der Haitsticrc. II. Aufl. 1901.
F. Enke, Stuttgart) and in my Lehrhuch 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 mmiber 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. TH. KITT.
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, w.e believe, an equal appreciation from others whose
work has fallen in similar lines.
The book reflects well the tendency of modern pathological
viii 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, 89,
91, 97, loi, 102, 103, 104, III 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.
William W. Cadbury.
September, 1906.
TABLE OF CONTENTS
PAGE
Preface to German Edition iii
Preface to American Edition vii
Introduction i
Definition of Patholog}' ; Conceptions of Disease ; Pro-
cesses of Disease.
History of Pathology lo
Disposition Toward Disease i6
Predisposition and Immunity ; Defensive Mechanisms
of the Body.
Congenital and Inherited Disease 30
Placental, Intrauterine Origin of Disease; Germinal
Variation ; Germinative Predisposition ; Hereditary
Conditions.
Causes of Disease ' 35
Disturbances of Nutrition and Alimentation 36
Respiratory Disturbances 38
Excessive Functional Activity . . . ". 40
Thermic Influences 41
Chilling- 45
Electrical Agencies 48
Mechanical and Traumatic Agencies 49
Chemical or Toxic Agents 50
Microbic or Infectious Agents 54
Animal Parasites 76
Course and Termination of Disease 91
Symptoms, Diagnosis, Natural and x\rtificial ]Means of
Recovery, Death.
Circulatory Disturbances 106
Disturbance;^ of Cardiac Efficiency 106
Local Variations in Amount of Blood in a part (Hy-.
persemia, Anaemia) 109
xii Table of Contents.
PAGE
Haemorrhage 119
Dropsy and CEdenia
Occlusion of Blood Vessels (Thrombosis and Embo-
lism)
Alterations of the Blood (Plethora, the xA.ngemias,
Leukaemia) 156
Disturbances of Metabolism, Retrograde Changes and Necrotic
Processes 165
Disturbances of Heat Regulation, Overheating, Fever. 165
Necrosis 1 76
Atrophy 185
Cloudy Swelling 190
The Fatty Changes 192
Hyaline Degeneration 199
Mucoid Degeneration 202
Colloid Degeneration 204
Glycogenic Infiltration 20s
Amyloid Degeneration 205
Pigmentation 209
Calcification and Concrement Formation 216
Processes of Repair and New Formation 232
Regeneration 232
Transplantation 25 1
Hypertrophy 254
Inflammation 258
Tuberculosis 291
Glanders 311
Actinomycosis 318
Botryomycosis 324
Tumors ( Autoblastomata) 325
Fibroma (p. :^4i)^Lipoiiia (p. 346) — Myxoma (p.
349) — Cliondroma (p. 350) — Osteoma (p. 353) —
Myoma (p. 356) — Neuroma, Glioma (p. 358) — Hccm-
angioma, Lymphangio'ma (p. 362) — Sarcoma (p. 365)
— Lymp/ioma (p. 372) — Melanoma (p. ^yy) — Eiido-,
Peri-thelioma. CJwIesteoma (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.
421).
Tabic of Contents. xiii
PAGE
Functional Disturbances 423
Nervous Disturbances; Disturbances of Motion 423
Digestive Disturbances 436
Respiratory Disturbances 448
Disturbances of Urinary Excretion 454
Disturbances of the Thyroid Function 459
Disturbances of the Sexual Function 461
Disturbances of the Cutaneous Function 462
Index 465
.■af
INTRODUCTION
Pathology (t6 7rd6'os, suffering; 6 x670s, science) may he defined
as the natural history of diseases, or as the scientiHc 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 o£. function
as to merit being considered diseased ; nevertheless the individual
may feel well and live many years. Moreover in healthy bodies
there mav 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 IiitroducfioiL
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" (imbeciUitas) 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 foetal 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 bodilv environment, disease should be thought of as being made
Nature of Disease. 3
up of anv chang-e of structure or modification of function which
may impaii' this harmony and adaptabiUty 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 afifections in type,
distribution and number.] The processes which go to make
up a disease are not fundamentally dififerent from the physiological
processes, are not features foreign to the operation and structure
of the healthv bodv. 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 Mrchow, be con-
sidered as heterotopic, heterochronic and heterouictric physiologi-
cal processes (^repos, another; 3 T6iros, place; xp^^o'^^ time; /x^rpov,
amount). As an illustration: a h?emorrhage into the ovary, caused
by the bursting of a follicle and ovulation, is normal, but a
haemorrhage 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 :
(i) 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
uraemia 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: ahia,
cause). In the origin of disease some cause is apt to act so as to
bring about material changes, chemical and physical, patholo^^ical
lesions {Iced ere, 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 (7; yheais, de-
velopment, beginning) ; that which concerns the observation of
the chronological succession of disease-events, the onset, course
Divisions of Pathology^ 5
aiul termination of disease, is known as Nosology ( ^ vdaos, sick-
ness).
The object of pathology is primarily the acquisition of knowl-
edge of the laws which govern pathological changes (Pafhognomy,
from yiyvwcTKU}, to becomc acquainted with) ; in addition, to point
how and why certain lesions and reaction^ 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 (irpo-
(pvXdaaw, to prevent or guard against something) and Therapy
i] eepaireia, therapcutics, from depaweiiw, 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 bi 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 afifections, 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 should 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 betw-een 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. \'eterinary medicine was prac-
ticed bv butchers, farriers and grooms, wdiose information and
practical knowledge were based upon the doctrines, conceptions
and reci]ies 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. jMorbid 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 symptomatologv of a case may thus furnish a basis for
the anatomical diagnosis and the anatomical conception of the dis-
ease in hand. IMany 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 dififerent from the
characteristics in health, and even the unaided eye sees at once
whv svmptoms 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 phvsiology 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 physiological
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 bodies 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. g
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 OF 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 w^as 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 Alkmseon (B. C. 54o).
Hippocrates IT, 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 supposedlv 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 inulonicdici, hippiatrcs (I'TTTros, horse: larpoi, physician),
kteiiiatres (kt>}vos, domestic ammsLl ; iarpdi, physician) and vcterinarii;
Early History. ii
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 formulated 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 hmuan bod)' 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
entirelv 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 {pnciuna, 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-
terial which had caused the "dyscrasia ;" and for this reason
evacuants, diaphoretics, diuretics and venesection played an mi-
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 c.toms, 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 Rdman 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 spurces 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, FaJlopius and Eustachius, the experimental
researches of Serv^etus 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 errojr, ascribing, un-
der the influence of prevailing views in natural science, the
various processes of disease and their causation now to this, ndw
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 bod\-, 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 eflrect of
"stimuli" and the irritability of the tissues (the theory of ex-
citability of Haller and Erown). Others, basing their views upon
mechanics, believed the vital phenomena of morbid disturbances
depended upon mechanical faults of relationship ("mechanical
school," founded by Santoro, 1 561-1635, Borelli, 1608-1677).
Still others spoke of "vital spirits" circulating in the body, of
"forces," of the power of the "entities" (Paracelsusf). or made
some injury to the immortal soul the real principle of disease
(G. E. Stahl. 1660-1734). These doctrines were denominated wVa/-
ism and airiiiiism. 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 Eichbaum, GachicMe df HcilJ;undc: Berlin. Pareys' Verl.. 1SS5.
tTheophrastus Bombastus, whose proper name was Paracelsus, distinguished
different forces, an ens astrale (power of the stars), an ens naturale, spirituale,
venerd, 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, "Dc Scdibus ct Causis Morbontin" (1761),
outlined the first comprehensive and system.itic 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, Corvisart,
Dupuytren, Auenbriigger, Laennec and Rokitansky.
The advances in physiology inaugurated bv Johannes Miiller
(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 Aitiology 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 onlv one large work on the anatomy of the horse (issued in
1598 by the \'enetian 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 (15 16-1565) and Aldrovandi (1522- 1605). Prac-
tice of veterinary medicine w^as 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, J\Iarx 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).
In 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 manv 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 DISEASE
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 animal body is dependent or with
which it is related, but may on occasion cause the onset of
disease — nutrimient, 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 inherited po-
tentiality of the organism, the functional capabilities of its cells
and tissues, and upon the efificiency 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 pcoduce 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 mem-
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 ; although, if
introduced by way of lesions 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 (micro-
phytes, vegetable microscopic organisms ; fnicro.coa, animal micro-
scopic organisms) gain entrance to the body by alimentation, or
by the respiratory path, or through ivounds, 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 work 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 foreign 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 difliiculty. 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 tis-
i8 Predisposition and Immunity.
sues of the immune animal have no affinity^ or but little affinity
(chemical affinity), toivard the toxines of the infection. The
poisonous elements simply do not enter into combination with
them. 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 sarne manner upon the
latter as would the toxine itself,
FYom 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 pointefl out especially by the ingenious investigations of
Metschnikoff, Leber, and Bordet. These phagocytes act as scaven-
gers, taking up and making awa}' 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 movement and approach of the phagocytes may
be induced bv a number of stimuli, as warmth or an acid, acting
upon their own tactile or chemical sensitiveness. Tn 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 (cheniota.vis) . [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 1^
actual volitional power to either originate or refrain from efiforts
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 addimoifs and cyfoscs), are products of the
cells, which are either given off by the living cells (Buchner) or
are set free by cellular destruction (Metschnikofif) ; 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 efifect, 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 completel}' 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 (i'Sios, •peculiar;
i] ffvyKpd(ns, combination).
As a rule, the predisposition or inimiiinty 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
?gain 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 afifected 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, if fed upon meat alone, are found as a rule to be
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 depre'ssing 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 condi-
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 Innnunify. 21
sliowing a diminished resistive power for a long time {local pre-
disposition; locus ininoris resistenticc), as, for example, mucous
membranes after catarrhs.
Predisposition to disease and (a ^natter of extreme impor-
tance) immunity against disease may he 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 immujiity 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 succe^ 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 immvmity from subsequent 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, t^eir 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
22 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 m.echanism 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
Ehrlich. [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 I in in unity. 23
"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 (toxophorc) , 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 tliat 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; there
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
I, II, III, etc., orders.
The first order (unieeptors) 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
Lysiiis. 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: dcsiiwji (se'w := I bind), immune body,
intermediary body, copula, immunisin, fi.vateur, sensitising body.
The alexine is also known as the complement, addiment and
cytosc. \\'hen 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-
ment] is spoken of as a cytolysin (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 fovmd to have lost its cytohtic 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 c}i;olysin
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
cvtolvsin combination] : thus we recognize amongf manv
those which act upon red blood cells (hccmolysins) , upon sperma-
♦Poisons of other types, alkaloids, glucosldes. saponines, which do not act by
forming chemical combination do not cause the formation of antitoxines In the
organism. (Ehrlich, H. Sachs.)
«
26 Predisposition and Immunity.
tozoa (spermolysins) , 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 reahzed that the principal feature
in the production of immunity against foreign celhtlar 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 C3'tolysin 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-Infections Immunity. 27
cause a flocculent precipitate. Init which will not (as a rule, and
never if certain m(3des 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 haemolysins 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 wilt 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 bodv 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 intensitv 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. \A'hen, 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 DISEASES
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 inherited (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 amniotic 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 foetal or emhryogenous anomalies,
Z'itia congenita, developmental defects or monstrosities. Except
when a uterine lesion is the cause of the deformation of the foetus,
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 sufferinig 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 niter-
preted, is comparable to acquirement by an external influence, only
tliat 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 {ovo genie or spermatogenie 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 off'spring 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 off'spring 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 structure is altered, as
germinal variations and so-called constitutional tendencies and
diseases.
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-
ple^ 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 vertebrae 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 Ijp) may be caused
by local amniotic trauma or may be an hereditary anomaly.
Heredity is best understood when it concerns chemical in-
Hucnces. As indicated by Ribbert, it may be conceived that the
whole bodv 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 iniinitiuciiig changes.
Should such a process befall both parents, both spermatozoon
Hereditary Disease. ' 33
and ovum are likely to be imnuine 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 equalities. 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 sufficientlv
intensified to reappear as a pathological fault (Ribbert). Hence we
distinguish: a direct li credit y from father and mother to the oiT-
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: Hsemophilia or hsemorrhagic
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, Lehrbn'ch der all gem. Pathologie. 1901.)
What parts respectively are taken by heredity and by external
influences in the development of congenital affections is in 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"], hsemoglobinsemia, 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. Dleckerhoff. Veher d. Erhfehler hei Zuchtpferden: Zcitschr. f. Vctcrinar-
hunde, 1902, Feb., p. 53.
CAUSES OF DISEASE
The influences Avhich lead to bodily injury, to pathological
lesions, and which are spoken of collectively as disease causes
(causer uwrhi) may be arranged in a number of classes.
There are influences dgainst which the strongest and most
resistive constitution is powerless and which inevitably induce
disease in the animal coming under their action ; such absolute
pathogenic influences 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 relative, 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 proximo). 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 auxilians).
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 protopbytes and protozoa.
9. 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
bodv-weight. emaciation and death in the course of from one to
four weeks. A\'ith 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 star\-ation 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, rvlascagni 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-salam.anders and turtles mav 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 is
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 slow^er. Usually the condition is ac-
companied by a diminution of erythrocytes in the blood (inanition
ancemia), tlie alimentary disease producing wide disturbance
through fluid-waste (diarrhoea) 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
physical 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 insufiicient 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 smotherinfi as meaning respiratory obstructiun, operative at
the respiratory orifices, mouth and nose- : clinking, respiratory obstruction operative
within the mouth, nasopharynx or oesophagus (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 terra is "Ersti-ckung."
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 placenta or
compression of the umbilical cord in the maternal canal prevents
ox}gen convection to the foetus.
Furthermore, passive congestion of the lungs, interference
with the emptying of the pulmonary veins and haemic changes in
which the blood corpuscles have lost their ability of taking up
oxygen (carbon monoxide poisoning) render dift'usion of the
gases so difficult that the same result of lowering oxygenation
arises, and the respiratory disturbance eventually advances to the
stage of sufifocation. 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 dyspncea (17 Smirvoia, from wviw, difficult breathing, shortness of
breathing), labored respiratory movements (sufi'ocative dyspnoea),
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 6 (7(pvy/j.6s, 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. insuflicient 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-
40 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-Hke, uncoagulated, dark condition of
the blood (excessive presence of carbonic acid, deficient decarboni-
zation) and in the presence of haemorrhages in the hmg 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 reconstitntion 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 parenchimatous 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 mav be
the cause of death in overheated animals. Horses suffering from
thrombosis of the abdominal aorta and its branches exhibit siens
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-
stinuilation 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 graduall}- and onl}- 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 func-
tional hypertrophy, that is, in an increased grozvth of the cellular
elements corresponding to the demand' for zvork. This may be
noted especially in tubular structures provided with muscular
walls (smooth muscle), where there is gradually and spontane-
ouslv developed an increasing competence for the w^ork 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. functional 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 hyperthermia 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 eft'ort 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 haemoglobin 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 hypersemia of the lungs, liver,
kidneys and brain. The names insolation and sunstroke are ap-
plied to that form of heat-stroke which is caused by the influence
of the direct heat-rays 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
fiffection is accompanied by convulsions and marked symptoms of
excitation (Birch-Hirschfeld).
The influence of heat locally applied occasions, lesions known
as hums (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 40° C. is pro-
ductive of an inflammatory reaction marked merely by dila-
tation of the capillaries (hyperemia) and redness of the part
{inflammatory hum, erythema, hum 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. {hum of the second or intcmiediate degree) is productive,
in addition to the hypersemia, of rapid exudation of serous
fluid from tha dilated vessels beneath the epithelial layer. The
cells of the stratum ]\Ialpighii 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 hypergemic papillje beneath are exposed, the
repair of the epidermis starting from the epithelium at the mar-
gins of the lesions or from remnants of the ]\'Ialpighian 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 third degree),
produce searing and charring {eschar formation) ; the burned
Thcnnic [nflnciiccs. 43
tissue coagulates ; the blood within the capillaries is coagulated
and stagnant, tlie 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
oedema and nephritis often developing in tlie 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, ]\Iaragliano, Castellino, Ponfick)
have showm 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 methoemoglobin)
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-
44 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 soHd (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 blood and tissues, which may destroy the
tissues (Koch, Ziegler).
Hibernating 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 anaemia, 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 anaemia), 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 hiftnences. 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 inllammation 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 (Baiit:^), 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).
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 afifections 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 aetiology 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 afifections 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, wdiile 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 cliilling 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 imexplained 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 (hsemoglobinuria) 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
hsemoglobinuria 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 consensnally or reflex! y 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 Influences. 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.
Hyper?emia). 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. \\'hy 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 i>ain and may abso-
lutely fail to give any idea concerning the anatomical changes
of the tissues.
Aft'ections 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 dift'erent
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 oft'ering 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 skin and laceration of the tissues. Death usuallv
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 in the
internal organs, the tissues may be lacerated, with which lesions
♦Birds sit on telegraph wires witli Impunity because they are not in contact
with the earth.
Electrical and Mechanical Influences. 49
haemorrhages of course occur. Along the entire course of the
current tree-Hke, branching Hues of singeing (hypersemia and
hremorrhages), 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 hcemorrhagic infarcts.
Mechanical Influences.
Pathological changes are very frequently produced by me-
chanical force. These are either lesions of tissue cohesion,
ruptures (breaks in continuity^ Icrsio continui) , or of compression,
as the constriction of a hollow organ, condensation of tissues
or displacement of organs. If this be caused by external forces
or foreign bodies the process is spoken of as traumatism {trauma,
rh rpavixa, lesiou, lat. IcTsio) . 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 internal 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 zvound,
hurt, tear (vidnus, 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 zvrenching or luxations; in the intes-
tines as ruptures (hernia), or tzvists (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 serioivs and perhaps fatal
effects upon the nervous system. For example, this occurs in vio-
lent concussion of the body {commotio from com-rnoveo) , 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 poisons; the actual process of introduction of
the poison and its action, as poisoning or intoxication. Probablv
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 bod\^ 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
eft'ect 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 mi)ieral 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 w'hose 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, w'hose 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 pow-erful poisons
contained in the higher plants are the vegetable alkaloids (mor-
phine, 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 toxines, to.ralbuuiens, foxenaymes.
(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 {viper a berus, the common adder of Ger-
52 Causes of Disease.
many; vipera Redii 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 tins 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: (i) Corrosive, locally irri-
tative poisons; (2) Parenchymatous poisons: (3) Hccmic poisons;
(4) Nerve and Cardiac poisons. I\Iany 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,! etc.). the caustic compounds of
the alkalies and alkaline earths (potassium and sodium hydrox-
•The following is taken from the works of Samuel, Zlegler and Blrch-
Hlrschfeld.
tCarbolic 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
vcsicatoria, 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 local and general pathological results.
The so-called hccmic 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
haemoglobin 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 haemoglobin to form carbon-
oxyd-haemoglobin, 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
sulphmethaemoglobin, 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-
methaemoglobin, bitter-almond odor in the organs). Potassium
chlorate, nitrobenzole, potassium nitrate and amyl nitrite cause
marked destruction of red corpuscles and transform haemoglobin
into methsemoglobin, in which the oxygen is more firmly fixed
than in the oxyhgemoglobin. The blood, and of the organs in such
instances the kidneys especially, take on a striking brown color.
Extensive hsemocytolysis, with liberation and solution of the
haemoglobin in the blood plasma, giving a blood-red color
to the urine (haemoglobinuria), 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 abnis precatorius).
Infectious Agencies.
By the term infection (inficere, 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 \vere caused by a Hving contagion (co)itagium
vk'uni sive aiiimafiiiii) . The nature of these conta^rions re-
maincd hidden, Iiowever, to the physicians of antiquity ; and the
impossibihty of determination led, especiahy 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 coiistititfio cpidcuiica or pcstilens.
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 possible 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 b}- 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
56 Causes of Disease.
blood and internal organs only after death of the animal (mostly
putrefactive organisms).
Those parts of the human or animal body 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 {(rairpbs, decayed; (pijrov,
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 phagoc3^tes 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. Vld.
for fuller consideration Kitt, Bakterienkunde f. Tierdrztc, IV. Aufl. Wien, 1903
Infectious Agents. 57
dal power ; and even thongh 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 inicrobe must possess peculiar toxic pozvers.
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
being heated (to 50° to 80° C.) 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 zvJieii introduced into a
susceptible animal there is invariably a speciHc 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 Iiaptophorc, anchors the
toxic molecule to the cellular protoplasm for which it has affinity ; the
second, or toxophorc 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 indift'erent
substance. This explains why certain animals show a natural
immunity against certain toxines and why the bacteria producing
tlie 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. 59
ture {toxalhnmoi, inycoprotciii, bacterial protein). 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-
tlammatory 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.
h\ 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 grovvth 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
6o 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. 6i
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 Tierarzte, 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 intestinal 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 subsequentlv 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 sexual congress (coital 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; kpvwthv, to conceal). This
Infectious Agents. 63
latter is often the case when we are deaUng with a folHcular in-
fection. The various pathogenic microbes do not possess uni-
form powers of disease production, of multipHcation 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
activity from various atria (tubercle bacilli). Others require
introduction in certain situations in order that they may show
pathogenic efitects, 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-
branes ; the bacteria of mastitis invade the lactiferous ducts
onh' ; the bacteria of calf diarrhoea 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 nuiltiph'. For example, the piro-
plasmata must get into the blood, because they can only obtain
their sustenance under the conditions aft"orded by the living blood
and die out in the body fluids. Other organisms, as the colon
bacillus and vibrio of Metschnikoft', 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. If the microbes
are capable of rapid multiplication and of generating large
amounts of toxic material (as the bacteria of chicken-septicaemia,
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 clinicalh' 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 inocu-
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
lnjcctiotis .liiciifs. 65
disease does not appear for a year. 'Jlie inllucnce exerted by
the virulence, the amount of toxine and the ])artieuhir infec-
tious germ u])(in the period of infection may he 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 (lisscmiiiaUoii and nniltiplicafioii of pafluii^ciiic i^cniis in
tJic body exhibit a number of peculiarities. .Some micro-organ-
isms remain closelv confined to the immediate vicinity of the
point of infection, giving rise from this localizetl situation tcj 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 may cause lesions only in the neighboring tissues or induce
intense general disturbance after absorption. The tetanus bacillus,
ft
for example, does not grow free in the body (except in the uter-
ine cavity, where, under anaerobic conditions, the organism can
accumulate in large quantities after having once lieen introduced) ;
in the course of a dav or two after inoculation it can no lonsrer
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 b\ 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 distributed from the point of
infection along tlic 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 infcctio)i) 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, until they finally reach
the blood. They ma}- also gain direct entrance into 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 hcemato-
gcnous 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 foci of infection, are caused, or the micro-
organisms are widely disseminated throughout the whole body
{general infection, hactericcmia). 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-pysemia. 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. 6y
tonitis as a consequence being- generally a dilluse 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 dift'erent 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-
ical one; it is governed both by the properties and the quantity
of the e.vfrcniely 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 eft'ects 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 mav occur in the same form from the
68 Causes of Disease.
effect of a variet\ of agencies. A nasal catarrh may be caused
by the inhalation of (hist, irritant gases, chemical llnids, 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 septicaemia, of moist gangrene and of mastitis). Such in-
fectious diseases are said to be polybacterial.
Variations in flic duration of infectious discuses, modifications
and degrees of anatomical changes, ore proportioned in the sei'cr-
ity of the infection to the grade of virulence of the microbes,
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 hyperaemia. 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. \'ariations of
susceptibility and resistive powers in different animal species and
individuals to precisely the same infectious agent may cause
Jiifcctioiis .li^ciits. 69
marked variations in the clinical and anatomical picture of
the same infectious disease. I'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 septicaemia, 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 septicaemia ; 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 ansemia as a re-
sult of the prolonged infection.
Recovery from an infectious disease usually leaves thereafter
a certain degree of ininiunity (v. active immunity, p. 2/).
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
m 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
invasion 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 epitheHum 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 {compUcations).
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-Vallee 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 (ectoge)ious infectious agents,
facultative parasitic microbes). The diseases arising from this
group affect individual animals here and there, or may attack a
Infectious Agents. 71
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 telluric origin, and it is customary to speak of
spontaneous disease or miasmatic {t6 /jLiaafia, from fxiaivu, 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 (entogeuous 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 i)i feet ions 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, und in more or less
direct manner have come from previously diseased individuals.
The difiference 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 afifecting 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 metaboUc
activity and metabohc 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
eolon 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
anaerobic conditions on a medium specially rich in albumen (eggs)
they acquire an intense virulence, and if fed to rats produce a
severe ami almost invariably fatal enteritis. Although such
transformation of a non-toxic saprophyte into a toxic pathogen
cannot ofif-hand be accomplished with other micro-organisms, this
isolated fact proves that it is possible for infections of a character
new and imknown 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 previoi:sly 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 widel}- 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 opportunitv 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, cudeuiic). Truly contagious diseases ma}-
also be endemic, provided in a certain district (irrespective of soil
Infections Agents. 73
conditions) there are al\va\s 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 aft'ected, 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.
SU^niARY OF THE AIOST IMPORTANT INFECTIOUS
DISEASES AND THEIR AGENTS.*
I. Bacteriaemias, Septicaemias.
Bacillus az'iscpticus [Boct. az'iscpticuin s. az'icidufu ) , septic:emia
of birds and rabbits (chicken cholera).
Bac. pleuriscpticus, sporadic and epidemic septicaemia of all
domestic animals (bac. hoznscpticus, suiscpticus) , deer and cattle
plagues, pastcurcUosis hovis.
Bac. antJiracis, anthrax of domestic animals and man.
Bac. a\icn:atis nialigi:i, spreading gangrene of domestic ani-
mals and man.
Bac. sarcoplixscuiafos boz'is. symptomatic anthrax of cattle.
Bac. gastroinycosis czis, bradsot of sheep. [Bradsot is a dis-
ease of sheep in northern Europe, by man\' regarded as a form
of symptomatic anthrax.]
Bac. pcstis iarandi, reindeer plague.
Bac. rhusiopathicc suis, swine erysipelas.
Bac. suipesfifer, hog cholera.
Bac. pcstis buboniccr, human bubonic ])lague, transmissible to
swine and rats.
*For detailed description and technique of investigations, v. Kitt, Bakterien-
kunde f. Ticrdrxtc, IV. Aufl., Wien, lOUo.
74 Causes of Disease.
II. Toxic Infections.
Bacillus t eta III, tetanus in all animals and man.
Bac. hotulinus, sausage poisoning in man.
Bac. enteritidis, meat poisoning in man.
Bae. dysenteries zitulorum, diarrhoea in calves.
Vibrio Metschnikovi, vibrio cholera of chickens [microspira
Metschnikovi, irregular] .
III. Inflammatory and Pyogenic Organisms.
Staphylococcus pyogenes aureus (albus, f!a-rus, citreus), sup-
puration of wounds, furunculosis.
Streptococcus phlogogenes sive pyogenes (various forms),
suppuration of wounds.
Micrococcus tetragenns, umbilical suppuration in calves.
Bacillus mallei, glanders in horses and man.
Bac. lymphangitidis ulcerosa;, lymphangitis in horses.
Saccharomyccs farciminosus. furunculosis in horses.
Strcptothrix farcini boiis, furunculosis in cattle [Nocard's
pseudotuberculous nodules in the skin and viscera of cattle].
Streptococcus equi, contagious coryza of the horse.
Bacillus acncos cqiii, contagious pustular dermatitis of horse.
Bacterium phlegniasice ubcris (a number of varieties), mastitis
in the cow.
Streptococcus mastitidis (a number of varieties), mastitis in
cow.
Micrococcus mastitidis gangramoscc oris, mastitis of sheep.
Bacillus py clone phritidis boris, nephritis of cow.
Bac. pyocyaneus, purulent inflammations.
Bac. coli connniiiiis (a number of varieties), various forms of
cellulitis, mastitis, nephritis and enteritis.
Botryomyccs ascofornians, suppuration and granuloma forma-
tion in horse.
Cladothrix canis, various suppurations in the dog.
IV. Diphtheritic Necroses.
Bacillus nccropJiorus, traumatic necrosis, multiple coagulation
necrosis of mucous membranes, liver and lungs in cow, horse and
sheep.
Bac. diphthericc colunibarum, pigeon diphtheria.
Infectious Agents. 75
Bac. diphtheria avium, chicken diphtheria.
Bac. diphthcricc Jioiniiiis, (hplitheria 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. bronchiolitidis vituli, cheesy pseudotuberculosis of the
lungs in the cow.
Bac. pseudotuberculosis oz'is, in sheep.
Actinomyces bozis, actinomycosis of cow (with varieties).
Streptothrix caprce, pseudotuberculosis of the goat.
VI. Specific Diseases of the Sexual Organs.
Bacillus abort ivus z'accaruui, epidemic abortion of cows.
Micrococcus abortivus equi, epidemic abortion of mares.
Streptococcus zaginalis vaccariim, contagious vaginitis of cows.
(Trypanosoma eqniperduni s. tJagelose), dourine in horse.
[SpirochcFta pallida, syphilis in man?]
VII. Pleuropneumonia.
The infectious agent of contagious pleuropneumonia of the
cow.
VIII. Epidemic Diseases Caused by TJltramicroscopic 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.
" Brucei, nagana in African animals.
" eqniperduni, dourine in horse.
76 Causes of Disease.
Trypanosoma Theileri, African cattle plague.
[ " Gamhiense, African sleeping sickness in man.]
Plasmodium malaria equorum, African equine malaria.
[Plasmodium of human malaria — tertian, quartan and a^stivo-
autumnal types.]
Piroplasma bigcminum, epidemic haemoglobinuria of cattle,
deer and sheep.
Piroplasma caninum, infectious jaundice of dog.
Sarcosporidia major and minor, parasites of muscle and cel-
lular tissue in swine, cattle, sheep, goats and horses.
Coceidium oviform e. dysentery of cow, intestinal and biliary
duct parasite of rabbit (also in man and dog).
Diseases Due to Mould Fungi.
Moiiilia eaitdida, thrush in man and birds.
Trichophyton to)isura}is (numerous varieties), bald patches in
cow, man and dog.
Achorion Selionlcinii (numerous varieties), favus in man and
lower animals.
Dermatomyces gallinarum, scab of cock's comb.
Aspergillus fumigatus, pulmonary mycosis in birds (excep-
tionally in horse and cow).
Animal Parasites.
Food and conditions favorable to the existence of a variety
of animals and plants are afforded by the human and animal
bodies, both in the fluids and tissues, and, too, in the nutrient
ingesta and in the excretory and waste matter. When some organ-
ism both acquires its nutrition and resides upon or in the body
of another individual the condition is spoken of as parasitism
(Trapa along with ; <^^-ros. food). A parasite, therefore, is a form
of life zi'hieh either transiently or pernianentl\' lives upon or
in the body of another organism for the purpose of obtaining its
nutritio)i tJierefrom (Braun. Heller).
According to their origin from one or other of the two kingdoms in
nature, they are separable into vegetable and animal parasites ; those which
hve on the surface of the body are spoken of as ectoparasites or external
parasites (epiphytes, epizoa), those whose habitats are within the body
as internal parasites or entoparasites (entophytes, entozoa).
In the preceding chapters the discussion concerned infestment
Animal Piirasilcs. yy
by microorganisnis ai^prcciablc only with the aid of the niiero-
scopc. the protophytcs and protozoa, a condition spoken of as in-
fection wlien leading" to disease. Some of these micfobes well
merit the name parasites, since the animal body in which they
exist is the source of their nutrition, but the toxic properties of
the most of them are so conspicuous that we are likely to think
of these not so much as ])arasites, but as comparable to poison-
ous plants.
A mmiber of forms of worms and arthropoda (zooparasites)
have gradually assumed the character of true parasites and actu-
ally live and subsist upon the body structures. ( )ccupation of the
body, either externally or internally, spoken of as i)n'asioii
(iiiz'adcrc, to penetrate), is apt to give rise to a varied group of
tissue alterations and disease processes (invasion diseases [iiifest-
ment] ). The individual in which such a zooparasite finds shelter is
to be looked upon as the host of the parasite. Some infest the host
only for a brief period as necessary for the acquirement of nutri-
tion (transiriif <^r tcutporary parasites) , or for the time essential
for the completion of one or more stages of their development,
among which groups respectively fleas and the larvfe of gadflies are
examples. Others are persistent and pass their entire existence as
parasites (habitual or pcniiaiicut parasites). The life of this
latter type ma\- be passed in some instances entirely in one host
(inono.rcnoiis parasites: ^bvos, one; ^evos, host), or may be dis-
tributed over several hosts (hetero.veiioiis parasites).
Invasion of a host at times is merely the result of accident,
in which case the parasite is usually taken in with food: in other
instances this or that parasite may by its own independent move-
ments gain entrance into the body.
Parasitism may he referred to two underlying conditions,
adaptability of the parasitic organism to the conditions of life af-
forded by the body of the host and the biological variability of the
former. Worms and arthropods which have assumed parasitic char-
acteristics undoubtedly at one time lived independently in nature. It
may be imagined that one of these low types of animals by acci-
dent entered the bodv of some higher animal, and, finding condi-
tions favorable for the acqiiiremcnt of food, remained and multi-
plied ; that the offspring, now native to the body of the host,
did not again seek a free state, but continued as parasites, being
from birth accustomed to the altered environments. Such sup-
position is justified by the fact that some parasites still show rudi-
78 Causes of Disease.
ments of organs worthless to them in their present form of life,
but which were evidently inherited from their free-living ancestors.
For example, in lingiiatnla tccnioidcs, a permanent parasite of the
nasal fossae of the dog, there are rudimentary feet, probably
better dev^eloped in the free-living predecessors, but stunted in these
parasitic descendants from lack of use. In the same way may be
explained the absence of wings in parasitic insects ; for example,
sheep lice have probabl\" developed through atrophy of their
wings from disuse of these organs, for there are allied species of
insects which are not parasitic and possess wings. On the other
hand, gradual adaptation to life upon an animal host leads to the
acquirement of new peculiarities, on the part of the parasite, as a
transformation of masticating mouth parts into piercing and
suctorial organs and the development of special types of organs
for attachment and holding. Such adaptations and transforma-
tions of structure are of such common occurrence throughout na-
ture, even in case of the human body (formation of a horny sole
on the back of the foot, originally soft, in cases where from some
disease the dorsum of the foot is turned down and walked on ;
transformation of the toes into prehensile organs by practice),
that, as it is true in the higher animals, there is no wonder that
it should occur in these lower invertebrates whose tissues are
much more capable of such adaptive growth. The newly ac-
quired characteristics become fixed in the succeeding generations
because of heredity and because of uniformity in the vital condi-
tions about them ; some species which have gradually assumed
parasitic nature are finally restricted entirely to a parasitic life
and are unable to live in the external world ; others pass only a
part of their lives, a definite developmental stage, as parasites, and
for the rest of their time live independently. There are certain
filarial worms which ordinarily live in moist earth, but which now
and again, as necessity arises, become parasitic. As the moisture
disappears these worm retreat into depressions where the moisture
is longest retained, but should a snail or earth-worm happen in
their way they pick out the cavities of these animals and creep
into them. In protracted drouths they are parasitic for a corre-
spondingly long period, and it has been observed that in such
parasitic existence they attain unusual size and produce a larger
number of ova than their free-living fellows (Braun, Heller). It
may be that the young brood continue in the snail and become
completely transformed into parasites, but the original ones, when
Animal Parasites. 79
wet weather returns, abandon their parasitic hiding places. L.
Oerley has succeeded in artificially causing a free species of worm
(rhabditis pellio) to live temporarily as parasites by introducing
them into the vagina of mice, where they continued to live and
multiply, although when placed in the digestive canal they died or
were expelled. Larvae of flies often resort to parasitism as oppor-
tunity is afforded; meat flies and other insects which are ordinar-
ilv saprophagous often oviposit upon some animal in wounds or
ulcers and the resultant maggots obtain their nutrition in the
same location as parasites, although succeeding generations con-
tinue as usual under other conditions of existence. It may be
supposed that frequently such assumptions of a parasitic existence
are brought about by the force of circumstances and end with
the death of the organism if it be incapable of adaptation, even if it
should succeed in getting nourishment from the body of the ani-
mal host. Only in case the intruding worm (or other form of
life) can successfully withstand the mechanical and chemical influ-
ences which oppose it, only in case it obtains a habitat where it is
possible for it to live, is it likely to be changed into a parasite.
Some worms may be -parasitic in different animal species;
trichinella is parasitic in man, hog, rat, mouse, cat. fox, polecat
and bear, and may be artificially induced to infest the dog, rabbit,
guinea-pig, sheep, horse and other mammals. In the same way the
liver fluke is found in a number of species. Other parasites, on
the contrary, occur in only one fixed species. For example, tcenia
solitmi and tcciiia saginata are found only in the human intestine;
crassicolis only in the cat ; in the intestine of another species they
die and it is impossible or only an exceptional case that they
should persist. Such exceptions, however, do occur naturally as
well as in artificial attempts to infest. For example, bothrioce-
phalus latns, whose normal host is man. is occasionally found in
the intestine of the dog; echynorhynchus gigas, a parasite of the
intestine of the hog, is in rare instances met in man. Such cases
are to be explained by exceptional opportunities for transmission.
The influence of parasites upon the host varies much accord-
ing to their habits and situation. In many instances the presence
of a parasite occasions no noticeable disturbances ; dogs may have
dozens of tapeworms in them without showing any evidence of
sickness, although in other cases even a small number of the same
tapeworms cause digestive disturbances. At one time it was sup-
posed that some parasites were of use to the host, as the larvae
8o Causes of Disease.
of one of the gastric flies (j^astrophilus sahttaris — so named from
this idea) ; it was thought that their presence in the stomach and
small intestine of the horse promoted the secretion of gastric
juice ; or it was believed that some parasites consumed superfluous
mucus. Although it is reasonable to suppose that some parasites
obtain their nutriment from the waste matter (as is true of the
infusoria and bacteria always present in the stomach in rumi-
nants) and take part in the breaking up the intestinal contents,
yet it is not to be concluded that the parasitic worms and arthro-
pods have any value whatever to their host. On the contrary, the
animal host, if rid of them, will tlirive equally and better. All
parasites exert from time to time some harmful influence, and
some are death-bearing guests.
In the first place, many parasites are harmful to their host and
productive of' disease by their wandering in the body and their
movements. Undoubtedly the itching caused by the crawling para-
sites inhabiting the skin-surface, and often giving the host no
rest day or night, has some influence upon the health ; here may
be mentioned the sheep-lice, itch-mites and the oxyurides inhabit-
ing the rectum and causing continual tickling sensations, as per-
fect torments which often give rise to emaciation (due to the in-
crease of metabolism following the incessant restlessness from the
itching). Other parasites make their way through the tissues by
boring, and thus where any considerable number penetrate into
the organs cause tissue destruction and occasion haemorrhages and
inflammatory lesions (lesions produced by liver flukes, larval tape-
worms and lingiiatulidse). They may give rise to a great variety
of disturbances, just as any foreign bodies in a mechanical way,
by compression of tissues, or by obstruction and narrowing of
tubular passages, as sudden death by invading the brain, paralysis
by pressure on the s])inal cord, atrophy of the liver by growth in
its parenchyma, blindness by penetrating into the eye, rupture or
thrombosis of the larger blood vessels, respiratory interference and
suffocation by lodgment in the air passages and lungs, and intesti-
nal obstruction. The parasites adhering to the intestinal mucous
membrane by booklets or suctorial apparatus often produce re-
flexly marked irritative or perhaps nervous phenomena ; and, too,
a toxic influence is to be ascribed to the metabolic products of a
number of worms which may be reasonably thought to explain
the occurrence of nervous changes and general loss of flesh (as in
Animal Parasites. 8i
case of echinococcus cysts, bothriocephalus and teniae*). Local
inflammatory lesions of the skin and mucous membranes are the
result of mechanical injuries caused by a variety of parasites.
The amount of nutritive substance abstracted by parasites from
the host is to be regarded as usually relatively insignificant.
Where, hov/ever, the parasites are blood-suckers, the host is placed
at special disadvantage ; the smallest of the round worms, if pres-
ent in large numbers, may cause serious loss of blood, and per-
haps the death of the host. The roe. the common deer and the
sheep, for instance, are uniformly killed by an anaemia if blood-
sucking strongylidas infest the rennet-stomach. Whole flocks of
poultry mav die out when the poultry mite, dcrmanyssus avium.
gets into the hennery and infests the skin of the fowls in vast
numbers, feeding daily upon the blood.
A century ago our appreciation of the life history of the parasites
and of the diseases caused by them was but vague. It is true that most
of the worms found in the human alimentary canal were known to the
students of natural history in antiquity: and as early as the seventeenth cen-
tur>- itchmites and their relation with the itch were fairly well known.
Yet it was for the most part believed that parasites had their origin in
inspissated juices or pathologically altered parts of tlie human or animal
body by a process of spontaneous generation (gcncratio ccqutvoca). When
the microscope came into use and it became possible to closely observe their
generative organs and their products (eggs), and particularly after attempts
came to be made to artificially transmit the parasites by experimental feed-
ing of the worms and their larvc-e, the real history of their development was
for the first time apprehended. Redi and Swammerdam, van Doeveren and
Pallas, Pastor Goeze, C. Fr. Miiller, Bojanus, Abildgard, toward the end
of the i8th and the beginning of the iQth century, Steenstrup, v. Baer,
V. Siebold, van Beneden, Kiichenmeister, in the middle of the latter
century, corrected the mistakes and hiatuses of the earlier views and
investigated the most interestmg parasites ; and in recent years the studies
of a large number of zoologists, physicians and veterinarians (Leuckart.
Zenker, M. Braun, Peroncito, Grassi, Railliet, Heller. Ziirn. L. G. Neumann.
V. Ratz and others) have contributed to extension of our knowledge in
this field to such a degree that pathology and practical hygiene have been
decidedly benefited by their investigations.
♦Persons handling ascaris megalocephala, the rouud worm of the horse, es-
pecially if engaged in mincing it, are apt to be directly affected by a conjunctivitlB
.-■nd lu-ticarial eruption frrmn a certain substance cxistinrr in the cu.tlcle of tho worm
(apparently a dermal secretion) which possesses irritative properties.
82 Causes of Disease.
TABLE OF PARASITIC ARTHROPODA OF THE DOMES-
TIC ANIMALS.*
I. Insects {Insecta).
1 — Blood-sucking Flies, attacking- the Skin. (After Neumann.)
Culex pipiens (and other gnats) in man.
Simulia reptans, horse ; mucous membranes of the head,
" maculatuin, horse, ruminants, man.
Tabanus hovinus, morio, aiitiimnalis, bromiiis, nisticus, fulvus,
albipcs, horse, ruminants, man.
Hcpmatopota pliiznalis, horse, ruminants, man.
Chrysops cacutiens, horse, ruminants, man.
Stomoxys calcitrans, horse,
Hamatobia stimulans, fcrox, irritans, serrata, horse, ruminants.
Glossina morsitans, horse, ruminants.
Hippobosca equina, horse, ruminants, dog.
Mclophagus oz'iniis, sheep.
2 — Flies Parasitic Upon or Beneath the Skin in Larval Stage.
Calliphora oomitoria, various domestic animals.
Sarcophaga carnaria, magnifica, JJ'ohlfarti.
Liicilia Ccusar, sericata, maceUaria.
Ochromyia anthropophaga, dog, cat, goat, man.
Hypodcrma lincata, sheep [cow].
" tarandi, reindeer.
" hovis, cow (even in the spinal canal).
" silenus, horse, ass.
Dermatobia noxiaUs, cow, dog.
3 — Flies Whose Larvae are Parasitic in the Intestines and Body
Cavities.
Gastrophihis eqiti, stomach and pharynx of [horse] .
" pecorum, stomach.
" diiodcnalis, duodenum of horse and exceptionally
in dog.
•Details of the life-history and the patholog-ical significance of the species
enumerated may be found in Kitt's "Lehrhuch der Spesiellen, Pathol. Anatomic der
Haustiere." [See also I'riedberger and Frohner, Veterinary Pritholonii, Amer.
Edition, 'W. T. Keener & Co., Chicago, 1904.)
Animal Parasites. 83
Gastrophilns hcomorrhoidalis, stomach, rectum of horse.
" flavipes, stomach of ass.
Oestrus ovis {Cephalomyia oris), nasal and brain cavities of
sheep.
4 — Fleas.
Pulcx irritans, man, dog, cat.
" serraticeps, dog.
" goniocephalus, rabbit.
" avium, chickens, pigeons and other birds.
penetrans, sen Sareopsylla penetrans, man, domestic ani-
mals (tropical).
Sareopsylla gallinaeea, domestic fowl in tropics.
5 — Lice.
Hccmatopinus macrocephalus, horse.
" eurysternus, cow.
" tenuirostris, cow.
" steiwpsu, goat.
" cameli. camel.
" piliferus, dog.
" latus, dog.
" ventricosus, rabbit.
6 — Parasites of Hair and Feathers.
Trichodcctcs pilosus, horse.
" panimpilosits, horse.
" scalaris, cow.
" spharoccphalus, sheep.
" climax, goat.
" latus, dog.
" suhrostratus, cat.
Melophagus ovinus, vid. blood-sucking diptera.
Goniodes dissimilis, Burnetii, Gonioeotes hologaster, gigas,
Lipcurus variabilis, hetcrographns, Mcnopon pallidum, biseriatum,
all in the hen.
Goniodes stylifer, polytrapeaius, Menopon biseriatum, turkey.
Goniodes nnmidianus, rectangulatus, Lip. numidice, Menop.
numidice, guinea fowl.
Goniodes falcicornis. parvieeps, rectangulatus, Menop. phcBOS-
tonium. horse.
84 Causes of Disease.
Goniodes colchicus, truncatus, chrysocephalus, Lipeurus varia-
bilis, Menop. productiim, biseriatum, pheasant.
Goniodes minor, compar, Lip. bantlus, Colpoceph. longicaudum,
Men. lainm, biseriatum, pigeon.
Docophorus ict erodes, adustus, Lipeurus jejunus, anseris, Trino-
ton conspiircatum, continuum, goose.
Docophorus icterodes, squaUdus, Trinotum luridum, Menopon
obscurum, duck.
Ornithobius bucephalus, swan.
II. Spiders. (Arachnoida.)
1 — Mites. Parasites Upon the Skin.
Demodex sive Acarus folliculorum canis, cati, suis, caprce, ovis,
etc. (in the sebaceous glands and hair folHcles).
Sarcoptes major s. scabiei communis, in and beneath the epi-
theHum, in horse, dog, sheep, goat, camel, monkey, man.
Sarcoptes minor, cat, rabbit.
Dermatocoptes communis, horse, cow and sheep ; also in goats.
" cuniculi, in ear of rabbit.
Dcrmatophagus communis, horse, sheep.
" auricularum felis, cat.
" " canis, dog.
" " cuniculi, rabbit.
Dermatoryctes mutans, fowds, foot itch.
Sarcoptes lavis, pigeons and fowds.
Epidermoptes bilobafus and bifurcatus, fowls.
HarpirhyncJius nidulans, pigeons, in the feather follicles.
Hypodcctes columbarum, pigeons, subcutaneous connective tis-
sue and body cavities.
Laminosioptes cysticola, fowls, connective tissue.
Cystodites nudus, fowls, pheasants, air spaces, lungs, liver,
kidneys.
Syringophilus bipectinatus, fowls, pigeons.
'■ uncinatus, peacocks, quills of feathers.
Analges minor, fowls, quills of feathers.
Dimorphus columbce, pigeon.
Leptiis autumnalis, dog, man.
Dermanyssus avium, birds, man, dog. cat, horse, cow (ear).
Gamasus ptcropoides, rabbit, mole, field mouse, cow (ear).
Cheyletus parasitivorox, rabbit.
Animal Parasites. 85
2 — Ticks. (Sucking blood from skin.)
Ixodes ricinus and hexagomis, man, dog, horse, cat, ruminants,
birds.
BoopJiilus annulatiis s. bozis, cow (America).
Dermacentor reticulatus, sheep, cow, horse, man (America).
" clectus, dog (America).
Argas miniatus, cow^
Amblyonima americanum, cow% man.
Ornithodorus Mcgnim, man, cow, sheep, horse, ass, dog.
Argas reflexns s. marginatus, pigeons.
3 — Pentastomes of the Viscera.
Linguatula tcenioides, dog, wolf, horse, goat, man (nasal pas-
sages).
Larval form, Linguatula denticulata (mesenteric lymph nodes,
lungs, liver), ruminants, horse, cat, rodents.
LIST OF WOR^IS PARASITIC IN THE DO:\IESTIC
ANIMALS.
I. Flatworms.
1 — Tapeworms.
Anoplocephala s. Tccnia plicata, horse.
perfoliata, horse.
" mammillana, horse.
Moniccia cxpaiisa, ruminants. : i
planissima^ ruminants.
" Benedini, ruminants.
" Neumanni, ruminants.
" trigonophora, ruminants.
" denticulata, ruminants.
" alba, ruminants.
TJiysanosoma ortinoides, sheep.
" Giardi. cow and sheep (hog).
Sfilcsia ccntripunctata, sheep.
globipuuciata, sheep.
Tcriiia nwrginata. dog; bladder worm, cysticcrcus tenuicolUs,
ruminants and hog.
Tccnia scrrata, dog; bladder worm, cysticcrcus pisiforniis, hare,
rabbit.
86 Causes of Disease.
TcEtiia echinococciis, dog, jackal, wolf; bladder worm, echinoc-
occiis polymorphns, man, ruminants, hog.
Tceriia canurus, dog; bladder worm, co'nurus cerehralis, rumi-
nants, horse.
Dipylidium caninum^ (Taenia cucumerina), dog, cat, man;
bladder worm, cryptocystis tricJiodectis et pulicis, larvae of dog
fleas and ticks.
Mesocestoides lineatus (Taenia litterata), dog, fox, cat.
Tcenia serialis. dog ; bladder worm, cysticercus s. coenurus seri-
alis, rabbit.
Tcenia Krabhei, dog; bladder worm, cyshcerciis tarandi, rein-
deer.
Bothriocephadus lotus, man. dog, cat ; larva, plerocercoid of
fishes.
Bothriocephalus cordatiis and fusciis, dog.
Tauia crassicollis, cat ; bladder worm, cysticercus fasciolaris,
mouse.
Dipylidium Chyzeri. PasquaJi. Trinchcsii, cat.
Tcenia solium^ man ; bladder worm, cysticercus ceJluloscB, hog,
dog, cat, sheep, roe, polar bear, rat, man.
Tcenia inerniis hoin. s. niediocanellata s. saginafa, man ; blad-
der worm, cysticercus inerniis, cow.
Drepanidiotccnia inf undihulif orrnis , fowl.
Dicranotcenia sphenoides, fowl.
Davainca proglottina.
" tetragona, eesticillus ectinohothrida, fowl; Fried-
bergeri, pheasant.
Bothriotcenia longicollis, fowl.
Drepanidiotcenia lanceolata, setigera, fasciata. anatina, gracilis,
Krabhei, tenitirostris, goose and duck.
Dicra>iotcenia furcigera, megalops, eoronula, duck.
Mesocestoides inibuti[ormis, duck.
Echinocotyle Rosseteri, duck.
Dazainea crassnla, pigeon.
Bothriocephalus colunibarum, pigeons.
2 — Fluke-worms.
Fasciola hepatica. distoniuni hepaticuni, rtmiinants, hog, ass,
horse, rodents, man (liver — errant examples in the lungs and
musculature ).
Animal Parasites. 87
Fasciola laiiccolata, distoimim s. dicrocceliiim lanceolatum, ru-
minants, hog, rodents (liver).
Fasciola magna, cow, elk [deer], (liver), (America, Italy).
Distomum truncatum, alhidiim and felineum, cat (liver).
Agamodistomiim snis, hog (muscle).
Distomum, echinostomum alatum, ducks and other water fowl,
exceptionally dog (intestine).
Amphistoma conicum, ruminants (first stomach).
" Collinsi, horse (intestine), (Egypt).
Gastrodisciis Sonsinoi, horse (intestine), (Egypt).
Monostoma verrucosum, duck, fowl, goose.
" attenuatum, goose (intestine).
Distoina oxycephalmn, duck, fowl, goose (intestine).
" dilatatum, armatum, lineare, ovatum, commutatum,
fowl (intestine).
Holostoma erraticum, duck (intestine).
Distomum hcematohium s. crassum (Bilharsia crassa), cattle,
sheep, monkey (urinary organs, intestine), (Mediterranean bor-
ders),
Distoiiiuiii Westermanni, cat [man] (lungs).
Distomum heterophyes, dog (intestine), (Japan).
Distomum pancrcaticum, cow, sheep, (Japan).
TI. Round Worms.
1 — Acanthocephalid Worms (Thorn-headed worms).
Echinorrhynchus gigas, hog, man (intestine).
" polymorphus, goose, duck (intestine).
2 — Common Round Worms.
Ascaris megalocephala, horse, ass (intestine).
" mystax, dog, cat (stomach, intestine).
" lumhricoidcs, man (intestine).
" suilla, hog (intestine).
" vitidi, cow (intestine). ■'
" ovis, sheep (intestine).
Hctcrakis uujculosa, pigeon (intestine).
" inflexa, fowl, turkey (intestine).
" papulosa s. vesicularis, fowl, peacock, guinea fowl,
turkey (intestine).
Heterakis diffcrens, fowl (intestine).
" dispar, duck, goose (intestine).
Gnathostoma hispidum, hog (stomach).
88 Causes of Disease.
3— Pin Worms.
O.vyuris 7 cniticiihiris, dog. man (rectum).
ciirvula, iiiastigodes, horse (colon and rectum).
ambigua, rabbit (caecum).
4 — Strongylus Worms.
Eustrongylits gigus, dog, horse, cow (kidneys, peritoneum,
heart, hver).
Etistrongylus tubifc.x, duck (intestine).
Strongylus anuafus s. sclcrostomuui aruiatuui, horse (intes-
tine) ; peritoneum (larvaj and embryos wander into the arteries,
brain, testes) ; str. arniatus has recently been subdivided by
Sticker into three species: Sclcr. edentatum, hidentatum, quadri-
dcntatum.
Strougylus tctracaiitJius (sclerosf. tctr.), horse (large intes-
tine).
Strongylus contort us^ ruminants (abomasum, small intestine).
Ostertagi, cow, sheep, goat (abomasum).
Ciirticci, cow, sheep (abomasum, small intestine).
oncophorus, cow (abomasum, small intestine).
Harkeri, cow (abomasum).
rctortcrformis, ruminants, hare, rabbit (abomasum,
small intestine). *
Strongylus lilicollis, sheep (small intestine).
radiatus, cow (small intestine).
inflatus, cow (colon).
.-I.vci. ass (stomach).
Iiypostoiuus, sheep, goat (intestine).
filar ia, sheep, goat, fallow deer, red deer (bronchi,
lungs).
Strongylus parodo.vus. hog, sheep (bronchi, lungs).
coin.niutatus, sheep, goat, hare (lungs, bronchi).
micrurus, cow, horse, red deer, fallow deer (bron-
chi, lungs).
Strongylus Amficldii, horse (lungs).
sagittatus, red deer (lungs).
capillaris, goat, sheep, chamois (bronchi, lungs).
den tat us, hog (large intestine).
" ruhidus, hog (America).
annidatus {Strong, s. Filaria tracheo-hronchialis) ,
dog (air passages).
A III III a I Parasites. 89
Strongylus vasoruin canis, dog (blood vessels).
" pussihis^ cat (lungs).
" tenuissimiis, horse (stomach).
" Icporum, hare,, rabbit (stomach), (America).
" tenuis, goose (caecum).
" nodularis, goose (pharynx).
" s. Syngamus trachealis, hronchialis, fowl, pheasant,
horse, goose, duck, etc. (air passages).
Dochinius trigonoccphahts, dog, cat (intestine).
stenocephahis, dog (intestine).
" tubceformis, cat (intestine).
" boz'is s. CEsophagostoma vcsiculosuui, cow (intes-
tine).
CEsophagostoiiia colninbiaiiuin, sheep, deer (intestine).
Uncinaria cernua, sheep, goat (intestine).
Olhdanits tricuspis, cat (stomach, embryos in the lung).
Strongyloides intestinalis s. Anguillula stercoralis, man, fowl
(intestine).
Anguillula vivipara, horse (colon).
Rhabdoncnia longum, sheep, hog (intestine).
5 — Whip Worms.
Tricocephaliis dispar, man, dog.
" affinis, ruminants (large intestine).
" crcnatus, hog (large intestine).
" depressiuscitliis, dog (large intestine).
Trichosoina ccropliUnm. cat (trachea, bronchi).
fclis cati, cat (urinary bladder).
longicoUc, fowls (csecum and rectum).
" aniiulotnrn, fowls (pharynx).
" coiitortnin, duck (crop, pharynx).
" collar e, fowls (intestine).
" tcnuissiiiiiiiii and brevicoUc, pigeon (small intes-
tine).
Trichina spiralis, hog, rat. man, all carnivora (intestine, em-
bryos and undeveloped trichinelke in muscle).
6 — Filariae.
Filaria papulosa s. equina, horse (peritoneum, pleura).
tercbra, cow, deer (peritoneum, eye).
90 Causes of Disease.
Filaria lacrymalis, horse, cow (conjunctival sac).
" imniitis, dog (heart) (Asia [America]).
" s. Spiroptera sanguinolenta, dog (stomach, aneurisms,
pharynx).
Filaria s. Spiroptera strongylina, hog (stomach).
" s. Spiroptera megastoma and microstoma, horse (stom-
ach) ; Gongylonema scutatiim, sheep, cow, horse (pharynx) ;
Gongylonema pulchrum, hog (pharynx, tongue).
Filaria s. Onchocerca reticulata, horse (tendons, ligamentum
nuchse).
Filaria hceniorrhagica, horse (skin).
DermoHliaria irritans, horse (skin).
Filaria uncinata, goose (pharynx, crop, intestine).
" nasnta, fowl (crop).
*' s. Dispharagits spiralis, fowl (pharynx, crop).
Tropidocera inflata, duck (crop).
7 — Annelides.
Hcemopis 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
{t6 <7r),xdov from ai)iJ.aivui, to denote ; (Jv^x-lvl^^TeLv, 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 (i, d^dy,u,^is, differentiation or thorough knowledge;
from 7a•"i'T^-«^ ^o 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
aft'ection, 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 prlnclpaT features of tbls chapter have been In Part adapted from
Handbuch der aUgem. Pathologie, Fhl und Wagner (Leipzig, 1870).
92 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 ^etiological 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 nosological, when indicating the nature of the process.
No diagnosis can be regarded as complete unless embodying the recogni-
tion of both location and nature of an affection, as well as of its aetiology,
in so far 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 oedema
of the dewlap. There are certain symptoms called pathognomonic
sympfouis, whicli 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; tho
ability to recognize and to determine the im.portance 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-
f j
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-
perience 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 aiiaiiiitcsis: ava-ixifj-vriffKO}, 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. Lchrhncli dcr kliiiiscJicii Unfersiicliuiigs-
methodcn, or ^loller, Klin. Diag. dcr dusscni KraiikJicHcii dcr
Haitsticrc. F. Enke, publisher.)
The art of diagnosis concerns itself, after the proper recog-
nition of the symptoms manifested, with the condition of the
oreans, finallv 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 wath those of each different known disease, and determina-
tion of the aft'ection 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 faiista ; unfavorable, prognosis
infansta ; or uncertain, prognosis anccps). The course and ter-
mination of many diseases may be predicted with more or less
certainty, inasmuch as examples of the aft'ections 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 bod}' 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-
ploying proper remedial measures.
Therapeutics (i) Oepawela, from eepairevco, to serve or cure) or
remedial treatment has to deal with eft"orts 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 (paUiative, 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, ansemic and hyperae-
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 {intermittent) 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 indefinite, irregular 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 mav be classed as sub-acute affections. In case of
g6 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 signifi-
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 Umit ; and,
moreover, w^e 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 dififerences 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 empirically
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) infection (time of en-
trance of the microbic cause), (b) incubation (a period without
symptoms, l)ut during whicli the .germs are multiplying in the
Stages of Disease. 97
economy to sufificicnt number to excite their definite elTects), (c)
prodrojiics (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) invasion (the period of develop-
ment of tlie specific symptoms of the afifection ; this, if it occur
rapidly, is said to be a fnuik iiiiasioii; if gradually, is called an
insidious iivz'asioji), (e) acme or fastigium (the period of fullest
intensity of the disease), (f) occasionally an amphibolic sta^c (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 (irregitlarities) 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 localizefl 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
m.anifested or open stage. Some diseases, even though they be
severe, remain latent because they are foUowed 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 local disease or disease of [this ov
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 disseminated (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 dissemination 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 focus 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 affection, 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 (i) by
continuity and contiguity of the tissues (per contimdtatem, per
contiguitafem) , (2) by the blood or lymphatic tissues {hcematogen-
oi!S, 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 uf Disease; Termimition 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 contigxiity 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,
mav give rise to an extensive pleuritis. Hccmatogenous extension
of a disease occurs when the pathogenic agents gain access to the
blood; IxmpJwgcnous cxtcnsioji. when such influences, through
the agency of the wandering cells, are mingled with the lymph
(cf. emboHsm). Sympathetic disturbances in function arc appar-
entlv in part the result of sensory and motor reflex action, in
part the result of primary changes, the etficiency 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), o'- 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:
1. 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.
lOO Termination of Disease.
Tcnniiiation 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. IVIany
corpuscular disturbing factors (as bacteria, dead cells, haemor-
rhagic foci) are removed through the activity 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 is also
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 of man. would threaten with
annihilation, all too soon, the creatures of the earth. The sienifi-
cance and success of medical science is particularly impressed
upon one when it is recalled how destructive epidemic diseases,
which in times past carried ofif millions of animals and men, have
in some instances been wholly eradicated, in other instances greatlv
diminished. By appreciation of the nature of a varied group of
affections, there has come the discovery of efficient methods for
Tcriniiialidii iii Recovery: Pcalli. loi
their cure and for proph>laxis 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 ofif premature death and may assist the
injured body to regain its health. Medical art can prevent fatal
haemorrhages, 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 [sequelcc 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 (e.vitiis lethalis or letalis,
from /t^f7/;;/, death; from Ky)et) forgetfulness, \avedvw 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 (anse-
mia, albuminous waste, closure of respiratory passages, elevation
or depression of body-temperature, reflex palsies). The more
important modes, therefore, by which this or that disease may
induce death, are :
1. 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
e.ritus lethalis per syncopeni, (tw-koitthv, 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. Mednllary 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 (exitns lethalis
per apoplexiain, d-n-owXricraei.i', to strike down).
4. Hceniorrhage, 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 haemor-
rhage induces ischsemia of the heart and coronary vessels, with
the result of cardiac cessation and at the same time the symptoms
of suffocation, due to an anaemia 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 ^apaiveiv, to
Tcniiiiiatioii in Death. 103
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. Physiologic) 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 haemor-
rhages or cardiac and cerebral paralysis. In the majority of in-
stances, however, death comes on gradually, with the manifesta-
tion of characteristic phenomena w'hich' predict the termination of
life, and which together constitute what is knowm as the death-
agony (t7 ayuvla, 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 i?
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 haemorrhage,
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
haemoglobin), 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 (asphyxia 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 anaemia.
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 hasmic 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 abnormalitv of the vascular
►See also Kitt, Lehrbuch der patliol. Anatomic d. Haustiere. II. Aufl.
Cardiac Hypertrophy. 107
system, of excessive blood pressure and of unusual quantities
of blood within the organ. Such 'Svork-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 insufficiency).
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). X'alvular
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 aft'erent 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
io8 Disturbances of Circulation.
pressure still higher. (Powerful muscular contractious force
larger amounts of blood into the right heart ; the ventricles become
engorged and the hsemic 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 that 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 hj'pertrophied 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 tlie 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 narrowin"; of the lumen and the in-
creased rigidity of the tubes ; and with the imperfection of circu-
lation 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 iiisutficioicy. It follows various influences afl'ecting the
myocardium or its ganglia, among wdiich as prominent examples
mav 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 atroi-)hy of the myocardium. All patholog-
ical changes which occasion cardiac insufiiciency are followed by
disturbances in the movement and distribution of the blood. A
fatigued and weakened heart is incapable of normal contraction,
expels from its chambers a smaller amount of blood than normally ;
in consequence the arteries are not properly filled, the blood press-
ure sinks in them and the movement of the current is slowed. The
aspirating power of a weak heart is also low and the blood moves
less freely from the venous side of the circulation, the veins becom-
ing engorged and the pressure raised. The results of these irregu-
larities differ somewhat as the left or right heart alone or the
whole organ is especially involved ; in one case the lesser circula-
tion, in the other the greater being the more disturbed. Many
variations, too, are occasioned by the grade of cardiac insufficiency
and by the nature of the original causes (cf. ancvmia and hypcr-
(DJua). The luyocardium being weak the cardiac cavities do not
contract as in normal conditions, contain an excess of blood, and
this engorgement gives occasion for dilatation of one or both sides
of the organ.
Left ventricular insufficiency determines imperfect filling of the aorta
and its branches, and in consequence deficiency in the amount of arterial'
blood going to the brain, skin, glands and elsewhere. The heart, however,
remains full and the blood is dammed back into the pulmonary veins, and
the right heart experiences marked difficulty in forcing the blood through
the lungs. Insufficience of the right heart, on the contrary, causes incqm;^
no Disturbances of Circulation.
plete filling of the pulmonary artery, pulmonary anaemia, and, of course, the
left heart in its turn receives unduly low amounts of blood. In the right
auricle and larger veins engorgement ?.nd tension become marked, tending
to cause a passive engorgement of the venous system throughout the body,
a cyanotic liver, cyanotic spleen, etc.
A heart reduced in its propulsive power is itself but poorly
supplied with blood because its own arteries are but incompletely
supplied. Any condition of fatigue which prevails may there-
fore easily become c.vhaiistion, complete functional inability, arrest
of cardiac action ( cardiac paralysis, cardiac syncope, cardiac col-
lapse). All these terminal changes interfering with circulatory
integrity are occasioned by any influences which impair the con-
tractile efficiency of the myocardium, any agencies which either
directly or indirectly reduce its muscular power (rupture, fatty
degeneration, inflammation, prevention of expansion of the heart
from some external interference, anaemia) ; in the same way the
action of some paralyzant toxine upon the cardiac ganglia, the
analogous action of thermic and electric agencies, excessive reflex
stimulation of the vagus or of the vagus nucleus in the medulla
oblongata (the latter from deficiency of the blood oxygen,
increased blood pressure in the brain, or toxines).
Just as in cases of diseases of the heart, affections of the
arteries and veins are apt to occasion irregularity of distribution
and movement of the blood in given organs and areas of the
body. Narrow'ing of the arteries from vasoconstriction (arterial
spasm), thrombus formation, inflammation and permanent shrink-
age raise the intracardiac blood pressure and occasion dilata-
tion and hypertrophy ; the organ to which such a constricted
artery is distributed is imperfectly supplied wath blood and a
variety of changes may in consequence occur in it (cf. ancrniia
and embolism). Decrease in the elasticity of the vascular walls
or paralysis of the arterial musculature permits the vessels to
dilate, the current to become slowed and the organ, congested.
Reduction in the muscular jionus of the vessels of the splanchnic
area from vasomotor paralysis, usually from toxic and infectious
influences, causes a massive congestion of the abdominal vessels ;
in consecjuence of which the general- blood pressure falls, cardiac
labor from the small amount of blood coming to the organ ensues,
and there is a fatal collapse (Krehl).
In the veins interference with the progression is occasioned
not only by cardiac weakness, cardiac lesions and pulmonary
Hypcrcctuia ami Anccmia. iii
affections which interfere with the aspiration factor of venous cir-
culation and h\- thromhosis of the veins ; but it should also be kept
in mind that any abnormal compression of these thin-walled veins
must interfere with the return flow of blood. The nearer the
heart such compression occurs the greater the harm to the gen-
eral body. Compression of the two venae cavre, which from the
compressibility of these vessels is quite possible from pleural effu-
sions, induce a reduction in the amount of blood entering the
cardiac chambers and venous congestion throughout the economy
(cf. hyperconiia).
The lymph supply and drainage are in close relation
with the abnormalities of the blood vascular system and blood
circulation ; imperfections in the lymphatic circulation give rise to
abnormal accumulations of fluid in the lymph vessels and serous
cavities and occasion a wide group of organic lesions.
Local Variations in Amount of Blood. Hyperaemia and Anaemia.
The amount of blood in the organs of even healthy individuals
is always subject to change and variation. The vessels are elastic
tubes which are expanded by greater internal blood pressure and
adjust themselves as their contents diminish. This is not merely
a passive accommodation, however ; they are capable of active
contraction and dilatation through the power of the smooth muscle
in their structure, such alterations of lumen being primarily under
control of nervous influences. The total quantity of blood in
the body, similarly subject to continual variation, is never so great
as to completely fill all the vessels were they fully dilated ; there
exists, however, a moderate fullness, varying here and there in
the organs as the blood-current meets resistance to its progression
or as the blood is drawn into special organs from dilatation of
this or that vascular area. The quantity of blood in the organs,
and the hsemic distribution in the body generally, physiologically
accommodates itself to the existing demands. More blood enters
an organ when functionating; the amount traversing it dimin-
ishes during periods of rest. The nervous stimulus which causes
an organ to actively functionate, at the same induces dila-
tation of its vessels, and in consequence a rich supply of blood is
afforded. This is especially recognized in muscle. Ranke
determined the blood content of the general musculature of rab-
bits at rest to be 36.6 per cent, of the total muscle bulk, and noted
this proportion nearly doubled (66 per cent.) when the muscles
112 Disturbances of Ci)'Ciilatio)i.
were thrown into tetanic contraction. (Internal organs like the
brain or intestine may tlms be relieved of excess of blood by
muscular movements.) When the stomach and intestine are filled
with food during digestion they are much richer in blood than
when empty. The influences which give rise to this stimulation
are variable and multiple, acting sometimes directly upon the
muscular coats of the blood vessel wall and the nervous apparatus
inherent in the wall, sometimes upon the vascular centre in the
medulla oblongata (mechanical, thermic, electric, chemical irri-
tants).
It is but a stc]) from the physiological to the pathological, and
there is no sharp line of differentiation ; change in the amount
of blood in a part becomes a pathological condition when it occurs
in an improper place, . or at a wrong time, or if it exceeds the
normal variations.
Increase in the quantity of blood in a part of the system, local
engorgement, hypcrcoiiia, may be of one or other of two types,
the result either of an excessive influx of blood to the part, or of
a diminished escape of blood from the part.
The first form, the basic feature of which consists of excessive
entrance of arterial blood into the tissues, is spoken of as active
hyperaemia, or, synonymously, as irrifafion-hyperccmia, congestive
hypcrccmia^ fluxion of blood or arterial hypcrcvnua. Increased
supplv of arterial blood may be caused by excessive blood pressure.
This is met where an artery is occluded or some part of the body is
for some reason prevented from receiving its proper supply : under
which circumstances the blood propelled from the heart passes
into the adjacent structures {collateral hypcrccmia), that is it
rushes into the pervious branches of the artery near the obstruction,
under the influence of the higher pressure. As a rule, however,
instead of the blood being forced into the part in question, there is a
lowering of the vascular tension, spoken of as a relaxation in
the arterial distribution (relaxation-hyperccmia), with a resultant
widening of the channels. The blood freely pours into the dilated
arterial branches and capillaries, and with increased force ; in a
w^ord it is drawn into the part. The degree of relaxation depends
largely upon the lack of tone of the smooth muscle of the vascular
wall and the congestion is therefore in such instance a myoparalytic
one. Every muscle being inseparable from its innervation, nervous
influences must finally be regarded as responsible for changes in
the vascular tension (tone). It is assumed that the vascular
Active Hypcrmnia. 113
nervous apparatus comprises two types of nerve fibres, vasodilator
and vasoconstrictor ; theoretically, therefore, stimulation of the
vasodilator nerves should occasion a widening of the blood chan-
nels (neurotonic congestion), and the same result should follow
paralysis of the vasoconstrictors (neuroparalytic congestion) , both
of these influences similarly reducing the tension of the muscular
elements of the arterial wall. This relation with nervous influ-
ences is well seen in the fact that after section of the cervical
sympathetic in rabbits the ear on the corresponding side becomes
hypergemic (CI. Bernard), and after section of the splanchnics the
vessels of all the abdominal viscera become distended and engorged
with blood (paralysis of the vasoconstrictors). Stimulation of the
nervi erigentes of the human penis causes a dilatation of the
arteries of the organ ; blushing in man is brought about by psychic
influences upon the dilator centre through reflex action ; certain
poisons, as nicotine and alcohol, are apparently stimulating to
the dilator centre. Generally the stinmlation or paralysis of the
vascular nervous apparatus indicated is the direct result of local
influence by physical or chemical agents. Thus hypergemia may be
induced mechanically by the removal of pressure acting upon the
vessels ; just as a sponge which has been squeezed and is then
released takes up water, so the blood flows in large amount, imme-
diatelv after removal of the pressure, into a tissue which has been
deprived of its blood for a long time because of compression. The
vessels here do not at once regain their contractility, but are
relaxed.
Similarly friction and scratching can induce hyperemia
mechanically, from the nervous stimulation thus originated.
Thermic influences of both types give rise to hypcnemia ; heat by
its direct relaxing influence upon the vessel walls, cold first
causing a vasoconstriction which later gives place to a paralyysis
of the vascular musculature. There is a special group of chemical
irritants as oil of mustard, cantharides, ammonia, alcohol, chloro-
form, ether, saline solutions, which, either by stimulating or
paralyzing the nerves of the vessel walls, cause a more or less
intense arterial hyperaemia ; these, because of the value of the
hyper?emia in the treatment of various affections, are of therapeutic
importance (rubefacients, drugs which cause reddening of the
skin). Probably in the erythemata which occur in various infec-
tious diseases there also exists a similar toxic stimulation or
paralysis of the vessel walls either from the bacteria or the
microbic products.
114 Disturbances of Circulation.
Active hypersemia is essentially an arterial and capillary dilata-
tion. The hyperaemic organ or tissue therefore manifests as one
of its features a red color, which is the more striking the paler the
tissue normally is, as in mucous and serous membranes, and may
be so pronounced that the distended arteries appear as fine deep-
red lines (branched or injection erythema). The rapidity of the
flow of the blood into and through the involved area, with but
little output of its oxygen, causes it to remain bright red and
pass thus into the veins. In peripheral parts of relatively lower
temperature previous to the increased blood supply, there is a rise
of temperature up to that of the blood. These peripheral parts,
particularly the skin, because of their greater heat loss and their
comparatively poor blood supply are lower in temperature than the
internal organs ; but with the access of more blood of the body
temperature the skin with its rate of heat dissipation unchanged
necessarily becomes warmer. The temperature attained does not,
however, exceed that of the internal organs ; and these, should they
become hyperaemic, do not suffer any increase of temperature.
\\'here there is marked capillary distension, provided the tissues
are not rigid, there ma}- also be induced some swelling.
The results of arterial hyperemia vary with its duration and
location. Hyperaemia of the brain is followed by unimportant or
marked disturbances of consciousness, dizziness and general excita-
tion (pressure of the engorged vessels on the nervous elements).
Hyperaemia of the sympathetic nerve does not cause either lachry-
mation or salivation, and it is doubtful whether an uncomplicated
hyperaemia causes any special lymph formation. In case of long
continuance of the hyperaemia there becomes apparent an increased
tissue proliferation ; this is probably not due to the increased blood
supply alone, the irritant which underlies the condition having also
in all likelihood some stimulative influence in its causation.
As a rule uncomplicated hyperaemia is a transitory condition ;
with the disappearance of the cause for the vascular relaxation the
contractility of the arteries returns. Otherwise the hyperaemia
may be regarded as the precursor and concomitant of inflammation.
Where large amounts of blood are drawn into extensive areas of
hyperaemia, a deficiency of blood (collateral anaemia) may be occa-
sioned in other regions.
Where the excess of blood exists in a part because of difficulty
in its exit from the part it is known as passive hyperaemia or
venous engorgement. This condition is encountered in connection
Passive Hypermnia. 115
with low arterial pressure, the blood not being properly propelled
through the capillaries, in connection with deficiency in the pro-
pelling power of the heart and arteries or complete loss of the
arterial reactions (atonic hypcmmia). When the blood is not kept
moving onward, in compliance with the law of gravitation it set-
tles into the dependent parts of the body. As the animal lies on
one side the lowest parts become the seat of special engorgement
(one half the lungs in the cadaver). This hypostatic or gravita-
tion hypercsmia (hypostasis) takes place because of the longer
persistence of the blood in fluid condition in the capillaries as
compared with the larger vessels. It may be noted in animals
unable to raise themselves from the ground in long protracted
diseases or in the agonal period, and may also develop after
death. It may, however, develop in a nondependent organ because
of reduction in its arterial supply, particularly if the blood pressure
in the venous trunk be so great that the blood presses back from
the veins into the capillaries no longer filled from the arterial
side. Since the progression of the blood in the veins depends
in part upon general muscular movements and the passage of
blood from the venae cavse is particularly favored by the inspira-
torv expansion of the thorax, deficiency in body movements and
in respiratory activity (pulmonary diseases), as may be expected,
promote the development of hypostatic congestion. The most
common obstacle to the venous circulation arises from compression
of the delicate walls of the veins by external pressure, kinking as
in intestinal volvulus, constriction or pressure from tumors; reduc-
tion of the venous lumen or actual obstruction from thrombosis
should also be mentioned in the same connection.
Passive congestion of the portal vein and its branches, afifecting
the spleen, stomach and intestines [and pancreas] is occa-
sioned by all diseases of the liver accompanied by shrinkage or
reduction of the capillary network of the organ, the condition
interfering with the progression of the portal blood through the
liver.
Widespread passive hyperaemia is met in case of cardiac valvu-
lar lesions because of the interferences oflr'ered to the ready move-
ment of the blood from the venge cavse and pulmonary veins.
A passive congestion caused by local interferences may have no
further results provided the venous trunk in question or its tributary
capillaries communicate by collateral circulation with other veins
which are not affected, the blood then passing freel}- through such
ii6 Disturbances of Circulation.
collateral anastomoses. This readily occurs if such paths are at all
numerous and large; and where they are of narrow calibre they
are gradually widened by the pressure of the obstructed blood, so
that even very small branches and capillaries come to assume con-
siderable dimensions permitting the blood to escape from the area
of obstruction practically unhampered (anastomotic compensation).
The possibility of such dilatation depends, however, upon the degree
and rate of development of the venous obstruction and requires
time. In the case of sudden venous obstruction and the existence
of few anastomotic channels, before the collateral branches can
adapt themselves to the congestion the disturbance of the circula-
tion may well induce important functional and vital changes in the
affected organs ; and, of course, such occurrences are to be ex-
pected if the obstructed veins have no communication with other
unobstructed channels (portal vein, the veins of the kidneys and
lungs). Even compression under the finger (in phlebotomy or in
a rabbit's ear) will show how the impeded blood causes the veins to
dilate and swell up ; all the rest of the phenomena of this form of
hypersemia may be followed up experimentally in the exposed
tongue of a frog or under the microscope, after the ligation of
the larger venous trunks so that the blood can pass out only
through the venules. The web of the frog's foot may be employed
for the same purpose after ligation of the femoral vein. At first
the blood in the engorged and expanding veins and capillaries
becomes slowed, then irregular, now flowing forward, now back-
ward, and sometimes stagnates totally. It can be seen that in
some places the current is reversed, that the blood is passing
out of the engorged area through the collateral branches, these
gradually dilating, and the stationary or slowly moving corpuscles
gradually being drawn into the current and after a time the proper
rate of circulation again assumed.
If a number of veins are occluded or cut off sufficient to entirely
or largely prevent collateral compensation, stagnation or stasis of
the blood takes place. In the affected parts of the vessel the red
blood corpuscles are packed so closely together that their outlines
can scarcely be distinguished and the blood completely fills the
vessel as a uniform red mass. Stasis becomes especially well
marked if, while the venous outlets are completely closed, the
blood continues to be forced in from the arteries. The capillaries
dilate to their fullest : their walls, permeable to the plasma even
before their distention, can no longer hold the fluid blood, but allow
Passive HypercEmia. 117
it to escape more or less freely according to the pressure, and may
in fact, rupture. However, even if the blood be not forced into the
area from the arteries, exudation of the fluid part of the blood
through the distended capillary walls may take place in ordinary
atonic hypostatic congestion, and there may even occur a diapcdesis
of red blood cells. The endothelium and vessel walls remain intact
only while they are being continually bathed with moving blood ; and
as soon as the circulation stops it may be accepted that a disturb-
ance of the endothelial nutrition exists, these cells then shrinking
and causing comparatively large open interstices, through which
exudation takes place. For these reasons passive hyperemia has
frequently associated \/ith it a congestion-transudation and haemor-
rhage. The latter may be sufficiently severe to make the whole
tissue dark red in color, infiltrated and completely occupied by
blood (haemorrhagic stasis, h?emorrhagic infarction).
The pressure occasioned by the distended vessels and the fluid
exudate, together with the impediment to circulation, may be fol-
lowed by cessation of function of the aft'ected tissues and finally
by their death. The longer the blood remains in the capillaries,
slowly giving oft' its oxygen and capable of but little or no renewal,
the darker it becomes ; the tissues in venous hyperemia arf there-
fore of a dark bluish red (cyanotic) hue. Such a tir.t (diffuse
cyanosis, black erythema) may be encountered (in hogs) extending
over practically the whole surface of the body in case of general
passive hyperaemia. The lack of oxygen and the excess of carbon
dioxide in the venous blood are partly responsible for the functional
disturbances arising from passive hypersemia of the various organs ;
these conditions act by stimulating the medulla, and occasion
dyspnoea, dizziness, convulsions, disturbances of consciousness,
muscular weakness and fatigue.
The superficial external parts of the body, when passively con-
gested, become cool because of the impeded circulation of blood
through them, because the blood is cooler than normal and the heat
dissipation not diminished.
In contrast to wdiat has been said above, a mild but persistent
passive hypersemia is apt to cause not only a swelling of the organ
affected (kidneys, lungs, liver, spleen) because of the permanent
engorgement and distention of the capillaries, but in addition may
induce an increase in size and induration from the production of
an excess of connective tissue in the part (Cf. hypertrophy).
ii8 Disturbances of Circulation.
Stasis and stagnation of the blood may at times be caused by substances
which act by inducing a withdrawal of the fluid elements and thus a
thickening of the blood (chemicals acting upon vessel walls). [This can
well be shown experimentally by bathing the mesentery of a frog, arranged
for demonstrating the blood current, with a hypertonic saline solution, a
rapid exosmosis of fluid taking place and the current being soon entirely
checked, with the vessels choked with corpuscles.]
Deficiency of blood in an organ may be part of anaemia
of the general body (general oligsemia or an?emia ; d priv., 6\lyos,
little, and al/xa, blood) or a consequence of local impediment to the
blood current (local anaemia, ischaemia, from taxeiv, to limit or
check). The blood supply to any part mdy be impeded by:
1. Pressure upon the part (coniprcssion aiuvniia) from in-
crease in. the bulk of adjacent organs, accumulations of fluid or any
other compressing influence upon the part from without, or by nar-
rowing of the capillaries by fat deposit, fluid or air in the paren-
chyma of the organ.
2. Narrowing, occlusion or fault of contractility of the arteries.
Here may be mentioned external pressure upon the vessel, ligation,
occlusion by solid bodies as by thrombi in the arterial lumen (cf.
thrombosis and embolism) , rigidity of the vascular walls from cal-
cification or sclerosis and spasm of the arterial musculature with
resultant contraction of the lumen {arterial ancemia or ischccmia,
occlusion ancrmia, spastic ancemia).
3. In addition, anaemia may involve a certain part of the body
in case the general blood distribution is irregular because the gen-
eral volume of blood passes to one large area to the deprivation
of other parts (collateral ancrmia); as when the posterior parts of
the body are markedly infiltrated with blood (symptomatic
anthrax) the fore parts are rendered ansemic, or as when interna!
haemorrhages occur the flesh is left ansemic, etc.
The organ or tissue deprived of its blood looks pale, the absence
of the blood tint permitting the peculiar hue to become more appar-
ent and more like the tissues of slaughtered animals or like a
washed tissue deprived of its blood by the washing. It contains
less fluid and but little blood appears on the sectioned surface, and
its volume is diminished because of the emptiness and collapse of
the vessels.
Ansemic parts at the exterior of the body, being exposed to the
air and losing their heat, feel cool, because with the loss of blood
their principal thermal substance is lost and they are capable of
producing little or no heat in themselves under the circumstances ;
Local Aiuviiiia: IJa-uiorrha^e. II9
and with the existing diminution of nutritive and secretory sub-
stances disturbances of nutrition and diminution of functional
aoility must ensue. In addition the products of previous meta-
bolic activity necessarily remain in the anaemic tissue and may act
unfavorably upon it. According to the grade of oxygen depriva-
tion, need for nutrition and rapidity of metabolism in the affected
structure there must sooner or later result a gradual death of the
anaemic part, because of the absence of blood. It should be kept
in mind, too, that the integrity of the endothelial lining of the
blood vessels depends upon the continuous flow of blood through
the vessel and that these cells gradually degenerate and become
permeable when the anaemia is complete. Should the blood again
flow through such capillaries which have been empty for perhaps
twenty-four hours it readily escapes through their walls, with con-
sequent haemorrhagic infiltration of the surrounding tissues.
(After interruption for as much as two hours the renal epithelial
cells become necrotic and consequently the renal function becomes
checked or ceases entirely.) Suspension of activity in vital organs
because of anaemia is a matter of extreme gravity. Cerebral
anaemia is quickly followed by unconsciousness ; and because of
degeneration of the central nervous tissue, even after but brief
periods of anaemia, this condition in the brain and spinal cord is
likely to give rise to destruction of the ganglion cells and focal
lesions with symptoms of paralysis. Complete anaemia of the myo-
cardium necessarily causes cessation of the heart's action.
Other parts of the system, as the skin and muscles, are less sen-
sitive to the effects of anaemia ; their tissue may withstand the
condition for some hours, as may readily be appreciated by the
practice of artificially causing an anaemia in surgical operations by
means of the Esmarch's elastic bandages. In case of such resistant
parts, if the cause of the anaemia be eliminated the results may be
but transient or only partial, as in case of the anaemia of cramps
(spastic anaemia) or anaemia caused by external pressure. Ob-
struction of an artery, and more particularly the anaemia resulting
therefrom, may be corrected if the blood supply can be quickly re-
established through the anastomotic vessels (so-called collateral
paths).
Loss of Blood; Haemorrhage.
The escape of blood from the vessels into the tissue spaces,
bodv cavities or to the free surfaces of the bodv is known as
I20 Disturbances of Circulation.
bleeding, haemorrhage {al^a, blood: ^^705, rupture) or extravasation
{ extra, without ; 'vas, vessel).
The most common causes of haemorrhage are wounds and
lacerations of the vessel walls. Anything which severs the con-
tinuity of the vascular wall by puncture, incision, tearing, con-
cussion or contusion affords opportunity for the effusion of blood
(traumatic liccniorrJiage). In the same way all conditions which
impair the resistive strength of the vessel walls to the pressure
of the blood favor haemorrhage, as the lesions caused by the
action of corrosive fluids, fatty degeneration of the walls of the
vessels, vascular inflammations leading to brittleness and fragility
of their tissues (corrosion hcruiorrJiage, spontaneous hcemorrhage).
Exaggeration of blood pressure (increase of pressure from sud-
den and powerful cardiac contraction and from hyperVemia) per-
mits the rupture of these weakened vessels, or perhaps even nor-
mal pressure may be sufficient. Rupture of the liver is not infre-
quently met with from such a cause after fatty degeneration of its
vessels and tissues. Or when the muscle of an artery (after
chronic inflammation) is in a degenerate state its walls may be
distended to form permanent dilatations [aneurisms] ; here the wall
comes to consist of but little more than connective tissue, which
tears when the distension becomes great.
Haemorrhages of the types mentioned are spoken of as haem-
orrhages per rhexin ( prj^is, rupture; prjyvwai, to burst through), or,
])articularly where the wall has been weakened by pathological
changes, as haemorrhages per diabrosin ( bia-^i^pdocrKiLv , to eat
through ) .
The blood maw however, leak out of the smaller vessels,
capillaries and veins, without the apparent existence of any lesion
in the continuity of structure, because of some abnormal pemie-
ability of their walls. Such haemorrhage is known under the
names diapedesi::, or luemorrhage per diapedesin ( from Sia-v-ndav,
to burst through). The increased permeability of the vessel wall
is explained by the fact that under the influence of toxic, infec-
tious, thermic or other injurious agencies, as well as from marked
engorgement and distension of the capillaries (passive hyperaemia,
stasis), the cement substance between the endothelial cells becomes
porous ; for example, the endothelial cells may shrink into globular
form and separate from each other, or openings may result
from destruction of the cells. The red corpuscles then slip
through between the cells or are forced out along with the plas-
Hemorrhage.
121
inatic exudate ; because of their elasticity these corpuscles are
easily able to pass through the most minute clefts of the cement
substance. There exist therefore in these cases minute micro-
scopic tears. Haemorrhage by diapedesis, however, may assume
important proportion and may be fatal because of its location (as
in the brain or stomach) or of its duration.
Since it is the bathing of the endothelium with nonnal
blood which is essential to its integrity, it may be easily appre-
hended that even a temporar\- interruption of the circulation to
FU
1.
Mesentery of the dog. (a) IliPmoirhago by diapedesis. (b) Ecchymosis
occurring in a similar manner, tlie opening in the wall of the cajiillary
having closed up again. The figure aU-o t-.hows an emigration of leucocytes.
Magnified 2.50 times. I After Thoma. )
the capillaries may render them abnormally permeable and be the
cause of diapedesis after restoration of the flow (cf. oiibolisDi).
Haemorrhages are also classed according to the type of vessel
from which the blood escapes, as arterial, z'enous and capillary
hcemorrhagcs ; where the blood oozes from a widely diffused fault
in the softer tissues, as in the liver, and the type of the bleeding
vessel cannot be made out, the term parenchymatous hcemorrhage
is appropriate.
The blood may escape freely to the exterior of the body or
122 Disturbances of Circulation.
into one of the internal body cavities (external and internal hcemor-
rliage, surface hcumorrhage and hccmorrhage into a cavity). When
the exuded blood fills the tissue spaces and completely saturates
the tissvies, the terms ]ia:niorrhagic infiltration or hccniorrhagic in-
^ farction {infarcere, to stop up or fill up) are applied, the latter term
being used particularly when the blood coagulates in the tissue
and remains in it as a dense compact mass [usually in a definite
circumscribed area of infiltration further described in connection
with embolism]. If the bloody effusion causes an extensive,
loose, gelatinous swelling of the tissue, diffusely filling the
structure [applied particularly to infiltration beneath some sur-
face], it is spoken of as a suffusioii {suffundcre, to pour) or
snggillation. Small circumscribed foci of haemorrhage, apparent
as spots and points from which the blood cannot be discharged
by pressure (especially in serous membranes), are called hccmor-
rhagicc niacnlosce, eccJiyinoscs [xv/Modv.to overflow), petechice (from
pidoccliio, louse or its bite; or from pediculce flea-bites [petigo,
eruption]), or vihiccs when in streaks {zibc.v^ a streak). When
the extravasated blood collects in a rounded mass, as when it
dissects u[) the capsule of an organ or a connective tissue
structure, or when it accumulates in a cavity or becomes
encapsulated by a surrounding inflannnatory zone, the mass
is spoken of as a hccniatonia (blood boil) or hccniorrhagic cyst.
Special terms are also employed for these effusions of blood
depending upon their location : an extravasation of blood into the
pleural cavity is termed hccmothorax ; into the peritoneal sac,
hcemoccclia ( koiXIo., the body cavity) ; into the pericardial cavity,
ha:mopericardium ; into the uterus, hcematometra (fj.r}Tpa, uterus) ;
into the sac of the tunica vaginalis testis, hccniatocele (/ctjXt?, rupture).
In addition special names have always been made use of in con-
nection with haemorrhage from special organs : epistaxis ( iin-aTA^iiv,
to drip) for nasal haemorrhage; liccniaturia (o^pov, urine) for the
escape of blood with the urine ; hcrniafcniesis ( efieiv, to vomit)
for gastric haemorrhage (also melcrna, fieXaiva vocros, from /xAas, black,
because of the dark brown color given the blood by the gastric
juice) ; haemoptysis {ittvuv, to spit) for expectoration of blood from
the lungs ; metrorrhagia for haemorrhage from the uterus ;
hccnwrrliagic apoplexy {dirowXiffanv, to strike down, to stun) for
Spontaneous haemorrhage of the brain.
Symptoms and Results. From its characteristic blood tint an
eft'usion of blood is easily recognizable anatomically as a dark red
accumulation of blood, or spot which cannot be effaced and which
Hemorrhage.
123
is more or less sharply circumscribed. Upon surfaces or in the
body cavities the extravasation presents a striking picture, in
profuse, partly coagulated, partly fluid masses, or in a gelatinous,
red, jelly-like tumor ex-
tending into the loose sub-
cutaneous or sub-mucous
tissue (haeniorrhage fol-
lowing contusions of the
abdominal walls, hremor-
rhagic stasis of the in-
testinal m u c o u s mem-
brane), or sharply outlined
in numerous definite drop- h
like flecks (not effaced on %
pressure) as seen in the ^
sub-serous cellular tissue
of the pleura, pericardium
and epicardium. In the
secretions it is easily ap-
preciated by the more or
less pronovmced blood tint
which it imparts to them ;
the intestinal contents may
assume a slightly reddish -
gray, cafe-au-lait color up
to a chocolate brown or
pure blood-red from the
admixture of blood ; the
gastric contents a sepia-
brown, the urine a blood-
red to black; the expecto-
rate and nasal secretion a
rusty, red-streaked or
foam y red appearance
(pulmonary oedema).
While it is usually easy
to detect the ruptured ves-
sel in case of massive
haemorrhages (as a ruptured aneurism, the eroded stump of a ves-
sel in hemorrhage from gastric ulcers), and the infiltration of
blood surrounding the lesion in the organ points to the origin
of the haemorrhage and indicates its intravital occurrence,
Fig. 2.
Ilaematoma of the spleen of horse.
124 Disturbances of Circulation.
yet in capillary diapedesis from a mucous membrane, as the gastric
or intestinal lining, the points of escape are invisible to the naked
eye, and only the blood deposit on the surface and the pallor of the
mucous membrane indicate the fact of extravasation. Arterial
haemorrhages are recognized in living animals by the bright red
color of the arterial blood, by the spurting character of the escaping
stream from the larger arteries, the spurts corresponding to the
cardiac contractions ; while the bleeding from the veins is con-
tinuous and without pulsation. However, an arterial spurting may
be prevented by the interposed parenchyma (Samuel). If the larger
vessels between the point of haemorrhage and the heart be com-
pressed the haemorrhage will diminish if it be arterial ; it will be
increased if venous.
The results of hcoiwrrJiage depend upon the quantity and the
duration of the bleeding, as well as the location of the lesion. In
case of loss of over one-third of the total volume of blood (about
3 to 4 per cent, of the body w^eight ; the average total quantity
being from one-tenth to one-twentieth of the weight of the body),
the flow continuing, the blood pressure falls. The vessel walls,
although capable of wide adaptation to the volume of blood within,
have become too wide for the diminished amount and cannot longer
advantageously propel it. A general oligaemia has been established,
indicated by the pallor of the mucous membranes, dizziness, faint-
ing (^an^mia of the brain) and convulsions, and the animal may
bleed to death. These results occur not only when the haemorrhage
is external, but also in copious haemorrhages into the intestinal
lumen, peritoneal cavity, etc. (internal haemorrhage).
Haemorrhage gradually ceases by the closure of the opening in
the vessel from the formation of a blood coagulum in the opening
(adhesion thrombus), the closure being facilitated by constriction
of the vascular lumen (contraction of the wall), external pressure
(by the tissue engorged with blood), and by the fall of blood
pressure. After such cessation the volume of the fluid portion of
the blood is soon restored. The watery element first passes into
the vessels from the tissues and for a time the blood is conse-
quently more fluid (hydraemic) than before the haemorrhage; but
gradually the blood cells, regain their normal numbers as their
regeneration (cf. chapter on regeneration) proceeds in the blood
forming organs.
At the site of haemorrhagic infiltrations the tissues present more
or less functional alteration. The presence of the extravasated
Hcem rrhage. 125
mass of blood exerts a certain amount of pressure and in conse-
quence the cells and tissues are forced apart, displaced by the in-
vading blood ; and hollow viscera are occluded by the coagulated
blood. Even small haemorrhages in the brain, according to their
precise location, occasion a loss of function in the area affected,
perhaps even to the extent of complete obliteration of conscious-
ness ; in the case of spinal haemorrhages palsies ensue : hccmorrhage
under the mucous lining of the air passages (fracture of the
trachea and larynx) forces the same into the lumen to such a
degree that the air passage is constricted and death from asphyxia
may result.
The escaped blood usuall}^ coagulates, precisely as the blood in
venesection (cf. chapter on thrombosis). Should this clot remain
in the tissue or in one of the serous sacs it acts as an inflammatory
excitant ; it attracts the leucocytes by chemotaxis and causes a
limiting zone of connective tissue proliferation about it. This
gradually forms a capsule about the collection of blood, transform-
ing it into a haemorrhagic cyst, often called a haematoma, in which
the disintegrating blood exists, partly as soft, elastic, fibrinous
masses, of a reddish or brownish color, partly as liquid serum ex-
pressed from the clot. Such h.Tmatomata, sometimes approaching
the size of a human head, are not infrequently seen in the spleen
of domestic animals, around the kidneys in swine, and in the pelvic
cavity of cattle as the results of contusion haemorrhages. On the
other hand the penetration of leucocytes to the mass and the pro-
liferation of fibroplastic and angioplastic tissue leads to the resorp-
tion of the blood. Its disintegrating elements are taken up by
the amoeboid cells and carried away ; the plasma is absorbed by
the cells and may pass off through the lymph paths. The red
corpuscles both in the tissue lymph and in the blood vessels begin
to swell and lose their color or to become shriveled. The coloring
matter, haemoglobin, having been dissolved out may soak through
the tissue dift"usely or may become deposited in the form of flakes,
granules or more rarely as crystals through the tissue. The
crystalline form is especially apt to occur where the blood has been
stagnant (haematoma), appearing as ruby-red to brown, minute
rhombic plates and needles (iron-free haematoidin) ; the granules
are yellow and angular, sometimes give an iron reaction (haemosi-
derin), sometimes undergo a change like the crystals b\' which the
iron is separated from the haemoglobin, iron-free haematoidin
(haemofuscin) remaining.
126 Disturbances of Circulation.
This blood precipitate is found microscopically not only at the
site of haemorrhage, especially in the amoeboid cells which are
loaded with it, but also in the nearest lymph glands which are often
found tinted all through by a rusty, reddish-brown color from the
quantity of blood pigment conveyed to them. In the dead body, on
account of sulphur products (sulphuretted hydrogen) of the
cadaveric bacteria, the site of a haemorrhagic infiltration may be
found changed to a slate gray to black hue by the sulphur com-
binations ; in life, too, in places where similar bacterial accumula-
tions and fermentations occur (intestine, abscess cavities, fistulous
paths, mycotic diseases of the bladder) the pigment may undergo
the same changes in color and thereafter remain as evidence of
previous haemorrhage.
Dropsy. Hydrops and Oedema.
Excessive accumulation of the tissue fluid or lymph in the
lymph spaces, lymph vessels and serous sacs (Ivmph sacs) is
spoken of as dropsy, hydrops (from vSa>p, water) or hydropsia,
and. if the accumulation has occasioned swelling of the tissue, as
oedema (from or5a;'. to swell). The process itself is described as
a dropsical transudation (from sudarc, to sweat) ; the accumulated
fluid as a transudate. Neither the process nor the transuded fluid
is essentially anything more than a quantitative disturbance of
physiological lymph-production. Lymph is originally derived from
the blood, and is regarded by many as a secretory product of the
endothelium of the capillaries, although the blood pressure is also
maintained as a factor in its production and accumulation, affecting
the filtration of the liquid part of the blood through the capillary
walls. [Whether the physical processes of dialysis and osmosis
should also be invoked here is debated. Lazarus-Barlow, in dis-
cussing the vital transudation of lymph, urges the importance of
tissue demands for lymph both for purposes of nutrition and for
its influence in diluting and removing various products of their
metabolic activities or of their degeneration, and points out that
in this last case there exists a possible explanation for the per-
sistence of an oedematous process in case the excretory organs as
the kidneys fail of eliminating from the blood the various waste
materials. Thus if, in a case of nephritis, the blood becomes sur-
charged with waste materials and if at the same time such waste
in a local area of special activity or of degeneration is excessive,
Dropsy. 127
the tissue demands for increased transudation are increased in
order to acconiplisli its removal by the lymph ; yet if the blood
already contain an excess of the very substance in question the
increased transudation only serves to more nearly complete a
vicious cycle, and adds to the existing accumulation.] Two
reasons may be assumed for the pathological increase of this
fluid in the tissues, either an obstruction to the lymph drainage,
or an unusual, exaggerated transudation ; both of which factors
may be operative at the same time. In_ view of the free anasto-
mosis and the great abundance of lymph channels, together with
the fact that lymph absorption is also accomplished by the capil-
laries and veins, obstruction of isolated lymph channels, it may
be said, does not ordinarily occasion lymph stasis. Even in case
of unusual formation of lymph there is no essential reason for
determination of any abnormal condition, as within certain limits
the paths of lymphatic drainage are capable of accommodating
and carrying ofl:" large quantities of fluid, provided the tissues
retain their ]iroper elasticity (Landerer), and the propulsive
forces (muscular movements, etc.) are of normal functional ex-
cellence. It is only when the increased transudation becomes ex-
treme and the lymphatic flow fails to keep pace, that cedema
develops.
The most common cause for such fault is passive hyperemia.
In case of passive congestion the blood pressure in the capillaries
becomes raised and the current of blood slowed, as a result of
which the endothelium of the walls of the capillaries becomes ab-
normally permeable and in conseqtience the fluid element of the
blood exudes profusely. This exudate is usually not as rich in
albumen as the normal lymph. As examples of oedema of this
type may be suggested that caused by compression (as oedema
of the lips by application of twitches to a horse's mouth), by
venous thrombosis, by cardiac lesions which impair the current
of blood in the ven^e cavie, by pulmonary changes which prevent
proper progression of blood from the right heart, by structural
faults of the liver causing obstruction of the portal capillaries and
producing portal congestion (dropsy or cedema from passive
congestion). Coincident interference with lymphatic drainage
may be determined perhaps by the pressure of fluid accumulations
in the thoracic or peritoneal cavities upon the thoracic duct, per-
haps by the loss of natural elasticity of the tissues, stretched and
128 Disturbances of Circulation.
distended by the increased and persistent pressure of the lymph-
atic transudate.
Increased transudation is observed also in connection with in-
flammation and changes of the vascular walls caused by toxic
chemical agents acting either locally or, when circulating in the
blood, widely {irritative or inflammatory dropsy). One should
recall in this relation the influence of the slowing of the blood
current and vascular dilatation, together with possible shrinkage
and separation of the endothelial cells, combining to render the
vessel walls more permeable ; moreover, a number of poisons, as
some of the products of metabolism, seem to directly stimulate
the endothelium to increased secretory activity, to possess what
might be called a "lymph-driving" ( lymphogogue) action. In
addition it may be pointed out that in inflamed tissues the lymph
flow is impaired by the fact that the inflammation occasions
coagulation of the lymph and impairs the elasticity of the tis-
sues. Such features explain the occurrence of cedema around
tissues which are the seat of purulent or hsemorrhagic inflamma-
tion (collateral cedema).
Dropsy is often concurrent with wasting diseases and abnormal
states of the blood characterized by poverty of its cellular ele-
ments and increase in its jiroportion of water, the so-called
cachectic or hydremic wdenia, as seen in cases of pulmonary
verminosis, fluke disease of the liver and chronic parenchymatous
nephritis. It is an open question in such cases whether the es-
sential fault in determining the dropsy is the dilution of the
blood which may perhaps make it filter more readily through the
vessel walls, or whether we should ascribe it to the presence of
metabolic products and other toxic matter in the circulating
blood impairing the vascular endothelium and permitting the
transudation because of an increased permeability. (Cohnheim
and Lichtheim failed to obtain dropsy by introducing large quan-
tities of sodium chloride solution into the blood of experiment
animals, even when as much as half of the blood was replaced
by the saline solution ; Gartner, however, succeeded in causing
an oedema in dogs by long continued infusion of salt solution.)
No satisfactory explanation exists for the rather common
congenital anasarca of aborted calves. According to the investi-
gations of L. Franks the thoracic duct is sometimes missing in
these "watei: calves" (or "Dunstkalbern") : while in other cases
Dropsy.
129
renal changes, perhaps the sequels of an intrauterine nephritis, are
met which may occasion dropsies because of retention of water
or on account of some infectious toxic influence present.
The dropsical transudate is usually a colorless or wine-yellow
water-like fluid, generally containing a smaller proportion of
albumen than the lymph and fluid exudates, as a rule showing
only 0.1 to 0.8 per cent, albumen, according to Perls up to 5
Fig 3.
Anasarca universalis congen., so-called water
calf.
per cent. (Lymph and blood plasma contain about 7 per cent.)
The proportion of salines is the same as in the plasma (0.8 per
cent). [The precise composition, particularly as relates to pro-
teid, varies in the different types of dropsical fluid; and even hi
the same subject the amount of proteid is not identical in fluid
from different parts of the body, that from the subcutaneous
tissue being usually marked by the lowest proteid content, while
130 Disturbances of CirciilatioJi.
that from the serous cavities, especially the pleura, is apt to be
richer in albumen.] In case of coincident escape of blood
corpuscles (in passive hypersemia) admixture of these elements
with the transudate may occur to a sufficient extent to give it a
blood-red color and occasion fibrin deposition {^hydrops hcemor-
rhagicus). In other instances admixture of fat from the blood
or from, fatty degeneration of the cellular elements macerated in
the fluid may give a milky appearance to it (hydrops adiposus,
chyliformis) ; and in abdominal dropsy a similar appearance may
be occasioned by rupture of the chylous vessels and admixture of
chyle with the fluid (hydrops chylosus).
The amount of fluid in the large body cavities may reach con-
siderable volume, 10. 50 to 100 liters in large domestic animals.
Such quantities of fluid are naturally capable of exerting marked
pressure upon the dift'erent adjacent organs, and distend the walls
of these cavities. Consequently in case of ascites the peritoneal
cavity is considerably enlarged and becomes a fluctuating sac ; the
pericardial sac attains a wide outline and fluctuates ; and even the
chest wall may be distended and barrel-shaped from the separation
and outward displacement of the lower ribs. In the foetus, in
which the fontanelles are still yielding, the covering of the brain
becomes a huge sac. partly membranous, partly made up of the
cranial bones forced apart and transformed into thin plates.
When the transudate fills the spaces of a tissue the porous cellular
structure becomes a gelatinous, amber-colored, swollen mass,
from the cut-surface of which a serous fluid drips and whose
doughy swelling retains for a long time the pressure marks of a
finger. Sometimes bladder-like collections or cysts may form
from the forcible distension of the connective tissue spaces.
Various terms have by custom been applied to these accumula-
tions of transuded fluid. CEdema of the skin is spoken of as
anasarca (from avi and adpi,, flesh; supply hydrops): collec-
tions in the pleural cavities as hydrothorax ; in the pericardial sac,
hydropericardhim; in the peritoneal cavity, ascites (from d<r/c6s,
bell}' ; namely, hydrops ascites) ; in the tunica vaginalis testis,
hydrocele (from v5wp-Kr)\-n . water rupture) ; in the cranial cavity,
hydrocephalus.
The result of the oedema depends upon the location and cause
of the condition. Local dropsies of the skin may last a long
time, but eventually disappear after the removal of the cause
and the resorption of the fluid. CEdema of the tissues about the
Thrombosis. 137
laryngeal entrance (oedema of the glottis) is dangerous, occasion-
ing asphyxiation by narrowing the air passages; oedema of the
lungs and of the brain may be fatal by causing functional dis-
turbances of these organs. The mechanical pressure effects of
collections of fluid in tlie serous cavities upon the blood circula-
tion, the compression and displacement of viscera (pressure on
the diaphragm), as secondary results of the dropsy, increase the
severity of the primary disease which was the cause of the dropsy
(affections of the heart, liver or kidneys).
Obstruction of Blood Vessels. Thrombosis and Embolism.
Obstruction of blood vessels may be due to the formation within
them of relatively solid plugs made up of the blood constituents,
this process being known as thrombosis ( 6 ep6ix(3os, mass; from
rp^cpw, to make firm or compact), or to forcible lodgment in their
limien of materials conveyed by the blood current, this latter pre cess
being known as embolism ( e/j.-pdWeiv . to throw in).
It is well known that blood outside the body clots in a few
minutes after its escape from the vessels, as after venesection.
There is formed from the blood a red jelly-like mass, the bloody
cnior saiigiiinis: over the surface of which there collects a pale
yellow fluid, the blood serum. The clot is primarily constituted
of fibres of coagulated fibrin, which include the blood plaques. In
case of slow coagulation the red corpuscles sink to the bottom of
the containing vessel and thus the superior part of the coagulum is
largely occupied by the lighter and therefore less readily sinking
white blood corpuscles ; for which reason the surface of the clot
shows a yellowish-white layer composed of fibrin and leucocytes,
the so-called huffy coat. The formation of fibrin is the main fea-
ture of extravascular coagulation, and can be directly followed in a
drop of blood under the microscope. In a blood drop placed upon
the cold slide the film can be observed to separate as fine threads,
and these, with the platelets adhering, unite with each other to form
a network (Birch-Hirschfeld). Fibrin is an albiuninous substance,
existing in solution in the circulating blood in the plasma (the
so-called fibrinogenous material or fibrinogen), which separates as
a coagulating calcium compound with proteid when acted upon in
th.e presence of calcium salts by a ferment known as the fibrin
ferment.
Following the apt comparison of Birch-Hirschfeld, blood coagulation
rnay be thought of as somewhat analogous to rennet coagulation of milk.
132 Disturbances of Circulation.
In the presence of lime salts of the milk, casein (which is similarly a
calcium proteid combination) is separated from the milk bj' the lab-
ferment, leaving a serum, the \vhe\-.
Coagulation of blood may be checked or inhibited by certain
chemicals which destroy the fermeiit or which dissolve the fibrin
immediately after it is formed (potassium citrate, or oxalate, extract
of the cephalic glands of the leech). [Extract of the cephalic end
of the hookworms of the dog possesses a similar property.]
So, too, coagulation fails if the inner surfaces of the vessel in which
the blood is caught be covered with vaseline, thus preventing adhe-
sion (Freund).
After death the blood clots qtiickly and in a manner similar to
extravascular coagtilation, especially in the heart and larger vessels ;
in the capillaries it remains fluid for a longer time. In the presence
of toxic substances having solvent action upon the blocxl and fibrin,
too, coagulation is incomplete (hccmolytic sttbstances, as some of
the bacterial products, presence of excessive amounts of carbon
dioxide in the blood). Cadarcric clots are homogeneotis. soft,
elastic, gelatinous masses which look like casts of the vessels, are
without lamination, and are either of a dark red color throughout
or of a more or less yellowish gray to amber hue with jelly-like
semi-transparent appearance. The latter form, comparable to the
"buffy coat" are met in anaemic states and gradual cardiac failure,
the blood cells in such instances settling and the fibrin containing a
large amount of serum. [In these heart-clots the dark red homo-
geneous examples are commonly interpreted as indicating rapid
death and quick coagulation before the corpuscles have had time
to separate ; they are thus referred to as post-mortcui clots. On
the other hand, the yellowish translucent coagula. occurring in slow
circulatory failtire, are often spoken of as aiifc-iiiortciii clots, from
the idea that they form or start to form during the period of slow-
ing of the current prior to death, the red cells at least sinking
more or less from the general blood volume prior to the actual
stoppage of the current and coagulation of the blood.]
Coagulation and thrombus formation within the vessels of the
living takes place from the following causes or favoring conditions :
I. Entrance of chemicals into the circulation favoring coagula-
tion of the blood (fcnunit thrombosis) : B\- the injection of ether
and other chemicals, the introduction of substances destructive to
the leucocytes, injections of emulsions of various parenchymatotis
tissues (brain, adrenals) or of the expressed juices of the thymus
Thrombosis.
133
body, testicles, etc., or of laked or altered blood, it is possible to
bring about extensive coagulation witb fatal effect. Such experi-
mental findings warrant the assumption that the occurrence of
tiirombosis is, at times, in infections and diseases accompanied by
tissue destruction dependent upon the coagulative action of microbic
poisons or tissue products permitting the formation of fibrin fer-
ment by the disintegration of leucocytes.
2. Slowing and cessation of the blood current : It has been
Fig. 4.
Cardiac valvular thrombosis (right ventrical of heart of hog).
shown by experiment that after double ligation of a vein or artery,
although the blood in the segment between the ligatures is entirely
stagnant, it may remain fluid for months (Baumgarten, Senftleben
and others). Nevertheless in situations where blood vessels are
expanded, particularly when the seat of pathological dilatations, and
when the flow of the blood is slackened, thrombi are particularly
likely to form, because these ectases favor the agglutination of
leucocytes and plaques from which arises the inception of the
thrombotic process (stagnation tiirombosis) .
134
Disturbances of Circulation.
3. Alterations of the lining of the vascular wall : Lesions of
the vascular intima resulting in the destruction of the endothelium
and thus causing a loss of the natural smoothness of its surface give
opportunity for adhesion of platelets and white blood corpuscles to
the roughened surfaces and give origin to thrombus formation
{adhesion thrombosis). In lacerations, incised and puncture
wounds as well as contusions of the vessels, thrombi invariably
form, an important feature in wounds both as regards healing and
preservation of life, the clot formation gradually closing the
rent in continuity of the vessel and checking the loss of blood.
Thrombosis also takes place in case of vascular changes caused bv
bacterial invasion, parasites, perforating neoplasms, and in vessels
in the neighborhood of active inflammatory lesions, as upon the
valves in case of endocarditis, in the vessels of the lungs in pneu-
Fig. 5.
Thrombosis in a cavernous angioma of tiie liver of a cow.
monia, in parasitism of the arteries by strongylits annatus, in case
of invasion of pyogenic bacteria in the umbilical vein, etc.
As a rule two or three conditions favoring thrombus formation
cooperate to cause it ; thus when a thrombus is formed after
bacterial invasion of a vessel, it is partly the result of special
ferment production, partly due to injury of the intima.
The composition of thrombi varies with the rapidity of forma-
tion and the causes of production. Those rapidly formed and
caused by special elaboration of ferment are often quite like the
clots of external haemorrhage, homogeneous and of a dark red color
throughout, being made up mainly of fibrin and red blood corpuscles
{homogeneous thrombi) ; microscopically the fibrin forms an intri-
cate reticulum of delicate threads in a radiating or stellate form
around ihe disintegrating leucocytes which furnish the fibrin fer-
ment (coagulation centers of Al. Schmidt and Ribbert). Stratified
T/iroinbosis. 135
or layered thrombi, usually forminf;' upon a limited area of the vessel
wall, Itegin b}' the adhesion of white blood corpuscles and plaques
to the altered part of the vessel wall and their accumulation at such
site ; upon this basis fibrin is deposited in layers of varying extent
and quantity, enclosing the corpuscular elements of the blood in its
structure. The arrangement of this coagulum is often such that
in microscopic sections the framework of the thrombus may be
observed to be formed of wavy trabecula of granular substance
made up of blood platelets (Ribbert) ; these bands always sur-
rounded by a broad zone of leucocytes and between them the net-
work of fibrin fibrils spread out with the red corpuscles included
in the reticulum (Ribbert). Corresponding" with the greater or
smaller amount of the constituent fibrin and cells and the types of
formation described, the general appearance of thrombi and their
color and consistence vary. There may be distinguished the follow-
ing varieties from this viewpoint:
I. Red thrombi, showing a homogeneous, blood red, gelatinous
mass, similar to the post-mortem clots ["'currant-jelly thrombi"].
I. White and grayish-red thrombi, reminding one of bacon-fat
or spinal-cord tissue or minced meat, not transparent, but opaque,
dull, of the consistence of soft rubber or cooked minced meat.
3. Mixed and stratified thrombi, made up of alternating layers
of red and white coagulum, well seen in cross-section, often arranged
concentrically like the tunics of an onion and separable like the
leaves of a book from each other. The reason for this lamination
and alternating arrangement is to be found in the fact that new
layers are not being continuous!}- formed upon the primary clot
but are deposited at intervals, the older layers thus attaining a cer-
tain degree of firmness, and the new ones not adhering so closely
to the previously formed strata and remaining easily separable from
them. Where such mode of increment is frequently repeated the
thrombus may exhibit quite a number of layers. The surface of
these thrombi may be either smooth or uneven, often marked by
ridges or ribs ; the latter peculiarity is due to the trabecula of blood
platelets and leucocytes extending to the surface and forming ledge-
like projections with trough-like depressions between them (similar
to the wavy deposit of river sand, and according to Zahn probably
produced by the wave-like motion of the blood). [Such appearance
may be produced, too, by the uneven contraction of the mass, the
shrinkage being most marked in the fibrinous network lying between
the coarser plaque-trabecula.]
136 Disturhances of Circulation.
The clots appearing at the beginning of thrombosis are known
as primary (autochthonous) thrombi; the coagula subsequently
deposited upon them as secondary or consecutive thrombi. The
former are more or less firmly attached to the vessel wall {parietal
thrombi) ; the latter usually lie free in the lumen as cylindrical
plugs with conical or rounded ends. The thrombus increases prin-
cipally in the direction of the blood stream, in the arteries toward
the periphery of the circulation, in the vei,ns centripetally. The
length may be quite considerable, as in those extending from the
veins in the neck down into the heart, or from the aorta at the
level of the renal artery down into the arteries of the popliteal space
and leg with or without (discontinuous) continuity. The thickness
depends upon the calibre of the blood vessel ; parietal clots are at
first flat, marked with wavy ridges, villous, or in the pockets of the
valves of the veins may form smoothl}' rounded plugs (zalviilar
thrombi) ; with growth the thrombus ma}- cause complete occlusion
of the vascular lumen (total occluding thrombi). In arteries
thrombi are usually smaller than the calibre of the relaxed vessel,
being compressed by the contraction of the i)ulsating vessel wall.
In aneurisms and in the cardiac chambers there occur huge irregular
nodulated thrombi, sometimes are large as the fist. Thrombi in
the course of time undergo a number of changes (metamorphoses)
as well might be supposed. They are but dead masses made up of
coagulated and necrotic elements and may shrink, becoming firmer,
drier and smaller; such changes depending upon changes in the
structure with homogenization of the fibrin and plaques and upon
pressure exerted by the walls of the vessels. In clots which have
undergone such changes there may occasionally take place a calcare-
ous deposit (vein stones, phleboliths). As a result of such shrink-
age the vascular lumen may again become partially permeable to the
blood. [The diminution in size of an old clot depends in an im-
portant degree upon the shrinkage of its own fibrinous network ;
this may be easily noted in the shrinkage which takes place in any
clot outside the body, with the separation of the serum originally
present in the coagulum, the question of compression by the vessel
walls being in such case entirely eliminated.] The most common
change consists in a softening of the thrombus, the clot being trans-
formed by fatty degeneration of its leucocytes [and liquefaction of
any of its elements] into a gray or grayish-red mass of pultaceous
consistence somewhat like minced meat. This change may be a
favoring circumstance, but is open to serious consequences. In
Thrombosis.
m
case the substance is broken up into a tinely granular falty material
this may be taken up by the blood current and washed away and
the lumen of the vessel may thus be
again established, or through the soft-
ened clot the blood stream may some-
times force one or more passageways
(canalization of the thrombus).
Should, however, larger fragments,
as a result of the degenerative
changes, bd loosened from the coagu-
lum and swept onward by the current
of blood they may find lodgment in
some other part of the circulator}' ap-
paratus and give rise to embolism.
A thrombus acts as a foreign
body u])on the living vessel walls
with which it is in contact ; and its
characteristic properties excite an in-
vasion by leucocytes and phagocytic
activity. The latter may, as is uni-
formly true in case of small traumatic
thrombi, bring about complete ab-
sorption of the clot, Coincidently
there is established an inflammation
of the vessel wall w'ith fibroplastic
and angioplastic proliferation, result-
ing in the formation of embryonic
connective tissue and vascular buds
from the endothelium and vasa vaso-
rum and their penetration into the
thrombus. These proliferating ele-
ments replace in time more or less
completely the clot substance. In
case the thrombus were a parietal
one, occupying onl\- one side of the
vessel wall, as after venesection, after
removal of the clot the connective
tissue contracts and shrinks into a
flat scar or mere thickening of the
wall. \Micre the thrombus occupies the whole lumen the
embryonic tissue develops about it, and in its growth pene-
a
r^
Fig. 6.
Schematic section of a throm-
bosed vein; somewhat en-
larged. (After Thoma. I
138
Disturbances of Circulation.
trates the mass ; and in the site of the clot there is formed a
mass of connective tissue. These changes are known under the
term organization of the thrombus. The vessel in the situation in
question is converted into a solid cord, its lumen completely
obliterated ; and as a result of shrinkage of the newly formed con-
nective tissue the part eventually may be seen as a thin string-like
obliterated section of the vascular tube. Now and again spaces
Fig. 7.
Embolism of branches of the pulmonary artery ; the superior embolus almost com-
pletely adherins; to the vessel walls and shmmken. Somewhat reduced.
(After Thoma.)
are left in the connective tissue, however, through which blood in
some degree may pass.
If a thrombus or a portion of a thrombus should break away, it
is carried forward with the blood current and must find lodgment
at some point where the calibre of the artery is less than the diam-
eter of the floating mass. The latter is then spoken of as an
embolus, and the process as embolism. Detachment is especially
likely to take place in connection with softening of a thrombus, in
Vv hich process the clot may easily crumble : however, even entire
Embolism. 1.^9
thrombi, no matter whether loosel\- or tirmly attached, may some-
times accidentally be torn loose by external force exerted upon the
vessel through movements occasioning twisting of the vessels or
increase of blood pressure. At the points of branching of the
vascular tubes it may happen that a thrombus or embolus may
strike upon the dividing angle and here again be broken into frag-
ments or may remain fixed at the point of division. It is quite
likely that an unusually long, flexible and tough thrombus may so
lodge at these places of division as to extend into both branches
of the vessel, riding as if in a saddle (riding embolus). A long
cvlindrical. flexible thrombus may, moreover, be thrown into folds,
twisted in serpentine fashion and compressed into a mass by the
force of the blood stream.
Although an embolus displaced from its original site is forced
into a relatively narrow portion of the vessel, it does not neces-
sarily at once completely occlude the lumen, since as a broken
fragment of a thrombus it need not retain the cylindrical shape
of the vascular tube, but may well be of irregular and angular
outline. Such emboli, particularly when of the riding type, are
apt to leave room free about them for the passage of blood. Cyl-
indrical or round emboli are comparatively easily forced into the
vascular lumen and give rise to complete obstruction. An embolus
which has become lodged tends to further enlargement, either by
the massive coagulation of the stagnant column of blood adjacent
or by the deposition of thrombotic layers. Sooner or later this
leads to complete obstruction of the vessel. In these cases it is
often difficult to determine whether there was primary thrombosis
or whether an embolism formed the nucleus of the blood clot,
which, from the formation of new layers, comes to completely fill
out the lumen of the vessel, and the original embolus may, more-
over, have been very small, and entirely hidden by the further
depositions.
The course traversed by an embolus is determined by cir-
culatory circumstances. An embolus carried from the veins must
always pass into the right heart and thence into the pulmonary
arteries; it may, however, adhere to the auriculo-vcntricular valve
leaflets in the heart. Its convection to the heart is easy, the veins
becoming wider and wider from the periphery centrally to the
venje cavse. If therefore a fragment become loosened from a
thrombus in veins of the foot, thymid. uterus or liver it would
be swept by a continually widening current to the heart. Commg
140
Disturbances of Circulation.
from the intestine, stomach or spleen in the portal vein, emboli
must lodge in the liver ; embolism of the latter organ arising also
from the umbilical vein, inasmuch as there is no direct communica-
Aorta
Niere
cava post.
Fig. 8.
Schematic representation of the circulation with fragments of thrombi at different
positions (cf. text). Lungencapillaren. pulmonary capillaries; Linke Herzk.,
left cardiac ventricle : Rechte Herzkammer. right cardiac ventricle ; Magen,
stomach ; Milz, spleen : Darm, intestine ; Nabel. umbilicus ; Leber, liver ; Niere,
kidney.
Embolism.
141
tion of the portal and umbilical veins with the vena cava, their
blood passin.c^ into the fine meshed capillary network of the portal
vein within the liver substance. (In calves, however, where the
ductus Arantii forms a direct passage between the uml)ilical vein
and the vena cava the lung may stand equal chance of embolism
haemo7rhof{
dalis\
Einige
'Dmndarmd.ste
coeci
Fig. 9.
Thrombosis of the colic arteries of a horse: ;i riding emljolus in arleri:i cceci.
Vordere Gekroswurzel, anterior mesenteric t runic ; einige diinndr.rmaste,
branches to small intestine.
from the last named source.) Emboli from the left heart, from the
lungs (pulmonary veins), entering the aorta and arterial tree always
find their way into the peripheral arterial branches, as from the
anterior portion of the aorta into the brain, from the posterior
aorta into the kidneys, pelvic arteries, etc., from the mesenteric
trunk into the arteries of the intestines. As a rule blgod. dots are
142 Disturbances of Circulation.
not so minute that they can be carried from the arteries through
the capillaries into the veins, for which reason such emboli from
the pulmonary arteries become fixed in their branches, that is, in
the lungs ; other types of emboli, however, as minute animal
parasites or bacteria, may traverse a capillary area and may there-
fore pass from the greater into the lesser circulation and in turn
arrive again in the greater.
In ver}' rare instances in human beings, where there is a patulous
foramen ovale, emboli have been encountered in tlie aorta and its branches
which did not originate in the left heart or lungs, but which passed
directly from the right into the left heart through the patulous opening.
When first seen, before the condition of the foramen ovale has been
noticed, the existence of such embolism seems inexplicable and confusing,
for which reason such an occurrence is spoken of as paradoxical embolism.
In addition, it should be mentioned that there is a possibility of retrograde
embolism of embolic substances in the veins. This, according to Ribbert,
may be explained on the supposition that clots or emboli of any type
which happen to lie close to the inner surface of a comparatively large
vein are always subject to slight backward repression by recurrent waves
of the venous blood (venous pulsation in passive congestion), somewhat
as at the shore the surging wave carries back with it a floating log into
the sea. If the venous current to the heart be weak^ as in congestive
states, it may not carry the embolus forward with it, while the more
powerful backward impulse forces it gradually back toward the periphery
to the capillaries. [This is well seen sometimes in cases of valvular
insufBciency and regurgitation.]
The results of thrombosis and enibolisni vary with the vascular
conditions, the size and nature of the obstructive substance and the
relative importance of the afifected organ. In part they are purely
mechanical, depending upon the degree of narrowing or obstruction
of the lumen occasioned by the process and the consequent dis-
turbance of circulation ; in part the results may be specific (pe-
culiar), the nature of the thrombus involving some special prop-
erties (as pyogenic or putrefactive agencies, or tumor forming
elements). Thrombosis of arteries occasions primarily an anaemia
of the organ or area supplied by the artery afifected. This anrcmia
in vital organs like the brain or heart or lungs necessarily imme-
diately induces disturbances of function dangerous to life itself
(fainting, cessation of cardiac action, phenomena of asphyxia), if
an important artery be involved and quick compensation by anasto-
motic blood supply is impossible. In case, however, branches of
the occluded or obstructed artery are so connected with other
adjacent arteries that a sufficient amount of blood is supplied to
Embolism.
143
the organ by these anastomoses or collateral communications, the
anaemia is likely to be only of short duration and without func-
tional disturbance. In many organs such collateral paths arc very
abundant, and in some, as in the muscles and hmgs. Ihey are so
numerous and of such calibre that sufficient blood is transmitted to
the blocked area of the artery by the ordinary collateral circula-
tion witliout any special effect. The blood which previously tra-
Fig. 10.
Femoral artery of a large dog, injected
three months after ligation. (After
Porta.)
Fig. 11.
Carotid artery of
a goat, injected
thirty -five months
a f t e r ligation.
(.\ftpr Torta.)
versed the occluded vessel is of course distributed throughout the
permeable branches arising proximal to the site of obstruction
and driven into these by the arterial pressure. The blood pressure
in these collateral paths must therefore be somewhat raised, for
which reason, as well as from the probability that the ansemic area
actually sucks in the blood from these paths, the blood in the
collaterals flows with increased rapidity. This excess of pressure
also determines an additional! dilatation of the collateral vessels,
144
Disturbances of Circulation.
corresponding at first merely to their distensibility ; but after the
dilatation has persisted for a time there also occurs a proliferation
of the cells of the vessel walls in consequence of the altered con-
ditions of tension, not only causing narrow arteries to assume
wide calibre, but changing capillary vessels into arteries. It is
in this manner that a tissue whose principal artery has been ligated
or occluded by thrombosis has its blood supply restored. The
development of collateral circulation, however, requires time before
complete compensation is attained ; and should the existing anasto-
Fig. 12.
Embolism of an artery with congestion of
its two vense comites.
Fig. 13.
Supply by anastomotic channels.
motic channels be very small, few or entirely absent, the tissue must
in the interim sufifer from the circulatory loss, be moi'e or less com-
pletely deprived of its nutriment and perish. This is particularly
true when there are absolutely no arterial anastomoses. Arteries
which possess no communicating channels with neighboring arterial
areas are commonly known as end-arteries, following Cohnheim.
Parts of organs supplied with no arterial anastomoses have of
course capillary communications with the adjacent tissues, but the
small amount of blood which passes through these minute channels
is often insufificient to maintain the nutrition of the area deprived
of its arterial supply ; only in case of very small areas is the
Infarction. 145
capillary supply sufficient for this purpose. Moreover it may hap-
pen that it is not one single artery that is blocked, but that at the
same time its anastomosing vessels are also occluded, under which
circumstances there necessarily result circulatory disturbances hav-
ing serious consequences. The area which is deprived of its blood
supply loses its blood color, and assumes a paler and drier appear-
ance than the surrounding tissue; the blood remaining in it be-
coming decolorized because its hccmoglobin is dissolved, disin-
tegrated or dispersed by diffusion, and the anaemic tissue, in which,
too, the lymph is stagnant and coagulates, undergoing regressive
metamorphoses. Such an ansmic and dead area is known as an
anccmic infarct.
A tissue which is thus cut out of the circulation and
deprived of its arterial blood supply is not necessarily anaemic
but on the contrary may be the scat of a distinctly pathological
engorgement as a result of regurgitation of blood from the veins.
Particularly where the veins of the part whose arterial supply
has been occluded anastornose with adjacent veins, the blood, which
in the latter vessels is under a certain amount of pressure, flows
over into the former and back into the anaemic network of capil-
laries ; just as the water from a brook moves back into the side
ditches of a stream if these have no fall. There is no force from
the arteries in such a site capable of driving the blood through the
afifected area and the capillaries in which the venous blood collects
become distended and their walls flaccid and permeable from the
lack of normal bathing with flowing blood. The venous blood
thus stagnating in the capillaries partly leaks through their w^alls,
partly undergoes coagulation; and the whole area thus engorged
with blood assumes a dark red hue. Such an area is spoken of as
a hccmorrhagic infarct (infarcire, to stop up). [Others would
refuse the importance attached by the author to the above idea of
a venous regurgitation giving rise to the engorgement of the in-
farcted area with blood. Anastomotic communications are usu-
ally more numerous and free between veins than between arteries ;
and if this be true and the author's views correct, anremic infarcts
should be the exception rather than of as common occurrence as
they actually appear. If venous reflux were as easy as supposed
by the older adherents of this theory, anaemic infarcts should be
practically unknown. From the editor's viewpoint the process is
more easily understood if we accept the belief, which seems rea-
sonable, that there are no true end-arteries and that there are al-
146 Disfurboiiccs of Circulation.
ways some small anastomotic channels between adjacent terminal
arterial areas. Through such anastomoses, inappreciable under
normal conditions but distended by the collateral rise of blood
pressure when the embolism diverts the blood into the surround-
ing areas of distribution, the blood enters the infarct. The ques-
tion whether in any given case an embolism should cause an anaemic
or a hemorrhagic type of infarct is largely determined by the
texture of the tissue in which the lesion occurs, anaemic infarcts
being met in relatively firm tissues as in the kidneys, and haemor-
rhagic in looser structures as in the lungs. The explanation of
such distribution is not entirely clear but probably rests in the
facility afforded by the tissues at the border of the infarct for dis-
tension of the capillary anastomotic channels entering the infarcted
area. Naturally the looser the texture, the greater the ease of
such dilatation. It should however be realized that the collateral
congestion existing along the border of the infarct is productive of
swelling and of pressure upon the periphery of the infarct.
Granted a fairly firm structure, such pressure should compress the
very channels of ingress into the interior of the infarct which are
here supposed to give opportunity for the entrance of blood : and
in such instances the part occluded should remain anaemic. If.
however, the tissue be. loose in texture such compression cannot be
of sufficient importance to occasion the interference with these
anastomotic channels just suggested ; and here the blood may by
such paths enter the area from the zone of collateral hyperaemia
and give rise to the appearance of a haemorrhagic infarct. In-
farcts of the lung are usually haemorrhagic in type in conformity
with the natural looseness of this tissue ; but the writer recalls
a recent case of an anaemic infarct of a collapsed lung, bear-
ing out the above theory. There is no objection to the author's
views in so far as entrance of blood to the infarct through venous
anastomoses may constitute a part of the process ; but to the
writer's mind it is excessive to suppose that this factor with reflux
of blood into and through the venules and capillaries irom the
veins is the sole explanation of the phenomenon ; and in his opinion
both arterial and venous anastomoses may contribute, regulated
however by the factors of border swelling, texture of tissue and
pressure, to determine to what degree the entrance of blood may
be possible] .
Microscopically a haemorrhagic infarct exhibits the capillaries of
the part turgid with blood and the lymph spaces and all the tissues
Iiifarcfioii. T47
infiltrated with lucniorrliagic ci'lusiun. Ju larj^e infarcts the con-
gestive reflux of venous blood is often restricted to the periphery
of the area alone, the central portions remaining anaemic and hav-
ing therefore only a red areola.
Infarcts as a rule are conical in shape, the apex of the cone
at the position of arterial occlusion, the expansion from this point
corresponding with the branching of the artery. From fusion of
closely situated infarcts or in those of flat organs like the wall of
the intestinal canal, the conical shape may be indefinite and the
outlines suggestive of a map. Hasmorrhagic as well as anaemic in-
farcts occasion destruction of the tissue, the circulation being en-
&i^ ,^-
•«•
Fig. 14.
Conical liaemorrhagic infarct.s in a portion of the Ividney of a cow.
tirely ended in the area involved ; the tissue with all the blood which
has engorged it being reduced to a mass of coagulated necrotic ma-
terial. Such an area excites an inflammation in the surrounding
tissue, to the formation of an actual inflammatory zone of demarca-
tion ; a wall of leucocytes collecting around the area of coagulated
material, fibroblastic and angioplastic cells from the surrounding
healthy structure penetrating the infarct, whether it be an.xmic or
hsemorrhagic, the blood and disintegrating tissue of the infarct
being removed by phagocytosis, and the site of the infarct being
eventually occupied by a mass of contracting connective tissue
(infarct scar). Such cicatrices are quite common in the kidneys
(cicatricial kidneys). When either an anremic or h?emorrhagic
infarct is related to some surface infected with bacteria these in-
148
Distiirhanccs of Circulation.
variably invade every part of its tissue, causing its destruction by
moist gangrene, as is regularly seen in such lesions of the in-
testine (septic destruction of the intestine).
Thrombi, developing in the veins so as to cause their occlusion,
of necessity interfere with the passage of the venous blood from
the peripher}^, and of course give rise to passive congestion. The
duration and termination of such cases also depend upon the
presence or absence of proper collateral communications. In case
of a partial or complete occlusion of unpaired venous trunks (vena
Fig-. 15.
Cicatricial shrinliage after embolism (hfemoi-rhagic infarcts) of the kidney
of a hog.
cava, portal vein) or in case of synchronous thrombosis of a num-
ber of venous tributaries (veins of the lung) a serious passive con-
gestion is occasioned, with stasis of the blood column, hremorrhagic
infiltrations or congestive transudations. Should there be a num-
ber of collateral branches of sufficient calibre the stagnation of
Wood will extend from the point of occlusion only to the first
collateral branch, and the blood wull pass without difficulty by the
collateral route to the heart ; should the anastomotic passageways
be narrow they may become dilated by the pressure of the ob-
structed blood and the tissue be gradually relieved of its congestion,
provided the degree of dilatation will accommodate the blood ac-
cumulated in the various venous channels of the structure. A'ery
small veins and the capillaries everywhere in the part may be so
distended as to serve the purposes of drainage, thus conducting
Embolism. 149
the blood by a round-about way into one of the venae cavee. Clots
and fragments of clots from the capillaries and veins pass as
emboli to the right heart and thence to the lungs.
In the same way as clots, a variety of substances may, if once
they have gained entrance to the blood, be carried along by the
current and give rise to embolism. Virchow and Cohnheim, whose
studies were fundamental to our kucnvledge of the embolic process,
showed that small balls of wax introduced into the blood vessels
are carried along by the current, lodge in some relatively narrower
place in the vascular tube, and give rise to all the mechanical con-
sequences of embolism. Sometimes parasitic worms which have
succeeded in making their way from the intestine into the radicles
of the portal vein are conveyed with the portal blood into the liver
and may be carried thence onward as emboli to the heart and lungs ;
very minute animal parasites, as the rounded oncospheres, measur-
ing only 20 to 40 micromillimeters in diameter, and larval tricliina",
may slip through the capillaries of the pulmonary circulation, often
measuring o.i mm. in diameter, and thus gaining access to the
arterial stream be carried to any of the organs. It may be easily
appreciated from this wliy the liver and lungs are the most
common sites for echinococcus cysts ; and the embolic mode of dis-
tribution of the parasites is recognized from their usual wide dis-
semination throughout the whole organ. Of the larger parasites
which the blood may aid in distributing, liver lUikes deserve special
mention ; these sometimes in their migrations in the hepatic par-
enchyma penetrate into the branches of the hepatic vein and may
pass with the blood through the right heart into the lungs. The
mechanical consequences of embolism by these animal parasites are
usually of little importance because of the minute size of the bodies
and the relative certainty of sufficient anastomotic supply to the
small areas affected ; and disturbances are only occasioned by
pressure, etc., in case the invading parasite increases in size. The
larger parasites like stroiii^ylus annatus are capable of directly
causing the same mechanical eft'ects as described iii connection
with blood clots (as cerebral embolism with infarction).
The entrance of air and of dro])lets of fluid fat may also oc-
casion circulatory disturbances in a jnirely mechanical manner, in
the same way as blood clots. Air cuibolisui is of rare occurence
and is met with in operations on the neck." The air which is
drawn by the suction force of the lieart through a valvular venesec-
*Traumatk- a^rrnmia was first observed in the horse l>y the French veterin-
arian, Verrier (1806).
150 Disturbances of Circulation.
tion wound into the jugular vein, or which is accidentally intro-
duced in intravenous injection, becomes mixed with the blood in
the form of bubbles of various sizes. In case of healthy animals
with normal blood pressure, moderately large quantities of air (5
to 10 cubic centimeters in dogs, sheep, horses) injected into the
jugular vein are sometimes born without harmful results, the air
disappearing quite rapidly by absorption in the circulating blood.
In animals . with low pressure and a tendency to accumulation in
the right heart (as after operations and after loss of blood in
parturition) the air bubbles are apt to accumulate in the right
heart and form a large elastic air cushion which is not forced
onward by systole, being only compressed by cardiac contraction
and expanding again in diastole. In consequence the blood is
dammed back in the right heart, and there results a marked dilata-
tion of the right ventricle, reaching two or three times its normal
volume. (Death takes place from the cardiac dilatation and suf-
focation, the blood being prevented access to the lungs. Accord-
ing to Frangois Franck it may also be possible that some of the
air passes through the lungs, and, traversing the left heart into
the coronary arteries, brings about embolic occlusion of the latter
and anaemia of the myocardium.*)
Fat ciiibolism is usually met in connection with severe con-
cussive lesions of the bone marrow (Ribbert). The occurrence of
fracture of a bone with such concussion allows lacerations of the
delicate walls of the venous capillaries to take place, after which
fat droplets from the fat cells abundantly present in the marrow
may pass into the blood (Ribbert). Access of fat into the blood
may also be thought possible from the liver cells in case of con-
tusion .of this organ, its cells also being usuall\' rich in fat (Rib-
bert). The oil droplets are first carried with the venous blood to
the lung, where they lodge in the small arteries and capillaries,
the capillary network often appearing turgid as if filled with a
fatty injection mass. From the occlusion thus brought about
haemorrhagic infarcts are formed in the lungs, usually a transient
condition (may be proved by injecting a fat emulsion into the
jugular). The liquid fat may. however, pass through the pulmon-
ary capillaries and be carried on into the left heart, whence it may
be conveyed with the aortic blood into the cardiac musculature
(coronary arteries), the renal glomeruli, or the brain and other
organs. The fat lodged in the coronary arteries, just as any other
*Recueil veier. 1903, p. 370.
Metastasis.
i=;i
emboli, occasions anaemic degeneration of the myocardium; in the
brain numerous small hccmorrhages ; and in ^uch or other analogous
manner fat embolism may prove fatal.
Sometimes after traumatic lesions of the tissues, cells are simi-
larly swept into the blood, as giant cells from the marrow or liver
cells, and lodge in the pulmonary capillaries because of their size.
This type of cellular embolism occasions no special disturbance, the
occlusive lesion being at the most a minute one and the cells soon
broken up or removed by phagocytosis. However, the entrance of
tumor cells or pathogenic bacteria into the blood, and the embolic
transmission of such bodies, are of much more importance. Their
mechanical effects in causing complete or partial occlusion of the
Fij
16.
Fat embolism of the lung, eight days after fracture of the leg. Drawn by
Dr. Ziesing; X -oO.
The capillary network of the alveolus to the right is cholved with blood, the
lower one with fat and the artery likewise Just above the latter are two
air bubbles (showing as dark rings) and several droplets of fat whicn na\e
escaped from it (with simple d.irk outline), (.\fter Perls.)
vessels are of minor significance because of their minute size ; but
because of their nature they induce specific changes, the process
being knowm as one of malignant embolism or as metastasis (Merdo-rao-ij,
displacement ) . We have here to deal with substances which have
already given rise to pathological processes in some part of the
system, and which are now, by being transported by the blood into
new situations in the body, inducing the same disturbances in the
latter. Emboli composed of tumor cells originate from autoblas-
152 Disturbances of Circulation.
tomata (neoplasms, tumors) whose cells in the growth of the
mass are penetrating the walls of the blood vessels and, picked up
5y the blood flowing by, are carried along with the stream. Wher-
ever they lodge a new autoblastic growth develops from the multi-
plication of the displaced cells, which retain their power of growth.
Since usually it is not one single cell which is thus swept from the
primary site, but whole groups of cells being loosened and
separated from each other in the circulating blood and scattered
throughout the capillary network of the organ into which they are
carried, the latter becomes riddled with tumor nodules (disseminated
or multiple embolism). In dogs, for example, which are suffer-
ing from cancer of the thyroid gland the lungs are as a rule occu-
pied by great numbers of nodules of the same carcinomatous char-
acter, the cells having penetrated from the cancerous alveoli of the
gland into the thyroid veins and having of course been carried into
the lungs. In the same way from cancers of the mammary glands,
the skin, the nose, etc., after invasion of the tributaries of the vena
cava, metastatic nodules develop in the lungs. Intestinal, gastric
and pancreatic cancers give rise to metastatic embolism in the liver,
the tumor cells primarily gaining access to the portal vein ; only in
case they pass through this organ does the lung become involved
by the tumor cells. [This is true in a general sense provided the
hsemic route is followed in metastasis. It should be added however
that these cells may find their way by the lymph stream through
the thoracic duct to the lungs, the liver being entirely escaped. So,
too, it is possible by the minor anastomotic communications be-
tween the portal system and the general venous system, as by way
of the veins of the smaller gastric curvature, lower oesophageal
and azygos veins, that the cells may be conveyed to the lungs
directly, the liver being evaded.]
Malignant bacterial emholisui is determined by the en-
trance of pathogenic bacteria into the blood vessels, quite com-
monly the pyogenic organisms ; more rarely the vegetable organ-
isms like the spores of moulds enter into consideration. Such
germs may gain entrance into the circulating blood through lesions
of the skin or mucous membranes. Lesions which were practically
imperceptible may serve as the point of entrance [it is also claimed
by a number of persons that in a limited degree bacteria may pass,
as it were be absorbed, through delicate mucous membranes with-
out the actual existence of any structural disturbance of the mem-
brane, as Ravenel has pointed out in case of tubercle bacilli passing
through the normal intestinal wall to the mesenteric glands],
Metastasis. 153
the bacteria first multipl_\ing- at this point of invasion and then
either by way of the lymph passages, conveyed to the blood.
or directly growing through or actively penetrating the deli-
cate walls of the capillaries. Some bacteria are motile and are
able to actively progress because of this property, or because of
their minute size ma}- be passively conveyed through the lymph
spaces. Generally at the point of entrance the local action of the
bacteria causes a focus of destruction varying in type with the
form of bacteria present, as a suppurative liquefaction or ichorous
softening (furuncle, suppurative wounds of the skin) ; coincidently
the destruction of the walls of the capillaries and veins permits
the bacteria to gain access to the blood and circulate with it and
to be carried to the heart and lung or from the intestine to the
liver. Bacteria, too. because of their minute size may traverse
capillary areas and therefore often pass from the lesser to the
general circulation and become scattered widely throughout the
system. In a strict sense they should be regarded as emboli, al-
though primarily because of their minuteness they occasion no me-
chanical disturbances but remain suspended here and there in the
vascular tubes, as at places where the blood current is temporarily
hindered (a joint) or where there are inequalities in the intima
(valves, sharp bends in the capillaries, renal glomeruli). At such
sites they induce the same type of changes as at the point of en-
trance, causing inflammatory reaction, suppuration, etc., and multi-
plving at first to the production of a definite metastatic focus and
later making their mechanical obstructive eflfects appreciable when
thev have developed into masses and clumps. In other cases the bac-
teria may from the first be disseminated in the blood in small clumps.
or as is usually the case they may adhere to bits of thrombi which
have been broken loose. Under such circumstances mechanical
occlusion and specific action are to be expected coincidently or in
close succession. Precisely as in case of simple embolism a smaller
or larger infarction is produced and within the tissue of the
infarct, filled up with coagulated blood and necrosed, the bacteria
mav multiply to great numbers, transforming the infarct, accord-
ing to the specific properties of the bacteria of the embolus, into a
suppurating focus or breaking it down into an ichorous mass.
The most common example of malignant embolism is met with
in umbilical phlebitis, frequently seen in newly born animals. In
case after section of the umbilical cord, dirt infected with bacteria
(from dung, pus, dust from the straw of the animal's bed, the
154 DistitrbanCiS of Circidafion.
coating of the tongue of the mother animal as she licks her
young) comes in contact with the umbilical wound, germs capable
of causing inflammation may penetrate into the umbilical vein
(motile bacteria). These microorganisms rapidly multiply in the
clotted blood which occupies the vein, penetrating it possiblv up to
the liver where the portal and umbilical veins unite. Thence by
the portal current particles of the softened and infected blood clot
are swept into the substance of
, -"'" -;?:t~-^. ^ the liver and give rise there to
multiple abscess formation. Iso-
lated bacteria or small clumps
of the germs are carried on-
:^*. ward trom the liver through
f.' *>pv the hepatic venules (in calves
perhaps directly by way of the
ductus Arantii) entering the
heart and lungs with the blood
; ' ■■ of the vena cava, with produc-
tion of further suppurative me-
Malig-nant hsemorrhagic infarct of the tastases Ul the latter. They may
uie^cemre. ''°''^- ^"PP^''"^""' *'^ moreover gain access to the
general circulation (pulmonary
veins, left heart, aorta), as the result of which extensive pyogenic
foci of inflammation of h?emotogenous embolic origin are produced
widely through the body, as in the kidneys, joints, eyes or brain.
Another striking example of embolic metastasis is seen in case of
tuberculosis, where the tubercle bacilli may be disseminated as
above (cf. chapter on tuberculosis).
lymphatic Thrombosis and Lymphogenous Embolism. The lymph
flowing through the lymph vessels, the onward movement of which
depends partly upon the pressure with which the fluid transudes
through the capillaries, partly upon the compression upon the
canals (just as a sponge is squeezed) by the movements and con-
tractions of the organs, is also subject to coagulation. For the
most part lymph coagulation is caused by the enzymes of in-
fectious toxine-producing organisms and b\- lesions of the Ivmph-
vessels witli adhesion of necrosing leucocytes and separatioli of
fibrin in the spaces. The lymph canals filled with lymph coagula
are to be seen as broad strands occupied by the coagulated ma-
terial, transparent and jelly-like, as in the interstices of the lung
in croupous pneumonia, and strikingly shown, too, in cutaneous
Lxiiiplialic Thrombosis and Embolism. 155
lymphangitis. Because of the rich and intricate anastomosis of
the lymphatics the esca|)e of an\- excess of lymph is easy by the
collateral paths, and nsually the obstruction is in time removed
by a fatty degeneration of the clot. Commonly the lymph stasis
therefore, is but a transient feature. Extensive lymph thrombosis
may hov^ever lead to a necrosis of the part involved, from failure
of removal of its metabolic products and the stagnation of the
lymph. Fragments of the thrombi loosened and carried away
give rise to little of pathological importance, because of the rich
collateral communication and the fact that the paths lead into the
lymphatic glands, as well as because of the fine or molecular dis-
integration of the coagulated material. Only in case of the
lymphatics of the mammary gland is there to be apprehended a
direct passage of such material into the blood with consequent
pulmonary embolism.
The lymph channels are important routes of transportation of
specific types of emboli, as tumor cells and bacteria as well as for
the convection of all sorts of material arising from the disintegra-
tion of tissues, dust particles, pigment, and any other minute solid
elements. Such substances are carried along, in part free in the
lymphplasm with its slow current, partly in the motile wandering
Ivmph corpuscles which load themselves with small particles; the
pathological significance of their convection varxing with the char-
acter of these bodies. Thus by the removal of cUsintegrated ma-
terial, cellular fragments or dead bacteria, a tissue or organ may
be restored to its proper functional capacity, a sort of street-clean-
ing being accomplished ; but on the other hand the convection of
toxic matter, of cells or microbes capable of multiplication, serves
to establish more local points (or generalization) of the disease. A
few examples may render this more clear. In case of hremorrhagic
extravasations, as after the fracture of a bone, the entire hsemor-
rhagic focus gradually disappears, the disintegrating blood corpus-
cles being taken up by the lymph corpuscles wandering about and
carried to the lymph glands for further destruction (as a result
of which the lymph glands in the neighborhood of such hsemor-
rhagic areas become the seat of a rusty brown discoloration).
Carbonaceous particles inhaled and lodged in the lung are carried
along the lymph passages to the bronchial lymph nodes, coloring
them black. Virulent streptococci wdiich have gained entrance to
the mouth and pharynx are taken up by leucocytes wandering out
and in the mucous lining, carried primarily to the pharyngeal
156 Disturbances of the Blood.
lymphglands, where they may perhaps multiply and give rise to
suppuration ; thence they may travel from one lymph node to
another (retropharyngeal, cervical, thoracic), in each setting up
new foci of suppuration, until they finally reach the blood and pro-
duce pyaemia.
No matter how minute the lesion of the skin or mucous mem-
brane, infectious bacteria may from some source gain access to
the lymphatic radicles and occasion their specific processes in the
lymph channels and at their points of deposit in the lymph glands
(cf. tuberculosis and carcinoma). Lymphogenous extension or
embolism is therefore to be regarded as an important factor in the
generalization of local infectious processes.
Pathological Changes of the Blood.
The blood supplies the tissues with the oxygen essential to their
life, besides the albuminates, carbohydrates and water ; it removes
their metabolic products and is the principal factor in the distribu-
tion of heat; it, therefore, maintains the functions of the nervous
system, the heart and all of the organs as their liquid nutrient, their
source of heat and their cleansing fluid. In its manifold relations
to the tissues, in its function of giving and receiving on so many
sides, there arises constant change in the quantity and composition
of the blood, limited, of course, within certain bounds and relations
set by the tissue requirements. When blood is lost, fluid is taken
into the vessels from the tissues and corpuscles are supplied by the
blood forming organs to the eventual restoration of the blood.
When an excessive amount of water is absorbed there follows rapid
excretion of the superfluous quantity through the kidneys ; and in
analogous fashion the variations in its chemical constitution are
continually undergoing adjustment. \\'e have yet to discover
wherein lies the exact and delicate regulation of the quantity and
quality of this complex liquid ; at all events the changes -in
chemical composition involve continually repeated stimulation of
the nerves of the blood vessel walls, of the cells of the hgemopoietic
organs and all secretory cells upon which the hremic composition
depends. As soon as this regulation is disturbed the variations
in the volume and proportionate composition of the blood deviate
from the physiological limits, and hcxmic anomalies* are said to
exist.
*The word ili/scrasia was formerly employed in this connection, but was wittiout
exact significance, being applied by some to any blood abnormality, by others to long
persisting faults in the proportionate presence of its constituents or simply to
impurities of the blood from the presence of special substances. The word may be
dispensed with.
Plethora and Oligcumia. 157
It can readily be appreciated why there are so many types and
degrees of blood abnormalities when it is recalled that of neces-
sity pathological changes in the blood must follow any alteration
in the efficiency of the organs, the metabolic processes of which arc
constantly removing from or adding to the blood so many elements.
The amount of blood obtainable from the domestic animals at
slaughter is subject to such wide variation, as Bollinger and Berg-
man have pointed out, that it is clear 'that we can have no safe
basis for determining the existence of an excessive volume, of a
condition which may be termed full bloodedness or plethora, in any
subject, either from the quantity obtained at slaughter or deduced
from symptoms. The healthy animal very quickly gets rid of ex-
cesses introduced experimentally into the body, whether it be
blood of the identical species, blood serum or indifferent fluids ; and
the transient plethora caused by transfusion causes no disturbances
worth mentioning. The blood vessels are in fact never filled to
their full capacity collectively ; the vast multitude of capillaries
capable of further dilatation can accommodate a large volume of
fluid in excess of their ordinary content. Experiment upon ani-
mals shows that in dogs the blood volume may be doubled by
transfusion, a quantity representing eight to twelve per cent, of the
body weight introduced, without injury to the animals; danger to
life occurs only after the introduction of a still greater amount
(Samuel). The excess of fluid transudes from the vessels and is
eliminated from the body in the course of a few days with the
urine; the superfluous blood cells are destroyed in the liver and
other organs. Whether a plethora of actual pathological signifi-
cance ever occurs in animals is quite unknown.
Diminution of the volume of the blood, known as blood
impoverishment, oligaemia or general anaemia, has associated
with it a decrease of the number of blood corpuscles, known
technically as oligocythcEmia; usually, too, the converse is true.
From a practical standpoint it is difficult to draw any fine distinc-
tions as to whether the blood is normal as far as the volume of its
fluid is concerned and only the cellular elements deficient, or
whether the plasma, its salts and other constituents have under-
gone the greater reduction ; for which we are accustomed to regard
the loss and destruction of the erythrocytes, the most conspicuous
of the blood constituents, as the principal pathological feature. In-
asmuch, however, as there is a close interrelation of these altera-
tions, the one dependent upon the other, there are apt to exist many
158 Disturbances of the Blood.
peculiar phenomena in these instances, which have thus far been
imperfectly studied ; for example, the red blood corpuscles may
undergo reduction and disintegration because the plasma contains
some unusual saline or an excess of water or because some spe-
cific hgemolytic substance has become mingled with it. Briefly
speaking, it is customary to speak of general anaemia in a subject
whose mucous membranes and skin persistently appear very pale,
whose muscular tissue and viscera have at autopsy the pallor char-
acteristic of a slaughtered animal and in which in life there ex-
isted a condition of general weakness. The contrast between
the peculiar tint of the organs and the deep red color given by the
full capillary blood serves better to indicate the reduction in the
volume of the blood than the amount which can be obtained in
the heart and large vessels and which can be estimated only with
extreme difficulty. Oligocythsemia is determined for a cubic milli-
meter of blood by microscopic counts of the cells with special
measuring apparatus; diminution of the hsemoglobin content can
be determined only by chemical methods. [Clinically this latter
is estimated by comparison of either the whole or the diluted blood
with standard color scales, each graduation of tint representing
a certain proportion of hsemoglobin. Matching of colors always
involves a large personal equation and at best can only be approxi-
mate, even were it established that the supposedly standard refer-
ence scale were entirely correct — which is not the case. How-
ever, as an approximation only and as a fairly ready means of
comparison, these color tests have at least a clinical value.]
The least complicated form of oligjemia is that occasioned by
blood loss from injury to the vascular apparatus, hcemorrhagic
anccmia, following wounds and lacerations of the vessels, venesec-
tion or the removal of blood by blood sucking parasites. A blood
loss exceeding three per cent, may be dangerous to life (external
or internal injuries) and sudden haemorrhages of still smaller vol-
ume from the large vessels may be fatal. [While exceptionally
this statement may be true where there are other factors as nerv-
ous shock involved, the limits of non-fatal blood loss as here given
are for ordinary cases quite too low. As much as one-third the
volume of blood has often been withdrawn without fatal collapse.]
The volume of fluid lost by non-fatal hgemorrhage is soon
restored by absorption of water from the tissues and ingesta ; while
the corpuscles and albuminous material are reformed in the course
oi a few weeks or months. In fatal haemorrhage there occur
Chaii^i^cs in the Erythrocytes in Anccniias. 159
phenomena of suffocation, lowering of blood pressure and uncon-
sciousness (ansemia of the brain). After haiimorrhage proteid
/netabolism is increased; metabohsm of fats is. however, decreased
because of the diminished power of combustion. Hence repeated
venesections are appropriate treatment where it is desired to in-
crease the deposition of fat and tlic\- are employed as aids to fat-
tening animals.
General anaemia may also be brought about by insufficient nutri-
tion or improper assimilation of food, as well as by diseases and
injuries of those tissues which supply definite blood constituents.
Here are particularly included various affections of the stomach and
intestine, hepatic diseases and alterations of the lymphatic tissues ;
but in arldition to such disturbances there is a wide further possi-
bility of the establishment of an ansemia from disease of the many
other tissues which contribute to blood formation. A number of
agencies are known to be capable of inducing the condition by caus-
ing the destruction of the blood corpuscles, perhaps to such a de-
gree that regenerative effort can no longer efficiently restore the
loss, as certain parasites of the blood (trypanosomes) and poison-
ous or toxic products of metabolism.
Among the most notable symptoms of man\- anremias are
changes in the form and structure of the erythrocytes. In place
of the circular discs there may be met irregular pyriform, club-
shaped or indented elements of various size, cells containing
vacuoles (cavities, hollow spaces), and nucleated red corpuscles.
A blood preparation showing such multiform cells of varying ap-
pearances is said to exhibit poikilocytosis ( ttoikIXos, variable, con-
fused, involved). Recently alterations in the staining reactions
of the corpuscles have been made out. The normal cells invariably
take up only one tint from certain staining combinations; the
stroma of young forms, degenerating and dead cells, however,
may assume several colors (polychromatophUia). The occurence
of nucleated red corpuscles in the circulating blood is an evidence
of active regeneration of these elements, and is often encountered
in the anaemias. Especially large cells of this type are sometimes
met {megalohlasts, gigantobhtsts), a peculiarity interpreted as
evidence that regeneration is taking place with extreme haste,
such cells, otherwise only seen in the bone marrow as early stages
of the erythrocytes, entering the circulation in these cases as im-
mature elements (Krehl). The increased cellular muhiplication
in the bone marrow, the principal site of the formation of erythro-
i6o Disturbances of the Blood.
cytes, causes in ansemias large areas of this tissue to return to the
condition of red marrow (normally only young growing animals
have much red marrow ; in adults medullary blood formation is
limited to a few bones according to the amount of blood required
to be formed ; change of the marrow to the red state and pro-
duction of this condition in many of the bones may be brought
about in animals by venesection — Naunyn, Litten and Orth).
In severe forms of ansemia not occasioned by actual blood loss the pro-
portion of iron in the liver, spleen and kidneys becomes abnormally high, this
feature invariably indicating exaggerated destruction of the red cells.
From a variety of causes, particularly the influence of certain
poisons (salts of the biliary acids, snake venom, bacterial toxines)
and, too, the transfusion of heterogeneous blood (blood from a
different species of animal), the h?emoglobin may undergo solution
and separation from the erythrocytes into the plasma {hccnio-
globincemia) . The coloring matter thus freed gives the plasma
or serum a difl^use wine-red color. A portion of the haemoglobin
is taken up by the liver and transformed into biliary pigment, and
the remnants of the injured and therefore disintegrating blood
corpuscles are to be found in the liver and in the spleen (also in
the marrow), these organs sometimes becoming considerably swol-
len and excessive bile formation taking place. The bulk of the
liberated haemoglobin is removed by the kidneys, causing more or
less harm to these organs and giving to the urine a blood red to
black discoloration (hcemoglobincemia) . These changes are ob-
served not only in association with severe infections and intoxica-
tions in cattle, but are also seen after muscular strain and chilling,
especially in horses and, too, in human beings (infectious, toxic,
paroxysmal, myogenous, rheumatic hsemoglobinuria). Some of
the haemoglobin in hjemoglobinaemia which remains in the blood is
converted into methasmoglobin ; this change may also affect the
coloring matter within the corpuscles, and is apt to result par-
ticularly from the action of certain poisons (antipyrin, potassium
chlorate). It gives rise to an appreciable sepia-brown coloration
of the blood (niethcemoglobincemia) . There always coexist with
this group of blood changes serious diseases of the subject ; the
haemoglobin, freed from the cells and altered in its constitution,
useless for respiratory purposes, is no longer capable of taking up
and giving off oxygen (Krehl), and the disintegrating blood cells
give origin to substances which may cause coagulation to take
The Leucocytes in Aiucinias. i6i
place here and there in the vessels, occlusion of the capillaries
and serious lesions of the renal epithelial cells.
Oligsemia is occasionally associated with a truly watery condition of
the blood, as where in case of haemorrhage, blood imiioverishment, inani-
tion, or renal disease the blood becomes deficient in albumen, the vessels
become filled with the fluid from the tissues in an effort to restore the
deficiency; such a condition is termed hydrccntia (oligccniia serosa). So.
too, the increase in the proportion of water with increase of the total
volume of blood (plethora aquosa. serosa) may lie thought of as a
pathological possibility; however, proper information is as yet lacking
concerning these pathological conditions and the relation between quanti-
tative changes of the serum albumen to the proportion of water in the
blood. Normally, large excesses of water known to be rapidly absorbed
from the stomach and intestine into the blood are quickly passed off
through the kidneys.
Of the pathological conditions of the leucocytes or white blood
cells and their reduction or increase in numbers in the circulating
blood our knowledge is only of the most superficial character.
To what extent the morphological and tinctorial peculiarities of the
individual forms and groups of leucocytes and lymphocytes nor-
mally found in the blood are characteristic of the origin and of the
role of these cells is a matter requiring further investigation.
These cells are of especial interest to the pathologist from the fact
that they are either attracted or repelled by chemical materials in
the tissues and by various particulate elements which may give
origin to the former (positive and negative cheinotaxis). Be-
cause of the power possessed by these cells of approaching or
receding from a given point like motile organisms, of taking into
their substance small bodies which they encounter — an act which
is to be regarded as an attempt to obtain nourishment (cellular
devouring capacity, pliogoeytosis) — they may be thought of as
playing the part of "scavengers of the organism"' (products of
disintegration, dust particles, dead cells and tissues, dead bacteria,
etc., all being removed in this manner). They may however by
identically the same mode of action come to serve as carriers of
infection in case a living bacterium or animal microorganism hap-
pen to be taken up by them. A microorganism not necessarily
destroyed in the substance of the leucocyte, but possibly actually
multiplying there, may be carried away to a new situation and
there renew its toxic influences, especiall\" if the phagocytic cell be
destroyed by its poison. [.Metschnikofif urges strongly that after
appropriation of a microbe by a phagocyte, the former may be
i62 Disturbances of the Blood.
regarded as entirely destroyed or as seriously impaired in its
vitality.] It is readily observed in suppurations undergoing
metastasis (cf. metastasis), in swine erysipelas and other bac-
terisemias, that many of the leucocytes are loaded with the specific
germs.
Negative chemotaxis, too, the movement of the leucocytes away
from certain poisons or more frequently the mere failure of attrac-
tion of the cell toward these substances, is capable of explaining a
number of points connected with disease and immunity. For ex-
ample, as shown by the extremely interesting studies of Besson,
Leclainche-Vallee, Vaillard and A^incent, non-virulent but living
germs (spores) of tetanus, malignant oedema and blackleg are
englobed by leucocytes and ingested and thus prevented from de-
velopment and from becoming virulent ; virulent germs of these
same sorts, however, prevent the leucocytes from entering the tis-
sues because of the toxines to which they give origin and are
therefore not taken up by the phagocytes, but continue their harm-
ful action upon the tissues in which they exist.
The general group of leucocytes in the blood is subject to con-
siderable variation in number, even under normal conditions.
After taking food or violent muscular exercise there may be
uniformly observed an increase in their number ( physiological
leucocytosis or hypcrlcucocytosis) , apparently occasioned by the
attractive influence exerted by various proteid matters, fatigue
stuffs, etc., which have entered the blood. In inflammations, sup-
purations, and infectious fevers a similar increase in the number
of V leucocytes distributed throughout the blood occurs {pathological
hyperleucocytosis) , similarly ascribable, so far as indicated by ex-
periment, to chemical attraction and the circulation in the blood
of substances stimulating the leucocyte-forming tissues to greater
production. (Injection of bacterial proteins and other proteids into
the blood is particularly likely to be followed by hyperleucocytosis).
[While there are a few exceptions to the usual occurrence of
leucocytosis in acute infections, it is in a general way to be in-
terpreted as an unfavorable feature when such increase fails to
take place (leucopenia) ; either the subject being in such deterio-
rated state that the usual reaction is impossible and the resistance
to the disease much below par, or the smallness of number of these
protective cells itself determining the failure of sufficient antago-
nism. Cases marked by such unusual leucopenia, with the excep-
tion as above suggested of a few special forms of disease, are apt
to terminate fatally.
f I'
The Leucocytes in Anccmias. 163
To a certain extent the increase of this or that particular form
of leucocyte is of diag-nostic importance. In brief we reco.^nize
as the most common form of white blood corpuscle the i)olymor-
phonuclear neutrophile cells (containing multiple nuclei or a single
polymorphous nucleus, and having numerous fine granules in the
cytoplasm wdiich elect a combination of the acid and alkaline dyes
in staining with such mixtures, becoming purplish with methylene
blue and eosin for example). An increase of these elements,
spoken of simply as leucocyfosis or hyperleucocytosis according to
its grade, is commonly m.et in a number of infections, particularly
those of the septic group. There are normally present in the
blood a few similar leucocytes which have, however, in their
cytoplasm rather coarse granules which, from an acid and basic
combination of dyes, select the former, being therefore called
oxvphile cells (or because eosin is the acid part of the common
methylene blue and eosin solutions and their cell granules appro-
priate the red of the eosin. these cells are often called eosinophile
cells). These oxyphile cells may become increased in a number
'of conditions, but this increase, know^n as eosiiiophilia, is especially
notable in the blood of animals or human beings subject to some
of the animal parasites as the trichina or hookworm. Tn pseu-
doleukremia and lymphatic leukaemia the lymphocytes, cells with
single large, deeply basic staining nuclei and with fine basophilic
granules in the scanty cytoplasm, are especially increased. Tn the
common lieno-medullary leukaemia there is special increase in a
large type of leucocyte not normally present in the blood but
natural to the bone-marrow", known as a myelocyte, with large
nucleus taking the basic stain faintly and with fine neutrophilic
granules in the cytoplasm.]
Where there is such an increase of leucocytes in the blood that
thev equal or exceed the number of erythrocytes in the drop from
which the cell count is made, or if certain cells normally present
in but meager numbers are unusually numerous [the mononuclear
cells above noted as myelocytes] the name leiikcvmia is employed
to denote the condition. [The actual number has been known
to equal that of the erythrocytes, but this is exceptional ; and the
present conception of leukaemia concerns rather the type of cell
present in the blood, the myelocyte, than the actual numbers at-
tained.] In this disease the blood is apt to be changed in its
macroscopic appearance as well, becoming of a light red or rasp-
berry color. There also occur hyperplastic changes in the various
164 Disturbances of the Blood.
lymphoid structures of the body (lymph glands [in lymphatic
leukaemia] ; bone-marrow and spleen [in lieno-medullary leu-
kaemia] ) ; and the coincidence of a general debility, fever, and
tendency to hemorrhage mark the condition as a serious affection.
Nothing definite is known of the aetiology of the affection either
in man or the animals; it has been conjectured, however, that the
cause may be of an infectious nature.
DISTURBANCES OF M-ETABOLISM; RETRO-
GRESSIVE AND NECROTIC PROCESSES
Faults of Heat Regulation; Hyperthermia; Fever.
The temperature peculiar to the various warni-blooded animals
is constantly maintained in health at the same level within narrow-
limitation by the delicate and accurate regulatory mechanism of
the body. With every change in the surrounding temperature and
other external influences there occurs special adaptation of heat
production and heat dissipation on the part of the animal body. If
an excess of heat be produced within the body from exaggeration
of metabolism (muscular activity, ingestion of large amounts of
food), excessive heat dissipation follows; the cutaneous blood ves-
sels dilate and the system loses in consequence a greater amount
of heat from its surface by conduction, by radiation and if need be
by perspiration, as well as by free evaporation of moisture in the
lungs. In case the body suffers unusual heat loss (cold environ-
ment) heat dissipation is diminished by constriction of the cutaneous
vessels, and the chemical activities in the tissues increase heat pro-
duction by accelerating decomposition, that is. the combustion of
carbohydrates and fats, particularly in the musculature. Rich
food suppl}- and bodil\- activity increase the production of heat ;
and by these means and by simple diminution of heat dissipation
the warm blooded animal is enabled to maintain its proper tem-
perature in spite of marked chilling.
The human being in state of health, possessing additional means
of conserving his warmth by a number of layers of warmed air
(clothes) about his body, maintains an average body temperature
of 37.2° — 37.4° C., the variation from morning to evening being
about one or one and one-half degrees. The horse, according to
Friedberger-Frohner, has a normal temperature of 37.5° — 38.5° C;
the cow, 38° — 39° C. ; the sheep and goat, 39° — 40.5° C. ; hog,
i66 Teuipcrafurc Disturbances.
38°— 40° C; dog, 37-5"— 39° C.; cat, 38°— 39° C. ; birds,
4i.5°-42.5° C.
The warm blooded animal maintains the constant physiological
level of temperature by the continued operation of the heat dis-
sipating powers ; if there were no such loss, the amount of heat
production would be sufficient to cause an increment of about one
degree centigrade in the temperature of the blood every half hour.
Passive Hyperthermia. By limitation of heat dissipation
the body may become overheated, particularly when the cause
is some external physical influence which hinders heat loss by
evaporation. Although in a dry atmosphere where there is no
restriction to evaporation the body is capable of enduring even high
temperatures of the surrounding air, the body heat increases rap-
idly in a hot, moist atmosphere, heat loss by evaporation being
impossible, and all the more if in addition there be increased pro-
duction from muscular exercise. In a warm bath of 40° — 41° C.
the human body temperature may even in half an hour reach 40° C. ;
in water of 37° C, it rises about 1° C. in an hour, and in an hour
and a half about 2° C.
Animals closely packed in hot railway cars experience consid-
erable increase of temperature ; in warm, damp air animals closely
herded in long drives (droves of hogs, oxen yoked to wagons) may
have their temperature reach more than 40° C. Under such cir-
cumstances where only external physical conditions render the
regulation of the body temperature impossible or where (perhaps
coincidently) unusual accession of heat production occurs because
of exceptional muscular exercise, there is really no true febrile tem-
perature present, but rather only a passive heat accumulation,
passive hyperthermia; the mechanism of heat dissipation is acting
in its fullest capacity and is insufficient only because the demands
upon it are excessive (Krehl). Thermolysis so far as the animal
body is concerned is not at fault ; but fails because of conditions
existing in the external surroundings.
Whether pathological results follow such passive hyperthermia
will depend upon the persistence of the condition and the subject's
power of adaptation. Men and animals living in tropical coun-
tries give evidence upon this last point ; and, too, it is commonly
seen that when a number of individuals are subjected to excessive
temperatures there are only certain ones who suffer pathologically,
those probably whose thermo-regulatory mechanism is of inferior
efficiency. Passive hyperthermia may reach 42° — 45° C, and may
Fever. 167
terminate fatally {heat stroke). The occurrence of a heat stroke
is marked by symptoms of general weakness, dizziness, fainting
attacks, and marked acceleration of the pulse, these probably being
mainly dependent upon disturbances of brain and myocardium, al-
though upon this point there is need of further study.
Fever {fehris, from fervere, to be hot) is a state of the body
in which because of some disturbance of metabolism the regulation
of the body temperature to a mean level has ceased. The chief
and most constant evidence of fever is the abnormal increase of
the temperature of the blood, or internal body temperature. This
febrile hyperthermia or fever heat may exceed the normal tem-
perature of the animal perhaps but half a degree or by from
two to five degrees centigrade. It is characterized by marked re-
sistance to influences causing heat dissipation and by considerable
variation ; and is accompanied by increased tissue waste, changes
in the type of and increased frequency of the arterial pulse, increase
in the rate of respiration, diminution and alterations in the various
secretions, particularly in the urine, disturbances in the sensory
apparatus, increased thirst and loss of appetite. This group of
symptoms, which occur with the heightened temperature and with
it go to make up the clinical picture of fever, are to a slight
extent directly dependent upon the increased temperature of the
blood (for example, the number of cardiac movements and respira-
tions), but for the greater part are the results of the complex
action of the causes of the fever. The main point in the conception
of fever, with its febrile excess of temperature, is that the latter
is not the mere result of external physical influences restricting
thermolysis, or of muscular activity, but that there are certain
metabolic processes in operation which are due to the presence of
special temperature producing substances {pyrogenetic substances)
which give origin to the hyperthermia. How the heat equilib-
rium is aft'ected by such substances, whether they directly dis-
engage the heat from the cells and cellular groups or whether
they act indirectly through a heat centre, is not as yet certain and
cannot even in a general way be explained. These pyrogenetic
substances vary much among themselves and the reaction? which
they give rise to are by no means uniform. P""ever may be thovight
of as an indicator (Wassermann) that some peculiar metabolic
processes are in operation in the body accompanied by tissue
destruction and the production of antitoxic and bactericidal sub-
stances and precipitins ; and may be considered as an associated
i68 Temperature Disturbances.
or partial inaiii testation of a complex reaction to which the or-
ganism is prompted by the invasion of substances foreign to the
system. From this it may be appreciated that the idea of febrile
temperature and of fever is in reality principally based on the
aetiology of the condition ; the existence of proper causes of fever,
the presence of pyrogenetic substances, is the factor determining
whether we are or are not to regard and speak of a hyperthermia
as febrile.
Microorganisms, both vegetable and animal, constitute a most
important group of these pyrogenic substances, acting especially
through their chemical toxic products. It is this fact which ex-
plains why the course of nearly all the acute infections is accom-
panied by fever. It can be promptly induced by infection with
various specific germs ; inoculation with anthrax bacilli or pyogenic
cocci, with trypanosomes or piroplasmata, each occasions a febrile
reaction. After Charrin and Ruffer pointed out that, by injecting
into rabbits cultures of bacillus pyocyaneus which had been
sterilized and freed from living germs, febrile temperature acces-
sion ma}' be induced, a number of observers have demonstrated
that similar effects may be obtained by employing the metabolic
products of a number of other bacteria. This means therefore
that we are here dealing with a group of soluble substances passing
from the substance of the microorganisms into the fluids and tissues
of the affected body, either secreted by the living bacteria or
representing some of the results of disintegration of the bacterial
body (toxines, proteins, alkaloids and a variety of substances of
different composition). According to E. Centanni, practically the
entire group of bacteria produce a practically uniform fever toxine
which he isolated from cultures and named pyrotoxina bacteritica,
and with which he was able to reproduce in rabbits all the main
clinical features of the infectious fevers.
This thermotoxine is, however, produced in varying quantity
by the individual types of bacteria ; injection of definite doses of
some forms of bacteria and culture filtrates occasioning no febrile
reaction ; some only after large doses ; others causing high fever
with the employment of extremely small amounts. Another
feature to be considered is that various kinds of bacteria known
to elaborate thermogenic substances do not act with uniformity
in the production of fever in all kinds of animals, and different
animals show even less uniformity in their susceptibility to the
fever toxines (Krehl) ; from which it may be assumed that the
Pet'cr. 169
p\ rogenetic substances of the different bacteria also liave a
qualitative variation, are just as different and specific as for
example diphtheria toxine and tetanus toxine ( W'assermann I. '1 he
pyrogenetic power of bacteria is not in any way related to their
pathogenicit}- (Kraus) ; there are bacteria of high grade viru-
lence which produce but little febrile disturbance (as tetanus
bacillus), and on the contrary there are non-pathogenic microbes
whose cultures nevertheless exhibit a (transitory) pyrotoxic
activitv. as those of bacillus prodigiosus and bacillus subiilis
(\'oges). A number of bacterial products when administered to
the smaller experiment animals in but small doses give rise tO'
increase of body temperature, while in large doses they cause it to
fall below normal; and there is a notable peculiarity in the action
of the substances obtained from cultures of the tubercle bacilku
and the glanders bacillus, very small doses of extracts of these cul-
tures causing fever to occur in tuberculous and glanders animals
but not in healthy ones (in the latter, however, a rise in tempera-
ture is produced when the extracts are given in large doses, which
would on the contrary produce depression of temperature in the
diseased animals with symptoms of fatal intoxication).
According to the experiments of Matthes the sterile, salt-free
hydration products of the albumen molecule, protalbumose,
deuteroalbumose, peptone, act in the same manner as the last named
agents, and it seems that in the protoplasm of all living cells
there exist certain proteid substances capable of inducing temper-
ature accession when injected or when set free in the body (Kraus,
Wassermann). By subcutaneous and intravenous injection of
blood or blood serum of a different species of animal, or by intro-
duction of iodide of potash solution or pure distilled water it is
possible to cause a rise of temperature, a phenomenon depending
upon the h^emol\tic influence of these substances, either the
hemoglobin thus freed or the fibrin ferment formed occasioning
the increase of temperature. The injection of fibrin ferment
promptly occasions marked increase of temperature, true also of
other ferments (pepsin, rennet, pancreatin. invertin) as well as
of the animal secretions (milk, urine). The purified enzymes are
apparently inert: but the same ferments in impure state (but
sterile), presumably containing some albuminous admixture, induce
an elevation of temperature from which it may be inferred that
the active principles are some type of albuminous body (Krehl).
However, the influence is not the property of any one single albu-
170 Temperature Distiirhances.
minous substance, various proteins, bacteria and other microorgan-
isms, the products of disintegration of red and white blood cor-
puscles and other tissue elements all possessing the same influence.
Foreign albuminates alwa_ys give rise to the development of
protective processes, of phagocytosis and the production of specific,
antibodies. Certain organs like bone marrow, spleen and lymph
glands are stimulated to special activity by the presence of these
foreign substances manifesting cellular hyperplasia (mitotic nuclear
figures) and probably producing special secretions. This increase
of their physiological activity is necessarily associated with
increased metabolism and the latter must occasion elevation of
temperature. The relation between the production of antibodies
and febrile attacks is very striking in many of the infectious dis-
eases. For example in case of pneumonia in human beings it is
known that in the course of the fever protective bodies are formed
in the bone marrow and that the fever diminishes as these sub-
stances begin to manifest their bactericidal action. After the crisis
these protective substances are found in considerable amounts in
the blood (Klemperer, Wassermann). In recurrent fever of man
the onset of the fever takes place as soon as the organisms appear
in the blood ; protective bodies are then formed by reaction of the
body cells and with their accession to the blood the microorgan-
isms are destroyed and the fever falls ; if these are removed the
spirilla return from their foci of deposit to the blood and the fever
returns. In other examples the beginning, rise and fall of the
fever are apparently dependent upon definite stages of develop-
ment of the infectious agents : in human malaria the fever begins
as soon as the parasites reach the phase of sporulation and is
checked if by the administration of quinine the maturation or rup-
tilre of the sporulating organism is prevented.
The connection of fever production with substances foreign to
the body (infectious and toxic) is so clear that if an animal mani-
fest febrile symptoms it seems a permissible conclusion that there
must be infectious or toxic substances circulating in its blood.
Often the fever is the only manifestation of the disease appreciable
during life to indicate the existence of an infection {essential
infectious fever) ; usually it appears as a precursor of other symp-
toms of the infectious cause {prodromal fever), or accompanies
local or general disease processes {secondary fever, traumatic
fever, pycviiiic, scpticcrmic, hectic fever, intfannnatory fever) ; and
may also develop after the employment of therapeutic measures
Fever. 171
which int;ro(hace inrogenctic substances into tlie body or occasion
their production in the system {infusion fever, deprivation fever).
The question has been asked whether fever is useful or harm-
ful to the body and whether it may not possibly have the definite
purpose of rendering infectious and toxic matters harmless. From
the fact shown b\- various experiments that temperatures from 40 to
42" C. may inhibit the growth of a number of bacteria, attenuate
their virulence or actually destroy them it has been conjectured
that the same effect is produced in the body by febrile h\perther-
mia, that the fever, "purifying by tire" as it were, is in reality a
factor in causing recovery. There are a number of experiments
which seem to uphold this idea : small experiment animals have
been showm to bear better (that is do not die as soon from) diph-
theria, chicken cholera and other infections if kept in an incubator
at 41 to 42° C. than when left in a lower atmosphere. The resistance,
however, does not depend upon the direct action of the higher tem-
perature on the microorganisms, as Wassermann has pointed out,
but upon the fact that the bod\- when kept warm is better able to
permit the action of its natural protective mechanism (phagocyt-
osis, antitoxine production). There is no evidence of any pur-
pose for the increased temperature: this is only 4 symptom and
a result of the exaggerated metabolism, and the favorable outcome
is brought about b\ the reactive production of antibodies. In a
similar manner the complications and sequels of a fever are not
to be imputed to the elevated temperature. C3f course, it does
cause increased rapidity of cardiac action and of respiration, loss
of appetite and perhaps parenchymatous changes : but the real point
of the fever is in the severity of the infection, in the toxic action of
the infectious microorganisms which contribute the real danger, and
the elevation of temperature is only the index of the latter. The
restilt of measures having for their purpose the reduction of tem-
perature (cold water treatment and antipyretics) is not in conflict
with this conception of the relative inutility of the tem-
perature in fever ; such m^easures manifest their beneficial influence
not only by reducing the temperature but also by inhibiting the
causes and by diminishing metabolism.
Stages of Fever. The febrile course is usually separable into a
number of periods or stages. The inception of the fever, its initial
period (pyrogenetic stage, stadium incrementi^ chill stage) mani-
fests itself by general symptoms of fatigue, weakness, rough.ening
of the hairy coat, loss of appetite and rise of the internal tempera-
1^2 Temperature Disturbances.
ture. In a number of affections it is marked by cJiills (trembling
and shivering throughout the body ) : during the paroxysm, the
internal temperature_is elevated from the first and continues high,
while the skin of the peripheral parts shows a lack of uniformity
in temperature, the feet, for example, being cold, the muzzle in
cattle and the nose in dogs, hot. The action of the heart is acceler-
ated, the pulse correspondingly increased in frequency, small and
tense ; and the respirations increased in number. The cause of the
chill is to be found in the spasmodic constriction of the cutaneous
vessels occasioned by the poisonous products of the infectious
agents: the loss of appetite and the occasional vomiting (in dogs)
may also be ascribed to a toxic influence acting upon the nervous
centres (Blumenthal ). The initial or chill stage lasts for from
half an hour to two hours, or, in cases where chills are absent,
for several days. The heated stage which follows, varying in dura-
tion with the particular disease from a few hours to a number of
weeks, is that in which the temperature elevation reaches its maxi-
mum level ; it is known as the fastigiiiin or acme (stadium acmeos).
In the remittant type, characterized by alternations of depressions of
the febrile temperature (reiiiissio)is) and succeeding reaccessions
{exacerbations ), the elevation of temperature manifests a number
of maximal points. The other s}niptoms keep pace with the hyper-
thermia (loss of appetite, increased thirst, general weakness,
diminution of the secretions, acceleration of respiration and pulse
rate, hot, dry skin). The intensity and duration of the fastigium
are expressive of the severity of the febrile disease, and estimated
by the height of the temperature and the strength of the heart's
action. In a -moderate fever the temperature should not rise beyond
40^ C. ; an intense fever is characterized by an elevation exceeding
40" C. A fever in which the cardiac action is strong and the pulse
tension high is said to be sthenic ; where the cardiac beat is weak
and without force and the pulse soft the fever is spoken of as
asthenic.
In the period of febrile decline {stadium dccrcmcnti or deferves-
cence) the body temperature returns to normal and the associated
symptoms diminish in their intensity. In case the fall of temper-
ature takes place rapidly (in a few hours or at the most within
three days), sometimes with marked perspiration and profuse
excretion of urine, it is spoken of as crisis. Sometimes just before
defervescence there are noted special exacerbations of the febrile
state (perturbatio critica) ; incase there is a period of several davs'
Fever. 1 73
duration in wliich tlicre is alternation of notable depression and
exacerbations of temperature it is spoken of as an ainphibolic sfai^e.
Tlie slow and Ji^radual type of defervescence is called lysis or rcsn-
liilinn. The decline of fever is believed to be due to the tornialion
somewhere in the or^-anism (bone marrow, spleen, liver, etc.)
during the febrile process of a large quantity of protective sub-
stances and to the destruction of the pyrogenetic substances present
in the system from the time when these protectives become predomi-
nant. Should the blood become rapidly filled with i)rotective sub-
stances from the sites of antitoxine j^iroductiou or with |)hagocytic
elements from hyperleucocytosis, the change in the case comes on
suddenly (crisis) in the first, or gradually (lysis) in the second
instance. The termination of the fever, at which time the normal
temperature again prevails or merely trifling variations continue,
brings back the appetite ; the pulse recovers its softness and even-
ness ; the functions of all the organs proceed as before the attack :
and there persist for a tiiue only weakness and general debility.
This is known as the period of convalescence. In case, however,
the febrile disease go on to an unfavorable termination, and there
appear irregular fluctuations in the temperature curve, a sudden
rise far above nonual or a subnormal depression, with signs of
impending death, we are then dealing with what is known as the
premortal [nioribund] stage [cf. p. 95].
When the stages above mentioned succeed each other in the
order indicated the course of the fever is said to be regular or
typical: if there be variations, it is said to be irregular or atypical.
If in this regular course, a fever should continue for only a few
hours or for a day, the whole process ending within this time, it is
described as an ephemeral fever. A fever of one or more weeks'
duration with a temperature curve showing daily an evening rise
and a morning fall comparable to those of the nonual body tem-
perature, but at a level above that of the nonual internal tempera-
ture, is said to be a continued fever: where the depressions and
exacerbations are more pronounced it is called discontinuous or
remittent. When the variations in temperature are so great that
between the times of high temperature accession, which take place
periodically (febrile paroxysms) Ahe^e occur periods of absence of
fever (apyre.via). the fever is said to be of an intermittent or
recurrent type.
Metabolism in Fever. 'J'he causes of fever are known to give
rise as a rule to increased destruction of the albuminates, esseti-
174 Temperature Disturbances.
tially an increase of oxidation (increased consumption of oxygen).
As a result of this heat production is increased.
There is, however, a well defined type of fever in which there is
no recognizable increase of heat production (Krehl), the febrile condition
resulting solely from diminution of heat dissipation.
This increase exists at the time of the initial stage and is marked
during the chill, the muscular contractions in this phenomenon add-
ing to the heat production. Heat dissipation is also increased in
fever; otherwise the temperature would continue to progressively
rise throughout the attack (Krehl). Dissipation is, however, less
than production. (It is only in the period of invasion that heat
dissipation is with any uniformity diminished, in the chill, by the
constriction of the cutaneous vessels.)
The increased albumen destruction by oxidation is shown by
the increased nitrogenous output in the urine, the increased elimina-
tion of carbonic acid and the lessened oxygen elimination. Coinci-
dently there is a retention of water ; Senator has shown that of the
ingested fluids, only one-third or less appears in the urine, a cir-
cumstance which cannot be explained by the amount lost by evapor-
ation from the skin (v. Leyden). The water may be supposed to
be used to keep in solution the large accumulation of products of
the increased metabolism in the tissues ; this idea receives corrobora-
tion in the fact that after the crisis when the retained substances are
being eliminated there occurs a polyuria without increase of inges-
tion of water (Blumenthal). A large part of the nitrogen produced
by the increased albumen destruction must come from the blood, the
disintegration of the latter being the cause of the high proportion
of potassium and urobilin met in the urine (Blumenthal). The uric
acid excretion is also increased, from which may be inferred a
marked destrtiction of the nucleo-albumens (Blumenthal).
Probably not all of the products of tissue disintegration are
eliminated from the system or consumed ; the urine does not con-
tain everything which underwent disintegration in the organism.
Probably during the fever some of its products are employed for
tissue reconstruction or in the formation of antitoxines. The
chlorides, phosphoric acid and sodium are found in the urine in
smaller proportion than normally. AA'ith the critical decline of the
fever, the tissue destruction ceases and the organism rapidly re-
stores its nitrogen-containing structures, the nitrogenovis excretion
falling below its intake and a distinct increase in body weight
ensuing (Blumenthal). Only in cases in which, because of re-
Fever.
175
sorption of exudates (pneumonia), there is a large amout of
nitrogen to be disposed of, is its elimination in the urine main-
tained above the usual proportion. As the result of the degenera-
tive changes which have taken place, fatty acids appear for a time
in the urine (fatty degeneration) ; and after a time sodium chloride
may be again found in large amounts.
In all febrile affections the kidneys are particularly likely to
be aft'ected. The poisonous bacterial products, and the substances
of greater or less toxicity which come from tissue destruction are
irritative to these organs, and render the glomeruli and renal
epithelial cells permeable to album.en. As a rule an albuminuria
of variable importance is established, an evidence of the existence
of a nephritis of an exudative type.
lZ3A5 6'ynp)0// 12 13 /^ 15 16 f? /8
Fig. 18.
Continued fever; epidemic pleurisy in a five-year-old horse (after Priedberger—
Frolmer) .
In some cases acetone is found in the urine, considered by some
authorities as indicative of fat consumption, but regarded by Bknnenthal
as originating from proteid through bacterial influences and oxidation.
[Acetone, diacetic acid and oxybutyric acid are all occasionally encoun-
tered in the urine in febrile states, just as in case of diabetes mcllitus,
and there is reason to suppose that in both conditions faults of carbo-
hydrate metabolism underlie their occurrence, although it is possible that
such substances may in less direct manner be products of fat or proteid
destruction, as above suggested.] The origin of diazo bodies (diazo
reaction of urine) has been attributed (Ehrlich) likewise to bacterial influ-
ences (in man in tuberculosis, typhoid fever, measles).
The existence of fever is most efficiently detected by thermo-
metric measurement of the body temperature. This is performed
in animals by introducing a suitable thermometer into the rectinn,
or in females into the vagina, allowing it to remain for five minutes,
after which the degree of temperature may be read off. A single
176
Necrosis.
observation may establish the presence of fever, but observations
made at regular intervals afford more complete and certain informa-
tion as to the existence and characteristic features of the fever and
are necessary in following its course. The normal temperature
characteristic of the animal must be known, together with the
subnormal and hypernormal (non-febrile) ranges when in health;
the differences peculiar to species and age, and the daily physio-
logical fluctuations. These are dealt with in works on normal
physiology, to which reference may be made (Cf. Friedberger and
Frohner, Lchrb. dcr kliniscJicii UntcrsitchiDii^sinctliodcii f. Tier-
ijrcfc).
The course of the fever can be luost satisfactorily followed bv
42"
^
/
2
3 V 5 <
5 7 s ;? /? // /f !3
\ ' '
1
\ 1
!
\ A
^Z"
/' \ \ 1
1
1 \ \ ft
1
1 \ \ i\
1 ■
'1 j
1 ' 1 \ 1 \ 1 1
1 ■
A '
1 \ 11
^0^
1
11
1 1 \ 1 \
fV ,
/ ii
\i \ r I
1
/ 1
1 U j \ \
/ 1
111
A
/ 1
'■11
^t it ^ ±i i -^
59°
y I
■ 1 ' \ i
A
11
1 / A 1
1
1
T7 \\ -^ -^^
1 |i
^' 1 M A 1
1/
j^vrX-t^ It
ZH'
^
izZT rr . x
i
i
_4_> _/_ _\ A ,
1
1
1/ y \ ^
;
1
\j y ^
H ^^ -\
1
il"
_J
._!_
1 ' '
Fig-. ]9.
llemittent fever : an infectious fever in an eight-year-old mare. (After Fried-
berger — Frohner. )
recording the degrees of temperature obtained from time to time
by thermometric reading upon a chart marked out with abscissa
lines, each as a point [with corresponding height from the normal
line according to the number of degrees of temperature observed],
thereafter connecting these points so as to construct a scale or
curve of the temperature range upon the chart, the temperature-
or fever-curve.
Necrosis.
Complete death of organs or parts of organs within the living
body, local death, is known as necrosis (^ viKpwais. death) ; when
this process of disintegration has associated with it the features
Causes of Xccrosis. 177
of degeneration it is also indicated by the term necrobiosis. Be-
tween the degenerations (the retrograde metamorphoses) and the
necroses it is impossible to draw any sharp line of difference. (There
are in addition a number of other expressions in use for the special
types of necrosis by which the death of a part in the living body is
seen to occur, which are often emplo\ed indifferently as synonyms —
vide infra). Even in normal life in the interchange going on in
the course of the physiological processes there is a certain amount
of the cellular material which is being broken down in the tissues,
consumed and replaced by new cells. The epidermal cells of the
skin are continually undergoing keratinization. later desquamat-
ing as dead structures, and newly formed cells from the stratum
Alalpighii take their place to undergo in their turn the same
change. In the same way the epithelium of various glands die
and contribute their own substance to their secretions, as the cells
of the sebaceous and mammary glands. The blood cells are also
perishable elements, some being all the time in course of disintegra-
tion and death, the formation of new cells continually proceeding
in the h?emopoietic parts (bone marrow and lymph glands) to
compensate for this loss. Other physiological instances of local
death are also seen in the loss of the milk teeth and in the nnunmi-
fication of the umbilical cord.
Pathological conditions capable of causing local death are
usually such as interfere with the nutrition of the cells and tissues^
and render the metabolic interchange between them and their
surroundings impossible. The most common is some interruption
of the blood supply : as thrombosis and embolism ( both of which
occlude the vascular lumen). ru])ture of the vessels, separation of
the cells or tissues from their sources of supply (traumatic, or the
undermining of the skin in case of subcutaneous suppuration), or
compression of the tissues which interferes with the entrance of
blood to the part. If the blood is unable to gain access to an
organ or some portion of an organ, no more than mere microscopic
parts of it can be maintained by the lymph ; with the exception of
the cornea and the cardiac valves, for which the lymphatic fluid
is the principal source of nutrition, no organ can withstand a pro-
tracted interruption of its blood supply. This is especially true
of gland cells ; according to Litten two hours are sufficient after
ligation of the renal arteries in rabbits to cause necrosis of the
renal epithelium, even though after removal of the ligatures the
circulation be re-established. Ehrlich and Rrieger 1 cited from Birch-
178 Necrosis.
Hirschfeld) observed a destruction of the gray matter as a result
of withholding the blood supply for a single hour in case of the
spinal cord. Interference ^Vith the venous outflow, if marked
enough to cause stasis in the capillaries, is also followed by nu-
tritive disturbances which terminate in gangrene.
The vitality of the tissues may also be overcome by chemical
and thermic influences producing coagulation or liquefaction of the
proteids and thus either directly or indirectly rendering the pro-
toplas^i incapable of appropriating nutrition and giving off its
metabolic products, as well as interfering with the interchange of
gases (burns, freezing, poisons like the acids and alkalies, the
digestive juices, bacterial poisons). Evaporation of moisture, as
in case of evisceration, causes necrosis of the exposed organs partly
by drying the protoplasm of the cells, partly by desiccating and
stagnating the blood and lymph. [An important adjuvant cause
of necrosis is also seen in the destruction of innervation of a part,
as may be observed in the massive and fulminating necrotic changes
met with in cases of lesions of the spinal cord at points of pressure
below the level of the spinal injury, the well known gangrenous
decubitus of such individuals. In some measure here, disregarding
the important pressure factor, the necrosis may depend upon
vascular changes due to the ner\'>ous lesion ; but there are reasons
for believing a more direct cellular failure results as well, from
the loss of the nervous trophic control.]
As a general rule the occurrence of necrosis is to be attributed
to a dual influence, the causative lesion having both a direct destruc-
tive power upon the tissue and at the same time interfering with
the circulation of its fluids.
The characteristics of necrotic and dying parts vary with their
structural peculiarities, the proportion of moisture in the organ,
the relation with the uninvolved parts, and external influences.
Dense structures like bones and teeth are subject to a simple
necrosis; these and the dense elastic tissues are extremely resistant
to physical and chemical agencies, retaining long after complete
death their form and general appearance as in life. Soft tissues
also, like the epithelium of the stomach, if killed by poisons having
disinfecting power (carbolic acid poisoning), may remain without
material change, with but little alteration of form, just as an'a-
tomical specimens preserved in alcohol or formaldehyde solutions.
In such instances the necrosis is primarily recognized by the reac-
tion in the surrounding healthy structures in their effort to isolate
the dead part (sequestration).
Dry Gangrene; Coagulation Necrosis. 179
Necrosis with desiccation and shrinkage {mortiUcatio sicca,
mummification, dry g-ang'rene) results from deprivation of moisture
by evaporation, compression, chemical action or prevention of
the entrance of iiuids to the part. A physiological prototype is ob-
served in the shriveling of the umbilical cord which is converted
in the course of a few days after birth into a dry brown parchment-
like mass. On a small scale desiccation from loss of moisture may
be seen in the formation of crusts (eschars) on the surface of
wounds and ulcers, upon which usually the exuded tluid, pus,
extravasated blood and a portion of the underlying tissue (cutis,
mucous membrane) are dried up into brown or black. crusts and
scabs (eschars from caustics, scabs of wounds and ulcers). Mum-
mification of deeper and more extensive type, changing the tissues
into a wrinkled, brown or black, tough, leathery material, or into
a completely dried hard mass, may affect the extremities, ears,
feet, tail or quite frequently the skin, as the result of the action
of poisons or complete exclusion of blood from the part involved,
as in swine-erysipelas, ergotism or occlusion thrombosis. A com-
mon example of this variety of necrosis is the leather-like mummi-
fication which takes place in a dead fcetus retained with its amnion
in the uterus in case the amniotic fluid has all drained away or
been absorbed, putrefaction being impossible because of the absence
of the necessary bacteria, the fcetus becoming a veritable mummy,
enclosed and compressed in the uterine sac.
Necrosis with coagulation, coagulation necrosis. Where
necrosed tissue assumes the character of an albuminous coagulate,
being changed into an elastic, dense, dull white, grayish yellow or
yellow, and more or less dry mass, the type of destruction i?
described, following Weigert, under the term coagulation necrosis
or sometimes caseation. This metamorphosis is peculiar in that
the dead area does not seem diminished or shrunken and has ap-
parently not suft'ered loss of its fluids, but rather tends to be some-
what increased in volume, projecting slightly above the surround-
ing structures. This swelling of the dead tissues depends upon
the diffusion of Ivmph from the adjacent parts through the necrotic
substance, saturating it. After this has taken place the coagulation
occurs in the same wa}- as in the formation of a blood clot, by the
action of an enzyme which is either derived from the necrotic cells
or originates from the primary cause of the necrosis. This variety
of necrosis is often induced by certain infectious germs (tubercle
bacilli, necrosing bacilli, bacilli of swine plague) which seem to
i8o Necrosis.
give off a ferment into the tissues ; it is also frequently seen in
infarcts caused by embolism and in new growths anaemic because
of deprivation of their blood supply, in which necessarily it must
be supposed that there is produced by the tissue disintegration
some substance comparable to fibrin ferment.
The saturation of a necrosed tissue by lymph is quite possible if
evaporation is prevented (for this reason coagulation-necrosis is most
commonly seen in parts enclosed from the air, internal organs and mucous
membranes) ; in moist, necrotic tissue the blood circulation is, it is true,
completely in abeyance, but the diffusion of the lymph and the immigra-
tion of lymph corpuscles may be expected.
[Many, among whom the editor would include himself, dif-
ferentiate between coagulation-necrosis and caseation, regarding
the latter as essentially a further destructive change, an advanced
fatty degeneration of the necrotic substance. Where an area of
coagulation necrosis, or what is practically the same thing, hyaline
degeneration (at least some forms of the latter), is retained in the
tissue and is not further disintegrated by liquefying processes
it becomes the seat of f^tty degeneration and is broken down into
a fine detritus, oil droplets, and often contains crystals of cholesterin
and fatty acids. When this is of advanced degree it is described
imder the name of caseation. Two varieties are commonly de-
picted, dry and moist. Grossly a dry cheesy focus is usually de-
fined, often encapsulated, whitish or yellowish in color, of a friable
or crumbling consistence, reminding one much of dry "cottage
cheese" ; and imder the microscope appears as a uniformly granular
mass, occasionally exhibiting a few persisting fragments of the
original cellular elements, scattered oil droplets and crystals, and
when stained selects diffusely the acid stains like eosin. A moist
cheesy focus (which may represent an area from which the moisture
has not been absorbed or which may be determined from a dry
focus by imbibition of lymph and by liquefaction of its own sub-
stance) is usually not so clearly defined as a dry caseated area, is
paler in color, softer in consistence (pasty or mushy, like "cottage
cheese" mixed with milk) ; and microscopically presents the same
appearance as mentioned for the dry variety with the additional
feature that usually the fat globules and crystals are more numer-
ous. Caseation is especially common in tuberculous and syphilitic
lesions, a form of coagulation (a variety of infectious hyalin de-
generation) preceding the fatty change ; it however may be met
as a late change in a varietv of lesjons, as in atherotna, in the ^^.n-
Liqiuiactiun-Xccrosis: Moist Goiii^rcnc. i8l
tents of a "residual abscess," etc. The moist cheesy matter is the
well known "pyoid" material of "cold abscesses." In dry casea-
tion calcification is apt to occur as a terminal change.]
Necrosis with softening, liquefaction-necrosis. Necrosing tissues
which are poor in coagulable albuminates but rich in fat and fatty
substances, and w^hich contain considerable fluid or are in position
to obtain it from the entrance of lymph, usually break down into a
soft pulpy mass or into a milk-like emulsion. The process may
occur as a primary one, as in the brain and cord, because of the
large amount of myelin contained by these parts (as also
seen in infarcts and haemorrhagic effusions) ; or it may occur
as a secondary change where an originally coagulated necrotic sub-
stance becomes macerated after fatty degeneration or saturation
with serous fluid, or is softened by the liquefying products of
various bacteria (soft caseation, purulent softening). [The type
of liquefaction here described is essentially the same mentioned
by the editor under the name of moist caseation in the last note.
There is a form of liquefaction however in which the fatty elements
mentioned by the author are absent or at least not important, the
necrotic tissues becoming converted into a clear, watery fluid. This
resultant fluid may in a greater or less measure be the product of
actual conversion of the solid substance into liquid ; in part it is
made up of lymph, which has penetrated the part. The disappear-
ance of the solid substance may be a mere solution of the soluble
portions in the absorbed fluid, but in addition the insoluble portions
may be rendered soluble or changed into fluid by the influence of
poisons (often bacterial), heat or cold or by enzymes originating
in the necrotic tissue itself or generated by the surrounding living
cells or by microorganisms present in the mass. Such material
is apt to be removed from the affected part, usually by absorption,
or may be retained within a capsule as a cyst.]
Necrosis with putrefaction, moist or putrid necrosis, gangrene
(^ Tct^ipaiva ) , Sphacelus (6 cr0dKe\os from <T<pd^€Lv , to kill), phagcdccna
(r, <t>a-yi^aLva) . Whcu uccrotic tissuc rich in fluid is open to access
of putrefactive bacteria a putrid decomposition sets in precisely as
in case of a piece of meat or a cadaver. The gangrenous area is
soft, pultaceous, filthy, dark brown to green or dark red in color,
stinking and permeated by putrid gases. The putrefactive bacteria
gain entrance from the surrounding air to the softened part through
lesions (from wounds or ulcers) of its protective covering (epi-
derm, skin) or from the canals lined by mucous membrane, upon
1 82
Necrosis.
the surfaces of which' there is apparently always present a rich
variety of bacteria (pharynx, stomach and intestines). The
putrefactive germs may be carried from such situations by the
lymphatic and blood streams into the internal organs, where new
foci of the putrefying process result from embolism. Tissues the
seat of marked hsemorrhagic infiltration and those with large lymph
spaces, are especially likely to become gangrenous, the stagnating
blood and rich supply of moisture favoring the multiplication of
the putrefactive organisms. The discolored liquid of the decom-
posing part is known as putrid icJidr.
Fig-. 20.
Microscopic section through a necrotic area in liver of cow; tlie border of
the coagulated necrotic material close to the normal tissue sliowing a
zone of cellular infiltration.
Microscopically, the principal change exhibited by necrosing tissues
is the disappearance of the nuclei, shown especially by their partial or
complete loss of the staining quality with the ordinary nuclear staining
reagents (hsematoxylin, carmine stains). Sections of normal tis.sues
present their cells and nuclei stained with clear definition and distinct
color; necrotic portions look as though they were without nuclei, and
either refuse to take the stain or only assume a faint diffuse coloration.
The nuclear changes may consist of a loss of a definite outline, accuinu-
Symptoms of A'ccrosis. 183
lation of the chromatin in fragments or clumps of irregular size and
a variety of angular or globular shapes in the nuclear stroma along the
periphery (karyorrliexis), or its escape into the cytoplasm (pyknosis of
Schwann and Albrecht), or its complete dissolution (karyolysis of Klebs).
Besides this fragmentation of the nuclei, displacement and solution of their
chromatin, there are also to be observed changes in the cellular proto-
plasm and in the intercellular substance, resulting in the loss of specific
structure. The cell protoplasm and supporting tissue are changed into
a turbid, lumpy, more or less homogeneous mass, in which the individual
cells can no longer be recognized. In case lymph diffusion in the
necrosed tissue follows and coagulation occurs, the dead area seems to
be filled with apparently • swollen, shining, strongly refractile, fibrin-like
masses of transudate (fibrinoid of Albrecht and Schwann) of lumpy,
trabecular or reticulate appearance. In necrosis with softening the de-
structive change is usually recognized by the fat droplets (fatty detritus) ;
and the ichor of gangrenous parts shows, in addition to shreds of the
various tissues, the remnants of the liquefied red blood cells in the form
of yellow and dark brown granules and clumps of blood pigment, and
sometimes such solid decomposition products as leucin, tyrosin, margarin
and triple phosphates, together with an enormous number of putrefactive
microorganisms.
Symptoms of necrosis. Local death of tissues causes their com-
plete loss of functional ability. \Mien the necrosed focus is of
small size and situated in the midst of healthy functionating tissue
of the same type and having the same character of activities,
there are often no symptoms, as in case of anaemic infarcts of the
kidney and spleen. The distribution and production of heat ceases
in the necrosed part with the cessation of the blood supply ; gross
areas of gangrene on the periphery of the body, as the skin, ears
or extremities, feeling cold. Because of the coincident death of
the sensory nerves within the gangrenous area the latter is itself
'analgesic, although the inflammatory reaction at the periphery
causes sensations of pain. Gangrene in its inception is further
recognizable in parts of the body exposed to view by the dark
brown, dirty dark red to dark green discoloration, by the desic-
cation, or by its putrid odor. In this latter form, that is, gangrene,
the parts assume a doughy, flabby consistence; and if the gases
cannot easily escape and accumulate deep in the meshes of the
tissue there may be felt by light palpation a crackling {crepitation)
of the breaking or displaced gas bubbles. The presence of the
gases gives the putrefying tissue a bloated, spongy appearance, the
cut surface full of small holes (gangrenous emphysema) ; together
with the ichorous fluid these gases often accumulate under the
epidermis in cutaneous gangrene and cause the formation of gan-
grenous blebs.
184 Necrosis.
Ter))iiiiatwiis. Dead tissue acts upon the surrounding healthy
structures as a foreign body, causing both mechanical and chemical
irritation ; in consequence of which an inflammatory reaction is
uniformly established in the adjacent healthy tissues. At the
periphery of the necrotic part there may be observed an inflam-
matory zone marked by greater or less inflammatory hyperaemia
and accumulation of leucocytes. From the action of the fluid
exudates penetrating the dead tissue and of the immigrated cells
removing the necrotic substance, partly by liquefaction and partly
by phagocytosis, necrosed parts of small size may be gradually
absorbed, especially foci softened down into detritus and small
infarcts. At the site of the necrosis there is then left a space, a
defect, which is later filled in by proliferation of the surrounding
tissvie or by inflammatory scar formation. Larger necrotic areas,
or such as apparently cannot be softened (mummified and coagu-
lated portions) resist absorption; these may be circumscribed by
the inflammation, encapsulated or completely separated from the
rest of the body {demarcation, dcuiarcating iiiflammatioi, sequestra-
tion or circumscribed necrosis). In this way while the invading"
mass of leucocytes and other exudates are softening down the tissue
at its borders there is also proceeding an inflammatory prolifera-
tion of connective tissue and blood vessels (fibroblasts, angioplasty
and blood vessel buds) to the formation of a protective wall. If
the dead material be situated at the surface of the skin or mucous
membrane it may be sloughed ofl:' (cutaneous slough), and the
defect repaired either by subsequent proliferation of the adjacent
tissue or by cicatrization. Necrotic parts situated deeply in the
body are surrounded by the demarcating tissues and come to be
enclosed in a dense capsule of connective tissue. Dead fragments
of bone separated from their circulatory supply (bone splinters)
are enclosed by an osteoplastic proliferation of the bone marrow
and periosteum and thus isolated as sequestra.
In case the gangrenous foci contain substances of toxic nature
the necrosis may assume a progressive character from the con-
vection of the toxic products of disintegration and putrefactive
bacteria by the invading leucocytes and lymph stream to other
parts. When the process is reproduced in the immediate vicinity
of the original focus it is spoken of as progressive necrosis or
gangrene ; when the putrefactive organisms are carried in the blood
to distant parts, causing synchronously the same processes in the
latter, these new foci are spoken of as secondary, metastatic gan-
Atrophy. 185
greiioiis foci, embolic ^i:;aiii^rciic. A general putrid intoxication
(saf>rd'i!iia. from ffawpbi , (lecomposed, and ai/ia , blood; mixed
septic intoxication ) may result from the toxines of putrefymg bac-
teria in the blood and the products of decomposition absorbed from
a gangrenous focus ; this is likely to run a fatal course with
symptoms of fever, collapse, marked cerebral disturbances, myo-
cardial degeneration, tendency to multiple haemorrhage, etc. The
poisons arising from putrefying matter or generated by special
putrefactive bacteria have hsemolytic properties and are paralyzant
to the cardiac ganglia or central nervous system.
Examples of this are frequently afforded in case of wounds of
the skin which favor putrid suppuration of the underlying tissue
(tooth bites, punctured wounds from stable forks), in putrefaction
of the retained placenta and gangrene of the uterus, in intestinal
strangulation, deglutition pneumonia and in escape of the contents
of the stomach and intestine in consequence of perforation of the
walls of these organs.
Atrophy.
The term atrophy is employed to indicate a diminution in volume
of an organ or tissue without essential alteration in its structure
and chemical compositiori. It involves a reduction in size of the
cells and tissues (simple atrophy) ; but this often proceeds to an
extent that actual loss of the cells results from their complete re-
gression { numerical atrophy). The name of the process, derived
from Tp6<pos. nourishment, and a privative, means, precisely, loss of
nutrition, and is used because atrophy in the main is due to in-
sufficient nutrition. This latter factor may depend upon the fact
that the cells actually do not receive sufficient nutriment (passive
atrophy) or that they lack the ability to appropriate that wdiich is
offered them (active atrophy), both of which conditions may syn-
chronously prevail and are impossible of definite separation in all
cases.
Atrophy of organs and their elements may in some cases be a
physiological phenomenon, a part of the cycle of their development
and natural wearing out. Certain structures dev^eloped in
embryonic life undergo retrogression even before birth or soon
after, as the Wolffian bodies, the ductus Botalli and ductus Arantii,
the umbilical vessels and the thymus gland. In the period of most
active growth the milk teeth disappear after atrophy of the dental
pulp. Throughout the entire lifetime there is a succession of atro-
i86 Retrogressive Processes.
i.'
phy of worn out, aged cells with replacement by new and func-
tionally capable cells, as the protective epithelial cells, glandular
cells or the blood corpuscles. Dependent largely upon inherited
capacity of length of life peculiar to the individual, sooner or later
a retardation in the cytogenic energy makes its appearance as a
characteristic of old age; this physiological loss of tissue-forming
power leading to shrinkage of the affected parts is termed senile
atrophy. This is particularly noticeable in the sexual glands. The
ovaries dwindle after the discharge of the ova generated in early
life ; no more follicles mature ; the connective tissue stroma and
tunica albuginea become dense and the organs assume a cicatricial
appearance. The testicular epithelium leaves off its spermatogenic
activity, becomes lower and smaller. In the same way in the lym-
phatic structures, the spleen, lymph nodes and bone marrow, the
ability for cellular proliferation is curtailed and hand in hand there
occurs reduction in the formation of blood corpuscles. Even the
skeletal system undergoes considerable atrophy in age. the bones be-
coming more porous and brittle and lose sensibly in weight ; a pro-
gressive thinning of the bone trabeculse is especially notable, probably
caused by increase in a special group of cells (giant cells or osteo-
clasts ; 6(TTiov, bone, and K\a(T(reiv, to break) which are concerned
in the absorption of calcareous matter. The ganglion cells of the
brain become reduced in size. At least in part senile atrophy is due
to a physical wearing out, as when certain structures become dilated
from mere loss of elastic resistive power (elastic fibres which have
lost their tone like a worn out rubber band).
The following pathological conditions productive of atrophy are
to be considered.
I. Lack of use of organs. Repeated physiological stimula-
tion is essential for- the preservation of all cells, keeping cellular
function active by constant use. Cessation of this tvpe of stimula-
tion and the resultant failure of function are productive of atrophy
(atrophy from inactivity). For instance, prolonged fixation of a
limb by skillful bandaging or the immobility from ankylosis of a
joint may be followed by atrophy of the muscles and bones of the
part. As the stimuli are conveyed by the nerve tracts it must be
evident that disturbances in the conductivity of the nerves or loss
of nervous impulse are especially apt to occasion atrophy (neuro-
pathic atrophy). This may be observed in palsies, as those of the
hind quarters (frequently seen in dogs from injuries to the spinal
cord), in which the musculature of the hind legs may be reduced a
Atrophy. 187
third or half in volume from the important loss in size and number
of the muscular fibres. Vice versa, if an organ to which they are
distributed undergo atrophy or be destroyed, the nerves become
atrophic ; the optic nerve atrophies completely in protracted disease
or destruction of its eye.
2. Compression. Continual pressure upon a tissue inter-
feres with growth, hinders the blood supply to it and its lymph
circulation, and directly causes diminution in the size of its cells.
Pressure atrophy is conspicuous wherever unavoidable, protracted
and gradually increasing compression of the tissues obtains. The
renal parenchyma becomes atrophic and eventually as thin as paper
from interference wdth the urinary discharge from the pelvis of the
kidney; nodular tumors produce depressions in the tissues in con-
tact with them ; an iron cavesson makes a deep groove in the nasal
bones; a hoof corn (growth of the horny hoof) causes a corre-
sponding pressure wear on the hoof bone. Many facial malforma-
tions may be explained as the result of amniotic bands being wound
about the jaws in the process of development, interfering with the
further growth of the upper and lower processes of the first visceral
arch. Cysticerci (echinococcus, ccei'iurus) in their growth cause
pressure atrophv of the substance of the organ in which they are
lodged (canurus upon the brain and skull). Even the cellular and
fibrillar connective tissue masses found in chronic inflammation as
well as merely a marked engorgement of the blood vessels may
serve as compressing influences upon the surrounding elements ; the
liver cells atrophy in chronic inflammation of the hepatic connective
tissue and in chronic passive congestion.
3. Deficient Nutrition. A diminution of nutritive supply
obviously must occasion atrophy (atropliy of inanition) . as the
tissues can only retain their dimensions and energy of growth when
proper pabulum is provided them from the blood. Insufficient
nutrition in diseases of the digestive organs which render difficult
the ingestion of food or absorbtion of nutrition, or deficiency of
local blood supply, allow the cells to waste away. In starvation, the
fat of the body is lost (91 to 93 per cent, of the loss in weight) ; and
the musculature (42 per cent, according to Samuel ) antl the cells of
various organs become smaller. According to Manawein in rabbits
the cells of the liver, which average 22.3 micromillimeters in meas-
urement, are reduced to 8.9 micromillimeters in diameter. The
loss of nutrition is an associated factor in pressure atrophy and
neuropathic atrophy.
i88
Rctvogressive Processes.
The loss of volume of the cells in atrophic conditions consists in
part in decrease of their so-called paraplastic substances, partly in
loss of their actively functionating constituents (Ribbert). The
former, including the stored-up nutrient matter (fat, glycogen) and
the cellular secretory products (mucin), are generally used up
without chance of replacement from the blood supply or from the
protoplasm ; the above-mentioned diminution of size of the liver
cells, for example, resulting, or of fat cells which after loss of their
Fig-. 21.
Fattv infiltration of tlie sural muscles in pseudoliypertropliic musouhir atropliy ;
X 220. (After Tlioma.j
fat are found shrunken into simple connective tissue spindle cells.
The functional substance, as the contractile substance of muscle
cells, undergoes metabolic alterations resulting in diminution of
its bulk. It is difficult to make out how intercellular substances
come to undergo the observed solution and removal, as it cannot
be here assumed that it is simply carried off by the lymph, the
appearance of giant cells indicating clearly that the processes opera-
tive are of complicated nature. In the bone marrow the presence
and increase of these elements seem to be related with the removal
Atrophy. 189
of the hard bone substance, the calcified lamell?e being Hterally
gnawed away by them. In addition muscle undergoing atroplT>' is
apt to show proliferation of the muscle nuclei, the sarcolemma
sheath often being full of nuclei and giving the impression of multi-
plication from lack of tissue pressure (lack of tissue tension) within
the empty sheath, as an associated phenomenon. This same ten-
dency to fill up spaces may also be observed in the fat cells, in
which, after the fat has been used up, there often accumulates a
watery or mucinous fluid, giving the adipose tissue a loose gelatin-
ous character (dropsical fat atrophy, often met in old horses in the
epicardium). Sometimes succeeding an atrophy in one tissue a
hypertrophy may take place in another, adjacent tissue; as when in
atrophy of muscular fibres the resulting space comes to be occupied
by proliferation of fat cells (atrophia miisculoruni lipoiuatosa).
The deposition of the brownish pig-ment granules accompanying vari-
ous atrophies (muscle, heart, hver, ganghonic nervous cells) is as yet
not satisfactorily explained. [There is no doubt, however, that in most
cases at least, this pigment is of haemic derivation, although the substance
has been in some degree modified by cellular metabolism, and may there-
fore be spoken of as autochthonous in conformity with its usual classifi-
cation. It is a common feature of atrophic parts, as might well be expected,
both from the importance of poor blood circulation as a causative factor
and also from the diminished support afforded the capillary walls of
the wasted tissue, that some degree of passive hypera;niia should prevail;
and it may be noted that the degree of this pigmentary change is usually
in direct relation with the degree of such congestion.]
Anatomically atrophic parts are usually characterized by dimin-
ution of volume, poor blood supply [poor circulation, not neces-
sarih- poverty of amount of blood present, however], loss of
their adipose tissue, by a tough, dry appearance and by the assump-
tion of a peculiar grayish tint sometimes approaching a brown .color.
The general bulk of the part may, however, be maintained by the
compensatory occupation of the space caused by the wasting of
its proper constituents by fat or connective tissue. Organs which,
because of their situation or the density of their peripheral structure,
are incapable of diminution may. however, manifest the presence
of atrophy by loss of weight, as the bones and lungs (osteoporosis
and emphysema''').
Atrophy invariably causes loss of function. Atrophic muscles
eventually are incapable of motion; glands secrete less efficiently;
bones become brittle: nervous structures lose their irritability and
♦For details of these conditions c.f. Kitt. Lehrb. (J. patliol. Anatomie i?-
ffaustiere, II. Aufl., Enke. Stuttgfirt, 1902,
190 Retrogressive Processes.
power of nervous conduction. Its consequence to the life of the
individual varies with the importance of the affected organ.
Atrophy of one of the bilaterally situated organs may be corrected
(compensated) by hypertrophy of the other, as in atrophy of one
kidney or of one lobe of the thyroid gland.
General atrophy of the organs involving the musculature, the
general fat of the body and the glands, associated with anaemia and
resulting from general disturbances of nutrition, is known as
cachexia (i] Kaxe^la, a bad condition; from ij ?|ts, condition, and *
KaKbs , bad), or when a phenomenon of old age, as marasmus
(tiapalvu, to fade).
Albuminous Degeneration or Cloudy Swelling.
Abnormal metabolic processes and lesions of the cellular proto-
plasm may often manifest themselves by increase of cellular volume
and the appearance of densely packed fine dust-like albuminous
particles in the cytoplasm, with consequent obscuration of the .
nucleus and the production of a turbidity in the cell substance. By
treatment with acetic acid (two per cent.) or potassium hydrate
(one per cent.) these granules are dissolved and the nucleus be-
comes clearly visible. Their solution in excess of acetic acid, brown
coloration with iodine and acquirement of a bright yellow tint
with nitric acid (xanthoprotein reaction) indicate the albuminous
character of these granules. Various cells, particularly those of
glandular type, are normally granular, but as a rule the nucleus is
easily made out and the cells are of their fixed size and shape ;
while the pathological granulation is distinguished by the swelling
and irregularity of outline of the cells and by the loss of their nor-
mal structural characteristics. In muscle fibres, which show the
change particularly well, the transverse striations are lost and the
myoplasm is filled with fine dust-like granules reminding one of
particles of India ink; hepatic and renal epithelium looks swollen,
expanded beyond the physiological limits, the former no longer
arranged in columns (spoken of as dissociation by Browicz), the
renal cells narrowing the uriniferous tubules to occlusion.
In sections this turbidity is usually not easily observed, being cleared
up by the processes of preparation (alcohol, xylol, etc.). The structural
lesion may also be inferred in cloudy swollen cells by the disappearance
of Altniann's granules (bioblasts). (Altmann claimed that in the cells
of the liver and kidneys there are fine granules around the nucleus ar-
ranged in regular rows, which could be uniformly demonstrated by certain
staining methods. In cloudy swelling these granules are no longer recog-
nizable.)
Cloudy SiccUijig.
191
This process, known as cloudy srvelliiig, albuiiiiiioiis turbidity
or albuminous degeneration, first described by Virchow, occurs
principally as a result of toxic influences, both definite poisons
(phosphorus, arsenic) and the toxines of infectious processes
(diphtheria, septicaemia), and, too, from autointoxication from in-
flammatory changes. It may be regarded as an expression of dis-
turbance of metabolism caused by such toxic action, with impair-
A
Fig. 22.
A, Cloudy sv.-elling-; B, Complete degenei--
ation of striated muscle fibres. In
B the middle fibre is normal, that to
the left in early, and that to the
right in advanced degeneration;
X 250. (After Perls.)
m
Fig 23.
Muscle of horse (htemoglobin-
aemia, 7 hours after the at-
tack); a. normal fibre; b, tur-
bid and granular fibre; c,
hyaline degenerated fibre.
(After Zschokke.)
ment of the elaboration of the nutrient matter appropriated b\
the cells. Either the protoplasm is incapable of assimilating the
albuminous bodies brought to it and they therefore accumulate m
undissolved condition; or, as Mrchow assumed, the cell is in a
condition of metabolic irritation in which there occurs an ex-
cessive separation of its albumens ; or it is a beginning cellular dis-
integration with formation of modified albumens in the tissue,
which are with difficulty soluble. [To a certain extent it seems
192
Retrogressive Processes.
probable, too, that the swelling of the cells is referable to an ex-
cessive presence of fluid, a cellular dropsy.]
Functional disturbances are occasioned by cloudy swelling, well
seen in the diminished contractile power in muscle. It is a repara-
ble process (recognizable in renal disease) provided the toxic sub-
stances which occasioned the protoplasmic fault are removed.
Anatomically organs which are affected by albuminous degenera-
tion are usually less transparent than normally because of the
turbidity of their cellular constituents, are more or less grayish or
clay-colored, dry, friable, soft, and look as if they had been scalded
or cooked.
The condition under discussion is very distinctly met in the psoas and
thigh muscles of the horse in myopathic hemoglobinuria, in the myocar-
dium in various infectious diseases (as pleuropnuemonia, tetanus), in the
liver and kidneys in phosphorus poisoning.
The Fatty Changes.
The presence of fat in the tissues is a physiological condition
depending in variable measure upon the nutrition brought about by
storage of the fat directlv derived from the food or formed within
a
Fig. 24.
Fatty infiltration of liver cells; a. normal hepatic cell; b-e, various stages of
development of fatty irflltralion; X 600. (After Thoma. )
the cells from the carbohydrates and albumens. Deposition of fat is
especially seen in the subcutaneous, submucous and subserous con-
nective tissue, in intermuscular septa and in the glandular epithelium
of the liver, mammary gland, sebaceous glands, and also in dogs
and cats in the renal epithelium. The affected cells show the
presence of fat as either large or small droplets ; and may either
have normal nuclei, with the cellular volume varying in size with the
amount of fat present {fat cells, fatty infiltration), or structural
changes are evident, which indicate a cellular destruction {fatty
degeneration, fatty metamorphosis). In this latter case the fat is
frequently found in innumerable luinute. highly refractile globules,
The Puffy Cliaiigcs.
193
the nuclei are obscured or destroyed, and the ciuthnes uf the cell>
irres-ular. The difference from albuminous ,G:ranules may l)e
recognized in teased preparations by the f.ict lliat the fat droplets
are not aft"ected by acetic acid and alkalies, and in microscopic
sections, which have been carried through alcohol and ether,
chloroform or xylol, by the removal of the fat by these reagents,
the places where it was present in the protoplasm consequently ap-
pearing as vacuoles (small holes or spaces — foam structure of the
Fig. 25.
Nodular fatty liver of dog; portion of a section under low magnitication. (After
Rauscher. )
cells). An excellent method of demonstrating the fat microscopic-
ally is by staining with Sudan III (an aniline dye), which may
be employed in teased tissue or frozen sections after hardening
with formol, but not after the use of fat solvent reagents, the fat
droplets being tinged an orange yellow color by the dye. Fat may
also be fixed by osmic acid, which makes it black and renders it
insoluble in alcohol, ether and chloroform ( it is. however, still
soluble in benzine, toluol and xylol — Diirk).
Fatty degeneration may be well seen in muscle fibres, in which
194
Retrogressive Processes.
the transverse stride are lost and the substance found thickly beset
by fine fat globules. Complete cellular destruction by fatty de-
generation is shown by the fact that finally nothing of the cell
..-.?f!Pii!&%>.
"^iJliF
Fig. 26.
Fat crystals (so-called margari-c acid needles); X 250. (After Perls.)
protoplasm remains but a mass of fat globules {fotty granular mass,
fatty detritus, from deter ere, to disintegrate ; [also often known
as compound granule cells]). Where the fatty metamorphosis
is further advanced crystallization of part of the fat in the
Fig. 27.
Cholesterin plates (after Perls) ; X 250.
TIic Faftv Chaiii'cs.
195
pulpv fatty remnants of the tissue may take place; these fat
crystals form clusters of needles. a])parently not rigid, but seem-
inglv easily bent ( margaric acid crystals), or may appear in the
form of thin ])lates w ith their corners broken out and superimposed
upon one another in a step-like fashion (cliolcstcriii plates, turning
red with the addition of sulphuric acid, and upon further addition
of iodine taking a violet or blue color).
The difference between fatty infiltration and fatty degeneration
as well as their genesis (whether the fat present in the cells is
derived from the fat brought to them or is produced by a local
splitting process) is in most cases impossible of determination;
sometimes even the microscopic picture is confused and even in
undoubted infiltration the cellular protoplasm may exhibit appear-
ances of alteration. ^loreover. it is often impossible to tell whether
the destruction of the cell was brought about by the fat accunuila-
tion, or because of some special aft'ection of the cell itself and the
fat in the latter case merely an associated or resultant phenomenon
of the destructive change.
Theoretically a dift'erence
may exist in the proportion
of moisture retained in the
tissue. In fatty infiltration
the water is forced out of the
tissue and may fall to below
50 per cent. : while in fatty
degeneration the proportion
of water in the tissue (75 to
78 per cent.) remains normal
(Perls). In fatty infiltration
the addition of fat to a liver
may sometimes be so marked
that it exceeds 40 per cent. ;
while the fatty degenerated organ scarcely ever contains more ^hm
8 per cent. (Perls).
It remains, therefore, a disputed question whether the fat is
formed by cellular function or whether it is entirely derived from
the food and is hence only transported fat. Undoubtedly the supply
of fat or carbohydrates plays an important part both in physiological
and pathological fatt\' degeneration. The studies of Rosenfeld
indicate that in experimental fatty degeneration of the liver, the
fat of this organ is not necessarily produced therein, but is
I'attj- degeneration of liver cells : a. liver
"cell of a man dead from acute phos-
phorus poisoning, in physiological salt
solution ; b. the same after removal
of the fat hy alcohol and oil of
origanum ; c, fattj' degenerated liver
celf of a woman dead from septico-
p.vjpmia, in physiological salt solu-
tion; X 600. (After Tliom.-i.)
ig6 Rctrogrcssiz'c Processes.
brought to the hver (via blood or lymph) after removal from
oth^r parts of the body (subcutaneous tissue), because when
sheep- fat was injected subcutaneously it later appeared in the liver
and formed the principal part of the fat of this organ.
Outside the body fat may be produced from proteid, as shown
by the investigations of \'oit, Pettenkofer and \"irchow. Examples
are met with in the formation of a peculiar wax-like substance
known as adipocere (adeps, fat, and eera. wax) in corpses, a fatty
change taking place in those parts of the body lying in water or
moist earth, as the result of which they acquire a spermaceti-like
nature : in fatty transformation of fat-free pulmonary tissue pre-
served in water (E. \'oit) ; in the possibility of fattening animals on
purely proteid diet (\^oit, Pettenkofer, Cremer). Pfliiger doubts,
however, whether in the body fat is formed from proteid decomposi-
tion. [The prevailing opinion is that direct transformation of pro-
teid into fat does not occur, and that when this is apparently the
case, as in the author's examples, there are intervening stages or spe-
cial causes. Thus glycogen may be formed from proteid by metabolic
changes and the possibility of fat production from this polysac-
charid must be apparent; or bacterial agency may be assumed in
many instances. The substance of the bacteria may here be held
a possible source of fat. and. too, their enzymes seem capable of
splitting the proteid molecule, with possible ultimate fat formation.
In one of these indirect modes it may be accepted that fat may be
produced from proteid ; and to whatever degree these may apply to
pathological changes in the living body it may be held that the fat
in question may have had an original proteid origin.
There is another possibility, related, it is true, with the following
paragraph, but not distinctly indicated by Professor Kitt, which
should be held as a possible explanation of the appearance of fat
in fatty degenerated cells. Fat combined in the general protoplas-
mic molecule may exist without being visible ; in case of disintegra-
tion of the protoplasm this combined fat may be set free and be-
come apparent.
And at last from the standpoint of application to the clinical
importance of the case, the really important point is not so much
the discovery of the fat in the cell as it is the fact that the cell
is undergoing a disintegrating process — and it is this which should
always be kept in mind. Whatever be the theoretical claims for
considering fatty infiltration and fatty metamorphosis together,
the student should, for practical purposes, hold them clearly sep-
The Fatty Changes. 197
arated. infiltration as a relatively unimportant accumulation of fat
from deposition, the fatty degeneration as a serious and eventually
fatal process of disintegration with the appearance of fat, for one
reason or another, in the degenerative protoplasm.]
Ribbert declares that the pathological essence of fatty metamor-
phosis is to be sought in the fact that the cells have undergone a
retrograde change which renders them incapable of further dealing
with the fat obtained from the blood, or that the cells actually
synthesize the carbohydrates, and possibl)' the albumen api^ropriated
from the blood, into fat, but cannot further deal with it, so that it
is not oxidized and remains unchanged. According to this view the
process is essentially one of disturbance of metabolism. The rela-
tion between pathological fatty degeneration and metabolic faults
is apparent, moreover, in the fact that it is especially likely to occur
whenever the processes of oxidation are impaired in the body ; as
in all disturbances accompanied by diminution in the red cells or
in the haemoglobin of the blood, the means of oxygen distribution ;
in general olig?emia caused liy blood loss or affections of the alimen-
tary tract ; in parasitic anremias and in local aucemias ; in the fatty
changes commonly resulting from imperfect vascularization and
its accompanying local anaemia, particularly in rapidly growing
tumors (carcinoma and sarcoma). Destruction of the erythrocytes
and consequent diminution of the oxygen content of the blood, or,
too, reduction in oxygen appropriation by the cells of a tissue be-
cause of some alteration, may result from various toxic causes ;
in these there arise, as important or associated lesions, fatty de-
generation of the liver, kidneys, myocardium and other structures.
If sets in with especial intensity and rapidity in phosphorus poison-
ing, in which the liver is usually dift"usely degenerated (phosphorus
liver), in poisoning with arsenic, antimony, iodoform, phenol and
in severe biliary intoxication of the blood (icterus). Bacterial
toxines in the circulating blood in infectious diseases likewise occa-
sion this metamorphosis.
In regard to excess of fat in the tissue there does not obtain
any sharp limit between the physiological and pathological grades.
"Marked general increase of adipose cells gives rise to a condition
of corpulence or obesity (ob-edere, to eat up), adipositas (adeps.
fat) or lipomatosis { x/ttos, fat). Peculiarities of metabolism here,
too, are essential basic factors, occurring in individuals both as
congenital and acquired faults and arising after atrophy of the
sexual glands or after castration.
198 Rcfrogrcssiz'c Processes.
According to the experiments of Lowy and Richter,* there is con-
siderable diminution in oxidation power connected with atrophy of the
sexual glands. The authors found that in bitches, seven weeks after
castration, the consumption of oxygen for each kilo, of body-weight was
reduced about twenty per cent., and in spite of increase in body weight
the total' gas interchange decreased about nine per cent., a reduction
followed up to about twelve months after operation ; in castration of
males the diminution of gas exchange set in within but a few days.
Inasmuch as this loss is immediately removed by feeding ovariin to
females and spermin and didymin to males after castration, and the
same disturbances recur after stopping the administration of these sub-
stances, it may be assumed that the sexual glands possess a chemical
function in connection with metabolism.
When obesity is referable to an especially rich stipply of fat
or fat-forming substances animals are said to be "fattened" (dietary
obesity, obesifas ex aliuieiitis). It is well known that this is favored
by repeated venesection ; the lowering of gaseous exchange from
the removal of blood corpuscles may be a factor in this case.
Local acctunulations of fat in the vicinity of atrophic tissues
are found, filling in the spaces left through the atrophy, as in atrophy
of the nmscles and kidneys (fat hypertrophy ex vacuo).
[Anatomically a part, as the liver, which is the seat of fatty
infiltration, is apt to be of a light yellowish color, enlarged, its
capsule tense and smooth and the margins tending to be rounded
when the amount of fat deposited is great. It cuts with lessened
resistance and the cut surface and the section knife are greasy.]
A pathological obesity (which is progressive) is anatomically
recognizable by the increase of the panniculus adiposus in the
subcutaneous tissue, the peritonetim, mesentery, epicardium and as
a diffuse extension through the tissues, as the muscles.
Fatty degeneration is characterized by a dull yellow, ochre or
clay-colored appearance of the organs, sometimes by distinct in-
crease of the volume [typically the reserve because of the cellular
destruction which is taking place], a pasty, doughy consistence or
friability, a greasy sensation given to the hand, and a greasy de-
posit on the knife used for section of the organ, and by indistinct
structural marking of the part. Sometimes the discoloration is in
streaks or flecks. The process may be associated with cloudy
swelling, when the parts look as if they had been cooked [and are
apt to be of increased vohnne from the latter degenerative change].
The pathological significance of fatty infiltration and of fatty
degeneration depends upon the extent and intensity of the process
♦Cited from Ilerm. Ilahn. Aiiat. 11. i)hi/s. Fohjecrschcln. <1. Kaatration. Sitznngs-
ber. d. Geaellsch. f. Morph. 11. IMiys. iu Miinchen, 190'2, XVIII, Heft 1.
Hyaline Degeneration. 199
and upon the relative importance of the affected tissues. Pre-
cisely in the same way . that fat in the adipose connective tissue
cells is a reserve and may be removed from these cells, there is
possible a recover}- from fatty infiltration in case of these or any
other fat containing" element, provided the cells are otherwise
healthy. Even fatty degeneration is recoverable to the extent
that replacement of loss in affected cells occurs from remaining
normal cells or nuclei (mitotic nuclear figures have been found in
fatty degenerated cells (Ribbert), and the ordinary recovery from
the infectious diseases in which muscular and hepatic fatty meta-
morphosis is apt to occur would substantiate this view^). The
massive increase of adipose tissue in the body may be harmful to
the rest of the tissue elements from the mechanical effects of dimin-
ishing space and compressing the cells against each other, as in
the heart, where in case of excessive fatty infiltration the fat pene-
trates between the cardiac muscle fibers. Liver cells, which are
the seat of marked fatty infiltration and consequent enlargement,
compress the capillaries distributed between the cell columns, and
in this way give rise to anaemia and its results. Both cells and
tissues are rendered softer and more friable by fatty degeneration
and this diminution of resistive power against mechanical influ-
ences may have serious consequences, as rupture of a degenerated
liver or of arteries with degenerated walls from increased blood
pressure. Advanced grades of fatty degeneration have, as might
well be expected, a serious influence upon cellular function apart
from the fact that this process is in itself an indication of patho-
logical disturbance of the cellular protoplasm. For example, an
intense fatty degeneration is capable of decidedly diminishing or
entireh. destroying the contractile power of muscular fibres (a cause
of cardiac dilatation and paralysis of the heart). In exceptional
circtmistances the process may be distinctly favorable to efforts
to effect recovery, facilitating the resorption or removal of in-
jurious substances like tumors or foci of purulent softening in the
tissues.
Hyaline Degeneration.
The transformation of a tissue into a microscopically homo-
geneous, glassy or transparent, colorless and highly refractile
coagulum is known as hyaline degeneration. There are produced
as a result of this change one or more types of albuminates, sepa-
rable chemically from each other with difficultv. the substance,
200
Retrogressive Processes.
hyaline (v. Reckling-hausen) , being characterized by its resistance
to acids, by being uninfluenced by water, alcohol or ether, and by
the fact that it is brilliantly stained with acid aniline dyes (eosin,
orange) and with carmine.
This degeneration, or, as Diirk calls it, homogenization, occurs
according to Ribbert as a local metabolic disturbance, in which the
tissues do not properly use up the proteid supplied to them, do not
assimilate it all or throw it off before it is completely converted.
Such' substance is then precipitated all through the tissue overlying
the intercellular substance and destroying the latter and the cells
themselves (Ribbert). Hyaline formation is met principally in
connective tissue and the vascular
apparatus, in h^emorrhagic and
anaemic infarcts, thrombi, false
membranes, in the areas of casea-
tion and in the connective tissue
of tuberculous lymph glands, in
neoplasms ; and to some extent the
substance occurs as a secretory
product, as the hyaline cylinders
of the uriniferous tubules.
[A number of pathologists use
the term hyaline in a broad sense
to include the entire group of
changes productive of a homogen-
eous and luore or less glass-like
substance, as amyloid, colloid and
mucinous luaterial, as well as that
above referred to ; inasmuch, how-
ever, as these are capable of dif-
ferentiation from the substance in
hand, it seems well to consider
them separately. The relation of
hyaline degeneration to coagula-
tion necrosis as intimated by the
above description is clear, the hva-
line change suggesting from its ap-
pearances and results the so-called
fibrinoid product referred to in the discussion of coagulation. Hva-
line substance is, however, not entirely uniform, and the result of
further study may be expected to further dift'erentiate it into a num-
Fig. 29.
Muscle of horse (hiPinoglnbinfPniia
ten days after attaok) : a. nor
mal fibre; b. hvalino lump.=;
(After Zschokke.)
H valine Pc\i:;ciicratioii. 20i
ber of similar but not identical albuminates. There are minor dif-
ferences recognized among the different examples in the staining
reactions, which indicate this multiplicity, but as yet it is impossible
to indicate a clear basis of separation. As a result of this uncer-
tainty, however, there have arisen a number of types tentatively
spoken of as forms of hyaline degeneration. Thus, the hyaline met
in dense connective tissues as scars, walls of sclerotic blood vessels,
etc., is usually regarded as the typical form, the fibrous tissue here
forming minute or grossly visible masses of the glassy transparent
matter, and grossly presenting an appearance very similar to hya-
line cartilage, the material being of about the same consistency
as the latter. Another form is met in tuberculous and syphilitic
lesions as a precursor of the later caseous change ; it is spoken of
as a "necrotic hyaline" and is apt to exist only in microscopically
appreciable amounts, but under the microscope presents the same
general appearances as the typical variety. In muscle a hyaline
change minutely distinguishable by the uniform alteration of the
muscle fibre into a homogeneous, glassy, cylindmid area or by the
formation of lumps of such a material within the fibre, and occa-
sionally extensive enough to give the tissue, when grossly examined,
a peculiar boiled appearance, is met in typhoid fever (Zenker's
hyaline degeneration) in man. in the hsemoglobinsmia of horses,
and in a variety of infectious diseases and local inflammatory
changes in muscle in various forms of animal life. This variety
closely resembles coagulation necrosis. In the blood a variety of
hyaline thrombi, usually minute and representing the primary forma-
tion of the clot, is due to a fusion of blood plaques or of blood
plaques and leucocytes ; and in old clots a change often spoken of
as "blood hyaline," leading to more or less homogenization of the
cellular and fibrinous constituents of the clot into a transparent,
structureless and yellow-colored (microscopically) or reddish
(grossly) material. Definite fibrinous exudates, as that of pleurisy
or pericarditis, and that of false membranes, as of diphtheria,
sometimes undergo a similar change (exudative hyaline), losing
all the reticular appearance of the earlier stages and presenting
uniformly glass-like sheets or bands or clumps of hyaline matter.
Within tumors, especially sarcomata, hyaline matter is often found ;
in some of the sarcomata mantles of the substance form over the
blood vessels or actually involve the vessels and render them im-
pervious (cylindromata). In various changes and in various situa-
tions in the body, rounded, spheroidal, minute masses, often show-
202 Retrogressive Processes.
a concentric marking in section, and reminding one of the well-
known corpora amylacea, but not responding to amyloid reagents,
are occasionally met, especially along the blood vessels ; these have
the appearance of hyaline matter and are tentatively classed with
this type of degeneration. \\'ithin the cells as well as between
them, in a number of tumors small globular masses responding to
the acid aniline dyes and having a hyaline appearance are not in-
frequently seen (Russel's acid fuchsin bodies) ; they were, when
first noted, interpreted by some as of parasitic nature, but are now
looked upon as a degenerated substance. The same bodies are not
very uncommon within the various cells, as those of the liver or
kidneys, in animals not subjects of neoplasms (intracellular
hyaline).
From the fact that these and even other examples are all re-
ferred to this process the confusion in our prevailing ideas must
be evident. The term "hyaloid" is often employed in order to
evade somewhat this confusion, when it is sought to describe a
clear, uniform, structureless substance suggesting true hyaline,
but not giving perfect staining reactions and not corresponding
chemically with amyloid, mucinous or colloid matter.
The cause of the change in a broad sense includes disturbances
of nutrition and the influence of local intoxications, but the details
of the action of these and of the development of hyaline and hya-
loid substances are confused and largely wanting. The change is
probably often that of a true coagulation necrosis; in some forms
it involves further alterations of coagulated matter: in others it
evidently does not mean the necrosis of the cells involved, but by its
advance leads to their death, and is thus rather a true metamorpho-
sis. When tissues are the seat of this change in its complete devel-
opment they are entirely functionless and dead ; and the hyaline
material after a variable time becomes the seat of fatty degeneration,
usually advancing to caseation and either softening or becoming
the set of terminal calcification. There is no evidence that indi-
vidual cells containing small globules of hyaline substance are
seriously incommoded by it, although the part of the cellular pro-
toplasm thus aflfected is probably useless and if the cells be greatly
involved it is probably eventually a serious lesion.]
Mucoid Degeneration.
The mucus or nmcin which is secreted by the mucous glands
of mucous memln-anes and is normally found in tendon sheaths,
Mucoid Degeneration. 203
biirsce, synovial membranes and in notable quantities in foetal con-
nective tissues, is often produced in excessive amounts in pathologi-
cal conditions and found in such quantities in the matrix of tissues
that it becomes evidence of a degenerative process. Increased se-
cretion of mucus from cells occurs for the most part as one of
the phenomena of inflammatory irritation, the mucus appearing as
an accumulation of a ropy fluid, resembling the albumen of an
egg (mucous catarrh ), sometimes more or less clouded from the
admixture of desquamated and exuded cells, hi connective tissue.
cartilage and bone, the occurrence of mucus causes a gelatinous
swelling, an appearance suggestive of head cheese.
Under the microscope mucus may be recognized as transparent
droplets coalescing into clumps (mucous spheroids), usually having
fairlv definite outlines. The cells in which the mucus is formed
generally swell up in one part, the mucin causing some nuclear
deformation from pressure, flattening it and pushing it toward
the base of the cell (transformation of cylindrical cells into goblet
cells) ; the mucus seems to originate from the nucleus in the form of
a chromatic substance thrown ofl:' in small globules (hyalosomes),
which take a uniform blue color with hsematoxxiin and respond
to the xanthroproteic test (yellow coloration with nitric acid).
[Mucoid connective tissues, under the microscope, are typified
by the gelatinous structure of the umbilical cord, and present a
delicate network of stellate cells, with mucin existing within the
reticular spaces as a transparent structureless intercellular sub-
stance.]
Physically, mucin is characterized by swelling in water and the diffi-
culty of passing it through a filter; chemically it is precipitated in white
flocculi by the addition of acetic acid (mucoid softening), but is not
precipitated by ferric chloride, mercuric chloride and nitrate of silver. It
is insoluble in alcohol and ether. There are apparently a number of
forms of mucin ( Birch-Hirschfeld), among them some which are not
thrown down by acetic acid (pseudo-mucin, metalbumin). [Three types
are commonly recognized, mucin, pseudo-mucin and paramucin. The first
and second are usually found as products of epithelial cells; the third
is more apt to be met in mucoid degeneration of connective tissue. I\Iucni
and pseudo-mucin when heated with a mineral acid give origin to a
substance capable of reducing Fehling's solution; paramucin will reduce
it directly. They all, as ?. rule, take a blue stain with hematoxylin, but
vary in their staining properties with aniline dyes. It should be noted
here that the mucoid cells, really "goblet epithelium." of certain cancers
were formerly regarded as colloid, and at present are often thus spoken of;
but it should be definitely understood that these so-called colloid cancers
are improperly named, and should be denominated mucoid cancers.]
204 Rctrogrcsskr Processes.
Mucoid degeneration of tissues should be considered as a de-
structive change; but the increased secretion of mucus may have
a favorable influence in pathological conditions, by the envelopment
of harmful corpuscular agencies and thus preventing inflammatory
irritation (dust particles, bacteria from the bronchial tubes. lar\nx,
pharynx and nose).
Colloid Degeneration.
Under the term colloid substances are included a number of
products of a gelatinous, brownish and tenacious character, remind-
ing one of half-set carpenter's glue, which, like mucus, originate
from the cells in "droplets, appear under the microscope as hyaline
balls and clumps and are entirely insoluble in alcohol, ether and
both hot and cold water. The substance dift'ers from mucus, how-
ever, in being completely soluble in acetic acid after a preliminary
swelling. This substance is normally found in the thyroid and
prostatic glands. Hypersecretion of the material leads to the forma-
tion of cysts (goitre of the thyroid gland, adrenal cysts in the
horse), which occasionally attain considerable dimensions (size of
a fist). [The cause of the process is unknown, but there is reason
to suspect that the product is the result of a change which follows
the fusion of the blood coloring matter with some of the mucin..
It involves epithelial structures, commonly the thyroid, but is not
infrequently met in the kidneys, adrenals, ovaries, the cerebral hy-
pophysis and elsewhere in the body. The colloid material is com-
monly found collected in spaces lined with epithelium (or spaces
which probably were originally so lined), as cysts which range from
a minute size to that of a walnut or rarely even that of a fist. The
substance is an albuminate of uncertain and probably variable com-
position. Its stift" gelatinous consistency, brownish-yellow color
and transparency, together with the other features above mentioned,
grossly differentiate it from mucus and the hyaline substance.
Alicroscopically the material is of a transparent, structureless ap-
pearance with yellowish tint, and typically takes the acid stains.
When W'ithin the cells and before merging with the general colloid
mass, the substance is colorless and appears in globules and small
clumps, which, however, eventually fuse homogeneously with the
mass of colloid in the acinus or cell-lined space. The cells thus
affected are apparently not altered primarily and are affected mainly
by the pressure of the collection of the colloid matter, which causes
more or less atrophy.]
(jlvco_<:;cnic J n/illralioii : ^Imyloid i'linni:;c.
205
Glycogenic Infiltration.
The glycogen which is physioloo-ically stored uj) in the liver
and which is also met in nuiscle, kidneys, uterus, placenta, cartilage,
squamous epithelium and in all of the organs of the foetus, may,
when circulating in abnormal amount in the blood (diabetes mel-
litus) be found in still cither cells, being present in considerable
proportions in such circumstances in the leucocytes and renal
epithelial cells. It is also found in pus corpuscles in supourative
aflfections, and in tumors of embryonic derivation the cells con-
tain glycogen. This C( au-
dition can scarcely be re-
garded as a special degenera-
tion, as the glycogen-bearing
cells show no other features
of alteration. The glycogen
exists in the cells merely
in the form of globules of
larger or smaller size, clumps
or granules, staining l)rown
with iodine and readily solu-
ble in water (or saliva).
[The condition known as
iodophilia, met typically in
septic conditions, is due to
the presence in the leuco-
cytes of these iodine staining
granules of glycogen. This
condition is demonstrable b\
making films of blocd from such cases ; these, while still moist,
being allowed to dry over iodine crystals.]
The condition is probably only an unusual metabolism, an ex-
ceptionally rich glycogen infiltration, in which, })ossibly, as sug-
gested by Ehrlich, the glycogen was uniformly distributed in the
living cells and separated in drops and lumps only as a jxist-
mortem phenomenon.
Fig. 30.
Olvciigt'uic infiltration of (lie livei- cells;
X 1,000. (After Thoma.)
Amyloid Degeneration.
The name amyloid (aniylimi, starch; e/5os . nature of) was ap-
plied by \'irchow to a substance which gives a color reaction
when treated with iodine and sulphuric acid somewhat similar
2o6 Retro o^rcssk'c Processes
^ '
to that of starch [when treated with iodine alone], and which is
found in the tissues as the result of a special process of meta-
morphosis.
[The editor is accustomed to regard the process not as a
metamorphosis or true degeneration as here indicated, but rather
as an infiltrative process. The reasons for this view are, it is
true, not absolutely convincing, but are suggestive. The material
may in accordance with this idea be supposed to exist in the
blood or elsewhere in a soluble pre-amyloid state and to be car-
ried by the blood to be deposited in its favorite seat, the walls
of arteries, where for some unknown local cause it is precipitated
as amyloid matter. Its common occurrence in the walls of arte-
ries rather than those of veins, its appearance in masses in inter-
cellular positions Avhere normally there scarcely exists material
which could b}- any known mode of transformation assume the
size of the common amyloid masses (as between the basement
membrane and epithelium of the renal tubules), are the jirincipal
basis for this opinion.]
When unstained, amyloid substance is, like hyaline or colloid,
of a glass-like, homogeneous appearance, and is principally found
deposited in the connective tissue framework of the blood vessels
in afifected organs as lumpy, swollen-looking, trabecular or clump-
like masses. While, however, the hyaline above discussed is
tinged like the tissues themselves a yellow straw color by iodine ;
amyloid substance takes a mahogan}-brown tint, sometimes with
a violet tone, and stands out conspicuously from the tissue. If
dilute sulphuric acid or zinc chloride be applied to such a prep-
aration, the amyloid substance takes on a deep violet to black
color ; its reaction being thus somewhat similar to that of starch
granules or cellulose, these, however, becoming blue directly on
the application of iodine alone. Other color reactions, charac-
teristic of amyloid substance, are given by various aniline dyes ;
methyl-violet staining it a ruby red, methyl-green a reddish
violet, in contrast to the bluish violet or green color given the
normal tissues. Amyloid is colored yellow by nitric acid, indi-
cating by this xanthoproteic reaction its albuminous nature.
According to the investigations of Kraw'kow this substance is
a compound of an albuminate with chondritin-sulphuric acid.
This latter substance, to which the iodine reaction is mainlv due
(Ribbert) is found normally in cartilage and elastic tissue.
Amyloid material, as such, does not exist normally in any part
Amyloid Infiltration. 207
of the body, but results from some disturbance of metabolism. It
woud appear that a hyaline, which either does not respond to
the above reactions at all or only partially, is a precursor of
amyloid.
Amvloid degeneration occurs especially after protracted sup-
purations ; this, and the fact that its deposition mainly takes place
in the connective tissue structures of blood vessels make it
plausible that some unused albuminate passes from the local sup-
purative areas into the blood and is deposited by the latter in
the tissues, where by the combination with the chondritin-sulphuric
acid it is changed into amyloid matter (Ribbert). Experimental
production of amyloid change lends some weight to this idea ;
abscesses have been produced in animals by injection with
pyogenic bacteria and predisposing chemicals (oil of turpen-
tine), and amyloid matter found in various organs after the
abscesses have existed for a long time (Ribbert). However, not
everv suppurative process results in amyloid change ; special
nutritive disturbances are also required for its production.
The process is far more commonly seen in man than in
animals. In man it is an ordinary accompaniment of advanced
tuberculosis, aside from its occurrence in chronic suppurations ;
but it is usually absent in this connection in animals, although it
has been observed as a degenerative accompaniment of tuber-
culosis in birds (Leisering. Roll, personal observations). In
horses it has been encountered a number of times, especially in
the liver b}- Rabe.
Organs, the seat of amyloid infiltration, become considerably
enlarged : their consistence is changed, becoming dense and
inelastic and more or less wax-like ; in section the tissue is
somewhat transparent and homogeneous, and is pale from an
anaemia. In man amyloid livers are suggestive of such names as
hacon-likc livers, zvaxy livers or zcooden livers: in the domestic
animals amyloid livers have a somewdiat different consistence,
the decidedly enlarged organ ( in the horse reaching eight to
fourteen kilograms in weight) becoming friable, and therefore
having a tendency to rupture. In the spleen, both in man and
animals (hog. dog), the process occurs either as a diffuse firm
enlargement of the organs with a translucent red or grayish red,
homogeneous appearance of the whole substance suggesting an
analogy to smoked salmon or bacon (ham spleen, bacon spleen),
or as a change limited to the splenic follicles, which in this case
2o8 Rctrogrcssk'c Processes.
stand out like swollen sago-grains (sago-sl^!ccii) . In the kidney
the substance is hkely to be deposited in the glonieruH. giving in
these early cases the appearance of glassy granules ; in more ad-
vanced cases the whole organ may. however, become waxy and firm.
Microscopic study shows very clearl_\- in these structures the
deposition just outside the capillaries and along the connective
tissue elements of the larger blood vessels. In the advanced
stages of the process the substance is seen in thick homogeneous,
bulging and lumpy strands. The glandular cells and connective
tissue corpuscles generally only suffer passively by pressure
atrophy, that is, they do not themselves become amyloid ; Johne.
however, states that in the horse the liver cells also become en-
larged, lobular and shining and lose their nuclei, this indicating,
therefore, their ])articipation in the process.
Amyloid infiltration may also occur as a purely local process,
especially in the connective tissue of tumors and inflammatory
thickenings of mucous membranes having a substructure rich
in elastic tissue, as in the growths in the nasal mucous mem-
branes of horses known as narioblastomata.
Finally, amyloid may be met in the form of concrement-like
deposits. The hyaline casts [waxy casts J forming in the urinary
tubules in inflammations of the kidneys sometimes show amyloid
reactions ; so, too, the round granules made up of epithelial
conglomerations and showing a concentric structure, which
are found in the prostate in man and in old dogs and oc-
casionally in the ependyma of the cerebral ventricles ( Bruck-
miiller. Johne). These bodies are known as corpora aniyJacca or
versicolorata in case they are colored brown, red and violet by
tincture of iodine atid sulphuric acid ; and as corpora flava when
they are merely turned yellow with iodine. Because of the
lack of uniformity of these color reactions, and because amyloid
substance in its earlier phases exhibits only the general charac-
teristics of hyaline, it is reasonable to suppose that albumens, so
modified as to appear hyaline, are precedents of the amyloid
material.
The pathological significance of amyloid degeneration depends
upon the extent to which it has proceeded. Small local deposits
are merely incidental. In diffuse infiltration the progressive
character of the process, the marked increase of the volume
of the organ, the consequences of pressure atrophy on the paren-
chymatous cells, constitute the most important factors in pro-
duction of immediate funtional disturbance of the organ.
Pigmentation. 209
Pigmentation.
Autochthonus Melanosis. — Normally the epithelial cells of
the cuticle, especially the deeper layers of the rete ^Malpighii, the
hairs and horns, the epithelium of various ingrowths from the
skin (for example, the mouth in dogs), besides the pigmented
epithelium of the retina and many ganglion cells, and in a num-
ber of situations the connective tissue elements (the cells of the
choroid, sclera, pia, and also the cutis), contain in variable
amounts coloring substance in the form of _\ellow, brown or
black granules (the former ha-niofusciii ; the latter, melanin).
The origin and formation of this pigment are as yet not en-
tirely clear. The entire lack of similarity to blood pigment,
especially the absence of iron as a constituent, the pigment granules
being, however, rich in sulphur and containing nitrogen
(v. Nenski, Sieber, Abel, Davids and Schmiedeberg), would in-
dicate that these granules are transformed from the albuminates
formed within the cells as products of a peculiar ("metabolic,"
from fiera^dWeLv , to transform, to change) cellular activity. It is
not known whether the material employed in the pigment pro-
duction is originally derived from the blood or whether it repre-
sents an excretory substance of the system and its production is
comparable to the formation of humus ; it can only be said that
in the same way as in early foetal life and tlience onward, forma-
tion of blood coloring matter takes place from the influence of
cellular activity, or as. under the influence of light, chlorophyl
formation is a form of cellular function, these pigments are de-
veloped within the cells.
Connective tissue cells have been noted in the linman coriuni loaded
with pigment and capable of movements which actually carry the pigment
into the epithelial ceils, and in some circumstances carry it away again
ichro)natoplu->rcs). This has been observed particularly in connection with
experimental transplantations; where a small bit of white skin has been
grafted upon a black (negro), after healing it becomes as dark as the
neighboring tissue from the penetration of chromatophores, and vice versa
in transplanting black skin upon a white person, loss of color takes place
in the graft by convection of the pigment through the agency of the
wandering chromatophore cells to the lymph glands. (The existence of
these wandering cells has been doubted by Kromayer.) According to
C. Gessard, the black pigment, especially of melanotic tumors, is produced
from oxidation of tyrosin (by an oxygenating diastase called tyrosinase")
An increased accumulation of autochthonous pigment, a liypcr-
pigmentosis or hyperchromatosis, occurs in the human skin in the
210 Retrogressive Processes.
form of brown or black patches, as similarly colored papillary
hypertrophies in the pigmented moles (nsevi), freckles (ephelides),
liver spots (chloasmata), lentigo; and is also met in increased
pigmentation of the cardiac muscle, of the enteric musculature
and in a special type of cutaneous pigmentation occurring in a
general disease (Morbus Addisonii). In some of the domestic
animals the congenital, brown, lentiginous spots are, according
to Schindelka, quite common ; the condition known as melanosis
maculosa in calves is especially frequent, such an excess of pig-
ment cells existing congenitally that spots of inky blackness may
be found in large numbers beneath the skin, between the muscles,
beneath the pleura and in the lungs, in the epicardium, in the
liver, in the submucosa of various mucous membranes and in the
membranes of the central nervous system. In foci of local over-
production there may often be observed in sheep an excess of
the black pigment in the pia mater. There is also seen in calves
and in adult cattle rather frequently a sepia-brown to ebony
black color of the kidneys, which, from the studies of L. Roth,
may be considered due to an infiltration of the epithelium of
the convoluted tubules and Henle's loops (the thicker limb) with
pigment granules which, in some cases, were identified as melanin,
in others as biliverdin. Unquestionably the pigment of melanomata
or melanosarcomata (cf. Tumors) is produced by metabolic ac-
tivity ; the proliferating cells contain within the protoplasm brown
and black granules in thickest profusion. According to the in-
vestigations of Berdez and Nenski the coloring matter of the
melanotic tumors is rich in sulphur; it is known as hippomclanin
and phymatorhasin.
Haematogenous Pigmentation, Hcemochromatosis. — The color-
ing matter of the blood, haemoglobin, in all conditions causing
haemolysis or destruction and washing out of red blood cor-
puscles, becomes freed from the cells ; and is partly distributed
in solution throughout the fluids and tissues, and may be in part
precipitated, as is indicated by the pigmentation of the tissues.
In the event of large numbers of red corpuscles undergoing
solution (haemolysis) within the blood passages, as in various
intoxications and infections (blood poisons, piroplasmosis), the
coloring matter (haemoglobin or methsemoglobin) is transferred
to the blood plasma. The blood becomes lake-tinged, and the
serum obtained after venesection from the clot is stained, instead
of limpid and yellowish, a deep red (hcemoglobinmnia). The
Pigmentation.
211
dissolved coloring matter may pass into the urine, producing
hcEmoglohiniiria and methcemoglobimiria, in which conditions the
urine assumes a bloody, dark-red or brownish black appearance.
Precisely as in normal life, the dead blood cells and their remnants
are taken up by leucocytes and carried to the lymph nodes, spleen,
bone marrow and elsewhere; in cases of exaggerated destruction
of the erythrocytes the same methods of transportation are car-
ried on in greater measure, and the renmants of hsemoglobin are
deposited in the various organs in proportion as this blood refuse
fails of complete destruction. Some of these derivatives retain
their iron (hceniosidcriii), as shown by microchemical reactions
(blackened by ammonium sulphide ; bluish green color on addition
of yellow^ ferrocyanide of potassium) ; others contain no iron
(hcemoftiscin and bilirubi)i) and may be seen as yellowish or brown
granules and clumps or as a diffuse, rust-colored or yellowish im-
pregnation of the tissues.
Hsemcglobin crystals from the blood of a
dog killed by chloroform inhalation ;
X 2.50. (After TTioma.)
Fig. 32.
IIa?matoidin crystals from a
large centrally softened
blood extravasation in the
peritoneal cavitv : X 2.jU.
(After Thoma.)
Haemorrhagic foci give rise to very profuse hematogenous pig-
mentation, both the minute extravasations arising by diapedesis
and the larger haemorrhages ; depending upon the amount of color-
ing matter deposited and the age of the lesion they cause a
rusty, ochre-like to black or slate-colored discoloration of the
tissues. The haemoglobin at first diffuses from the escaped blood
corpuscles and soaks through (is imbibed by) the tissues in the
neighborhood of the haemorrhagic focus ; the washed out cor-
212 Retrogressive Processes.
puscles disintegrate and are carried off by other cells, especially
leucocytes, by their phagocytic action. Just as in the above-men-
tioned intravascular liquefaction of the blood cells, the haemoglobin
in its freed condition is changed into amorphous masses and
granules of a yellow or reddish-brown color, partly deposited in
the intercellular substance of the tissue and partly taken up by
leucocytes, endothelial and other cells. Blood extravasations may
also contain crystalline deposits especially in the form of rhombic
plates and needles of a ruby-red or yelowish-red tint, known as
liccmatoidiii (identical with bilirubin). This is particularly seen
where fluid blood remains stagnant for a long time.
Tissues discolored bj' hssmosiderin may become slate-colored or black-
ened (formation of iron sulphide, pseudomelanosis) in places where they
come in contact with sulphuretted hydrogen (in the intestinal canal after
death, or in ichorous cavities and putrefying hsemorrhagic exudates).
Icterus, Jaundice. — Staining of the tissues by biliary coloring
matter is known as icterus {h Urepo's) \ it occurs as the result of
the entrance of bile or biliary pigment into the blood und
fluids of the body. The common causes of such absorption of
bile are diseases which occasion obstruction to its passage to the
intestine, and therefore result in a biliary stasis (icterus from
stasis), and all conditions which are accompanied by obstruction
or narrowing of the biliary channels (obstruction from gall stones,
compression by tumors, swelling of the mucous lining of the
passages), providing the liver tissue meanwhile continues its pro-
duction of bile. (In hepatic diseases which lead to destruction
of the liver cells or to a lowered production of bile, of course
obstruction of the ducts cannot occasion any jaundice or only
minor grades of the symptom, as may be observed in distomiasis
of the liver, in which condition this feature is usually absent.)
In case the bile can no longer escape it first collects in the bile
capillaries. This may be observed under the microscope as an
engorgement of the intraacinous biliary tubes which look as if
actuallv injected with greenish bile substance; and the stasis may
be further traced into the intercellular secretory alveoli and
tubules. In case of rupture of these delicate capillaries the bile
may gain entrance into the adjoining lymph-spaces, and be car-
ried by way of the lymph channels into the blood (thoracic duct).
At other times it probably escapes directly from the liver cells into
the blood capillaries ; it is assumed that within the liver cells, in addition
to the biliary secretary vacuoles, there is another canalicular system which
carries urea and sugar into the blood capillaries. (Nauwerk, Browicz.)
Pigmentation. 213
Biliary stasis may also depend upon an excessive production
of the secretion, inasmuch as the profusely produced bile may
also be sometimes too concentrated and thick and flow with
difficulty, the cells in consequence becoming clogged. A hyper-
cholia of this type occurs in conditions which cause a marked
destruction of red blood cells, and the haemoglobin set free
en masse is then worked over in the liver and renders the bile
particularly rich in its pigmentary matter. It is possible, too,
that the bile may be thickened and less fluid or may diffuse
directlv into the blood vessels because of disease of the liver cells.
This is met in a number of intoxications and infectious diseases,
where, as the cause of the jaundice cannot be referred to a condi-
tion of biliary stasis, it is spoken of as a resorption jaundiee or
infectious or toxic paracholia. (Pick.)
It was formerly believed that the formation of biliary coloring matter
in quantities sufficient to cause jaundice could also take place outside
the liver, in the blood; and a hsematogenous jaundice was spoken of.
From the studies of Minkowski and Xaunyn, however, it may be consid-
ered established that, even in cases where a simple increase of destruction
of erythrocytes causes this symptom, it is not produced except with the
intervention of the liver, and that the transformation of the haemoglobin
into biliary pigment is accomplished in the liver. Birds jaundiced by
arseniuretted hydrogen rapidly lost their icterus after extirpation of the
liver, and where the liver had been previously ablated, jaundice could not
be produced in any degree at all. [The term "local hsematogenous jaun-
dice" is sometimes applied to the yellowish discolorations of fading bruise
marks; it is permissible only in a general w\ay, and in precise discus-
sions the pigment must be understood as not identical with the jaundice
pigment. Although there may be more or less hsematoidin present, there
are also less closely allied blood pigments.]
The entrance of the bile into the blood is followed by an
impregnation of all the tissues to which the blood vessels are
distributed with the biliary coloring matter, this giving them a
biliary tint of various shades. In the living body this is apt to
be particularly conspicuous in the conjunctiva and sclera; in the
dead animal the yellow color is principall}- apparent in the stib-
cutaneous tissues, the fat, intermuscular connective tissue, the
lungs, I'ver and kidneys, the mucous membranes and their mus-
cular coats. Where the normal color of an organ was pale the
discoloration may take on an intense citron-yellow hue ; the dark
liver and kidney tissue becomes saffron yellow to olive green or
o-reenish-black. Even the bones as well as fibrinous blood clots
and the blood serum assume a biliary tint. As the pigment gains
214 Retrogressive Processes.
access to all the glands their secretions also become yellowish ;
and the pigment is especially noticeable in the urine. [The
saliva, gastric and pancreatic juice, tears and mucus are apt
to be free from coloration.] Only cartilage, the cornea and
the enamel of the teeth, and, too, the brain, take up but little of
the color. Because of the diffuse uniformity of impregnation
of the intercellular substance and of the cells with the coloring
matter, it at times is not noticeable under the microscope (per-
haps washed away in the details of preparation of the specimen) ;
but in other instances some of the cells, as those of the liver, are
stained an intense yellow or yellowish-brown, and granular and
coarser deposits of a yellow, brownish or green color are found
in the protoplasm, especially in the hepatic and renal epithelial
cells. The pigment is sometimes seen in crystalline form (ruby-
red rhombic plates of bilirubin) in the kidneys, spleen and bone
marrow.
Jaundice may be a transitory condition ; the liver after removal
of the interference to the passage of the bile resuming its
normal functions and the resorbed bile being eliminated by the
urine, etc. In case of more prolonged duration faults of the
organism become apparent. In the first place the absence of a
sufficient amount of bile in the intestine may interfere with diges-
tion; in the second place the bile stasis in the liver may cause
pressure upon the liver cells and can give rise to degenerative
and necrotic changes ; thirdly the mingling of the bile with the
blood brings into the latter and into the different organs sub-
stances which are haemolytic and have other toxic influences.
The biliary coloring matter and, too, the biliary acids are to be
included among such toxic substances, the latter undoubtedly being
toxic to the nervous system. [It is supposed that the itching
complained of by jaundiced human beings, and to some extent
present in animals, is due to an irritation of the skin by the
biliary pigment ; and the slowing of the cardiac rate in jaundice
is directly referable to the action of the biliary acids or their salts
upon the vagus, or in marked instances upon the heart itself.]
Moreover, the influence of substances produced in intestinal putre-
faction should be kept in mind, these materials being absorbed
from the intestines and passed through the diseased liver which
is no longer able to neutralize their poisonous properties. Severe
cerebral symptoms developing in cases of biliary obstruction and
sometimes fatal (convulsions, coma, delirium), accompanied by
Pigmentation. 215
high fever, indicate the existence of such an autointoxication,
which is designated as icterus gravis and cholcemia.
Exogenous Pigmentation. — When the tissues are impregnated
with pigmentary substances which gain access to the body from
the exterior the process is known as exogenous pigmentation.
"The most common example is the deposition of carbonaceous ma-
terial (anthracosis) in the lung, practically always found in man
from inhalation of the particles ; it also occurs in dogs which
are compelled to pass much of their time in smoky places,
and in horses kept for a long time in coal mines. The in-
haled dust, except that which is removed by the bronchial
mucus and by the ciliary activity of the tracheal cells, re-
mains suspended in the alveoli [and smaller tubes], is taken up
by wandering cells (dust cells) : part being carried in
the pulmonary lymph channels and reaching the lymph glands
of the lungs and bronchial tree, part being deposited in the lymph
spaces of the lungs. Wirying with the quantity of carbon thus
deposited, the lungs and lymph glands become mottled and of a
grav slaty appearance or uniformly and completely blackened.*
Dark pigmentations may also be caused by the deposition of
mercurv, lead and silver, observed som.etimes after medicinal
administration of preparations of these metals, as in case of the
black color of the intestinal villi in the horse after the adminis-
tration of calomel. It is usually the result of the formation of
mercuric and plumbic sulphides from contact with the sulphuretted
hydrogen of the gastro-intestinal contents. In employing nitrate
of silver in internal medication it is absorbed from the alimentary
tract and deposited in extremely fine granules (reduced to metallic
silver) in all the different organs, skin, conjunctiva, kidneys, etc.,
and gives them a grayish pigmentation. The condition is known
as argyria.
By means of subcutaneous and intravenous injections of staining
solutions (carmine, indigo-carmine, methylene blue) the tissues of the body
may be colored bUie or red. The protoplasm of many cells takes up the
stain diffusely in part ; sometimes instead a granular deposition takes place
from combination of the piginent with certain granular constituents of the
cells (Arnold, Ribbert).
[The eff'ect of external or exogenous pigmentation is usually
trivial aside from the mere discoloration and is only important
when intense or as a predisposing cause to more serious dis-
*For details cf. Path. Anatomie d. Haustiere. II. Aufl. Stuttgart, Ferd. Enke.
2i6 Retrogressive Processes.
turbances. Each pigment particle is essentially a foreign body
and indnces a certain amount of inflammatory reaction, usually of
low grade and productive of an increased amount of fibrous tis-
sue. Parts the seat of marked pigmentation, as the lungs and
bronchial glands, become more or less indurated. The possibility
of infection by tuberculosis, especially noted in man, becomes more
easy when previous dust inhalation has induced a chronic bron-
chitis and has induced the secondary faults of pulmonary blood
and Ivmph drainage and has lowered the general vital resistance of
their tissue b\- a prolonged chronic interstitial inflammation. In
less important organs than the lungs, of course, the changes occa-
sioned by external pigmentary deposit are proportionately less
serious.]
Calcification and the Formation of Calculi.
Calcium salts are normally present in solution in the body
fluids (calcium glycerin-phosphate, carbonate, lactate, oxalate, etc.).
Deposition of lime in solid form takes place normally in the bones
and teeth of man and the animals ; and in herbivora there is nor-
malh- excreted in the urine such large amounts of calcium salts
that by mere cooling they precipitate and the urine at time of
voidance may even be turbid from their presence (horse). Cal-
cium impregnates the matrix of bone and teeth with so much
uniformity of distribution that it is not apparent in definite masses,
being recognized only by the solidity of the structure and by
chemical analysis ; in the urine it separates as amorphous granular
and crystalline forms.
The deposition of calcium salts in other parts than those men-
tioned is pathological and is known under the names calcification,
cretaceous iniiltration, petrification and incrustation.
The basis for this deposition is probably to be sought in the
removal of the substances favoring the maintenance of the lime in
solution, as free carbonic acid, and the transformation of earthy
salts, which are soluble in water, into insoluble calcium compounds,
and, too, in increased supply of lime. Thus, pathologically, calcifica-
tion is apt to occur in dead or altered tissues in which free carbonic
acid exists in lowered amount and in which gaseous interchange
by the cells is essentially impaired, or may appear in secretions and
excretions where it leads to the formation of concretions. [Klotz
{Jour, of Exper. Med., 1905, vii, p. 633) has recently attempted
to explain pathological calcification in necrotic degenerative areas
Calcification. 217
upon the assumption of a previous fatty degeneration of these
structures, soaps of lime being formed primarily by combination
of lime brought in solution by the juices permeating the altered
tissues with the fatty acids. These soaps are later further changed
by substitution of the fatty acids by carbonic acid and phosphoric
acid. Wells {Jour, of Med. Research, 1906, X. S. ix, p. 491) can-
not find evidence of constant and important occurrence of these
soaps as a stage in the process, although in traces he finds such
soaps to exist in areas of calcification. Fischler and Gross (Zieg-
ler's Bcitragc, 1905, Festschrift fiir Arnold, p. 326) have also
found evidence of the presence of such soaps in atheroma and in
the margins of infarcts, but not in caseous areas, and are unable
to definitely declare that soap formation is an essential stage in
calcification. Wells regards pathological calcification as probably
essentially similar to normal deposition, and inclines to the idea
that there exists or is produced in the area some substance having
particular affinity for calcium, although he is unable to indicate its
nature ; it is not. however, dependent upon the vital state, as in
cartilage it exists both when the cartilage is Hving and after
it is boiled.]
In distinction from physological calcification, in which a perfectly
homogeneous combination of the lime with the matrix obtains, patholog-
ical calcification is manifested on microscopic examination by the presence
of fine, highly refractile granules, looking like particles of fat and pig-
ments, which, with direct light (complete closure of the ■ substage dia-
phragm), have a dull, glistening, whitish appearance, and are found both
within and between the cells. On the addition of acids (especially hydro-
chloric acid) the calcium salts are dissolved and the presence of calcium
car'conate is indicated by the immediate effervescence (carbonic acid). With
pure sulplniric acid great numbers of crystals of gypsum (calcium sulphate )
separate in delicate pointed crystals, scattered all through the tissue. A
calcified tissue (the same in case of partial calcification) takes a very
intense dark blue stain with ha?matoxylin.
Ossified tissue differs from merely calcified structures by the forma-
tion of lamellae of the matrix (Haversian lamcllre) and the inclusion
of the bone cells in the intricately branched lacunae.
Petrification of tissues renders them as hard as bone and gives
them a dirty white appearance. As a senile change this is occasion-
ally met as spots isolated in the cartilaginous nasal septum in cattle,
in the laryngeal cartilages of dogs, and quite uniformly in the costal
cartilages of old animals. (These foci become easily visible as
opaque points on drying the cartilage.) With much less frequence
than in man, calcification of the vessel walls is observed in animals
2l8
Retrogressive Processes.
as a rather rare occurrence, transforming the intima of the vessel,
as the aorta, into a rough, scaly surface, or appearing as flat plaque-
like or disc-like areas, making the vessel at such places rigid and
inelastic. The greatest tendency to this change is found in the
large verminous aneurisms in horses, which form brittle, hard
enlargements of the arteries. The intima and the media in these
lesions are the especial seat of the calcification, preceded by hyaline
degeneration.
Fig. 33.
Portion of liver of a liorse with calcification of necrotic parasitic foci
Trolldenier.)
(After
In greater measure newly-formed inflammatory connective tissue
is rather often affected; thus the cicatrized castration wound of
the abdominal wall in hogs may be observed changed into a calcified
plate as broad as a hand, and the opening into a hernial sac in um-
bilical hernias in the same animals is sometimes changed into a cal-
cified ring of connective tissue. Calcareous plates in the connective
tissue of the cow's udder are sometimes found ; and even the con-
nective tissue of the lungs is in rare instances (in cattle) trans-
Calcification. 219
formed into a branched, rigid and corset-like enclosing structure.
In the dense membranes of the spinal cord, in dogs, calcareous in-
filtration gives rise to rigid thickenings which feel like splinters
of wood. Bursce and tendon sheaths in horses may become ex-
tensively calcified and ossified. The colloid matter often met in the
thyroid gland and sometimes involving the connective tissue as well
as the acini, may occasionally terminate in calcification of the organ
(stoa.e goitre, slniDia pctrifica}is,m dogs). The herbivora and also
hogs are with special freciuence subject to calcareous infiltration of
tuberculous caseated tissues. The yellow, cheesy foci produced
by coagulation necrosis are frequently full of sandy, gritty particles
and are very hard. In the end dead parasites and the connective
tissue capsules which are formed about such foreign bodies in the
parenchymatous organs, as echinococci and round worms in the
livers of horses, become so permeated with lime salts that they form
stony, bone-like or mortar-like, chalky masses.
In women, dead foetuses long retained in the uterus or peritoneal
cavity may become so completely calcified as to be of stone-like hardness
{petrified foetus, lithopcrdion) ; in our dom.estic animals the dead embryos,
which are often found, usually remain more or less leathery, pliable and
merely mummified. [In the museum of the Medical Department of the
University of Pennsylvania there is a thoroughly calcified excellent example
of a lithopa^dion taken, after death, from the uterus of a mare, and pre-
sented to Dr. James of the above-named institution in 185 1 by -\Ir. Kearney
of Gloucester County, New Jersey.]
Zschokke (Schicci::. Archil'. 1902) has descrilK-d a peculiar crystalline
deposit observed in the liver of a cow confined to the interstitial spaces
as white foci, scattered here and there. The abundant precipitate was
made up of rounded and rhombohedral crystals (about the size of white
blood corpuscles), the chemical nature of which was not precisely deter-
mined, although with the iodine-sulphuric acid test they showed some
relation to cholesterin.
Solid u.norganized bodies which are formed in the secretions and
cavities of the body are called concretions. They are formed by
the precipitation of salts which have become insoluble ; their chemi-
cal composition depending upon the ingredients of the normal se-
cretions and its existing changes, and therefore not uniform.
Sometimes they contain organic matter mingled with the saline
constituents ; or they may be foreign bodies or exudates which have
become encrusted with salts. The fundamental conditions for the
formation of these bodies include the following:
I. Supersafnnttion of the saline solution (Klimmer) and dim-
inution of the medium of solution. Just as the crystalline salt
220
Retrogressive Processes.
separates from a saturated solution of copper sulphate or from
Carlsbad-Sprudel water, in the same manner the salts of a secre-
tion, like the urine, may precipitate, especially should there occur
a loss of its fluid or of substances which keep the salts in solution.
2. Retention of secretions or excretions in their storage reser-
voirs.
3. Chemical decomposition of the secretion, with the formation
of insoluble products, as may result from the presence of bacteria
( ammoniacal fermentation ) .
4. Presence of a foreign body or any organic material which
serves as a nucleus for the deposition of crystals, or as a supporting
framework for the precipi-
tated salts, as bits of wood,
particles of food, or viscid
degenerative products.
Urinary Calculi {Uro-
lithiasis s^ravel, concrc-
nicnta urinaria). — The sa-
line constituents of the
urine may be precipitated
in the kidneys, in the renal
pelvis and in the urinary
bladder and give rise to the
formation of urinary gravel,
urinary sand, and larger
urinary calculi. Even nor-
mally in the horse, calcium
carbonate separates in the
pelves of the kidneys and
in the bladder from the al-
kaline urine, the latter being turbid even when freshly passed in
consequence ; in the other herbivora it becomes cloudy soon after it
is voided because of loss of the solvent power of its fluid on cool-
ing. The acid urine of carnivora and omnivora is, on the contrary,
clear and permits sedimentation only after decomposition and long
standing. The causes of urinary calculus formation may include
such structural elements as parasites, blood clots and coagulated
fibrin, shreds of necrotic tissue, tube casts and epithelial cells, these
substances afifording a place of attachment for deposition of the
inorganic substances. The presence of living or dead bacteria is
especially apt to cause precipitation, these at times forming small
Fig. 34.
T'rinnr.v falciilus from renal pelvis of
horse.
Concremcnt Poniiatioii. ■ 221
masses and favoring", as do protein chimps, the adhesion of any
precipitate, and, too, perhaps causing ammoniacal fermentation.
A high proportion of sahnes in the nrine is, as pointed out hy
Klininier. an important feature. This authority questions whether
the presence of albuminoid or mucoid substances, such as are occa-
sioned in the urinary tract l)y inflammation, provides any means of
cohesion, as a sort of paste. .Some such organic stroma is uniformly
found, especially because the concretions determine a catarrhal pro-
cess at times, as a result of which layers of mucus and albuminous
material are found between the mineral deposits ; such viscid matter
is, however, also found in loose sediments and perhaps may in
reality interfere with calculus formation by preventing [approxima-
tion and] cohesion of the particles. Such organic framework is not,
as pointed out by Moritz, peculiar to calculi, but is, too, an
important feature in any
urinary crystal, whatever
it ma\- be. The size and ^■\<^^'v^'^>-<S^- \
shape of urinary concre-
tions varies widely with ' /<.■*-'/ -CC^lNV^^^^$^W<0 -" « , ^
the species of animal, the
site of formation and the
composition. Renal cal- '''"^i;^^.-?
culi are usually round, '^
•^ Fig. 35.
pearl-shaped, like writing y^^.^^^^ calculus from a horse,
sand, millet seed or hemp
seed : those of the renal pelvis are irregular, warty, or correspond to
the shape of the pelvic cavity, crcscentic, and may reach a size nearly
that of a fist. Tn the bladder the urine throws down a slimy, sandy
material which forms a thick, soup-like urine or masses which
may attain several pounds in weight and assume the shape of
half of a pear (corresponding to the interior of the bladder and
flattened on one side by the passage of the urine). When com-
pact, vesical calculi are lentil shaped, oval, flattened or faceted
from pressure, polished or sometimes rough and mulberry-like,
gland shaped, and range in size from that of a millet seed to the
size of a double fist. Small concretions met with in the ureters or
urethra, and often impacted in these passages, are not formed in
this situation, but are swept from the kidneys or bladder. The
color of urinary calculi is usually brown, metallic, bronze-like ;
some concretions are, however, gray, ye^lo^^•ish or piu'c white, anc|
occasionally reddish ones are met.
222
Retrogressive Processes.
In construction and chemical composition of urinary calculi a
large variety of substances take part ; and the concrement is rarely
made up of but a single chemical constituent, but usually contains
a number of ingredients. In horses these calculi generally contain
carbonates and phosphates of lime, carbonate of magnesia, traces
of iron and occasionally silicates ; those of the cow, sheep and goat
are at times rich in silicates or magnesium phosphate, but also
contain calcium carbonate or triple phosphate. In swine they are
made up either of triple phosphate or calcium and magnesium
carbonate and phosphate ; and oxylate concretions also occur. The
uroliths of carnivora are a mixture of calcium carbonate, phosphate
and urate, or are composed in other cases of uric acid or sodium
»
Fig. 36.
Eenal calculi from cow.
and ammunium urates or of calcium-ammonio-magnesium-phcs-
phate. The tabular forms, when fresh of soft consistence and of
greasy, slimy appearance, are mainly made up of cystin. The
color of urinary concretions is given by the pigment of the urine
or biliary pigment ; occasionally hsematin has been found to explain
the existence of a black color, or carbonate of iron that of a
metallic bronze luster (Fiirstenberg, Pflug, Miiller, Dammann,
Klimmer).
The especial causes of danger in connection with urinary calculi
are to be found in the disturbances of urinary flow which they
occasion, giving rise perhaps to urinary retention. In addition
these foreign bodies act as irritants to the mucous membranes in
Concrement Formation. 223
varying grade; may cause dysuria (tenesmus) and pain of intense
severity (spasm of the involuntary musculature of the ureters,
bladder and urethra), local inflammation and erosion, obstruction
of urine, dilatation of the bladder and possibly rupture, hydrone-
phrosis, and submucous urinary infiltration and urinary intoxica-
tion of the blood. (For details cf. SpccicUc pat hoi Anatomic d.
Hausfior, II. Bd.).
Gall Stones (Cholelithiasis).— Although in man gall stones are
comparatively common (25 per cent, of women sufifer from them),
they are rather rare in animals. They are found as soft or half
solid, slippery bodies in the gall ducts and gall bladder, about the
size of a hazelnut but sometimes even larger than a fist, usually
multiple in numbers and often occurring in hundreds. Their color
is either a fine saiTron or ochre yellow, brick red or dark brown,
or they are whitish and chalky, with a yellowish or a greenish color
on the outside or in layers internally. The larger ones are rounded
or oval in form and in section they show a laminated structure ; or
thev are from mutual pressure faceted and polyhedral because of
their softness.
Their composition varies. From analyses made by INIaly, Phip-
son, Hermann, of the gall stones of cattle, these concretions were
found peculiarly rich in bilirubin or the compound of bilirubin with
calcium (28-61 per cent.) and poor in cholesterin (only 1.35 per
cent. ; according to Zschokke, 10-15 per cent.) . E. Voit found in a gall
stone of a horse but little biliary pigment, no cholesterin, large
amounts of biliary acids, and in the ash chiefly calcium phosphate.
In the large examples not infrequently food particles (bits of cereals
or of hay or straw) are present, apparently forced from the intestine
into the widely dilated and relaxed biliary canal (peristalsis).*
The origin of gall stones is not as yet entirely clear. Accord-
ing to Naunyn the mucous membrane of the gall passages in
catarrhal conditions produces a secretion rich in calcium salts, and
at the same time albumen is exuded into the bile. The presence
of the albumen favors the precipitation of the lime, and the increased
proportion of bilirubin may be explained by the thickening of
the bile from retardation of its flow. [The solid pigmentary sub-
stance in gall stones is a definite chemical combination between
calcium and bilirubin, the latter having feeble acid combining
powers.]
♦Occasionally in swine and doer accnmulations of ordinary sand (silicate and
quartz fragments) have heen found, which could not possibly get into the biliar;r
passages except from duodenal contractions.
224
Retrogressive Processes.
Cholesterin gall stones are apparently the result of a pathological
secretion from the biliary mucous membrane ; according to Gamgee, in
cholecystitis there may be observed myeline-like masses in the epithelial
cells, a lump}% glistening substance, which floats on bile and which, on
the addition of acetic acid, crystallizes as cholesterin. These cholesterin
clumps are regarded as the stage preceding the deposition of cholesterin
for the formation of calculi (Naunyn).
7.
X
ww^iml.'
Fig. 37.
Gallstones from cow. (After Trolldenier. ,)
It has been pointed otit. too, that colon bacteria or a mixed
infection penetrating from the intestine may set up a cholangitis
and cause disintegration of the secretion and exudate and in this
way give origin to calculus formation (Halia, Naunyn).
The presence of biliary concretions may produce no symptoms as
long as the bile is able to flow without interference; but at times
by obstructing the biliary passages they cause biliary stasis and
jaundice or, by involvement of the cystic duct, retention of the
mucus in the gall bladder with marked dilatation of the latter
{hydrops z-esicce fellecs). These calculi with their b^^cteria and
Coitcrcnioit Poiinatioii.
225
particles of food within llicni may excite inflammatory changes, and
give origin to hihary colic from the s])asm and inllammation of the
muscular wall of the bladder; and it is possible that rupture of the
latter may occur.
Salivary Calculi (calculi salii'ulcs). — Small concretions and cal-
culi are formed from the calcium salts of the secretion (calcium
ry
Fig. 38.
Sectioned surface of a gall stone of a cow. (After Trolldenier. )
carbonate and phosphate) and from carbonate of magnesium, potas-
sium and sodium in the ducts of the oral salivary glands (parotid,
sublingual and submaxillary) and of the pancreas (abdominal
salivary gland). These concretions are usually chalky. In the
horse salivary calculi sometimes form in Steno's duct to the size
of a goose egg (200 to 600 grams in weight), often having as a
nucleus a bit of chaff, a piece of straw or an oat seed, which has
in some way gotten in from the mouth. According to Galippe
bacteria by inducing fermentative changes in the saliva seem to
be the occasion for the separation of the salts.
226
Retrogressive Processes.
The larger calculi cause distension of the passages and retention
of the secretion. The earthy salts of the saliva may also precipitate
in the mouth cavity. Mixed with desquamated epithelium and
oral vegetable organisms they accumulate as hard, brittle, dirty-
white deposits, particularly about the neck of the teeth, forming
the so-called tartar (common in dogs, rare in horses).
Intestinal Calculi. Fecal Concretions. — Indigestible parts of
the food and earthy substances with them sometimes accumulate
in the large intestine in more or less compact masses,
which may have important consequences upon and menace the
Fig. 39.
Vegetable concretion from the colon of a horse.
health of the animal. In the dog, more rarely in the cat, bone frag-
ments in the fecal material, forming in hard, dirty brow'n to black
sausage-shaped masses, and perhaps reaching the thickness of the
human arm, are quite likely to block up the rectum and colon and
cause erosion and necrotic ulcers of the mucous membrane, obstruct-
ing all the rest of the intestinal contents, and producing fecal
fistulse and rupture of the intestine. In horses concretions made up
of vegetable fibres are often formed in the c?ecum and colon, com-
pressed into ball-like clumps, sometimes attaining the size of a
human head, and more or less encrusted with mineral matter
(phytoconcrements, mixed conerements).
Concvcuicnt lu>niiatioii.
227
In the parts of the large intestine just mentioned there are also
found not infrequently hard, stony concretions {intestinal calculi,
enteroliths), ranging in weight up to eleven kilograms, looking
not unlike billiard balls or bowling balls, or sometimes of pyramidal
shape from being worn off on the sides. The main constituent of
these dense calculi is, according to Fiirstenberg and Gurlt, ammonio-
magnesium phosphate (over ninety per cent.), the precipitation of
which occurs especially in feeding wheat and rye bran (the horses
belonging to millers and bakers), such a food containing a large
amount of magnesium phosphate. This is dissolved in the acid
intestinal juice and in case of the development of ammoniacal com-
pounds unites with the ammonia to form the almost insoluble triple
Fig. 40.
Half of a fractured laiiiellaterl enterolith from a horse.
phosphate. The marked sluggishness of peristalsis which obtains
with this diet, and ammoniacal fermentation of the intestinal con-
tents by bacteria, aid in the formation of the calculi. Usually the
larger examples are single : but of the smaller sizes there may be
dozens or hundreds in one intestine. In addition to pressure ero-
sions caused in the mucous membrane by these calculi, they may
produce fatal results, especially by accidental impaction and ob-
struction at some narrow part of the intestinal tube. (For details
cf. SpczicUe pathol. Anatomic d. Haiisticrc, II. Aufl. 1902, Stutt-
gart, Enke's Verlag.) Horses which take in sand and mud in
drinking from pools (and the same is true of hogs from swallowing
ground while rooting) occasionally get large masses of such ma-
terial into the intestine and may as a result suffer from the forma-
tion of diverticula.
228
Retrogressive Processes.
In pigs bristles which are swallowed may be massed together
in the intestine by the peristaltic movements into cylindrical bristle
balls; in ruminants hair which has been swallowed may form in
the abomasum one or more spherical felt-like bunches, and in the
same way remnants of plant fibres may also be compressed into
similar balls here {piUconcrcniciits, phytoconcrements, bezoars).
Fig. 41.
Cut surface of half of an enterolith from horse (one-half reduced).
Pus concretions result from the inspissation of pus retained in
old abscesses and other places, possibly with more or less calcifica-
tion. In the air chambers of horses they are met quite commonly,
supposed to be due to the compression of thick streptococcus pus
by muscular pressure (movements of chewing and swallowing),
often into chestnut-like or potato-like masses. In cattle tubercu-
lous caseated masses in bronchiectatic cavities may form hard
lumps, perhaps reaching the size of a fist.
Gout.
229
Gout.
This name is applied to a disturbance of metabolism characterized by
accumulation and deposition of urates of the alkalies in the tissues, the
joints being special seats of uratic deposits, and developing painful nodular
swellings (gouty nodes; tophi, from t64) os, cretaceous stone). In man
this is a common affection, but a rarit}' among mammalian animals.
Only one case is on record (Bruckmiiller) in a hunting dog. (In two
published cases in swine [Virchow, Mendelsohn] there was not a deposi-
Flg. 42.
Pus concretions from au air ohamljei- of house (reduced one-half).
tion of urates, but it would seem that the whitish, chalky masses found
in the joints were composed of guanin, or, according to Voit, of tyrosin.)
Genuine gout, however, is common in pigeons, chickens, parrots, ostriches,
and is quite frequent in birds of prey (Kionka) ; it has been observed, too,
in reptiles (alligators, snakes).
The symptoms of avian gout manifest themselves by progressive weak-
ness of the bird, with loss of appetite and emaciation. The legs present
230 Gout.
more or less prominent arthritic swelling and are unfit either for standing
or walking. Sometimes there is also a swelling of the wing joints, and
in case of chickens, a strong bluish-black discoloration of the comb becomes
apparent. At autopsy of birds dead from the affection after a course
of some weeks or months, there is at times found within and about the
joints a deposit of white, chalky, mortar-like material; and the serous
membranes (membranes of thoracic and peritoneal air chambers and peri-
cardium), the epicardium and the liver are apt to be found the seat of
similar deposits, as though powdered with plaster of Paris. The kidneys
are thickly beset with white points and sometimes the ureter is completely
filled with white plugs. Microscopic examination shows the condition
.to consist of a deposit of and infiltration with crystals of sodium urate
(plates and needle-shaped crystals grouped in stellate bunches).
As far as the causative conditions and nature of the metabolic dis-
turbances, fundamental to the affection, are concerned, but little has been
definitely established in case of human beings. Practically all that is known
is that certain kinds of food (large amounts of albuminates, highly sea-
soned meats [meats rich in nucleo-proteids], alcohol), lead-poisoning and
a predisposition of the individual play a part. It has been established
in case of avian gout, by the highly interesting investigations of Ebstein,
Kionka and Kossa, that a number of poisons which injure the renal
tissue and, too, exclusive meat diet are capable of inducing in experimental
cases the characteristic features of gout. As early as 1766 Galvani pointed
out that chickens became gouty after ligature of both ureters, an ob-
servation which has been repeated by Zaleski, Colasanti, Schroder and
others. Ebstein injected subcutaneously in chickens neutral chromate of
potassium in separate doses of 0.32 gram, with the idea of impairing the
excretion of uric acid by producing serious renal lesions ; with this dosage
the birds lived for some weeks, and, as a matter of fact, Ebstein estab-
lished that they undoubtedly became gouty. The same results were obtained
by v. Kossa in chickens by intramuscular injections of solutions of oxalic
acid, phenol, acetone, aloin, corrosive sublimate and, too, cane sugar.
Kionka drew attention to the fact that carnivorous birds are the ones
which are especially subject to gout, and from a series of studies estab-
lished the fact that chickens on exclusive meat diet (160 grams a day),
to which they may become accustomed, may become gouty in the course
of a few weeks or several months and then die of the affection. The
large, heavy breeds showed greater tendency in this direction than the
commoner small chickens. There were noted a great increase in the
production of uric acid with this diet and a correspondingly high dis-
charge of uric acid (8-9.5 grams each day) and of nitrogen (3-4-5 grams
a day) in the excreta. Since M. Kochmann has shown that in dogs, also,
when fed exclusively with horse flesh, the renal and hepatic parenchyma
suffers a change (parenchymatous nephritis and hepatitis), and the poisons
above mentioned give similar results, v. Kossa looks upon the nephritis
as the cause of the toxic gout interfering with the elimination of urates
just as if the ureters were ligated. Under natural conditions almost every
chronic nephritis in birds may be followed by gout. Ziirn once observed
the affection after feeding ustUago maidis to chickens. The common
Gout. 231
occurrence of the disease in birds of prey kept in captivity and having
insufficient exercise, favors the view that muscular activity lowers the
disposition, or, in other words, uric acid is destroyed in the working
muscles. The difference, not merely in diet, but in the possibility of
destruction of uric acid in the muscles, liver, kidneys and spleen are
probably reasons for the rare occurrence of gout in mammals and the
fact that it is never seen in herbivora.
[In man the affection, characterized not only by the joint changes, but
also by widespread sclerotic lesions, especially of the arterial system, is
referred to uric acid and certain precursors of this substance, the purin
bodies. These are particularly the products of metabolism of nucleo-
albumens, and much' importance is ascribed to diet rich in these albumi-
nates, young meats,' pancreas, liver, etc. Other factors, as insufficient
exercise, etc., are also deemed important.]
PROCESSES OF REPAIR AND NEW FORMATION
Regeneration.
By the term regeneration is meant a process' of new formation
of tissue which occurs in connection with tissue loss, replacing such
loss and then ceasing.
Renewal by metabolism of the functional capability of cells
remaining alive after fatigue and exhausting diseases is known as
recovery or rccoiisfitiifioii. In the living organism cellular material
is being continually used up and in consequence there are always
some cells being destroyed and new ones growing to take their place.
The cellular covering of those surfaces which are in relation with
the external world and from which the cells are loosened by
mechanical influences (epithelium of the skin and mucous mem-
branes), is especially subject to continual losses and compensation
for such losses by a succession of new cells. In the glands, too,
there is apparently a continual change of old and new cells, as the
function of the gland cells cannot but occasion in them aging and
death ; this exchange is an active one in the tissues of the testicles
during the period of seminal production, and in the ovary, too, the
formation of ova is in a measure a regenerative production. In
some glands which form their secretions without particular destruc-
tion of their cells (mammary glands, kidneys, sweat glands),
renewal in this sense is, however, not recognizable ; and in case
of the important elements of the central nervous system, the
ganglionic cells, it is a question whether they are at all subject to
change or persist throughout the whole life of the individual.
The cellular constituents of the blood and lymph are very perish-
able, and in the spleen, bone marrow and lymph nodes compensatory
production of these corpuscles is unceasingly going on.
A regenerative process may be regarded as pathological only
in the sense that it occurs in connection with unusual losses of
substance or pathological lesions of tissues, as after ruptures in
continuity ; it is in reality only an exacerbation of physiological
histogenesis as the processes of growth in both are identical.
Reasons for Regeneration. 233
The causes, or better, the reasons why, after tissue injuries and
losses, regenerative growth occurs, are complex. Normal increase
of cells depends upon inherent peculiarities of the cells themselves.
The capacity for multiplication is characteristic of all cells for a
certain time after they are formed; it is most active during em-
bryonic life and in youth, diminishing and, within certain limits,
ceasing after the full development of the body, as determined by
the relative tension of the tissues and the inherited characteristics
(phylogenetic). From those influences exerted by the tissues upon
each other and by which mutual restraint is maintained so that
an overgrowth of one cannot take place at the expense of the rest,
the normal inter-resistance of tissues, the so-called tissue tension,'^'-
takes its significance. (However, as ^larchand has suggested,
mechanical resistance to growth does not alone explain tissue
equilibrium ; there are other participating influences, as nutrition.
The constancy of the shape and size of the organs and the cells is
a fundamental peculiarity of the species.)
\\'e mav see in many cases where removal of normal tissue
resistance has taken place (where, for example, the tissue tension
has been released by the formation of cavities) the parts bordering
on such situations assume active growth. This is very strikingly
apparent where there is a cleft in the diaphragm next to the liver,
as the result of which the liver tissue invariably grows through the
round or oval diaphragmatic opening into the chest cavity (as a
button goes through a buttonhole), the otherwise uniform opposi-
tion which the diaphragm exerts upon the anterior surface of the
liver being interrupted at this position and lost. In any defect
produced by trauma or analogous loss of continuity of the tissues
the normal resistance is more or less lowered and the adjacent cells
are able to penetrate into the vacant space and fill it (vacuum
growth). As a result of the displacement of the cells thus pene-
trating the vacant area from their original station, space is afforded
in the latter position as well, thus giving opportunity for further
proliferation of the elements persisting there (Ribbert). According
to Ribbert the displacement of cells even from distant positions
may be explained by such a release of tension ; thus in the regenera-
tion of blood, leucocytes pass into the circulation and spaces are
left in the bone marrow, which are filled by newly forming cells.
and with the passage of these the process repeats itself indefi-
* Ribbert means by tissue tension not only pj-essure conditions, but all the
opposing influences of the various tissues upon each other.
234 Regeneration.
nitely. Anything, even hypersemia, which tends to separate the
tissues, has in Ribbert's opinion the same effect to decrease tension
and produce space. Although objection may be made that the dis-
tending cause must also have a pressure effect which should inter-
fere with growth, it must be granted that the vessels distended
and engorged in hypersemic conditions separate from each other
the closely packed cells, and that similarly the filling up of the
lymph spaces with exuded material forces the cells apart and in
this sense has an influence to relieve tension. The release of
mechanical tension is, however, not invariably the only cause of
tissue growth ; there are other factors which are operative to di-
rectly stimulate cellular proliferation. There can be no doubt that
increase of nutrition, provided the cells are in condition to
assimilate it, must necessarily favor multiplication. Especially in
inflammatory regeneration it may be appreciated that there is such
a rich nutritive supply possible for the cells at the periphery of
the inflammatory focus from the albuminous fluid exudates, fibrin
and products of disintegration of leucocytes and blood coagula.
that there cannot but coexist a condition of extra nutrition of
these elements along with relaxation of and space formation in
the tissue. The multiplication of tissue in chronic inflammations,
protracted hyperemias and lym])li congestions may also be partly
explained by this idea.
In addition it is possible that the elevation of temperature
attending inflammatory processes may play a part, as it
is well known that warmth is an important stimulus to cellular
activity and therefore to cellulai" proliferation. Chemical agents
should also be included among the important factors of stimulation
of cell multiplication. Just as the mobile leucocytes are attracted
by nutritive substances and other materials and assume a phagocytic
activity, the fixed cells respond to the chemotactic stimulus of
nutrient matter. They do not merely manifest evidence of phago-
cytic action which underlies their hypernutrition and consequent
cell division, but there may be distinctly recognized, as in the
regeneration of nerves, that there exists some special substance
exerting attraction, which determines the direction of growth of
the proliferating cells. Fibrin especially seems to exert this two-
fold influence ; in most cases where a layer of fibrin overlies the
tissue, the latter is apt to soon proliferate into the fibrin
(Marchand). The substances set free by the destruction of leu-
cocytes are apparently capable of exerting a chemical stimulus
Reasons for Rci^^ciicratioii. 235
in this sense. According to ]\larchand many cells have a tendency
to adhere to their support with as broad a base as possible until
forced off by other cells of the same type, as may be seen in the
wav young connective tissue cells force their way into the smallest
cellulose meshes of elder pith, necessarily passing through its nar-
row pores and changing their shape to marked degrees. This tactile
stimulus perhaps explains the tendency of connective tissue cor-
puscles to apply themselves about foreign bodies, fibrin fibrils and
analogous objects.
In most cases the causes enumerated are combined to give origin
to the stimulus for cellular proliferation ; for example, where granu-
lation tissue grows up and out of a wound in a luxurious manner
instead of ceasing to grow after filling the wound and then
cicatrizing, the condition may be ascribed to the combined influence
of a number of the conditions above indicated, as the absence of
pressure opposition, excess of nutrition and the action of special
irritants (saliva, medicaments).
Regenerative capacity is possessed by the cells and tissues of
animals in varying degree. In in,vertebrates and the lower verte-
brates the power of replacement or regeneration of important parts
after loss is common to all the tissues. Both pieces of a divided
earthworm grow into perfect creatures ; salamanders and lizards
can reproduce completely the loss of a tail, with bones, muscles, and
even the portion of spinal cord belonging thereto ; salamanders can
form a new leg in place of one cut oft", or an inferior maxilla
(Samuel, Ribbert). This extensive regenerative capacity has been
tentatively explained by the supposition that such low forms of
animals are more commonly subjected to injuries of the type indi-
cated and so their cells, naturally and because of their, less com-
plicated structure, retain their power of adaptation better than those
of the higher animals. In the latter the cellular construction is
more complicated and more fully developed for special functional
requirements, and possess a less marked tendency to divide in
comparison with the simple cell forms, are less independent, and in
some degree require the co-operation of other cells in their nutritive
processes. The more a type of tissue or cell departs from its
embryonic state and the higher differentiation it attains, the more
difficulty it experiences in attempting regeneration. The epithelium
of the skin and mucous membranes and connective tissue retain
their power of adjustment in response to the numerous faults to
which they are liable, and easily and quickly regenerate in the
higher as well as the lower forms of life ; but the ganglionic
236 Regeneration.
nervous cells and striated muscle, which can only exist, from a
functional standpoint, in connection with nerves and which are of
a decidedly complex structure, and in the same way glandular cells,
regenerate only under special circumstances or not at all.
[The conditions, then, which underlie cellular regeneration may
be summarized somewhat as follows: Only cells which from the
simplicity of their structure and function or from the fact that they
have not advanced far from their embryonic state are likely to mul-
tiply with any comparative ease. Any cell must be provided with
sufficient nutrition to maintain its cellular activity and life if it be
expected to divide, and extra nutrition as met in hypersemia favors
multiplication. Cells capable of division cannot, however, prolif-
erate if there be important mechanical or physiological opposition
exerted by the other cells and structures of the body, and release
of such mutual tension (mechanical, nervous, chemical) must be
afforded before proliferation is possible. But in addition a definite
stimulus to division should exist. This stimulus may be of chem-
ical nature, perhaps afforded by special chemical substances coming
to the part from previous cellular disintegration (here the brilliant
results of Jacques Loeb in producing multiplication and develop-
ment of unfertilized ova of sea-urchins by immersion in special
chemical solutions are strongly corroborative), electrical (here, too,
the work of Loeb and his associates is illuminating), thermic or
mechanical.]
In the adult organism of animals and birds the somatic cells
reproduce in their process of division and multiplication only cells
of their own type (omnis celhila e ccUula cjusdem generis) ; in other
words, a newly formed tissue is invariably the product of tissue of
the same kind. It was formerly believed the various types of cells
could in their multiplication produce opposite types and that in the
same way as the various organs arise by their differentiation from
the three embryonic layers similar transformations of tissue could
take place in the restoration of post embryonic defects. A certain
capacity for transformation (metaplasia) is possible in related
types of cells and their matrix products. Thus the different
varieties of epithelial cells may be changed by external influences
(pressure) ; and within the group of connective tissues transforma-
tions occur, as the formation of bone and cartilage from fibrous
connective tissue. But connective tissue is never changed into
epithelium, or the latter into connective tissue, the four distinct
groups of primary tissues (epithelium, connective tissue, nervous
tissue and muscle) never interchanging.
Regeneration of Conneetive Tissue. 237
The nature and method of celhilar proHfcration, as far as
nuclear and celhilar division is concerned, is in general the same as
in normal life, although there are pathological irregularities met
in the chromatin network and detailed structure of the protoplasm.
The replacement of lost tissue originates from the cells which hap-
pen to remain unchanged at the site of the defect or exist imme-
diateh- about it. If there are elements present in such a position, of
the same kind as those lost and capable of multiplication, their pro-
liferation may completely restore the fault, the area of loss being
filled up with identically similar elements with the same functional
abilities (simple or eo)iipIefe re^i^-eiierafioii) . Should the proper
cells be absent from the vicinity of the faulty area regeneration
will be incomplete (false), and the space will be occupied by cica-
tricial tissue derived from the connective tissue structures every-
where present.
Kegeneration of Connective Tissue and Bloodvessels. The con-
nective tissue framework is the tissue which takes the principal
part in repair in lesions of any kind, whether traumatic lesions of
continuity or necrobiotic destruction of the parenchyma of organs ;
usuallv the first elements to multiply being the connective tissue
cells, these taking the place of the various elements incapable of
regeneration. For this purpose their power of movement and of
taking up otlier cells and all sorts of disintegration products
makes them of value to the organism in the removal of
substance which has become useless, and in the construction
of a protective wall about foreign bodies. The greater
part of the connective tissue seen in sections is made up of minute
narrow spindle cells, almost completely occupied by dark elongated
nuclei, and intervening bundles of fibrils. In case of prolifera-
tion of this tissue these spindle shaped elements multiply, the
nuclei undergoing mitotic division and the protoplasm increasing
in volume. The newly formed connective tissue corpuscles are
thicker and polymorphous, sometimes rounded or polyhedral, and
provided with a number of processes; they usually lie closely sit-
uated, often in rows one after another, and show their active
part in the proliferation b\- the presence of mitotic nuclear
figures (one cell sometimes contain'ng two or three nuclei). As
they approach the type of embryonic mesoblastic cells and repre-
sent the young germinal elements of connective tissue they are
known (Lebert) as fibroplasts (irXdacHv. to form), or Hhrohlasts
(^Xa'TTdvw. to germinate). In connection with the multiplication
of these cells there also occurs a new formation of the connective.
238
Regeneration.
tissue fibrils, the processes of the fibroblasts splitting up into fine
threads, at first in a brush like fashion, the protoplasm of the
cell gradually changing completely into a bundle of parallel fibrils
(Diirk, Neumann, Ziegler). Thus by the splitting of the enlarged
cell-body into fibrils the cell comes to resume the type of the fixed
connective tissue corpuscles, and the mass of proliferated fibroplastic
tissue assumes the character of adult connective tissue structure.
In addition to the fibrils the protoplasm of the connective tissue
cells gives ofif a greater or less amount of a soft mucoid inter-
cellular substance (Marchand). The young fibroblasts are con-
^
■■H-
**
Fig. 43.
Fibroblasts and augiopla.sts in granulation tissue of licrse.
tractile and consequently are inconstant in form ; they can project
processes of their substance and thus can surround other cells,
shreds of tissues and nutrient substances and incorporate them
like phagocytes. They can also change tlieir position^ this property
explaining the fact already mentioned that foci of disintegration,
areas of h senior rli,age and situations of other types of lesions are
penetrated and occupied, and foreign bodies are encapsulated by
these elements. Their motile power is so marked that if. for ex-
Regeitcrafio/i of Coiinccfk'c 7'issiic. 239
ample, a bit of sponge or fragment of elder ])ith be introduced into
a tissue or serous cavity it becomes completely penetrated by these
fibroblasts.
Along with the connective tissue cells proper, the endothelial
cells of the blood and lymphatic vessels take part in the new forma-
tion of connective tissue. In both forms of cells mitosis prevails
profusely ; the young endothelial elements resulting from the cell di-
vision are like the other fibroblasts, being distinguishable from those
derived from the spindle cells only at their places of origin from the
blood vessels, where they are forming capillary tubes. Whether
endothelial cells ever form fibrils or solely develop into vessels is
not fully determined (for details consult ]\Iarchand). Another
long debated question, whether the leucocytes actually take part in
the connective tissue formation and are transformed into connec-
tive tissue cells, may be answered on the basis of more recent
studies (Marchand) that the white corpuscles which exude from
the blood vessels are principally concerned in the removal of for-
eign matter and products of disintegration, that they furnish nutri-
tive substance in case of their own destruction, but are incapable
of forming intercellular material and therefore cannot be consid-
ered as actual constructive elements of the connective tissue. The
presence of these leucocytes in every area of proliferating connec-
tive tissue is therefore dependent upon their entrance partly from
the vessels, partly from points of lymphoid development to be
found commonly along the bloodvessels in any tissue. The whole
cellular group more or less closely approaching leucocytes and cells
from the lymph glands (lymphocytes), but because of their more
conspicuous cytoplasm or a variety of granulations of their proto-
plasm given other names (plasma cells, iiiasf cells, leucocytoid cells,
polyhlasts, klasinafocytes) , are also found in the growing connective
tissue. The origin of these cells and tlie question of their relationship
is still rather uncertain ; probably they are all immigrants originating
from lymphocyte depots. Giant cells (polykaryocytes) are also often
observed in developing connective tissue, and multinucleated cells,
especially when foreign bodies are present ; they are formed partly
from the multiplying spindle cells, partly from endothelial cells, and
may be regarded as cells whose protoplasm has increased and whose
nuclei have multiplied more rapidly than cell division could keep pace
(proliferation giant cells). According to another view they are
caused by coalescence of closely grouped embryonic cells (congluti-
nation giant cells).
Opinions concerning the mode of origin of elastic fibres in the re-
240
Regeneration.
generation of connective tissue are not fully formulated ; their forma-
tion is, however, a slow process. It is only after four or six weeks
or after several months after repair by the fibroplastic tissue that
elastic fibrils appear in the intercellular substance; and even after
years these do not attain the diameter of the original elastic ele-
ments.
Connective tissue, modified to form adipose tissue by fatty infiltra-
tion, is capable of proliferation to the same extent as ordinary connective
tissue cells. The nucleated protoplasmic remnant of the fat cell undergoes
division, and the new cells usually at first accumulate in the fat vacuole
within the old cell membrane.
Formation of blood z'csscls takes place by a process of budding
and division of the endothelial cells from the existing capillaries.
The protoplasm of the endothelial cells in the walls of the old ca-
pillaries which have remained intact send out pointed, conical proc-
esses, which lengthen out in thread like manner, and penetrate
■■-g^S*'*^'
•;U3^jg^<
Fig. 44.
Vascular sprouts, highly magnitied : (after 'i'homa). The long thread-like ends
of the sprouts are only partly reproduced.
between the proliferating fibroblasts. Coincidently mitosis of these
endothelial cells takes place and at the base of the bud cellular
division begins and the endothelial cells (angioplasts) proliferate.
These new elements lie alongside of each other and fuse, with their
often curved and reticular branches, into solid cords of cells.
From these the capillary tubes are produced by the forcible pene-
tration of the blood from the old vessel in between the dividing
endothelial elements, thus making a space filled with blood. This
proceeding at all places where these buds are forming, gradually
the whole network becomes canalized. From some of the capillaries
arteries are formed, from others veins, the lumen of the tubes
Formation of Blood Vessels. 241
being widened by blood pressure and growth of the wall (increase
of surface by multiplication of the parietal endothelial cells) ;
smooth muscle grow-ing from the existing arteries into the newly
formed vessels, and the surrounding fibroplastic tissue aiding in the
formation of elastic fibres. (Regeneration of blood vessels has
been especially studied by J. Arnold, Jos. ]\Ieyer, Billroth, C. Weil
and Thoma.)
The development of angio-fibroplastic tissue is accompanied by
more or less manifest phenomena of inflammation (hyperemia,
exudation of leucocytes) and is therefore in a sense a result of pro-
ductive inflammation. Depending upon the number of blood ves-
sels present and the relative amount of proliferated connective tissue
the new structure presents a reddish-gray, grayish-white or pure
white, swollen appearance, semitransparent and of a shape conform-
ing to that of the lesion which it has followed. \Mien it develops
diffusely, as in parenchymatous organs, to replace destroyed gland-
ular tissue, it gives rise to more or less marked induration of the
part (indurative inflammation), or forms translucent hard thicken-
ings (in fasciae, serous membranes), bands of adhesion (adhesive
inflammation) and sometimes villus-like fringes. In focal devel-
opment it forms white trabecular or nodular connective tissue
masses (in infarcts of the kidney) ; as the result of a demarcating
inflammation about some blood clot or foreign body it constitutes
a connective tissue capsule. On the free surfaces of wounds the
new formation is seen as a finely granular soft tissue, producing an
exudate, with a deep red or reddish gray color from the abundance
of capillary buds in its structure : it is known as gramilation-tissue.
All fibro-angioplastic tissue is at first likely to form a greater
bulk than the lesion which it replaces. There exists an excessive
production of the young cells and these cause an excess of inter-
cellular material. \\'ith restoration of normal tissue tension and
maturation of the growing tissue, these originally enlarged cells
shrink and the intercellular substance decreases ; the fibrils are ar-
ranged in a parallel fashion from the tension and pressure of the
neighboring structures influencing them; some of the capillaries
become obliterated, that is, narrowed, from pressure by the shrink-
ing fibroplastic tissue. In this way, too, the whole tissue, some-
times, because elastic tissue is produced in deficient amount or not
at all, becomes dense and hard and is changed into cicatricial tissue.
This is apt to contract still further, thus forming in the surface of
the skin and organs depressions or indentations of radiating stellate
form.
242 Regeneration.
Regeneration of Epiderm and Epithelium of Mucous Mem-
branes. — The epithelium on the surface of the skin and mucous
membranes is capable of very rapid and complete regeneration.
Because of the continual loss of cells from desquamation as they
grow old the tissue is always prepared for and actively engaged in
regeneration. Either because of cellular tactile irritability (v. p.
235) or because the removal of tissue resistance in defects mechan-
ically causes it to undergo a regressive development, the new tissue
is very apt to spread out upon the free surfaces and to some extent
to increase in volume, a flat cell thus arising from a cylindrical cell
at the border of the lesion. The new cells are always formed from
existing epithelium and can only be produced providing vitally
capable cells of the same tissue are present in the vicinity of the
lesion.
The formerly accepted belief that epithelial cells could develop from
connective tissue has been shown to be erroneous.
In case of superficial loss of epithelium (abrasions, epithelial ne-
croses) the new surface cells grow over the denuded papilhe from
the margin of the surrounding epiderm. Within three-quarters
of an hour after a wound has been inflicted, under the microscope
there may be observed enlargement of nuclei and direct and indi-
rect nuclear division in the cells of the stratum ]\Ialpighii, both in
the margins of the lesion and at some distance from it ; after eight
or ten hours the epidermal border is visibly thickened ; and small
lesions only a few millimeters in circumference may be covered by
several lavers of epithelium in the course of forty-eight hours.
The epithelium actually spreads over the surface of the wound,
either from active motile power or because the superficial cells are
dislodged by those growing back of them in the deeper layers.
If the part deprived of epithelium is covered by fibrin, blood or pus,
a granulating surface, the proliferating epithelium at the margin
forces its way beneath the coagulated crust over the cicatrizing
connective tissue ; in these cases the epithelial layer is often rid-
dled with leucocytes, and afterward in the clefts and spaces thus
produced new cells may grow, forming branched plugs made up of
concentrically laminated, keratosed, epidermal balls (horny pearls,
atypical epithelial proliferation of Friedlander). Occasionally the
epithelium may penetrate along fistulous passages ; as in a perforating
dental alveolar fistula (horse) the squamous epithelium may grow
through the alveolus from the mouth into the nasal cavity.*
* Penetrative growth of epithelium at the border of ulcers and fistuljp
may determine a free atypical new formation of this tissue and thus give
rise to cancer.
Regeneration of Epithclhun of Cornea, Hair, Hoof. 243
The advancing margin of the epiderm may be seen as a bluish
white wavy zone, sometimes with a rosy tint from the hypersemic
substructures showing through. Sometimes in addition to the epi-
dermal growth at the margins of the lesion, islands of epithelium
may be observed in the midst of the new surface. These may origi-
nate from the remnants of the ducts of sweat glands or hair folli-
cles (the cells of which are practically identical with those of the
surface) which were left intact because of the superficial extent
of tlie loss of substance ; or may arise from epithelial cells separated
from the border and caused to adhere to the surface of the wound
by the application of a bandage.
The proliferation of the epithelium does not stop until the free
surface of the lesion is completely covered. Epithelial scars are for
a long time devoid of pigment and in a dark skin the cicatrix is
conspicuous because of its whiteness.
The corneal epithelium is ver}- quickly reformed after destruc-
tion, a circular loss of three millimeters diameter being perhaps re-
placed in the course of from thirty-six to forty-eight hours. The
cells at the margin, moving in by amoeboid power and flattening out
to form at first a protective single celled layer, spread out over the
surface ; these multiply, showing mitotic figures and multinuclear
examples, and build up the layers of corneal epithelium ; the cells
assume a cuboidal shape and the lesion is completely repaired. In
case of wounds of deeper extent or those perforating the whole
thickness of the cornea and involving the corneal connective tissue
and Descemet's membrane, the lesion is at first filled up by fibrin
(from tlie aqueous humor). The rapidly growing epithelium ex-
tends over this and forces itself into the depth of the wound like
a plug. The connective tissue is formed subsequently, and on the
posterior surface the endothelium of Descemet's membrane regen-
erates its single layer of cubical cells. A milk white spot remains
at the site, the result of cicatricial production by the newly formed
connective tissue.
(Regeneration of the cornea has been exhaustively studied, especially
from an experimental standpoint, in animals; for details cf. Marchand.)
Regeneration of hair can occur only in case the hair follicles
or portions of them remain. In all deep cutaneous lesions the cica-
trix is permanently smooth and devoid of hair.
Regeneration of horny tissue of the hoof. After injuries to the
keratous envelope or after it has been ruptured from suppurations
of the corium the horny layer may be regenerated by proliferation
244 Regeneration.
of the keratogenous cells over the surface of the granulating papillae
and fleshy laminse of the persisting cutis (the latter the seat of
compensatory and sometimes regenerative changes) and the forma-
tion of a new protective layer over the denuded papillary surface
(Gutenacker). The first formed cells are pushed forward by suc-
ceeding new growth and form keratous tubules by arranging them-
selves in circles about the papillae ; later interpapillary keratous
substance is deposited in the intervals between the tubules as a yel-
low, perhaps soft and incompletely keratosed, and usually very
thick mass (cicatricial keratin). In parts where there are no
papillae the keratogcnous cells are arranged in irregular, superim-
posed layers. Operative denudations of the corium of the hoof
from five to ten square centimeters in area may be completely over-
grown by new horny substance in the course of from four to six
weeks.
(For details cf. Lchrb. d. Cliinirgic, by Frohner, and /f M/feranfe-
heiten, by Gutenacker.)
Regeneration, compensatory for losses of cylindrieal epithelium
upon mucous membranes, proceeds in the same way as the process
in the epiderm. The epithelial cells growing in from the periphery
over the surface of the lesion at first assume flat, then cubical and
finally cylindrical shapes and in appropriate cells it is even possi-
ble that the ciliated border will be reformed. The surface epithe-
lium of a wound of the gastric mucous membrane of a dog may be
completely reformed in from four to ten days.
Regeneration of Glands. — Epithelium of glands is very irregular
in its regenerative ability. The epithelium of glands of the mucous
membranes corresponds histologically with that of the surface of
the membrane, as in the intestine or uterus ; and therefore in these
parts epithelial repair over cicatrices, ulcers and wounds may, be-
sides merely covering the surface of the lesion, sometimes also ap-
parently attempt gland formation in points of depression. The
epithelial cells formed in such cases grow from remnants of in-
volved glandular structures or from the uninvolved adjacent tissue
over the seat of the lesion. The depressions occur at the
expense of the young growing connective tissue or granula-
tion tissue which is being developed at the same time ; but the more
marked the retraction of the scar the less successful the glandular
reformation. Ponfick, Gluck and v. Meister in their interesting ex-
periments have pointed out in connection with regeneration of
the liver that after operative removal of a portion of the hepatic
tissue from rabbits, rats and dogs a remarkable regenerative activity
Regeneration of Glands, Spleen, Lymph Glands. 245
occurs. Alter ablation of half of the bulk of the organ new liver
tissue developed from the remaining- portion by luxuriant prolif-
eration of the hepatic cells, setting in as early as the third to the
fifth day; after an average of from forty to sixty days the part lost
was completely restored in volume and weight. It is conceivable
that after other local lesions liver tissue may regenerate, yet after
traumatic lesions or destruction of hepatic parenchyma by the pene-
tration of parasites nothing but cicatricial connective tissue is seen
at the site of the defects, always containing on microscopic examina-
tion decidedly proliferated bile ducts, but without evidence of
formation of functionally capable liver cells. This probably
is due to the fact that in the type of defects under con-
sideration the connective tissue framework has also undergone
pathological changes, and perfect restoration of functionating
parenchymatous cells can only be expected when the connective
tissue basic structures are in normal condition (Ribbert). The
enormous enlargement of the liver sometimes seen in tuberculosis
and echinococcus disease is apparently due not merely to the
foreign elements and to connective tissue hypertrophy, but may
possibly be dependent upon a vicarious hypertrophy or regeneration
of the hepatic parenchyma.
It is not certain in case of the kidney whether epithelial cells
lost in consequence of inflammations and degenerations of the paren-
chyma can be restored completely. Lesions from infarction, suppu-
ration or trauma always heal by cicatrization. There may, how-
ever, take place a compensatory hypertrophy of adjacent tubules
and glomeruli to occupy the space caused by shrinkage of such
scars, which in a measure may compensate for the lesion.
The tissue of the testicles and ovaries has but little regenerative
power ; space caused by trauma and degeneration is always filled in
by cicatricial tissue. On the other hand the glandular epithelium
of the mammary gland, thyroid, salivary and lachrymal glands is
capable of extensive proliferation from remaining portions of the
alveolar tissue, with formation of new ducts and glandular acini
lined with secreting epithelium.
The spleen and lymph nodes although subject to continual
change of their cellular constituents and capable of originating in
pathological conditions a marked excess of their lymphoid tissue,
do not regenerate after traumatic lesions, being invariably subject
to cicatricial repair.
Striated muscle, when the fibres have been partially destroyed
by degeneration of their substance, is able to regenerate in a certain
246 Regeneration.
measure ; at least microscopically proliferation of remnants of nu-
cleated sarcoplasm may be observed, whole chains or rows of new
nuclei being produced b}- direct nuclear division, these in asso-
ciation with proliferation of the sarcoplasm by longitudinal divis-
ion going to form the so-called muscle cylinders (\\'aldeyerj and
lateral olT-shoots known as muscle buds (Naumannj. Apparently
the sheath of the sarcolemma develops from the surrounding con-
nective tissue, which is also proliferating; and the developing sar-
coplasm takes on a fibrillar structure. In tramnatic lesions connec-
tive tissue formation predominates, the healing of the wound usually
giving rise not to the reconstruction of the contractile elements,
but to the formation of dense scars.
Smooth muscle even in traumatic lesions exhibits active mitosis,
and multiplication of the muscle of the blood vessel walls is to be
observed in granulating tissue ; but in lesions of muscular tunics,
as of the stomach, intestine or uterus, complete restitutio ad inte-
grum has never been observed, scar formation taking place instead.
Eegeneration of tendon tissue (studies of this process being
often afiforded in the rather common performance of tenotomy)
begins, according to Alarchand, principally from the loose cellular
tissue between the bundles of tendon fibrils. This formative ma-
terial, composed principally of spindle cells, develops (by mitosis)
into the cleft between the cut ends of the tendon, which is filled up
with blood or exudate, and unites the tendon stumps as a soft gray-
ish fibroplastic mass. Later the fibroblasts form a fibrillar matrix,
the fibrils arranged parallel with each other, and the tendon scar
gradually acquires great firmness. According to Paget a divided
tendon of Achilles of a rabbit may be found united as early as from
three to five days and in ten days may be of sufficient strength to
require a tensile force of twenty-eight pounds to tear it apart.
Lesions of cartilage, as that of the air passages, the auricle, or
ribs, are restored by connective tissue formation from the perichon-
drium, the cells of which give origin to a fibrillar, collagenous sub-
stance. The latter may become homogeneous and by a metaplastic
process the connective tissue thickening be converted into hyaline
cartilage ; and it is possible that by an infiltration of calcareous
salts ossification of the embryonic tissue occupying the space of
the lesion may ensue. The cartilage itself takes no part in the
process of restoration and connective tissue scar formation is usually
but slight.
New formation of osseous tissue after fractures and operative
lesions arises exclusively from the periosteum and bone marrow
Regeneration of Bone. 247
and ends by complete restitution of tlie most dense osseous sub-
stance. The special bone cells embedded in a dense solid calcified
matrix are unable to take part in the construction of new tissue
because they have no space for any activity. The osteoblasts of
the periosteum and marrow, the bone forming cells, are connective
tissue cells which possess the peculiar ability of giving origin to an
intercellular material with an affinity for lime salts or of them-
selves producing calcification of the matrix and thus supplying the
basic osseous material. They are, however, also capable of produc-
ing fibrillar connective tissue and may act precisely as fibroblasts;
and finally may become transformed into cartilage cells, form a
homogeneous inter-cellular material and remain in the lacunae
within the latter. In bone repair therefore there is first noted a
fibroplastic callus which becomes partly changed into cartilage and
later into calcified osseous tissue. Coincidently the blood vessels of
the bone proliferate, complete analogy to the vascularized fibro-
plastic callus existing in the healing of lesions of the soft parts.
The name callus is applied to the whole of the tissue arising in the
osteogenetic process, its origin giving the basis for differentiating
between periosteal and myelogenous callus; tliat portion which de-
velops between the separated fragments is known as the iiitcruicd-
iate callus.
In the neighborhood of the seat of fracture all of the periosteal
and marrow cells and vascular endothelial cells become swollen, nu-
clear division actively proceeds, and cellular proliferation is so lux-
uriant that the capillaries are often found occluded by young endo-
thelial cells and giving off profuse vascular buds ; the whole cellular
callus forming a growth decidedly exceeding the diameter of the
bone itself (the widei tlie space between the bone fragments the
greater this mass).
This callus, at first consisting of connective tissue and some-
times called the provisional callus, has to do with the removal of the
clotted blood occasioned by the fracture and other tissue remnants,
even of small splinters of bone (the limy material of which is dis-
solved by the proliferating cells), through phagocytic cells originat-
ing from its newly forming constituents. It has a bacon-like, cartilag-
inous appearance, surrounds the ends of the bone as a thick girdle,
occupies the medullary cavity at the level of the fracture and the
whole space between the broken ends. The newly formed material
is markedly in excess, and after calcification the osseous scar unites
the fragments as a clumsy, thick enlargement of the shaft of more
or less spindle shape, ^^'ith calcification, which renders the callus
248 Regeneration.
hard like ivory and of the compactness of cortical bone, the osteo-
blasts in the provisional callus are gradually enclosed in the calci-
fying matrix and shrink into the spindle-shaped and stellate form of
bone corpuscles ; the newly formed vessels with their contained blood
persist in the calcifying osteoplastic tissue, giving an analogy to
the svstem of the Haversian canals of bone. There is, however, no
lamellated structure in the tissue. After the osseous scar has become
hard and the bone is again strong enough to sustain weight and
muscular strain, a reduction of the excessive callus sets in, aplana-
tion of the callus; the external bulging of the bone diminishes; the
periosteum becomes closely adherent; the medullary callus becomes
porous, the medullary canal opens and the medullary substance be-
comes full of fat. These changes in the callus are brought about
by the growth of blood vessels into it from the marrow, and by
the influence of multinucleated giant cells of the medulla known as
osteoclasts ( KXacnye^v , to break) because of their agency in breaking
down osseous tissue (Rindfleisch ). The shrinkage is explained by
the biological law that lack of use causes structures to become
atrophic, only functionating parts being maintained. Hence in
conformity with this rule only those portions of the bony tissue
which are required to sustain weight or to oppose strain persist as
compact structures.
It is well known tliat the texture of any bone shows an arrange-
ment of its osseous trabecula conforming to the mechanical forces
acting upon it; this functional adaptation is operative as well as all
pathological conditions which occasion new mechanical features. In
the regenerated bone tissue the resumption of function not only
assures the maintenance of the osseous scar, but in addition de-
termines the precise arrangement of its osseous trabecula by fur-
ther thickening of those portions which are most heavily taxed : the
direction of the trabecular adjustment develops in correspondence
with the lines of stress determined by their functional relations in
supporting the body weight and opposing muscular strain.
Regeneration of Nerves. — Peripheral nerves severed from their
connection with the central nervous system by section, contusion
or other destructive lesion, degenerate from the point of the lesion
centrifugally to their peripheral end fibres, their axis-cylinders and
medullary sheaths being destroyed (broken down into myelin and
fat droplets) ; but the neurolemma and its nuclei remain intact
(Nasse, Waller, Lent, Benecke and others). The degeneration
may also extend centrally in the divided nerve for the distance of
one segment (to the first node of Ranvier). Conductivity ceases
Regeneration of Nerves.
249
instantly when continuity is interrupted (provided there are no col-
lateral paths). The space intervening- between the central and periph-
eral portions is filled at first with fibroplastic cicatricial tissue ;
but later a complete regeneration of the nerve fibres is accomplished
and in the course of two or more months the nervous function is
fully reestablished. This later development of the nerve fibres, as
Fig. 45.
Degenpi-ation of nerve fibres after sec-
tion. I. normal nerve fibre. II and III.
different degrees of destruction. S.
nein-filemma slieatli of Scliwann. ///,
medullary slieatb. A, axis cylinder. 7.-,
nucleus of neurolemma. L. Lanter-
mann's constriction of the medullary
sheath, int. myelin gloliules. «. remains
of axi.s cylinder, w, proliferating cells
of neurolemma. Partly schematic. X 476.
(After Thoma.)
§ |i
Fig. 4G.
Growths of the axis cylinder in the
central stump of a divided nerve. aS'.
neurolemma sheath of Schwann, m,
medullary sheath. A, axis cylinder of
undegenerated part of the nerve. A'.
newly formed axis cylinder, fc, nucleus
of neurolemma. ir, ic, proliferated
neurolemma cells, mt, myelin globules.
Scliruiatic, based on an illustration from
Eichhorst. X 470. (After Thoma.)
indicated b\- the microscopic findings, which are demonstrable with
much difficulty, may be explained in two ways. The majority of
investigators adhere to the views advanced by Waller and Strobe,
according to whicl;i regeneration is the result of a growth of the
axis cylinders of the central stump, these advancing into the young
cicatricial mass and growing beyond it, the delicate fibres of the
250 Regeneration.
axis-cylinders meanwhile undergoing subdivision. It is a striking
phenomenon in this process that the newly formed fibres of a divided
nerve should grow into the original areas of distribution. The
opinion most nearly explaining this assumes that the old paths of
distribution persist as actually empty tubes, or as the neurolemma
tubes of Schwann containing merely a softened fatty detritus, and
that the sprouts of axis cylinder substance find here the line of least
resistance in their penetration. It has, however, been shown that
after resection the nerve-sprouts, in spite of the insertion of special
interfering objects, follow along their original direction; and the
interesting experiments of Forsmann show that the nerve stump
will not invariably push its way into empty glass tubes which have
been inserted but will on the contrary always force its sprouts into
glass tubes containing nerve or brain substance, even if these be ar-
ranged in the wrong direction. It seems probable therefore that
chemotactic force, exerted by the degenerating nerve matter of the
peripheral portion of the nerve, determines the line of extension of
the growing nerve fibres (neurotropism).
The force of growth of the central stump is usually very marked.
V'anlair succeeded in enclosing calcareous tubes, made of bone, be-
tween the two ends of a divided nerve, and the growing sprouts not
only found their way into the lumen of the tubes, but even into the
Haversian canals (Thoma). Sometimes the budding axis cylinders
form tumor-like masses in the scar tissue around the stump, the so-
called amputation neuromata.
As the neurolemma with its nuclei remains intact in the degen-
erated peripheral fibres, it is possible that the formation of new
medullary substance may arise from this source in case the new
axis cylinders grow into these preformed paths. Proliferative phe-
nomena in the cells of the neurolemma have been actually observed
(Eichhorst, L. Mayer, v. Bi^ingner), and consequently the view is
held that this sheath, by dififerentiation of its protoplasm, may give
rise in segments to the axis cylinder and medullary sheath ; that
in this way from the old sheath new nerve fibres may be formed,
the segments then growing together to form continuous threads.
Ganglionic cells and the massive nervous tissue of the brain and
cord are incapable of regeneration. It is well known from numer-
ous experiments upon animals and studies in man in connection
with injuries, partial ablations and other types of loss of substance,
as from haemorrhage, degeneration, etc., that even in case the usual
Transplantation. 251
fatal complications do not develop such lesions do not end in
new formation of nervous elements but in fibroplastic cicatrization.
Regeneration of Blood Corpuscles and Lymph Cells. — The resto-
ration of blood cells does not take place within the blood vessels, but
originates in those organs in which normally the continual replace-
ment of worn out cells of the blood and lymph is accomplished, par-
ticularly the bone marrow, spleen, lymph nodes and in lymphoid
germinal foci scattered about in various tissues. The red blood
corpuscles develop entirely from cells of the medulla of bones and
are nucleated when first formed ; b}' the time they have entered the
circulation their nuclei have disappeared. Serious or repeated loss
of blood cells calls forth so marked a proliferation of the hemo-
poietic marrow tissue that the fatty marrow of the long bones comes
to resume its embryonic character and is changed into red marrow.
The colorless corpuscles are produced by proliferation of the leuco-
cvtes and Ivmphocvtes in the structures mentioned and pass out into
tlie blood.
The fluid portion of the blood is renewed by the passage of
water and salts from the tissues into the lymph and blood capilla-
ries.
Transplantation.
Some cells and tissues can maintain their vitality for some time
after their removal from the animal body and are capable of renew-
ing their growth if artificially implanted upon another part of the
same body or in another animal.* Experiments in transplanation
have been performed frequently and sometimes successfully by
surgeons ever since the fifteenth century, for the purpose of re-
storing denuded parts of the skin and other tissues in man ; and,
too. the same experiments have been repeatedly performed in ani-
mals in order to obtain theoretical grounds for operative procedures
and explanations of pathological questions.
It is most easilv and successfully performed in lower animals.
Born has succeeded in causing adhesive growth in pieces cut rflf
from larval amphibians to take place in various ways, as of the
head end of one larva to the tail end of another. Joest succeeded
in uniting the opposite ends of earthworms. As interesting trifles,
after the castration of cocks the spurs used to be often cut off and
* Inoreranic particles, as bits of ivory, wire or bullets, if they get into or
are introduoed into the tissues (implantation. Insertion) may be encapsulated,
that is. surrounded bv connective tissue. Even living- or dead tissues may
be similarly surrounded, as an extracted tooth may be thus held in an alveolus
in which it is implanted. In transplantation, also known as grafting (French,
<i>Tffe). there is not merely an encapsulation or adherence of the tissue
to the' structure, but in addition it multiplies in the site of Implantation and
forms part of the organic structure with the tissue about it.
252 Transplantation.
inserted into a split in the comb of the capon, becoming attached
by growth in this situation (Aldrovandi, Worm, in the seventeenth
century ; Baronio in 1804). The spur, if engrafted when very young,
may grow in this new and well vascularized base to become several
inches in length ; and sometimes tlie central bony core grows, carry-
ing over it a horny epidermal covering, so as to produce two spurs
growing alongside of each other. Embryonic tissue with undiffer-
entiated cells shows a moderate capacity for growth when trans-
planted. Fere grafted bits of blastoderm (forty-eight hours) and
the eyes of six to eight day chick embryos under the skin of young
chickens and noted that the mesoblastic tissue underwent more or
less further development to the production of small tumors (con-
taining cartilage and in one case small feathers), which persisted for
about a month. Such a result has an important bearing in explain-
ing the conditions involved in the origin of tumors.
Transplantation of tissues is more difficult in mammals. The
possibility is best realized when the part to be transplanted can
retain connection with its neighboring structures by a bridge, as
where a flap of skin is twisted around and stitched to an adjoining
part, the nutrition of the flap being at least partially maintained
(as in the operation of rhinoplasty in man). The result in trans-
planting unattached and completely separated bits of the corium
and of the epiderm is not at all uniform. In this procedure, recom-
mended by Reverdin and Thiersch for quickly obtaining an epi-
dermal surface over large superficial wounds, which has been tested
by many investigators, especially by ]\Iarchand and Enderlin experi-
mentally, the transplanted fragments adhere by a layer of coagulated
blood and lymph to the fresh or granulating wound. Later on there
occurs an active vascular and cellular proliferation in the substruc-
ture, the fibroblasts and angioplasts of the latter growing up into
and through the engrafted cuticular fragment, which is actually re-
placed by the new connective tissue. The epithelium desquam-
ates and only to a very slight extent is the graft the starting point
for the formation of the new layer of skin. In reality the new
graft is more like a piece of plaster, beneath which the formation
of new elements from the adjacent structures may take place with
facility (Diirk). For success in such transplanations the size of
the bit of tissue transplanted should be taken into consideration
(even particles no larger than a pea may disintegrate in the central
part because too much time is required to afford them proper nour-
ishment), as well as the question whether the base of implantation
affords thoroughly favorable conditions for nutrition. For example
Transplantation of Skin and Glands. 253
suppuration of the granulating- surface interferes with proper at-
tachment; and, as the function of the tissue depends greatly upon
nervous influences growth of a transplanted fragment is sometimes
prevciited because of the lack of any natural nervous comnuniica-
tion. Again the portion to be transplanted ought to be kept as
nearly as possible at its proper vital temperature (tissues have been
successfully grafted, however, even after having been ke]it for
from one to four days).
While transplantation of bits of skin to new positions in the
same individual, as to the ear in a rabbit, has met with fair suc-
cess, attempts to graft from one individual to another have not
been so successful ; and transplantation from the skin of an animal
to man has failed in most instances. Efforts to transplant mucous
membranes (that of the lip to the lid) and of keratous tissues (in
the repair of corneal lesions), both in man and animals, have shown
little uniformity. In transplanting cartilage, periosteal and bony tis-
sue the graft as a rule persists for a long time and there may be
noted a certain amount of increase of the cartilaginous and perios-
teal cells. However, this is not active enough to permit it to be
said that there is an artive part taken by the graft in the repair of
an existing lesion ; but rather that the fibroblasts, angioplasts and
osteoplasts at the border of the lesion grow into the transplanted
tissue and gradually take its place. Inasmuch as the transplantation
of such material (small fragments or pieces of bone, the length of
a finger, not necessarily fresh bone but with equally good results
in the use of macerated or boiled bone or bone sterilized by heat)
may materially aid and hasten the restoration of a given defect
and the formation of a solidly ossified scar in it. the method has
gained considerable importance in surgery.
Experiments by Ribbert. Lengemann, Lubarch and Enderlen
have proved that transplantation of small pieces of salivary glands,
sebaceous glands, mammary tissue, thyroid gland, epididymis, ova-
rian tissue, and liver tissue into the peritoneal cavity, anterior cham-
ber of the eye. under the skin and within the lymph glands, is fol-
lowed by more or less perfect adhesive growth and actual prolifera-
tion of the glandular epithelium, with formation of new cellular
extensions with development of gland spaces and persistence of the
vitality of the transported tissue. Ribbert's graft of mammary
gland tissue into the ear of a young guinea pig has special interest
from the fact that when the animal bore young the transplanted
gland began to secrete milk.
254 Hypertrophy.
Operative grafting of thyroid tissue in case of loss of this organ
(as in goitre and operation for the removal of goitre), which is
apt to cause serious and even fatal disease, may successfully com-
pensate for the loss and is therefore of value from a therapeutic
point of view.*
Hypertrophy. G-igantism.
By the term liypcrtrophy is meant the increase of the essential
tissue of a part of the body, leading to enlargement of that part.
Literally the term reallj- means excess of nutrition {virep and Tp6(pos,
nutrition), and from ancient times it -.vas used to express increase in
volume of tissues and organs when it was supposed that this depended
upon an increase of the nutritive supply to the ::tructure involved. Theo-
retically and from the microscopic findings, two types of increase in
volume may be conceived of : hypertrophy, in which the cellular elements
are seen to be increased in size, and hyperplasia, where a numerical
increase in the cells is the b.'isir, for the increase in the c'imtnsions of
the organ. [These are often spoken of as simple hypertrophy and numeri-
cal hypertrophy.!
Where the increase of tissue involves the functionating elements
of an organ or part, as the parenchyma of a gland or the muscle
cells, it is spoken of as true hypcrtropliy; where, however, it con-
sists in an increase of the supporting tissue or so-called interstitial
substance alone (connective tissue, fat) it is a false hypertrophy.
True hypertrophies occur because of increased demands upon
the activities of an organ and because of its increased functional
effort. Such examples are termed ivork hypertrophies. This is most
frequently seen in muscles, a very common example being met in the
increase in the skeletal muscles in gymnasts and the arm muscles of
wood choppers and smiths. The increased cardiac force in those
conditions of life in man and animals requiring continuously special
power of the heart is an expression of an hypertrophy. The heart
possesses in a marked degree the power of accommodation to in-
creased demands upon its ability ; its muscular substance in case
of permanent increase of labor increases {accommodative hyper-
trophy) up to a certain degree, determined largely by the relation
to the body weight. According to tlie investigations of Bollinger
and Parrot all animals wdiich are required to exert much muscular
energy because of their mode of life possess a heart heavier in
proportion to the body weight than those animals which lead a
sluggish life, as the dog in comparison with the hog, the deer in
* In man thyroid preparation.s may be administered by the mouth.
Compensatory Hypertrophy. 255
comparison with the sheep. There are marked differences in this con-
nection between those birds which are good fliers and the domes-
tic fowls which stay more on the ground. (For details cf. Kitt,
Pathol. Anatomic dor Haustierc, 11 Bd. Chapter on the Heart.
\ei-l. V. F. Enke, Stuttgart. II Aufl. 1901.)
All diseases which increase the work of emptying the ventricles
of the heart in the period of systole and which force the heart to
continuously increased pumping effort, give rise to cardiac hyper-
trophies, usually confined to one part of the organ according to the
position of the opposition to the cardiac effort. Chronic valvular
lesions, which interfere with the ready passage of the blood from the
auricles into the ventricles, after a primary dilatation of the
auricles cause hypertrophy of the auricular walls; stenosis of the
semilunar aortic valves causes hypertrophy of the left ventricle,
stenosis of the pulmonar}- valve a hypertrophy of the right ventricle ;
It is only by a heightened muscular force that the blood can be
pressed forward in such conditions. If the cardiac hypertrophy
is for a long time sufficient to accomplish the increased demands
put upon its functional capability and thus prevents the serious
results of tlie original disease or compensates for them, it is spoken
of as a compensatory hypcrtropJiy.
Smooth muscles also become hypertrophied in case of increase
of function, physiologically seen in the pregnant uterus, patholog-
ically observed in marked degree in the intestinal wall where con-
strictions in the lumen gradually develop, over which the chyme can
be driven only by increased peristaltic force. The same thing is
seen in case of the urinary bladder, resulting from narrowing of
the neck of the viscus by prostatic enlargements or from involve-
ment by urinary calculi, etc. : and in the oesophagus in case of stric-
tures. In all these cases there occurs both a multiplication and an
increase in size of the muscle cells.
In the glands of the body true hypertrophy and the necessity for
increased effort become apparent where smaller or larger portions
of the glandular parenchyma are destroyed, and are restored or re-
placed by regeneration. In case this cannot fully obtain or does
not occur at all, as in the liver tissue (after echinococcosis or chron-
ic inflammations) the remaining portions of the organ become en-
larged and the general volume of the liver may thus become greater
than normal. Especially in case of bilateral organs where one be-
comes entirely incapable of function, the remaining one acts for
the former, performs a correspondingly greater amount of work
and hypertrophies (compensatory or vicarious hypertrophy). Where
256 Hypertrophy.
one kidney is removed in an experiment, in the course of but a few
days thereafter the other begins to enlarge ; and it is not infrequent
in slaughtered animals to find one kidney shrunken up and the other
from one to two-thirds larger than the normal organ. The reason
that the increase in volume does not reach double the normal is
because all of the constituent elements do not hypertrophy in even
proportion, the process involving particularly tlie secretory struc-
tures, the glomeruli and the convoluted tubules, the epithelial cells
of w^hich enlarge and the coils become more intricately convoluted
and therefore longer. Of course compensation for a functional dis-
turbance of a gland by hypertrophy can result only in case there
exist analogous tissue or a glandular rest."-^' In this sense the
lymph glands and the bone marrow, for example, might substitute
for loss of the spleen, but not other kinds of glands.
As a reason why glandular organs are forced to higher secretory
activity in case of removal of a portion of their parenchyma, it may
be assumed that following the ablation of the organic parenchyma
there accumulate in the blood certain secretory stimulants, sub-
stances which stimulate the gland cells. \\'hether these substances
act directly on tlie protoplasm to stimulate it to productive activity,
or whether the more active protoplasm takes up more nutritive ma-
terial and is therefore enabled to throw off more products, is un-
certain (Ribbert). The fact that muscles in a state of increased
activity receive an augmented blood supply and in case of destruc-
tive changes in an organ a similar hypersemia develops in its remain-
ing tissue (due to the accumulation of materials no longer se-
creted) suggests according to Ribbert an explanation for the oc-
currence of hypertrophy, in that the persistent congestion distends
the tissue, with the result of separating the individual cells from
each other and thus gives origin to space for the increase of vol-
ume and for the multiplication of cells. Not only is it to be sup-
posed that free spaces exist between the cells but the protoplasm
itself is substantially distended, its individual molecules separated
from each other and this intracellular increase of space affords op-
portunity for assumption of further elements which go to make
up the protoplasm. Ribbert's theory of mechanical origin of tissue
growth (cf. Regeneration) finds special applicability in the devel-
opment of cardiac hypertrophy and the hypertrophy of muscular
♦ [What is meant here is the persistence in undeveloped form of tissue
capable of taking up the morpholoR>' and function ot the adult tissue which
has been lost. TTnus in the formation of an organ there may be embryonic
elements in excess which are not employed in the formation or subsequent
development of the organ, remaining- as "rests" and undifferentiated. In
case of loss of substance of the organ such representatives may perhaps develop
to maturity and compensate for the destroyed portions.]
I'acunm, Xcn'ous, / iillniiiiitatory 11 ypcrtroplix. 257
canals (vessels, intestine, nrinarx- liladder or i^iillet ) . the cause in
such instance always heing a retention of the contents ( increase
of blood pressure, influence of calculi, obstruction to the movement
of tlie chyme, etc.) causing primarily distension of the lumen of
the part and stretching of the muscular wall.
That a diminution of the factors of resistance of growth, of tissue
resistance, favors hypertrophy (z'aciiuin hypertrophy) is apparent
in the liver in case of the existence of a diaphragmatic cleft ; the
liver tissue invariably grows through such an opening, and, just as
a button goes through a liutton hole, forms a new liver lobe pro-
truding into the thorax, the soft and elastic lung tissue ofifering but
little opposition. Such intrathoracic hepatic lobes may sometimes
be found larger than a fist (in sheep, cattle, swine).
[The influence of nervous factors in some cases of hypertrophy
can scarcely be doubted, although it is probable that for the most
part such influence operates in ways conforming with the causes
above mentioned. The ability to take up and assimilate nutrition
is in relation with the trophic influence of the nervous system, and
the condition of the vessels supplying nutrition has even more ap-
parent dependence upon the nervous functions ; and so, too, the rela-
tive tone or the opposite condition of relaxation of tissues is regu-
lated by nervous factors. Variations in functional activity are often
determined by nervous influences. Leaving aside such influences
in which perhaps the nervous factor may determine hypertrophy
by evident involvement of such influences as increase of blood sup-
ply, the provision of mechanical relaxation of tissue or the stimu-
lation of functional activity, there are more obscure examples (pos-
sibly in the end explicable on the same grounds but not clearly
showing such reasons for growth) which for the time are properly
spoken of as nervous hypertrophies, as the enlargements in acro-
megaly, for example, or the papillary enlargements of the skin in
many warts.]
Connective tissue hypertrophies are usuall}- the result of chronic
inflammation and chronic passive hyperaemia. in either of which
there are features of tissue destruction and of tissue dilatation.
Where the liver becomes enlarged and the seat of connective tissue
induration from chronic inflammation there occurs primarily a de-
struction of the liver cells and a coincident growth of the support-
ing tissue ; the termination of chronic lymphangitis of the cellular
tissue of the foot in pachydermia (rufifle foot or bristle foot in the
horse) may be explained by the idea that at first the connective
tissue spaces are filled with lymph and exudate and later become oc-
258 Inflanunation.
cupied by the proliferating connective tissue. The formation of
thick, keratous epidermal layers (keratoses) over callosities of the
skin or inflamed and distended bursje is to be ascribed less to the
direct influence of external pressure than to the pressure exerted
from beneath by the hard and thickened cutis upon the epiderm
(see also chapters on Regeneration and Inflammation).
The occurrence of congenital hypertrophies of certain parts of the
body may be due to a number of causes. Some examples are compen-
satory hypertrophies, as when one kidney fails to develop the other grows
to unusual size; others are due to chronic passive hyperemia in the foetus
caused by constrictions by amniotic bands, as the hypertrophy of the pinna
of the ear or of the penis, (cf. Chapter on i\ialformations, Spcziellc
patJiol. Anatomic der Hausticre, I Bd.).
Inflammation.
The term inflammation is applied to a condition of local irrita-
tion of the tissues, the seat of some type of injury, in which there
occur, as phenomena of reaction to the irritant, changes in the
blood current and lymphatic floiv, exudation of the constituents of
the blood, excessive secretion of glands, phagocytosis and prolifer-
ation of the tissues.
In dealing with inflammation we have to do with a series of
processes which are nothing more than modifications and exaggera-
tions of physiological procedures, in this case having for their ob-
ject the defense of the organism against the harmful influences and
the compensation for local disturbances of nutrition, and represent-
ing abilities of the animal organism acquired through phylogenetic
adaptation. (Leber, Aletschnikoff, Diirk, ]\Iarchand, Schmauss and
otliers).
In the lowest unicellular organisms, as the amcebae, the phe-
nomena of reaction to harmful influences are manifested by the
properties of chemotaxis, phagocytosis and intracellular digestion.
In the more highly organized forms of life, made up of dififerentiated
cells, these defensive functions are assumed by certain groups of
cells (Diirk) ; and in conformity with the complexity of structure
and interdependence of tissues and organs and the variability of
the injuries, these regulative and reparatory processes are made up
of a number of separate phenomena which in their synchronous
and consecutive operations are grouped together under the com-
prehensive term, inflammation.
In the class of harmful agents capable of inducing inflammation,
the causes of intlannnation or irritants, are included a great variety
Causes of Iiiflamination. 259
of foreign bodies, parasites, infectious substances, poisons and ther-
mic influences which arc spoken of as external eaitses. These
do not act in reahty as the immediate causes of the process but
produce primarily some type or other of tissue change, as necroses,
degenerations and injuries, and the inflammatory reaction is di-
rectly due to an effort to compensate for these latter.
[It is not the heat of the flame or the steel of the knife which
actually causes the inflammation ; these are probably at once with-
drawn. They, however, alter the cells and tissues, and the inflam-
matory reaction arises in reality to eliminate or isolate these altered
structures and prevent their acting as irritants, and to make re-
pairs for their loss..] One and the same influence, depending upon
the intensity and duration of its operation, may be responsible for
a number of types of tissue alteration; an irritant poison, an acid,
may in different degrees of concentration, heat or cold, give rise
perhaps to a simple hyper?emia, to a superficial inflammation or to
deep ecshars. Strictly speaking tissue necrosis is always produced,
sometimes only superficially, affecting only epithelium and vascular
endothelium and essentially microscopic in extent, at other times
extending more deeply or involving decidedly larger areas and ap-
preciable to the unaided eye. In the first instance reparation is ac-
complished so quickly b}- phagocytosis and prompt regeneration that
the full picture. of inflammation is not developed, these two factors
of inflammation alone occurring in the tissue; in case of the de-
struction of a larger amount of tissue, however, provided it is not
fatal directly or from complicating infection and putrefaction, the
inflammatory reaction with its entire group of phenomena results.
A given infectious agent may in one case give rise to a rapid general
infectious process with fatal termination or in another only to a
typical local inflammation, as illustrated by the varying effects of
bacillus anise pticus in the virulent or attenuated state and in the
particular state of individual predisposition of the subject. In reality
the animal body reacts to all physical and chemical injuries by the
production of an inflammatory process, provided time be afforded;
that is. provided the injury does not involve a vital tissue or organ
to such a degree as to immediately produce death from the func-
tional disturbance. Where bacteria of extreme virulence, with
haemolytic power and capable of rapid extension, invade the sys-
tem, a bacteriasmia or toxic infection is said to exist ; in such cases
there is not enough time permitted for compensation by an inflam-
matorv reaction for the disturbances occasioned. Were the micro-
organisms of lower virulence, did they multiply more slowly at the
26o Iiiflamuwtion.
focus of infection so that their toxines might be restrained or ren-
dered in some measure inert, or if the animal body be especially
well provided with bactericidal substances, the course of the disease
would be protracted and there would be time for the tissue to set
into activity some or all of the reactions belonging to the inflam-
matory process. Inflammation may therefore, as the combined man-
ifestation of a number of defensive efforts directed against harm-
ful agencies, be looked upon as a curative process. When the forces
brought into activity succeed in eliminating the source of harm the
inflanmiation reaches in a relative measure its physiological termi-
nation (Diirk ) ; when, however, the reaction directed to the removal
of harmful influences is not successful in elimijiating them, when,
perhaps, the latter multiply in the system, the organism perishes in
spite of the inflammation, not necessarily because of the inflamma-
tion but because of the infection or intoxication, or possibly actually
because of the inflammatory reaction from the series of functional
disturbances of the organs resulting from its onset.
The Phenomena of Inflammation, — From the earliest centuries
of our era, when the Roman physicians Celsus and Galen at-
tempted to formulate a conception of inflammation, there have
been recognized as cardinal symptoms of the process in the
grossly visible parts of the living body: increased heat, redness,
szvellinj:^- and increased sensifiTcness of the inflamed part (calor.
rubor, tumor, dolor), to which may be added disturbance of
fnncfion {fnnctio Jccsa) as a fifth. These fundamental symptoms
are, it is true, clearly appreciable in most acute, that is, rapidly
developed, inflammations of the skin and mucous membranes ;
but they are not invariably to be noted in the entire course of the
process. The older the inflammation becomes, the more likely are
these features to»be lost one after another ; and a chronic inflamma-
tion beginning gradually and continuing in low grade may not show
anv of them. Moreover the supposition that internal organs in in-
flammation show the same intense redness, swelling, increase of
temperature, and increased sensibility to pain, is only partly correct ;
and here too the chronic inflammations are especially likely riot to
be characterized by such phenomena.
In the efifort to analyze the nature of inflammation from an
anatomical standpoint modern studies, have furnished definite ex-
planations of the above mentioned symptoms of Galen and have
given sufficient insight into the inflammatory process to afiford a
fairlv precise knowledge of the character of the changes and the
methods followed bv the tissues in their inflammatory reactions to
Phenomena of I)ifIaim)iatioii.
261
irritants. Thanks to the studies of Mrchow, Recklinghausen,
Cohnheim, Ziegler, Alarchand and others, the various steps which
develop and take part in the process in inflamed tissues have come
to be well understood. Only in connection wnth relatively unim-
portant questions do there still exist differences of opinion and theo-
retical discussions, involving- for instance such points as whether
the proliferation attending inflammation is produced by excess of
nutrition or lack of tissue tension, whetlier it may be assumed or
not that there is a functional stinmlation to excite cell formation, or
Fig. 47.
Emigration of the leucocytes in frog's mesentery, six liours after exposure. Tlio
cells shaded with lines are the red corpuscles ; the stippled ones are tlie
leucocytes; X 2511. (After I'erls.)
whether certain granular changes of the cells should be spoken of as
inflammatory or regarded as degenerative.
The inflammatory process ma}^ be directly traced (Cohnheim's
experiment*) under the microscope in transparent inflamed living
tissue, as the mesentery of a frog or rabbit, or in the expanded
wing of a bat or the tongue of a frog drawn out from the mouth
or in the web of a frog's foot, the inflammation being excited in
such tissue by the application of a caustic or the production of a
minute traumatic lesion.
The first step of inflammation in a vascular tissue consists of
*For details cf. Kitt. Baktoirnkinulc uiul pathol. iitlkruskopic ju>' Tier'drzte.
IV Aufl. W^en, M. Perles Verlag, 1903.
262
Inflammation.
distension of the blood vessels, hypersemia. In the exposed or irri-
tated parts there may be first observed a dilatation of the arteries
and later of the capillaries and veins. With this the blood current
is first accelerated, but with the occurrence of dilatation of the veins
of the tissue the circulation becomes slowed. Here or there it may
stop for a variable period, and the corpuscles which previously
were forced along in the central part of the stream become dis-
tributed uniformly throughout the lumen of the vessel in the stag-
nating blood. In addition the delicate capillaries, through which
previously plasma mainly flowed with here and there a blood cell,
are found engorged with blood corpuscles. With this slowing of
the current the sluggishly moving white blood cells tend to collect
A
a
■iS-'-
Fig. 48.
Various steps iu the passage of a white blood corpuscle through the wall of a
vessel. On the left of the short lines which represent the vessel walls, is
supposed to be the intravascular blood; on the right the tissue; X 1,0"0.
(After Thoma.)
more and more on the inner surface of the vessel wall, giving rise
to the so-called marginal deposition of the white corpuscles, and as
additional ones are continually added from the blood the capillaries
may, from their increasing accumulation, be found completely oc-
cluded by leucocytes. There may next be observed a very charac-
teristic feature, the exudation or emigration from the vessels of
large numbers of the white corpuscles into the area of inflammation.
These motile amoeboid cells, which were more or less flattened
against the internal surface of the vessel, penetrate the capillary or
venous walls by protruding a pseudopod-like process of their pro-
toplasm through it (mainly at the cement lines between the endo-
thelial cells) the rest of the protoplasm following in a distinctly
Phenomena of JitHainmation.
263
flowing manner until the whole cell is on the outside. In the living
specimen all of the steps of the passage, so like a creeping move-
ment, ma}' be followed ; and in sections of an inflamed tissue cells may
be found partly outside and partly within the vessels, fixed in their
constricted condition and reminding one very much of the appear-
ance of a wasp with its abdomen constricted from the thorax. Some-
times these cells show a long stretched out protoplasmic process,
swollen out into a button in case a part of tlie substance with the
nucleus has moved forward. The leucocytes which have escaped
Fig. 49.
An inflammatory focus the seat of cellular infiltration in tlie tissue of the kidney.
(Section of the kidney of a cat.)
from the vessels continue their creeping movement and thus dis-
tribute themselves in the spaces and interstices of the tissue of
the inflaminatory area between the connective tissue cells and fibril-
lary bundles, and wandering on between the epithelial cells to the
free surface of the part.
As new cells are constantly passing from the vessels the inflamed
tissue becomes thickly studded with leucocytes, constituting a con-
dition known as eelhilar infiltration.' A number of authors believe
that the leucocytes after their egress from the vessels multiply in
the tissues by amitosis (direct division), and, too, that the lymphoid
264 Inflammation.
cells find their way into the part from the lymphatic foci scattered
about in all organs.
Along- with the leucocytes the fluid blood plasma also escapes in
greater or less amount from the distended vessels, by a process of
leaking through the walls through the openings made by the leuco-
cytes and directly through the endothelial cells which have from
injury become more readily penetrable; or, as some maintain, the
fluid is given off to the tissues as a secretion of the endothelium.
It is possible that red blood cells may also escape from the vessels,
mixed with the fluid, being passively forced through any existing
openings by the extra blood pressure. The transuded blood plasma
with its celhflar elements is known briefl\- as the exudate (from
e.vsudare, to exude).
The histological events just detailed place us in a position to
understand why and how the phenomena spoken of as the cardinal
'symptoms of inflammation are produced.
The redness (rubor) is the result of the hyper?emia. In earlv
stages of the process and in the peripheral zone of an inflammatorv
area, where the blood current is accelerated, this hypersemia has the
characteristics of an arterial hyperjemia, the vessels showing up
conspicuously with a scarlet red color as if injected (injection red-
ness, branched redness). The more pronounced the slowing of the
current and the more the stagnating blood gives off its oxygen to the
inflamed tissue the more the color approximates that of the venous
blood, becoming darker and of a more violet hue and becoming
more and more dift'use as the dilatation of all the capillaries de-
velops. The heat (calor) depends upon the increased rapidity of
flow and the volume of arterial blood; the more rapid the current,
the less opportunity being aft'orded for loss of heat and the more
nearly the temperature of the inflamed part approximates the tem-
perature of the blood itself. The heat of an inflamed area is only
noticeable on the exterior of the body, in comparison with the parts
whose temperature is unchanged, and is not above the temperature
of the general blood. The internal organs do not become essentially
warmer than the blood, special increase of temperature from meta-
bolic changes not taking place in inflamed parts (Perls, Ribbert).
[It is claimed by some, however, on the basis of experiments carried
on it is true with difficulty and open therefore to a chance of error,
that the blood coming from an inflamed part is of higher tempera-
ture than that of the arterial blood going to such a part, and that
increase of temperature is actually, therefore, produced in inflamma-
tion presumably from an increased metaboUsm which obtains.]
Signs of IiiflaDiiiHition. 265
The szi'dliiig (tumor) of an inflamed tissue is easily comprehended.
The exudate fills up the lymph spaces and stretches the structures
apart ; the vessels are dilated, and the lymph is prevented from es-
caping readily from the tissue because of loss of elasticity of the
interstitial substance (Landerer). In consequence a turgescence,
appreciable as an oedematous swelling in inflamed areas on the
periphery of the body, occurs. In chronic inflammations the con-
nective tissue proliferation gives to the organ or its connective
tissue frame-work more or less increase of volume. The pain
(dolor) is attributable to the pressure exerted by the exudate and
swollen tissue upon the sensory nerve filaments, or to direct irrita-
tion of the latter. In addition this fault interferes with the trans-
mission of nervous impulses, in consequence of which arises
functional disturbance, in addition to the disturbance occasioned by
the primary influence of the cause of the inflammation (death of
tissue) and the simple mechanical disturbances produced by the
collection of exudate in cavities (as the air spaces of the lung or
the pleural cavities), the overgrowth of tissue, etc.
As already stated, the processes involved in inflammation are
nothing but modifications of physiological processes. Exudation of
plasma and leucocytes and their movement through the tissues are
continuallv going on under normal conditions ; the ordinary lymph
formation is the result of a normal process which in inflammation
is clearlv only exaggerated. The reason for this heterometria.
and more particularly for the circulatory disturbances, may be found
in certain physical and chemical changes in the vessel wall. All
inflammatory excitants apparently exert, directly or indirectly,
chemical influences leading to changes of the endothelium of the
vessels and thus making the vessel wall more permeable than nor-
mally. It can be shown for example that the endothelial cells may
be caused to shrink, contract into spherical form, and thus give rise
to imperfections in their interstitial cement. These openings pro-
duced pathologically facilitate the leakage of the plasma and the
emigration of the leucocytes through the wall and make it possible
for the red cells to undergo diapedesis. Changes in the tension
of the vascular wall, relaxation of the arterial musculature, neces-
sarily accompany lesions of the endothelial cells and the surrounding
tissues, and this in turn occasions dilatation of the vessels. In every
case, too, the nervous system, especially the network of vasodilators
and vasoconstrictors distributed about the vessels, takes part in
bringing about the vascular dilatation, these nerves being affected,
irritatecl or paralyzed, by the original cause of the inflammation.
266 Inflammation.
The acceleration of the blood current which is seen in the early
stages depends on the passage of the blood from narrow into wider
channels [an explanation sufficient for the short period required for
the filling of the additional space afforded by the dilated lumen of
the vessel, but not clearly satisfying for its continuation even for the
time it does prevail before stasis sets in, and for its longer persist-
ence at the periphery of the inflamed area] ; the slowing of
the current upon the transudation of the plasma, and the endothelial
changes, both of which tend to cause a more concentrated condition
of the blood. [Here, too, there should be considered the probability
of relative inefficience in the outflow of the blood, loss of tone of
the venous walls and loss of elasticity of the surrounding tissues,
local compression of the walls of the capillaries and venules by exu-
date and proliferating or swollen and degenerate cells, all of which
introduce elements of a relatively passive factor in the process for
retardation of the escaping current.] The marginal deposition
of the white corpuscles is explained by Hering and Schklarewski by
the fact that when liquids containing light bodies in suspension are
passed through tubes these bodies tend to move along the periphery
as the rapidity of the current is slowed ; they call attention to the
lower specific gravity of the white in comparison with the red cells
and their viscidity and tendency to adhere from their tactile irri-
tability. The movement of these cells, physiologically determined
everywhere by their tactile and chemotactic sensibility, is stimu-
lated in inflamed tissues both by the causes of the inflammation
and by the lesions occasioned by these causes. The studies of
Pfefifer, Buchner and others have made us acquainted with a series
of substances which possess marked power of attraction for leu-
coc>'tes, especially certain proteins of the bacterial body ; and in the
destruction of tissue induced as a primary effect of the untoward,
influences exerted by the causes of inflammation certain chemical
substances, as the alkali albuminates, are set free which have a sim-
ilar attractive influence upon the leucoc>i:es. According to Thoma,
even a variation in the amount of saline matter in a tissue will
occasion a movement of the leucocytes.
The spaces produced between the endothelial cells are appar-
ently not primarily due to perforative efforts by the leucocytes, but
result from distension of the vessel or from shrinkage of the endo-
thelial cells ; and the leucocytes possessing tactile sensibility, closely
adapting their substance to the surface and fitting into every varia-
tion, extend their processes, tentatively and uncertainly, through
Exudate and Proliferate. 267
any existing openings. The presence of any substance with chemo-
tactic power determines the direction taken in the further move-
ments of these cells.
The majority (about seventy per cent.) of the motile cells col-
lectively spoken of as leucocytes, which are found in an infiam-
matory focus, are characterized by the possession of multiple
nuclei, or one polymorphous nucleus, and very fine granulations only
seen in fresh specimens. These polymorphonuclear forms are re-
garded as the characteristic white blood cells and arise from the
bone marrow (where they are mononuclear, acquiring biscuit and
clover leaf types of nuclei only in passing into the blood as the
result of nuclear division or fragmentation). Besides these, which
are described by Ehrlich as neutrophilic leucocytes, there are met
in inflamed tissues forms containing coarser granules which, be-
cause of the readiness of their granules to take up intensely 'the
acid aniline dyes, like eosin, are known as eosinophile leucocytes;
and others with special tinctorial tendency of their coarse granules
for the alkaline anilines (gentian violet), known as mast cells.
Mononuclear (single nucleus) cells are also comparatively numer-
ous in inflamed tissue, the nucleus round and rich in chromatin,
and the cytoplasm showing as a very narrow margin about the
small or large nucleus. These are regarded as lymphocytes, which
have originated from the lymph glands or germinal lymphatic
centres. As above mentioned, the great increase of these cells
depends in part upon a chemical stimulation acting not only on the
blood vessel walls but also upon the foci of lymphoid cells dis-
tributed in all the tissues and causing enlargement of these lymph-
cell forming centres; and in the second place, as many of these
cells have come from the marrow, it may be inferred that these
chemical substances, which act locally in the inflammatory area as
chemotactic agents and stimulants to proliferation, are also present
in the circulating blood and with it pass into the bone marrow and
there exert the same influence, that is, stimulate this tissue to the
formation of leucocytes. Often in inflammation there is not only a
swelling of the lymph follicles, but even a hyperplasia or meta-
plasia (change of red marrow into lymphoid) of the bone marrow
referable to its exaggerated function.
The causes of inflammation and the chemotactic substances set
free in the affected tissue have, moreover, a stimulating influence
upon the proliferation of the fixed eells. The endothelial cells of
the blood vessels and lymphatics and the connective tissue cells
take part in the proliferation in every inflammation, the beginning
268
tnflmnmation.
of proliferation being indicated by the appearance of mitotic
changes. After conclusion of mitosis the cellular division takes
place, the protoplasm also increasing in volume. The young cells
arising from this proliferation persist in part in the inflamed tissue,
and after the formation of an intercellular substance constitute an
inflanuuatory embryonic tissue, made up of fibroblasts and angio-
plasts, which serves the purpose of restoration of the original lesion
(cf. Regeneration, p. 237). In part these cells disappear, and they
may perhaps exhibit motile activity. A number of the proliferating
Fig. 50.
Inflammatory focus in kidrey of calf, sliowing cellular infiltration.
connective tissue cells and endothelial cells are sometimes changed
by direct nuclear division into multi-nucleated giant cells. The forma-
tion of these giant cells is by some supposed to be due to a chemo-
tactic influence bringing a number of cells together and causing
their fusion ; another suggestion is that the cause of the inflam-
matory change has in some way disturbed the protoplasm of a cell
so as to interfere with division of the cell substance, although
nuclear division goes on. This type of cell is met especially in
inflammation excited by foreign bodies, about which corpuscular
elements the giant cells are found deposited in a manner explain-
Demarcation and Phagocytosis.
269
ing how the inflammatory reaction is able to carry out its protec-
tive purpose by removal or encapsulation of the harmful substances.
Demarcation and Phagocytosis are two important functions of
the cells coming into consideration in the inflammatory process.
The motile cells of leucocytic and lymphoid types, distinguished
generally for their phagocytic properties even in normal circum-
stances, arc attracted by the metabolic products of an injured tis-
sue or bv the chemical influences of the inflammatory agents. They
take u]) all the substances in a disintegrating tissue which are acces-
Fig. 51.
Inflammatory scar in the kidney of a hug.
sible and with which they can deal, as albuminous granules, blood
remnants, pigmentary granules and fat globules, and, indeed, all
sorts of minute particulate elements, as vegetable and animal micro-
organisms ; carrying these objects off or destroying and rendering
them inert by the influence of the digestive power of their proto-
plasm. However, this power of phagocytosis also resides in the
fixed cells. In the chemotactic accumulation of the cells, which
takes place around foreign bodies or necrosed tissue, the leucocy-
tes, fibroblasts and angioplasts and giant cells form a protective
wall which either permanently imprisons the foreign body or from.
270 ' Inflammation.
which fresh cells constantly move into the dead structure, grow
all through it and break it down, bearing away particles of the
disintegrated material or any minute foreign elements (bacteria,
etc.), and in this way gradually removing tlie agents producing the
inflammation.
These features have been studied experimentally in a variety
of ways. They may be easily observed by injecting into a tissue
an emulsion containing fine particles of carmine. An inflamma-
tion is determined in the course of which the leucocytes and fibro-
blasts become loaded with pigment granules, and giant cells are
formed which also englobe the pigment particles. Some of the
carmine is carried out of the area by the motile cells ; when larger
amounts have been introduced tlie parts which cannot be carried
away are encapsulated by the connective tissue cells and the cica-
tricial tissue arising from the latter. When porous foreign bodies
like bits of sponge or elder pith are introduced aseptically into the
subcutaneous tissue or into the peritoneum, at first the exuding
plasma and a large number of leucocytes occupy the spaces in the
substance, but later the connective tissue corpuscles and vascular
buds penetrate into them and take up all the available space (this
reactive proliferation is seen as early as the second day).
After transformation into scar tissue (v. p. 241) the connective
tissue is found surrounding and filling all tlie spaces of the foreign
substance and isolating it from the rest of the organism (Ribbert).
Solid foreign material like silk thread, cat gut, silver wire, intro-
duced aseptically as sutures by surgeons, or bullets, needles, bits of
glass, w^ood splinters, or hairs which have gotten into wounds, pro-
vided they have no bacteria upon them and are truly aseptic for-
eign bodies in the tissue, are always surrounded by a wall of leu-
cocytes and proliferating connective tissue and thus encapsulated.
The inflammatory reaction about a foreign body always depends
upon the soluble chemotactic substances which arise from the mate-
rial. About some bodies which give rise to but little substance of
this sort (aseptic cat-gut, silver wire) it may be very unimportant;
inflammation ceases entirely after these substances are completely
extracted from the foreign body, that is when it can no longer
give ofif soluble chemotactic material. The functional activity and
the movement of the cells mentioned toward the foreign matter can
be beautifully demonstrated, as pointed out by Ribbert. by inject-
ing liquefied agar or a blue-stained mass of gelatin into the sub-
cutaneous tissue or anterior chamber of the eye. Soon after the
jelly has hardened in the body it is surrounded by leucocytes and
Iniiamiuatioii in Non-Vascular Parts. 271
fibroblasts which approach; these cells push forward and into the
jelly like a phalanx of soldiery, break it down and gradually carry
it entirely away; and the local inflammatory condition disappears
with the removal of the foreign matter, the leucocytes and other
cells being able to return whence tliey came, or some perhaps dying
and undergoing disintegration.
Hc-emorrhagic effusions, blood clots, masses of fibrin, coagu-
lated or completely necrosed tissue and loose bits of bone are all in
the same way objects for phagocytic activity of the cells, making
their appearance in the tissue reactions in inflammation. All dead
tissue, in fact, is the same thing as a foreign body in relation to
the functionating living tissue adjacent to it; it is a source of
chemotactic substances and acts as an excitant of inflammation. So,
too, just as non-vital foreign bodies, the living organisms which
enter the body from the exterior, the animal parasites and all
microbes, are to be looked upon as irritants and as causative of
inflammation to a greater or less degree, according to the chemo-
tactic substances which they contain.
Inflammation in non-vascular parts of the body, of which there
are two which require special mention, the cornea and the cardiac
valves (cartilage and the calcified bone substance, which are also
avascular, have no marked inflammatory reactive power and are
subject merely to retrograde metamorphoses), presents practically
the same features as in the vascular tissues, save that emigration
and exudation of course cannot take place where there are no ves-
sels, but do occur from vessels at a distance. Numerous investi-
gators, particularly His and Virchow, and besides these Cohnheim,
Fuchs, Eberth. Ranvier, Giiterbock. Ribbert and Marchand, have
engaged in studies in connection with the process in question, and
have thereby materially added to our appreciation of the nature of
inflammation. Where the cornea has been injured by some trau-
matic lesion, by a foreign body, or some type of infection, leuco-
cytes actively penetrate to the focus from the blood vessels which
encircle the margin of the cornea in the conjunctiva. Although
these vessels are situated some distance from the focus of injury
there are to be noted in them the same dilatation, slowing of the
current and emigration as if they were immediately in the injured
area. It is probable that these vessels are influenced by reflex ner-
vous action, and it cannot be doubted that the injured corneal tissue
exerts a strong chemical attraction for the leucocytes by means of
substances dissolved in the corneal lymph and reaching the corneal
margin in the latter or exerting a far-reaching influence from
2^2 Inflammation.
within tlie corneal mass. The leucocytes which escape from the
blooci vessels at the corneal border find their way along the spaces
of the corneal tissue to the point of injury and there collect about
it. This can be observed in the frog's cornea which has been
touched with a corrosive, if the animal be killed a day or two later
and the excised cornea spread out on a glass slide, as the leucocytes
of this cold-blooded animal retain tlieir motility for a considerable
time. The wandering cells are found elongated and conforming
in shape to the narrow tissue spaces, their presence giving the cor-
nea a milky cloudiness. At the same time the corneal cells are
found proliferating; they undergo division and become slightly
motile in response to the chemotactic agent connected with the
inflammation. If the inflammation continue for a comparatively
long time, eventually the marginal vessels begin to send vascular
buds into the cornea ; these may penetrate so far that the cornea
becomes covered or completely penetrated by a network of vessels,
a pannus ( •v tti^j/tj, a cloth). This proliferation is also, according
to Ribbert, probably due to a chemotactic stimulus affecting the
endothelial cells. The opacity which involves the cornea in the
course of the process mentioned may entirely disappear with the
completion of repair; the transparency returns because the cells
creep back and the fluid washes out the products of disintegration
and the capillaries undergo regressive changes. In other cases a
whitish scar remains as a remnant of the proliferated tissue.
Inflammation of the cardiac z'ah'cs, according to Ribbert, is not
attended by penetration of leucocytes into the tissue at all ; aside
from the formation of adhesive clots, which develop upon the
roughened (from endothelial lesion) leaflet, the only evidence of
reaction consists in a multiplication of the fixed cells of the endo-
cardium and, in case the process continue for a time, of the pene-
tration of the capillary vessels from the base of the valve into its
substance.
Anatomical Types of Inflammation and Exudation. — lExudation
of blood plasma, emigration of leucocytes and sometimes diapedesis
of red cells occur in varying degree, depending upon the causes of
the inflammation, its duration and local conditions ; and give rise
to special appearances which form the basis for differentiating a
number of forms of inflammation and exudate.
The volume of exudate varies within wide limits ; it may be so
small that the inflammatory focus can be found practically only
with the aid of the microscope, or there may be such a quantity of
fluid that many liters may be removed (from the larger cavities of
Serous and Fibrinous liifhuiiinatious. 273
the body). The exudate may exist in the lymph spaces of the tissues,
fining them completely (infiltration), or may escape to the surfaces,
where it forms a deposit upon the latter ; it may collect in the body
cavities or may find free exit from the body. Even in normal con-
ditions leucocytes find their way between epithelial cells, and when
the epithelial tissues are loosened in inflammation or actually des-
quamated the exudate is given easy access to the free surface. The
qualitative composition of the exudate is by no means uniform ;
sometimes the major portion is plasma and cells are but scantily
met in it, sometimes the reverse is true. In addition admixtures of
tlie secretions of organs may be found present, or products of tis-
sue disintegration or changes due to coagulation, putrefaction or
inspissation. all of which serve to give a very variable character to
the exudation.
The terms serous exudate and serous inflammation are employed
in connection with an aqueous product of inflammatory extravasa-
tion : the fluid is rich in albumen, like the serum of the blood, lim-
pid or slightly clouded, of a yellow wine tint, or sometimes red
from the presence of erythrocytes. When it soaks through a tissue-
and gives it a juicy gelatinous appearance the structure is said to be
the seat of iiif^aiiiinatory a^ieuia; collecting in the sacs of joints,
tendon sheaths and the serous cavities the expression inflammatory
dropsx is applied. In the skin surfaces, which are covered with
squamous epithelium, the upper layers of which are but slightly
permeable for fluids, it may collect in the more easily penetrated
deeper layers of the rete ]\Ialpighii and raise up the superior strata
to the formation of blisters. In mucous membranes the fluid passes
through the epithelial layer and mingles with the physiological secre-
tion and the desquamated cells of the membrane, escaping with
these ; in this case the term catarrhal exudate (Karap^o}. to flow
away) is employed. Such catarrhal exudate may be very thin and
water like, or may be viscid. The irritation of the inflammatory
condition invariably induces an increase of secretion (increased flow
of tears, increased secretion of nasal mucus).
It is said to be a fibrinous exudate in case the exuded fluid under-
goes coagulation by precipitation of fibrin. This form is met par-
ticularly on the free surfaces of serous membranes and mucous
membranes, within joints and in the lung, and to a less degree in
the meshes of the tissue. Coagulation occurs in case the fibrin
forming substance, which is always abundantly present in every
exudate, comes in contact with fibrin ferment, the latter being sup-
plied by necrosing cells, especially leucocytes and endothelial cells.
274
Inflammation.
The fibrinous exudate may form delicate or thick, more or. less ad-
herent, grayish white to yellow deposits or flocculent precipitates
of a semi-transparent, elastic type. On the surfaces of serous mem-
branes it may be observed as a frost-like deposit of thick patches
of coagulated substance which can be torn off in shreds, look some-
thing like omelet and perhaps cover considerable areas of the
serous surface (false membrane). The viscidity of the exudate is
responsible for the fact that on opposed surfaces which move over
«&'iL
Fig. 52.
Fibrinous exudate on surface of heart of tow (traumatic pericarditis).
each other (pleura, diaphragm, peritoneum) the layers of exudate
in rubbing upon each other leave the fibrinous material stretched
and dragged into a reticular, villous appearance, reminding one of
butter on two pieces of bread which have been pressed together
and then pulled apart, or of the ridged appearance of tripe {dry ox
fibrinous e.viidation) . In other instances the coagula of fibrin are
so large as to appear as elastic rind-like layers, thick as one's hand,
riddled with tiny holes which contain serum ; or the serous exudate
Fibrinous I n/Janinuitioiis. 275
may predominate and flakes of fibrin be found floating in it, in a
state of fine division (sero-fibrinous exudation). On the mucous
membranes also the fibrin may be encountered as membranous lay-
ers, which may be pulled ofif in sticky shreds, and which sometimes
form distinct casts of the canal ; these are spoken of usually as
croupous exudates (according- to Roth tlie word croupous has a
Scottish origin). Croupous membranes may be tough or soft and
grumous, depending upon the proportionate number of cells present
■%
V
Fig. 53.
Enteritis membranacea of cat (section). To tlie left tlie pseiirlomembrane cover-
ing the intestinal villi, wliicli are the seat of cellular infiltration and des-
(inamation ; to the right the muscular layers and the serosa with its adipose
tissue.
and the existence of some degree of degeneration ; they vary from
one-half to ten millimeters in thickness ; when separated in the form
of tubes they are full of the contents of the mucous canal, as the
intestine, in which they develop ; in other instances, as in the lungs,
they form solid coagula. Under the microscope, at the beginning
of fibrin separation the fibrin threads can often be seen arranged in
a stellate, tuft-like manner about the cells which give origin to the
fibrin ferment (Hauser) ; sometimes the fibrillar material is depos-
ited in parallel layers or is formed in a reticulum, the meshes of
2y(i
Inflammation.
which are occupied by leucocytes, desquamated epitheUum and
serum. By the cohesion of the fibrin, originally separated in the
form of fine fibrils, thick homogeneous trabecula are sometimes pro-
duced (hyaline fibrin).
Fibrin may be well demonstrated in
microscopic sections by Weigert's double
staining method, the fibrin taking an in-
tense blue tint, and the rest of the tissue
a red contrast color.
Inflammations of mucous mem-
branes, in which in addition to the
formation of a fibrinous exudate there
takes place a coagulation necrosis of
the tissue of the mucous membrane,
are spoken of as diphtheritic inflam-
inations {5i<t>eipa, membrane). The
coagulation-necrotic mass is here
seen as a grayish-yellow to straw-
colored or dirty gray, soft and pulta-
ceous or drier, very opaque and usu-
ally fragmented material. which
stands out sharply from the slightly
transparent normal tissues as a
thicker, somewhat swollen, promi-
nent part. Here the deeper parts of
the mucous membrane are permeated
with the exudate, and the substance
cannot be as readily separated from
the underlying tissue as the ordinary
croupous exudate, the mucous mem-
brane being torn when attempts are
made to scrape it away.
This combined inflammation and
p. g^ necrosis in its typical form is met in
Croupous membrane in trachea the digestive tract of swine afifccted
(opened) of cow. ^^..^j^ ^^^^.^^ ^\?igix^, and is oftcn Seen
in calves in the pharynx and larynx following traumatic
infectious influences, in birds in the mucous membranes of
the head, and in horses in the larynx and trachea after drenching.
There are a number of microorganisms (bacillus necrophorus,
suipestifer, streptococci and others) which are capable of inducing
coagulation necrosis of tissues and giving rise to the anatomical
picture of a diphtheroid inflammation.^
Suppurative Infiamviation.
277
(In man the name diphtheria is applied to a specific infectious disease
caused by bacillus diphthcrice, usually accompanied by deeply penetrating
fibrinous inflamnialion of the pharyngeal mucous membrane. Anatomically
similar conditions, due, however, to other causative agents, are spoken of
as diphtheroid, to distinguish them from true diphtheria. This name
diphtheria has not been happily chosen, however, as it really means inflam-
mation of the membrane.)
Suppurative InflammatioH with its product pus (Latin, pus;
Greek, rb niov) is characterized by the hquefaction of the exudate
and inflamed tissue (purulent softening) and by the important pres-
ence in the exudate of fatty degenerating- leucocytes which have lost
their power of movement ; in addition it is always the result of in-
fection with microorganisms known collectively as the pyogenic
bacteria (pus bacteria). There are a number of these microorgan-
isms occurring free in nature, mainly belonging to the groups of
staphylococci, streptococci and colon bacilli, which are liable to gain
access to the tissues through traumatic lesions or which may even
penetrate from the unbroken surface through the pores of the skin
Fig. .:.r>. #
Small intestine (laid opeu) of liog showing diphtheritic inflammation in swine
plague.
or through lymph follicles. In addition to these specific pyogenic
bacteria, whose most important influence is the production of pus,
there are many other microphytes which are also capable of induc-
ing suppuration, but which, because of special peculiarities of their
toxic properties and the peculiarities of the diseases which they
cause, receive special names, as the glanders bacillus, bacterium of
chicken cholera, and actinomyces. Wherever suppuration occurs in
a part an infection is to be suspected. This statement, first empha-
sized by Lister and Hunter, and of the utmost importance in sur-
gery, is not impaired by the fact that suppuration may be artificially
produced in experimental manner without the aid of bacteria by
means of aseptic chemicals as by subcutaneous injection of turpen-
tine, croton oil, chloride of zinc or corrosive sublimate, under con-
ditions which thoroughly exclude the possibility of infection. Such
an aseptic suppuration occurs under natural conditions only in the
rarest instances, and dififers from the ordinary bacterial suppuration
2^ Im&immtHi/tiom.
m its (ddfiaaite local Himaitatoooi. Bacterial suppaisi^on. is progressive
aaad as aoDOnaii^aaaied by a naacsre or less serere f ■dmle geaeral reac-
tkm (om itioe paat of tbiae solsject.
As it as ©gimaMy pos^Me to abtain a snjjpEuatiTe inflammaticm by
aaoeasss ©ff sterille germ-free cnltiarts of t2ie p^-ogenic organisms or
fillltinates wMda coanain goiIt "fee metabolic pnodocts of the bacteria,
at aaaay tie ac"'^*"-'! tbsl l3ae pjog-eaoic actioai of bacteria is anotiier
mstottKne ©f _-.- al acbTit}-; am important factor, hovre^-er, being
ifflne pjreseare ©f ititese Irving organisms wMd3 nraltiply in the tissue.
Hae coaac^ati'GBoi ©f smpfraratioaii is tibeT«f ore aaa setiological one. The
j(y©geaaac csqgaaaisms exert, aiaparenitlT by -mpaais of tjaeir toxines
mlnada aaie •(Si&ised tiiTongli the lissnes, an exfcremelj- strong diemo-
tadtic srtimnkis mpom dae lencocites and in tbis ysrsy indiace a greatl}-
hacres.S'ed emigiatiom of ttliese c^Hs: at the ^mte time they have an
WE^mtaM. Iianiimfiiall irnfliaejaoe tipon the -sralls of the vessels and nerves,
IS camsimg Ih3"]j>eTaBmia aaad voluminoiis exudatioii, and produce
^sdfaod" "-=*--- -- -' "--^' -T^e tissues irhidi <&€}- involve.
Tims: power of .. .^--:. -'--: ^:--;-,^. i.. . -jnen and gelatine may be rec-
oganizerd am cnltnres of the organism grown in solid gelatine and
soOadafied Mood isenmm, tiiese media being dissolved by peptonizing
eaazyimes prodimoed by Jlae lacteria. Leber has pointed oat, however,
ttiaat iagaaefoctiocEi of tiae tissntes is to some degree dae to the influence
©ff tine eanaigTated leucocytes or a jsrofceolytic enzymt. given off by
ItJaese cdDls; for exa mp le, the lifoefaction attending streptococcus in-
fedtaonas aairaisit of aaecessit}- he caused by "fee cells, as these organisms
do aaot llagsaefy itSae atoove naentioned ' " ~ ' ^ia.
I^ appeare as a 'dul! 3-ellow, ->.„,... r..-g: ten or graiiish- white
ihmid, opagaae aaad creaany, thin and irmlky or more thick like egg-
aUBaaaanein, aDOGfirdaaag to l3ae amount of plasma it contains, becoming
!re«3dMiHginay or of a caie-S3i-1ait color in case of greater diapedesis
V- red (Dorpmsdks. It is often mixed with fibrin in the form of
^mmaRH ^ - - . wiuada gives the pus a dough}- consistence
-' : • ..lemt issrmdaie) aaad fills the tissues with a fine reticulated
str. ;: - -
''- :• ■'•'; ."-fscope pus shows great numbers of leucoc}i:es,
-• ■ .1 p--j: " " ' '!}-morf'-' ---'•" -ar t\-pe. showing instead
..: - -~'—j~ '..„_ :. „ ...^5 a r._j;. .tr of nodular Ctectiit and
die t:-.:-L; :.::'=^' ^-nd fragmented portions of nucl^ir substance.
TBne icomtiimal};^' ' • ; . 'ating leiacoc}'tes, among' which are also mono-
aaaadlear t; l - : fs. ar^ sianilar to those found in the blood- In most
off jheptm^ aaad C" 'I3- im alL aaecinosis is recognizable because of
TOirocfear feagaaae' ' and naoire certainly hy the presence of fatt}-
Pus.
279
degeneration. The colls become highly granular, the protoplasm
full of fat vacuoles, and irregular, and finally the cells become
nothing more than a bunch of fat globules held together by
the protoplasmic remains (fatty granular cells) or falling
apart into faffy detritus. The leucocytes, now known as pits
corpuscles, and incapable of further motility, are suspended in
the fluid portion of the exuded plasma, here known as the
Fig. 56.
rus from cow; unstained microscopic preparation of pus cells (highly magnified).
pus scrum {liquor puris]. or are deposited in the meshes of the
tissue. The cells of the tissue in which the suppuration has taken
place are also the seat of marked fatty degeneration ; the connective
tissue corpuscles and cells of the vessel walls often exhibit phagocytic
appearances and are found with leucocytes englobed within their
substance ; and in chronic inflammations always multiply, thus lead-
ing to restoration of the lesion or its encapsulation. The pyogenic
28o
Inflammation.
bacteria arc usually found in comparatively large numbers in the pus
serum and sometimes the leucocytes are loaded with them. Accord-
ing to the manner of commencement of the process a single variety
may be found present as a perfectly pure culture, or there may be a
number of forms associated together. As occasionally occurs in
chronic cases, if no microorganisms can be discovered it may be
assumed that the bacteria have gradually died in the pus and have
undergone disintegration. If the suppuration occurs on the surface
of a mucous membrane it is spoken of as a purulent catarrh,
^H
^^
^i.
ii;'t
>'
Fig. 57.
I'ilni preparation of pus cells, stained with fuclisin (liighly magnified).
pyorrha-a, or blciiorrha'a {^Xiuvn, mucus; pew, to flow). In such
cases the blood vessels of the mucosa and submucosa are found
dilated, containing large numbers of leucocytes, and the latter cells
profusely accumulated in the meshes of the whole mucous mem-
brane and penetrating between the epithelial cells of the surface.
The epithelium is loosened, often hanging loosely in shreds. In
addition the formation of Jiiucus is increased, and many epithelial
cells may be found transformed into goblet cells.
This viscid secretion, mixed with desquamated epithelium and
Suppurative Iiiflaiinnation.
281
emigrated leucocytes, constitutes the tluid catarrhal secretion. On
serous surfaces exudation is also attended with desquamation of
the endothelial cells, antl the exudate accumulates in the cavity
lined -by the serous membrane. A collection of pus in one of the
larg-e structural cavities of the body (pleura, joint, antrum of High-
more) is called an empyema {^n-wveiv, to contain pus). When pus
is distributed all through the spaces and meshes of tissue, it gives
the latter a dull yellowish-white or gray color and can be expressed
irom it in drops by squeezing between the fingers (purulent infil-
a —
Fig. u8.
riuulent nephritis of mixed type, from calf: «. microscopic abscess: h. eml)oliis : c.
normal urinary tubules : d. urinary tubules devoid of their epithelium, con-
taining coagulated material.
tration). Where it collects in larger lymph spaces or occurs in cav-
ities formed by local liquefaction of the tissue, it constitutes an
abscess (pus sac), that is, a hollow space filled with pus; from pro-
gressive tissue destruction and continued entrance of leucocytes
such an abscess may attain considerable dimensions (size of a fist
or head). A circumscribed collection of pus in the stratum Mal-
pighii. elevating the keratous epiderm over it. constitutes a
pustule (pus vesicle). When a ])urulent infiltration extends over a
large area of subcutaneous, subiiuicous or other loose cellular tis-
282
IiiHanimation.
sue, with production of spaces filled with pus and confluence of
abscesses the condition is called a phlegmon. Where the tissue soft-
ening or the gravitation of the pus into dependent positions allows
the exudate to escape the abscess is said to break or perforate ; and
if in such instances there are formed narrow canals lined with pus
and reaching to the surface these are called fistnlcv. A loss of sub-
stance upon the external surface or in mucous membranes caused
by suppurative destruction of the tissue is known as an ulcere the
process as ulceration.
In chronic suppurations in the zone between the dead tissue
breaking down into pus and the normal tissues, there occurs a fibro-
Fig. 59.
Section through a calf's kidney ricldlecl witii embolic abscesses ; calyces and pelvis
full of purulent masses.
angioplastic proliferation, as a bacony, light gray, firm tissue. The
suppurating focus is encapsulated by this demarcating growtli, that
is, it is enclosed in an abscess wall, which on its inner surface
usually has a grimy, grayish-yellow or slate-gray color. As long as
virulent pyogenic bacteria exist in the cavity this abscess membrane
continues to give rise to more pus [only in the sense that the exuda-
tive processes which underlie the appearance of the leucocytes and
fluid are largely going on within it, and not in the sense of a secre-
tion as formerly believed] in the focus, for which reason it
is sometimes known also as a pyogenic membrane. The involuntary
muscle and elastic tissue of arteries exhibit marked resistance to
purulent softening; in suppurative cavities, as of the lungs or udder
or of a muscular tissue, vessels are often found as bridge-like
n(iViiorrliai:;ic, CJangrenons IiiHaimiutlioiis. 283
bands running across the space, perhaps as thick as a lead pencil,
their walls not destroyed by the suppurative process but hardened
by cicatricial proliferation and resisting destruction.
The vascular connective tissue which develops upon exposed
suppurating surfaces (ulcers, surfaces of wounds) presents a red-
dish-gray color and a granular or finely nodular, uneven appearance
{gramilatioii tissue) ; purulent exudate arises from this also so long
as the microorganismal cause of inflammation continues active. This
tissue serves to restore the tissue loss, filling out the cavity into scar
tissue (cf. Regeneration).
With multiplication of the pyogenic organisms in the affected
tissue not only does the local suppurative inflammation become cor-
respondingly prolonged, but there arises the probability of its exten-
sion. The bacteria advancing along the lymph spaces give rise
to fresh inflammatory reaction in a constantly expanding area. The
fact that the leucocytes have wandered into the suppurating area,
may take up some of the bacteria and carry them some distance
away, until stopped by the occurrence of paralysis and death
and their transporting function thus ended, gives an excellent
opportunity for the entrance of pus-producing germs into the lymph
channels, lymph nodes and even tlie blood. Malignant and activelv
multiplying organisms, over which the bactericidal forces of the
blood have no influence and the phagocytic cells no power,
are thus likely to set up new foci of suppuration, so-called metas-
tatic suppuration, in the lymph glands and_ any other places into
which they have been carried as emboli.
We speak of iKTinorrhagie iiiflammatioii, where the exudate
contains a notable admixture of red blood cells, and is consequently
of a reddish, grayish-red to dark red, chocolate or cafe-au-lait ap-
pearance. Serous as well as fibrinous and purulent exudates mav
assume this character, which may be regarded as indicative of
some especially severe disturbance of the vessel walls, which in
turn has occasioned marked slowing of the blood current in the
inflamed part, diapedesis of the erytlirocytes or actual rupture of
the vessels, and is therefore accompanied by stasis and haemorrhage.
Putrefaction of the exudate and of the inflamed tissue {ichorous,
gangrenous or putrid inflammation) is necessarily the result of the
invasion of putrefying bacteria into the necrotic tissue and the
masses of blood and exudate, dead material like the tissue itself. This
combination of inflammation and moist gangrene, or, rather, the
secondary changes produced by gangrene, breaks down the tissue
or exudate into a dirty, grayish-green or dark green, malodorous
284 Inflammation.
material and indicates an unfavorable prognosis for the inflamma-
tion because of tlie almost unavoidable absorbtion of toxic matter
into the fluids of the body.
All chronic inflammations, whatever the character of the exu-
date, result in the production of vascular connective tissue ; the
existence of a bacony, indurated, semitransparent or opaque milky
tissue in or about an inflammatory area is a distinct evidence of
its chronicity. This is said to be a productive iniiammution. What
factors are responsible for this tissue formation cannot be definitely
determined. It may be assumed that the same chemotactic in-
fluences, which are at the bottom of the escape of the leucocytes
from the vessels, stimulate the physiological formative energy of
the cells, in other words exert a demand for growth. The young
cells derived from these fixed cells are capable of some degree of
motility and indeed do move ; and the growing connective tissue cells
and endothelial cells are forced to take the direction in which
chemotactic and nutritive materials are located. The primary exu-'
date, especially fibrin, possesses this power of attraction, the fibro-
blasts beneath a fibrinous covering being found actively proliferat-
ing and pushing into the fibrin. It is possible that the infiltration
of a tissue with exudate directly occasions an excessive nutrition
of the cells, enabling them to form more protoplasm and then di-
vide ; and again the formation of spaces and the loss of substance
of the tissues should be considered, these factors favoring the de-
velopment of inflammation, and having a tendency to increase physi-
ological regeneration by release of tissue tension. The area of the
proliferation depends upon the extent and duration of the inflam-
mation. As already stated, the embryonic tissue appears in the form
of granulations upon free surfaces (wounds, ulcers, fistulous pas-
sages, serous membranes). With a reddish-gray or fleshy red color,
it presents a granular, uneven, undulating surface, from which in
aseptic inflammation is given ofif a serous, reddish, viscid exudate,
or when bacteria are present a purulent fluid. The granular appear-
ance which gives to the tissue its name (grainihiiii, a small grain)
is due to the projection of the outward growing capillaries which
extend out in loops and intertwine about the arteries like the top
branches of the trees in a leafy wood. The precise tint of the
granulation tissue, at times more deeply red or again more grayish
red, depends upon the relative engorgement of the capillaries or
the predominance of the gray color of the cells lying between the
vessels. These intercapillary cells are leucocytes and fibroblasts,
usually spindle shaped. On serous surfaces granulation tissue is apt
Chronic Inflammation.
285
to present a villous appearance, with finger-like, reddish and later
whitish processes (filaments) ; growing in a lluid exudate this new
tissue is found floating and waving back and forth with the move-
ments of the viscera. When there is motionless contact with an
opposed and similarly inflamed surface, the two surfaces become
adherent, at first by the embryonic tissue, but later by capillary
anastomoses and the thorough interlacing of the developing tissue.
Thus adiicsivc inflammation, the formation of adhesive bands, often
in the form of broad connective tissue cords, results. When
Fig. 60.
Granulation tissue from skin of horse.
the embryonic tissue develops beneath a serous surface it may give
rise to broad flat pale areas of thickening, the so-called milk patches.
About abscesses it forms abscess walls; along fasciae or extending
along other connective tissue structures (submucous, subcutaneous
tissue or about fistulous passages) it forms extensive indurated
layers. When the process involves the connective tissue structures
of an organ diffusely, as between the columns of liver cells or in
the kidney, this interstitial inflammation occasions a widespread
firm induration of the organ {indurative intlammation). The in-
flammatory embryonic tissue gradually becomes pale and firm and
0-- THF
'~^F
286 Inflammation.
tough, the young fibroblastic elements like the cells from which
they were derived giving rise to a fibrillar intercellular substance
(cf. Regeneration). The bundles of fibrils continually growing
thicker add firmness to the tissue, and with the cessation of inflam-
mation the young tissue shrinks gradually to smaller bulk. By
such changes it is transformed into scar tissue, here producing the
depressed scars of surfaces, there constricting the lumen of tubes
(stenosis, atresia), or again permanently and securely enclosing
necrotic tissue or foreign bodies (encapsulation). Productive in-
flammation usually stops when the lesion which caused the inflam-
mation has been finally dealt with, that is after elimination or en-
capsulation of the foreign body, necrotic tissue or other substance
which originated the inflammatory process. Where, however, the
irritation continues and final cicatrization is delayed tlie prolifera-
tive changes sometimes take on an exuberant character. This may
be particularly well seen in superficial granulations, which may
grow up out of the lesion as projecting tumor-like masses (zvild
flesh, caro lu.vnrians, granuloma) [proud flesh] perhaps as large
as a human head. Indeed, interstitial proliferation of fibroblasts
proceeding uninterruptedly for a long time may produce a mass of
young inflammatory tissue far in excess of the original tissue it
replaced and producing huge connective tissue enlargements {fihro-
matous inflammation, fibrous hypertrophy^). On mucous membranes
as that of the gall bladder, such proliferations meet but little re-
sistance from the fluid in the cavity and often give rise to villous
enlargements (polyps).
Specific Inflammations. — There are a number of parasitic micro-
organisms or infections which induce inflammatory changes but
which give rise to tissue reactions of such special peculiarity that it
is possible to conclude the agency of some one special infection
from the nature of the inflammatory proliferation and the changes
which take place in the products of the inflammation. Although
the ordinary inflammatory irritants, the thermic, toxic and mechani-
cal causes, act according to the intensity of their influence to cause
now this now that type of exudate, there are some causative in-
fluences which give rise to inflammatory reactions invariably having
the same appearance and constant characteristics. These infectious
agents are said to act specifically (that is peculiarly). Usually these
types of disease are considered under special names, and will here
be treated of in special chapters (v. Tuberculosis, Actinomycosis,
Botryomycosis, Glanders).
Parciichyiiiafous Iii/hunination. 287
Parenchymatous, Degenerative Inflammation.— The inflammatory pro-
cesses almost exclusively run their course in the vascular connective
tissue of the organ; the other constituents, gland cells, muscles or nerves,
take a more or less passive part. Inasmuch, however, as there may often
be noted in the tissue elements constituting the organic parenchyma
mitntivc disturbances and regressive metamorphoses, either as primary
changes produced by the cause of the inflammation, or as secondary
alterations, due to the inflammatory process itself, it has become more or
less customary to speak of such instances under the names parenchymatous
or degenerative inflammatiou. Due to the action of irritants which
primarily cause inflammatory changes in the interstitial tissue, there often
occur such changes as cloudy swelling, fatty degeneration or necrosis m
parenchymatous organs like the liver, kidneys or brain, of so marked a
character that the real signs of inflammation in these cases almost entirely
disappear, and perhaps can only be demonstrated by means of the micro-
scope. The process and condition might well be summarily relegated,
because of its principal features, to the degenerations. As the type of the
degeneration is sometimes a complex one, made up of a number of forms
of regressive changes, it is customary when some of the other features
of inflammation coexist (hypersemia, swelling, induration) and the gross
anatomical picture does not necessitate their separation, to employ the
term "degenerative inflammation" for the combination of the two processes.
[The editor feels that here too much stress is laid upon the passivity
of the parenchymatous tissues in inflammation. They are, it is true, not
the elements which strikingly react in the process, and their regressive
changes are usually much more apparent than their active participation.
Yet they do react and in practically the same way, as by proliferation, to
some degree in this or that inflammatory process. A hepatitis is more
apt, it is true, to exhibit the liver cells swollen and granular, yet occa-
sionally there are found cells with karyokinetic figures in their
nuclei ; direct nuclear division is not infrequently seen in the nuclei of
muscle fibres in the case of myositis ; the axis cylinder buds in the
inflammation caused by traumatic injury of a nerve, or the new growth
of muscle spindles in the inflammation about a similar lesion of muscular
tissue, argue to the same end. Proliferation commonly takes place in
the epithelium of an inflamed mucous membrane or in a gland, and while
parenchymatous cells probably take no part in ordinary encapsulation of
foreign bodies, they may take part in elimination. They probably exert
no unimportant part in the destruction or dimunition of virulence of
many toxic chemicals, as is a generally accepted function of the liver ;
and their aid in excretory elimination from the body of the same type
of irritants, and in a minor measure of particulate elements, as unfit and
perhaps harmful albuminous granules, cannot be overlooked. That they
are in a way phagocytic is evinced by their assumption of pigment
material, changing it, i^ is true, in many cases by their metabolic activity.
A microorganism may lodge upon some epithelial cell on a mucous sur-
face, on a duct, or even in an acinus of some gland, and fail to be dis-
lodged. The cell may react to the irritant microbic influences by pouring out
a volume of secretion, possibly mucus, in which the microorganism is
288 Inflammation.
caught and with which it is carried away. Or the microbe may destroy
the cell, which itself then becomes a further source of irritation. The
cell may, it is true, desquamate from mere necrotic loss of adhesion to its
basement membrane ; but at times — and too soon to permit of classing
the phenomenon as anything but tlie result of an inflammatory prolifera-
tion — one or more young cells grow up at its base and dislodge the cell
with its bacterial burden, both being carried off by the fluid on the
surface (as in a proliferative catarrh). As far as the proliferative feature
of inflammation is concerned, it is essentially the same as the author has
detailed in the chapter on Regeneration ; regeneration is one part of
inflammation. Therefore it may be probably claimed that in some meas-
ure, often insignificant, it is true, but in some cases clear and well marked,
all the capabilities detailed as regenerative for parenchymatous cells are
possible for inflammation. One should therefore be willing to accept a
proliferative parenchymatous inHammatioii as well as the more striking
degenerative inflannnation, which alone may be inferred from the author's
paragraph as characterizing parenchymatous structures in the inflammatory
process. Moreover, from a theoretical standpoint, what has just been
said may be understood as indicating that parenchymatous cells are
capable of participating in all the ways ascribed to other fixed cells ;
practically they do not manifest such ability in a degree comparable to
that exhibited by the connective tissues. These features are considered
further on by the author, who would exclude as normal some of these
minor reactions.]
The nomenclature and classification of inflammatory processes
include consideration^ of the retiology {traumatic, toxic, thermic,
infections inflammations) , the duration of the process {acute, sub-
acute, chronic) and the form of exudate and other anatomical fea-
tures {fibrinous, serous, purulent, etc.).
The scientific name {terminus technicus) used to express an in-
flammation of an organ is constructed by adding to the root of the
Latin or Greek word for the organ tlie termination itis (really from
the feminine form of the major name ending in ,js) ; for example,
wXevpa., lining of chest' cavity, irXevptT-ns , one suffering in the pleura,
irXevpiTLs 1 supply vosds ) , inflammation of the pleura. In this way for
example are built up such words as : gastritis, inflammation of the
stomach; arthritis, inflammation of a joint; peritonitis, inflamma-
tion of the peritoneum ; osteitis, inflammation of bone, etc. In
case of inflammation of the serous covering of an organ the prefix
"peri" is added to flie name (irepl, about, around) ; in inflammation
of the connective tissue alongside of rn organ, the prefix "para"
(Trapa, alongside) ; for example metritis, perimetritis, parametritis.
Special names are applied to some inflanimations : pneumonia (not
pulmonitis) for pulmonary inflamniattqn,; angina for infl.amrnation
Termination of Inflammation. 289
of the soft palate and neighboring structures ; coryca, for nasal ca-
tarrh; erysipelas for a special inflammation of the skin.
As above stated inflammation is a local reactive process in which
the mechanisms of tlie body underlying its protection from harmful
influences and its compensation for disturbances are aroused to an
especially intense activity. This defensive and compensatory func-
tion exists even in normal conditions, as a vital cellular phenomenon
of the animal body. Reactions of the same kind are almost all the
time going on in the system ; here and there cells are dying and are
being made away with by phagocytosis, and are being replaced by
regenerative proliferation. ^Microorganisms are deposited at many
points on a mucous membrane in communicating relation with the
outside world and are rendered harmless by phagocytosis ; in the
stomach and intestinal canal there often accumulate toxic sub-
stances, formed from the food, which cause a hyperaemia and
are swept away by the increased secretion, or are taken up
by the emigrated leucoc}i;es (being quickly rendered inert in
the liver) and only transiently excite some of the individual
inflammatory phenomena. Insignificant and minor grades of
inflammation are thus not infrequently induced, but these are
not classed as inflammations. They are regarded as physiological
phagocytosis, functional hyperaemia, physiological regeneration, each
running its individual course; they are not considered as disturb-
ances. We only speak of inflammation when these reactive phe-
nomena occur together and in unusually marked degree and when
the causative injury or the reactive process itself is productive of
functional faults in the affected part.
Termination of Inflammations. — Since inflammation in many in-
stances serves successfully to do away with useless and injurious
materials and to restore the injured tissue or at least to replace
faults with cicatricial tissue, it may be looked upon as a regulative
and defensive effort of important use to the economy. In this adap-
tive eft'ort. with much propriety of comparison, the advancing leu-
cocvtes mav be likened to mobilized troops or to a body of street
cleaners ; but it cannot be said that the cells of the body pursue any
fixed plan of procedure always under nervous control, but rather that
the whole process is in reality the occurrence, it may be said the
accidental occurrence, of phenomena of physiological motility and
secretion of living protoplasm excited by external stimuli. The
physiological component processes of inflammation are the same as
the cellular functions of phagocytosis and secretion which take
place in digestion, the result of mechanical and chemical excitation,
290 Inflamination.
peculiar, however^ in that these cellular activities are not confined to
any single organ but extend to all the organs, to the vascular con-
nective tissue framework of all parts of the body.
The favorable or unfavorable outcome of inflammation depends
upon accidental factors, upon the nature and mode of action of the
causative agents, upon the location of tlie part injured and the de-
gree of functional disturbance which the inflamed organ experiences.
Of the individual reactions which in combination constitute inflam-
mation, it can be accepted that phagocytosis removes structures
killed by harmful foreign bodies, that the exudation exerts a di-
gestive action upon and washes away injurious substances, that the
blood plasma (and possibly too a secretion given off from the leuco-
cytes) supplies antitoxic substances, and that the tissues are brought
into a state of regenerative ability by the increased nutritive supply.
AH of these factors combine to bring about compensation for the
influences of a variety of harmful agencies. When the irritant is
removed or encapsulated the condition of special stimulation ceases
and the inflammation ends m resolution, because no more fresh cells
advance into the area and those which have previously escaped from
the vessels either break down and are reabsorbed as detritus with the
other i)arts of the exudate by the veins and lymphatics, or, in case
they retain their power of movement, pass off to other places toward
which they are attracted by nutrient matter.
The inflammatory process cannot invariably bring about com-
plete regeneration of destroyed tissue ; as a rule onlv the connective
tissue is fully replaced, the specific elements which are lost, as
glandular or ganglionic cells, not being reformed. It is in this way,
by the formation of connective tissue to occupy the space of a lesion,
that inflammation brings about healing of the lesion. The inflamma-
tory connective tissue growth which paves the way for encapsula-
tion of foreign bodies and demarcation of dead tissue is in the same
way to be regarded as an attempt at healing.
However, there are also disadvantageous features connected with
inflammation. Adhesions between organs, the occupation of cavities
by masses of exudate, as in the lung or pleura, exudative effusions
in the brain or in the kidneys, occasion functional disturbances,
which, depending on the importance of the affected organ, may
threaten tlie life of the subject ; and inflammation may terminate in
death. This does not, however, essentially alter the conception of
inflammation as a defensive effort. Ribbert compares it to an
army, which, it is true, is in the main a valuable organization, but
which ma\' fail at times to overpower a stronger enemy or which
Tiibcrcitlosis. 291
may from the cost of organization and armament, financially ruin
a land. The fatal termination and the local disadvantages of the
disease are, strictly speaking, not attributable to the inflammation
but to the causes of the inflammation.
Tuberculosis.
Tuberculosis is a contagious infectious disease having a very
wide distribution among man and the domestic animals, caused by
the tubercle bacillus discovered by Robert Koch in 1882, and char-
acterized anatomically by the formation of minute nodular inflam-
matory foci (tiibcrculuiu, a small node) which uniformly undergo
necrotic disintegration and by their progressive increase destroy the
tissue involved by them.
This malady, the most common of all diseases, manifests itself
in man generally as a pulmonary affection of years' duration, causing
pulmonarv zvasting and consumption (phthisis, iromcpdlu, to waste,
consume) , but also producing painful destruction of bones and joints,
ulceration of the intestines, and tuberculous disease of the lymph
nodes, brain and other structures. Year after year tuberculosis car-
ries ofif over a million people in Europe, or nearly three thousand
every day, and must therefore be regarded as the most deadly of all
plagues, decimating the populace, and hurrying to death the effi-
cient youth and destroying the earning capacity of 'families by the
tedious course of the afifection and death of their members.
The disease is no less a calamity to the cattle industry. Among
domestic animals cattle and swine are most frequently affected;
ten, twenty, yes eighty per cent, of the cattle brought to the larger
stock yards in some districts are diseased. The financial losses oc-
casioned by the affection of so many animals may be estimated by
hundreds of thousands of dollars annually, for these include
such varied elements as loss of weight and forced slaughter, impair-
ment of milk production and of edibility of the meat, and sterility or
transmission of the disease to offspring. Tuberculosis in cattle be-
comes doubly important when the danger to human health is con-
templated, because the milk of animals with tuberculosis of the udder
can transmit the disease to children and adults.
The effort to overcome this infectious disease, which has been
continuallv on the increase during recent decades in man and in
animals, has therefore come to be one of the most important aims of
medicine, an object of municipal and national thoug-ht, and a matter
of interest both to the community and to the individual.
292 specific Inflammations.
The communicability of pulmonary consumption was suspected
even by the physicians of antiquity (Hippocrates, Isocrates) and
had obtained some credence among the laity. ]\Iore or less energetic
measures (burning of beds and linen used by consumptives, disinfec-
tion of furniture and dwellings by means of smoke, etc.) were
practiced as early as 1750 at Nancy, 1782 at Naples and about
the beginning of the nineteenth century were ordered and carried
out by authority of court, but were without result because of
their insufificiency to remove all the factors of infection.
According to Nocard* phthisis is said to have been declared a
contagious disease in one of the Gothic laws.
Under the influence of the erroneous teaching of Broussais that
phthisis arose spontaneously as a result of meteorological conditions,
social misery, etc., and the widely spread mistaken conception which
prevailed after the discovery of the tubercle bacillus to the effect
that this disease germ is omnipresent (ubiquitous), efforts toward
prophylaxis remained restricted. With the idea that predisposition
was the most important fault it w'as considered impossible to root out
the evil ; or it was held that the difficulties involved in the campaign
were insurmountable because of the impracticability of enforcing
the necessary rules of procedure. The old suspicion of the conta-
gious character of the disease received the first important confirma-
tion in the studies of Klencke (1843) ^"*^^ \'illemin (1865-1868),
the latter proving by a series of positive experiments the inocula-
bility of human tuberculosis and pearl disease of cattle into rabbits,
etc., and establishing the identity of animal and human tuberculosis.
Thereafter numerous investigators interested themselves in Ville-
min's teaching and repeatedly carried out similar experiments, some-
times confirming, sometimes opposing his results. (For details cf.
writings of Johne and Nocard.) With the discovery of the tubercule
bacillus by Robert Koch and the ingenious labors of this German
investigator, which have completely unraveled the aetiology of tuber-
culosis- of man and animals, all doubts as to the nature of the af-
fection disappeared. Koch succeeded in discovering and demon-
strating the tubercle bacillus by a special method of staining devised
by him ; and it is always possible by means of this method in case of
tuberculosis to recognize the tubercle bacillus in diseased parts and
material discharged from them both in man and in animals. This
microorganism presents itself as a rod-shaped microphvte, from two
to four micromillimeters in length and from three to five-tenths
* E. Nocard, Lea Tuberculoses Animales; Encyclop^die Scientlflque des Aide
^rt'moire. Paris : Masson.
Tuberculosis. 293
micromillimeters in width (about one-fourth to three-fourths the
diameter of a red blood corpuscle). Koch also pointed out the possi-
bility and methods of growing the tubercle bacillus in artificial nutri-
tive media outside the animal body ; and thousands of experiments
have contributed to the proof that by inoculation of artificially culti-
vated germs tuberculosis may be reproduced in all its forms in any
of the warm-blooded animals.
The tubercle bacillus does not
grow free in nature ; occurring only v^ \
where it is deposited with tuberculous *"*" V
discharges. It multiplies in this cli-
mate but not outside the animal body ^ —
and only within the organs of the "Ny " ^
animal or human economy. In the '/ v, ^
free state the germ of tuberculosis — --x^
may retain its vitality and virulence
when dried and in the dark for a
long time (more than a vear) ; but a
* ^ - Fig. 61.
variety of conditions may serve to tubercle bacilli ia bronchial
render the infectious material harm- ^ucus of cow; x about
less or destroy it. Sunlight, for ex-
ample, will kill the organism in as short a time as two to four
hours and even dififuse daylight will destfoy it. Rain has a favor-
able influence in washing away the vehicle of the contagion and
thus exposing it to light; a temperature of 50° -70° C. developing
in manure wall also kill it.
For such reasons tuberculosis must be regarded as a true con-
tagious affection. Its transmission from one human being to another
occurs chiefly from the expectorated sputum, which, dried and blown
about as dust, gains access to the pharynx and air passages by in-
halation, sometimes a portion being swallowed and finding its way
from the intestines into the . tissues or sometimes infecting the
pharyngeal tissues and air passages. Tiny drops of saliva or
mucus containing the organism may sometimes be discharged in
talking or sneezing and in case these are directly inhaled by a
second individual, or if they fall upon the food and are ingested
with it, they may give occasion for development of tuberculosis.
The number of tubercle bacilli in such expectorated matter may be
enormous ; in a single drop of microscopic size there may be hun-
dreds and it has been estimated that one consumptive human being
may give off seventy-two hundred millions of tubercle bacilli in the
course of a single day (Heller).
294 Specific IiiHaDniiatioiis.
The contagion is carried from animal to animal in the same way.
Cattle and hogs affected with pulmonary tuberculosis discharge
bronchial mucus loaded with tubercle bacilli by their coughing ; and
this is inhaled as fine spray-like droplets by other animals standing
near h\, or falls upon the fodder or into the water and with these
substances may gain entrance to a new animal body. One of the
most important sources of tuberculous infection both for man and an-
imals is the milk of cattle affected by tuberculosis of the udder ;
milk from such a source may, as shown by Bangs, remain apparently
normal even for weeks though it contain millions of tubercle bacilli.
If swallowed in raw state, as used in the feeding of calves and pigs,
such milk gives rise to infection of tlie body by way of the alimen-
tary canal and chyle vessels, as proved by experimental feeding.
The general milk from a dairy may become infected if there be
but one cow^ in the stalls with tuberculosis of the udder, provided
that cow be milked with the rest and her milk mixed with that
from the other cows.
Again the intestinal discharges of consumptive animals contain
the infection, either because these animals, as is often the case,
have tuberculous ulcers of the intestine, the bacilli from which be-
come mixed with the excrement, or because the animals swallow
their pulmonary expectorate and the bacilli pass through the bowel
without being all destroyed. The vaginal discharge from cows with
uterine tuberculosis furnishes another source of infection. Th'2
straw saturated with these infectious discharges, should it happen
to be eaten by other cattle with their fodder, may serve as a means
of transmission of the disease. Occasionally infection occurs in
coition, as the vaginal secretion may be carried from one animal to
another by the male, or the latter, when tuberculous, may transmit
his own bacilli in the spermatic fluid. Tuberculous infection of
cutaneous wounds is rare among animals, although occasionally in
man post mortem section of tuberculous organs gives opportunity
for this mode of infection.
The horse is usually infected with tuberculosis by eating straw
(soiled with the tuberculous discharges of cattle) ; the dog often
by licking up human tuberculous sputum ; the cat by drinking tuber-
culous milk. The disease develops in fowls where the latter have
opportunities to pick up human sputum or tuberculous discharges
from horses, cattle or hogs ; the excrement of chickens already
affected with intestinal tuberculosis, however, affords the greatest
chance for the infection of the other feathered inhabitants of the
premises (soiling of food, ground, etc.).
Tuberculosis. ' 295
Tuberculous human beings and animals are sources of further
infection only as they throw off materials containing tubercle bacilli.
The foci of the disease which exist within the animal,* shut off from
the exterior, as tuberculous lymph glands, do not give off bacilli
in such a way that they may be transmitted to another animal.
For example, the milk of cows which do not have tuberculosis of
the udder is harmless even though there are tuberculous lymph
glands and serous membranes in the animals ; the meat of a tuber-
culous animal is free from danger as long as it does not contain
actual tubercles or as long as the lymph nodes situated in the flesh
remain free from tubercle bacilli. (For further details consult
Ostertag: Zeitsclir. fiir Flcisch- unci Milchhygiene, 1890-1903.)
Concerning the question of inheritance of tuberculosis, observa-
tions running over a number of years upon the condition of calves
born of tuberculous cows,' with control by tuberculin injections
and slaughtering (Bang), as well as a series of experiments upon
pregnant tuberculous guinea pigs (Gartner), give positive informa-
tion. Tuberculosis may be acquired through the placenta. Alany
examples of this have been found in newly born calves and children,
and occasionally too in the miscarried foetus. In such cases the
liver and periportal lymph nodes are invariably involved and the
disease is apt to be more or less distributed to other lymph glands
and organs. When it has been possible to investigate the mother
of the tuberculous offspring, invariably a tuberculous affection of
the uterus and sometimes of the chorion were found. The tubercle
bacillus is scarcely likely to pass directly from the blood of the
mother to the foetus (the blood is separate in the two parts of the
placenta) ; but if during pregnancy the uterus should become in-
volved by tuberculosis (focal, as in one cornu) the tubercle bacilli
find their way into the placental milky humor and penetrate the
fcEtal placenta, and then pass with the blood of the umbilical vein
to the liver of the foetus. In this way the latter is born into the
world a subject of tuberculosis; but it is possible that after birth
the disease may progress very slowly and remain latent for months.
A conceptional or germinal infection, that is through the ovum or
spermatozoon, is so improbable that it may be said to be entirely iin-
possible. Supposing the possibility that a fertilized ovum could be
infected by tubercle bacilli, it would die from the caseating influence
of these germs long before it could develop into an embryo, or else
the embryo in its earliest stages of germ vesicle and formation
of the blastodermic layers would already be but a degenerating mal-
formation. When it is remembered that of the millions of sperma-
296 specific Inflammations.
tozoa which enter the female genital canal in coition only a single
one passes through the micropyle of tlie ovum, it cannot but be a
strange coincidence that just this very one should carry with it a
tubercle bacillus. ("Tubercle bacilli in the sperm are scarcely likely
to adhere to the spermatozoa but are more likely to remain in the
fluid.) And, too, if the fertilizing spermatozoon accompanied by
a bacillus should penetrate into an ovum the bacillus as it multiplied
would at once seriously interfere with the process of multiplication
of the copulated cells and quickly put an end to the embryonic
germ by coagulation necrosis. The assumption tliat tubercle bacilli
may somehow lie dormant in an ovum in course of embryonic de-
velopment, and later when the fcetus has been formed start to mul-
tiply, is without foundation and is in contradiction to all our knowl-
edge of the growth of vegetable microorganisms in the animal body.
[Mafucci's experiments in chicken eggs (Centralbl. f. Bakt. u.
Parasitcnk., 1889, p. 237.) are usually offered as contradicting this
contention. He inoculated eggs with tubercle bacilli and then in-
cubated them. Out of eighteen eggs he obtained one dead and
eight living chicks. He was unable to find tubercle bacilli in the
dead chick, and examining the unfertile and rotten eggs which
failed to hatch he was unable to be satisfied of any growth of the
tubercle bacilli in them. His chicks were at first apparently healthy,
but later died with well defined tuberculous lesions. That latency
of infections is possible in relation with embryonic development is
also indicated by the transmission of the psorosperms of pchrine,
pointed out by Pasteur, through the ova of silk worm moths to the
silk worms, which at first seem healthy but soon die from the dis-
ease.]
Attempts to prove from genealogical tables and statistics that
there is a true hereditary transmission of tuberculosis from parents
to offspring must always meet with the objection that children or
calves may be born free from the disease and may acquire the tuber-
culosis in the first years of tlieir lives from living in the presence of
their tuberculous parents. The above principal modes of trans-
mission of the tuberculous virus have been proved by great num-
bers of experiments. With human tuberculous sputum as well as
material obtained from tuberculous foci of the lungs, liver, lymph
nodes, intestine, etc., human or animal, and, too, with pure cultures
of tubercle bacilli, typical tuberculous disease can be caused either
by feeding, inhalation, or by subcutaneous, intraperitoneal or intra-
venous injection in all susceptible species of animals. There are,
however, certain differences, or rather dissimilarities, in pathogenic
Tuberculosis. 297
ability in tubercle bacilli derived from human beings and from
various types of animals, referable to the source of the virus. For
example, as shown by R. Koch and Schiitz in a long series of experi-
ments, and even earlier by Putz (1882) and Smith (1896), it is not
as a rule easy to render cattle, sheep and swine tuberculous by
using tubercle bacilli from a human source (even in case of inoc-
ulation of large quantities) ; and it is also difficult to infect birds
with tuberculous material derived from man or mammals. These
negative results at first caused doubt as to the identity of the tuber-
culosis of all individuals. However, it was recognized that no dis-
tinct line of difference could be drawn between the organisms, for
even a few positive results were sufficient to show the identity of
the affection in man and in animals. Positive cases of the kind re-
quired have been obtained in such abundant number and from ex-
periments of indisputable accuracy that the possibility of infecting
man with bovine tuberculosis and of the transmission of human
tuberculosis to the domestic animals cannot be denied. Besides the
older experiments of Bollinger, Klebs, Chauveau and the later ones
of Sidney Martin, Frothingham. Arloing. de Jong, Stuurmann,
Thomassen, Prettner, Klebs and Rievel who were successful in
inoculating cattle with tuberculous virus from man, tlie examples
collected by Johne. Ostertag and Xocard and Leclainche of wound
inoculation in man, occasionally actually occurring in the
course of slaughtering operations and meat inspection, speak
strongly for the idea that bovine tuberculosis is an infection of no lit-
tle importance to man. Important contributions have also been made
in this connection by Johannes Fibiger and C. O. Jensen, goihg to
show that tubercle bacilli virulent to man may also be highly viru-
lent to cattle, and confirming the belief that many cases of intestinal
tuberculosis in children are properly attributed to the ingestion of
cow's milk containing tubercle bacilli, von Behring arrives at the
same conclusion, finding that some strains of tubercle bacilli obtained
by culture from human source possess high grade of virulence for
cattle while other strains have no pathogenic influence for cattle
at all. Further the observations made by Eberlein and Cadiot, in-
dicating the acquirement by man of the infection from tuberculous
parrots and the rather common transmission of the disease to parrots
from consumptive human beings, as well as the transmissibility by
inoculation of bovine tuberculosis to apes, proved by Nocard, force
the assumption of an ^etiological relationship of the disease or of a
family identity of the tubercle bacilli of heterogeneous derivation.
[Recently Koch has brought forward anew the idea of specific dif-
298 specific Iiiflaiiu)iatio)is.
ference between the bacilli of human and bovine tuberculosis, but
has met strong opposition at the hands of a large number of stu-
dents. In this country Ravenel and Pearson have shown distinctly
the identity of the microorganisms; and the work of these investi-
gators in inducing immunity in cattle against bovine tuberculosis
by vaccination with cultures of human tubercle bacilli of low viru-
lence is of extreme significance.]
The variations in pathogenic power exhibited by the bacilli ob-
tained from different sources find their explanation in the adaptation
of the organisms to the different animal bodies. It is obvious and
reasonable that, in case of transmission of consumption which has
been going on for centuries from one human being to another, in
which the tubercle bacilli of every generation always grow ex-
clusively in the human body, the organisms may come to adapt
themselves to the conditions of nutrition which the human system
supplies to them, and that they attain their greatest infectious power
for it and find more difficulty of growth in another type of animal
body. In the same way tubercle bacilli which have passed through
many generations in the bodies of herbivora become as it were accli-
mated, and are best able to infect again an animal of the same species.
The tubercle bacilli of birds (whose normal body temperature is
known to be 41° -42° C, and whose tissues and fluids from their
known resistance to tetanus virus, etc., must have totally different
affinities from those of mammals) are particularly changed in their
biological characteristics so that thev seem to be of a totallv different
stock ; and, too, it is difficult to successfully induce a growth of
tubercle bacilli from mammals in the avian body. However, now
and again birds have been rendered typically tuberculous by inocu-
lation with mammalian tuberculosis, and conversely horses (No-
card) have been infected with avian tuberculosis; and therefore the
differences may be considered as merely expressions of a varia-
bility of biological properties. We must consider tuberculosis of
man and the animals as caused by one and the sanie infectious
agency, zvhich from long transmission througJi one particular animal
species may develop definite varieties and strains of uneven patho-
genic pozi'cr. (For further details consult Xocard-Leclainche : Les
Maladies Microbiennes des Aniinau.v. III. Ed.. Paris, 1903.)
The anatomical lesions determined by the tubercle bacillus are
as follows : After being conveyed into the body of a man or ani-
mal the tubercle bacillus multiplies into masses, provided it finds a
suitable soil at the temperature of the' animal ; penetrates by growth
into the tissues and is carried more widely by the wandering
Tuberculosis.
299
cells. Its deposition, along with the toxine which it produces,
causes a reaction on the part of the tissue as about a foreign
body, in which, however, the special toxic action of the micro-
organism takes part and gives rise to coagulation necrosis.
The first evidence of reaction as shown by the studies of
EmboL_ .
cheesy centre
tissue ; X 00
Vlg. 02.
lie miliary tubercle from lung of liorse (after Johne) ; a. giant cells: h,
lieesy centre: r, small as yet not caseated tubercle; cl, surrounding pulnionai-y
issue ; X 00.
Baumgarten, Johne and others is the appearance of karyokinetic
figures in the fixed connective tissue cells and endothelial cells,
and side by side with this an increase of the latter. The prolifer-
ating fibroblasts, among which usually giant cells occur, surround
the tubercle bacilli ; and further out
immigrating leucocytes
300 Specific Inflammations.
or lymphocytes collect about the periphery of the focus occupied
by the bacilli. In this manner a rounded cellular nodule is
formed, at first microscopic in size, but later increasing in bulk to
that of the head of a pin or millet seed, and known when visible
to the naked eye as a suhmiliary and miliary tubercle (niilium, a
millet seed). It is of a gray, opal-glass-like color, with a dead-white
to yellowish point in the centre which indicates the early stage of
coagulation necrosis (caseation). [The central cells of the unde-
••;- 'fa^sSv-iix , . y^^,-' r^iji ;::<'•'
Fig. UJ.
Miliary tubercle (higher magnification): a, giant cell: b. caseated centre; c, zone
of epithelioid cells ; d, zone of lymphoid cells.
generated miliary tubercle, in and among which the tubercle bacilli
are found, are of uncertain origin. They are commonly spoken of
as endothelioid or epithelioid from the comparatively large amount
of protoplasm and the rather pale and vesicular nucleus, and are
distinguishable by these features from the ordinary fibroblasts. They
vary in shape but are more commonly of a rather flattened spindle
form than otherwise. The author's view that these are essentially
the same as young connective tissue corpuscles and tlie product of
proliferation of the fixed connective tissue cells is accepted by some;
Tuberculosis.
301
others believe, as the name endotheHoid would suggest (epithehoid
synonymous and used rather to indicate the general epithelial-like
appearance than referring to the source of these elements),
that they are derived from the endothelial cells, mainlv those of the
lymph spaces in which the bacilli are lodged. The true lympho-
cytic nature and origin of the peripheral zone of small mono-
nuclear cells is commonly accepted. There is considerable uncer-
tainty as to the mode of formation of the giant cells. According to
some they are the result of the fusion of cells undergoing hyaline
or coagulative change ; and are therefore looked upon by these per-
sons as evidence of beginning or advancing degeneration in the
focus. From this standpoint a miliary tubercle when exhibiting one
or more giant cells in its structure is essentially a degenerating
tubercle. Others believe that they are the result of inefficient proto-
plasmic division of growing cells, in other words are of a prolif-
erative type of development and not of the significance just indi-
cated. Tubercles of fresh and undegenerated structure are com-
monly called gray tubercles ; older and degenerated ones, yellow
tubercles. |
The site of formation of the tubercle is in the connective tissue
framework of the affected part or in the walls of the blood vessels
and in the lymphatic foci of die tissue. This gives the cellular pro-
liferation a connective tissue frame work or reticulum as a skeleton,
which may, however, be in part, too, a product of the fibroblasts
and giant cells, which of course also supply an intercellular sub-
stance. Although endothelial cells also take part in the formation
of the cellular nodule these do not develop into vascular buds, and
the miliary tubercle is avascular. The endothelial cells in their pro-
liferation may occlude the lumen of the capillary vessels ; and more-
over by the growth of the cellular mass the vessels may be com-
pressed. In contrast to these factors the tuberculous reaction may
also present itself as a dift'use proliferation, without production of
sharply defined nodules and with the formation of new blood ves-
sels. In this case there is found a soft, gray or grayish red layer,
especially seen in serous surfaces (bovine heart), which is not likely
to undergo more than a slight caseation, or. if it does, only after
considerable time. This, too, always has a distinct granular appear-
ance looking as if caused by fusion of closely set miliary tubercles.
This diffuse growth is due to the fact that separate groups of tuber-
cle bacilli do not here occur as the centres of nodular circumscribed
cellular collections, but that large numbers of the organisms are
scattered all through the tissue.
302
specific I)if!aiiiinatioiis.
This inflammatory reaction is not characterized merely by the
marked collection of wandering cells in the tuberculous tissue, but
also by actual exudation upon the surfaces of the organs. Especially
in the pleural cavity of dogs tliis may be seen as a marked sero-cel-
lular collection of fluid, the result of a purely tuberculous granula-
tion ; and in various tuberculous tissues microscopic examination
shows the appearance of thread-like (fibrinoid, Schmauss and Al-
Fig. 64.
Miliary tubercle in the liver of a dog (slightly magnified).
brecht) coagulation masses lying between the proliferating and de-
generating cells and suggesting an exudative origin.
With the proliferation of the tubercle bacilli and their extension
into the adjacent tissues the amount of toxic material given of¥
by them and taken up by the lymph becomes increased. The casea-
tion is to be ascribed to the influence of this substance ; and in pro-
portion to the latter the caseous areas grow' larger as the reactive
cell proliferation increases the size of the nodule. At first puncti-
form or streaked cloudy specks appear and the necrotic foci fuse
into progressively larger and larger, dry, anaemic or (after a fatty
Tiiherciilosis.
303
disintegration) into soft, partly purulent, partly caseous areas of
very variable size. Such necrosed parts may become impregnated
with lime salts (especially in cattle) and eventually assume a
chalky, plaster-like or sandy appearance.
Just as in chronic productive inflammation the fibr()])]astic tissue
is changed into a firm cicatricial mass, the proliferated connective
tissue cells of a tubercle are also able to assume a genuine fibro-
Fig. 65.
Funguus tubercle with giant cells (without caseatiou) from the larynx of a cow.
plastic function, particularly in the formation of a fibrillar matrix
and may thus give to the tubercle a firm fibrous character.
It may therefore be appreciated that the anatomical forms of
tuberculosis vary considerably according to the tissue predisposition
in the diiTerent animal species, and the extent and duration of the
process. The principal forms are: miliary tuberculosis, tubercu-
lous ulceration, tuberculous cheesy infiltration, tuberculous cavities,
■fungous granulontatons tuberculosis (or tuberculoma).
The miliary tubercle, the earliest product of the reactive process
of the disease, as already stated, appears as a gray or yellowish-red
304
Specific Inflammations.
nodule of the size of a pin head or millet seed ; these may be single
or multiple, may be scattered widely over a large surface and dis-
seminated in the same way throughout the organic substance, par-
Fig. 66.
Tuberculosis of liver of a pheasant. The tubercles show a sharp limitation of
the cheesy centres.
Fig. 67.
Tuberculosis of liver of dog. (After Cadiot.)
ticularly on serous surfaces and in the lungs. They develop to visible
size within from fourteen to thirty days after infection ; the micro-
scopic stages at the very beginning may be made out as early as
from five to ten days. If the organ is the seat of submiliary or
Tuberculosis.
305
miliary nodules alone, all of the same age, that is of uniform size,
it is said to be involved by acute miliary tuberculosis. With local
multiplication of the tubercle bacilli, the nodules enlarge to the size
of a lentil, pea or nut, these larger forms usually showing their
origin from fusion or conglomeration of smaller miliary tubercles.
This condition constitutes what is known as chronic miliary tubercu-
losis. On serous surfaces the formation of nodular masses gives
rise to the so-called pearl disease.
The tuberculous fungous granuloma is the result of a progres-
sive formation of cellular nodules and their profuse growth on free
surfaces; it is chiefly met with in . — _^
the thoracic serous membranes and
peritoneum and sometimes, too, in
the intestinal nmcous membrane. By
the synchronous development of the
nodules and of a vascular connective
tissue growth, there may be produced
ofravish-white, gravish-red and yellow-
ish-red tumor-like masses from the size
of an egg to that of a fist, which are
piled up about and over each other as
large excrescences, covering consider-
able surface areas and reaching per-
haps a weight of from twenty to forty
kilogrammes. Caseation of these tu-
berculomata, which also occasion adhe-
sions of the serous surfaces, at first
appears in punctiform foci and in
small spots in the granulation tissue,
as yellow or light yellow opacities, and
can advance to complete transforma-
tion of the whole bunch of nodules into
a mass which on section looks like corn-bread, yellow, hard, gritty
and partly calcified.
Tuberculous ulcers, especially in the bowel, larynx and bron-
chial tree, result from the maceration and disintegration of the
caseated parts as well as from a purulent softening of the tuber-
cles developing in the mucous surfaces (lymph follicles). These
areas of tissue destruction are circular or oblong, shallow or some-
times a millimeter in depth, as large as a lentil to a little over a
centimeter in diameter, or in the bowel reaching perhaps the length
of a finger and two fingers in breadth. The base of the eroded spot
Figr. 68.
Ulcerative tuberculosis of intes-
tine of cow. (Mucous sur-
face of small intestine.)
3o6
Specific Inflauiuiations.
is mottled grayish-red and yellowish, and minute tubercles can be
distinguished growing on the base and margins of the ulcer. The
base looks granulated; the bordering wall of mucous membrane is
thickened and sometimes a marginal circlet of projecting miliary
tubercles can be seen about it.
Fig. 69.
Chronic miliary tuberculo.sis and lobular tuberculosis of lung of horse.
Cheesy tuberculous i)ifiltration, apt to be found involving Ivmph
nodes or lungs, changes the affected area of the organ into a very
large, hard, densely caseated mass of a yellowish white to chrome
yellow color, reminding one much of the boiled yolk of an egg.
This change is apt to be very diffuse and is generallv accompanied
Tuberculosis.
307
^\
'^,.
by the formation of a firm bacony connective tissue of the nature
of a confluence of fibrous tubercles, or in other words a
chronic tuberculous inflammation. Lymph glands, the seat of
tuberculous infiltration, may grow to enormous
masses as thick as an arm, or the size of loaves of
bread. .Bunches of tuberculous pulmonary lobules
are converted into dry necrotic masses as big
as a fist and comparable in appearance to Edam
cheese or Swiss cheese ; or sometimes whole
lobes are changed into large, lumpy masses,
hard, weighing over a kilogram, and riddled
with points of cheesy softening.
Tuberculous an'ities, developing in the
areas of cheesy infiltration, are cavities varying
from the size of a nut or fist to a span [a span is
nine inches] and a half in diameter. They con-
tain a greasy, caseous and slimy mass of detritus
and are limited by a wall of pale, indurated
fibrous tissue or by the tissue of the organ modi-
fied by the dift'erent color shades given by the
tuberculous inflammation., and giving rise to the
cavities by degenerative changes affecting it.
These more important types of tuberculous
changes* may combine in various ways anil
there are apt to be, too, special modifications due
to peculiarities of the tissues in the various types
of animals. While cheesy areas in cattle usually
have an intense yellow color, in horses and car-
nivora they are apt to be whiter and sometimes
quite milky. They are not at all uniform in
consistence, sometimes dry and cheesy, some-
times soft and pultaceous or possibly broken
down into a pus-like fluid. Caseation may in
some instances be absent and the tubercles
may be of. a more cellular character, look-
ing like the tissue of lymph glands ; or they may become hard
and fibrous (in horse).
The entrance of tubercle bacilli into a tissue generally occurring
at places where lymph nodes He exposed (pharynx, intestine) at first
causes a primary local tuberculosis at the point of infection. How-
*Foi- detailed examples cf. KUt, LcIiiIiikIi d. iii>c.~. imtli. Aunt., 11. .\iitl.,
Stuttgrart, 100.'?. F. Enke.
'■-i
Fig. 70.
'riiherculoiis rib of
cow (fresli sec-
tion).
3o8
Specific Inflammations.
ever the point of infection may escape involvement provided the
tubercle bacilli are rapidly carried onward by the lymph, under
which circumstances the tuberculous inflammation may first show
itself in the lymph glands. After feeding tuberculous material to
hogs the mucous membrane of the intestine is uniformly unaffected
and the disease primarily occurs in the mesenteric lymph nodes.
[Ravenel has produced a similar primary involvement of the lymph
nodes of the mesentery in dogs by feeding the tubercle bacilli
rubbed up in butter, having previously starved the experiment ani-
mal for a time.] After being taken up by the chylous vessels the
tuberculous virus passes into the blood by way of the thoracic duct
and thence into the lungs, and after traversing the lesser circulation
is carried to all of the organs. The different organs do not all show
wm^^
Fig. 71.
Portion of lung of horse showing miliary tubercles and tuberculous infiltration.
a uniform predisposition to the influences of the bacilli, that is,
they do not all offer equally favorable conditions for the nutrition
of the microorganisms. The lungs, lymph glands and especially the
general lymphatic tissues (bone-marrow, spleen), are places where
the bacillus most readily lodges. For this reason the lungs may
become the seat of the primary involvement after feeding tubercle
bacilli to an animal, and the existence of the pulmonary afifection
is by no means to be looked upon as indicating that infection took
place by inhalation.
The primary, and in fact the only tuberculous focus may be en-
countered in the interior of bones, or in lymph glands or the tes-
ticle. In such instances isolated tubercle bacilli which have gained
access to the blood may have been caught and lodged in any such
Tuberculosis.
309
situation and there caused the disease. Generally the whole
path traversed hy the l)acilli is mapped out l)y foci of the
disease, first the primary local focus and after it the neighl^oring
regional infection, then the secondary tuberculosis of the lymph
glands which receive the lymph from the afifected part. From the
latter along the lymphatics or, as above mentioned, by the chylous
route, the germs find their way into the blood or may directly pene-
trate through the walls of the blood vessels in the course of the tu-
berculous proliferation ; and then, depending upon whether many or
only isolated bacilli are carried to the various organs, there is pro-
Uteriiit^ tuliorcuUisis, from cow.
duced a iiictastafic, hccmafogciifliis, embolic, multiple or dissemi-
nated miliary tuberculosis of the lungs, brain, liver, kidneys, etc.
Muscle (meat) shows the greatest degree of resistance, usually only
the intermuscular lymph nodes being affected. This general inva-
sion of the tuberculous virus with its resulting tuberculous foci is
spoken of as general tuberculosis. The metastatic miliary nodules
of course increase in size, and by confluence and advancing casea-
tion cause progressive extension of the tuberculous destructive
changes. Finally, too, contact infection along mucous membranes
occurs from the convection of the germs over the surface with its
fluid secretion, as infection of the larynx from the lungs, of the
vulva from the uterus, etc.
310 Specific Iiiflaniniations.
The symptoms of tuberculosis appreciable during the hfe of the
affected animal vary widely with the different situations of the pri-
mary disease. Fuller details than space here permits are contained
in the publications of Johne, Siedamgrotzky, Albrecht, Lydtin and
other authors and particularly the text books of Friedberger and
Frohner, Dieckerhoff, Csokor, Nocard-Leclainche and AIoussu.
Pulmonary tuberculosis manifests itself by a remittent fever, im-
paired condition of nutrition in spite of good appetite, induration
of the skin (hide binding) associated with loss of subcutaneous
fat, rapid and difficult breathing, a feeble dry cough, impairment of
percussion resonance and the presence of rales. Chronic tiatulence,
as pointed out by Johne, is a frequent evidence of the existence of
greatly enlarged tuberculous mediastinal lymph glands from pres-
sure on the gullet, interfering with belching. Tuberculosis of
the mammary gland may be recognized by a gradually increasing
induration and diffuse painless swelling in one, two or all parts of
the udder, with synchronous enlargement of the supramammary
lymph nodes. In this condition the milk may be quite normal in
appearance for weeks or at least only changed in that it
is more watery, thinner (in the last stages only may one notice the
admixture of small fiakes of a pus-like appearance). Superficial
lymphatic glands, as the retropharyngeal, often become very large
in tuberculosis, hard and nodular. Tuberculosis of the brain com-
monly shows the violent symptoms of meningitis (excitement, un-
consciousness). In tuberculosis of the ovary symp.^toms of sexual
desire are sometimes observed. Tuberculosis of serous membranes
can in some cases only be made out by the detection of friction
sounds or by palpation of the peritoneum through the rectum ; it
may exist extensively without the occurrence of any emaciation of
the animal (so-called "fat Frenchmen"), but on the contrary with
preservation of an excellent state of nutrition. In the same way
involvement of the deeper lymph glands, liver and intestine is apt
to escape diagnosis during life.
Diagnosis can be positively confirmed by the microscopic exam-
ination of the various emanations (milk, vaginal discharge, bron-
chial mucus, etc.) by determination of the tubercle bacilli therein.
As a valuable aid to diagnosis especially in the latent forms of
the disease, the use of luberculin may be approved ; this is a decoc-
tion of cultures of the tubercle bacillus [sterilized by filtration
through porcelain] which has the effect of causing a febrile
reaction in tuberculous subjects, non-tuberculous individuals, how-
ever, manifesting no reaction to similar doses of the material.
danders. 31 1
Tuberculosis can be successfully coniljuted as purely conta-
gious-infectious disease by regulations contemplating required dis-
infection of all effluvia containing tubercle bacilli. Recently a
.metbod of protective inoculation of cattle against tuberculosis bas
been discovered by v. Behring, immunizing the animals by means
of strains of tubercle bacilli of low virulence. [Dixon in 1889
found that he obtained resistance in rabbits against virulent bovine
bacilli after having previously inoculated them with material from
an old laboratory culture containing club-shaped and branching
forms. It is of interest, too, that successful vaccination of cattle
against virulent bovine tuberculosis has been practiced by Pearson
in this country, using cultures of human tubercle bacilli of low
virulence. I Cows which have obtained a high degree of immuniza-
tion produce milk which possesses a certain amount of immunizing
bodies ; and it may be hoped that either by using such milk or the
serum of highly immunized animals there may be obtained aho a
curative method for consumption in man.
Glanders.
Glanders (mallcosis) is a contagious disease caused by the glan-
ders bacillus {bacillus mallei), occurring in the horse, ass and mule,
but very infectious and dangerous, to man and also transmissible to
carnivora, sheep, goat, guinea-pig, liAlge-hog, field-mouse, rabbit
and camel. The cow is entirely immune even after every effort at
inoculation ; and the hog can be infected only with considerable dif-
ficulty; domestic fowls are also immune.
This infectious malady causes both in its acute and chronic course
(the latter, perhaps persisting for years) a purulent fibroplastic in-
flammatory change, developing mainly in the skin and respiratory
mucous membranes. Pathological changes also invariably occur in
the lymph vessels and lymphatic glands ; and in addition metastatic
foci may follow in the spleen, liver, testicles, kidneys, sometimes in
the flesh, and finally a general blood infection results.
The microorganism of the disease, the glanders bacillus, discov-
ered by Schiitz and Loeffler, is always present in all tissues the seat
of glanders changes, in the discharges of the subject mixed with
glanders pus. and is sometimes found in the blood. It is a short rod-
shaped organism, measuring from two to five micromillimeters in
length and from one-half to one micromillimeter in width. It does
not exist free in nature, but multiplies • exclusively in the animal
body (cf. contagions diseases, p. yx) ; only under special conditions
312 specific Inilammations.
can it be grown* in the incubator on nutrient media (glycerine
bouillon, serum, agar, potatoes).
Transmission of the infectious agents from one animal to an-
other or to man is the result of a close relationship (living together)
or actual contact of the diseased animals with others ; and may take
place when the vehicle of the contagion (pus, nasal discharge, etc.)
gets upon the fodder and in the water, or when discharged in cough-
ing or blown out in sprays of fine drop-
^ js ^ lets and iniialed by other animals. If
* \ « ^ the material should lodge on the skin
\-'
\ ^ ''\' N and mucous membranes it may pene-
Jfvv* \ "trate even through apparently intact
"^ pores (transmission by blankets, saddles
^ . • and harness soiled with the pus). Ar-
1 tificially the disease may be reproduced
* / f-T '-'-^ cutaneous, subcutaneous, intraperi-
i ^ toneal and other forms of inoculation.
Fig. 73. and by feeding the glanders germs to
Glanders bacilli (from cui- the susceptible animals. From the ex-
ture).
permiental studies of Nocard and
Leclainche, Galtier, Conte, Renault, Cadear and Malet, the
smallest lesion of the epithelium in mucous membranes
may serve as a point of entrance for the germ, as the trivial lesion
which is produced by rubbing with a piece of linen cloth or the
tiny epithelial abrasions about the nostrils caused by bits of food-
stuff. In guinea-pigs the infection may be successfully produced by
dropping the glanders bacilli into the conjunctival sac upon the in-
tact mucous surface, probably through the lymph follicles and tear
ducts. In feeding experiments the lymph-follicles of the pharnyx
and intestine are the points of entrance of the infection. Inhala-
tion of tlie germs distributed by spraying also occasions infection of
the pharyngeal mucous membrane. The infection develops most
rapidly after intravenous and intracranial injection.
The bacilli multiply at first locally upon and within the tissue
(lymph spaces, lymph follicles) to which they have gained access,
and produce by the influence of their metabolic products a progres-
sive cellular necrosis with destruction of the nuclei (formation of
granules and globules, fragmentation of chromatin) and trans-
formation of the cells into finely granular detritus. Coincidentlv
tliere is seen a continual emigration of the white blood corpuscles,
* For details cf. Kitt, Bakterienkundc fur Tlerarxtc. IV Aufl., Wien. 1903
Glanders.
313
that is. a local inflammation, which in the chronic form of the affec-
tion also produces a wall of demarcation by fibroblasts. With
the persistent and progressive multiplication of the bacilli in the
Fig. 74.
Microscopic section through a glanders nodnle in hmg of horse.
Fig 75.
Glanders nodules, erosions and ulcers of the nasal septum of horse.
inflamed and necrobiotic tissue,, this limiting new tissue is, however,
continuallv being broken down and the area of destruction is
widened. ' The virus being taken up by the leucocytes, multiplying
314
Specific Inflammations.
mmm^^W}
in the lymph spaces and therefore open to lymph convection, is dis-
seminated in the vicinity of the primary focus, passes along the
lymph vessels and into the blood ; and new points of deposition and
new foci of the disease occur locally and metastatically. The bacilli
are also carried by currents of secretion and may lodge in a fresh
position on the mucous membrane, here again to give rise to new
colonies, as where they are carried from the lungs to the larynx
and pharynx. The metabolic prod-
ucts of the organisms, developing in
the system, by their toxic influences
occasion fever and wasting.
The visible anatomical changes
of the disease vary considerably with
the virulence of the affection and the
tissue predisposition of the particu-
lar kind of animal. The principal
types are the glanders nodules,
glanders abscesses, gla)iders indu-
rations and glanders infiltrations.
Glanders nodules, developing
niainl}- in the lungs and parenchyma-
tous organs, appear as grayish-white,
semitransparent. opalescent, rounded
])rominences or deposits ranging from
the size of a grain of sand to that
of a pea, their central portion break-
ing down into a yellowish-gray,
purulent or dry cheesy material. In
the lung they are often surrounded
by a dark red area. The glanders
ulcers present themselves on the mu-
cous membranes of the respiratory
tract as shallow or deep lesions, varying from the size of a lentil
to that of a silver dollar ; the loss of substance giving the mucous
membrane an appearance of being eaten or gnawed. The larger
ones have thick, wall-like, eroded margins. These ulcers have a
bacon-like gray color, with the bordering mucous membrane often
dark red and hyperaemic, bleeding on the least provocation. There
are usually large numbers upon an affected mucous membrane.
The glanders ulcers of the skin range from the size of a lentil to
that of a half dollar, are of a dirty grayish-red color, covered with
Fig. 76.
Glanders induration of the uasal
mucous memibrane of tbe
horse.
Glanders.
315
pus and half dried crusts, and (he surrounding hairs are soiled with
pus. These ulcers often undenuine the skin producing crater-like
openings (like the anus of a chicken) and are apt to.be found in
rows one after another and alongside of each other.
Glanders abscesses are commonly found in the skin as some-
what rounded boils of the size of a hazel nut or a walnut, with the
hair lost from over their surface. They fluctuate and contain a
thin, oily, yellow or yellowish-red pus, sometimes a rather thick and
mushy detritus, and their wall is made up of bacony, eroded cutis
Fig. 77.
Glanders uodules and iudurations of lung (;f horse. Natural size.
and induration tissue. They are apt to be found in rows enclosed
in the swollen, dense lymphatic cords ; that is they form foci of sup-
puration interrupting the lymph vessels like a rosary.
Glanders Uidurations occur on mucous membranes as the result
of a demarcating fibroplastic proliferation in the form of solid, nod-
ular or ridge-like, thick prominences of the mucous membrane, with
a yellowish-gray to reddish-yellow color, and a smooth slippery sur-
face. These thickenings may appear as isolated prominences of the
size of a hemp seed or oat seed, or may be fused so as to form hard
stellate and radiating scars like frost-cr\stals. not extending deeply.
3i6
Specific Inflammations.
and projecting- somewhat above the surface. They are scattered all
over the surface of the mucous membrane, often in large numbers,
and may sometimes occur in rows. Sometimes this chronic indura-
tive inflammation may form patches of thickening a finger's length
in extent and several centimeters broad, standing out like cushions
in marked relief, sometimes of dull grayish-yellow color or mottled
with bright red points, and their smooth surface covered with a
viscid pus. Occasionally warty, soft, raspberry-colored, projecting
granulations are found grow'ing from the mucous membranes.
In the lungs indurative patches are met sometimes about suppu-
Fig. 78.
<;iander.s nhscesses of the skin (jf horse.
(Photographed by Dr. Jakob.)
rating and caseating glanders nodules as bacony, grayish-white
zones of demarcating tissue, sending radiations into the pulmo-
nary tissue; sometimes as broad yellowish-white, poorly defined
areas of connective tissue, merging into the pulmonary structure,
involving numerous lobules and changing them into a dense mass,
and cutting with a tough, leathery resistance. On the inside of such
areas are met dull yellow, ochre-colored, moist cheesy or dry
plaster-like deposits.
Glanders infiltrations develop in the lung as true pneumonias of
catarrhal, suppurative or croupous types, and as a sclerosing form ;
tlie former in acute, the latter in chronic glanders. Especiallv in
Glanders.
317
the cat family the hing's arc involved just as in croupous pneumonia
and show stages of red and gray hepatization. In the horse the
lungs are apt to show a confused mixture of inflammatory changes ;
groups of lobules are found all through the lungs forming wedge-
shaped, swollen areas of a densely elastic consistence cutting like
bacon, mottled reddish-yellow or grayish-yellow and leaving on the
knife blade a turbid muco-purulcnt juice. In tlie chronic type the
pulmonary tissue is changed into an extremely tough, light grayish-
yellow mass of connective tissue riddled with confluent cavities about
as large as a thumb's breadth, filled with a slimy, oily pus and having
a deeply reddened inner surface. In this type of change the lymph
%;\>^"
Fig 79.
Large glanders ulcer of nasal septum of horse.
glands become very large and swollen, soft like marrow ; afterwards
densely indurated and changed into a tough white connective tissue,
forming nodular bunches as large as a goose tgg which become ad-
herent to the surrounding structures by similar fibrous bands. In
the interior of these hyperplastic and inflamed lymph glands is
encountered either a purulent softening in isolated spots or exten-
sive purulent liquefaction with cavity formation, or an indurated,
drv cheesy necrotic focus. The multiplication of the glanders
bacilli in the lymph paths, besides causing them to swell up like
cords, also gives rise to a diiTuse gelatinous infiltration (especially
because of the lymph stagnation), and, if the inflammation become
chronic, to broad connective tissue thickenings ; so that, for example,
the loose cellular tissue of the skin becomes the seat of gelatinous
thickening with extensive indurations all through it (pachydermia,
elephantiasis) with foci of suppurative necrotic destruction running
all through the skin and subcutaneous tissue.
3i8 Specific Inflammations.
These more important anatomical changes of glanders are met
associated with each other and succeeding one another ; so that
along with the pneumonic infiltration of the pulmonary lobules
glanders nodules are apt to be met in the same case; along with
the abscesses, ulcers also are encountered, the latter developing
from the former, and the diffuse infiltrations occurring a§ a
terminal chang-e.
Glanders generally may be considered as an irrecoverable infec-
tious disease ; exceptions have been met occasionally in man, guinea-
pigs and horses, but are so rare that attempts to cure are hardly
worth the effort in the case of animals, and seem to be injudicious,
when the daily danger is considered of the transmission of the in-
fection to man and other animals from the subjects dragging out
the course of their disease for months and years. The only rational
method of exterminating tlie disease consists in killing the animals
and carefully doing away with every chance of harm from any ani-
mal known to be afflicted with glanders ; and these provisions should
be made binding by law.
For details concerning the aetiology, symptoms and prophylaxis, refer-
ence may be made to Friedberger and Frohner, Vcicrinary Pathology,
Amer. Ed., W. T. Keener & Co., Chicago, 1904; Xocard-Leclainche, Lcs
maladies microbiennes des anitiiaux. Ill edition, Paris, 1903.
Actinomycosis.
Actinomycosis {SlktU, ray; tJ.vKr,s, iungns) , or Ray-fungus Disease,
is a form of wound infection manifesting itself bv the anatomical
changes of a suppurating granulomatous inflammation ; it may be
caused by several varieties of a group of fungi known as the rav
fungi or actinomycetes. It occurs not infrequently in man, cattle
and swine and has been exceptionally observed also in sheep, hart
and roe deer, dogs, cats and elephants.
The fungi which cause the affection were first discovered bv
Langenbeck in 1845 i" the carious lumbar vertebrae of a man, later
by Rivolta in 1868 in tumors of the jaw in cattle and by C. Hahn
in 1870 in the tongue in cattle ; and have been more fully investigated
by Bollinger. Harz, Johne, Israel, Ponfick. Gasperini, Berestnew,
Bostrom and others. They have wide distribution in nature, existing
especially in field soil and the beards of cereals. The usual mode
of infection b\" the ra}- ftingi is through wounds made by small for-
eign bodies penetrating into the skin or inucous membranes, as sharp
Actinomycosis.
319
spicules of grain or other stiff particles of food t(^ which the fungi
are adherent; or they may gain access to the tissues- through
scratches and similar lesions of the skin. ' Examples of such mode
of infection are common. Persons who put heads of grain into their
mouths or who accidentally swallow portions of such heads or who
have been injured while harvesting, have been known to develop
at the points of injury (gums, throat, hands) actinomycotic ab-
scesses and growths. Swine pastured in stubble land where their
teats are casilv wounded by the stiff straw stubble are not infre-
Zu nffen b csis
©?*■
Rachenrvand
Fig. 80.
Fiiugous actinomvonsis in pharynx of cow. Actiiioin iiciiiit . actinomycotic tumor.
h'lUliciiinnul, wall of pharynx. Zuninnhnxix. base ot tongue.
quenth known to develop actinomycosis of a mammary gland.
Cattle frequently show actinomycosis of the t®ngue, gums or lips
along with the presence in the tissues oi spicules of grain or other
food materials which have been forcibly lodged in between the teeth,
in the pharynx, etc. Occasionally in castration the fungi from the
straw of the bedding get into the operation wound and set up acti-
nomycosis of the stump of the seminal cord and scrotum (for de-
tails cf. Schlegel and Kitt*). The occurrence of actinomycosis oc-
casioned in some such accidental way (pasturing in stubble fields)
*Hnnrn>. der pathoij. Mikrnon/.. v. Kolle and Wassermann : Gustav Fischer,
Jena, 1003. Kift liactcncnktindr fiir Tierdrzte, W Autl. W len.. 1JU4,
320 specific Inflammations.
has more frequently been observed than an actual epidemic affection
(Bang, C. O. Jensen, Preusse).
Transmission of actinomycosis from one animal to another or to
man is very improbable ; the few alleged cases of such an occurrence
which have been recorded in literature might equally well have been
caused by traumatic infection. Artificial transmission by inocula-
tion has been successful only in a few cases (Johne, Wolff and Is-
rael, Ponfick and others), and in these the experiment animal had
to receive rather deep inoculation with comparatively large amounts
of the infectious material (intraperitoneal, subcutaneous injection);
while in ordinary wound infection and feeding transmission failed
completely.
The anatomical changes brought about by the actinomycotic in-
fection include the formation of actinomycotic nodules, abscesses
and fungous granulomatous proliferations, sometimes accompanied
by indurative connective tissue proliferations.
The actinomycotic nodules (actinomycosis nodularis) are small
inflammatory foci of the size of a millet seed to that of a pea, yellow-
ish-red or grayish-yellow in color, composed of a soft granulation
tissue, which is developed as the product of a demarcating inflam-
mation about the fungus which acts as a foreign body. They show
one or a number of opaque yellow punctiform spots from the pres-
ence in minute foci within them of the yellow colored clumps of
fungi and pus cells. • When they are in the parenchyma of an organ
they are surrounded by a connective tissue
^■^.-^^^^rr/flff'^ ^°"^ °^ induration ; when on mucous surfaces
^M^^^W?^>P^MM. t'ley break through and project somewhat.
^^■'^^M'^-'^^^F ^cti^^omycotic abscesses (actinomycosis
^'?^iii^^ pi^rulenta, apostematosa) are areas of soften-
mg from the size of a plum stone to that of a
'^' ■ , human head, with purulent content which
Actinomj'cotic clump.
fAftci- ostertag.) either appears as a thin mushy fluid, creamy
and of a sulphur yellow color, enclosed in a
white indurated abscess wall, or the areas are made up of a flabbv,
grayish-yellow to reddish-yellow matrix, which contains the infil-
trating pus, not in separate foci large enough to allow it to be taken
out in a spoon, but just as though it were in a fine sponge. In the
latter case there is no real abscess membrane present, although the
surrounding tissue for some distance is converted into an indurated,
dense white connective tissue.
The fungous actinomycotic grozvths (actinomycosis fungosa)
look like mushrooms or soft cushions, projecting above the surface
Actinomxcosis.
321
of the skin or mucous membrane. They are more or less peduncu-
lated growths, varying in size from that of a nut to that of a fist,
covered with blood and pus and crusts, with an elastic, soft consist-
ence, on section looking like bacon, grayish-white or grayish-red,
and thickly beset with points of suppuration or the described flabby
yellow patches of softening.
&
^/.^•i
i A?':
j'^^'i
-%
X*
O U^}:''
Fig. 82.
\„dnlp .,f actinomvcosiy (high uiaguitteation ) : </. fibroblastic and epithcliuid l)ui-
der'; b, leucocytic central pdrtion : c, actmoniyces.
All three of these forms may occur together and pass into each
other. For example, after rupture of an abscess the granulomatous
proliferation springs up and grows out as a fungous mass; or the
small nodules, because of the progressive multiplication of the fungi,
become confluent and form the larger flabby areas of softening ; or
the bacon-like connective tissue growth prevails, and this causes
more or less marked induration of the organ.
The most characteristic thing about the actinomycotic growth is
the fungus. This may be recognized even by the unaided eye as
minute granules the size of a sand grain, soft like tallow or some-
times of a chalky consistence, of a sulphur-yellow color or white;
322
SpeciHc IiiHamiiiotiojis.
they may often be present in large numbers in the softened areas
and the pus from this may sometimes have an ahnost sand-Hke, gritty
consistence. Under the microscope the fungi may be discerned in
Fig. 83.
Head of cow with actinomycosis of Jaw. (After Moiissu.)
unstained preparations as strongly refractive, gray or shining-yellow
clumps of club-shaped filaments arranged in the form of a rosette
(fungus glands) : in stained sections the filamentous, intricately
Fig. 84.
Actinomycosis of tbe nasal mucous membi-ane of cow.
branched mycelium forming the matrix may be seen, and the
clump, with its budding elements swollen into club shape and
growing out from the periphery in radiating fashion.* The
* For fuller description cf. Kitt, Bakterienkunde f. Tierarste, IV Aufl., Wien.
M. Perles Verl. 1903.
Actiiioiitycosis. 323
clumps of fungi are always surrounded by leucocytes in the fatty
and granular detritus, sometimes, too, with here and there a giant
cell. About this central, softened focus proliferating fibroplastic
tissue is formed, vascular and full of emigrated leucocytes, as a
zone of varying width.
Actinomycosis is primarily a local affection, rutming a course of
months or years in duration. As the fungi penetrate the lymph
spaces and are carried to new positions fresh eru])tions in multiple
foci of infiammation along the lymph vessels and in the lymph glands
arise, with purulent softening and coincident production of new
tissue in the soft parts and in the bones. By hgemic convection
also the process may become a general one, a number of organs,
bones, etc., becoming synchronously or one after another involved.
[In cattle one of the most common and characteristic results of
actinomycotic infection is that seen in involvement of the jaw,
which may well illustrate many of the features of the disease. The
infection here is supposed to take place by the penetration of a
small spicule of grass or beard of grain into the gum along
the root of the tooth, such a foreign element having upon it
the actinomycotic fungus. In unknown way die fungus penetrates
along the root well into the alveolar process of the jaw, and there
produces the small nodules above described, each undergoing cen-
tral softening and disintegration, and being surrounded by a zone
of new tissue formation at its periphery. Gradually the process
loosens the teeth; and as they are elevated in their sockets by the
inflammatory tissue, and chewing becomes painful, the animal
stops eating. Sometimes the teeth are forced up so tliat the animal
is unable to close the mouth without pain, and the teeth may even
be lost. The process gradually spreads throughout the alveolar
bone and into and through the whole thickness of the jaw, the in-
flammatory change about each nodule at first causing absorbtion
of the calcareous matter, and thus giving the fungi a chance to
spread in this softened tissue. As each nodule grows older, the
formative tissue at its periphery produces new bone : and from the
coincident operation of the two factors of bone destruction and
bone formation the jaw becomes enormously enlarged ("big-jaw"),
riddled with the small points of softening representing the different
actinomycotic foci and with fistulous paths running all through the
mass, connecting these points of disintegration. The jaw may thus
have developed wdthin and upon it a tumor-like mass the size of a
double fist or much larger, composed of a coarse framework of
324 specific Inflammations.
newly formed bone like a coarse calcareous sponge, tlie meshes of
which are occupied by the actinomycotic nodules and their purulent
matter. Fistulous sinuses discharge upon the surface and into the
mouth ; and in the purulent material are to be seen the tiny yellow
sand-like grains known as "sulphur grains," consisting of the fungi
themselves. The animal may die from starvation ; the process may
extend along the ramus of the jaw to the base of the skull and
gradually advance by the same changes through the latter and cause
death from a purulent meningitis ; or the fungi may be carried
along the lymphatics of the neck to the thorax, producing an acti-
nomycotic pleurisy and entering the lung to cause fibrosis and puru-
lent destruction of these organs. Occasionally the fungi swallowed
with tlie discharge into the mouth give rise to alimentary actino-
mycotic abscesses.]
Lignieres and Spitz have described an epidemic disease of cattle
similar to actinomycosis occurring in Argentina, in which the skin and
lymph glands are principally involved (rarely the bones of the face and
tongue). The yellow fungus grains are not present, and another species of
microphyte which does not stain by Gram's method is regarded as the
cause {actiiiobacillosis).
Botryomycosis.
By the term botryomycosis is meant a productive inflamma-
tion which leads to the formation of fibrous growths or cicatri-
cial indurations attended invariably with suppuration and fistula
formation or the production of brownish to yellowish-red foci of
softening, and which are caused by infection with botryomyces
ascoformans. The disease is quite common in the horse; and
has been met a very few times also in the cow and hog (Csokor,
Wilbrandt).
The fungus which is the productive agent of the disease, dis-
covered independently by Bollinger in 1870, Rivolta and Micel-
lone in 1879, and by Rabe and Johne, presents itself in the dis-
eased tissue as a deposit of fine sand-like granules, visible to the
naked eye. iMicroscopically it is characterized by the occurrence
of the fungi in blackberry-like masses (fifty to one hundred
micromillimeters in size) made up of conglomerated round, disc-
like masses of cocci grouped together in zoogloese.*
This fungus gains entrance to the tissue by infection of
wounds ; apparentl\- it may find its way through small excoria-
* For fuller description cf. Kltt, Bakterienkunde fiir Tier'drzte. IV Aufl.,
Wien, 1903.
Botryomxcosis Tnnwrs.
325
tions in the epiderni nr llin)nj;h tlie o-lands of the skin, as botryo-
mycotic growths develop especially at places in the skin which
are frequently subject to friction (places worn by harness and
saddle.) Very frequently the growth involves the stump of the.
spermatic cord after castration, or the udder and penis sheath, as
well as the bursas and fasciae of. the withers, elbow and shoul-
der. The tissue invaded by these microorganisms becomes the
seat of a chronic inrtammation. At tirst it has a grayish-red color,
later becoming pale and translucent (like
bacon) ; and eventually a white cicatricial
connective tissue develops in the mass,
spreading through the loose cellular tissue
and over the surfaces of the fasciae and
producing enormous induration and thick-
ening* of the part. Or the process may
be more definitely limited to spheroidal
nodular masses which project from the sur-
face as fibroma-like tumors, ranging in size
from that of a fist to that of a human head
or larger. The growth of the clumps of
microorganisms in this fibroplastic tissue brings about foci of
softening of a viscid purulent type, sometimes of a distinct yel-
low color like ordinary pus, but commonly of a safit'ron or
orange tint, with formation of fistula? to the surface and paths of
confluence in the mass. As the result of multiple coincident or
successive infection of the skin there often are met dozens of these
botryomycomata in one subject. Convection of the microbic agents
by the lymph and blood leads to metastatic growths, especially in
the lungs.
Fig. 85.
Botiyoinyces ascofonnans
(low power).
For fuller account cf. Kitt. Sprcicllc patliol.
II. Aufl. F. Enke, Stuttgart, 1901.
\natoinic dcr Ilaiiticri
New Growths, Tumors, Autoblastomata.
By the terms new growths, tumors, new formations, neo-
plasms, autoblastomata (Klebs). ore meant tissue proliferations
of persistently progressive eliaracter, li'hieh alter the conforma-
tion of the part and disturb its function. These growths appear
as excessive tissite accumulations caused by cells of the animal
body which have become parasitic in nature and Avhich invade
the soft structures or skeleton of the animal as more or less
isolated and independent bodies. Enlarging sometimes slowly,
326 Tumors.
sometimes rapidly, and never undergoing diminution, they inter-
fere with the other tissues, perhaps by robbing them of their
nutrition, perhaps by some of the products of their metaboHc
changes, but particularly in a mechanical way by their pressure
influences.
It has been only within the last sixty years, since Rudolf
Virchow by comprehensive histological studies and critical
examination of the older literature established a new basis for
the systematic consideration of the different types of tumors,
that a scientific conception of the origin and nature of new
growths has entered into their study {oncology; 6 6yKos, node).
Previous to this period tumors were classified mainly from their
external appearances and their gross anatomical characteristics,
and were named frequently from incidental features often of
merely accidental prominence ; and no real knowdedge was had
of the developmental history of these growths. Although in
our present knowledge of the development of tumors there are
many missing links, we nevertheless possess from microscopic
and experimental investigations sufficient information in regard
to their nature to permit us to clearly recognize* their derivation
from the cells of the body, the mode of their extension and their
actual method of growth, and the significance of the pathological
process in its bearing upon the life of the subject.
Tumors may te classified from their histogenesis, that is,
from their structure and from their origin and construction from
the cells and tissues of the body. There are no foreign tumor ele-
ments brought into the body from without ; tumors are offsprings
of the body cells, and are accordingly found to consist of these
and of the intercellular substances of the various tis-;ues. They
develop according to the same laws which govern the embryonic
development and later growth of the individual and the processes
of regeneration ; and they arise from the four primary types of
body tissue (connective tissue in all its forms, epithelium, muscle
and nervous tissue.)
Just as the tumor cells present the same form and the same
mode of multiplication as the mother cells from which they are
derived, the intercellular substances, as products of the cells, are
the same as are produced by the original cells. Generally, there-
fore, the source of a tumor can be determined from the character
of its tissue ; although because of the fact that they grow^ more
or less independently, as isolated masses of tissue, it is quite
reasonable to expect more or less modifications in the structure
Classification of Tmnors. 327
and adaptation of the cells and matrix of tumors. The cells
frequently do not attain the same size as the mother cells or
may be larger than the latter ; cellular division takes place some-
times as a direct process, sometimes indirectly with mitotic
changes. The mitotic figures, which are likely to be found in
great numbers, especially in rapidly growing tumors, and the
process of cellular division often show irregularities pointing to
a pathological disturbance of the process. The chromatin fila-
ments derived from the chromatin skein (chromatosomes) may
be too numerous or asNinmetrical ; or there may be found giant
mitoses, karyokinetic figures in multipolar arrangement, arranged
about a number of attraction centres (centrosomes), or giant
cells. The cells may also, as stated by Ribbert, exhibit altera-
tions which may be regarded as regressive in character, as a
return to an embryonic state in which there is but little evidence of
differentiation ; or they may really be embryonic cells whose
power of forming normally functionating organs has been lost
(a change designated by Hansemann by the term Anaplasia) .
The cellular type and the character of the tissue of the growth
furnish the basis for nomenclature of tumors. Many tumors are
made up of but a single kind of tissue, as fibrous connective
tissue, fat tissue or cartilage, or at least mainly of one type (the
accompanying bloodvessels are not regarded as a special form of
tissue but as essential constituents of any form) ; such growths
are called simple autohlastomata. Others, no less numerous,
contain two or more tissues, as is obviously required in epithelial
new growths because epithelium always requires a connective
tissue substructure, and as is likely to occur, too, in other tumors
from the mixture of the various forms of connective tissue, as
cartilage, bone or fat ; we therefore recognize as a second group,
the compound autohlastomata or mixed tumors.
It should be recognized, too, that tumors as independent devel-
opments, although relying on the animal body for their nutri-
tion, yet having their own blood vessels and carrying on a
separate metabolism, are subject to all the pathological processes
which may affect the normal tissues of the body. A tumor may
become the seat of passive hyperaemia, of inflammatory reaction ;
and any kind of degeneration and necrosis may occur in the
tumor structure. Tumors are sometimes subject to traumatic
influences from without (strangulation, wrenching, penetration
by foreign bodies or bacteria) which may occasion tissue
changes; sometimes the conditions of nutrition become so un-
328 Tumors.
favorable from irregularities of g'rowth of the individual con-
stituents of the tumor (as the imperfect development of blood
vessels) or from the absence of ducts for the escape of secre-
tions, or from the retention of metabolic products, that regres-
sive metamorphoses, as fatty degeneration, calcification, mucoid
degeneration, etc., necessarily take place. When such condi-
tions prevail and when the structure of the growth is modified by
this or that change there is often considerable difficulty in deter-
mining the derivation of the tumor and there may be much un-
certainty under which group of tumors a given neoplasm should
be classed. In such cases we follow the proverb : a potiori fiat
deiiominafio ; and the anatomical term is given from the pre-
dominating type of tissue present.
Growth of Tumors. — Derived from one or more tissues, tumors
at first form cellular masses (or a tissue complex). These in-
crease in size as the internal portions of the new formation
multiply, that is, by centra! growth; or they enlarge by progres-
sive multiplication of the outer portions, that is, by peripheral
or appositional growth. The increase in size and extension of
the tumor therefore may take place by one or other of two ways ;
either by the tumor growing "as a bulb, lying in the soil and
developing, presses aside the ground" (Diirk). "as a rubber bal-
loon which one inflates'' (Ribbert) (expansile growth), or by
the tumor tissue sending out processes into the neighboring struc-
tures as a plant forces its roots into the earth (infiltration growth).
It was formerly believed that the enlargement took place by the
surrounding tissues becoming gradually involved in the same
proliferative process, being actually infected (local infection) ; but
this is not probable, as we may usually recognize under the micro-
scope that the proliferating cells of the :neoplastic primary focus,
that is, the first elements of the tumor, are extending into the
surrounding tissue, growing mto the interior of the tissue or
toward the surface of the part. The surrounding tissue supplies
only the nutrition for growth and takes part only in this sense
that its blood vessels and supporting tissue may be appropriated
by the new growth, and that it may also multiply as the result
of the changes in tissue tension which may be produced (v.
chapter on Regeneration) ; otherwise, however, the surrounding
tissue plays but a passive part, like the soil in relation to the
seed of grain.
External Shape of Tumors. — In correspondence with their
mode of growth autoblastomata form usually circinnscribed
Tumor Shapes; Sii^nificance of Tumors. 329
tumors well tlefined from the normal tissues. They may develop
as nodes (tuherous growths) which lie embedded in the tissue
like the yolk within an egg, or niay protrude as tuberosities; they
may grow out from the surface of an organ as pedunculated
protuberances, with thick pedicle like a mushroom (fungous form),
or with slender pedicle and provided with free offshoots like a
polyp with its tentacles (polypous shape), or like a tree (den-
tritic), like a coral stalk or like cauliflower; or, in the infiltrating
varieties they may occasion a uniform szcelling of the affected
organ. [Anv tumor growing from a surface and provided with a
slender pedicle may be spoken of as a polyp or a polypoid
groii'th, whether branched or smooth. A form known as a flat
tabular s-u'elling is often encountered where upon a surface the
growth has produced a more or less uniform swelling with a
flattened surface, as is often seen where the surface of a growth
is opposed by a second surface causing pressure. The causes
determining the various shapes of tumors include such factors as
the mode of growth (central growth producing a regular ap-
pearance of the periphery, while infiltrative growths are apt to
be irregular and ragged in outline), pressure, (as just suggested
in connection with the flat tabular swelling, or the preservation of
the spheroidal shape of v node by the pressure from all sides by
the surrounding tissues, or where an analogous growth appears
as a tuberosity or polyp if developing close to a surface, being thus
relieved of pressure on the surface side), and the original structure
from which the tumor arises (as where a surface growth, a
papilloma, takes on ■ a villous type of branching following the
natural formation of villi from the original tissue, as in the
intestine.)]
The Pathological Significance of Tumors is determined pri-
marilv bv their location, their size and the mechanical pressure
which the}' exert upon the adjacent tissues. By pressure upon
the peripheral tissues a tumor as it grows in size occasions some-
times trifling and at other times serious disturbance of func-
tion, varying with the particular organ affected. A small
tumor in the brain or in the cranial cavity may by compression
of the fonuer or of the cerebral vessels bring about most intense
nervous troubles and terminate fatally; and by obstructing the
larynx, gullet or intestinal canal a comparatively small growth may
endanger life. Pressure upon bloodvessels may occasion a great
variety of circulatory disturbances. But, on the other hand, even
330 Tumors.
large growths of the skin or subcutaneous tissue often produce
only the most trifling effects.
In the second place the pathological significance depends
upon the degree of special power which the tumor possesses to
disseminate through the system. The less a tumor involves
strictly the surface of an organ or the less it remains closely
confined to its point of origin as a single isolated growth, and
the more it sends out oilshoots which extend into the lymph-
passages and bloodvessels and thus obtains opportunity for its
cells to be loosened and carried into new locations in the body,
the more the development of the neoplasm acquires specially
dangerous characteristics. The outshoots of a tumor, made up of
its proliferating cells, force their way first in the surrounding tis-
sue, especially the connective tissue lymph spaces, which repre-
sent the beginnings of tlie lymph passages, causing a continually
increasing portion of the organ in which the growth occurs to be
destroyed by the infiltration (the tumor therefore spoken of as a
destructive growth or locally penetrating grozcth). In such new
formations the external, visible outlines are usually not its actual
limits; the apparently healthy adjacent tissue may conceal the
roots of the tumor only to be found microscopically. The sur-
geon, whose skill can in many cases aft'ord permanent recovery
by removal of the growth, is unable occasionally (for technical
reasons or because the precise limits of tht individual roots
cannot be recognized by the unaided eye) to remove the entire
tumor in the operation performed for its ablation ; from the
portions thus left, earlier or later the same tumor may return in
the original site or close by (recurrence of tuuior). The tumor
cells grow into the- lymph passages, sometimes as continuous
cords or roots ; or the cells may become loosened or be carried
away by the lymph current or perhaps by leucocytes. The
same thing occurs where the roots of the tumor penetrate through
the wall of a blood vessel, sometimes developing as long pro-
cesses within its lumen ; and particles of the growth may be
swept off by the blood current. Under such circumstances, at a
shorter or longer distance from the (primary) autoblastoma (the
principal tumor) arise secondary tiiinors. daughter tumors or
metastatic tumors. The lymphogenous metastases are carried
into the immediately adjacent tissues and into the lymphatic
glands draining the site of the original growth; the embolic
(haematogenous) ones pass into the lungs or the organs of
the greater circulation (v. chapter on Embolism). When in this
Pathological Si^^nUicancc of Tumors. 331
manner the tunuir is disseminated widely to the various organs,
we speak of the generalisation of the tumor. This lodgment and
development of daughter nodules from the cells which have be-
come freed from a tumor, an actual form of seeding by trans-
plantation, is met also at contact points on mucous and serous
surfaces. For example, an ovarian tumor may become dissem-
inated all over the peritoneum by having its cells loosened and
scattered over the serous membrane ; a tumor of the costal pleura
may become transplanted to the visceral pleura ; one of the
upper lip to the lower lip. The cellular elements of the growth
in such instances are freed and distributed by the movements of
the viscera, or by the friction of contiguous surfaces.
All secondary growths correspond closely with the primary
tumor from which they arose in their histological structure;
where a cancer of the gum metastasizes to the retropharyngeal
lymph glands and lungs the metastatic formations are composed
of squamous epithelial cells just as is the primary tumor. They
need not necessarily be smaller than the original giowth, and
are often of larger size than the latter.
Tumors which can be completely removed, which are not metastatic
and do not recur, are ordinarily called, from the clinical point of view,
benign (innocent) ; those which penetrate into the adjacent tissues and are
removed in their entirety with difficulty, or are recurrent and give rise
to metastases, are called malignant (harmful). To the extent that experi-
ence shows that one or othe-- of these results may generally be expected
in operations for removal, the classification into these two types may be
accepted; but the differences are not to be depended upon, as some tumors
which do not form metastases recur if not completely removed, and
tumors which are ordinarily regarded as benign may occasionally produce
metastases; and, again, well-known malignant growths often remain strictly
localized and harmless for a long time, and if they are removed early
enough will not recur.
As a further factor by which tumors may affect the system,
it should be recalled that within these neoplasms all sorts of
metabolic products and decomposition substances are being freed,
and these may by absorption have toxic influences upon the
possessor of the growth. It is quite common to meet with in-
flammatory changes in the tissue about a tumor and the growth
itself may be found richly infiltrated with immigrating leucocytes,
or rnay be found undergoing suppurative or gangrenous changes.
This may be due to the fact that tumors which happen to be situated
on exposed surfaces are invaded by bacteria, and the toxines
of the latter excite inflammation ; but there is little doubt that
332 Tumors.
some tumors give off into the surrounding tissues metabolic pro-
ducts having chemotactic power and thus stimulate leucocytes
to escape from the vessels. To all appearances we may ascribe
to the products of disintegration Occasioned by bacterial contam-
inations and occurring in connection with the various degenera-
tions in tumors the fact that in a number of these growths
there occur general nutritive disturbances (oligsemia, loss of
appetite, marked loss of strength, emaciation), which look like
the result of a chronic intoxication — a condition known as tumor
cachexia.
Just as the specifically differentiated cells of the body give
off specific products, in the same way the different kinds of
tumor cells, as the offspring of this or that variety of physio-
logical cells, produce in more or less similar manner the sub-
stances characteristic of the latter ; it may be claimed that they
too perform physiological functions.* This function, however,
is only in the rarest instances of any service to the general
system ; being without au}^ relation to the co-ordinated activities
of the rest of the organs, it is merely a vital phenomenon of
the independent cellular complex of the tumor. The formation
of intercellular substances by the tumor cells, as the formation
of osteoid callus in tumors arising from periosteum, is an
example of such function ; but tumors originating from gland-
ular cells and having gland-like structure show this power
especially, and are able to produce the sam'e secretory sub-
stances as the corresponding glands. Thus cancers of the intes-
tinal mucous membrane secrete mucus from goblet cells; thyroid
cancers produce colloid ; tumors of the mammary gland form a
secretion analogous to milk (but pathologically altered), and
tumors arising from liver cells often secrete so much bile that
the growth becomes thoroughly infiltrated with it (icteric). E.
Albrecht has observed that the formation of red blood corpuscles
normally performed by the bone marrow may also be carried
on by a tumor of the dura mater made up of endothelial cells
and erythroblasts.
As all offsprings of given cells manifest an ability given them
by heredity to perform the same fimctions as their predecessors,
it may be expected that the metastatic nodules also show the
same phenomenon. For example, one of a number of metastatic
nodes which had formed in the lung from a tumor originating in
*E. Albrecht, Sitsungshericlit d. morph. pln/s. Gesellschaft in Miinchen,
1901. Heft II.
Causes of Tumors. 333
the liver produced bile in tliis position, (lenerall}- the secretions
of tumors are apt to be the seat of pathological changes, as ordi-
narily there are no channels for discharge in the growth and the
secretion therefore is stagnant; and moreover the function would
be more or less abnormal, because of the abnormal topographical
relations of the proliferated glandular epithelium, the failure of
complete differentiation of the cells, or the reversion of tumor
cells to embryonic type and the lack of relation with the nervous
system of the host of the tumor.
There are conditions however under which the secretory pro-
ducts of a tumor are not devoid of value to the body, particu-
larly tumors of glands which produce internal secretions of im-
portance to metabolism and whose destruction would be ominous
to the well-being of the body, as the thyroid gland and pancreas.
The fact that growths from these glands may also produce
internal secretions may in some measure compensate for the
death or destruction of the organ by the tumor.
[Of all the body functions, that of growth (and that is rather
a mere vital phenomenon and not a dift'erentiated function) is the
one which is best and most completely manifested, being in line
with the embryonic characteristics which tumors as a class
possess. The example of the performance of a function of value
to the economy selected by the author in the preceding para-
graph is practically the only one which may be named. The
fat which accumulates in a lipoma is of no service to the host
of the tumor even if he be starving; the connective tissue of a
fibroma is of no connective or supportive value, but rather a
continual source of annoyance from weight and pressure. Even
the function of growth, most nearly typifying natural energy, is,
as the author points out. irregular in the manner of its occurrence,
is without efficient organogenic power and especially abnormal in
that it has no definite period of cessation.]
Aetiology of Tumors. — We possess but few facts and have but
a meagre idea about the mode of origin of tumors. Many the-
ories have been framed to explain the luxuriant growth of the
cells, but the diffiiculty of positive proof leaves us in uncer-
tainty between probabilities and theoretical dicta. Mere supposi-
tions that as the result of the action of a given stimulus this kind
or that kind of cells are excited into irrepressible multiplication,
revert to their embryonic characteristics or undergo biological
changes as expressed by the terms metaplasia or anaplasia,
are in no sense satisfying, but merely serve to conceal our igno-
334 Tumors.
ranee of the origin of these growths and to bring into the prob-
lem new difficulties.
Among the more prominently urged hypotheses may be men-
tioned the idea that an infections cause underlies the cellular
proliferation, a view which has had numerous adherents in re-
cent years. At first bacteria were sought as causative factors,
some of which as the causes of productive inflammation had mani-
fested functions suggesting analogies with tumor formation ;
but nothing has been shown beyond the mere secondary presence in
tumors of various saprophytes, pyogenic and other bacteria ; and
no microphytes have been encountered which can be regarded
as responsible for the proliferation of cells into tumors. In time
the line of investigation was directed to the protozoa. The in-
clusions, often shown by a variety of methods of staining in many
tumor cells, and apparently of foreign character (that is, intracellu-
lar and nuclear structures not conforming to normal parts of cells),
led a number of microscopists to regard them as of some type
of protozoan character and as the parasitic causes of cancer and
malignant tumors generally. However subsequent investigations
directed to the final proof of this discovery have shown that these
supposedly foreign elements are nothing more than altered blood
corpuscles, lymphocytes, nuclei of the tumor cells, degeneration
products or artefacts, produced by stains and reagents in the
tissues. In the same way the discovery of yeast fungi having
pathogenic properties capable of causing inflammatory granu-
lomatous formations by inoculations in small experiment ani-
mals, resulted in no definite or generally applicable conclusions ;
because these blastomycetes were not to be found in true tumors.
or if occasionally found occurred only on the surface of the
growth and failed to give rise to characteristic tumors. With
the demonstration of parasites as causative agents left in this unsat-
isfactory condition, consideration should be given to the so-called
invisible microorganisms ; or we should remember that perhaps
with our present technique the infectious agents in question
cannot be rendered visible.
A number of investigators insist upon the possibility that an
infectious factor underlies some types of tumors (Sticker),
because as a matter of fact there have been noted a number of
peculiar circumstances which point to the existence of a general
extraneous (not individual) cause; as the endemic occurrence of
cancer, its occurrence in connection with dermal excoriations, or
Causes of Tumors. 335
the occurrence of dermal proliferatimis ( pai)ill(iinata ) in a number
of horses in the same stable.
However, a great number of objections have been raised against
the parasitic hypothesis, especially by Ribbert, which leave this
method of causation in extreme doubt. In the first place the
various forms of tumors always have their fixed tissue-charac-
teristics, and the cells of the metastatic nodules , invariably con-
form with th(^se of the original growth ; if an infection were the
cause of the tumors it would always have to cause the production
of the same kind of cells in the various organs (that is, the cause
of a cylindrical cell cancer in the intestine would have to be
able to form cylindrical intestinal epithelium in the interior of
the liver; the cause of a squamous epithelioma would have to
form keratous flat epithelial cells in the lymph glands). How
that could occur cannot be understood; it would have to be
assumed that the cells were so intimately associated with the
parasites that both should always go together and grow together.
If such symbiosis be claimed to actually exist, then,, as Ribbert
logically argues, it must be assumed that the microorganism
invariably divides at the same time as the tumor cells so that
one of its offspring may be present in each of the two new
cells. "If this be not essential, it may be asked how the cells
which do not contain parasites come to proliferate any further.
If they are able to multiply, however, without the existence
of their parasites, why was it of essential importance that
the latter should have ever been present?" (Ribbert). Then
there is the established fact that every tumor grows from its own
substance under direct pressure contact from the contiguous
parts, and the surrounding tissue does not become infected; there-
fore the parasite would have to confine its multiplication strictly
within the tumor cells. This would be strange ; and the question
naturally arises, why, for example, the neighboring- epithelia
which are quite like those of a skin cancer do not furnish equally
favorable soil for the development of the microorganisms. In
the end, as Ribbert emphasizes, we should have to assume
that for every new growth, for every type of cell of malignant
tumors, there exists a special type of infectious agent incapable
of infecting otlier cells, as one special form for cylindrical cell
cancers, another, for squamous cell cancers, etc. The genesis of
tumors would become progressively more and more complicated
if such ideas w^ere to prevail.
336 Tumors.
The explanatory theories of Cohnheim and Ribbert based
upon considerations of embryology and mechanical conditions for
growth are far more simple. Tumors have been repeatedly met
in the new born ; for example a melano-sarcoma in a calf, a
papilloma in a foal, and a number of growths, which although
first noted in young animals were of a composition necessitating
an embryonal origin for their development, as dermoid cysts,
dental teratomata, branchial cleft teratomata. In the earliest
stages of embryonic development w^hen in a great variety of ways
there occur formation of folds and of buds, pressure displace-
ments and separations of the cells growing with unequal rapidity,
it is possible that cells and groups of cells may be cut off from
the rest, misplaced or isolated. Such misplaced cells will for
the most part perish, because of the necessarily occurring nutri-
tive disturbances ; but where according to circumstances the
nutrition remains sufficient the misplaced cells will continue to
grow and multiply, and there is necessaril\' produced from them
a structure which is apparently a foreign growth and not nor-
mally belonging to the structure of the tissues and organs. The
formation of blood vessels probably proceeds in a more or less
atypical manner in such separated and misplaced groups of cells.
as a result of which their growth is in one instance a very slow
one, in another an exuberant cellular proliferation. The experi-
mental studies of Roux have shown that by artificial isolation
and misplacement of segmentation cells each one is capable of
growing into an embryo; and Barfurth has observed that after
needling an ^gg in the gastrula stage tumor-like formations
(dern^oid-like) develop from the misplaced cells. J^Ioreover Rib-
bert has succeeded, by transplantation of fragments of the auricle
of a rabbit, in obtaining polypoid nodules persisting for more
than a year, consisting of skin, fibrous tissue,- cartilage and
bone ; and in other experiments tumor-like structures from bits
of the notochord, by transplantation to the anterior surface of the
intervertebral tissues. Occasionally the accidental or intentional
operative transplantation of epithelium or bits of skin into a
wound has resulted in the formation of a small epithelial cyst or
dermoid cyst from the engrafted tissue, which may be regarded
as evidence in the same line with the larger congenital growths
of this type. The fact that experiments of this sort have thus far
failed to produce larger tumors of progressiva and persistent
character of growth is not an argument against this theory ; we
must remember, as Ribbert insists, that our technique in artificial
Causes of Tumors. 337
isolation and transplantation of tissues is as yet not delicate
enough to prevent damaging the tissues and thus causing the
failure of the desired results.
Cohnheim extended his theory of the embryonic origin of
timiors to a wider application by advancing the hypothesis that
at an early period of embryonal developinent more cells may be
formed than are needed in the construction of the organs and
that some of these cells may remain unused as "rests," retaining,
because of their embryonal nature, a marked capacity for prolif-
eration ; and that from such excesses of cellular material tumors
may develop. The views advanced by Cohnheim, to whom we
are indebted for first pointing out the important significance of
foetal isolation of cells in connection with tumor formation, are
coming to be recognized as valid ; that from isolated segmenta-
tion cells, which have actually been observed, tissues and organs
may originate, and in all probability, too, independent tissue
formations and therefore autoblastomata.
In a somewhat different form practically the same hypothesis has been
recently advanced by J. Beard. Beard suggests that from every fertilized
ovum a number of germ cells originate (?), from which, however, only
one goes to form the embryo, the remaining wandering into the embryonic
mass and entering into the formation of the chorion (or the sexual cells?).
It may be possible that a tumor might develop from such wandering germ
cell if it stray to an improper part, and that such a tumor may be abso-
lutely nothing but an incompletely developed (rudimentary) embryo (which,
of course, is applicable for a number of tumors, especially the true
teratomata).
As a further application of Cohnheim's theory, which it is
true afifords a satisfactory explanation, not for all but for a
number of tumors, Ribbert has suggested that cells may escape
from their normal connection also in extra-uterine life and thus
become misplaced and in consequence provide the nucleus for a tu-
mor formation. It has been repeatedly noticed that tumors have
developed after a traumatic lesion, at the site of injury by foreign
bodies, after contusion, etc., as osteomata of the jaw after contu-
sion, large chondromata in animals and man after fracture of the
ribs at the seat of the fracture, cancer of the cheek in man after
being hit by a stone, cancer of the lip at the place where the
mouthpiece of a tobacco pipe has been frequently rubbing. As
it is ver}' difficult to think of such cases being due to any specific
irritative influence of the foreign body which caused the injury,
we are forced to consider changes in the positions of the cells,
338 Tumors.
displacements and isolations of osteoblasts, cartilage tissue or
epithelium, as causative of the autoblastomatous new formations.
It is not rare to see connective tissue proliferations of considerable
extent, completely reproducing the characteristics of fibromata,
developing from injuries of the tendon sheaths (horse and cow)
or of the tongue (cow) ; the growth is apparently the product of
a chronic inflammatory^ process and the result of an excessive
growth of granulation tissue. \Miether some special irritant,
perhaps bacteria, bring about such tumor-like formations,
whether absence of tissue tension occasioned by the trauma is
the single or principal reason for its occurrence, remains an
open question. At all events it is recognized that there are no
sharp lines of difference between tumors and regenerative prolif-
erations, and that the hypertrophies, which are regarded as sim-
ple proliferations in vacuo (as of liver) may pass over into
tumors.
Objections have been urged from various sides (Hansemann,
Hanau, Ziegler) to the opinions of Ribbert (who also accepts
inflammatory processes as possible causes for the inception of cel-
lular proliferations, as in case of epithelial cells). It has been
urged that if the above-mentioned displacements and isolations
of cells of epithelium were sufficient to call a cancer into exis-
tence, there necessarily should develop numberless cancers as
results of chronic inflammatory phlegmons ; that the cells of the
tumors ought not to appear merely as normal elements in luxuri-
ant multiplication, but the general rule should be that there exist
a special change, a differentiation of the cells (even though the
causes of cellular dift'erentiation be entirely unknown).
Although we still await the solution of questions regarding
the conditions which underlie the origin of tumors, and concerning
the transformation of this or that kind of cell into tumor cells,
it is at least certain that tumor cells are tissue elements zvhich
hare become independent and m(iy be looked upon as cells zvhich
have actually become parasitic. This conception of the nature of
tumors (for which from this point of view the name autoblasto-
mata, proposed by Klebs, is most appropriate) has received im-
portant support in the extremely interesting experimental studies
of a veterinarian, C. O. Jensen. This investigator succeeded in
carrying a carcinomatous tumor of a mouse through nineteen
generations in mice by transplantation, and in demonstrating that
infection played no part in the process but that the transplanted
tumor cells, themselves parasitic upon the individuals in whom
Causes of Tumors. 339
they were transplanted, continued to grow and form tumors of
the size of walnuts, growths of considerable size wdien that of
the experimental animal is taken into consideration.* Earlier
than this Hanau had succeeded in transferring an unquestionable
skin cancer of one rat to other rats wath similar results (in peri-
toneal cavity) ; and L. Loeb and Velich have successfully trans-
planted rat sarcomas, and Aloran has transplanted adenocarcin-
omata of a white mouse a number of times. [Still more recently
L. Loeb has carried an adenocarcinomatous tumor of a Japanese
dancing mouse through a number of generations, eventually find-
ing a change in the nature of the tumor which took on the histo-
logical characteristics of a spindle cell sarcoma. Other investi-
gators have described similar success in transplantation ; and
Loeb's instance of change in the tumor characteristics is not an
isolated one.] (Attempts to transplant sarcomas and can-
cers in dogs undertaken as much as ten years ago by Piitz and
other investigators have thus far failed.) The point of special
interest in Jensen's studies is the discovery that it is possible,
by special methods of implanting the tumor cells, to render the
diseased mice immune so that the tumors, which are present in
them and which are ordinarilv fatal, disappear and the subjects
recover. Jensen brought about this result in two ways, first by
treating the diseased mouse wath its own tumor cells, substances
developing in consequence in the blood (cytotoxins), which in-
hibited further extension of the tumor cells at the original site
(v. Chapter on Immunity) : and second by repeated introduction
of the tumor cells into rabbits (not susceptible to the mouse
carcinoma) he obtained a serum wdiich manifested specific cyto-
toxic action. [In a similar set of transplanted adenocarcinomata
of mice Gaylord found that some of the affected individuals re-
covered naturally, their tumors after more or less growth under-
going atrophy and disappearing. From such individuals he ob-
tained a serum which, when introduced into mice with marked
tumor growths, uniformly caused their disappearance by its
cytolytic power.]
The tissue of tumors isolated from the body will retain its vitality at
a temperature of from i°-3° C. for about eighteen days, at room tempera-
ture for about twelve days, but at body temperature for scarcely twenty-
four hours. This difference is supposed to be due to the cells passing
into a sort of resting condition at the lower temperatures, while at the
body temperature they cannot avoid metabolism.
♦For details v. Centralbl. f. Bakteriol. u. Par-asitenkiaulc, 1903, No. 1, ;>^XX!V
Pd.
340 Tumors.
Statistics of Tumors in Animals; Influence of Age and Sex.— It has only
been within very recent times that any attempt has been undertaken to
systematically collect the material relating to- the frequence of tumor occur-
rence in animals (Johne, Frohner, Casper, Sticker). It is very difficult
at the present time to draw any comparison of these data with those
of man whose tumor involvements have for many years been subjects
of careful, conscientious and extensive statistics in literature. The early
slaughtering of the food animals is partly at fault, as many tumors are
not apt to appear until advancing age. This is especially true of cancer,
according to Frohner; which in dogs is not encountered at all for the first
two years, and is met with any degree of frequency only in old dogs;
eighty-seven per cent, of his animals affected with cancers were over five
years of age, fifty-four per cent, over seven years old (in man cancer is
most frequent between the fortieth and seventieth year — about seventy per
cent.). While in man cancer is of special frequence on the lips, stomach
and uterus, in these sites the tumors are very rare in animals (gastric
cancer has been observed but one time in the dog— Eberlein). Sarcomata,
however, are mainly met in young animals.
As far as sex may have influence upon tumor formation, it can merely
be said that the female sexual apparatus in animals is far less frequently
involved by malignant tumors than in mankind; only in the mammary
glands of bitches are various tumors to be met with any frequence, while
cancers of the genital tract occur only as great rarities.
As indicative of an influence exerted by the species upon the devel-
opment of tumors, it may be stated that cancer is relatively frequent in
dogs, melanosarcoma and cancer in horses, and sarcomas in cattle and
swine (Casper).
Resume of Tumors. — The nomenclature and classification of
tumors is, as explained on p. 326, mainly dependent upon their his-
togenesis, origin and tissue composition. The existence of many
types of component tissues, together with the fact that cells of mul-
tiplying tissue may present all sorts of shapes, and that sometimes
unusual tissues take part in the formation and that it is often im-
possible to determine from what normal type of tissue the tumor
had its origin, make it difficult to carry out the classification
strictly upon this basis. A certain number of tumors present
themselves always in the same forms and these can be sharply
defined; but there are others which are of mixed structure and
of intermediate types.
The principal types of tumors may be distinguished as fol-
lows :
I — Fibroma^ simple fibrous connective tissue tumor or fibrous
tumor.
2 — Lipoma^ fatty tumor.
3 — Myxoma, mucoid tumor.
Fibroma. 341
4 — Chondroma, cartilaginous tumor.
5 — Osteoma, bone tumor,
6 — Myoma, niuscular tumor.
7 — Neuroma and Glioma, nerve tumors.
8 — Hemangioma, Lymphangioma, vascular tumors.
9 — Sarcoma, atypical connective tissue tumor.
10 — Lymphoma, lymph g'land tumor.
II — Melanoma, pigmented tumor.
1 2 — Endothelioma, Perithelioma, Cholesteatoma.
13 — Papilloma.
14 — Adenoma, epithelial glandular tumor.
15 — Carcinoma, atypical epithelial cancer growth.
16 — Epithelial cysts, Dermoids (skin tumors), Odontoma, Com-
pound Teratomata.
The Lidii'idual Types of Tumors.
Fibromata.
A fibroma, or fibrous connective tissue tumor, is a growth
made up of adult fibrous connective tissue, that is, of connective
tissue cells, fibrils and bloodvessels.
Fibromata vary in consistence with the degree of predom-
inance of their fibrillar basic substance, with the density or
looseness of the bundles in which the fil:)res are united and the
relative presence of blood vessels and lymph vessels. From this
point of view two types of these tumors are distinguished, the
hard and the soft fibroma.
The hard fibroma (fibroma durum) is met as rounded nodes
of very dense consistence, usually presenting the firmness and
appearance of tendon tissue, cutting with a tough resistance and
creaking on section. The cut surface which shows but little
moisture and is nearly dry, is of a white or light yellow color,
with intermingled shining and dead w'hite markings from the
intricately interwoven bundles of fibres (depending on whether
these are cut in longitudinal or transverse planes of section), and
with a fibrous appearance. The tumor as it expands in growth
is usually sharply defined, presses upon the adjacent structures
and has no tendency to penetrate them ; the surrounding tissue,
however, being thinned more and more as the layer over the
growth is stretched. The stretching and loss of tissue tension
may cause coincident proliferation of these adjacent structures, as
epithelium, over the tumor. Under the microscope the bundles
342 Tumors.
of fibres, compactly arranged and thick, may be seen running in
a wavy course, usually arranged concentrically about the blood-
vessels and often of considerable length. Between the fibres are
spindle cells with spindle shaped nuclei, and occasionally elastic
fibres are intermingled.
Sometimes the fibroma develops as a dift'use growth, giving
rise to large wooden-like thickenings of the subcutaneous tissue,
with radiating extensions running into the surrounding struc-
tures.
v'^A ;
\
\^
/ '
^l^c
*
*^- I aT
s
'^. ' ,^cV»'
■/
f
Fig. 86.
Hard fibroma : subcutaneous nodule, from horse.
The soft fibroma (fibroma moUe) is characterized by its softer
consistence, and the greater proportion of bloodvessels and lym-
phatics in its construction.^ It is in consequence of a more reddish-
gray color, is sometimes gelatinous ; and its shape is sometimes
nodular or lobulated, sometimes with a villous papillary surface.
Under the microscope it contains in addition to the loosely ar-
ranged bundles of fibres numerous spindle and rounded connec-
tive tissue cells and wandering corpuscles, and is quite rich in
Fibroma.
343
blood vessels. The soft character o'f the growth is due partly to
the numerous cells it contains, partly to the presence of lymph
fluid, especially where the latter is practically stagnant because
of twisting- of the pedicle of a pedunculated tumor. In such cases
the bundles of fibres and cellular groups are separated from
Fig. 87.
Fibroma (myxomatous) of the end of cow's tail.
344
Tumors.
each other and meshes are formed and become more or less dis-
tended, and the cells take on branched, stellate shapes. Such
a growth is also known as fibroma myxoiiiatodes or Hbromyxoma
from the gelatinous change present in it ; the more vascular
reddish ones as raspberry polyps, fibroma angiomatodcs, caver-
iiosum or tclcangiectaticum.
Occasionally calcification or even ossification takes place in
Fig. 88.
Section of a flbroma from a liorse.
the tissue of fibromata, producing dull white foci of bony hard-
ness (fibroma pctrificans, ossificans).
Sometimes the fibrous tissue formation is found about the
bloodvessels or about the glandular ducts or nerves, arranged in
circular concentric whorls and systems of bundles about these
structures ; such growths being described under the terms plcxi-
form or pericanalicular fibromata.
Fibromata growing from scars or imperfectly cicatrized granulation
tissue from wounds are apt to become especially dense, consisting of thick,
closel}' packed, interwoven bundles of fine fibrils, are known in human
Fibroma. 345
medicine as keloids (x^^V, the claws of a crab), because of the resemblance
of the rounded or finger-like nodes to the legs of a crab ; in man spon-
taneous keloids arc encountered as tumor formations, apparently hereditary
in families.
The fibromatous tisstte may combine with fat tissue, bone or
muscle giving rise to fibroUpomata, fibro-ostcomata or fibromy-
omata, or, when the second type of tissue predominates, to lipo-
Hbromata, ostcofibroinata or niyofibromata. [It is not a matter
of special importance, but generally the name of the tissue
predominating is given as the basic name of the combined tumor,
contrary to the above statement. Thus wdiere in a tumor com-
posed of fibres and adipose tissue the former predominates the
growth is known usually as a lipofibroma : where the latter is
the more important constituent, the term fibrolipoma is used.]
In case of an associated proliferation of the epithelium
covering a fibroma, or of glandular tissue the resultant com-
binations are known as Hbropapillomata and Hbroadcnomata.
Soft fibromata, more particularly because of active proliferation
of their cells and from the fact that these young cells are not apt
to maintain uniformity of shape but assume in varying measure
embryonal characteristics in size and shape, occasionally acquire
features which may justify the name fibrosarcoma.
Fibromata are of slow growth, usually single tumors, but
sometimes primarily multiple, ranging in size from that of a
nut to that of a human head or even larger, being known to
weigh as much as one hundred, and even one hundred and sev-
enty-eight kilograms (Wehenkel, Siedamgrotzky). Because of
the wide distribution of fibrous connective tissue structures
their development may take place in practically any part of the
body, although there are certain parts in which they appear with
especial frequence. The places of election are the skin and
subcutaneous tissue, especially of the front of the breast (horse),
the dewlap (cow), the elbows (dog), and the end of the tail
(cow). In these situations they form hard nodular swellings
or nodes covered with epidermis, or in other instances lobulated
pedunculated growths {fibroma pcndulans). As multiple pri-
mary formations Siedamgrotzky once counted in a thirteen-year-
old stallion more than a hundred fibromata in the skin, which had
grown in the course of three months in the breast, abdomen,
neck and face, to sizes varying" from that of a hazel nut to that of
the palm of the hand. Similar multiplicity, warranting the term
fibromatosis, has been observed in dogs by Frohner and Cadiot
346 ' Tumors.
(cited by Casper). Fibromata are frequently found in the tongue
of the cow, as well as in the vagina, in the latter situation as
pedunculated growths of large size projecting into the vaginal
canal. Those fibromata which are found in horses and cattle
after injury of the skin and tendon sheaths at the joints of the
feet may form enormous masses ; they are apt to have the sur-
faces covered with granulation tissue. Fibromyxomata are es-
pecially common at the end of the tail and in the heart (epicar-
dium and endocardium) as pedunculated growths, as well as in
the naso-pharnyx (where they are found hanging from the wall
covered with mucous membrane and are known as nasal polyps).
The author has observed a perfect string of hard rounded fibro-
mata in the lung of a horse (for details v. Kitt, Lelirhnch d.
spezicUcu pathol. Anatomic d. Haiisticrc, Verl. v. Enke, Stutt-
gart, II. Aufl., 1901).
A fibroma may sometimes be harmful because of its size and
location (occlusion of passages, pressure upon vital organs), but
does not give rise to metastasis and usually does not recur after
extirpation.
The hard fibromata of the skin ami tongue undoubtedly are
often results of traumatic lesions. The connective tissue scle-
roses resulting from injuries by foreign bodies, or that arising
after healing of an actinomycotic area, a chronic botryomycosis
or even a malignant oedematous infection, may be sometimes
such hard, definitely outlined, biscuit-shaped or nodular deposits
and prominences that an anatomical distinction between these
sequels of chronic productive inflammation and true tumors can-
not be made.
Lipomata.
The lipoma or fatty tumor is made up of adipose tissue, of
clusters of fat cells in various stages of development, along
with bloodvessels and fibrous connective tissue. The fat cells
are apt to be larger than those of normal adipose tissue. These
tumors arise from situations normally rich in adipose tissue, as
the mesentery or subserous peritoneal fat. where they frequentl}'
occur in the horse. The peritoneal adipose tissue often forms
lobular appendages, which when much overgrown and stretched
by the intestinal movements become pedunculated and present
themselves as pearshaped masses or tumors of the size of a fist.
They may give rise to fatal intestinal entanglements. In case
Lipoma.
347
..^C^^^
<r^ V /-
--4»_
Fig. 89.
Lipoma.
Fig. 90.
Loop of intestine of horse strangulated from ilie entanglement of a lipoma.
348 Tumors.
of rupture of the pedicle such lipomata become loose in the
peritoneal cavity and may be found at autopsy as compressed
free bodies. These peritoneal lipomata present a smooth surface,
are semitransparent, yellowish or white. Lobulated lipomata are
found also in the cow and hog in the omentum, and in the intes-
tine and perirenal fat; in these animals the fat is firm and white.
The subcutaneous tissue is a frequent site in the horse, especially
in the neighborhood of the knees where tliey may attain very large
size (twenty-six and a half kilograms in a case reported by
Moller) ; and in the dog especially on the inner surface of the thigh,
in the fold of the knee (Frohner), and in the breast (Stockfleth).
As submucous growths they have been found in the uterus (a lipo-
ma of a cow recorded by Lund reaching a weight of seventy-five
kilograms), and in the membrana nictitans in the horse and dog
(Frohner). Here, too, their shape is nodular or lobular and the
growth is usually well circumscribed and therefore easily shelled
out.
Sometimes lipomata appear in positions where adipose tissue
does not normally exist; thus two lipomata of the size of a
child's head have been found in a dog's liver by Trasbot, small
lipomata in the kidneys of the same animal (Bruckmiiller), and
Kuhnau encountered a rare instance of a lipoma of the brain in a
three-year-old beef (four centimeters in diameter, rounded and
arising from one of the bloodvessels of the pia mater). This
last instance was congenital. According to Bostrom it is pos-
sible that a bit of germinal fat tissue of the skin of the embryo
might have been separated and been misplaced in the cranial
area. Lubarsch suggests that intraparenchymatous renal lipo-
mata take their origin from portions of the renal capsule.
Lipomata occur as either single or multiple primary growths.
They may occasionally undergo mucoid degeneration (lipoma
myxomatodes), calcification {lipoma pctrificans) or dry anaemic
necrosis. When the combined fibrous connective tissue is espe-
cially abundant they may be very firm (lipofibroma). They
are slow in growth, but as above stated may attain considerable
size. Those which are situated subcutaneously may be easily
extirpated ; they are not recurrent and do not give rise to
metastases.
Tumors. 349
Myxomata.
A myxoma, a mucous connective tissue tumor, is a neoplasm
which consists either entirely or in part of gelatinous embryonic
connective tissue ; and therefore its tissue closely simulates the
Wharton's jelly of the umbilical cord in consistence, transparency
and texture. It is characterized microscopically by an intercel-
lular substance rich in mucin, in which are sparsely scattered
cells of spindle and highly branched stellate forms with long
^
•^^
^:j
\
hi
^%
S.
Fig. 91.
Myxoma.
slender prolongations; while here and there are to be seen blood
vessels and a small amount of fil^rillar connective tissue. In
fresh material the mucinous substance may be precipitated by
the addition of acetic acid. Often only individual portions of
the tumor are conspicuously myxomatous, the remainder being
made up of fat tissue or dense fibrous tissue (myxolipoma, myxo-
Hhroma) ; and many luxuriantly growing types show features
of transition to sarcoma and mixed tumors (myxosarcomata^.
Occasionally fibromata and lipomata of pedunculated shape.
350
Chondroma.
which have become oedematous from lymphstasis, simulate
myxomata (fibroma myxomatodes), the absence of mucin or its
scanty proportion in the fluid content distinguishing them from
the true myxoma.
Myxomata develop as single or more or less multiple primary
growths according to their situation, and as sarcomatous mixed
tumors capable of metastasis and of
embryonic appearance. They are es-
pecially met upon and in the heart
of cattle (when the subperi cardial
and subendocardial foetal mucous tis-
sue acts as their developmental sub-
stance) as rounded, lobulated growths
ranging in size from that of a nut to
tliat of a fist ; they also occur in the
nose in the cow and horse, in the
parotid, and in one case in the dog
around the spinal cord (Holzmann).
and, too, in cattle along the nerve
trunks (neuromyxoma). The gela-
tinous, glassy, swollen, yellowish
(sometimes like flesh of the cod-
fish) appearance, their softness and the ropy mucoid character of
their substance, constitute their important distinguishing features.
Fig. 02.
Myxofibroma of the heart, from
cow.
Chondromata.
A chondroma or cartilaginous tumor has, in addition to a
vascular fibrous connective tissue framework, as its main con-
stituent cartilaginous tissue, usually of the hyaline type, and
contains cartilaginous cells of very irregular size encapsulated in
this substance without regularity of arrangement. The fibrous
tissue forms a capsule and the trabecular framework about the dif-
ferent cartilaginous areas (which occur as islands and lobulated
nodules in the tumor) and acts as their nutritive perichondrium.
Besides the pure chondromata there are met manv mixed
types, made up of fibrous tissue, bone and glandular tissue, in
which cartilage enters as only one of the constituents ; and modifi-
cations may also result from the rather marked tendencv of the
cartilage to metamorphosis, both regressive and progressive. Mu-
coid degeneration with production of gelatinous softened foci
(cysts), and calcification, giving rise to white opaque patches
Chondroma.
351
(chondroma cysticum, myxomatodes, petrificans) are especially
likely to be observed; and sometimes ossification (chondroma
ossificans) takes place.
.^"^
r
X
^
l-Hf
A
V
Fig. 93.
Chondroflbroma of ovary of sheep (the uterus to the left).
Chondromata are nodular, nodose, lobulated. rounded tumors
of dense (in case of myxomatous change or when other tissues
are combined they are softer) consistence; showing their car-
tilaginous substance as a milk-white, grayish and bluish w^hite,
semitransparent material. They may attain considerable dimen-
sions, perhaps the size of a human head, and may weigh from
ten to twenty-eight kilograms. According to their location the
cartilaginous tumors may arise from previously existing cartilage
(ecchondromata) . or may develop within the bone marrow or in
the soft tissues which do not contain cartilage (enchondromafa).
The former originate from the perichondrium, the cells of which
are usually concerned in formation of cartilage ; the latter arise
probablv from misplaced embryonic cartilaginous rudiments.
352 Tumors.
Isolations of bits of tissue from either of these sources may occur
in embryonic Hfe from developmental faults, as in the formation
of the branchial arches or the primitive vertebrae and embryonal
elements of the ribs. The fact that chondromata may be congen-
ital is an argument for this view. In the postfcetal period car-
tilaginous isolations may take place from disturbance in growth
in the skeleton (rachitis) ; and traumatic lesions, as fractures of
ribs, may give origin to separation of bits of perichondrium, and
Fig. 94.
• Section of a chondroma from a hen.
these in association with profuse callus formation might develop
into chondromatous tumors.
Chondromata are most common in the bony framework of the
chest as the result of fractures of the ribs, projecting into the
chest cavity or beneath the skin as large tumor masses; they are
also frequently met in the neighborhood of the jaw and thyroid
gland, originating from remnants of the branchial cartilages, in
goats, horses, dogs and cattle. /\s mixed growths (chondro-
adenoma) they have been seen a number of times in the lungs,
mammary gland and in the testicles in animals. As exceptionally
rare instances may be mentioned enchondromata of the vitreous
Osteoma. ■ 353
humor of both eyes in a cong-enitally blind colt (Renner), and
a chondroma the size of a fist in the wall of a calf's stomach
(first stomach).
A chondroma should be looked ujjon as a dan.ijerons growth,
at times because of the position it may occupy, but also because
of its usual!}- marked tendency to grow large, and further because
it can give rise to metastasis. The cartilaginous masses hap-
pening to penetrate by growth into the veins sometimes develop
long processes within the lumen of the vessels, which are of
course obstructed; and any little portions which luay be carried
awav bv the blood may form metastatic nodes in other organs.
In man there are seen from time to time pea-sized growths of cartilag-
inous tissue, peculiar in the marked vacuolation of their cells and in their
gelatinous consistence, at the base of the skull in the neighborhood of the
spheno-occipital suture; these, because of the bladder-like, swollen character
of the cells, were formerly known as cccliondromafa physaliformia, but are
recognized to be remnants of the notochord and are called chordomata.
Osteomata.
Bv the term osteoma or bone tumor is meant a definite new
formation presenting the structure of bone tissue and its mar-
row. According to the density of the calcified bone substance
there are distinguished (i) the cbiiniatcd osteoma (osteo))ia
chur Ileum ) which is of ivory-like hardness like the dense cortical
bone; (2) the spongy osteoma (osteoma spongiosum), of a more
cancellous t}pe, containing considerable marrow substance ; and
(3) the meduUar\ osteoma (osteoma medullosum) composed
principallv of marrow. In most instances the structure of the
bone (calcified matrix in lamellar arrangement about Haversian
canals, bone corpuscles in lacunre. bloodvessels, marrow cells
and fat) is characteristic; but. often as far as the marrow is
concerned, abnormalities are common, the medullary spaces being
occupied perhaps rather by spindle cells and fibrous connective
tissue (osteofibroma) or showing ^-^pecial abundance of round cells
and giant cells (osteosarcoma). Where the bone trabecula have
no lamellated structure and the bone corpuscles do not show
the usual projecting branches the specimen is spoken of as an
osteoid sarcoma.
In manv cases it is dif^cult and even impossible to determine
whether a tumor-like osseous groAvth is really of autoblasto-
matous origin or is the product of inflaiumatory proliferation,
because definite lines of separation between the two cannot be
354 Tumors.
drawn. For this reason visually only the more massive, large and
clearly defined bony growths are called osteomata, and the rest
are known collectively as ostcopJiytcs. The small protuberances,
of the size of a pea to that of a nut, projecting from the surface
of bones, are also called c.rosfoscs ; the flat superficial thickenings
around bone shafts, periostoscs; those which grow along bones
as bony formations in fasciae and connective tissue, parosloses;
an ivory-like, hard, well-defined formation in the interior of
bones, an cnostosis. Dififuse thickenings of the bones in the
skeleton from osseous hyperplasia are known as hyperostoses;
osteophytes with cartilaginous coverings, as cartilaginous osteo-
phytes.
The osteophytes and osteomata growing from the skeleton
develop principally from the osteoblastic layer of the periosteum
or from cartilaginous developmental bases (aulage) ; some are
congenital or from their position may be looked upon as caused
b\' disturbances of embryonal development and as referable to in-
clusive misplacement of bits of the embryonic bone tissue af-
fected. This view is especially applicable to the rather common
large osteomata of the head cavities (cattle, horses), arising from
the sphenoid, ethmoid or the turbinate bones ; in their gradual
enlargement they press upon the surrounding bony walls, force
the jaw and nose out of position, project into the maxillary sinus,
nasal cavities or into the orbit or cranial cavity, and obstruct
these spaces with continuous pressure upon the respective soft
parts. Other forms which are located on the outside of bones,
sometimes as broad expanded growths or arising from slender
pedicles, probably are caused by traumatic influences ; and the
exostoses which are met commonly in the under jaw of the horse
apparently arise from isolated osteoplastic foci ; and the large
osteomata on the horn process in cattle are probably due to loss
of tissue tension caused by injur}- to the horn capsule.
A remarkable variety of pathological bone proliferation is the
progressive osteitosis met ^^•ith in young dogs. It consists in
the occurrence of bone formation at the places of attachment
of the tendons and muscles of the lower jaw and extremities,
causing as it progressively advances an atrophy of the muscles
and giving the animal a stifif awkward gait : it is accompanied
by marked thickening of all the bones of the skeleton. The
disease is similar to the aft'ection in man known as myositis
ossificans progressiva, and is apparently an abnormality of de-
velopment, in which as Ribbert supposes the intermuscular con-
Osteoma.
355
nective tissue acts as a derivative of the periosteum. In fresh
specimens the periosteum and muscular connective tissue of
these cases appear to be merged into one mass of bacony, cartila-
ginous and rigid character; after maceration, brittle, papyraceous
Fig. 05.
Osteoma on the horn process of a cow.
and gland-like plaques and nodosities of bone are found along
the muscular attachments.
Osseous growths of irregular and flat shape {ossiUcatio
raconosa, plana) and intermediate types approaching compact
osteomata have been encountered as isolated deposits and in combi-
nation with cartilage and fibrous tissue occasionally in the lungs
(cowO, peritoneum and mesentery (cow, hog, dog), upon and
within the udder (cow% dog), testicles (horse), in the vitreous
humor of the e}'e (horse), and in the right cardiac auricle of the
horse. The attempt to explain the origin of these bone forma-
Fig. 96.
Section of above osteoma of horn process.
tions must rest with the assumption of the possibility of a meta-
plasia of fibrillar connective tissue into a calcified matrix, with
transformation of'the connective tissue corpuscles into bone cor-
puscles.
356 Tumors.
Myomata.
A myoma or muscle tissue tumor is composed of muscle
fibres, together with an accompanying vascular connective tissue.
Corresponding with the two varieties of muscle, these tumors
occur in two forms, one, the leiomyoma {myoma IccviccUulai'c),
composed of smooth muscle cells, and the other, rhabdomyoma
{myoma striocellularc) , a tumor made up of transversely striated
fibres.
The latter {rhabdomyoma) is a very rare tumor; and never
shows the muscle tissue in a state of perfect development like
that of the muscles of the body. The muscle fibres are rather of
an embrvonic type and are usually mingled with embryonic con-
nective tissue {rhabdomyosarcoma, rliabdomyoma sarcomatodes)
or combined with glandular tissue in addition {rJiabdomyoaden-
osarcoma). The muscle fibres are thinner than normally,
ribbon shaped ; their transverse striae are not complete and are only
apparent along the edges of the fibres, a richly nucleated sarco-
plasm occupying the interior of the fibres. Numerous spindle
cells with longitudinal striations may be noticed in addition,
which may be looked upon as early stages or as muscle fibres per-
sisting in undeveloped condition. These muscle elements are not
arranged in compact parallel bundles but are scattered about in
irregular manner. They are therefore not of as deep red a color
as normal striated muscle, having rather a pale reddish-gray
tint. Thev occur as more or less well defined nodes ; and rarely
occur in situations where striated muscle tissue exists normally
but rather in complete heterotopism, in organs which have no
such basic elements. This would indicate that rhabdomyomata
originate in muscle germinal tissue misplaced in embryonal life.
This is doubtless true of the tumors in question Avhich develop
from the kidney, the muscular elements in their structure appa-
rently originating from misplaced portions of the myotomes of
the primitive vertebral column. Johne has recorded an adeno-
sarco-rhabdomyoma of this type from the kidney (hog) which
weighed fourteen kilograms. (In man rhabdomyomata have
been recognized frequently in the kidneys, testis, uterine wall,
urinary bladder and the oesophagus.) Besides the case above
mentioned, contributed by Johne, there are only two instances of
rhabdomyomata in animals recorded in literature (Casper). One
was observed by Gratia in an old horse in a dissecting room, a
fusiform tumor about eight or ten centimeters in length, in the
Myoma, 357
vagus nerve trunk abont the middle c)t the neck; the other was
found by Kolessnikow, growing in the tail and perianal con-
nective tissue of a twenty-year-old stallion, a tumor containing
pigment cells {rhabdoniyosarcoina melanodes), which had given
rise to numerous metastases in the liver, spleen, peritoneum and
pleura.
The Icioiiiyoina is found more frequently and in easily recog-
nized forms in animals: in case of extensive combination with
if. f > t«- "^
/
^*-%«-
^*«»
Fig. 97.
Leiomyoma (from utei-us) : «. ijlace shuwlng buadle of muscle fibres cut transversely.
tibrous connective tissue, as may sometimes be seen, the growth
is spoken of as a myofibroma. These tumors always develop
in a structure rich in smooth muscle, and are consequently met
principally in the muscular wall of the uterus and vagina (in cow
and hog, less frequently in the dog), of the intestine and stomach
(horse), urinary bladder (dog), now and again in the testis
(horse), and in the subcutaneous tissue (horse). They are
rounded or globular, firm tumor masses, which are sometimes
found projecting from their places of origin, covered over
smoothly with mucous or serous membrane, presenting on their
358 Tumors.
cut surface a fibrous or striated appearance, of a reddish-gray or
pale gray color. Especially the leiomyomata growing from the
uterus and hanging to this organ in the peritoneal sac, may attain
enormous size, possibly as large as a well filled horse's stomach,
weighing from thirteen to thirty-six, to one hundred kilograms.
The smooth muscle fibres, easily recognized by their long
fusiform shape and rod-shaped nuclei, are arranged parallel to
one another in bundles interlacing in every direction with each
other in confused manner. In sections the fascicles are found
cut longitudinally, obliquely and transversely, and between these
the vascular connective tissue may be 'observed in variable
amount as clearer threads. In pedunculated examples where the
myomata have in consequence been subject to twisting, circu-
latory disturbances are often determined, as results of which
congestive haemorrhages, cedematous appearance, anaemic necroses
and fatty degeneration may take place in the tumor mass.
In man epithelial inclusions and hollow tubules have been
noted in the myomata of the genital organs, this histological
feature giving support to the view that the myoma in this
situation is related to embryonal disturbances which have occa-
sioned misplacement and isolation of portions of the Wolffian
body or of the Miillerian ducts (adenomyomata).
Leiomyomata are usually single primary growths [in human
beings they are often multiple], and give rise to harm only
by their volume. They are not recurrent tumors [and are not
metastatic]
Neuromata and Gliomata.
A neuroma, or nervous tissue tumor, strictly speaking must
be made up of nerve fibres or gangliomic cells in luxuriant prolif-
eration, accompanied by a supporting framework and by bloodves-
sels. If we exclude the terminal thickenings of nerve stumps
occasionally occurring after neurotomy, the so-called amputation
neuromata (v., p. 250), from the list of true tumors (because their
growth ceases after a time), it may be said that the formation of
true neuromata in animals has as yet never been certainly proved
to occur. Even in man but few instances of this type of neoplasm
are known, situated in the sympathetic area (especially coeliac gan-
glion and pelvic plexus), as nodes ranging up to the size of a
child's head.
The growths summarily designated by the name neuroma in
Neuroma.
359
the literature are nenrofihromata and neuromyxomata, tumors
which develop in corded, fusiform or cylindrical thickenings up
to the size of a finger, or in nodular shape up to the size of a
Fig. 98.
Neuroflbromatosis of bi-achial plexus of cow.
potato, on the nerve trunks. Their formation results from a
marked proliferation of the -perineural connective tissue and
nerve sheath about the nerve fibres. The proliferated mass has
360 Tumors.
a grayish-red, seniitransparent appearance and usually extends
along many adjacent nerves as a nerve plexus, giving rise to
an extensively intertwining growth { plcxiform or vine-like neuro-
fibroma). Tumors of this kind have been observed, especially in
cattle, involving the brachial plexus and the dorsal, costal and
sternal nerves (Ostertag, Alorot, Blanc, author's personal obser-
vation), and producing in these structures hundreds of nodular
thickenings. Morot counted in one case thirteen hundred and
fifteen neuromyxomata in an old cow and traced them even to
the nerves of the pharynx and heart. Leisering observed similar
growths in a horse with extensive involvement of a number of
nerve trunks.
An embryonic developmental disturbance of unknown nature
has been regarded as the basic factor for the neurofibromata and
neuromata observed in man, because the growths have been met
as congenital and inherited faults.
Glioma or ncuro glioma, the tumor of nervous connective tis-
sue substance, is produced by proliferation of the glia cells of the
central nervous system or the granular layer of the retina of the
eye, and occurs primarily only in these two positions. In animals
it has been recognized with certainty but twice, once by Gratia
in a dog's brain (ganglion Gasseri) and again by Piana in the
spinal cord of a dog, in both instances causing palsies from
pressure upon the central nervous substance and the emerging
trunks.
The gliomata of the human brain are usually embedded in
the brain tissue without sharp definition from the latter and are
so merged with it that they are only recognizable as diffuse
grayish or reddish firm areas. They are made up of protoplasmic
cells with numerous fibrils projecting in a radiating fashion from
all sides of the cell (spider cells, astrocytes) ; and in this fibrillar
meshwork there are in some instances also present polymor-
phous sarcomatous or ganglionic cells, and epithelial inclusions
may be observed (spaces lined with cylindrical epithelium). This
last feature and the occurrence of these growths in newly born
children confirm the belief that disturbances of development of
the cerebral vesicles are the basis of these neuroglia growths, for
example isolation of offshoots from parts covered by ependyma
(perhaps, too, transformation of the glia cells to embryonic cel-
lular type, the glia tissue being originally an epithelial tissue
differentiated into a supporting material).
Cliunia. 3^1
Retinal gliomata of man spread out as grayish nodular tumors
over the inner surface of the globe of the e\e, but are also met per-
forating the sclera, growing along the optic nerve and perhaps es-
caping into the orbit ; they occur as congenital growths sometimes
involving both eyes, and have been observed in a few instances in
several children of the same parents. For these reasons and be,-
cause of their structure they may invariably be referred for their
origin to developmental faults. They are only in part composed
of glia tissue, being principally made up of neural epithelium of
the retina reverted to embryonal type, arranged in thick sheath-
like layers around the synchronously proliferating bloodvessels.
[These so-called retinal gliomata are the subject of considerable
controversy. The presence of any true glia tissue comparable
to that of the brain is in itself questionable, and the evident part
taken by the retinal neuroepithelial tissues has led to their being
denominated neuroepitheliomata. These neuroepithelial cells are
frequently found in a so-called rosette arrangement, as the cylin-
drical epithelium seen in sections of small ducts. The tumor in
its infiltrating and metastatic character is a very different growth
from the glioma of the brain ; the former is rapidly fatal, while
the latter shows little tendency lieyond a slow peripheral infiltra-
tive enlargenient to extend, and persons may have harbored these
growths for years with little definite evidence of their presence.
The more separate arrangement of the cells of the true glioma,
the branching fibrils of the cells preventing close adjustment, is
not seen in the retinal glioma, whose cells are very closely packed and
evidently have but few^ and insignificant projections upon them
(in fact one must examine with great care even after special
staining to think that these projections exist in any comparable
degree). The editor would regard favorably the separation of
these growths from the class of true gliomata, preferring the
more distinctive and well justified term of neuroepithelioma.
The true glioma of the brain is usually single; sometimes sev-
eral have been found, usually in close relation and probably in
reality representing the same growth. A\hen pure and free from
sarcomatous combination the tumor should be regarded as rela-
tively benign save for its pressure effects. Distant metastasis is
rare; although local metastasis from peripheral infiltration is
the rule.]
362
Tumors.
Haemangiomata and Lymphangiomata.
The hccmaugioiiia, or blood vessel tumor, is made up of dis-
tended and proliferated vascular tubes filled with blood, together
with the connective tissue supporting these vessels. Strictly speak-
ing, a true vessel tumor must consist for the most part at least of
vessels which have been newly formed, and should not be a tumor-
like enlargement made up simply of pre-existing vessels Avhich
have become enlarged from some pathological cause. It is, how-
ever, difficult to make a distinction between these two conditions,
partly possible only by examination of microscopic sections. There-
fore in a gross anatomical sense there is usually included under the
term hsemangioma, in a tentative way, a second variety which is
made up of blood lacunae, which give rise to a nodular irregularity
in shape and a spongy consistence of the part affected [caz'ernous
hcemangionia] .
Fig. t)!).
Portion of cavernciis angioma of cow, seat of multiple thrombi.
In man hsemangeiomata are represented first by the invariably
congenital blood-red or bluish-red, sharply outlined areas of skin,
in which the tissue of the cutis, often to the depth of the sub-
cutaneous fat, is filled completely with thin-walled bloodvessels in
a definitely limited area {Hccniangioma teleangicctaticum, ncc-
z'lis vascnlosus, Hammcus, vinosiis, wine mark).
Such independent vascular tumors, caused by a disturbance of
tissue development, are, it appears, but rarely met in animals, prob-
ably because the pigment and hair of the skin conceals their pres-
ence. However, Leisering observed an angioma as large as a hen's
&gg in a dog, in the subcutaneous tissue (under surface of the tail) ;
Siedamgrotzky a similar one in a poodle, showing as a bluish-black
area through the skin ; Bonnet a fibroangioma as large as a child's
head with a strong connective tissue stroma in a horse, in the papil-
Hcsmangioma.
363
lary bodies of the root of the tcail. Similar teleangiectases are more
frequently recorded as occurring- in the nasal septum in the horse
(Liipke, Hofmann, Diegendesch, et al), appearing as superficial
red or bluish-red, smooth, easily bleeding areas.
The very common capillary teleangiectases in the bovine liver,
multiple purplish-red or Ijluish-rcd spots showing through the Glis-
sonian capsule, and appearing as finely spongy, bloody areas in
section, are to be regarded according to the studies of Stroh as due
to passive hyperaemia (pressure by the paunch in tympanites).
The second type of angioma above mentioned is the cavernous
angioma of the human liver, occurring in similar' forms in the cow
and horse. A system of blood spaces is formed in the liver, com-
r'
/
V
^
^
(1
H
:,.^)Ki'
■w^
^-^^■
Fig. 100.
Portions of an angiomatous liver of a horse.
parable to the erectile tissue of the penis or to coarse sponge, with
cavernous passages of very irregular width and varicose, interrupted
by projecting ledge-like bands of connective tissue. The area, recog-
nizable from the external surface by the superficial dark red eleva-
tions and the increased volume of the involved lobe of the liver, is
not sharply outlined, and contains quantities of tarry blood and fre-
quently also firm laminated clots. Between the connective tissue
septa islets of liver structure sometimes persist. The whole appear-
ance gives one the impression of a bunch of distended veins, dilated
VERSITY J
OF
364
Tumors.
from passive congestion, or a nodular h£emorrhagic focus, rather
than of a neoplasm. In man, however, such foci have been ob-
served in congenital occurrences ; and Ribbert suspects as the fun-
damental cause some developmental disturbances of the affected
part of the liver.
The name lymphangioma, or lymph vessel tumor, is applied to
congenital tumors in man, which occur as independent bunches of
lymph vessels (that is, not in direct relation with the lymph vessels
Fig. 101.
Cavernou.s angioma : 0, lacuna filled with blood ; h, indurated intervascular
connective tissue.
of the adjacent tissues). They are especially seen in the neck, in
the mesentery, the lips and the genital organs, sometimes not well
defined and causing rather a diffuse swelling of the part. They are
made up of channel-like, anastomosing, multiloculated passages
filled with lymph, their walls of fibrous tissue lined with endothe-
lium.
There is only one definite and certain record of the occurrence
of tliis type of tumor in animals, published by H. Markus ;* on the
* Monatsheft f. pr. Tierlieilk. Stuttgart, 1902, p. 185.
Lyiiipliaiigioiiia ; Sarcoma. 365
costal, pulmonary and pericardial pleura of a horse there were found
numerous superficial, vesicular growths from the size of a pin's head
to that of a nut or pigeon's egg, some with broad surface, others
pedunculated, exuding a serous fluid on section from the spongy
tissue. Microscopically, they consisted of a loculatcd connective
tissue framework, the spaces lined with endothelium and containing
scattered l\niph cells. The growth was entirely local, the lymph
glands not afifected.
Schindelka observed in a cat as an anomah', perhaps of tlii^ same
categorj', a number of tumors about all the nipples, ranging in size from
that of a hazel nut to that of a hen's egg. encircling the nipples and hang-
ing loosely, filled with fluid and fluctuating like a leather bottle when
handled ; firm lymph cords, of the thickness of the little finger and varicose,
branched out from these formations into the skin.
Now and dien large, tortuous lymph vessels filled with lymph are found
in the horse in the heart or mesentery, which are, however, merely lymph-
angiectases.
Sarcomata.
The name sarcoma (o-dp^. Hesh; fleshy ttimor, from its similarity
to proud flesh or exuberant granulation tissue) was applied by \'ir-
chow to those connective tissue tumors which do not possess the
definitive characteristics of a fibroma, chondroma, lipoma, etc., that
is, which are not composed entirely of matttre fibrous tissue, carti-
lage, bone, etc.. btit throughout their continuous growth are made
up of cells of the connective tissue group persisting in their embry-
onic characters. They are new growths whose tissue shows no
tendency to maturation and is composed principally just as in
embryonic life of undifterentiatcd mesoblastic cells and scanty in-
tercellular substance, and whicli are distinguished from the simple
connective tissue tumors particularly b\- thc'r malignant character,
their rapid and destructive growth, their tendency to recurrence
after removal and their formation of metastases.
The sarcomata are classified from two standpoints : first, from
the predominating t\pe of the cells of the growth ; and second,
from the admixture of mature tissue with the embryonic cells.
Many sarcomata are characterized by a special predominating
tvpe of cell ; and although the shape of a cell does not alone deter-
mine the character of a tumor, the tissues of origin and the nature of
growth being also taken into consideration, it gives the microscopic
picture of a tumor an individuality of importance in nomenclature,
and characteristic because of the deficiency of fully mattered types oi
366
Tumors.
tissue. Those forms of sarcoma whose cells do not grow with any
special uniformity, but rather as a motley mass of various forms in
atypical embryonal proliferation, cannot of course be named from
the cellular character. These instances, as a rule, represent the
malignant form of fibroma, chondroma, osteoma or melanoma, or
are mixed tumors ; in these cases a combined expression is used.
The completely developed tissue forms, as it were, the framework or
stroma, and the cells the parenchyma.
(@
g/»* ^® J
.%..
V i
3^
• t%r^
■^:.;''"^c>5 7
Fig. 102.
Alveolar round cell sarcoma, from testicle (human).
The principal types of sarcoma may be divided as follows :
A — Cellular Sarcomata: the round cell sarcoma, spindle cell sar-
coma, giant cell sarcoma, stellate cell sarcoma, polymorphocellular
sarcoma.
B — Combined Sarcomata: the fibrosarcoma, liposarcoma, chon-
drosarcoma, osteosarcoma, myxosarcoma, myosarcoma, gliosarcoma,
lymphosarcoma, melanosarcoma.
In stricter application it would be well to determine precisely, as Borst
and Diirk have urged, whether the embryonal cells were present from the
Sarcoma. 367
beginning, and their proliferation and that of the mature types of cells
have from the first developed side by side, or whether a simple tumor
originally existed and later assumed a typical growth from changes in the
cellular proliferate. In the former case the combined types of tissue may
lie indicated l)y the use of two nouns (as fibro-sarcoma) ; in the latter
.by the adjective prefix "sarcomatous" [the change into sarcomatous type
may be expressed]. In the course of clinical observations, where the
succession of various features is recognizable, such distinctions may be occa-
sionally made ; but in purely anatomical considerations they cannot be made.
Fig. 103.
Spindle cell sarcoma, from periosteal origin : a, transverse section of hnnrlle of
splndlo cells ; b, capillary blood vessel.
The round cell sarcoma (sarcoma globocclliihirc) consists either
of cells of the appearance of lymphocyteSj small round elements with
narrow cytoplasm and granttlar nucleus (small cell sarcoma), or of
large round and polymorphous cells (large cell sarcoma), closely
packed together and with such a small amount of fibrillar intercellu-
lar substance that the cells are but loosely attached. The tumor
has a very soft consistence and is of a grayish to a grayish-red
color. When the supportive tissue enclosing the round cells is
arranged in a reticular manner, forming a fine fibrillar meshw^ork,
and the tumor has originated from one of the lymphatic structures
368 Tumors.
(spleen, lymph glands, bone marrow), it is known as a lympho-
sarcoma.
The spindle cell sarcoiiia (sarcoma fnsiccUidarc) also presents
both small and large cellular elements and originates from ordinary
connective tissue. Its spindle shaped, more or less elongated cells
contain one or more round to fusiform nuclei, are placed parallel
to each other, arranged along the bloodvessels in bundles inter-
twining in different directions, and are comparable to the fibro-
id u-
Fig. 104.
(jlant cell sarcoma, from human jaw : a, capillary blood channel : h, giant cell ;
c, sarcomatous cells, In this specimen of spindle type.
blasts of granulation tissue. The bloodvessels are also of em-
bryonic type, persisting as simple endothelial channels, often distin-
guishable from lymph spaces merely by the fact that they contain
red blood cells. Where the intercellular fibrillar substance is more
prominently developed the spindle cell sarcoma becomes a fibro-
sarcoma.
The giant cell sarcoma (sarcoma gigantocelhdarc). The pres-
ence of numerous giant cells in a connective tissue tumor, always
a striking feature of the microscopic sections, gives origin to the
term giant cell sarcoma. The large polynucleated cells thus known
Sarcojiia. 369
are usually derivatives of the marrow or periosteum where they
occur normally (known as myeloplaxes). They differ from the
degenerative types of giant cells (formed in tubercles and about
foreign bodies) in the fact that their nuclei are not located about
the periphery but are scattered well .in the interior and all through
the cell protoplasm ; but all sorts of variations may be found (com- .
pletely divided or wreath-like clumping of the nuclei, giant nuclei,
eccentric dividing forms, budding nuclei). The number of nuclei
in one cell may reach not merely a dozen or two, but hundreds.
The cells, whose dimensions may exceed ten to thirty times that of
a white blood corpuscle, are irregularly rounded, their margins
jagged, are flattened out like large fibroblasts and are often vacuo-
lated with fat droplets. In addition to the giant cells there are
usually numerous round and spindle shaped cells in the tumor, and
a rich supply of capillary vessels from which blood extravasations
are frequently found in the tissue, and which give the tumor a
dark-red or brownish-red color. From its medullary origin the
giant cell sarcoma is often called a iuycIoi:;ciious sarcoma or 111 ye-
loma; and when a homogeneous intercellular substance is present,
becoming calcified and forming cartilaginous islands or bony tra-
becula. the combined appearances are denoted by the terms osteoid
sarcoma and osteochondrosarcoma.
The stellate or reticular cell sarcoma (sarcoma sfellocelluhve)
is characterized by highly branched cells forming an intricate mesh-
work, usually enclosing between their projections a mucoid, glass-
like intercellular material, giving to the growth characteristics
commonly indicated by the term myxosarcoma.
The polvmorphoeellular sarcoma (sarcoma mi.vfoccllulare) is a
name given to tliose connective tissue tumors whose cellular con-
stituents follow no one cellular form, but are made up of a con-
fused mixture of round, spindle, stellate and giant cells, or the bulk
of whose cells are elements of variable form, irregularly polygonal,
enclosed in a comparatively small amount of intercellular matrix.
The morphological appearance of sarcoma cells, the size and
polygonal shape of their cellular substance and their alveolated
arrangement make it often very difficult to determine to which of
the classes of sarcomata described and specially named by differ-
ent authors a given sarcomatous neoplasm should be referred.
This difficulty and the lack of finality in our histogenic basis of
classification are apparent in the frequent employment of combined
names indicating the mental uncertainty of the pathologist, as sar-
coma carcinomatodes, or carcinoma sarcomatodes: and it is not an
370
Tumors.
uncommon thing for good histologists to make use of different
diagnostic terms to describe one and the same tumor, one perhaps
calHng it sarcoma, others endothehoma, perithelioma or alveolar
sarcoma. This is but natural when one considers the number and
variability of connective tissue tumors and their combinations, the
differences of composition which exist in different parts of one indi-
vidual growth and the changes and metaplasias which are possible,
these features preventing any schematic and clearly defined classi-
fication.
The macroscopic appearances of sarcomata are naturally very
variable on account of the many types of histological structure
which they may present. Some are soft, others hard ; their color is
generally a grayish-white, similar to the tissue of lymph glands or
foetal brain tissue (hence the old terms medullary sarcoma and
encephaloid sarcoma). They are usually rapidly growing tumors,
some growing in nodular, nodal or lobulated forms, others as infil-
trative growths. Their expansion not only occasions considerable
pressure upon the surrounding tissues and organs, but by stretching
the tissues they approach the surface of the organ, break through
the mucous membrane or external skin, or destroy the part from
which they arise by their deeper growth. By their infiltrative
growth and penetration between the tissues sarcomatous formations
occaeion marked enlargement in bulk and expansion of the part
aft'ected. Isolated tumors, reaching from five to seventeen kilograms
in weight, and enlargements of organs of perhaps twice or three
times the normal size, are not uncommon in sarcomatosis of the
kidneys, liver, rectum, spleen and lymph glands. The great tendency
to infiltration occasions daughter nodes in the vicinity of the orig-
inal growth and leads to metastases, which are especially likely to
follow the blood current. Penetration into blood vessels is often
apparent to the unaided eye in case of large veins, as those of the
liver. The tissue increase, both in the orimarv and secondarv
tumors, is always due to the independent proliferation of the sar-
coma cells, the formation of blood vessels (associated prolifera-
tion), however, proceeding directly from the organ in which the
sarcoma cells are distributed, apparently from a peculiar influ-
ence exerted by the tumor cells upon the endothelium (Ribbert).
These vessels, proliferating in association with the tumor cells, for
the most part maintain their capillary type, often, of course, as
wide endothelial tubes ; the frequence of haemorrhage in the sar-
coma substance being due to the thinness of their walls. Because
of this abnormality in the blood supply, which may not keep pace
Sarcoma. 371
with the rapid exuberance of th? celhilar growth, various retro-
grade metamorphoses are possible, of which fatty degeneration is
the most common.
Nothing certain is known of the development and cause of origin
of sarcomata. Now and again sarcomata and their combined
growths are met following traumatism (fractures of bone, contu-
sions and injuries to the soft parts) ; from the analogy shown by lux-
uriant traumatic granulation tissue growth to the sarcomata, it may
be supposed that some instances are due to lesions causing loss
of tissue tension, and further investigation of convincing ex-
amples would be of much interest in this line. In the second place
sarcomata may be thought of as perhaps related in their origin with
faults of development, both because they are common in man and
animals in early life and because their cellular character is sugges-
tive of embryonal conditions.
The principal seats of primary sarcoma formation in animals
are the bones (jaw in dogs and horses, cranial cavity in cattle), the
lymphatic glands and spleen (dogs, cattle), and the intestine (cat-
tle) (Frohner, Leisering, Dieckerhoff, Siedamgrotzky, Casper).
[Of the sarcomas it may be said in a general way, to which ex-
ceptions are not infrequent, that the spindle cell varieties more
commonly arise from the denser types of connective tissue as the
periosteum, fasci?e, intermuscular septa and capsules or framework
of organs ; and that the round cell forms more commonly originate
from the softer and more cellular types of connective tissue, as the
lymphoid structures and the intraparenchymatous intercellular con-
nective tissue of organs. The giant cell sarcoma is practically lim-
ited to the bone marrow, usually growing toward the ends of the
shafts of the long bones.
In the same comprehensive way, again with many exceptions, it
may be expected that the round cell types are the larger, more irreg-
ular and more infiltrative as primary growths, and of a soft fleshy
consistence, highly vascular, and, before the blood has been washed
out, of a red, translucent, soft fleshy appearance (paler, as above de-
scribed, after the blood has been removed or if the growth when
obfained from the subject is relatively freed from its blood con-
tents) ; the spindle cell form tending in the same general and un-
fixed manner to be smaller in size, less infiltrative, but rarely encap-
sulated, more regular in outline and nodular or lobulated, somewhat
firmer in consistence and of a lighter color than the round cell varie-
ties. The giant cell sarcoma usually causes an expansion of the
bone shaft, is covered with a thin and generally imperfect shell of
372 Tumors.
bone, the interior sarcomatous mass soft (sometimes almost mushy),
deep red and hgemorrhagic and bleeding freely when cut into. The
hsemorrhagic tendency is often so pronounced that the term aneu-
rismal sarcoma has been applied to describe this feature of marked
vascularity.
Of the sarcomata above described by the author, the highest
grade of malignancy from metastasis is met among the round cell
varieties, especially the small round cell sarcoma and the alveolar
round cell sarcoma ; spindle cell sarcomata are also decidedly metas-
tatic in the small cell form ; the large spindle cell sarcoma being
sometimes metastatic, but especially showing its power in this direc-
tion by recurrence after removal (hence sometimes called recurrent
fibroid tumor). The giant cell sarcoma is often said not to give"
rise to metastasis ; but this not strictly the case, as in man the editor
has encountered two well-established instances of metastatic for-
mations of this type, once from a myeloid sarcoma of the upper end
of the tibia to one of the tarsal bones, and again from a similar
growth in the upper end of the shaft of the femur to the pelvis].
Lymphomata.
By the names lyinphoniata or lyinpho-sarcomata are meant pro-
gressive proliferations of a tissue of the type of that of the lym-
phatic glands, originating from the lymphatic structures of the
body. Lymphatic tissue is found in the lymph glands, bone marrow,
spleen and thymus gland and is represented, too, by microscopically
small developmental areas of lymphocytes widely distributed
through the connective tissue of the system. The number and size
On
of these depots and developmental foci of the leucocytes and
lymphocytes vary considerably in dififerent individuals, even physio-
logicallv. For example, the thymus gland is often found double the
size attributed to it as normal, and in some calves the intestinal
lymphatic glands are so much enlarged and so confluent that the
mucous membrane in its entire extent may approach a centimeter
in thickness, without the possibility of speaking of this '^o-called
lymphatismus [status lyiuphaticus] directly as a pathological
condition (Johne). So, too, in calves and also in goats, hogs and
dogs, enlargements of the lymph glands are found which are due to
proliferation of their lymphoid tissue, and from one standpoint may
be regarded as hyperplasias, but which assume the character of
tumors in their progressive infiltrative extension and are very
dpvibtfyl so far as the history of their causation is concerned. These
Lymphoma.
373
growths are spoken of as lymphomatosis, progressive lymphomata,
Hodgk ill's Disease or malignant lymphosareomatosis. The afifec-
tion manifests itself by a gradual enlargement of one group of
lymph glands in excess of the rest. In all parts where the glands
are palpable, as in the flexures of joints, in front and back of joints,
along the neck, in the throat, they may be recognized as rounded
^,^/l^r^'.
Fig. 105.
Urinary bladder of cow beset witli l.vmiibi.mara (laid open).
oval movable bodies, enlarged to the size of a nut or that of a fist.
At autopsy the l}Tnph glands of the interior of the body are also
found changed into large nodulated masses, sometimes reaching
the size of a human head. At first the capsules of the glands are
retained and. as a consequence, the nodular enlargements are well
defined ; their consistence varies, sometimes soft, sometimes firm,
and the surface of section has throughout a uniform grayish-white
374
Tumors.
color. The minute structure of these enlarged glands corresponds
more or less closely to that of normal ones, but differentiation into
follicles, lymph cords and lymph sinuses is less marked, and the tis-
sue is more uniform. The tumor mass is made up of a finely fibrillar
or more coarsely trabecular network of connective tissue and blood
vessels in which are uniformly distributed, in close apposition to
each other, cells of the type of lymphocytes. In addition to the
small rounded lymphocytes with round nuclei rich in chromatin,
there may be found larger cells like those often met as early or
provisional forms in the germinal centers of the follicles, and once
and a while a few giant cells (Ribbert). Besides the proper lymph
nodes the follicles of the intestine, pharnyx, and especially the
lymphatic foci of the spleen, also undergo enlargement. The last-
Fig. 106.
Malignant lymphoma in kidney of hog.
named organ may reach very marked excess of volume, either show-
ing its Malpighian bodies increased to the size of a millet seed or
a pea (follicular hyperplasia of the spleen), or the whole pulp as
well evincing great increase of its lymphatic constituents as a
grayish-red swollen mass {diffuse splenic hyperplasia).
In the course of the progressive proliferation the lymphatic
tissue passes beyond its original limits, the capsules of the lymph
nodes are broken through and the bunches of glands coalesce into
shapeless masses. Diffuse. extension takes place, the adjacent soft
parts becoming occupied by the penetrating lymphoma, and an infil-
trative type of enlargement is assumed from which the glandular
parenchymatous structures, like the liver and kidneys, may also
become diffusely and very markedly enlarged. The infiltrating
lymphoid tissue gives to the parenchyma of such parts a pale gray
Lymphoma.
375
color, which may be either diffuse or present an irregular mottling.
The infiltration follows along the lymph spaces of the connective
tissue, especially along the perivascular lymph channels, and may
lead by special local accumulations of the tumor cells to the pro-
duction of new tumor-like nodes as well. The lymphosarcomatous
cells, however, also penetrate into the blood vessels, and by con-
Fig. Ill
Multiple lymphomata in liver of hog (general progressive lumphomatosis).
vection may occasion metastatic nodules in various organs, especially
in their lymphatic structures. The fact that the lymph glands in
order of position undergo enlargement one after another, and that
the metastases are principally located in the lymphatic structures,
may, it is thought, be due to chemotactic influences of related
type's of cells (Ribbert). It may be that the lymphosarcoma cells
Z7^
Tumors.
are lodged in the lymph centres having passed through the capil-
laries, because the lymph cells present in these foci have an attrac-
tion for them ; besides, apart from such a mode, the tumor cells
carried in the lymph stream are bound to enter the lymph glands,
where they are filtered from the lymph and remain. According to
Ribbert's views, progressive lymphomatosis is a true tumor forma-
tion. The successively involved glands show the inception of the
new formation often by well defined foci, sometimes only to be
recognized in the peripheral sinus of the node, this arguing for
I-ympliosarconat(isis of liver of cow (low power).
Fig. 108.
transference of the tumor element from a primary focus. By others
it is believed that some infectious process, bacterial in nature, is
connected, and that the microorganisms gain access to the lymph
glands in the lymph circulation and set up proliferative processes
in the nodes ; but as yet nioculation expenments have given no posi-
tive evidence. [The author's statement is true; yet glandular en-
largements, clinically regarded as belonging to Hodgkin's disease,
have repeatedly been found to be tuberculous in nature. The
lymphomatoses probably should be looked upon as of two types, one
Melanoma. t,J7
of which is best regarded as merely a lymphatic hyperplasia occas-
sioned by microorganisms or toxic substances which are in some
way brought to the lymph nodes (and some of these are tuberculous,
the remainder probably being products of a variety of microbic and
toxic influences). The second group may be properly referred to
the class of the sarcomas and spoken of as lymphosarcoma and
lymphadenoid sarcoma. The term lymphoma may be provisionally
retained to cover the group of uncertain or indistinguishable exam-
ples, but has no other place properly in tumor nomenclature. If
we limit ourselves to that series of cases, to which, from their
higher infiltrative and metastatic tendency (especially where we can
recognize that the secondary nodules are true metastases and not
mere hyperplasias of previously existing lymphoid foci which may
have been induced by an original microbic or toxic cause), the
name sarcoma may be reasonably applied. It should be added that
lymphosarcoma is a highly malignant type of sarcoma, ranking with
the ordinary small round cell variety in the severity of malignancy
from metastasis. It is. of course, difficult to make the separa-
tion in a large group of cases, but as far as possible we should
endeavor to exclude from the term lymphosarcoma tliose cases in
which enlargements manifest any appearances of infectious origin.
Where among these there is evidence of tuberculosis of course
the case is promptly referred to as tuberculous lymphatic hyper-
plasia. For the rest of the cases the non-distinctive term Hodg-
kin's disease may be employed if desired ; and it is well to keep
clearl}' in mind that the affection known as lymphatic leub^emia,
both acute and chronic, bears close relationship with the latter
group.]
Melanomata.
A mclaiionia. iiiclaiiosarcoiua (cliroiiiatoplwroma), or pig-
mented tumor, is characterized by a black-brown or slate-gray
color produced by the pigment cells (chromatophores) which
constitute the growth. Normally pigment cells are found as
specially difterentiated connective tissue elements in the skin
and choroid coat of the e_\e, and in some animals, as sheep, also in
the 'pia mater of the brain. The melanomata take their origin
from these cells and are therefore found most frequently in the
skin, being especially common in horses. It is peculiar that gray
and light colored horses, which as foals had a dark coat of hair,
should be especially prone to these tumors ; and it may be
378
Tumors.
presumed that irregularities of their loss of pigment underlies
the anomaly. Melanoma may, however, also occur in brown
horses and has been seen once in a black (Hall). In most
instances these growths develop in horses in the region of the root
of the tail, the anus and external genitalia. In these positions
they form nodes which protrude like boils beneath the skin,
attaining the size of several fists and several kilograms in weight.
Secondary nodes are formed along the lymph passages, so that
in the cellular tissue of the pelvis there may be found whole
chains of tumor nodes ; and by infiltrative growth the tumor
Fig. 109.
Section through horse's tall involved by melanoma.
may completely invade the cutis and subcutaneous tissue, and
cause widespread thickening and swelling. The growth is
usually slow ; it may continue for several years as a circum-
scribed and strictly local process, at other times being highly
metastatic and causing an extensive generalized melanosarco-
matosis, with secondary nodes in the lung, pleura, spleen, liver,
kidneys, bones, musculature and elsewhere. Melanomata of the
same nature as the above have been met also as primary growths
in the cellular tissue near the parotid gland, in the pancreas
(Kasewurm), intestine (Csokor), at the base of the heart (Dex-
ler), and in the spleen.
*
Melanoma.
379
In cattle melanomata are of less frequent occurrence. Metz
saw two cases in white animals ; in one the tumor was situated
in the dewlap, in the second in the pelvic cavity near the uterus.
Hamburger found one tumor of this kind in the diaphragm ;
Hoare removed a melanoma weighing fifteen kilograms from the
temporal region of a brown ox. Bollinger has recorded the
occurrence of a congenital melanoma of the size of a fist in the
cranial cavity of a thirty-day-old calf; Wulf, a similar growtk
in the subcutaneous tissue of the ankle of a calf. In sheep
Worseley has reported a case of melanosarcomatosis involving
~^^
r^-^-^-^.
Fig. 110.
Microscopic section of sliin of horse infiltrated with melanoma.
the lumbar region, mammary glands, lungs and liver. In the dog
the author has observed a melanoma, springing from the gums,
and Bruckmiiller one at the base of the brain.
Some melanomata have a firm, rather dry appearance ; others
are found of soft consistence. The cut surface is uniformly
dark, or sepia-brown or slaty ; when handled the fingers are
soiled as if with shoe-blacking.
Microscopically the pigment is found in the form of brown-
ish black granules, which are distributed in the fluids of the
380 Tumors. .
tumor and within the cells. The latter elements are seen as
variably shaped, irregularly rounded, fusiform and branched
cells, their cytoplasm usually so thickly loaded with the dark
brown granules that the nucleus is obscured ; at places, however,
they may be found entirely free from pigment. The cells are
usually so closely packed together that their outlines cannot
always be dififerentiated. The tumor tissue is very clearly
defined from the rest of the tissues, into the lymph spaces of
which the neoplasm can be seen to be extending its way, afford-
ing an excellent demonstration under the microscope of the
mode of propagation of these growths. The cells are so easily
loosened in the softer specimens that the tumor mass may stand
out like thick pultaceous material ; Csokor has observed in the
case of a horse with the intestinal mucous membrane (colon)
the seat of melanoma, the discharge of black fecal matter ; and
Bollinger, Bruckmiiller and Semmer have found the pigment
gramdes in the blood (melan:cmia).
The pigment material known as melanin, certainly does not
come from the blood (iron free), but is formed by a specific
activity of the chromatophorous cells, as Berdez and Nencki
have shown ; the important proportion of sulphur in its compo-
sition suggests that it is a derivative of albuminous bodies.
The orisfin of melanomata is necessarilv in some wav related
to developmental disturbances which give rise to excessive pro-
duction or misplacement of pigment cells; their occurrence as
congenital tumors and the fact that in man the growths are
known to frequently take their start from congenital pigment
moles of the skin, are evidence in favor of such a view.
The malignancy of these growths is not uniform; as above
stated, some may remain in their primary situation for years
without appreciable enlargement, and may not recur when re-
moved, but others, especially the softer forms, spread rapidly and
widely and give rise to great numbers of secondary nodes. [The
melanotic sarcoma of man. most commonly met in the eye, is ex-
tremely malignant, ranking probably first of all in the list of sar-
comata in this respect.]
Endotheliomata, Peritheliomata, Cholesteatomata.
By the term endothelioma is meant a tumor which is com-
posed of endothelial cells of connective tissue derivation, espe-
cially those of blood vessels and lymph vessels, as well as those
Endothelioma. 381
of the dura mater of the brain and spinal cord. EndotheHomata
in their structure stand relatively midway between the atypical
connective tissue growths and epithelial tumors, and resemble now
one and now the other of these so closel}- as to make their distinc-
tion from sarcomata or carcinomata often practically impossible
where only single bits of die growths are subjected to micro-
scopic examination. They dilTer from cancers in the history of
their development, the latter taking their origin from epithelium,
v if '• • ' '' ' " c f- .f 5^
_ _ ". , _ ^. Jt, «», -K. ^t
Fig. 111.
Endothelioma of lymphgland (human): a, lymphoid tissue of gland; h, leucocytes
in nearly obliterated lymph-sinus ; c, endotlielial cells proliferated from lining
of lymph-sinus.
either ectodermal or entodermal, while the true endotheliomata
are of mesoblastic origin. It is more difficult to define them
from sarcomata, the cells of the latter being also derived from the
middle germinal layer ; and for this reason some authors speak
of them as endothelial sarcomata. (The layer of so-called endo-
thelial cells lining the large serous cavities of the body, the coelo-
matous lining, is to be regarded- as epithelial and the tumors
which arise from these cells are therefore to be classed as
cancers.)
382 Tumors.
The cells of an endothelionia present the same polygonal,
flattened, fusiform and polyhedral forms as the fibroblasts and
angioblasts, the cells of the blood and lymph vessels being, in
fact, formed originally of the same material. In the tumors they
are arranged as scales, or in cylindrical cords or in hollow tubu-
lar manner so as to form a network with thickened nodal points,
and are supported by a vascular stroma. The microscopic appear-
ance is therefore very like that of an alveolar sarcoma or carci-
noma; sometimes the arrangement of the cells in lamellae may be
concentric like the tunic of an onion.
Those endotheliomata which take their origin from the outer
coat (adventitia) of the bloodvessels (from the perithelial cells)
and are recognized as forming mantles of tumor cells about the
blood vessel and its branches, are generally spoken of as pcri-
theliomata.
Retrograde changes which occur in endotheliomata may give
an unusual appearance to some forms, in consequence of which
special names are applied. As an example the cylindrical cords
may undergo, hyaline degeneration of their endothelial cells, be
transformed into shining homogeneous structures, standing out
conspicuously in transverse section like hyaline, concentrically
laminated balls or masses ; this appearance has led to their being
called cylindroniata. In other instances calcareous deposits (in
the form of globules, needles and club-shaped masses) occur in
the structure of the growth, giving a grittiness to the tumor in
section and making the cut surface rough and sandy ; these are
especially met in the brain and are known as psammomata {acer-
vuloma, sand tumor). The endotheliomata which -develop from
the choroid plexus of the brain are always richly infiltrated with
cholesterin deposits, and are called in a superficial way choles-
teatomata.
However these changes or depositions which give occasion for the special
names indicated are not absolutely restricted to one particular type of tumor.
In the collection of lime and cholesterin it must be kept in mind that the
cells of the neoplasm are preserving qualities of the cells from which they
had their derivation, for brain sand and cholesterin are found normally also
in the pineal gland and in the choroid tissue. True epithelial tumors, how-
ever, which occur in the cranial cavity and are referable to inclusions of
epidermoidal rests usually contain cholesterin, and it is also met in dermoid
cysts or epidermoid cysts of the subcutaneous tissue; these types requiring
the acceptance of a further class, the epithelial cholesteatomata.
Contributions recording the' occurrence of endotheliomata in
animals are very meagrely found in literature. Dexler met in a
Cholesteatoma; Papilloma. 383
dog- an endothelioma originating from the spinal dura mater;
Kijnnemann a psammoma of the cranial dura mater about the
size of a duck's egg, overlying the anterior part of the brain in
a cow. Cholesteatomata have been found rather frequently in
the lateral ventricles in the horse ; met in this location they are
rounded, reniform nodes, varying in size from that of a lentil to
that of an egg, usually occurring bilaterally, a tumor suspended
from the choroid plexus in each ventricle. The surface is smooth
and shining, sometimes granular; the color white, gray or grayish-
yellow; the consistence about that of the liver, the cut surface
slightly gritty and the cholesterin recognizable in tiny opalescent,
shiny spots. Microscopically these tumors are made up of blood-
vessels, a loose connective tissue stroma and the endothelial ele-
ments, which have grown from the bloodvessel wall ; between
these cells, in the vessel walls and in the widened lumina of the
latter the cholesterin may be seen in the form of superimposed,
step-like plates with the borders broken out. In addition round
cells and pigmentary deposits may also be found. (Cornil and
Ranvier speak of the tumors in question as angiolithic sarco-
mata; Casper employs the term hsemangiosarcoma perivascu-
losum).
[The position taken by the author in excluding from the
endotheliomata tumors originating from endothelium of the
large serous sacs, is not generally accepted ; and endotheliomata
of the pleura especially have been frequently described.
Endotheliomata as a rule are slowly growing tumors and
although capable of metastasis are generally not marked by
many secondary formations. This, however, 'in some individual
examples is quite reversed and high metastatic malignancy is
manifested. So, too, in most cases they are not recurrent after
extirpation, but here again exceptions must be recognized.
They may occur as multiple primary growths. The subdivisions
above mentioned, cylindroma, cholesteatoma and psammoma.
are as a rule merely local growths, and arc among the least
metastatic forms of endotheliomata.]
Papillomata.
The name papilloma is applied as a comprehensive, even if
not well chosen, term for fibroepithelial neoplasms which occur
on the surface of the skin and mucous membranes in the form
of warty, conical, coralline, villous or nodular proliferations of
384
Tumors.
the papilla and their overlying epithehum. The physiological
prototype of this combination of tissue and its source of develop-
ment are in fact the epithelial-covered papillae of the skin, but
in their pathological proliferation the quantitive relations be-
tween the two forms of tissue are very irregular. In some
tumors the connective tissue growth is so predominant that the
tumor practically consists of thick clumps of this tissue covered
only^ by a thin layer of epithelium rather stretched over the mass
Fig. 112.
Cutaneous papillomatosis of beef.
than growing with it (for which reason some authors prefer to
speak of such a specimen as fibroma papillare), the superficial
papillary structure being only recognizable under the micro-
scope. In other instances the fibrous tissue of the base of the
tumor sends out long branched villous processes, or may undergo
changes which give it a soft, oedematous or very vascular appear-
ance ; and again the keratous epithelium may form so thick a
laver as to throw the connective tissue substructure into insig-
nificance. Different types of these iibroepithelial autoblastomata
may be distinguished by taking such features into consideration.
Papilloma.
385
On the skin and nmcons membranes covered with <;quamons
epithelium they occur as rounded projections, sometimes only
as large as a pea or nut (zvarts, z'crniccc) , simple local hyper-
plasias of the papillary body with smooth epidermal covering; or
they sometimes occur in clumps, like grapes, as cauliflower
tumors of the size of a tist [ paj^illouia tiibcrositiii, polyposuin. coral-
IlforiJic), with superficial subdivisions, provided with l)road
f
^'-
'1.^^
X J
if.
y^-j
<
-\.;V
'^'^^f;
It. 3
klfis 11 \
y Jl / r ^'^^^r^
Fig. 113.
Section (,f papilloma of cow.
peduncks or hanging suspended by a thin stretched-out pedicle ;
or again as thread-like or bristle-like projections (pa/^iUonia fiU-
forme).
Under the microscope, varying with these external shapes
of the growth, the connective tissue, wdiich is made up merely
of spindle cells and fibrils with bloodvessels, may be seen as
papillae of varying length and thickness and of all sorts of
shapes, with knotted and clubbed branches and secondary point-
ed projections; and the epiderm in a single* or multiple layer
extends over this, following the depressions and clefts, in which
386
Tumors.
the epithelium may become keratosed and formed into concen-
trically laminated arrang^ements (horny pearls).
Sometimes these papillomata occur congenitally (two cases
of the kind in question fully described by Pirl and Trolldenier*
v> %
^*.5
Fig. 114.
Papilloma coralliforme in gullet of cow. (T"he oesophagus has been everted and
the mucous surface exposed ; the partly smooth appearance is due to the fact
that a piece of wood has been forced into the lumen of the tube turned in-
side out.) (Photograph.)
in foals), probably due to traumatic intrauterine lesions of
the skin caused by amniotic threads. By some authors an inf^c-
* Monatshep f, p, TierJieilk, 1903.
I\ipiili)iiia.
387
tious cause is suspected for ccM-tain forms of papillomata because
the affection often appears in a number of animals at the same
time in one stalile in wide distribution over the cutaneous sur-
face; development after chronic .intiammatory irritation of tlie
skin has also been observed. Especiall}- in the skin of the udder
of the cow and in young- cattle, but also in other positions in this
species there often develop g-reat numbers of w^arty and nodular
papillomata which ma\- weigh en jiuissc many pounds. These
superficially divided growths, which are of course exposed to
traumatic influences and contamination
witli foul pus, are apt to become mal-
odorous from maceration of the desqua-
mated epiderm retained in the depres-
sions ; they often become oedematous
and swollen, and may become more or
less suppurative and putrefactive from
the influence of microorganisms, which
may have gained access into these
parts. In similar manner the jiapillo-
mata frequently developing in the frog
of the horse's hoof (known as hoof
cancer or frog cancer) are apt to break
down into a foul-smelling mass because
of incomplete keratinization of the
epithelial surface layer and contact with
all sorts of germs and putrid material
(dung, foul pus).
A favorite location for these tumors
is the oesophagus of cattle, where the
papillfe project into the lumen of the
tube either as thorn-like, bristle-like or
brush-like prominences, or as circumscribed villous or coralline
growths, or as firm nodular bunches ; the passage of food, es-
pecially the return of the cud (in ruminants) being more or
less interfered with. Papillomata often occur also in the psalter
of cattle as berry-like, slightly cedematous, swollen-looking
growths, ranging in size from the millet seed size normal to the
papillae of the part, to pendant rosette-like bunches of projections
half the length of the finger, clul)-shapefl and covered smooth.ly
with epithelium. In dogs the lips, buccal cavity, foreskin and
anus are the principal sites of papillomata.
Fig. ll.">.
Congenital papillnma (if pinna
of colt. I After Troll-
denier.)
388 Tumors.
In the urinary and gall bladders of cattle, in the former also
of horses, dogs and swine, papillary mucous membrane prolifera-
tions occur, usually projecting as long villous, highly branched
growths with a common pedicle into the cavity of the viscus. like
the tentacles of a polyp {papilloma polyposum) ; they are usually
very soft, succulent, their connective tissue oedematous and per-
haps actually myxomatous (papilloma polyposum myxo'matodcs),
or in other cases the seat of a cellular infiltration and presenting
evidence of inflammatory involvement. Inflammatory changes
in the last named situations are so frequently accompanied by
mucous membrane proliferations that some causal relationship
may be assumed and the hyperplasia of the mucous membrane
regarded as a sequel to a productive inflammation (Zellhuber).
Where the epithelium of the papillary growth of the skin is
not desquamated in scales, but in its active proliferation forms
thicker and thicker horny layers, there is produced a hard body
which continually grows more and more prominent and acquires
the form of a horn-like outgrowth, a cutaneous horn (coniii cuta-
neiim). These structures are very frequently seen in cattle,
especiallv in range cattle, occasionally attaining a length of half
a meter, growing from the forehead or neck, or as a short
conical horn from the skin of the udder. Now and then large
spirally curved cutaneous horns are seen in goats in the thoracic
and abdominal walls; in sheep in the car and back; in horses and
dogs as small claw-like horns in the car and in other parts of the
body. (For fuller description see Casper, Pathol, d. Gcschzviilste
b. Ticrcn. Wiesbaden, 1899; Kitt, Spcz. pathol. Anatomic. II. Aufl.,
Stuttgart, 1901.)
Papillomata and cutaneous horns are regarded as benign, non-
recurrent, persistently local new growths ; they manifest an unfavor-
able tendency only from their size and situation.
* Adenoma.
An adenoma, or [epithelial] glandular tumor, is a prolif-
eration of glandular tissue, with reproduction of its structural
type, in the forni of a tumor. Epithelium and a vascular con-
nective tissue stroma in definite structural relations constitute
glands, and the two forms of tissue in common contribute to the
formation of the adenoma. Whedier the epithelium was the
primary proliferating element and, as Borst believes, the con-
nective tissue cells took a relatively secondary part because
Adenoma.
3%
of their tactile sensibility, is an open- question. In some adeno-
mata the reverse is apparently the case, the connective tissue
proliferation apparently being- the major feature, in its prolifera-
tion causing- expansion of the surfaces of the gland lumina and
thus ali'ording space for the epithelial gland lining to develop.
Both tissues proliferate side by side in mutual interdependence
in the production of gland tissue.
There are as many varieties of adenoma as there are different
glands in the animal body, and as the tumor invariably takes its
origin from a gland it always represents a histological copy of
the particular gland in question. The growth has, too, in all
instances the same type of epithelium which characterized the
original gland, and the same kind of connective tissue stroma is
f^ig IIG.
Adenoma, of size of human head, of the gall ducts iu the liver of cow ;
(cut surface).
preserved in more or less precise simulation of the structure
peculiar to the parent gland. Corresponding to the dififerent
glands these tumors may be divided into major types of tiihular,
alveolar and follicular adenomata; and depending upon their
origin it is customary to speak of them as sweat-gland, seba-
ceous, hepatic, salivary, .renal and other adenomata.
In this pathological proliferation of the glandular tissue there
occur, how^ever, manifold modifications and abnormal features.
The epithelium, although generally exhibiting the same structure
and even secretory function as the original type, is often increased
390
Tumors.
in size or may be present in a greater number of layers, and its
secretion may be of a degenerative character (for example, from
the assumption of mucoid change by the adenomatous cells or
their destruction by excessive fat production). The connective
tissue, which in direct limiting relations to the epithelium forms
its tunica propria and in lobulated types of gland tissue forms a
meshwork of septa, is often developed in special excess, forming
denseh' fibrous sclerotic trabecula which embrace the glandu-
lar ducts in compact circular investing bands {adenofibronia
pcricanalicularc) or form club-shaped or finger-like projections,
stretching the adenomatous lumina, increasing the surface of
the glandular canals and extending into the latter as villous
papillae (adcuofibroiita iiitracanaliciilarc, adciiojiia papUUfcnim).
/
/
W
Fig. 117.
Adenoma flavnm of liver of cow.
The tubular or vesicular spaces of the adenoma, by continu-
ous and progressive formation of hollow buds lined with epi-
thelium, become more and more branched and more irregular than
in the normal gland; and by this intricate projection of epithelial-
covered connective tissue processes into their interior become
changed into tortuous passages and openings, which may become
quite large. The cut surface of an adenoma ma}^ in this way
come to closely resemble a section through a head of cabbage,
in which spaces are to be seen between the layers of leaves. As
these adenomata are completely isolated new grow^ths and their
Adenoma. 391
canalicular systems are in no way in communication with the
emerging ducts of the noniuil t^huuls, an accumulation of secre-
tory material and desquamated epithelial cells is likely to be
retained in their passages and spaces : thus in an adenoma of
the mammary gland milk is found as a pathological product ; in
follicular adenomata of the thyroid, masses of colloid matter; in
adenomata of mucous glands, mucin. As a result of the reten-
tion of such material the walls of the canals and alveoli become
stretched, and this feature, together with continuous enlargement
of their surfaces from increase of the epithelial lining and the
connective tissue framework, may make the distended cavities
visible to the naked eye. To tumors thus altered and containing
cavities filled with fluid the term cysfadc)io}na is applied ; and
where villous projections of the lining membranes extend into
the cavities the growth is known as cystadcnonia papilliferum
phylloidcs.
The growing vascular connective tissue of the adenomatous
structure is sometimes the seat of haemorrhagic effusions or
oedematous swelling, due to passive congestion and transudation
caused by kinking of the folds and villi projecting into the
cysts. Other regressive changes, as fatty degeneration or coagu-
lation necrosis, may also be observed. In some instances the
stroma of the tumor is a tissue very rich in cells and of a
reticular structure resembling a sarcoma or myxoma (adenosarcoma,
adeiioinyxoma, adenoma sarcomatodes, my.vomatodes) .
Finally glandular tumors, which in typical cases are usually
distinctly limited from the organ in which they are situated,
may become atypical and send out infiltrating processes into the
surrounding tissue, penetrating into the lymph vessels and
bloodvessels and thus assume the character of a malignant fibro-
epithelial growth. These forms are known by the names adenoma
destruens, adenoearcinoma [)nalignaut adenoma].
Two points may be considered in attemptmg an explanation
of the setiology of adenomata. The definitely circumscribed
nodular adenomata w'hich develop in or close to parenchymatous
organs are doubtless of foetal origin, coming from misplaced,
independently developing parts of a gland. Those growing as
single or multiple tumors from mucous surfaces, sometimes
occupving extensive areas of the mucous membrane, often show
in themselves, just as the neighboring parts of the membrane
mav also show, evidences of chronic inflammatory change, recog-
nizable bv cellular infiltration and by giving rise to a mixed secre-
392
Tumors.
tory and exudative type of product. These peculiarities as well
as the clinical course of such cases, suggestive of their origin as
direct sequences of chronic inflammatory processes, force the
conclusion that injuries capable of causing inflammation may
either directly or indirectly (disturbance of tissue tension) give
origin to adenoma production. Mucous membrane and glandu-
lar vegetations of this type are usually spoken of as glandular
Iiypcrf>lasias or mucous membrane polyps. It should be recog-
nized, however, that such superficially situated adenomata may
become inflamed secondarily, from their coming in contact with
irritants.
The most frequent type of adenomata occurring in animals
are those of the sebaceous and sweat glands {adenoma seba-
ceum, sudoriparuni) in the skin of the dog; among them particu-
larly growths originating from the perianal glands, presenting
rounded, nodular and lobulated forms, of a reddish yellow or light
yellow color and giving oft* a fatty, greasy fluid (a number of
descriptions of Siedamgrotzky, Lienaux. Werner). True ade-
nomata of the liver are also comparatively common in cattle and
sheep (Bollinger. [Martin. Siedamgrotzky. Johne. personal obser-
vations) as sharply defined tumors, surrounded by a connective
tissue capsule, situated in the midst of the hepatic tissue. These
may sometimes be found as large as a human head, composed
of liver cells and delicate cob-web like connective tissue septa.
They are usually very striking because of their bile-stained yel-
low to green hue. Similar to these there also occur in the liver
gall-duct tumors, with dense fibrous stroma, having, in conse-
quence, a firm consistency and appearing as light yellow nodular
deposits ranging in size from that of a potato to that of a human
head. The mammary gland in dogs is another frequent site for
cystadenomata and combined adenofibromata or for transitional
forms becoming cancerous. In the lungs adenomata of nodular
form may originate from the bronchial mucous glands, obs-erved
in sheep (A. Eber) and horse.
Although in man mucous membrane polyps occur quite fre-
quently in the nose, such growths are more uncommon in animals ;
in the horse they are met hanging into the naso-pharynx, hyper-
plasias perhaps as large as a fist, lobulated, elongated, slippery and
of mucoid consistence, composed of soft mucous membrane tissue.
There is difficulty in trying to accurately define thyroid adenomata.
The colloid secreting epithelium of this organ in its proliferation
sometimes gives rise to a general enlargement of the gland, the con-
Adenoma. 393
clition known as goitre (struma) ; and sometimes leads to nodular
formations which originate from isolated and independently growing
cellular foci and are called adenomata, cystadenomata, or adenocar-
cinomata, but which are usually accompanied by diffuse enlargement
of tlie rest of the parenchyma of the organ. In the same way pro-
liferation of the glandular tissue of the ovary and testicle is usually
diff\ise, and the distinction detween hypertrophy and true tumor
formation is difficult here as well as in the previous example. The
cells are usually of an indifferent type and can scarcely be distin-
guished from sarcoma cells. In these cases the terms ovarioblastoma
or orchidoblastoma are convenient names, according to the organ
involved. They may be seen as solid growths or with cyst forma-
tion associated, the whole organ involved, the tumors reaching enor-
mous size, weighing perhaps ten or fifteen kilograms and often at-
taining the dimensions of a human head or even twice that of the
full stomach of a horse (in horses, cattle, sheep).
In the kidneys true adenomata of the uriniferous tubules have
never been observed. The tissue proliferations which develop here
in the form of tumors, as a rule are of the destructive adenocarcino-
matous type and convert the organ into a shapeless, soft material
which may break through the capsule. This substance is sometimes
as soft as marrow, gray to brownish-red in color, and is made up of
large canals lined by cylindrical epithelium. In other cases the
growth is combined with sarcoma and^ possibly also with muscle
fibres and constitutes an adeno-rhabdomyomatous sarcoma (Johne).
[Some of the tumors described as renal adenomata are in real-
ity hypcnicphroinata (v. p. 397) ; although the latter growths, which
occur in the kidney as their most frequent seat, are ordinarily easily
distinguishable. In man there occasionally are seen in sections of
kidneys small isolated foci of tubular structure, with the tubules
either small and compressed or at places distended into cystic spaces.
In the latter papillary proliferations may be found projecting; the
w'hole appearance corresponding with the adenoma papilliferum
above described. In these cases as a rule the foci are small, perhaps
microscopic, and the general picture of the structures suggests their
isolation from the rest of the tissue by an inflammatory change.
Rarely larger nodules of this character are met, to which we cannot
refrain from applying the term adenoma.
The prognosis of the tumors of the adenomatous group is funda-
mentally favorable ; the true adenomata' being entirely free from any
tendency to infiltrate or to give rise to metastasis. Such growths
are harmful merely from their local influences. The variety above
394 Tumors.
mentioned as destructive or malignant adenoma or adenocarcinoma
is essentially cancerous in its nature and is malignant both bv local
extension and by metastasis. Any adenoma may be regarded with
suspicion and dealt with accordingly, when it is recalled that it is not
very uncommon for these growths to lose their purely adenomatous
character and become changed into adenocarcinomata.]
Carcinomata.
A carcinoma or cancer is a malignant new growth composed of
epithelium and connective tissue, characterized by a persistent and
progressive penetration of its epithelial elements into the underl> ing
tissues. The cancers always originate from epithelium, either surface
epithelium or the glandular epithelial cells of functionating organs,
or from islets of epithelial cells formed in foetal life and occurring
in unusual situations. They may also take tlieir origin from pre-
viously existing papillomata, adenomata and cystomata, these having
from unknown cause assumed a proliferation of their epithelial cells
with departure from their ordinary forms and boundaries.
The proliferating epithelium forming the cancerous parenchvma
or body of the cancer behaves as a foreign intruder ; It assumes
an independent status by no longer remaining confined to the surface
which it previously covered, breaking through its normal limiting
structures and playing the part of epithelial cells which have be-
come practically parasitic. These cells, derivatives of previously
existing epithelium, by their penetrative growth and active multi-
plication usually form in the deeper structures solid cords or duct-
like processes which branch like the roots of a tree and are contin-
ually sending out new projections into the tissue. These retain-
ing their continuity with each other result in forming a network
or meshwork [of epithelial character throughout the invaded
tissue] varying in its density and with irregular nodal point?
(Ribbert). This net-like and corded arrangement of the epithelial
roots is due to the fact that the cells in their penetration follow the
lines of least resistance and therefore penetrate the lumen of the
lymph passages, come to completely fill them with their growth and
therefore to assume their shape. After occupying all the lymph
spaces of the connective tissue the epithelial roots may penetrate
into the tissue itself in such numbers as to practically constitute a
difl-'use infiltration (Ribbert).
In microscopic sections the continuity of the cords is not entirely appre-
ciated, as each sectional layer, of course, contains only segments of them.
Cancer. 395
In serial sections or in plastic reconstruction of tlie general tumor-picture
by means of the methods of planar modeling, one may always convince
himself of the interconnection of all the epithelial cords (Diirk).
The connective tissue of the organ in which the epithelial cells
are in active cancerous proliferation, does not, however, act in a
purely passive manner, as a tissue shoved aside and compressed by
the epithelial growth ; but reacts by an inflammatory change which
in its chronic course leads to tlie production of a connective tissue
hyperplasia. The epithelial masses act precisely like foreign bodies,
attract leucocytes to them 1)y chemotaxis, the latter cells collecting
about the margins of the epithelium just as in a demarcating inflam-
mation and sometimes producing a marked cellular infiltration of the
connective tissue. At the same time the fixed connective tissue cells
proliferate and form a fibrous stroma (framework of the cancer)
of varying texture, containing young bloodvessels and enclosing epi-
thelial nests.
The distinction from the typical fibroepithelial tumors [adenoma,
papilloma] lies in the fact that in the latter the epithelium and
connective tissue are united in common growth to form a tissue com-
plex, a compound tumor basis ; while in cancer in reality only the
epithelium is the basic tumor element, and the connective tissue
growing along with it is the result of a productive inflammation and
belongs properly to the organ in which the cancer is located. The
cancer stroma therefore is but the interstitial tissue of the affected
organ, involved bv inflammation. The epithelial elements of the
cancer develop in the organ in which the tumor originally (prim-
arily) gre\v, from cells, it is true, already present therein ; but the
epithelial cells of the organ are not uniformly changed into cancer
cells, do not all take part in the tumor construction. The growth
and extension of the latter involves invariably a fixed group of cells
acting as the germinal elements of the tumor, toward the multipli-
cation of which the other epithelial cells remain passive.
The microscopic studies of Ribbert have furnished a number of
considerations which concern the histological production of the pri-
mary stage of this type of tumor, the start of the cancer formation.
Ribbert refers the origin of the growth to an isolation from the cel-
lular union in an organ of individual epithelial cells or a group of
cells, as an epithelial ingrowth, a separated bit of epiderm, or a
lobule of a gland : this subsequently assuming independent prolifer-
ation. This isolation from physiological connection is usually
brought about, as Ribbert recognized in microscopic sections in the
396 Tumors.
initial stages of skin cancers, by the intrusion of connective tissue,
stimulated to proliferation by inflammation, between the epithelial
cells. In other words, according to Ribbert cancers always start on
a base of chronically inflamed tissue. The epithelial cells do not
make the initial penetration into unaltered connective tissue ; the
primary change being the inception of the inflammatory prolifera-
tion of the subepithelial connective tissue, which raises the epithe-
lium and, as the proliferating connective tissue elements invade the
deeper epithelial layers and destroy the intercellular cement,
separates isolated cells from their proper relations and thus mis-
places them. The isolated epithelium, now situated in the midst
of the connective tissue and sufficiently nourished by it, begins
to nuiltiply ; and, being prevented from growing upward toward
the surface of the skin or mucous membrane, and its relations with
the general epithelial tissue, its nerves and normal substratum
(papillary layer) being destroyed, it must necessarily penetrate
irregularly into the tissues along the course of the lymph spaces.
Thus it comes to force its radicles and cords in every direction
and to form the beginning of the cancer.
As a matter of fact cancers do occur with frequence in places
where for some time previously inflammatory irritation has existed.
In man, for example, cancer of the lip is especially likely to be met
in persons who smoke pipes habitually, and, too, just in the corner
of the mouth which is always exposed to irritation from the juices
from the pipe. The influence of soot as an irritant capable of in-
ducing cancer is well seen in chimneysweeps (chimney sweep's can-
cer) ; and that of paraffine has become well known among the em-
ployees of parafline factories as causing epidermoidal proliferations
(paraffine cancer of tlie hands). A. Sticker has called attention to
several examples which indicate a causative relation of external
influences upon the establishment of cancer, as the occurrence of
skin cancer in cattle after branding (Mac Fadyan), and beneath the
chin in swine from chaffing (Eggeling). Possibly the frequence of
cancer of the anus of dogs has some connection with external inju-
ries (from the animal scraping the anal region along the ground, so-
called "sleigh-driving").
The origin of cancer should not, therefore, be attributed to any
one cause, as a definite cancer parasite or an infectious agent, but
may be determined from any influence (traumatic, chemical, infec-
tious) which occasions chronic inflammation and because of which,
as a result of the inflammatory process, an isolation of the living
Cancer. 397
epithelial cells, retaining their power of proliferation, occurs. It is
of course true that inflammations of surfaces covered by epithelium
and epithelial organs are frequently seen without resultant cancer
production, even though it may be presumed that isolations of
epithelial cells may often obtain in connection with these processes.
But, as Ribbert insists in case of such exceptions, much depends
upon the length of time over which the inflammation extends. In
acute inflammations the epithelium is apt to be injured, and even if
isolated cells be misplaced in the subjacent tissues the process is of
too short duration to allow the cells to accommodate themselves to
their new surroundings; they therefore perish (Ribbert). In the
same way as an inflammatory connective tissue production, epithe-
lial cells may in papillary and polypous new* growths be cut off and
isolated by the proliferation of the stroma, or whole cores or
bunches of them : and thus a primarily benign tumor may be con-
verted into a malignant one by the progressive growth of such
cells into the underlying tissues. The change of fibroepithelial
growths which for years have been of simple type into destructive
cancers is a well authenticated observation in human medicine.
Finally, epithelial misplacements, which may accidentally be caused
in foetal life in the processes of arrangement of the various tissues,
in the formation of folds and cavities which are taking place
among the tissues in the construction of the various organs, may
furnish the original substance for a subsequent cancer.
A good example of this is afforded by the nodular growths met in the
human kidney cortex, originating from misplaced adrenal tissue. They are
met as single or multiple growths, well defined; and sometimes destroy the
kidney, penetrate into the blood vessels, and give rise to fatal metastasis.
These nodes are of a yellowish color from the fat which they contain, and
under the microscope are seen to be made up of cords of cells arranged
in parallel lines along the blood vessels, and resembling in their appearance
the epithelium of the suprarenal bodies (hypernephroma, adrenal cancer).
LThese growths are also met with not very infrequently in the kidneys of
cattle and occasionally in hogs; they are not confined to the kidney, but
may be found in any of the structures near the adrenals or in the adrenals
themselves, where they may either represent foetal rests, or may have started
from isolated parts or inclusions of the tissue of the organ caused by inflam-
matory sejparations.]
Ribbert's attempted explanation of the genesis of cancer is not
as vet accepted by many pathologists. Inflammatory changes are
often not demonstrable at the places of origin of cancers ; and some
authors do not believe that the atypical proliferation of the epithe-
lium is a result of the invasive growth of the comiective tissue but
39^ Tumors.
that some otlier as yet unknown causes underlie the irregular pro-
gressive proliferation which these cells manifest (in other words,
that the epithelial multiplication is the primary process) ; and search
lor some kind of infectious agent is not as yet abandoned. The
occasional endemic occurrence of cancer (also observed bv Eggel-
ing in hogs in a certain locality) and isolated cases which suggest
the transmissibility of certain forms of cancer continue to keep the
question of the infectiousness of cancer in discussion. A. Sticker,
for example, has called attention to a dog which for a long time
liad been in the habit of lying by the bed of a man suffering from
cancer of the stomach and ate all sorts of material which the man
had vomited, and which became affected by a general carcinomato-
sis (lungs, liver, omental sac. but not the alimentary canal). This
may have been a mere coincidence, but the possibility of an etio-
logical relationship between the two cases cannot be entirelv ig-
nored. ( Cf. p. 334. ) Experimental attempts to prove an infectious
nature as existing in these growths (inoculation and feeding ex-
periments) have hitherto always failed. Trasbot obtained no posi-
tive result from hundreds of such attempts : Duplay and Cazin
failed in over one hundred and twenty experiments in dogs and rats ;
Gratia and Lienaux, Cadiot and Gilbert had no more success in
numerous attempts to transmit tliese tumors, employing all sorts
of methods of inoculation (from dog to dog, from man to dog).
The transplantation of certain forms of cancer in rats and mice has
alone succeeded (Hanau. ]\Ioraus. C. O. Jensen) : but the methods
employed do not indicate that an infectious agent was operative^
but rather that the cells of the cancer used in the experiment were
capable of multiplying if placed in uninjured condition in a new
specifically similar soil (i. e., transplanted to the same species of
animal as that from which derived), and of continuous develop-
ment into an independently growing tumor tissue in their practically
parasitic colonization and multiplication, (cf. Definition of tumors
P- 325-) [Transplantation of cancers in animals has invariably
shown that success is to be expected only when the animal to which
the tumor is transplanted is of the same species as that from which
it was derived, even varieties of the same species making the result
doubtful. In this country Leo Loeb, Gaylord, Herzog and others
have carried various cancerous growths or mixed cancers through a
number of generations in rats and mice. In these experiments actual
portions of the living growth (bits may retain life for some hours
-when kept in moderate refrigeration after removal from the origi-
nal animal) must be introduced into the experiment animals and
Cancer. 399
filtered extracts arc not followed by success. Ehrlich {Berlin.
Klin. Woehenschr., No. 28, 1905; Xo. 2, 1906) and Loeb {Univ.
of Penna. Med. Bull., July, 1905) have both recorded the occurrence
of sarcoma succeeding the original carcinomatous tumors after
some generations of transmissions. This would not necessarily
suggest the direct transformation of the cancer into sarcoma, as
much as that in the course of growth the proliferating epithelium
had induced such changes in the connective tissue portions of
the lumr)r as to cause them to acquire an analogous energy of
atypical proliferation, and that perhaps this latter tissue or, what
perhaps is more ])robable, immune bodies, reactively de-
veloping to the cancer, have caused the disappearance of the epi-
thelium itself. The known spontaneous disappearance of cancers
(cf. Gaylord and Clowes : Sitrgcry, Gynecology and Obstetrics,
June, 1906) speaks in favor of the existence of such cytolytic factors.
Gaylord's success in obtaining a serum from mice spontaneously
recovering from cancers, which on injection into mice having in
their bodies actively growing tumors of the same strain cawses
them to recover, speaks in the same line ; and the fact that an ex-
tract of a tumor (v. p. 339) injected into the body of the original
animal having other nodes of the same growth in its body, strongly
supports the same idea. Tentatively then it may be held that in case
of cancers at least the present tendency is not so much to accept the
existence of a specific parasitic cause for the growth as to believe
that once established as an independent focus of growth by some
such method as is suggested in Ribbert's isolation theory, the epi-
thelial cells become themselves, as it were, practically parasitic in
the organism of which they were once an integral part : that they
grow as parasites and act as parasites : and that the body reacts to
their presence as it does to other parasitic organisms, and endeav-
ors (sometimes successfully) to produce cytolytic or other protec-
tive reactions which will tend to destroy the cancer cells. This
view opens an attractive and wide field for application in many lines,
not merely therapeutic, and suggests reasons which may explain
the special prevalence or special failure of secondary growths in
different systems and organs of the body, as it may be supposed
that all parts are more or less open by the lymph or blood streams
to the reception of secondary tumor emboli.]
All other contributions dealing with cancer parasites (cancer
bacilli, blastomycetes, etc.) recognized by microscopic methods have
originated from mistaken interpretations of the microscopic pic-
tures presented in various examples.
400
Tumors.
The dissemination of the cancer into the tissues, as above indi-
cated, occurs primarily from the penetration of the multiplying epi-
thelium into the lymph spaces. They here form tubular or solid
laminated cords, push aside the endothelium and other connective
tissue elements, and by continuous progression of growth force their
way deeper into the tissues, between the muscle fibres and beyond.
In this way, for example, a growth on the surface of a mucous
Fig. 118.
Lung of dog with metastatic cancer nodes (tliyroid cancer).
membrane forces its way through the muscularis mucosa and onward
into the muscular tunics and serous coat of the tube. In the lymph
passages, by continuity of growth the cords of cancer cells may
extend as far as the nearest lymph glands ; or individual cells loos-
ened in some way may be carried by the lymph current to the latter
and to more distant portions of the lymphatic system. Multiplica-
tion of the tumor cells in the tissue of the lymph nodes, and the re-
active inflammatory proliferation of the connective tissue of these
Cancer. 401
structures, lead to marked chronic enlargement of the glands
(lympJwgciioiis cancer metastases), one of the clinical character-
istics of the cancerous affection. Passing from the lymph glands
the cells of the growth may hy following the course of the efferent
lymph vessels, pass into the blood (anterior vena cava) ; or they
may gain entrance to the blood by direct penetration of the blood
vessel wall in their growth. In either event the cells are carried
onward with the blood stream and form new foci wherever they
may lodge in the capillaries and give rise to the formation of nodes
(hcrmatogeiious, eiiibolic cancer metastases).
]\Ietastatic nodes are as a rule round, and multiple or dissemi-
nated because the cells have been widely scattered through an ex-
tensive area of vascular distribution. As a rule they are first sit-
uated in the lungs, because the cells are very likely to penetrate
into a vein and be carried throiigh the right heart and into the
lungs ; in case of primary cancer of the stomach, intestine or pan-
creas the liver is apt to be involved, by convection through the por-
tal vein. Should isolated cells pass through the pulmonary capil-
laries and get into the general circulation b}- way of the leff heart,
other portions of the body, as the spleen, kidneys or bones, may be
involved by dissemination of the metastatic cells. Sometimes, too.
when these cells .penetrate into bloodvessels they grow into cord-
like processes along the vascular lumen ; solid plugs of cancer cells
as thick as lead pencils may occasionally be found extending in
the thyroid veins from a cancer of the thyroid gland, even down
into the thoracic cavity. The vascular lumen becomes more or less
obstructed and the secondary thrombi formed are verv likclv to be
invaded by the cancer cells.
As the tumor enlarges it compresses and pushes aside all the
elements of the organ with which it comes in contact ; in their pene-
tration into the deeper tissues and by their lateral extensions the
cellular roots of the cancer distend and occupy the lymph spaces,
pushing aside whatever gland-tissue, muscle or nerve may be
present, spreading out beneath the epithelial covering of mucous
membranes or integument and perforating layers of epithelium which
they may encounter. Pressure atrophy and necrosis of the surround-
ing tissue and tissue-destruction from the accompanying inflamma-
tion result from the cancerous infiltration, even hard bone and
cartilage, perhaps, being broken down by these changes. As the tu-
mor tissue nniltiplies beneath the epithelial la\ er of a surface it raises
it up, spreads out in larger and larger area close to the surface
402
Tumors.
and develops in nodular prominences. By cropping out on the
surface, by perforation at one or more places of such a protuber-
ance, it ma}' become a direct surface growth with nodulated, uneven,
undulating elevations and more or less fissured surface. The in-
flammatory infiltration of the stroma, exaggerated by the entrance
of extraneous irritants into the exposed growth (contact with air,
intestinal contents, dirt or bacteria), is likely in such event to bring
about an ulcerative, foully suppurating destruction of the surface
of the cancer (cancerous ulcer). In case of penetration into asep-
tic cavities, especially the peritoneal (gastric cancer, cancer of the
Fig. 110.
Cancer of tail of cow.
intestine, cancer of kidney), transplantation of epithelial cells loos-
ened from the growth may be brought about by the intestinal peris-
talsis (by movements of the lungs, diaphragm and heart in the
chest) and give rise to extensive secondary carcinomatosis in the
serous membranes by their growth. The secondary formations are
at first small grayish-white nodules (iiiiliary carcinomatosis), but
later, by confluence of the enlarging cancerous foci and the accom-
panying inflammatory changes, a diffuse cancerous peritonitis or
pleuritis may be established.
The morphology of the epithelial cells of which a cancer is com-
posed corresponds in a general way wifli that of the epithelium
Cancer.
403
from which the tumor took its orig-in ; in a greater or less measure
the cancer cells preserve the peculiarities of the epithelium of the
place of inception, -as a tendency to kcratinization, to formation of
mucin and other secretory substances. This retention of original
characteristics, which is well seen in the metastatic nodes, often
makes it possible to determine from microscopic examination the
primary source or origin of a cancer. This is, however, often sub-
ject to modification. The growth of epithelial cells in unfamiliar
positions, their separation from their normal substructures, must
directly, because of the altered nutritional conditions and the vari-
ous factors of tissue resistance, occasion variation in their
shape and size. In consequence we often ^neet with morphological
variations and anomalies which differ so widely from the original
Fig. 120.
Cancer of glans penis of horse.
characteristics of the mother cells, that it may be quite impossible
to come to any conclusion as to the source and type of the tumor
from the morphology of its individual cells. In addition to this
polymorphism of the cancer cells there may also occur one or other
of a variety of retrograde metamorphoses in the luxuriantly growl-
ing and irregularly nourished cells, rendering them completely un-
recognizable ; so that at times the real character of the cellular ele-
ments can be made out only in the more recent parts of the tumor.
Corresponding to the major types of cutaneous, mucous mem-
brane and glandular epithelium, three classes of cancers may with
Diirk be recognized :
I — Surface cell cancers of the skin and mucous nuvnhranes cov-
ered -with flat epithelium (called brietly by most authors squamous
epitheliomafa.)
404
Tumors.
2 — Surface cell cancers of nnicoiis meuihranes covered with cyl-
indrical epithelium (cylindrical cell cancers).
3 — Glandular cell cancers [carcinomata].
Squamous epitheliomata, originating from the skin and mucous
membranes covered with squamous epitheUum, manifest their epi-
theUal proHferation by forming soHd cords of cells penetrating the
deeper tissues, these cords for the most part made up of cells of the
type found in the stratum ^Nlalpighii. The prickle and ridged borders
of the cells, the protoplasmic processes extending through the in-
Fig. 121.
Secondary carcinomatosis of serous surface of liver and omentum of horse ;
primary growth of cancer in the ovary.
tercellular cement (so-called intercellular bridges) are usually well
marked, and the cells are arranged in layers as over the papillary
layer of the cutis ; and in consequence we usually find' the cells next
to the stroma of the tumor of a cylindrical form, the next layers
cubical, and the inner parts of the cord occupied by squamous cells.
The epithelium in its growth has no opportunity for desquamation
in these connective tissue spaces, and the old and first formed layers
must necessarily be found in the central part of the plug-like cord ;
being derivatives of epithelium subject normally to keratous
change, the cells of a squamous epithelioma usually also undergo
Cancer.
405
keratinization, and here, to(\ the change affects the older cellular
elements. The interior of the cancer roots show these fiat cells,
homogeneous and staining diffusely with eosin or fuchsine, with
their nuclei poorly shown or entirely lost, precisely as those of the
surface of the epiderm. In consequence on cross section an onion-
like concentric lamination of the cells is apparent, with the cells
bent in crescentic manner and applied upon each other like flat
Fig. 122.
Microscopic section of a sqiiainons epithelioma of urinary lilaclder of cow (low
power). Epithelial cords have grown in between the saiootli muscle fibres.
scales. These horny plugs can sometimes be picked out entire with
the knife and are called cancer pearls ["pearly bodies," "squamous
cell or concentric nests"]. The arrangement of layers otherwise
is apt to be quite irregular, the composite network of epithelial
roots forming at places broad, thick masses with wavy outline, at
others delicate, line-like threads.
The stroma of the squamous cell cancer, present in varying pro-
portions in dift"erent cases, is usual!}- the seat of a marked round
4o6
Tumors.
cell infiltration, a true inflammatory infiltration; and the wandering
cells may be found penetrating even into the epithelial plugs.
In cylindrical cell cancers the cylindrical epithelium, extending
in its proliferation into the deeper tissues, laterally and, together
with its connective tissue, also superficially, usually forms gland-
like tubes which branch out in different directions as narrow or
wide hollow oft'shoots. The proliferating columnar cells may re-
Fig. 123.
Microscopic section of a siiiiamous epithelioma of glans penis of liorse.
main in a single layer or become stratified, in the latter case under-
going various changes in shape corresponding with the prevailing
pressure conditions, goblet cells peculiar to the mucous membrane
often being met in great numbers.
Glandular cell cancers, as far as the morphology of their cells
is concerned, are as varied as the types of cells in the different
glands of the body. As in adenomata, in these growths the specific
gland tissue repeats itself in tumor form. The retention of the
Cancer.
407
tubular arraugement of the cells, and the simple (one layer) lining
of these tubes may so well preserve the gland pattern that the name
adcno-carciiioiiia has been applied to these and to the tubule-forming
cylindrical cell cancers. The resemblance to the original gland may
be so great that not merely the morphology of the most of the tumor
cells remains unchanged, hut even the production of secretory sub-
stances in the tumor tissue is distinctly analogous. Thus hepatic
cancers have epithelial cells of precisely the same type as the polygo-
PI
S~4^^
^^^^' v^^-^^
Fig. 124.
Microscopic section (if adenocarcincma of icidney of horse.
nal hepatic cells, arranged in anastomosing trabecular columns, with
capillaries and scanty connective tissue extending between them ;
and these epithelial cells secrete bile, the tumor sometimes being
stained an intense yellow or green color from the latter. Thyroid
cancers, made up of low. cubical, thyroid epithelial cells and a vas-
cular stroma, show as a rule a practical duplication of the structure
of the thyroid gland in the production of colloid material and in
the alveolar distension of their epithelial ofifshoots. Cancers of the
intestinal glands repeat the tubular invaginations of the Lieber-
4o8
Tumors.
kiihn's crypts with of course considerable enlargement of the lumina,
and are characterized l)y marked production of mucin and by the
presence of numerous goblet cells among the lining epithelium.
Mammary cancers have so marked a tendency to *fat formation from
their cells arranged in alveoli, that milk-like fluid is usually found
filling the tubular cancerous spaces ; and ovarian cancers undergo
the formation of cysts which might well be mistaken for the
follicles.
^ <i / f^y
xJ
'9i>
''■■'^■.
1
^;\i':i$
h
<5»0
#
Fiji
lu.J.
Hard adenocarfiuoma of mammary gland of a Ijitcli ; shows the predominance of
the connective tissue stroma, the preservation of duct and acinous arrange-
ment of epithelium (as at a), but also the irregular and excessive epithelial
formation of solid cords and infiltration of tissues by their penetrating
anastomoses (as at b).
The same structure, too, is repeated in the metastatic nodes in
the lungs, peritoneum and elsewhere, proving their derivation from
the primary tumor and its original source.
This correspondence in cellular character between the carcinoma
and the gland from which it originated is, however, not always ap-
parent, the atypical nature of the growth manifesting itself in the
extension of the cells beyond their normal limiting membranes,
Cancer. 409
their dissemination in the surrounding tissue and their metastasis,
and in the fact that the epithelial outgrowths do not form com-
pletely hollow passages, but are seen in massive proliferation as
solid cellular roots. The ducts of the involved structure are filled
with epithelium, and Uie cells show a great variety of altered shapes
depending upon the pressure conditions prevailing, fusiform,
rounded, irree:ular. etc. The connective stroma varies much in its
degree of development, and is sometimes found in villous masses, in
folds and laminated processes just as in adenomata, especially when
there are spaces and large cavities in the tumor {cyisto carcinoma
papular e).
[The essence of the histological fault of any cancer lies in the
fact that in its proliferation the epithelium of the tumor does not
maintain its normal topographical relations, but grows tlirough its
limiting membrane and is found infiltrating to a greater or less
desfree the tissue about it, either as isolated cells or as roots or cord-
like groups of cells. In most cases, too, increase in the amount of
epithelium is recognizable not only by this infiltrative or metastatic
excess but by an excessive number of cells upon the surface in-
volved, or within the tubular spacer or the alveoli of the afifected
portion of the gland ; thus instead of a single layer of cells lining the
tubular canals of a cancerous area of endometrium, it is common
to find a number of layers and the tubules distended and branched
as the author above indicates. This excess, however, is by no means
an essential feature, many scirrhous carcinomata showing a mani-
fest reduction in the epithelial elements below^ that realized as nor-
mal to the original gland and to the ordinary cancers of the
same organ ; and in such cases one finds not only relatively few
epithelial areas but also no excess of layers in the tubular lumina,
the cells which do line such spaces being in fact themselves small,
atrophic or degenerative. It will be found, however, that many of
the cells in these have no relations to tubes or alveoli and' are clearly
free in the lymph spaces of the connective tissue stroma; and care-
ful examination of the gland-like spaces or tubes will somewhere
show the direct gro\vth of the epithelium into the surrounding
tissue beyond the proper membrane. The existence of karyokinetic
nuclear figures is of some value as indicating the active prolif-
erating state of the epithelium.
. The editor believes that for practical purposes in microscopic
diagnosis of cancers of the author's two varieties, cylindrical cell
and glandular cell cancer, it is appropriate to recognize two types
according to the existence or non-existence of marked resemblance
^
410
Tumors.
to glands. Those cancers which exhibit a distinct tubular or acinous
structure (from which, however, the deviations just indicated are
evident) are adciiocarciiwinafa. All of the types of cancer here
under discussion may be said, at least in their early period, to be
adenocarcinomata. Those in which the proliferative and infiltra-
tive processes have so advanced as to destroy the original gland
resemblance, so that definite tubes or acini are not well or numer-
ously recognizable, may well be called carcinoiiia simplex. These
merely represent more advanced stages of the first, and. are more
common as actively growing and extending cancers.
The stroma of true cancer, as the author remarks, is exceedingly
variable and is often the basis for special sub-divisions of the
growths. Thus it may be relatively small in amount, the epithelial
elements predominating ; this condition underlies the group of soft
cancers (medullary cancers). Or it may be greatly in excess,
markedly predominating over the epithelium of the growth, dense
and fibrous ; such growths are the well known hard cancers or
scirrhous cancers (substantive scirrhns). The connective tissue
stroma may exceptionally be found largely or totally of a gela-
tinous type {carcinoma myxomatodes) ; or highly cellular and evi-
dently of a sarcomatous type {carcinoma sarcomatodes). Other
types of connective tissue may also be encountered in varying
amounts in the more highly mixed cancers.]
TJic cvternal shape and other macroscopic characters of cancer
vary with the location of the original growth, the structural con-
stituents of the tumor and the age of the neoplasm. Cancers de-
veloping on the free surfaces of the skin and mucous membranes
[squamous epitheliomata, surface adenocarcinomata^ often appear
as cancerous ulcers. The infiltrative growth causes a thickening
of the membrane, with the [ulcerated] exposed surface uneven
with nodular prominences, suppurating, red or dirty dark brown,
and perhaps covered with crusts, with the base and wall shown
in cross sections as a more or less defined growth and as a light
gray bacony zone often penetrating by root-like extensions into the
deeper tissue. The normal epiderm is usually sharply defined along
the border of the ulcerating exposed tumor surface. In mucous
membranes, as the urinary bladder, cancer often forms merely super-
ficial, undulating, slightly elevated thickenings [flat tabular swell-
ings], recognizable from simple inflammatory changes by the
accompanying enlargement of the lymph glands, the infiltration of
the growth into the muscular layers and by the definition of the
Cancer.
411
Sfravish-white medullarv tumor tissue sccu in cross sec-
tion. Of course the microscope affords the coiichisive diagnosis.
These surface cancers may also develop into cauliflower forms
Fig. 126.
Cancer of gum (squamous epithelioma) of liorse.
(carviol), masses of a light gray to more reddish hue, growing
from the surface of the skin or mucous membrane, the surface sub-
divided and overlaid by a suppurating, ichorous, pulpy mass of dis-
integrating cancer tissue.
412 Tumors.
In the interior organs cancers form nodes of widely varying
dimensions, sometimes sharply circumscribed and rounded, or with
their tissue gradually merging by infiltrative extension with that
of the synchronously enlarging organ. The whole organ, as a
kidney, may be incorporated into the tumor tissue, and in its stead a
shapeless mass of cancer is met weighing perhaps from one to
fifteen kilograms. The tendency to perforate to the surface of the
involved orgfan is a marked characteristic of cancers. Another
peculiar feature is the production of cancer umbilication, seen
rather irregularly in the smaller nodes [secondary nodes] about
to perforate through serous surfaces ; it is a central depression
seen in these nodes due to the prominence of the marginal
growth and destruction of the interior of the node. On section
of cancers a milky fluid or juice, briefly known as "cancer milk,"
may frequently be obtained by scraping the cut surface or may be
expressed in drops by compression with the fingers ; upon micro-
scopic examination it is apparently almost entirely composed of the
epithelial cells (with fatty degenerative changes) of which the
cancer is constructed.
The secretion of mucus and of colloid substance, as seen in
adenocarcinomata of mucous membranes and follicular glands
(ovary, thyroid) and the retention of these materials in the tumor
tissue sometimes gives an unusual softness and transparency to the
cancerous growth, the name gelatinous cancer being often used in
connection with such examples. [The term colloid cancer has, from
confusion, 'been employed indiscriminately in these cases. Colloid
cancer, using the term in its strict sense, is practically confined to
the thyroid gland, and even there much of the gelatinous material
contained in it is not definitely colloid, but rather mucoid. The
use of the term colloid for these gelatinous cancers in other situa-
tions of the body (stomach, intestine, ovary, etc.) is almost sure
to be wrong; the change really being a collection of some type
of mucin within the epithelial cells and perhaps also in the tissue.
The cells which in older text books are described as "colloid seal-
ring cells" are really nothing but mucoid goblet cells, quite like those
found in a catarrhal mucous surface, but modified by pressure so as
to have a rounded shape, flie mucin in their interior pressing the
nucleus and a part of the cytoplasm to one side so as to form the
prominence compared to the seal of a ring.] On the other
hand some cancers come to be very dense and cicatricial in consist-
ence in case the associated growth of their connective tissue should
be unusually marked in quantity, jn density of fibrillation and in-
Cancer. 413
durative. The epithelial elements in such examples may become
very unimportant structural factors; these hard specimens arc
known by the names scirrhus. scirrlious cancer.
According to statistics compiled by Casper, Frohner and Sticker,
cancers [among animals] are most frequent among dogs (three
per cent.) ; horses rank next in order, and after them cats.
Just as in man cancer in animals is a disease developing principally
in middle and later life. This is probably the reason for the in-
frequence of these tumors in cattle, sheep, goats and swine, such
animals not attaining an advanced age because of their use for meat
supplv. The skin and its junctions wdth the mucous membranes
are the most frequent seat of growth [for squamous epitheliomata] ,
anal cancer in the dog and cancer of the glans penis, gums
and lips in the horse being frequently met with. The mammary
glands and thyroid gland of the dog are comparatively frequent
points of primary involvement [adenocarcinoma or carcinoma sim-
plex according to the degree of atypical structure to which the
growth is advanced].
In human beings cancer of the stomach and of the female uro-
genital organs constitute a high proportion of these growths; in
animals these organs are afifected by cancer to a far less degree.*
As far as the rest of the body is concerned it may be said that pri-
marv cancer has been observed in all the epithelial organs. In
structures which do not possess epithelial cells (lymphglands, mar-
row, spleen, muscles, etc.) cancer can occur only in metastases (in
rare exceptions also from embryonal germinal misplacements).
Such metastatic growths sometimes become of greater bulk than
the primary tumor, especially those of lymph glands. f
The general peculiarities of cancerous growths, their irrepressi-
ble penetration into the tissues in every direction, the difficulty of
thorough operative removal of all their roots which is only occa-
sionally successful in the early stages of the cancer and if incom-
' pletely accomplished invariably results in recurrence, the destruc-
tion of the affected organ and the certainty of metastasis, stamp these
tumors as highly malignant autoblastomata. In the course of the
cancerous affection, the severity of which is determined by the rap-
iditv of dissemination and the location of the growth and the impor-
tance of the tissue involved, there usually develops a condition of
* For details see esp-cially the statistics of Sticker, ArcJiiv. f. Kliiiisch. Chir-
itrgie, Bd. 6.5, Berlin, 1901'.
t If the primarv growth has been removed by operation and this fact be
nnknown to the examiner, or if the scar at the affected place be oyorlookech the
secondary formations mav give the erroneous impression of being primary tumors.
414 Tumors.
general emaciation, anaemia and bodily weakness, known as can-
cerous cachexia, due at least in part to the reaction upon the
system by toxic products formed in the cancerous tissue.
[The cachexia of cancer is of course induced the more early and
markedly in case the cancer involve some of the organs of nutri-
tional importance to the- animal, as the alimentary tube or pancreas;
the faults of nutrition being important contributors to the produc-
tion of oligaemia and loss of flesh and strength. The idea of toxic
factors, although usually not urged by writers because of our ig-
norance, is, however, probably an important one, these toxines aris-
ing from the secretory activity of the tumor tissue or as products
of tissue metabolism or destruction. The metastatic tendency, in-
volving the progressive affection of more and more of the body by
cancerous foci, must of course be an important factor of malig-
nance. The occurrence of metastases varies greatly with the type
of the tumor and with the definite resistive power which the body
exerts against these practically parasitic cells, this resistance being
apparently not at all uniformly possessed by the various organic
systems or by different individuals. In a general way it may be
said that the squamous epitheliomata are likely to disseminate more
slowly than the other varieties, progressing more regularly by a con-
tinuous invasion of the lymph spaces and channels, and therefore
showing a greater tendency to local and neighboring infiltration and
node production. Distant metastases are to be met with but are not
as frequent as in the cylindrical cell and glandular cell cancers. Of
the latter groups in a rough way, to which exceptions are common,
it may be said that those that manifest in their structure the great-
est departure from the tubular and acinous types (carcinoma sim-
plex) are those showing the more rapid and extensive metastatic
tendency ; the adenocarcinomatous forms the less. Both are, how-
ever, more apt to give distant metastasis than the squamous cell
form. The condition of the stroma makes a difference as well, the
soft medullary types with a small amount of stroma being more
metastatic and the hard scirrhous varieties tending to remain local
for a longer period. It is said that cancers as a group are char-
acteristically generalized by way of the lymphatic system, in contrast
to sarcomata which are more frequently conveyed by the blood cur-
rent. This is, in the main, true, and the usual rule is to find the
lymph glands into which the lymph drainage of the cancerous part
passes the seat of secondary cancers. Yet it is by no mean? neces-
sarv. The route of metastasis and in a great measure the tendency
Epithelial Cysts. 415
to give rise to metastasis are explicable on meclianical grounds.
The cells of squamous epitheliomata are usually large cells and are
less easily displaced from their site of formation than many of the
smaller cells of the cylindrical cell and glandular types of cancers ;
and as a group all epithelial cells are larger and less easily dis-
placed than the small round cells of small round cell sarcoma. These
last mentioned growths have cells comparable to the small lympho-
cytes which are always and readily passing with the blood through-
out its entire capillary system. It amounts therefore to the general
rule that, whatever tumor cells may be able to gain entrance to some
small capillary blood vessels in the tissue in which they are growing,
the sarcoma cells have a better chance of convection than do the
epithelial cells. On the other hand sarcomas in their growth, direct-
ly from and in the connective tissue structures in which the blood-
vessels are distributed, are more favorably situated as early tumors
to gain access to these vessels than are the epithelial cells, which
primarily are separated from the blood stream not alone by the ves-
sel walls but by more or less connective tissue and by remnants, at
least, of a membrana propria. In their mode of growth cancers
primarily are more likely to gain entrance to the lymph spaces an 1
channels, and are therefore from the first more favorably situated
to follow this system provided the spaces and channels are of suf-
ficient calibre to allow the convection of the epithelial cells (as they
usually are, in comparison with the minute blood capillaries). Yet
granting such factors as these, as determining the usual course and
occurrence of metastasis, exceptions must arise and are constant'y
being seen. If a sarcoma grow in lymphatic tissue (a lymphosar-
coma for example) it is very likely, whatever the size of its cells,
to follow the lymph current to the neighboring nodes; and if in
some situation (as in stomach or intestinal wall where the larger
radicles of the portal vein are close to the cancerous growth start-
ing in the mucosa) the cancer cells be afforded easy access to
bloodvessels of sufficient calibre to accommodate their size they wiU
be found to give rise to hsematogenous metastasis (as the portal
convection of gastric cancer to the liver).]
Epithelial Cysts, Dermoid Cysts, Odontomata, Mixed Teratomata.
There are a number of tumor-like formations which, as hollow
epithelial lined sacs, limited to their place of development, originate
from embryonic cellular misplacements. These are cysts ( v kv<ttis.
vesicle) which arc not jiroduccd from mature glandular organs
41 6 Tumors.
fmm simple retention of their contents and dilatation of their
canals and are not formed in the loose structures of the body from
exudation into them or from liquefaction of the tissues themselves,
but take their inception in early embryonic life from displaced and
isolated portions of organs, organic rests and hollow ofifshoots of
such structures, and acquire an independence of growth.
The simplest type of these cysts is the epidermoid cystoma or
epithelioma cysticum, a sac of the size of a nut, a hen's egg or even
of a fist, which is completely filled with loosened squamous epider-
mal cells almost all in a keratous condition; sometimes cholesterin
is found mixed in with these. Bonnet met a genuine example of this
type in the cranial cavity of a horse. All these cysts containing
squamous epithelium doubtless originate from ectodermal cellular
inclusions in foetal life, conceivable as occurring from friction of the
skin by amniotic strands. Their occurrence in the cranial vault, near
the aural and temporal region, suggests that displaced portions of
the epithelium of the branchial arches constituted their original sub-
stance, and in case of those developing in the brain, from the med-
ullar}- folds, the ectoderm must certainly play a part in their
origin. Experimental studies by Schweninger, E. Kaufmann and
Ribbert show that epithelial cysts can be readily produced artifi-
cially by insertion of a bit of epiderm, conjunctiva or tracheal mu-
cous membrane into the peritoneum or under the skin. When the
epithelial cells are supported by a little connective tissue to preserve
their nutrition they grow over the interior surfaces of the wound
with which they have been placed in contact, and form the lining of
the hollow space, the latter being occupied by the wound secretions
and desquamated epithelium. Epithelial lined cysts may also be
produced, as pointed out by these authors, by suturing over a cir-
cumscribed bit of epiderm the adjacent loosened borders of skin;
the bit of epiderm beneath the sutured parts grows and fills in the
space beneath the elevated cutis (Ribbert). In man as the result of
accidental misplacement of epithelium in operations, or of cutaneous
lacerations, similar cyst formations are well known to occur. Such
results are known as traumatic epithelial cysts.
As derivatives of the skin in its entirety, of the cutis with its
glands, of hairs and epiderm, may be mentioned the dermoid cysts
or hair follicle tumors (dermatocystis congenita or cystoma der-
moides), which occur comparatively frequently in cattle and horses,
situated in the subcutaneous connective tissue. They appear from
the exterior as flat cutaneous swellings or may be found acci-
dentally in skinning or eating beef. The cyst varies from the size
*
Dermoid Cysts. 417
of a nut to tliat of a fist, is rounded and liUcd with a hunch of
tang-led hair and a (hrt\ l)ro\vn fluid consisting of secretion fnjui
the sweat-glands, fat and desquamated epithelial cells. The wall
of the sac. which may be easily shelled out of its bed, is thin, quite
like the iibrous structure of the cutis, and lined on the inside
with cpiderm and attached hairs, loosened hairs occurring in the
contents as free bunches. .Microscopically the wall has all the
appearances of the cutaneous structure. These dermoid cysts are
met particularly in the region of the neck and jaw, generally
developing in these situations from tissue derived from the
branchial arches (braj!chi(\Q:ciioiis cysts) ; they are also met about
the shoulder or elbows, in which cases they may be referred to
faults in the development of the anterior liml) bud (Leisering.
Johne. Grams and others), in the umbilical region, and in the
testicles and ovaries.
As earlv as 1854 Remak explained the origin of dermoid cysts
bv conceiving an al)normal development of the arches and resultant
enclosure of a bit of the germinal epidermal layer as their basis ;
and it mav also be possible that injuries caused to the skin in the
region of fissures may give rise to them, provided the borders of
the fissures become the seat of a cicatrizing proliferation and.
further, provided the base of the skin fissure becomes isolated and
brought to lie underneath the scar.
The dermoid cysts of birds contain feathers ( fcalhcr-folliclc
cysts, cxstonia pcuuifcruni ) and are found from the size of an egg
to that of a fist within the abdominal cavity of geese. UK^re rarelv in
ducks and chickens. The cyst, surrounded by a thick layer of fat,
is sometimes free in the ])eritoneum or may l)e attached by a peri-
toneal fold to the ovary and lumbar region. The number of feath-
ers (the plume not unfolded because wet with fluid) may reach
several hundred.
Analogous to tlie dermoid cyst but not growing in cystic form, and
appearing as protruding islands of hairy skin, are the dermoid fcratoinata
of the cornea (also of palpcbra tcrtia). which are met comparatively com-
monly in cattle and dogs. They are congenital anomalies and originate
from a misplacement or transplantation in the formation of the palpebral
fissure.
In the same way as from the epidcrm and cutis cystic foci ma_\-
arise from separation or misplacement of their cells, epithelial
lined cysts may also develop from the mucous membrane
tubules and glandular ducts in embryonic life from budding or
other anomalies of development, particularly from "rests" of
4i8
Tumors.
gland tissue (adenocystoma). These entodermal cysts are lined
by columnar epithelium, sometimes ciliated, and in man are found
in the liver, intestine or peritoneum, in the neighborhood of the
trachea and bronchi, and in the neck, var\ing- in size from that
of a pin-head to that of an adult human head. In animals they
most usually arise from rests of the original urinary structures,
Fig. 127.
Cystic kidney of hog (section).
the Miillerian or AVolffian ducts, and are found as transparent
vesicles of the size of a millet seed or pea or sometimes larger,
along the broad ligaments of the uterus, in the fimbriae of the
oviduct, and in the epididymis. The congenital cysts of the
ovary, occurring as single or multilocular and closely packed
cysts of this organ, and containing a thin mucoid and sometimes
bloody material, are further examples of the same type. Con-
genital cysts of the kidney are also regarded as results of devel-
opmental disturbances, converting the kidneys, usually bilater-
ally, into a grape-like mass of vesicles with watery contents,
between which an inconspicuous amount of parenchyma is found
reduced mainly to thin connective tissue septa (cystic kidneys,
vesiculated kidneys). This anomaly is supposed to be due to a
failure of union between the uriniferous tubules and the develop-
ing glomeruli, these two parts growing separately (Ribbert).
The term odontoma and odontohlastoma are applied to mon-
Odontoma.
419
strous tooth-formations, which arise from faults in the embry-
onic development of dental suijstanccs and present themselves
either as excrescences on the teeth, of bone-like hardness and
composed of cement and dentine, or as abnormities in which an
entire tooth has been changed into a shapeless, nodular form
with enlargement; or in which in combination with an accom-
panving proliferation of the soft connective tissues a compound
dental tumor has been produced. These neoplasms arc always
congenital, either becoming apparent at the time of the eruption of
the tooth or the teeth fail to erupt and a tumor slowly develops
in the alveolar portion of the jaw beneath the gum, bulging the
latter and expanding the bone as it enlarges within the alveolus.
The composition and form of these odon-
toblastomata var}' considerabl\- with the
part taken by the different tissues con-
cerned in embryonic tooth formation, the
dentine and its covering of enamel, the den-
tal sac and the peripheral alveolar bone.
The simple odontoma durum, now and
then seen on single teeth in the cow and
horse, occurs as a mass about the size of
a nut, rounded, hard as bone, and usually
surrounding the crown or niore rarely the
root of the tooth. In other instances, as
observed by \Xe6\ and ^^lagitot. the whole
tooth lying within the alveolar process is
changed into a mass of bony hardness as
large as an orange or possibly weigh-
ing as much as a kilogram. The name
odontoma mi.vfum is applied to a growth composed partly of
fibrous tissue, bloodvessels, odontoblasts and agglomerated tooth
papilL-e, with the hard parts in rudimentary unshaped masses of
dentine and enamel over the surface or mixed in the interior.
Sutton has met with a mixed growth of this type weighing seven
hundred grams in a horse. Similar tumors, sometimes only
enclosing in their structure a single hard rudiment of a tooth, or
sometimes containing a number, possibly several dozen, mis-
shapen or fairly well formed teeth, occur as cysts or bunches
of cysts, completely included by fibrogelatinous dental sacs and
alveolar bone capsules (odontocystoma capsulars cystoma dcnti-
fcrum alveolare). In other instances the proliferation of the
bony capsule is especially marked, surrounding the dental sac-
Fig. 128.
Odontoma of incisor tooth
of cow (natural size).
420
Tumors.
cular tumor and the deformed tooth, and giving- rise to the type
known as osteocystoma capsiilare dcntifernm. Occasionally in
young horses at the base of the ear over the temporal bone cysts
may be found which contain one or several imperfect teeth,
usually opening by a fistulous sinus upon the skin ; these are
blind tubular invaginations from the skin, lined with mucous
membrane and provided with a bony covering or with small
bone platelets in simulation of the alveolar process of the jaw;
they originate from the branchial arches and are known as
Fig. 129^
Odontocyst of lower jaw of cow.
Fig. 130.
Osteocystoma dentiferum of liorse.
branchiogenoiis dental foUicidar cysts {odonto-temtoma bran-
chiale, odontocystis braiichiogcnetica).'^ This type of cysts is
only rarely met in other animals; Siedamgrotzky encountered
two dental cysts in the ethmoidal turbinate in a hog; Verwey has
recorded one in the petrous portion of the temporal bone in
a dog; Hertwig met a dental cyst in an ox.
Teeth are sometimes found in dermoid cysts and teratomata
in other parts of the body, especially in this type of growth in
* For fuller description v. Kitt, Lehrbuch der pathol, AnatonUe der Haustieve,
Stuttgart, F. Euke's Verl. II Aufl., 1901.
Doiti^crous Cysts. 421
the ovary and testicle [heterotopic odontoteratomata). Gurlt
recorded a testicular tumor of a horse, about the size of a fist,
of stony hardness, containing six molar teeth (three separate,
three merged together), together with thin plates of bone repre-
senting a rudimentary alveolar process, and a fibrous capsule;
in a second instance the egg-sized tumor contained, besides a
single tooth, a lot of hair and a fiuid material made up of a
mixture of perspiratory and sebaceous material.
In addition to the above cysts and dentigerous tumors there
occur, especially in the sexual glands of both sexes, a number
of other tumors of complex composition, sometimes showing an
irregular mixture of heterogeneous tissues of all three embryo-
blastic layers, sometimes a definite tissue arrangement repre-
senting clearly the structure of a number of organs. Because of
their close relation to monsters the collective names teratoma or
emhrxoma are used in connection with these peculiar formations,
which undoubtedly originate from embryonal cells or tissues
which have been segregated and become independent at an early
developmental period.
The external tumors of this type, growing in the superficial
tegumental tissue or in the mouth, are possibly the results of
partial cleavage from amniotic threads, as it is known that
indentation of an embryonic tissue can cause its division and
double development; and even transplantation may be effected
from injuries caused by amniotic bands. These external tera-
tomata usually appear as tumor-like, pedunculated formations,
of lobulated outline, and are composed of hairy skin, rudimen-
tary jaws with teeth and mucous memlDrane covering, fat tissue,
nerves, muscle and glandular structures. (For illustrations and
details v. E. Sigl, Monatshcft f. pr. Tierheilknnde, Stuttgart.
1902.) The compound teratomata developing in t}ie interior of
the body, especially in the ovary and testicle, may sometimes
originate from germinal segregations from the primitive seg-
ments of the vertebral column or from the indifferent cells of the
Wolffian body; or it is possible, as Marchand's theory would
make plausible, that they may arise from the separate develop-
ment of one segmentation cell. According to the experimental
studies of Roux and others each one of the primitive segmenta-
tion products of the ovum— that is, each segmentation cell— is
capable of producing an entire embryo; thus the possibility
arises that an isolated segmentation cell in course of progressive
development may form a group of embryonic tissues, which be-
422 Tumors.
cause of irregular nutrition succeed in their later growth in
forming only an amorphous body of all sorts of organic struc-
tures mixed together. This, it is likely, enclosed within the indi-
vidual formed from the other segmentation cells, remains without
further development, as a tumor. []\Iany of the so-called ovarian
dermoid cysts met in human beings are properly of this last
type, complex teratomata, frequently containing tissues evidently
from two or all three of the embryoblastic layers. It has been
suggested in addition to the above explanations for such terato-
mata in the sexual organs that they may be the result of seg-
mentation and development of an unfertilized ovum directly
within the ovary, a parthenogenetic development. This idea has
no wide acceptance, but it should be recalled that partheno-
genetic development is well known in many lower forms of life,
and that Jacques Loeb has succeeded in causing the development
of unfertilized ova of sea-urchins by chemical stimulation. It
should be added moreover that L. Loeb (Archir. f. uiikrosk.
Anat. It. Eutzi'icklungsgeschicht. Bd. 65, 1905) has demonstrated
kar3'okinetic changes and segmentation of the ovum in the ovary
of the unfertilized guinea-pig. The theoretical possibility of this
mode of origin of ovarian teratomata should therefore be accepted ;
although evidence of its actual prevalence is not clear.]
FUNCTIONAL ABNORMALITIES
Nervous Disturbances — Disturbances of Motion.
The nervous system regulates the functions of the organs and
is the intermediary between the corporeal and psychical func-
tions of the polycellular animal organism. The nervous matter
may be excited by both external and internal agencies (stimuli),
and being thus stimulated gives to the tissues the impulse for
the manifestation of the powers peculiar to them. Alterations
in the excitability of the nervous system and abnormal stimuli
which occasion such variations, may result in functional dis-
turbances of the nervous apparatus and the organs dependent
upon it. Where the whole central system is altered, these dis-
turbances are general and may manifest themselves in the widest
possible range (general nervous syinptojns) of abnormal nerv-
ous phenomena (sensory, motor, secretory, reflex). Where
definite localities in the central nervous system are subjected
to injury, we speak of central local involveynent and focal symp-
toms. In this connection, too, nuclear involvement where the
nucleus is affected, is differentiated from supra-nuclear in-
volvement, where the course of the conduction within the
central system — that is. above the level of the nucleus — is
the part disturbed; and according as the focus affected lies
within the brain, in the medulla oblongata or in the spinal cord
the lesion is said to be cerebral, bulbar or spinal. Where a
nerve is injured in its course beyond its point of exit from the
brain or spinal cord to it's area of distribution or wdthin the
latter, peripheral aft'ections ensue.
General Nervous Disturbances. — The brain and medulla to-
gether constitute the central organ presiding over the whole
category of functional activities, and therefore everything which
causes depression or excitation of cerebral activity must of nec-
essity bring about a great variety and general distribution of
disturbances. Every lesion of the deeper centres of the medulla
424 Xei'Z'oits Distitrbaiices.
oblongata, in which the circulatory and respiratory regulative
apparatus are located, must necessarily inhibit or depress these
most vitally important functions and thus threaten life. Lesions
of the cerebral cortex bring about varying grades of disturbance
of consciousness, which, including all phases of mentality, may be
collectivel}' spoken of as psychical disturbances.
The most severe of the ps}-chic paralyses is cerebrospinal
cuiicnssioii {commotio cerebri et meduUcc). After more or less
severe concussion of the head or the whole body by a fall, blow
()r kick, the functions of the brain and cord cease. Anatomically
there is often nothing to be found in such a case, beyond slight
luemorrhagic effusions upon the membranes and the skull, and
gross lesions of the nervous structures are absent. The severe
symptom complex can only be explained by supposing that
through the influence of the concussion waves upon the exceed-
ingl\- complicated mechanism of the nervous system (compres-
sion alternating with stretching force) minute structural changes
nuist be induced, as destruction of the delicate dendrites of the
nerve cells (Krehl).
Cessation of the cerebral function is manifested by complete
loss of consciousness, loss of all voluntary muscular motility,
loss of pupillary reactions, weak pulse and coolness of the exter-
nal surface ; and tends usually, in a few minutes, hours or days
to death. In other and milder instances only a transient loss of
sensibility occurs. When the cord is the main part involved by the
concussion there are met paralysis of the extremities, loss of sensa-
tion in the latter and in the trunk, and disturbances of respiration,
as the principal symptoms. Sudden and usually brief disturb-
ance of equilibrium and inability to maintain an upright posture
(dizziness, I'erti'i^o), associated with loss of consciousness (faint,
syncope), occur from disturbance of the blood circulation in the
cerebral cortex and in the cerebellum ; they niay result too from
trivial grades of general anjemia of the brain, as a decrease in
the arterial supply, and also occur in passive congestion (cardiac
disease, compression of jugular veins) or from anatomical
changes of the cerebellum, aural disease and toxic influences.
In uncomplicated loss of consciousness the cerebral cortex is
alone the seat of involvement ; the animal suddenly begins to go
slowly, stops for a moment, staggefs, leans against the shafts
or other support, turns around in a circle and falls ; then, after
remaining motionless for a few minutes, attempts with labored
movements of the limbs to get up. and is gradually able to rise and
Psychic Disturbances. 4^5
resume consciousness. Sometimes vomiting (in dogs) and invol-
untary discharge of urine and feces ensue.
(For details see Friedberger-Frohner, Veterinary Pathology, Amer.
Ed., 1904. W. T. Keener & Co., Chicago.)
Persistent unconsciousness, coma {to KWfxa, lethargy, from
KOiixdw, to hill to sleep), or sopor {sopor, a sleeping draught), is a
state of insensibility which is met in serious brain afifections,
intoxications (uremia) and particularly in connection with
haemorrhages from the cerebral vessels; in the last when it
occurs suddenly and paralysis results, the process is usually called
a brain or nerrous stroke (apoplexia cercbralis, nervosa:
dKOTr\-n<raeiu, to Strike down). When unconsciousness occurs par-
oxysmally, accompanied by muscular spasms and loss of sensa-
tion it is known as falling sickness or epilepsy { v iTrlXvi^i^ ) ; it de-
pends ui)on some functional disturbance of the cortical centres,
the real cause of which is, however, unknown. Compression of
the intracranial structures, as from blood clots, tumors, increased
pressure of the cerebro-spinal fluid, or collections of exudate,
give rise to the symptoms of compression of the brain (brain
depression). These consist of general dulHng of the senses, a
somnolent, lethargic attitude, staggering and awkward gait and
diminution of sensibility. The animal stands as though deaf,
leans against some adjacent body for support, hangs its head or
supports it against the wall or manger, and the eyelids are closed
as if in sleep and the pupils dilated. The animal may be hard to
move from one spot and may continue for hours at a time in some
abnormal posture (legs crossed or kneeling), or may run about
with staggering gait into the wall and all sorts of obstacles, or
may continually move about in a ring; it is apathetic when
spoken to. touched, whipped, bitten by flies, etc.; takes no food,
or holds its food in the mouth without chewing, pushes its nose
deep into the water in drinking; and may show other special
pressure symptoms according to the particular part of the brain
• affected (reversed movements, riding paces, focal movements,
dancing or rolling movements, or pressing toward one side). In
the man and the dog there are also observed peculiar alterations
of the eye-ground, so-called [choke disc] papillary conges-
tion (really a papillitis, inflammation of the papilla and optic
"nerve); in horses with blind staggers these are not noted
(merely an ansemia recognized — Friedberger-Frohner). These
symptoms depend upon the fact that in the first place in the
426 Nervous Disturbances.
conditions indicated disturbances of the blood circulation arise,
as compresison of the large veins before opening into the rigid
walled sinuses, with resultant stasis, interference with the escape
of venous blood and cerebro-spinal fluid, and the production of
increased pressure upon the brain substance ; that, further, in
the conditions mentioned increased formation of this fluid and
special tissue changes in the brain may obtain, and perhaps, too,
toxic influences (bacterial toxines^ autotoxines).
Psychical excitement has its causative factors in hypersemia
of the brain, cerebral inflammatory changes, heat or toxic influ-
ences, and occurs in a number of difl^erent degrees of severity.
The main symptoms are manifested as attacks of insanity
{mania, delirium fnribundum). The animals in these attacks
suddenl}^ lose their docility, try to free themselves from their
fastenings, bite their owm bodies, make attacks in whatever way
is natural to them (strike out, kick, try to bite), run into obstacles
and violently knock them over, stand up on their hind legs and
throw themselves about with shrill cries, grit their teeth and
froth at the mouth ; the eyes become staring and wild, the con-
junctivae injected; and finally the animals collapse and go into
spasms and convulsions. Especially in dogs of usually aitec-
tionate and lively disposition, well-trained and possessed of
special intelligence we meet with the widest range of mental
disturbances, from melancholia to hallucinations (fancied per-
ceptions), marked confusion and insane outbursts, as in rabies
(depressed stupid condition, snapping at the air, purposeless
wandering about, sudden attacks of desire to bite, tearing of the
animal's own flesh), or in poisoning with deadly night-shade or in
sunstroke. Similar symptoms of excitement are seen in dogs
in the autointoxication produced by the portal blood, that is, the
absorbed products of albuminous decomposition in the intes-
tine, in Eck's fistula [fistula made between the portal vein and
vena cava with diversion of the portal blood from the liver].
Special nervous excitement and reflex psychic conditions occur
in some of the diseases of the genital organs (ovarian cysts,
ovarian tuberculosis, uterine affections, undescended testicle),
the ' affected animals manifesting (uterine, ovarian, orchitic
psychoses) an exaggerated sexual desire (nymphomania, satyriasis,
erotomania, rutting, sexual insanity).
There are, too, a number of vague nervous conditions which
l^ad to perversions of taste (perversions of appetite) manifested
Psychic Distuyhauccs ; Motor Disturbances. 427
in animals, especiall}- by the group of symptoms known as
''licking" or pica (wool-eating sheep), the animals showing
an inexpressible desire to lick all sorts of objects, even nauseat-
ing substances, and to eat them ; an ultimately fatal cachexia
developing in the chronic forms of these morbid appetites.
[Analogous to the pica of chlorosis and other anaemias in man,
and the dirt-eating habit of the an?emic hosts of uncinaria ;
probably many cases in animals are really expressions of a simi-
lar parasitism.] In rabid dogs there is a strong tendency to
swallow foreign bodies. In sows the habit of eating the pigs and
in ruminants of devouring the placenta are expressions of psychic
abnormalities.
(For fuller details see Friedberger-Frohner, Veterinary Patliology,
Amer. Ed., 1904. W. T. Keener & Co., Chicago.)
Motor Disturbances. — Aluscular movements are normally —
I, Voluntary, stimulated by the psycho-motor elements of the
gray cortical substance of the brain; 2. automatic, caused by chem-
ical stimuli, independently of voluntary influence, occurring
rhythmically and at all times present; 3. reflex, performed
unconsciously and caused by transmission of sensory excitation
to the motor apparatus; 4, co-ordinated and combined, the rapid
succession and repetition of voluntary and involuntary move-
ments as group actions, represented by facility of movement
acquired from practice (Samuel). Disturbances of movement
(motility) depend either upon pathological changes f'n the mus-
cles, tendons, bones and joints, or upon changes in the motor
nerves. The motor tract begins in the large ganglionic cells of
the central convolutions, passes by the long pyramidal fibres to
the cells of the anterior horns of the spinal cord and thence pass
peripherally by the nerves distributed to the muscles. In addition
those fibres and cells of the cerebral cortex which are concerned in
perception, ideation and volitional stimulation are more or less in-
volved in the production of voluntary movements. The complicated
and widely distributed tract may be exposed at any point in its
entire length to influences which are capable of interfering with
its functions. Such disturbances manifest themselves either as
pathological exaggeration or pathological impairment of motility.
Pathological exaggeration of motility is manifested by spasms;
spasm or hyperkincsis (17 Kii>r)<ns) may be defined as a paroxysmal
muscular contraction which is occasioned by pathological stimu-
lation or which, if caused by ordinary stimuli, exceeds normal
428 Xerz'oits Disturbances.
degrees of contraction. A\'hen the members of the body are
thrown into motion by these contractions alternating with relaxa-
tion the spasm is said to be clonic (6 kUvos , violent movement) or
alternating; when the contraction persists for a longer time,
causing maintenance of rigidity in one position, it is said to be
tonic (0 TOfos. tension). Tonus and clonus may succeed each
other alternately. The mildest form of spasm is tremor, really
a quick succession of contractions of single muscles or muscle
groups, the coarser types evident as visible and palpable jerkings.
These muscular contractions or spasms are spoken of as convul-
sions when they give rise to excessive movement of the body
and limbs, or violent tremors of the whole body (Samuel). Tonic
spasm of individual muscles or of only one group of muscles is
also termed a cramp (as of the jaw-muscles, trismus, from rpl^ui,
to grit) : the powerful and long continued contractions of the
greater part of the musculature, tetanus ( reivu, to strain) ; a
general body rigidity, without any important contraction (merely
the ordinary contraction to maintain position), catalepsy; long-
continued shortening of individual groups of muscles, with perma-
ment deformity as a consequence, contracture (distinguished as
active, spastic or reflcxophile in distinction from the passive con-
tractures not of nervous origin met in disease of joints). Convul-
sions when accompanied by loss of consciousness are described
as epileptic or epileptiform.
We know in connection with the causes of spasms that they
may be induced by a group of poisons or chemical irritants
(tetanotoxine, strychnine, ergotin, lead, carbonic acid gas), and
may be produced by poisonous substances arising as metabolic
products in the body (in uraemia), and that muscular contrac-
tions may result (directly or reflexly) from mechanical excitation
(section, torsion, crushing). In certain instances the spasms
are caused by local lesions of the peripheral nerves, of the cord
or of the brain (focal lesions), as the convulsions of suffocation
by lack of oxygen supplied to the medulla oblongata, those of
tetanus by the chemical combination of the toxine with the
nervous substance of the spinal cord. The more minute lesions
which take place in such examples are as yet not known, and the
extremely confused ideas we possess of the relations between
processes of excitation and inhibition prevent, for the present,
any satisfactory explanation of the conditions involved.
The results of spasms vary with the location of the causa-
tive influence in the svstem. When the cause is directlv in the
Mot<)r nishirbditccs.
429
muscles the cfifccts of the spasms arc of little importance, except
that in kmg; standin^^ contracture atrophy is likely to develop.
Spasm of the respiratory muscles of necessity causes fatal suffo-
cation because of interference willi respiratory movements.
Spasms of the muscles of mastication cause starvation. In other
examples a fatal termination may be explained by the primary or
some collateral action exerted by the poisons causing' the con-
vulsions, the tetanus poison for example acting both by the
lesions induced in the ganglionic cells and by a hemolytic action.
It should be kept in mind that th.e spasms themselves are noth-
ing more than the symptoms of the actual nervous disturbances.
(For details v. Friedberger-Fr(")lincr, Lchrbucli tier klinischcn fJiilcr-
siichifiii^siiicfliodcii f. Ticrarztc. III. Aufl. Stuttgart. F. Enke.)
Loss of muscular power is termed [^als\ (akiiicsis [a. prii'.,]
TyKij/T/o-is, nv)vement ) and may be differentiated into a complete loss of
mobility (paralysis) , or ])artial loss {paresis) in which the power
of the muscles to perform movements is only reduced in degree.
In case of deficiency in co-ordination, where the movements are
performed clumsily and hesitatingly, the term ataxia ( a priv.,
ij Td^ts, arrangement ) is employed. Loss of motion occurs in
pathological changes which directly inhibit muscular contractility
(atrophy, inflanuuation, rupture, degenerations), or interfere with
the movements of the bones (ankylosis of joints), or in conditions
of inefificient innervation which induce palsy both indirectly by
reducing the stimulus for contraction and by causing local
changes [in the muscle].
A faulty innervation itself is usuall}' the result of anatomical
changes involving the ganglionic cells or nerve fibres and thus
interfering with the formation of impulses or interrupting their
transmission, as for example stretching^, disintegration of the
nervous substance by pressure (tumors), or destruction and degen-
eration from poisons (toxines, lead), or disturbances of blood sup-
ply. The location of the changes may be in the central motor,
apparatus, cerebral cortex or cord (cerebral or spinal palsy), or
in the nerve trunks and their terminations (peripheral palsy).
The central and some of the peripheral palsies are usually
unilateral (hemiplegia) because they are 'usually due to focal
lesions, to local changes, in one of the bilaterally i^laced nerve
ganglia or nerves; wdiile spinal palsies generally involve both
sides of tlie body (paraplegia) because in the comparatively small
transverse area of the spinal cord the lesion causing the anatomical
430
Nervous Disturbances.
changes is apt to occupy the whole extent of the transverse section
{transverse spinal palsy).
Inhibition of the motor centres may also be caused by exces-
sive stimulation of the sensory nerves in a reflex manner (so-
called reflex paralysis or neurolytic palsy), as where complete
paralysis of the posteripr part of the body occurs after forcible
compression of the kidney, bladder, ureter or a portion of the
bowel (Samuel).
Results and terminations of palsies. The results of motor loss
vary with the duration, extent of disturbance, the importance
Fig. 131.
Paralysis of ttie posterior part of the body : transverse spinal palsy. (Photograph
by D:-. Jakob.)
of the affected muscles and of the causative lesion. In paralysis
of the heart and respiratory muscles death at once ensues from
cessation of circulation and gas interchange. Indirectly palsies
of the pharyngeal muscles, the bladder, the intestine or the
extremities may result in death because of the development of
various possible complications (aspiration of fluid in the air
passages causing aspiration pneumonia ; retention of urine and
fecal material with production of dilatation, inflammation and
erosion of the mucous membrane : hypostases and decubitus with
blood poisoning, etc.). In case of paresis of the sphincter of the
bladder the urine constantly dribbles and the same symptom con-
Sensory Disturbances. 431
stantly occurs with palsy of the sphincter and detrusor muscles ;
when the detrusor alone is paralyzed and the sphincter is intact the
urine collects in the bladder. Paralyses due to destruction of
ganglion cells are irreparable; but peripheral palsies may some-
times recover by regeneration of nerve fibres. When regenera-
tion of nerves does not occur in the spinal palsies due to destruc-
tion of the gray matter and anterior nerve roots, the paralyzed
muscles undergo atrophy and degeneration, with rapid loss of
electrical irritability. Tn case of central palsies atrophy does
not occur (Samuel). *
Sensory Disturbances. — The sensory nerves transmit pres-
sure and temperature sensations, special sensations (smell,
taste, sight, hearing), and the so-called general sensations
(hunger, thirst, special cutaneous sensations, sense of position).
It is assumed that just as for the special senses there are par-
ticular nerves, there are also for every other sort of sensation
special nerves; and it is knov/n that nerves sensitive to pres-
sure, pain, cold and heat have entirely specialized and character-
istic endings (v. Frey, Krehl). From these local receptive end-
organs the sensation is conveyed ccntripetally to the perceptive
psycho-sensory parts of the brain, where proper distribution is
made to the tracts and innumerable connections occur with the
reflex and automatic nerves and ganglia. Disturbances of sensation
may be considered as of two types, pathological excitation and
pathological depression of sensation. Pathological excitation of
sensory nerves gives rise to symptoms of sensory irritation of
the most varied forms and grades, according to the kind and
position of the terminal organ and the lesions. Sensation of
pain is caused by stimulation of the nerves of pain, which are
distributed in profusion and have their terminations in the skin,
at the mucous membrane orifices, serous and synovial mem-
branes; these peripheral parts of the body therefore being capable
of manifesting the most severe attacks , of pain. Mechanical,
chemical and thermic stimuli induce this symptom. If the
nerve be in a condition of exaggerated irritability (hyperces-
thesia) ordinary physiological variations (muscular action, ten-
sion of tissue, congestion) are sufficient to bring on pain. Cer-
tain forms of pain apparently develop spontaneously (nenralgia),
that is, without demonstrable anatomical lesions and from unknown
changes. The tracts extending from the muscles, bones and
glands and into the central nervous system are less sensitive to
pain; although painful symptoms may be noticed arising from
432
Xerz'oiis Disturbances.
sach locations also, as in affections of the spinal cord. In the
brain, as indicated by the absence of pain during operative pro-
cedures, the sensibility to pain is very low, at least in the cortical
areas. Only hairs, hoof, and cartilage, provided the matrix be
not also involved, are entirely devoid of the sense of pain, be-
cause of the absence of nerves from these structures.
The existence of pain is shown in animals partly by general
symptoms (restlessness, pawing, stamping, running about, roll-
ing over, groaning, sighing, gritting the teeth, whining and cry-
ing shrilly), partly by local symptoms which suggest and more
or less clearly indicate the location of the painful trouble
(scratching, hobbling, protective movements when touched, strik-
ing against the abdomen, looking around toward the posterior
part of the body, arching of the back, symptoms of colic).
Itching, indicated by the tendency to scratch, is met in cuta-
neous aft'ections, in some intoxications and general disturbances :
it must be due to an irritation of the nerve endings (pressure
points, Krehl), but the mode of origin is unknown.
The irritative symptoms, ''formication," "going to sleep" of
some part, which are caused by pressure upon nerve trunks
iparcrsthcsia), light and color phenomena from irritation in the
optic tract (pJiotopsia, chrotnopsia), abnormal temperature sen-
sations, cannot be determined in animals, as they are subjective
perceptions.
Pathological di^niniition of sensation. Tn lesions which inter-
rupt the course of the nerves at any position or render function-
less the parts subjected to irritation, sensation is entirely lost
or diminished or its transmission slowed. Sensory palsy (anccs-
thesia) may be induced by traumatic destruction of continuity
(nerve section, crushing), by freezing, cauterizing the endings,
by local anaemia, oedema, degeneration or atrophy of the peripheral
nerves or brain and cord segments, as well as by the local and
general action of certain medicaments (anodynes and anaes-
thetics, as morphine, chloroform, ether, chloral hydrate). Paraly-
sis of sensation may be total, so that practically every kind of sen-
sation is lost : or it may be partial, as when the sense of pain is
abolished and the pressure sense or sensitiveness to electrical irri-
tation is retained, or where the special senses are destroyed but the
sense of pain is intact.
The results of disturbed sensation depend upon the impor-
tance of the physiological functions abolished. Anaesthesias of
Sensory I)is!iirbaiiccs. 433
the optic system cause visual weakness (amblyopia) or com-
plete blindness (aiiuuirosis) . Auccsthesias of the auditory nerves
produce nervous difficulty of hearing- (hy/'iicusis) or com-
plete deafness (aiiaciisis). Loss of the sensory jiower of peri])h-
eral nerves is sometimes a source of danger for the tissues
(for "the senses are the guardians of health"), which become
conscious of every injury from the stimulus of pain and arc tlius
able to call into action every protective means and measure the
body possesses. ' In ansesthesia of the conjunctiva the entrance
of foreign bodies to the eye or conjunctival sac is not rcali;-ed, and
such substances are not carried off b\- the How of tc;irs. After
section of the sensory nerves of the foot, penetration of a nail into
the frog- is not evinced by lameness, and the ensuing inflannna-
tion and gangrene of the hoof proceed unnoticed — conditions of
serious consequence to the life of the subject. Interruption
of the sensory portion of the reflex arc puts an end to the tendon
reflexes, which cease in anaesthesia of the peripheral nerves because
the path of conduction to the reflex centre (pyramids) is broken.
If. however, the latter be intact and the communication between
the brain and ganglion be destroyed the tendon rcHexes are ex-
aggerated (central inhibition may also exist). (Krehl.)
Loss of the so-called motor senses destroys the coordination of
movements and causes the appearance of synijitoms of vertigo (v. p.
424). The sense of station of the limbs, which renders i)ossible the
acts of walking, standing and especially of orientation in sjiacc.
depends upon coordination of the optic and auditory organs, and
especially those portions of the latter enclosed in the i)etrous ])or-
tion of the temporal bone, as well as of the centripetal sensations
from the muscles, tendons, bones, joints, fasciae and skin.
Where there is loss of a single sense, as that of sight. orientatitMi
mav be possible from increased acuteness of other senses (tactile
sense, hearing) up to a certain degree Loss of sensory muscle im-
pulses or deficient transmission of these impulses or anaesthesia
of the cerebral or spinal centres cause more or less loss of power
of bodily motion. Disturbances of equilibration of the body occur
especially in diseases of the organs in the semicircular canals, in the
saccule and utricle, as well as of the central communications of these
structures with the cerebellum. How far in these instances we have
to deal with a pathological stimulation or pai-al\sis. whether there
exist a destructive phenomenon or one caused 1)\- deficient transmis-
sion of imi)ulses, are (luestious difficult to decide l)eeause of the
434 Nervous Disturbances.
complexity of the nervous mechanism and even more because of the
great variety of processes and causes possible in case of such dii^-
turbances.
Trophic, vasomotor and secretory disturbances depending upon
nervous influences. — Of the vast number of cells which make up the
animal body, there are, it is true, some cells, which are independent
of the nervous system, acquiring their nutrition and performing
their function by means of their own parenchyma alone. These are
the isolated blood cells and lymph cells. All the other cells and tis-
sues, however, in the matter of their metabolism, growth and main-
tenance of existence, depend upon the nervous system ; and die if
they be separated from it. The part played by the nerves in tliis
connection is known as the trophic influence. This is most clearly
apparent in nerve fibres themselves, which invariably degenerate if
divided from their ganglia or if the latter be the seat of disease. In
warm-blooded animals disintegration in the form of fatty degenera-
tion sets in as early as from four to six days. A nerve fibre may
be looked upon as the elongated process of a ganglion cell, and in
this conception disintegration is easily understood when it is re-
called that, as taught by *Verworn and Krehl, any part of a cell
which has been separated from its nucleus is sure to die. There is.
it is true, a certain degree of individuality of the different segments
of the nerve fibres so far as concerns their nutrition, metabolism and
diseases, but permanent maintenance of their integrity is only as-
sured by their continuity with the ganglion cells. And reversely the
central portions of a neuron (that is to say, the ganglion cell) suffer
if their connection with the peripheral nerves is broken ; for example,
after section of a nerve atrophy of the central portion also occurs,
perhaps extending to the ganglion. It is recognized that the integ-
rity of the ganglia and nerves is dependent upon the exercise of
their function, that functional stimulation is essential for mainte-
nance of their nutrition and life. Atrophy usually appears in the
voluntary muscles as soon as they lose the influence of their proper
ganglion cells in the anterior horns of the cord or of the equally
important cerebral parts ; that is, when these become diseased or the
communicating paths are interrupted or injured. The muscles, there-
after incapable of voluntary movements, are thus rendered immobile
(inactive, or paralyzed), become decreased in volume from diminu-
tion in size of their individual fibres (simple atrophy, atrophy from
disease), or may perhaps undergo granular and fragmentary disin-
tegration of their contractile material (degeneration atrophy) ; a
rapid shrinkage resulting, arid transformation of the muscle into flat,
Trophic, Secretory and Vasomotor Disturbances. 435
thin bands of fibrous connective tissue. To what degree this
atrophy may be due simply to the motor inactivity or is dependent
upon a loss of proper nutritive influences as the principal factor is
not certain. In simple disuse of muscles, as that obtaining in case
of disease of the joints and bones or artificial fixation, atrophy may
not appear for a long time, and the structure and electrical irrita-
bility remain unchanged, because the motionless muscle is still in
connection with its unaltered ganglion cell, performs other functions
as heat production and metabolism, and continues to receive impulses
of various kinds. In a neuropathic paralysis, however, the muscle
no longer receives stimuli from the nerves and its metabolism no
longer is as active; and atrophy may set in as early as within the
first week after the nerve lesion, and may be so marked that in the
course of a month tlie muscle may be reduced to half its former
thickness. From these considerations it is evident that not mere
inactivity alone, but the loss of some special trophic relation between
the nerves and muscle, determine the issue.
The most common example of such neuropathic atrn]i]iy is ^^een
in the shrinkage of the posterior crico-arytenoid muscle in laryngeal
hemiplegia (laryngeal wheezing in the horse).
(For details v. Friedberger-Frohner. Veterinary Pathology, Amer. Ed..
W. T. Keener & Co., Chicago; Dexler, Die Ncrvenkrankheiten des Pfcrdes,
1S99 (Denticke's Verl.) ; Thomassen. Moiiafsheft f. praht. Tierhcilkunde.)
In the same way in case of disease or loss of continuity of the
nerves nutritional disturbances develop in the bones (rarefaction,
atrophv), the salivary glands and testicles (diminution in size, de-
generation of the parenchymatous cells). The effect of castration
upon the development of the body and the change of physical habit
is presumably also to be attributed to some trophic influence of the
nervous system.
Secretory disturbances resulting from nervous lesions conform
closely to the known physiology of glandular activity. It is well
known that by direct or indirect stimulation of the secretory nerves
of the salivary glands (facial nerve, gustatory nerve, trigeminus
and branch of glosso-pharyngeal : stimulation by digitalin, pilocarpin,
or inflammation) an increased, sometimes permanently increased,
secretion of saliva results. Similarly a flow of tears is induced by
stimulation of the lachrymal nerve, cervical sympathetic, trigeminus,
and, too, reflexly by irritation of the nasal mucous membrane.
Vasomotor disturbances (angioneuroses) manifest themselves by
abnormal dilatation or constriction of the vessels, the former deter-
436 Disturbances of Digestion.
mining a hypergemia, the latter an ansemia of the organ affected.
Centres for the vascular nerves are located in the floor of the fourth
ventricle, in the dorsal and lumbar cord and in the ganglionic and
nervous plexuses which regulate the tone or ordinary state of con-
traction of the arteries and the dilatation or constriction of the ves-
sels to any calibre, and which are located about the walls of the ves-
sels themselves. Stimulation of the fibres regarded as vasoconstric-
tor causes diminution of calibre, auc-emia and lowered temperature
of the organ involved ; afterwards passing into paralysis, from
which dilatation results. Paralysis of the vascular nervous centres
also induces dilatation of the vessels and rapid lowering of blood
pressure (section of cord, paralyzing poisons). Stimulation of the
vasodilators causes marked dilatation of arteries, capillaries and
veins and is induced especially by local toxic influences.
Disturbances of Digestion.
Diseases of the mouth, tongue, jaws and teeth all interfere with
the taking of food and with mastication as well as the insalivation
of the food within the mouth. The supply of nutritive material is
thus diminished according to the grade and duration of such faults,
and conditions of failure of nutrition and starvation are brought
about. As the secretion of the gastric glands is in reflex associated
relation with the movements of chewing so as to insure the imme-
diate bathing of the swallowed bolus in proper juices (Pawlow), it
is to be expected that in case of insufficient mastication the food
taken into the stomach will be provided with a deficient amount of
gastric juice and will therefore of necessity remain a longer time
in the stomach.
The movements of mastication mechanically cleanse the mouth of
its mucus and bacteria (immediately after prolonged chewing of
food the mouth is almost aseptic) ; anything which causes diminu-
tion of these movements favors marked accumulation of micro-
organisms, as a result of which acid fermentations take place in the
mouth, facilitating decay of the teeth, accumulation of tartar on the
teeth, pharyngeal catarrh, etc.
In various diseases of the mouth (as foot and mouth disease),
in a number of toxic disturbances (mercurialism) and nervous affec-
tions (trigeminus), there ensues from direct or indirect nervous
irritation an increased flow of saliva, the secretion dribbling from
the mouth (salivation, ptyalisui). Dribbling of saliva may also be a
symptom of paralysis of the lips.
Discuses of Pharynx^ (Esophagus and Stomach. 437
Diseases of the pharynx and the adjacent structures niav, on the
one hand, give rise to faults of obtaining food (painful inflamma-
tions), and on the other hand if swallowing is interfered with by
such conditions important complications may arise as consequences.
As the respiratory and alimentary canals cross in the pharynx and
the epiglottal orifice must be closed in the act of swallowing and the
nasal cavity must also be shut off from the mouth by the superior
pharyngeal wall, there arises a danger in all affections which dimin-
ish the contractile power of the musculature of the pharyngeal walls
(peripharyngeal oedema, inflammations, etc.) that particles of food
and saliva may And their way into the nose or into the larynx and
lungs. Sometimes the food and drink runs back (regurgitates) into
the nose, or in case of pharyngeal palsy remains in the pharynx
itself ; and under such circumstances drops and particles of the
pharyngeal mucus and food may be drawn into the respiratory pas-
sages (aspirated). The fluids of the pharynx and mouth are apt
to contain great numbers of bacteria, and these foreign agents mav
cause in the lungs the most serious inflammatory disturbances, ter-
minating in gangrene {gangrenous inhalation pnciinioiiia) .
Diseases of the Oesophagus may cause important interference
with nutrition. Both by constrictions and, too, by patholog-
ical dilatations of the gullet the food is prevented from passing
regularlv into the stomach. The larger fragments lodge at the
place of stenosis and in any dilated parts, or in case of paralysis
lie stagnant in the lumen of tlie tube and block the passage.
This induces retching movementjs (antiperistaltic contractions)
on the part of the cesophageal musculature, or if the oesophageal
muscles are paralyzed vomiting movements on the part of the
stomach (pressure b\' the stagnant mass and by the oesophagus,
stuffed full like a sausage, upon the \agus nerves). Further-
more these stagnating masses of food undergo fermentation,
cause injury to the mucous membrane and may in this way lead
to rupture of the oesophagus ; and in the latter event, from
escape of septic materials, the surrounding tissue (cellular tis-
sue of neck, mediastinum and thoracic cavity) is apt to undergo
suppuration and gangrene. In ruminants from partial or com-
plete obstruction of the oesophagus (new growths, pressure from
enlarged mediastinal lymph nodes) regurgitation of the gastric
contents and eructation of gases from the stomach are interfered
with, with tlie resultant development of clironic flatulence.
Diseases of the Stomach. — The efficiency of the gastric func-
438 Disturbances of Digestion. %
tion is disturbed in two ways in disease, the gastric secretion be-
ing 'affected in the first place and in the second the gastric motihty
being more or less affected. Usually both factors are involved
at the same time, being directly or indirectly dependent upon
each other. Disturbances of secretion are for the most part
characterized by such features as diminution of the gastric juice,
decrease in the proportion of acid (subacidity) and of pepsin
resulting from degeneration of the glandular epithelium in acute
and chronic catarrhs, anaemia, etc., or by continuous secretion of
gastric juice without intervals ol rest (caused by local inflamma-
tory stimulation of the nerves of the mucous membrane). In
the latter condition the secretion is apt to be poor in its hydro-
chloric acid and peptic enzyme, and its increased volume accounted
for by hypersecretion of mucus. The secretion under such cir-
cumstances is likely to be of diminished functional value, or to be
entirely incapable of digestive action, such a condition being
termed dyspepsia. Although the passage of tlie gastric contents
into the intestine is the principal -factor in preventing serious
prevalence of bacteria in tlie stomach, the acid of the gastric juice
has a part in restricting the growth of bacteria and the occurrence
of putrefactive changes in the viscus. A gastric juice poor in acid
must be decidedly diminished in its antiseptic action, and for this
reason a num.ber of types of bacteria grow luxuriantly in the
stomach in dyspeptic conditions. The gastric contents are often,
in these instances, found to be neutral or alkaline in reaction, and
putrefactive fermentation is present; where in spite of deficiency
of hydrochloric acid an acid reaction prevails (dyspepsia acida),
this is due to the formation of acetic acid (from alcohol, yeast
fermentation) and lactic and butyric acids (from glucose, through
the activity of bacteria).
In other cases there may exist a hypersecretion with excessive
hydrochloric acid production, or the latter (hyperacidity) may
obtain without any increase in the digestive fluid (as a result ol
special conditions of irritation), with the effect of inhibiting starch
digestion and causing gastric pain and vomiting (Krehl).
The products of fermentation and putrefaction of the gastric
contents act as toxic irritants upon the mucous membrane, and
may occasion further degenerative and inflammatory changes in
that tissue. Under these and other circumstances, which induce
(whether from circulatory disturbances or from the local lesions
and toxic influences) paralysis or weakness of gastric peristalsis
Diseases of the Stomach. 439
(gastric atony), the churning and mixing of the gastric contents
with the secretion are not thoroughly accompUshed. When the
ingested matter is thus inefficiently dealt with the undigested
material is apt as a result to remain stagnant in the viscus, and
this in turn favors increased fermentation and putrefaction. As
gases are very likely to be present among the products of these
processes, flatulence of the stomach {meteorisin, from nereupi^eiv,
to inflate) may be expected, varying in its intensity ac-
cording as to whether the gas finds its way through the pylorus,
is absorbed or finds an outlet through the gullet in belching, or
whether it fails to escape.
Delay in emptying of the stomach or retention of the contents
favors gastric dilatation. A distended stomach because of its
increased volume causes pressure influtnces upon the adjacent
parts, compresses the liver, vena cava, etc., interferes with the
diaphragmatic movements and thus renders respiration difficult.
Even in moderate degrees of distension the absorptive powers
of the gastric mucous membrane is dinnnished because of the
tension of the lymphatics and blood vessels. The distended wall
of the stomach may rupture and fatal haemorrhage from the torn
blood vessels quickly terminate life. Digestive faults in the first
stomach of ruminants occur in the same general way as above,
but with the difference that there is here no secretion from the
gastric mucous membrane and we have to consider merely the
macerating properties of the fluid swallowed, mixed with saliva.
In these animals accumulation of gas and tremendous distension
invariably occur, either suddenly or gradually, when the con-
tractile power of the wall of the paunch is lost. This may be
caused by a number of influences, as chilling" of the mucous sur-
face of the paunch by frozen or rain-drenched food, overfeeding
or overwork without allowance of time for rumination, or toxic
substances capable of causing paresis of the gastric wall and met
in various food stufifs. as lucerne or clover. ^leteorism may also
be noticed when belching of gas is prevented by constrictions of
the oesophagus.
Exaggerated gastric mbvemcnts occur especially in connection
with pyloric obstruction, or from the influences of chemical ma-
terials which directly irritate the mucous membrane of the viscus
or the smooth muscle of its walls, or mav be caused indirectlv
by influences acting on the medulla oblongata (reflexly and by
irritation of the vagus). The violent contractions of the muscle
440 Disturbances of Digestion.
of tlu' organ may ^ause it to be rapidly emplied into the intes-
tine, or. in association with the mnscles of respiration (spasmodic
contraction of the muscles of the abdominal wall and diaphragm),
may cause vomiting (■z'oiiiitiis) . It may be safely assumed that,
as in man, more or less gastric pain is caused also in animals by
various affections. Distension of the stomach, the marked stretch-
ing of the wall, give rise. to a sense of pressure: and the local
effects of poisons, of increased proportions of acid, and of toxic
bacterial products upon the sensory nerve fibres of the mucous
membrane, and especially the occurrence of spasms of the gastric
muscles, must surely often cause intense pain. It is known that
in man migraine and vertigo as well as epileptiform convulsions
may he of gastric origin,*- apparently from vagus irritation; and
some of the nervous symptom groups, as distemper of dogs, may
perhap> l:e expltiined by gastric changes.
Diseases of the Intestines. — In all intestinal diseases the
micru-organisms, which teem in the contents and cause all sorts
of disintegrative changes in the material, play an important part.
Bacteria of many t_\pes, yeasts and hyphomycetes, as well as in-
fusoria, are to l)e found in the intestine of the healthy human be-
ing and animal, being introduced with the food. Pasteur and
Schottelius have pointed out that the presence of these corn-
mensualists is an absolute necessity for the herbiverous animal,
the bacterial processes being adjuvants in the digestion of the
food ( it has been impossible to keep alive chicks hatched in
sterile surroundings upon artificially sterilized food) ; although
young guinea pigs have shown their alnlitv to live and thrive on
pure milk diet without bacteria in llun- intestine (Thierfelder
and Xuttal).
The harmlessness of the ordinary intestinal bacteria is due
to the fact that the healthy epithelium of the gastric and intestinal
mucous membrane acts as an impenetrable barrier against them;
the protective means possessed by these cells being apparently
their strongly acid, albumen precipitating nucleinic acids (Klem-
perer). Again it is possible that the intestinal epithelium, as well
as the rest of the tissue in every indivklual. may become accus-
tomed to the toxic products of the ordinary intestinal bac-
teria, just as the epithelium of the stomach and upper part
of the intestine is acid proof ; or it may be that an immunity
is obtained by the formation of antibodies. Then too the
acid gastric and small intestinal juice, as well as the bile,
Diseases of Ihe J iilestiiies. 441
surely possess sonic degree of influence inhibiting- the multipH-
cation of tlie inicro])hytes taken in with tlie food Marked ex-
cessive prevalenc<^ of l)acteria i.^, however, niainl\ ])revented by
the comparatively rapid passage of the chyme through the small
intestine and the discharge of large quantities of microorganisms
periodically with the dejecta from the large bowel in regular
defecation.
Ir conditions which interfere with the normal passage of the
chvme through the intestinal tract, as in stagnation of the intes-
tinal contents from obstruction, strictures, etc., or where the
epithelium of the mucous membrane has undergone changes
(degeneration, necrosis, desquamation), even the ordinary in-
testinal bacteria are capable of causing harm ; and this is obvi-
ously possible where other types of microphytes having special
toxic properties are introduced, these perhaps causing epithelial
necroses or their toxic products being absorbed. We should re-
gard, at any rate, as harmful products of ordinary intestinal
bacteria the products of acid fermentation of the carbohydrates
(lactic acid, butyric acid, acetic acid), these when present in large
amount causing erosion of the mucous membrane (especially
the delicate mucous membranes of young individuals), and gases,
as hydrogen and methane and sulphuretted hydrogen, arising in
albumen putrefaction.
The metabolic products of the bacteria themselves are even
more numerous and their influences varied. But little is known
of their relation with the pathology of the intestine, and
there is so nmch confusion as" to the nature of these some-
times poisonous su1)stances. and their relation to the alkaloids,
albuminates, enzymes, etc., that it is at present best to be satis-
fied with their tentative classification into toxines and endotoxines.
We can only speak in a general way of the bacterial processes in
the intestinal canal as the source of pathogenic and fatal changes,
and say that on the one hand they occasion local lesions like
inflammations, hcemorrhages or necroses, and on the other hand
give rise to general intoxications. Similar efifects may be pro-
duced bv the ingestion of various chemical substances (poisons
taken in with the food).-
In many intestinal affections disturbances of the absorptive
power of the mucous meiubrane ensue. This is especially true
of the diffuse lesions ; although in circumscribed changes the
intervening portions of mucous membrane remaining unaltered
442 Dishtrbanccs of Digestion.
continue to act and to transmit as usual the sugar and albu-
men to the blood and the fat to the chylous vessels. The
causes of impairment of absorbent power lie primarily in the
alterations of the intestinal epithelium, which normally acts
in fact by attracting the nutrient substance to it (Krehl), and in
the second place in the disturbances in the lymph follicles of the
intestine ; and, too, the passage of the intestinal contents may
be too rapid to favor absorption, the period of contact of the
nutrient material with the intestinal mucous surface being
curtailed. The terms looseness of the bozvels or diarrhoea are
applied to the accelerated passage of the chyme through
the intestine, apparent from the fluid or thin intestinal dis-
charges. The usual cause of this condition is a heightened peris-
taltic action of the intestinal musculature; which may prevail
throughout the intestinal tract or be restricted to the large intes-
tine, and is due to irritation of the sensory nerve filaments in
the mucous membrane, with transmission of the impulse to the
motor nerves of the intestinal muscles. According to Cohnheim
extensive and general movements of the intestine can be aroused,
starting from any level of the gastro-intestinal canal, by merely
moderately strong irritation. Hand in hand with the increased
movement hypersecretion from the mucous membrane may take
place, a transudation from the blood vessels, as another effect
of local irritation. The irritant substances are of innumerable
chemical types, including materials ingested from the outside of
the body (drastic purgatives) or decomposition products formed
in the bowel itself. According! to Krehl the ocganic acids and
gases (carbonic acid, hydrogen) are especially efficient in stim-
ulating intestinal movements. When the intestinal mucous
membrane is already inflamed and hypersemic even an ordinary
amount of irritation is sufficient to cause increased peristalsis, as
the nerves are even then subjected to pressure from the distended
blood vessels and transudate (Cohnheim) or are deprived of
their protective covering because of the defects in the mucous
membrane. Diarrhoeas may also be caused, however, by
prevention of absorption of water from the intestine, which
may be the case when salines are present in the gut, these sub-
stances having- a strong tendency to combine with water and
being themselves difficult of absorption (saline laxatives). Sud-
den changes of the blood currents and the blood gases, soaking
or chilling the skin, or putrid blood poisoning are also factors
Diseases of the Intestines. 443
which directly or indirectly are liable to cause spasmodic contrac-
tions of the intestinal muscles (dyspcristalsis).
As already stated the absorption of nutritive material is dis-
turbed in diarrhcEas; but in addition the digestive secretions and
the digestible constituents of the food are carried out of the body
by the frequent dejections. Besides there are losses of the
epithelium of the mucous membrane, losses of the inflammatory
albuminous transudate or of blood; so that the body suffers also
a loss of its circulatory and organic albumens. For these reasons
diarrhreas weaken the strength of the subject, bring about a
state of inanition and may perhaps be fatal. Although resorption
is reduced in diarrhoeas it is not entirely checked, being main-
tained in this or that segment of the bowel; because of this it is
possible, in addition to the disturbances mentioned, that re-
sorption of toxic substances may prevail, this feature adding
complications to the morbid condition and aiding in bringing
about a fatal termination.
There are a variety of influences which may retard the pas-
sage of the chyme or completely stop its movement. Infrequent
defecation, protracted retention of the chyme in the large gut,
obstipation or constipation (constipare, to render compact), or
simple stoppage of the bowel, is usually due to the character of
the food, which ma\- cause the chyme to be too thick because of
insufficient presence of water or which does not stimulate the
mucous membrane enough and causes an atony of the muscles of
the intestine (from feeding bones to dogs, bran to horses). A
constriction or complete closure of the intestinal lumen, stenosis,
obturation or occlusion,* may be due to presence of foreign bodies
(enteroliths, concretions, swallowed stones, cork stoppers, etc.),
to tumors or to cicatrices. Or the intestine may be compressed
or squeezed from without {strangnlation of intestine, incarcera-
tion) when caught in some opening (rupture, hernia), or sur-
rounded by some band : may be twisted {intestinal tzvist, volvulus) ;
or become impermeable because one segment becomes invag-
inated in another (intestinal intussusception, invagination). The
obstruction of the lumen in all such cases causes a retention
of the chyme with accumulation toward the stomach, and the
possibilitv of passage of the intestinal contents, both food refuse
and gases, to the anus is interrupted. The chyme stagnating
abpve the obstruction, in which the processes of bacterial decom-
*0'bstfucre, to barricade, stop up ; occlvdere, to close up ; ohtururc, to divert,
according to Roth, probably from 9vpa, door.
^^_|. Disturbances of Digestion.
position are continually going on, distends the intestine, partic-
ularly by gaseous inflation. If the lumen is merely narrowed and
not completely obstructed and if the obstructing cause is slow-
in development, a compensatory hypertrophy of the musculature
mav ensue (v. p. 255), and for a time overcome the difficulty;
the strengthened wall by its more forceful contractions succeed-
ing in forcing the tiuid chyme through the narrowed passage.
Where occlusion is sudden and complete, however, the retained
contents accumulate in such amounts and the gaseous distension
becomes so intense that serious symptoms and results are in-
duced. The pressure, whether from without or from \\ithin the
gut, upon the nerves of the intestinal wall and mucous membrane
and their irritation by the chemical substances in the contents,
cause violent contractions, spasms of the smooth muscles ; which,
either by anti-peristaltic movements or because of mere disten-
sion of the tube, and because from vagus irritation retching
movements are set up, induce overflow and regurgitation of the
chyme into the stomach, a process known as ileus (6 d\eb?,
from etX^o., I close, or dXiw. I turn, according to Roth) or
niiscrcrc. l)ecause of the frightful torture which it causes.
The violent muscular spasms of the intestine are accom-
panied by severe pains, colicky pains or griping (i)Kw\iK-n, sup-
ply v6sos ; from t6 kwUv, the colon), giving place to an intestinal
paralysis due to fatigue of the U'uscular tissues and the stretch-
ing of the wall from gas accumulation. The distension as well
as the spasmodic muscular contractions may lead to rupture of
the intestine, along with pressure upon the neighboring organs
antl the large blood vessels of the abdominal cavity. The
stretching of the nerve fibres (splanchnic) with its reflex effect
upon the heart, the continuous vomiting and the absorption of
toxic substances, make up a group of processes which, with rapid
loss of strength, cause the death of the animal. In conditions in
which strangulation of the bowel causes the occlusion there are
added to the above phenomena disturbances of the blood cir-
culation in the intestine, venous congestion, congestive haemor-
rhages and transudates, and gangrene. Gangrene necessarily
must result from the penetration of the intestinal bacteria into
the tissues which are engorged with blood, without the least cir-
culation and therefore necrosing.
Diseases of the Liver. — The manifold functions of the liver
make it easilv realized that any alTection of this organ which is
Diseases of the Liver. 445
associated with destruction of its secretory parenchyma or with
disturbances in the entrance or exit of blood, should be followed
by numerous reactive efifects upon the general body. The chem-
ical function of the liver does not extend merely to the production
of bile and furnishing of glycogen, but is directed to the pro-
duction of a large number of enzymes having for their purpose
the dissolution, transformation, precipitation or complete de-
struction of toxic material circulating through the blood, but
brought to the liver especially from the intestine. The liver
possesses, therefore, an antitoxic function, and is a toxolytic
organ of the greatest importance. According to Bangger and
Zschokke the following enzymes have been isolated from the
liver or bile; maltase, glykase, a proteolytic ferment (similar to
trypsin), nucleinic ferment, aldehydase, Hpase, fibrin ferment, a
milk curdling ferment : and there have also been recognized a fer-
ment capable of forming ammonium and urea from the amido
acids, one forming glycogen from sugar or the reverse change
(of sugar from glycogen), another forming iron and bilirubin
from hemoglobin, and finally one causing the combination of
cholic acid with glycocol and taurin. and of phenol with ethyl-
sulphuric acid. A large number of alkaloids are rendered com-
pletely or partly inert by the liver. Schiflf proved experimentally
that a dose of nicotine, which is fatal if injected into a peripheral
vein, is Vv'ithout effect if injected through the portal vein, and
that an infusion of nicotine made into an emulsion with fresh
liver tissue loses its toxic properties, while if rubbed up with
muscle or nervous tissue quickly evinces its toxicity. In the
same way strychnine, cicutine. veratrine, caffeine, atropine, curare
and animal toxines. extracts from putrefied tissue, have been
found to be less toxic if mixed with liver tissue or injected by
wav of the portal vein so that they must first pass through the
liver. Roger has shown that the portal blood before coming to
the liver contains a considerable amount of toxic substances
apparently absorbed from the intestine: the blood of the other
veins of the bodv. on the contrary, showing a far less toxic quality
in spite of the fact ihat it carries with it various metaboHc prod-
ucts from the tissues. The intestine is a chemical laboratory in
which a great quantity of bodies of the most varied character are
formed from the combination of the digestive juices with the
food: and then, too, the myriads of bacteria which inhabit the
intestine give origin to products of more or less toxic nature.
446 . Disturbances of Digestion.
Bile, peptones, ferments, various vegetable acids, gases, the in-
testinal putrefaction substances, various alkaloids and proteid
bodies are to be met; and are, it is true, largely carried out of the
system with the feces, but to a certain degree are also absorbed
by the portal venous radicles. The liver serves as a cleansing
apparatus, and frees the portal blood from these harmful ingre-
dients. As soon as the liver becomes affected by diseases which
reduce its antitoxic functional ability, these substances must
necessarily pass through the organ without being transformed and
gain entrance to the general circulation and be- changed possibly
by other tissues or be eliminated by the kidneys, lungs and per-
spiration. The kidne}'- is particularly capable of acting in place
of the liver in purifying the blood. It has been shown that th^
urine in hepatic diseases and in conditions which cause an in-
creased albumen disintegration (whether in the liver itself or
elsewhere) acquires decidedly increased toxic properties and
contains instead of or along with urea large amounts of am-
moniacal compounds or acid bodies, as amido acids (leucin,
tvrosin), aromatic oxyacids. acetone and albumoses. Such ma-
terials are. however, injurious to the kidneys and for this reason
disease of the liver is frequently complicated by pathological
changes in the kidneys. In case of failure of the compensatory
function of the kidneys, and especially if poisonous substances no
longer neutralized by the liver parenchyma are passing into the
blood, there may ensue symptoms of general intoxication acting
particularly upon the central nervous system. These phenomena
may be met in varying grades of severity, as convulsive or stupor-
ous conditions of acute or protracted course, according to the
extent of destruction of liver cells, the increase of albuminous
■disintegration in the liver and the access of infectious factors.
The most important poisonous material wdiicli occurs in case of
destruction of the hepatic function concerned in the transforma-
tion of albuminates into urea and uric acid, is carbamic acid : the
entrance of this material into the blood, as seen in animals de-
prived of the liver or having an Eck's fistula (Minkowski*), causes
very intense cerebral disturbances.
Stagnation of bile, besides causing biliary staining of the liver
and the rest of the body structures, the so-called icterus (x. p.
212), is also responsible for cerebral toxic symptoms (spasms
and stupor), because of complex conditions of intoxication simi-
♦ For details see Kitt, Pathol. Andtcnnie iler Haitstinc, II Aiifl. 1 Bd., p. 595.
Diseases of the Pancreas. 447
lar to the above. The choHc acid especially is toxic to the nerv-
ous structures, but the biliary pigments are not entirely inert; and
haemolysis also plays a part {chohonia). Obstruction of bile
from the intestine and, too, diminished or completely checked
production of bile -{oligocholia, acholia), because of degeneration
of the hepatic parenchyma, disturb the formation of the chyme;
absorbtion of fat is made difficult in the absence of bile and the
loss of the antiseptic influence of bile may cause intestinal catarrh
from putrefaction of the ingesta.
Hepatic diseases also affect the nutrition of the tissues, from
bringing about changes in the character of the blood. The Hver
is the storehouse for the sugar of the blood (E. Voit), which it
elaborates from the material brought to it from the intestine by
the portal vein ; it stores up fat, and consumes the debris of broken
down corpuscles; and in case of loss of these functions the body
must suft'er from the abnormalities in some of its important
sources of energy. Further there may be mentioned altera-
tions which are brought about by mechanical interference with
the blood circulation, as in diffuse induration of the liver; all dis-
eases which tend to occlude the blood capillaries and cause com-
pression and narrowing of the innumerable intrahepatic ramifica-
tions of the portal vein bring about passive congestion of the
organs in which the portal vein originates, the stomach, intestine,
spleen, and the visceral portion of the peritoneum. From this'
condition, dropsical transudation, ascites, is apt to develop.
Diseases of the Pancreas. — Diseases of this organ causing
atrophic changes of the glandular parenchyma, render the
formation and discharge (into the intestine) of its secretion
impossible, have an important influence upon digestion of proteids
and absorbtion of fats, may be followed by diabetes, and lead to
serious and progressive emaciation. Especially in case of the
horse, an animal possessing a relatively small stomach and only
a short period of gastric digestion, the loss of the pancreatic func-
tion cannot be compensated for by other glands and gives origin
to a fatal cachexia (Siedamgrotzky). Observations on dogs, cats,
hogs, rabbits, pigeons, birds of prey, after extirpation of the gland
or restriction of its secretion from the intestine by ligature of
the duct, have shown that in case of failure of the pancreatic
jivce fats are no longer absorbed (only in natural emulsion is
fat absorbed to the extent of thirty to forty per cent. ; all the
neutral fat reappears in the feces; and only part of the fats is
448 Disturbances of Rcspiratioii.
split) ; only about forty-four per cent, of the proteids are absorbed
(Abelmann, Krelil), and sixty to eighty per cent, of the carbo-
hydrates. The latter and the sugar formed within the body from
the albumens are excreted unchanged in the urine (Minkowski).
The diabetes thus produced varies in its severity according as to
whether the gland has been completely or only partially removed
in operation, whether it is generally involved by disease, or
whether portions of the gland remain in functionating condition.
In dogs and cats after total ablation of the organ, the urine
usually contains as high as eight to ten per cent, of sugar ; and
the animal may be expected to die from the progressive cachexia
in the course of fifteen to twenty days. Diabetes fails, if. in ex-
perimental removal, a sufiicient amount of the gland is left or
transplanted under the skin ; and occlusion of the duct (ligature,
obstruction by calculi) does not invarial)ly cause diabetes, as
the secretory substance may then be absorbed through the lym-
phatics and be conveyed to the blood. The active agent involved
is believed to be a ferment whose function is the destruction of
the sugar in the blood ; if this be wanting the sugar necessarily
accumulates in the blood and passes unchanged into the urine.
It is of further interest to recall that in diffuse carcinomatosis of
the pancreas diabetes may similarly be absent, apparently because
the tumor cells, as the offspring of the secreting gland cells, are
capable of carrying on the function of the latter to an extent suffi-
cient for the metaboHc demands in this direction.
The effects of failure of the pancreatic juice to pass into the
intestine mav, in normal conditions of the intestine, be practically
compensated (not in tlie horse — v. supra) by tlie fat-splitting
power of the bile and the intestinal bacteria, the latter causing
proteid putrefaction at the same time.
Disturbances of Respiration.
The constant intake of oxygen and output of carbonic acid
gas is the first vital requirement of the cells of the animal
body. In foetal life this interchange of gases is performed by
means of the placental circulation, in post-natal life by the en-
trance of atmospheric air to the respiratory surfaces of the lungs;
and the red blood corpuscles act as essential agents in causing
the interchange. The inspiration of the atmospheric air and flie
output of that which has been rendered unfit, constituting what
is known as the external respiration, may be impaired by closure
Faults of External Respiration. 449
and constriction of the respiratory passages, diminution of the
respiratory surfaces of the Kings, and by any interference with
the movements of the respiratory muscles. In conditions of ob-
struction of the nasal passages (swelHng of the nasal mucous
membrane, tumors), breathing may for the time be still accom-
plished through the mouth; obstruction of the larnyx and tra-
.chea with its branches, by foreign bodies or tumors in the lumen,
spasm of the glottis, external pressure (thyroid tumors, oesopha-
geal diverticula, strangulation), or collection of exudates in the
tubes, causes difficulty of respiration (dyspna^a, air hunger) in
proportion to the extent of the obstruction. Proportionately to
the degree of diminution of entrance of air to the lungs the blood
becomes impoverished in oxygen and its carbonic acid content
increases. Lack of oxygen and excess of carbonic acid in the
blood act to stimulate the respiratory centre in the medulla ob-
longata (point of exit of the vagus) ; this stimulation, and prob-
ably the mechanical influence of incomplete filling of the pulmo-
nary alveoli, which directly afifects the fibres of the vagus, bring
about an increased contraction of the inspiratory muscles. In-
spiration becomes stronger, more powerful, deeper and longer
in duration, because the narrowed lumen of ihe tubes does no't
admit the external air to pass readily into the alveoli and the de-
mand for oxygen in the medulla oblongata is not at once satis-
fied (Krehl). The air becomes rarified in the lung and the in-
tra-alveolar pressure less than the external pressure upon the
outside of the body; and for this reason inspiratory retractions oi
the intercostal tissues may be noted. Because the air cannot pass
out through the narrowed portions of ^e tract with the usual
ease, the lung does not collapse as rapidly as normally and ex-
piration is also prolonged (Krehl).
Contraction of the diaphragm is the main factor of the inspir-
atory forces, the contraction of this broad muscular sheet, arch-
ing anteriorly . because of the pressure oi the abdominal viscera,
causes it to assume a flatter plane and thus increases the thoracic
space, the elevation of the chest wall, especially the lower ribs
(by the levator costarnm muscles) aiding in producing this ef-
fect. Expiration is due to cessation of the diaphragmatic contrac-
tion (termination of its tension) and that of the levator muscles, as
well as to the elastic contraction of the lung expanded in inspira-
tion. Ruptures of the diaphragm (excluding here the question
of hcxmorrhage from the ruptured blood vessels and hernia of
450 Disturbances of Respiration.
the abdominal viscera into the thoracic cavity) usually rapidly
cause death because of the resulting impossibility of breathing.
Difficulty of respiration is similarly occasioned by embarrassment
of and pressure upon the diaphragm by meteorism of the abdom-
inal organs, tumors, etc., where the alteration of contracting
movements and resting stages is lost in consequence of tetanic
spasm of the thoracic muscles and diaphragm. When air gains
entrance to one of the pleural spaces because of a wound of the
thoracic wall or rupture of the lung (perforating wounds, rupture
of suppurating foci), the lung afifected contracts from the action
of its elastic tissue and, because being no longer impervious to
air, it must adapt itself to the intrathoracic conditions (the me-
diastinum is pressed toward the opposite side by the entering air
and may even be ruptured) ; expansion of the lung is, therefore,
no longer possible, as the organ cannot follow the movements of
the chest wall and lies loosely (that is. fixed only at its root) in
the chest cavity. The thorax and lungs cannot properly expand
and collapse if the chest cavities are occupied by fluid exudates
(dropsy, pleurisy), or if the respiratory surfaces of the lungs are
lessened, if a greater or less portion of the pulmonary alveoli are
filled up or solidified by pressure of collections of exuded material,
tumors or parasites and thus deprived of their air. However,
even on the contrary if the lungs are excessively inflated, over-
distended, a condition known as emphysema, aeration of the or-
gans and interchange of gases with the blood are impaired ; the
lung not collapsing properly in this condition, the air escaping
with difficulty ( the carbonic acid is unable to pass out by dif-
fusion to a sufficient degree), f.nd the capillaries narrowed by
being stretched and not permitting the blood to flow readily through
their lumina. Under any such condition breathing becomes
labored and air hunger becomes apparent. In addition circula-
torv disturbances are induced, sometimes due to pressure upon
the thin walled veins bv accumulations of fluid in the chest cavity
and bv the uninterrupted enlargement of volume of the lungs,
this causing congestion in practically all of the veins (v. dropsy),
the factor of aspiration of venous blood fails ; and as terminal
features difficulties of discharge of the blood from the right heart
grow apace (resistance in pulmonary arterial area), if the vas-
cular distribution in the lungs be embarrassed by pressure or
obstructive influences ( secondary cardiac hypertrophy and dila-
tation).
Respiratory Motor Disturbances. 451
In some affections the respiratory movements arc accelerated
and more or less superficial. Increased frequence of respiration
is met particularly in febrile affections and inflammatory affec-
tions involving tlie bronchioles. The causes underlying rapid and at
the same time superficial breathing are not understood; it is sup-
posed that the responsible influences are related with the in-
creased internal temperature or some irritation of the sensory
vagus filaments. Respiratory disturbances may also be brought
about bv cerebral lesions. Affections of the nervous substance
of the brain which do not induce paralysis of the medulla oblon-
gata, accumulation of fluid, parasites, haemorrhages or toxic and
infectious irritants, may cause an increase of intra-cerebral pres-
sure, this apparently disturbing the stimulation of the respiratory
centre, respiration becoming slowed even though the air is not
in anv way obstructed in its passage to the alveoli.
When the inspired air contains poisonous gases, it is to be
expected that according to the character of these substances and
their quantitative admixture in the atmosphere there will be man-
ifested either violent coughing or suffocative symptoms (ammonia
for example) ; and inflammatory local disturbances will be induced
(inhalation of formol vapor) ; or that some blood change (as in
carbon monoxide poisoning) will be brought about by limitation
of the atmospheric oxygen and alteration of the haemoglobin.
The respiratory variations are the result of regulative pro-
cesses set into activity automatically and reflexly by the respira-
torv centre. Deeper or accelerated respiratory movements may,
to a greater or less degree, compensate for faults of gaseous in-
terchange of the blood and the tissues. \Mth cessation of the fault,
as by removal of an obstruction to the entrance of air to the lungs,
and coincidently with the moment when the medulla oblongata
again receives a proper amount of oxygenated blood, the special
stimulation of the centre ends and the respiratory movements again
become normal. Where the causes, however, continue operative
and become more marked, and even the excited respiratory move-
ments finally become incapable of relieving the air hunger of the
tissues, asphyxia (siiffocatiou) must ensue. As long as the brain
retains its normal irritability the labored and deep respiratory
efforts indicate medullary irritation, and in the latter case the
rate of cardiac action is also slowed from the marked irritation
of the vagus, and the cutaneous vessels are dilated because of
irritation of the vasomotor center (Krehl); after a time tonic-
452 Disturbances of Respiration.
clonic convulsions occur and death follows after a short period of
paralysis (Krehl). Where the irritability of the central nervous
system is diminished (haemorrhages into the brain, increased
intracranial pressure, toxic or infectious influences) the symptoms
caused by diminution in oxygen supply are less violent; the
gradual and progressive increase of carbon dioxide produces a
cerebral narcosis, the respiratory movements become gradually
weaker and life ebbs away with the advancing paralysis of the
central nervous organs (Krehl).
The respiratory tubes are provided with a number of pro-
tective mechanisms, which serve to remove foreign particles
which have gotten into the air passages. The. passage to the
trachea and lungs leads over an area, the naso-pharynx, richly
inhabited by bacteria and often the point of lodgment of foreign
bodies; the narrow laryngeal opening is the threshold separating
this septic territory from the tracheal system. Of course, the
larger foreign particles which get into the nose and pharynx
and which irritate the nerves of the mucous surface and thus in-
duce sneezing and snorting, are from time to time discharged,
and the entrances for air are kept free for the passage of air;
but motile virulent organisms may easily pass in, and aspiration
of small drops of septic mucus and saliva or even food particles
may readily occur. In this case (these substances having passed
into the trachea and bronchi) the continued activity of the ciUated
cells serves to remove these foreign particles, carrying them back
to the trachea and larynx. The mucus secreted over the whole
surface of the tubes serves to envelop the foreign elements, and,
too, dilutes the poisonous substances and renders them inert.
Moreover, the numerous depots of lymphoid cells may make an
efficient phagocytosis possible and thus facilitate the removal of
very minute foreign particles. In addition the reflex production
of coughing, which forcibly discharges foreign objects, the col-
lections of mucus to which they are adherent and any other
injurious contents of the trachea, is manifested and acts to cleanse
the upper portion of the tubes. Excitation of cough is prin-
cipally induced by local irritation of the sensor}^ vagus fibres in
the larynx and trachea, and may also originate in the pleura, a
special group of movements of the respiratory muscles being ex-
cited reflexly through the medulla oblongata. Cough begins with
a deep inspiration, followed by a forcible expiration ; the air under
high pressure in the lungs forces its way out through the opening
Coughing. 453
of the opposing rima glottidis and drives everything in the larynx
and trachea (to a certain extent, too, that which is in the pharynx)
out into the mouth (Krehl). Foreign bodies, exudates, etc.,
lodged below the bifurcation of the wind pipe may also at times
be carried out ; but there is a chance that objects in this position
may be driven deeper into the bronchial tubes (Krehl). Expec-
toration, removal of such substances from the chest (or better,
the lungs) is accomplished primarily by the ciliated epithelium
and the upward convection, by this means, of the mucous vehicle;
the stimulus to cough acting upon the expectorate (sputum)
only from the level of the bifurcation upwards.
These defensive mechanisms may be of no efficience it the
harmful chemical, bacterial or mechanical agents are of such a
character that they paralyze and destroy the epithelial cells and
their ciliary action, and the phagocytes or the smooth muscles
of the bronchial tubes, or if the foreign bodies are held firmly
because of swelling of the bronchial mucous membrane, or if the
obstruction be tightly fixed because of its size; and may be in-
effective because of lesion or disease of the motor or sensory ap-
paratus involved in coughing movements. The retention of for-
eign bodies and pathological secretions may be followed by
asphyxia, because of the obstruction to the air passages ; or may
be the cause of such serious effects as gangrene of the lung, etc.,
as the obstructing substances usually carry bacteria with them,
(Under normal conditions the pulmonary alveoli, the bronchial
tubes and trachea are sterile, because in the first place the bacteria
entering with the air lodge on the mucous membrane of the
nose and pharynx, where the current of air first strikes at an angle
and sweeps over the moist surface, and in the second place be-
cause they are carried up and out by the activity of the ciliated
cells.)
The act of coughing may itself be dangerous. In conditions
which increase the irritability of the respirator}- mucous mem-
brane or of the pleura T inflammations) frequent coughing is ex-
cited without there being anything requiring removal in the air
passages. The violent expiratory force of coughing raises the
intra-pulmonary air pressure and may thus cause pulmonary dis-
tension (emphysema) : it interferes with the return flow of venous
blood into the thorax and heart, to the extent that the latter
may be practically empty, raises the arterial pressure all over
the body, and may cause rupture of the vessels (KrehlV The
454 Urinary Disturbances.
violent respiratory paroxysms by increasing the abdominal pres-
sure may force the abdominal viscera into abnormally or normally
existing openings and thus cause displacements [hernia].
Disturbances of the TJrinary Excretion.
The excretion from the blood of material no longer useful to
the system through the kidneys, is subject to pathological faults
if the quantity and quality of the blood passing through these
organs are seriously changed, and if the renal parenchyma is the
seat of pathological lesions. Increase in the quantity of the urine
(polyuria), especially of the proportion of water in it, is met
when the quantity of blood passing through the kidneys is greater
than usual, that is. where arterial pressure is increased without
any narrowing of the renal vessels, or where with the ordinary ,
blood pressure the renal vessels are dilated. A more or less
marked polyuria is met in a number of the acute and most of the
chronic inflammations of the kidneys, and, too, after administra-
tion of diuretic drugs, in connection with certain intoxications
(mouldy oats, cantharidts, colchicum, oil of turpentine), after
resorption of transudates and exudates, in the stage of crisis in
febrile infectious disease and in the conditions spoken of as dia-
betes insipidus and diabetes mellitus. It may be readily under-
stood that to a certain degree this phenomenon is due to chemical
stimulation of the renal parenchyma with secondarily increased
permeability of the dilated blood vessels, or to increased secretory
action of the vascular endothlium and renal epithelium: on the
other hand the causes of the increase of blood pressure, apart
from increased ingestion of fluids, are as yet by no means clear.
Cardiac hypertrophy, vaso-motor disturbances originating in the
medulla, and paralysis of the renal nerves are worthy of consid-
eration in this relation. The causative factors underlying the
large output of urine occurring in so-called urinary flux or diabetes
isipidus ( Siapaivu. to pass through; insipidus, tasteless — in dis-
tinction from diabetes mellitus) are equally obscure.
Better information obtains in regard to the causes of diminu-
tion of the quantity of urine (oliguria) and of total suppression
of urine (anuria). It must be obvious that all conditions in
which the urinary passages are obstructed, as the urethra and
ureters, by calculi, tumors, strictures, occlusion of the collecting
tubules of the renal papill?e by the shrinkage of the connective
tissue about them or the retention of urinary casts, plugs of
Albiiiiiiiiitria. 455
exudate, etc.. must offer a resistauce to the outflow of urine; and
any severe renal inflammations in which the epithehal cells be-
come degenerated must reduce or stop entirely the secretory
power of the organ. In the first group the urine is danmied
back and pressure atrophy of the renal parenchyma takes place,
the cortical portion continuing to secrete for a time and urine
being unable to escape ; and in the other type of cases the pas-
sages are open, but the original secretory disturbance determines
a diminished production and a pathological composition of the
urine. In case of unilateral disease such faults may be compen-
sated by the opposite organ which remains functionally capable,
which receives a larger proportion of the substance requiring ex-
cretion in the urine, functionates more freely and becomes hyper-
trophied. The secretion of urine nni«t decrease also in conditions
in which a diminished amount of blood flows into the kidneys as
the result of narrowing of their blood vessels, as from shrinkage
of the renal capillaries and atrophy of the glomeruli ( in chronic
interstitial nephritis), from thrombosis of the renal arteries, or
notably from lowering of blood pressure as in cardiac failure and
a number of the above mentioned conditions. In the same way
a reduction in the output of urine takes place when large quan-
tities of fluid escape from the body by other routes or where the
fluid is kept back in the tissues as in fevers, diarrhceas, or forma-
tion of fluid exudates and transudates in the body cavities.
One of the most important pathological phenomena is the ex-
cretion of albumen with the urine, alhniuiunria. In normal con-
ditions, at least in states in which it is impossible to clearly dis-
tinguish between normal and pathological conditions, it is true
there is a very small quantity of the blood albumen passed
through the kidneys, so small tb.at it can only be recognized in
nurposefully concentrated urine and by special methods of de-
termination, as after fatigue from physical exertion (so-called
physiological and accidental albuminurias). When the amount
'^f albumen passed in the urine becomes sufllicient to be recog-
nized by the ordinary albumen reagents, there is reason to ap-
prehend the pathological disturbance of the renal function. This
may be of a quickly transitory nature, of no particular importance
and indistinguishable from the above mentioned non-pathogenic
symptomatic conditions; but as a rule it is an indication of some
lesion of the renal parenchyma.
AH sorts of poisonous substances, both those of external
456 Urinary Disturbances.
source (metallic salts, ethereal oils, etc.), and especially the tox-
ines of infectious diseases and the products of intracorporeal
tissue disintegration and metabolism, may give rise to lesions of
the renal epithelial cells and their basement membranes, making
it possible for the albumen of the blood to pass through them.
In most cases an inflammation of the organ is also present, this
factor introducing additional features of increased permeability
of the blood vessels, exudation, desquamation of the epithelium
and the formation of albuminous casts, blood casts, etc. Some
authors look upon evers^ albuminuria as the result of an exuda-
tive nephritis of some degree of severity, now unimportant, now
serious.
(For fuller details v. Friedberger-Frohner, Lehrbnch d. klin. Unter-
suchungsmcthodcn. Verlag von F. Enke, Stuttgart, III. Aufl.)
Another important symptom, often met in man. but uncom-
mon in animals, is the excretion of sugar in the urine. Although
the blood contains a considerable amount of sugar (as much as
0.2 per cent."), only minute traces pass into the urine normally.
In conditions in which unusual amounts of sugar are brought
into the blood {alimentary hyperglyccemia) , and the liver and
muscles are no longer able to use it up, the kidneys excrete the
excess (glycosuria) ; milk sugar passes most readily and in order
thereafter levulose. cane sugar and grape sugar (Krehl). It was
discovered by Mering that the administration of the glucoside
phloridzin. which contains about forty per cent, of sugar, is fol-
lowed by a glycosuria in which not onh' does a considerable
amount of the unchanged glucoside pass ofif in the urine, but also
sugar from the blood (dextrose) and from the liver (glycogen),
probably because of some secondary toxic lesion of the renal
epithelial cells.
A transitory glycosuria, ending in the course of few hours,
occurs after puncture of Claude Bernard's glycosuric point, a
procedure consisting in making a fine puncture in a certain spot
in the floor of the fourth ventricle of the brain. A similar glyco-
suria may also be observed after lesions in other parts of the
central- nervous system and in a number of intoxications and in-
fectious diseases (as in morphine poisoning, curare poisoning and
rabies). If the splanchnic be cut at the same time, or the liver
be extirpated, or if fasting animals are employed, the glycosuric
puncture does not succeed or is uncertain, and therefore the
Diabetes Mellitus. 457
quantity of glycogen in the liver has something to do with the
glycosuria; the precise character of the nervous influence is, how-
ever, unknown.
Where the excretion is a persistent and, too, a progressive
symptom, provided no unusual quantities of sugar are ingested
with the food, there may be said to exist a special disturbance of
metabolism, diabetes mellitus (mel, honey; SiajSalvw, , to pass
through). In this affection even the ingestion of starch causes
the appearance of grape sugar in the urine, so markedly, in fact.
that the greatest portion of the starch instead of being assim-
ilated passes ofif as sugar; and the urine only remains free from
sugar if carbohvdrates are entirely excluded from the food (Krehl
and others). While in the milder cases of this disease the amount
of proteid ingested has no influence upon the glycosuria, although
the sugar is formed normally from proteid also, and while in
these cases an increased supply of albuminous diet seems to be
quite advantageous to the nutrition of the body, there are cases
of a severe type in which even a strict meat diet and even absti-
nence from all food do not permit the urine to become free from
susrar. Of what nature the metabolic disturbances mav be which
ar^ responsible for the imjierfect manner in whicli the carbo-
hydrates and the glycogen formed from proteid are dealt with is
still rather obscure and confused fcf. Krehl). In a measure the
liver normally prevents the direct passage of carbohydrates into
the circulation and has the power of removing sugar from tlie
portal blood and of storing glycogen. Diseases of the liver affect-
ing this function permit a hyperglycremia to develop ; (according
to Bimes it ought to be possible to recognize the existence of
hepatic disease bv feeding molasses, as in case the liver Avere
normal the urine would remain free from sugar while otherwise
glucose would become demonstrable in it). Especial informa-
tion has been obtained from the excellent investigations of Mering
and Minkowski in relation to the pancreas, which have shown
that diabetes mellitus occurs when this gland is lost (extirpation
degeneration") and that either the pancreatic juice or the glandu-
lar parenchyma, the blood from which passes to the liver by the
portal vein, has in common with the liver a regulative influence
upon the amotmt of sugar in the blood or some power of fixation
of excesses of sugar (v. p. 448). [The generally favored view
at present among the profession would refer the pancreatic fault
to some disease of the islands of Langerhans .(Opie). It is be-
458 Urinary Disturbances.
lieved that these special structures secrete and give into the blood
of the pancreatic vein a substance which is either itself a glycolytic
ferment or which is not a ferment, but a more simple substance
acting to energise a glycolytic ferment in the muscles and other
tissues of the body. This glycolytic ferment is regarded as es-
sential to the final transformations and chemical decomposition
of the sugar in the system in order that it may be assimilated:
in its absence assimilation ' is impossible and the body suffer.^
by its inability to make use of the carbohydrates furnished to it,
and at the same time the sugar in the blood accunmlates and
when in excess (above 0.4 per cent.) is excreted in the urine.]
In its chronic form diabetes, an expression of metabolic fault
and at times accompanied by fauhs of the liver and pancreas,
causes more or less harm to the whole body. When the incom-
plete assimilation of carbohydrates is not compensated by the
supply of albuminates and fat, especially when the associated
diseases do not permit the assimilation of these last named sub-
stances, the general nutrition must of necessity fail. In serious
cases there is apt to be present, as well, a marked proteid disin-
tegration, and albuminuria appears as a symptom, together with
degeneration of the lens and retina, disease of the blood vessel
walls and a weakened resistive state of the tissues, which induces
s. special predisposition to tuberculosis and gangrene (in man).
Disturbances of micturition include difficult micturition
(dysiiria) caused by strictures and obstructions to the pnth of
outflow (the dribbling forced passage, with tenesmus and frequent
call to urinate, is called strangury) ; complete repression of mictu-
rition ( ischuria, retention of urine), in which case the bladder is
full because of spasm of the sphincter or paralysis of the detrusor
musculature; and inability to retain the urine (enuresis, incon-
tinentia urincr). due to a paralysis of the sphincter of the bladder
developing in disease of the spinal cord and of the bladder itself.
(For details cf. Friedberger-Frohner, Klinische Untersuchungsmetho-
dcn.)
Diseases of the urinary apparatus are more or less painful ;
affections of the passages being particularly apt to cause intense
pains, to be attributed in part to muscle spasms, partly to me-
chanical irritation (foreign bodies) of the sensory filaments of
the mucous membrane or to specially induced irritability (ulcers,
abrasions, inflammations) of these filaments.
Urccmia; Thyroid Disturbances. 459
The effect of disturbances of the uropoietic system upon the
general body depends upon the extent and the kind of the
changes. All the bacterial processes in the kidneys and in the
collecting- receptacles (bladder, renal pelves) as well as the
damming back of the urine in the ureters bilaterally, sooner or
later bring about symptoms of intoxication, manifesting them-
selves especially by symptoms of cerebral depression, less fre-
quently cerebral excitation, included collectively under the
term urcniiia. This is partly referable to the impaired excretion
from the blood of substances no longer of use in the economy
and having toxic influences when retained, as the products of
proteid decomposition particularly; and the kidney is itself a place
in which special metabolic processes are carried on, the products
of which, as hippuric acid ( Bunge and Schmiedeberg), if retained
may apparently take part in the production of uraemia. The
regulation of the proportion of water in the blood is apt to be
disturbed in chronic renal aft'ections ; and, too, because of shrink-
age of the comparatively large capillary area of the kidneys, a
certain amount of resistance is likely to develop to the arterial
blood flow ; in these chronic affections, therefore, hydremia, cardiac
hypertrophy and general dropsy may be expected as secondary
features.
Disturbances of the Thyroid Function-
Destruction of the thyroid tissue by atrophy, degenerative
processes or heterologous tumors, involves the loss of an organic
function of vital importance ; disturbances of nutrition, loss of
physical strength and spasmodic attacks being induced, indicative
of a general autointoxication of the body and leading to a fatal
termination. In case of total extirpation of the thyroid gland
[including the parathyroids] intense nervous symptoms (delirium,
tetanic convulsions, and so-called tetany) quickly appear, as ob-
served in man. Dogs usually die after such operations in from
three to twenty-eight days and, too, under circumstances where
injurv to nerves, etc.. cannot be held responsible. After removal
of large portions of the thyroid there is also danger of autointoxi-
cation. Where the symptoms develop slowly, as is particularly
true in pathological atrophy of the glandular tissue, the resultant
condition is spoken of as cachexia strumipriva or athyrea; and
besides the nervous symptoms there may be observed spasmodic
460 Athyrea; Hyperthyrea.
dyspnoea, disturbances of growth, dilution of the blood and
cutaneous changes (falling out of hair, thickening and mucoid
degeneration of the subcutaneous tissue — myxcedema atrophicum,
stnimosum, operativum). Practically the same results are ob-
tained from experiments on monkeys, sheep, goats, hogs and dogs
as are observed in man after goitre operations (Hofmeister and
Eiselberg).
[The acute results mentioned, tetany, dyspnoea, convulsions,
palsies and death in a few days after ablation, are now generally
attributed to loss of the parathyroid glandules ; removal of the
thyroid alone is not essentially fatal, and is followed by chronic
metabolic disturbances in animals comparable to myxcedema in
man. The precise interrelation which probably exists between the
thyroid and parathyroids is not understood.]
It has been assumed (Rogowitsch) that the thyroid gland has
as its function the removal or neutralization of metabolic products
the retention of which in the system would produce toxic efifects,
that the organ probably, therefore, elaborates a secretory sub-
stance essential to the regulation of metabolism, which is appar-
ently carried into the blood from the follicles by way of the ex-
tremely delicate lymph channels (Lubarsch). This assumption is
founded upon the fact that a fatal result of operative removal
may be avoided by removing only one lobe of the gland and by
leaving some remnant of thyroid tissue or by favoring restoration
of the tissue by artificial means (transplantation of thyroid, in-
jection of thyroid extract), or if the parathyroids remain and take
up a vicarious [ ?] activity. It seems probable that the hypophysis
is able in some degree to compensate for loss of the thyroid by
vicarious hypertrophy; at least in thyroidcctomized rabbits en-
largements of the pituitary body have been observed (Rogo-
witsch, Stieda, Hofmeister).
In connection with enlargements of the thyroid {struma hyper-
plastica and, too, carciiiosa) a type of intoxication has been ob-
served, apparently the very opposite to that following extirpa-
tion of the organ, the so-called Basedozv's disease {hyperthyrea,
dysthyrea) ; this condition is very like the symptoms of intoxica-
tion which occur both in healthy human beings and animals
after large doses of thyroid extract, as accelerated and energetic
cardiac action (tachycardia), cardiac dilatation and cardiac hyper-
trophy, epileptiform seizures, prominence of the eyeballs (goggle-
Sexual Dislurbonces. 461
eyes, exophthalmiis), and various results of these disturbances.
The condition apparently depends, as pointed out by Mobius,
Greenfield, Rehn and others, upon a functional disturbance of the
organ which occasions either a quantitative or qualitative change
in the secretion (an excess of the secretion or one in which there
is a chemical change) ; but there are numerous uncertainties in
relation to these points, as for example, the failure of a case of
Basedow's disease to recover after extirpation or atrophy of the
gland (Lubarsch). Jewsejenko claims to have met this last dis-
ease also in animals (dog, horse) ; Reynard and Rongieux have
observed stupidity in dogs and horses after development of goitre.
Cretinism- and chondrodystrophy have been regarded as dependent upon
the thyroid function, but according to Lubarsch's studies there is appar-
ently no setiological relationship.
Disturbances of the Sexual Function.
Diseases and congenital anomalies of the sexual glands render
the individual impotent to produce viable offspring, in males pre-
venting formation of semen or procreation {impotence, impo-
tentia generandi ct coeundi), in female animals interfering with
ovulation, fertilization of the ovum and maturation of the embryo
{barrenness, sterility). Even general diseases (as fever, various
painftd affections of the muscles and joints, diseases of the spinal
cord) may indirectly influence the sexual function (loss of ex-
citabihty, mechanical interferences). According to Zschokke
even if only one ovary is diseased there is, as a rule, a disturb-
ance of the general sexual vitality. A number of affections of
the sexual glands, as tuberculosis of the ovaries, chronic inflam-
mation or cystic changes of these organs, or undescended testicle,
are apt to be accompanied by special excitability of the sexual
appetite (constant rutting, buUit.g, horsing, nymphomania, saty-
riasis), sometimes with violence of temper. In other cases, how-
ever, destruction of the sexual glands by disease or removal b)»
castration is followed by suppression of sexual vitality, altera-
tions in the state of nutrition, and changes in the bodily struc-
ture (change in the type of horns in oxen, loss of antlers in stag
and roe-deer, shape of body approximating female type, fat ac-
ctmiulation, gentle disposition in castrated male animals).
(For details cf. Zschokke, >Dic Unfruchtbarkcit dcs Rindes, Zurich,
1900.)
462 Disturbances of Cutaneous Function.
Local abnormalities of the uterus may, in a mechanical way,
determine the development of embryonal monstrosities or the
death and premature expulsion of the foetus {miscarriage, abor-
tion).
In cows and goats, less frequently in hogs, a form of paralysis
not infrequently appears within the first few days after parturi-
tion, at the time of establishment of lactation, the so-called
paralytic calf-fei'cr or paralysis of parturition. The cause of the
condition, as Schmidt (Kolding) has pointed out, depends on an
autointoxication related with the formation of colostrum. The
colostrum milk is very rich in disintegrating epithelium of the
mammary gland and apparently contains decomposition products
from these elements, which, if absorbed in large amounts, are
capable of giving rise to toxic efTeets. The condition is met espe-
cially in animals producing large amounts of milk, in case of un-
usually marked colostrum formation. The excellent results of
therapeutic measures directed to reduce the milk secretion and
causing oxidation of the poisonous products by introducing oxy-
gen into the udder and thus rendering them inert, permit the
acceptance of Schmidt's theory as well founded.
Disturbances of the Cutaneous Function.
The skin, with its epidermal covering, is an organ of defense
to the body against the harmful influences of the exterior. Any
traumatic denudation of the papillary layer or deeper wound de-
stroys the protection it aiTords, and not only exposes the denuded
surface to the drying influences of the air, but serves as a focus of
entrance of infectious agents as well, since the injury opens easy
access into the lymphatic paths. Long continued soaking of the
epiderm causes its maceration (by nasal discharge, urine, etc.),
continuous pressure leads to callosites or by contusion at places
which overlie bony prominences to ruptures of \\essels, haemor-
rhages, and in this way to disturbances of nutrition which may
cause necrosis of the skin (decubitus, decubital gangrene). The
loss of albuminates occasioned by leakage of lymph in case of
denudation of the epiderm (running sores of the skin and mouth)
may cause material deterioration of the state of nutrition of the
body (Landois).
To what extent disturbances may be caused by suppression
of the cutaneous interchange of gases (output of water and car-
Disltirbanccs of Perspiration. 463
bonic acid gas in the perspiration) we have but Httle knowledge.
According to Ellenberger in horses, which were shaved and then
covered with a coat of varnisli, there appeared slowing of respira-
tion, acceleration of pulse, a fall of the body temperature of one
to one and a half degrees centigrade, symptoms of uneasiness,
muscular twitchings, polyuria and increa'sed excretions of urea,
these symptoms soon disappearing; the animals took their food
without being at all urged and at the end of the experiment
showed a greater body weight than at the start. Hogs and dogs,
after being varnished, showed no disturbances of health beyond a
depression of the body temperature (cited from Schindelka).
Sheep, however, after being coated with varnish, apparently suffer
considerably (Ellenberger), and rabbits die if no more than one-
eighth of their body surface be covered with varnish, apparently
because of excessive heat dissipation (Landois, Fourcault, Bec-
querel and Brechet) ; in case the whole surface of the body is
varnished the temperature at once drops (to 19^ C).
For consideration of chilling of the skin. cf. p. 45.
Because of the vast numbers of sensory nerves ending in the
skin tiie least denudation of the papillary layer and inflanmiator\-
swelling of the cutis, as well as contact with foreign bodies, oc-
casion marked sensations of pain. . .
Pathological increase of ])erspiration, liypcridrosis (i8p6w, to
sweat), may be met in a great variety of conditions which give
rise to an excited state of the perspiratory centres in the medulla
oblongata and cord (excess of carbon dioxide in the blood, de-
ficiency of oxygen, sensory and psychic stimulation). Sweating
may be general or local, sometimes unilateral, or limited by a trans-
verse border strictly to the posterior portion of the body. In
these latter examples disturbances in the nervous distribution are
usually at the bottom of the trouble ; the abnormality is especially
striking in dogs which do not sweat normally.
Diminished secretion from the glands allied to sweat glands,
which are met in the nmzzles of the ruminants, the snout in pigs
and nose in dogs, as a result of which these parts, otherwise
always moist, come to feel (lr\ , is a marked symptom in all febrile
diseases.
In case of the entrance of urine into the peritoneal caviiy
after rupture of the bladder, or in urinaty infiltration of the cellu-
lar tissue after rupture of the urethra, the perspiration may take
464 Disturbances of Cutaneous Function.
on a urine-like odor; and in distemper in dogs and in the pock of
sheep the skin gives off an unpleasant, offensive odor.
A rough, bristling appearance of the hair, brittle, dry wool,
is a symptom of chronic nutritive fauhs; the same may be said
of diminution of the subcutaneous fat, when it becames tight, in-
elastic and adherent to the underlying fascise (so-called hide-
binding of the skin).
(For details v. Friedberger-Frohner, Lehrhuch d. klinisch. Untersiich-
ungstnethodcn f. Ticrarzte, Verl. von Ferd. Enke, Stuttgart, III. Auil.)
O--- THE '^
UNIVERSITY
I'latc I.
Fig. 1. Acute fibrinous pleurisy of horse. Yellow fibrinous exudate spread
over tne reddened, somewhat clouded, pleura of the right lung.
I
"^..A
lung.
Fig. 2. Chronic cheesy tuberculous pneumonia. Section of lobe of cow's
^- THE
DIVERSITY
OF
rioic II.
Fig. 1. Gangrene of skin of lower jaw of hog.
-s
\
%
Fig. 2. Hyperaemia of sl<in in swine erysipelas.
/
,^
Fig 1. Section of scrotum of bull with cheesy coagulation necrosis of tes-
ticle: the scrotal sac was filled with a sero-purulent exudate: the tunica vagmahs
communis and subcutaneous tissue were surrounded by a dense abscess capsule,
and a large blood clot was seen distributed throughout the sac.
Fig. 2. Focalized necrosis of liver of cow: the section shows the nodules of
coagulation necrosis of natural size.
■ t J
ri<(lr I
Fig. 1. Acute croupous enteritis; a portion of cow's intestine laid open;
the mucous membrane is the seat of hyperaemia and false membrane formation.
X V
Fig. 2. Fatty hvc of hog.
OF THE
UNIVERSITY
OF
INDEX
A PAGE
Actinomycosis 3iS
Fungous Growths of 320
" Fungus of 321
Actmomycotic Abscesses 320
" Nodules 320
Active Hyper3emia 112
Immunization 2S
Acute Diseases 95
Adenocarcinoma 39i) 407
Adenocystoma 4^8
Adenofibroma Pericaniliculare . . 390
Adenoma 388
^Etiology of 391:
" Varieties of 389
Adenosarcoma 39i
Agglutinins 26
Air Embolism 149
" Hunger 449
Akinesis 429
Albuminous Degeneration 190
Albuminuria 455
Alexins 19
Algor Mortis 104
Alimentation, Disturbances of . . . 36
Amaurosis 433
Amblyopia 433
Amboceptor 25
Amputation Neuroma 250, 358
Amyloid Degeneration 205
'' " of Liver . . . 207
" " Spleen . . 208
" Reaction 206
Ansemia 1 18, 157
Anaemic Infarct 145
Anassthesia 432
Anamnesis 93
Anasarca 130
Anatomical-pathological Proces-
ses 3
Anatomical T\pes of< Inflamma-
tion and Exudate 272
Angioneurosis 435
Angioplasts 240
Animal Parasites 76
" Poisons 51
Ante-mortem Clots 132
Anthracosis 215
Antibodies 22
PAGE
Antitoxine 24
Anuria 454
Apoplexy 425
Apparent Death ■ 105
Argyria 215
Aristotole 11
Ascites 130, 447
Asphyxia 38, 45i
" as Cause of Death.... 39
Ataxia 429
Athyrea 459
Atony of Stomach 439
Atrophy 185
Causes of 186
Autoblastomata 325
Autochthonous i\Ielanosis 209
" Thrombi 136
B
Bacillus ]\Iallei 311
Bacteria 54
" Mode of Invasion of. . 61
" Specific Action of 67
Bacterisemia 66
Basedow's Disease 460
Bile, Abnormal Secretion of . . . . 446
Biliary Stasis 212, 446
Blood Corpuscles, Regeneration
of 251
Blood, Impoverishment of 157
" Pathological Changes of. 156
" Variations in Ill
. " Vessels, Regeneration of. 240
Bone, Regeneration of 246
Botryomycosis 324
" Fungus of 324
Brain, Compression of 425
" " Svmptoms of 425
" Stroke ' 425
BufYy Coat 131
Burns 42
Fatality of 43
C
Cachectic CEdema 128
Cachexia 190
of Cancer 4^4
" Strumipriva 459
466
Index.
PAGE
Cadaveric Clots 132
Calcification 216
Calculi 216, 219
Biliary 222,
Intestinal 226
" Required Conditions of. 219
" Salivary 225
" Urinary 220
Callus 247
Cancer 394
Cachexia of 414
Cellular Morphology of. 402
Colloid 412
Cylindrical Cell 406
" Dissemination of 400
Glandular Cell 406
" Gross Appearance of . . . 410
" Metastasis of 401
Origin of 396
Pearls 405
" Scirrhus 413
" Transplantation of 398
Varieties of 403
Carcinoma 394
Cardiac Hypertrophy 106
" Insufficiency 109
Cardinal Symptoms 260
Cartilage, Regeneration of 246
Caseation I79
Catalepsy 428
Catarrhal Exudate 273
Catching Cold 45
Causes of Disease 35
Cavernous Hsemangioma ...362,363
Cellular Pathology 14
Cerebro-spinal Concussion 424
Cheesy Tuberculous Infiltration. 306
Chemical Agents 50
Chemico-pathological Processes. 4
Chemotaxis 18, 161
Chilblain 45
ChoLiemia 447
Cholelithiasis 223
Cholesteatoma 382
Cholesterin 195
Chondroma 35^
Chronic Diseases 95
Chronic Inflammation 284
Circulation, Disturbances of.... 106
Circulation, Schema of 140
Classification of Inflammatory
Processes 288
Clinical Observation
Clonic Spasms 428
Clot, Absorption of 125
" Formation 131
Cloudy Swelling 190
Coagulation Necrosis 179
Coagulins 26
Cohnheim's Theor>' 2)2)(>
PAGE
Colic 444
Collateral Circulation 143
CEdema 128
Colloid Degeneration 204
" Substances 204
Coma 425
Commotio Cerebri 424
Comparative Pathology 14
Compensation for Circulatory
Abnormalities 106
Compensatory Hypertrophy .... 255
Complements I9> 25
Complications 99
Concretions 216, 219
Concussion 50, 424
Congenital Diseases 30
Connective Tissue, Regeneration
of 237
Consciousness, Loss of 424
Consecutive Thrombi 136
Constipation 443
Constitutional Predisposition ... 31
(Contagious Diseases 71
Continued Fever 173
Convalescence I73
Convulsions 428
Corpora Amylacea 208
Flava 208
" Versicolorata 208
Corrosive Poisons 52
Cough 452
Cramp 428
Croupous Exudate 275
Inflammation 275
Cruor Sanguinis 131
Cylindrical Cell Cancer 406
Cylindroma 382
Cystic Tumors 415
Cystoma Penniferum 417
Cj'tolysins 25
D
Death loi
" Agony 103
" Causes of 102
" Local 176
Signs of 104
Decubitus 462
Degenerative Processes —
Albuminous 190
Amyloid 205
Colloid 204
Fatty 192
Hyaline I99
Mucoid 202
Delirium 426
Demarcating Inflammation . . 184, 2fcg
Depression of the Brain 425
Dermoid Cysts 416
Index
467
PAGE
Diabetes Insipidus 454
Mellitus 448, 457
Diagnosis Qi; 9i
Diapedesis 120
Diarrhoea 442
Digestive Disturbances 436
Dilatation of the Heart 109
Diphtheritic Inflammation ...... 276
Direct Symptoms 92
Disease i
" Causes of 35
Conception of 2
Course of 91- 94
Periods of 96
" Recovery from 100
Symptoms of 91, 99
" Termination of • ■ 99
Diseases. Congenital and Inher-
ited 30
Diseases of First Stomach 439
" Intestines 44°
"Jaw 436
" Liver 444
" Mouth 436
" CEsophagus 437
" Pancreas 447
" Pharvnx 437
" Stomach 437
" Teeth 436
Dissemination of Germs in the
Body 65
Disturbances of Alimentation
and Nutrition 3^
Disturbances of Circulation 106
Disturbances of Excretion of
Urine •. • 454
Disturbances of Function of Skin 462
Disturbances of JNIetabolism .... 165
Disturbances of Respiration .... 448
Disturbances of Sexual Func-
tion 461
Disturbances of Thyroid Func-
tion 459
Dizziness 424
Dropsical Transudate 129
Dropsy 126
Dwarfism 3^
Dyspepsia 438
Acida 438
Dysperistalsis 443
DyspncEa 449
Dysuria 458
E
Ecchondroma 35i
Ecchymoses 122
Ectogenous and Entogenous In-
fectious Agents 70, 71
Ehrlich's Theory 22
Electrical Influences 48
PAGE
Emboli 131, 138, 149
" Course of I39
Embryoma 421
Emphysema 450) 453
Empyema 281
Enchondroma 35^
Endarteries I44
Endemic Disease 72
Endothelioma 380
Endotoxines 58
Enostoses 354
Enteroliths 227
Enuresis 458
Eosinophilia 163
Ephemeral Fever...- 1/3
Epidemic Disease 73
Epiderm and Epithelium, Re-
generation of 242
Epilepsy 425. 428
Epithelial Cysts 4^5
Exhaustion 40
Exitus Lethalis loi
Exogenous Pigmentation 215
Exostoses 354
Expectoration 453
Experimental Pathology 8
External Respiration 448
Exudate 264
Eye in Death 105
F
Fainting 424
Falling Sickness 425
False Membrane 274
Fat Embolism 150
Fatty Changes 192
" Degeneration I93> 198
Infiltration 192
Faults of Heat Regulation 165
Fecal Concretions 226
Fever ■ 165
" Production of 168
Stages of 171
Types of I70
Fibrino-purulent Exudate 278
Fibrinous Exudate 273
Fibroblasts ~37
Fibroma 34i
Durum 34i
Growth of 345
Molle 342
Fibromatosis 345
Fistula 282
Flatulence 439
Food. Deprivation of 36
Freezing 44
Functional Abnormalities 423
" Overstimulation .... 40
" Pathological Disturb-
ances 4
468
Index.
G PAGE
Galen '• . . , I2
Gall Stones ^23
" " Composition of .... 223
Gangrene 181
Gangrenous Emphysema 183
Gastric Atony 439
Gelatinous Cancer 412
General Nervous Disturbances.. 423
Pathology 5
Germinal Variation 32
Giant Cells 239
" Cell Sarcoma 368
Gigantism 3i> 254
Glanders '. 311
'■ Abscesses .• 315
Bacillus of 311
Indurations 315
• '• Nodules 314
Ulcers 314
Glands. Regeneration of 244
Glandular Cell Cancers 406
Glioma 360
Retinal 361
Glycogenic Infiltration 205
Glycosuria 456
Gout 229
Granulation Tissue ....241. 283. 285
H
Hemangioma 3^^
Ha;matemesis 122
Hematocele 122
Haematogenous Pigmentation . .. 210
Hsematoma 122
Hematuria 122
Hemic Poisons 53
Hemochromatosis 210
Hemoglobinemia 160, 210
Hemoglobinuria 160, 211
Hemolysins 25
Hemopericardium 122
Hemoptysis 122
Hemorrhage 119
Results of 124
" Symptoms of 122
" Varieties of 121
Hemorrhagic Anemia 158
" Infarct I45
" Inflammation .... 283
Hemosiderin 211
Hemothorax ._ 122
Haptophore 23
Health, Definition of i
Heart, Condition of, in Disease. 106
Heat Regulation, Faults of 165
" Stroke 41
Hemiplegia 429
Hereditary Defects of Animals. . 34
" Man .... 33
PAGE
Heredity, Atavistic 33
Collateral 33
Direct 33 '
Latent 33
Heterotopic, Heterochronic and
Heterometric Processes ...... 3
Hippocrates 1 1
History of Pathology 10
Hodgkin's Disease 373
Homogeneous Thrombi 134
Hoof, Regeneration of 243
Host of a Parasite 7?
Humoral Pathology n
Hyalin Degeneration 199
Hydremia 161
Hydrocele 130
Hydrocephalus 130
Hydropericardium 130
Hydrops 126
Hydrothorax 130
Hyperacidity 438
Hyperemia 112
Hyperesthesia 43^
Hypercholia 213
Hyperchromatosis 209
Hyperglycemia 45^
Hyperidrosis 463
Hyperkinesis 427
Hj'perleucocytosis 162
Hypernephroma 393. 397
Hyperthermia 41, 165
Passive 166
Hypertrophy 254
I
Icterus 212, 446
Idiosyncrasy 20
Ileus 444
Immunity 16
Acquired 21
Active 28
Natural 24
Passive 28
Relative 20
Impotence 461
Incubation, Period of 64
Indirect Symptoms 92
Infarction 145
Infection 54
Embolic 05
" General 66
Local 65
Regional 65
Infectious Agencies ■• 54
" Diseases and Their
Agents, Table of . . 73
Matter 55
Inflammation 258
" Anatomical Types of 272
Cardiac Valves 272
Index.
469
PAGE
Inriainmation, Cardinal Symptoms
of 260
Causes of 258
Chronic 284
Corneal 271
Interstitial 285
" Nomenclature and
Classification .... 288
" Phenomena of .... 260
" Productive 284
Specific 286
" Suppurative 277
" Termination of .... 289
Inflammatory CEdema 128, 273
Inherited Diseases 30
Insanity 426
Intermittent Disease 95
Intestinal Calculi 226
Intestines, Diseases of 440
" Fermentation in .... 441
Intoxication 50
Intrauterine Disease, Origin of. . 31
Intussusception 443
Irritability, Psychic 426
Ischsemia 118
Itching 432
J
Jaundice 212
" Sequels to 214
L
Latent Disease 97
Leiomyoma 357
Leucocytosis 162
Leucopenia 162
Leukaemia 163
"Licking" 427
Lightning Stroke 48
Lipoma 346
Occurrence of 348
Liquefaction Necrosis 181
Liver, Diseases of 444
" Functions of 445
Local Variations in Amount of
Blood Ill
Low Temperatures. Effects of. . 43
Lungs, Diseases of 448
Lymphangioma 364
Lymphatic Thrombosis 154
Lymphatismus 27^
Lymphogenous Embolism 154
Lymphoma ^,72
M
Malignant Embolism 151
Mania 426
PAGE
-Marasmus 190
^Mechanical Influences 49
]\Ielanin 209
Melanoma 2>77
Melanosarcoma 377
Melanosis 209
Metabolism in Fever 173
Metastasis 151
jNIeteorism 439
Methaemoglobin 160
Metrorrhagia 122
Miasmatic Disease 71
]\Iicrobes 54
Microphytes 17
Microzoa 17
Miliary Tubercle 300, 303
Alineral Poisons 51
Miscarriage 162
Miserere 444
Mixed Infection 69
Thrombi 135
Motor Disturbances 427
Automatic . 427
Coordinated 427
Reflex 427
Voluntary . 427
JMucoid Degeneration 202
Mummification 179
Muscle, Regeneration of 245
Myelogenous Sarcoma 369
Myoma 356
Myositis Ossificans Progressiva. 355
Myxcedema 460
Myxoma 349
Myxosarcoma ....'. 369
N
Necrosis 176
Causes of 177
Symptoms of 183
" Terminations of 184
" with Coagulation 179
" " Desiccation .... 179
Putrefaction . . . 181
Softening 181
Neoplasms 325
Nerves, Regeneration of 248
Nervous Disturbances 423
" Hypertrophy 257
Neuralgia 431
Neurofibroma 359
Neuroma 358
" Amputation 250, 358
Neuromyxoma 359
New Growths 325
Nosolog>^ 5
Nutrition, Disturbances of 36
Nymphomania 426
470
Index.
O PAGE
Obesity 197
Obstruction of Intestines 443
" Blood Vessels... 131
Occluding Thrombi 136
Odontoblastoma 418
Odontoma 418
" Durum 419
" Mixtum 419
CEdema 126
" Results of 130
Oligsemia 157
Oligocythsemia 157
Oliguria 454
Oncology 326
Organization of Thrombi 138
Osteoclasts 248
Osteocystoma 420
Osteoma 353
" Varieties of 353
Osteo-sarcoma 353
Oxygen Supply, Deprivation of.. 38
P
Pain 431
Palsy 429
" Results of 430
Pancreas, Diseases of 447
Pandemic Disease 72,
Papilloma 383
Paradoxical Embolism 142
Parsesthesia 432
Paralysis 429
Paralytic Calf Fever . . 462
Paraplegia 429
Parasites 76
Table of 82
Parasitic Diseases 76
Parenchymatous Inflammation. . 287
" Poisons 53
Passive Congestion 115, 127
" Hypersemia 114
" Hyperthermia 166
Pathogenesis 4
Pathogenic Microorganisms .... 55
Pathognomonic Symptoms 92
Pathognomy 5
Pathological Changes of the
Blood 156
Pathological Processes, Classes
of 3
Pathology i
" History of 10
Periostoses 354
Perithelioma ■ 382
Petechise 122
Petrification 216
Phagocytosis 18, 161
Pharynx, Diseases of 437
Phlegmon 282
Pigmentation 209
Pigmented Tumor t,-/~
PAGE
Placental Origin of Disease 30
Plethora 157
Poikilocytosis 159
Poisons 50
" Classification of 52
Polychromatophilia 159
Polymorphocellular Sarcoma.... 369
Polyuria 454
Post-mortem Clots 132
Precipitins 26
Predisposition 16
Pressure Atrophy 187
Primary Lesion 98
" Thrombi . .'. 136
Processes of Repair and New
Formation 232
Productive Inflammation 284
Prognosis 94
Progressive Inflammatory Ostei-
tosis 355
Prophylaxis 5
Protective Substances 21
Proud Flesh 28^
Psammoina 382
Psychical Disturbances 424
" Excitement 426
Ptyalism 436
Pus 277
Concretions 228
Putrefaction After Death 105
" of Exudate 283
Putrid Necrosis 181
R
Ray Fungus 321
Receptor 22
Recovery from Disease 100
Red Thrombi I35
Regeneration 232
" Capacity for 235
" of Blood and Lymph 251
" Blood Vessels ... 240
" Bone and Car-
tilage 246
" " Connective Tissue 237
" Corneal Epithe-
lium 243
" " Epiderm and Epi-
thelium 242
" " Glands 244
" Hair 243
" " Hornv Tissue. . . 243
" Muscle 245
" " Nerves 2.18
" Tendon Tissue. . 246
Remittent Disease 95
Resistance to Disease 16
Respiration, Disturbances of.... 448
Respiratory Faults 38
Retrograde Embolism 142
Rhabdomyoma 356
Index,
471
PAGE
Riding F.niliolus I39
Rigor Mortis 104
Round Cell Sarcoma 36/
S
Sago Spleen 208
Salivary Calculi 225
Salivation 436
Sapreniia 185
Saprophytes 56
Sarcoma 365
Cells of •• 365
Classes of .. 366
■' Development and AiU-
ology of 371
" Gross Appearances of. 370
Scars Following Infarction 147
Scirrhus Cancers 41 3
Secondarv Lesions 98
" ' Thrombi 136
Secretory Abnormalities 435
Sensation, Pathological Diminu-
tion of 43 '
Sensory Disturbances 431
Sequestration 178, 184
Sero-fibrinous Exudate 275
Serous Inflammation 273
Exudate 273
Sexual Organs, Diseases of.... 461
Shock 50
Side-chains 22
Skin Diseases 462
Spasms 427
Results of 429
Special Pathology 5
Spindle Cell Sarcoma 368
Squamous Epithelioma 404
Starvation 36
Stellate Cell Sarcoma 369
Sterility 461
Stomach, Diseases of 437
Strangulation of Intestine 443
Stratified Thrombi 135
Struma Petrificans 2ig
Sudden Death 103
Sufit'ocation 451
Suffusion of Blood 122
Suppuration 277
Symptomatology Qi
Symptoms of Death 104
Syncope 424
T
Tendon Tissue. Regeneration of. 246
Teratoma 4i5- 42t
Terminations of Disease 99
Therapeutics 94
Therapy 5
Thermic Influences 41
Thermometry I75
Thrombosis 131
PAGE
Thrombosis, Causes of 132
Results of 142
Thyrt)i<l Function, Disturbances
of 459
Tissue Immunity 63
" Predisposition 63
Tonic Spasms 428
Toxalbumens 51
Toxincs 51. 57
Toxophore 23
Transplantation 251
Traumatic Influences 49
Trophic Disturbances 434
Tuberculin 310
Tuberculosis • . . ■ 291
" Anatonn"cal Lesions
of 298
Bacillus of 292
Heredity of 295
" Mode of Contagion. 294
Symptoms of 310
Tuberculous Cavities 307
" Granuloma 305
Ulcers 305
Tumors 325
.Etiology of 3.V^
" " " Cohnheim's
Theory . . 3,Vi
Classification of 34°
" External Shape of -^28
Growth of 328
" Pathological Signiticance
of 329
U
Ubiquitous Disease 72
Ulcer 282
UnderuMtrition 38
Uniceptors 24
Uraemia 459
Urinarv Calculi 220
" ' Gravel 220
Organs, Diseases of.... 454
Urolithiasis 220
V
Valvular Thrombi 136
Vasomotor Disturbances 435
Vegetable Poisons 5'
Vertigo 424
Vibices 122
Virulence of Toxines 58, 59
Vomiting 44°
Vomitus 440
W
Wart 385
Water, Withdrawal of 37
White Thrombi 135
Work Hypertrophy 254
W. T. KEENER & COMPANY
Medical Publishers and Importers
90 WABASH AVENUE. - - CHICAGO
text-book of comp-\rative general pathol-
ogy for the use of practitioners and
stlT)ents of veterin-Ary medicine.
By prof. dr. TH. KITT. of MuincH.
Auttorized translation from the German by Ds. William W. Cadjbl'ky,
Assistant Demoijstrator of Pathplogy; Edited by Dr. Att.fn J. Smith,
Professor of Pathology in the University of Pennsylvania.
One volume, royal 8vo. With four colored plates and one hundred and
thirty-one illustrations in the text. Cloth, $5.25 net
Kitt's work on General Pathology is the only especi-al text-
book on Veterinarv- Pathology published. Heretofore students
and veterinarv- surgeons have had to consult works on human
medicine in order to learn the foundations of pathology- ; this vol-
ume, however, is ■wnritten with special reference to the student of
animal medicine.
After an introductory review of the general conceptions of
disease and of the history of patholog}'. the causes of disease are
discussed: then pathologic disturbances under four main headings.
viz.: (r) Circulatory Disorders; (2) Metabolic Disorders, Degen-
erations and* Necroses: (3) Reparatory Processes and ProHfera-
tion: (4) Functional Disorders. All of the most common and
characteristic processes are illustrated by a number of original
drawings and colored plates.
The style of the book is terse and concise and all the defini-
tions are clear cut: the work is thoroughly up to date, as all the
results of the recent investigations with the pathology and etiologv'
of disease are included in the text and are described in a very
simple and popular manner. The practicing veterinarian will find
in this book a modem work, convenient for ready reference, and
containing evervi:hing that we know to-day regarding Veterinary
Patholos^'.
W. T. Keener & Co.^ CniCAGa
SURGICAL DISEASES OF THE DOG AND CAT.
With Chapters on An?esthetics and Obstetrics.
(Second Edition of Canine and Feline Surgery.)
By FREDERICK T. G. HOBDAY, R R. C. V. S., F. R. S. E.
Member of the Board of Examiners of tlie Royal College of Veterinary
Surgeons ; Late Professor in the Royal Veterinary College, London ;
Consulting Veterinary Surgeon to the British Bulldog and Griffon
Bruxellois Clubs; Honorary Veterinary Surgeon to the Ladies' Ken-
nel Association, the Fox-Terrier Club, etc.
One volume, 366 pages, 5^x8^ inches.- With 241 illnstrations.
Cloth, $3.25 net.
"The reception accorded to the first edition has proved that
a small text-book of the kind was distinctly wanted, and in pre-
senting a second and enlarged edition the author regrets that
illness and other causes have allowed the first to remain so long
out of print.
By the request of numerous friends, the work has been en-
larged to include symptoms and general details of treatment other
than that which may be described as purely surgical, although the
original idea of the author to keep the book as a handy manual for
their final-year student has still been adhered to.
The introduction of antiseptics has revolutionized all of the
old-fashioned ideas, and has benefited the animal world to almost
as great an extent as that of man.
It is true that we have not quite the same advantages as our
confreres in human surgical practice, but it is astonishing what
can be done by strict attention to the principles introduced by the
discoveries of Pasteur, and applied to surgery by the teachings of
Lister.
Operations which only a few years ago were looked upon
beforehand with dread are now done every day, and owners of pet
animals have learned to appreciate the value of modern antiseptic
methods almost as much as the members of the profession them-
selves." — Extract from Preface.
W. T. Keener & Co., Chicago.
SPECIMEN PAGE.
OPERATIONS ON THE MOUTH, PHARYNX, ETC. 133
After-treatment consists merely in the application of a
little antiseptic lotion (boric acid, chinosol, or permanganate
of potash) several times a day.
Sarcoma or Carcinoma — Symptoms. — As a general rule
the first signs will merely be a capricious appetite and diffi-
culty in swallowing, the animal appearing to have a very sore
throat. There is salivation, and, after the trouble has existed
-7=!€^^
Fig. 102. — Carcinoma of the
Pharynx and Cervical Glands
of a Terrier.
Fig. 103. — Endothelioma per-
forating the Palate of a Creat
Dane.
for a few weeks, a gradual emaciation of the body will be
observed. It is not uncommon upon discovering a sore at
the back of the mouth, such as is illustrated in Fig. 102, for a
diagnosis to be made of an injury from a sharp bone or a
piece of stick. This had been actually done in each of the
cases from which Figs. 102 and 103 were sketched. All doubt
on this question can be set aside if the wound has a ragged,
ulcerated appearance, shows no tendency to heal after careful
AN UNIVERSAL STANDARD.
FRIEDBERGER & FROHNER'S
VETERINARY PATHOLOGY.
(Authorized Translation)
Bv M. H. HAYES, F. R. C. V. S.
Author of "Points of the Horse," "Veterinary Notes for Horse Owners," etc.
Edited by JOHN DUNSTAN, M. R. C. V. S.
Professor of Surgery and Therapeutics at the Royal (Dick) Veterinary
College, Edinburgh.
There has long been wanting in Veterinary Hterature a com-
prehensive text-book deaHng with the Diseases of Animals from
their clinical, pathological and therapeutic standpoints and which
might have some claim to the term "modern." This gap was effi-
cientl}- filled in Germany by P'riedberger and Frohner's splendid
production, the value of which was soon correctly estimated by
veterinary surgeons of all nations.
The late Captain Hayes, the most prolific English veterinary
writer of modern times and editor of many valuable works on
veterinary and equine matters, ever quick to appreciate merit,
bought the right to translate the work into English. Two editions
of the first volimie were published during his life, and he was
engaged on the translation of the second volume at the time of his
^eath. Dr. Dunstan was requested by ]\Irs. Hayes to complete
this volume. The work has also been translated into French and
Russian and is the recognized text-book in American and Euro-
pean Veterinary Colleges.
Two volumes, 8vo. 1,285 pages. Cloth. Price per set, $8.00 net.
CONTENTS.
VOLUME I.
Chapter I, Infective Diseases; II, Miscellaneous Infective Diseases; III,
Chronic Constitutional Diseases ; IV, Addenda to Infective Diseases ;
V, Notes on Bacteriology; VI, The Terms Infection and Contagium.
VOLUME 11.
Chapter 1, Diseases of the Organs of Digestion; II, Diseases of the
Esophagus; III, Diseases of the Stomach; IV, Diseases of the Liver;
V, Diseases of the Peritoneum; VI. Diseases of the Spleen; VII,
Diseases of the Urinary Organs ; VIII, Diseases of the Sexual
Organs; IX, Diseases of the Heart and Larger Blood Vessels ;^ X,
Skin Diseases; XL Diseases of the Locomotory Organs; XII, Trichi-
nosis in Swine; XIII, The Measles of Domestic Animals; XIV,
Miescher's Tubes or Rainey's Corpuscles; XV. Diseases of the Nervous
System; XVI, Diseases of the Spinal Cord and of Its Membranes;
XVII, Diseases of the Peripheral Nerves; XVIII, Neurosis without
Known Anatomical Basis; XIX. Appendix to Diseases of the Nervous
System; XX, Diseases of the Respiratory System; XXI, Diseases of
the Accessory Cavities of the Nose; XXII. Diseases of the Larynx;
XXIII. Diseases of the Trachea and Bronchi; XXIV, Diseases of the
Lungs; XXV, Diseases of the Pleura; XXVI, Appendix to Diseases
of the Respiratory Organs.
OPINIONS OF FRIEDBERGER & FROHNER.
"It is this work tliat I recommend to my students, and believe that of all
works on Veterinary Medicine, it is the best adapted to class room use."—
Leonard Pearson. Dean and Professor of Practice Veterinary Medicine, De-
partment of Veterinary Medicine, TTniversity of Pennsylvania.
"Hope you will be amply repaid for its production— this, the most modern
and bes't text-book we have."— J. L. Robertson. Professor of Veterinary Medi-
cine. New York Veterinary College.
"I take pleasure in making a very favorable report, after a careful review,
on Veterinary . Pathology bv Friedberger and Frohner, translated by M. H.
Hayes, F. R. C. V. S., and consider it the best work to-day on theory and
practice of Veterinary Medicinp for stud^Mts' use, and have recommended it to
the students of the Chicago Veterinarv College."
(Signed) A. H. B.\KER. V. S..
Dean 'of Faculty and Professor of Theory and Practice.
"I find that the print is excellent, that the tmnslator has put the t'-chnioal
statements into free and easily understood English language, making the text
easily comprehended by the .average student. You will note by the catalogue
mailed you this day this work has been adopted as the text-book of this
college."— S. Stewart. M. D., D. V. S., Professor of Veterinary Medicine. Kaii,sis
City Veterinary College.
"For many years Friedberger and Frohner's 'Lehrbuch der Speciellen
Pathologie und Therapie der Hausthiere' has been considered by competent
.iudges to be the best treatise on diseases of animals and their treatment. It
is not alone of inestimable value to the practitioner, but it must be regarded as
an important addition to medical literature, fo which the research scholar
gladly turns. The work has already been translated into French and Russian,
and is used as a text-book in those countries. An English translation should,
therefore, be hailed with delight, as there is no really good English work
covering the Practice of Veterinary Medicine." — Boston Medical and Surgical
Journal.
M Ordering FRIEDBERGER and FROHNER to ensure latest edition specify Hayes' Translation.
W. T. Keener & Co., Chicago.
Tiie only strictly up-to-date Veterinary Physiology in the English language.
ESSENTIALS OF PHYSIOLOGY FOR
VETERINARY STUDENTS
By D. NOEL PATON. M. D., B. Sc, F. R. C. P., Ed.
Superintendent of Research Laboratory of the Roj-al College of Physicians
of Edinburgh ; Lecturer on Physiology, School of Medicine of the
Royal College, Edinburgh : Examiner in Physiology in the University
of Glasgow and for the Royal College of Physicians, Edinburgh, and
late Examiner in the L^niversity of Edinburgh ; Examiner in Physiology
for the Royal College of Veterinary Surgeons ; Late Professor of
Physiolog}', Royal Dick Veterinary College, Edinburgh.
One volume. 428 pages, 5^x8^ inches. Profusely illustrated.
Cloth, $3.00 net.
Between the Physiology of man and that of domestic animals
there is no fundamental difference and most of our knowledge of
human physiology has been acquired from experiments tipoii the
lower animals. Btit while the tissues of a man. a dog and a horse
act mttch in the same manner, the mode of ntitrition of these tis-
sues is somewhat dift'erei>t and rec[uires special attention in the
case of each.
In this volume the attempt is made to give the Essentials of
General Physiology and of the special physiology of the domestic
animals in a form suitable to the requirements of students and .
practitioners of veterinary medicine.
OPINION.
"The examination which we have been able to give this work
has left a ver\- favorable impression, as it appears that the essen-
tials have been included, with nothing omitted except the padding,
which in some text-books of physiology reqtiire a vast amount of
reading to extract them, resulting in much confusion to students
and those who do not have the time nor inclination to make the
search for facts.
"We recommend the work heartily in the sense that it reduces
the study of physiology to a 'reasonable' basis, and the atithor has
done for the reader what is a difficult task upon his own account.
Well printed, well bound, intelligently illustrated, ]\Iessrs. Keener
have placed a 'reasonable" physiology before the profession at a
reasonable price." — Am. Vet. Reviezv.
W. T. Keener & Co., Chicago.
specimen Page of Patau's Veterinary Physiology.
THE FOOD AND DIGESTION
307
up and prepared for digestion. In the horse the lips are
long and prehensile, and are essential for the taking of food.
Into the mouth three pairs of compound glands — the
Salivary Glands — open. The
parotid, lined entirely by
enzyme-secreting epithelium,
opens on the side of the
cheek, while the submaxillary
gland, composed partly of acini
with enzyme - secreting, and
partly of acini with mucin-
secreting epithelium, and the
sub-lingual, composed entirely
of mucin-secreting acini, open
under the tongue (S.G.).
The tongue in the horse is
smooth, but in the ox, and
especially in the cat, it is
covered with a fine fur of
processes, the filiform papilla,
which are of use in passing
the food backwards along its
surface in the act of swalloAv-
ing. (For Organs of Taste see
p. 132.)
Posteriorly, the mouth opens
into the pharynx (Ph.) or upper
part of the gullet. In the
horse the soft palate is very
long, reaching to the base
of the epiglottis, and, unless
during swallowing, shutting oft
the mouth from the pharynx
(Fig. 137). On each side,
between the mouth and the
pharynx, is the tonsil (T.), an almond-Hke mass of lymphoid
tissue. The pharynx is a cavity which can be shut off
above from the posterior nares by raising the soft palate,
and by pulling forward the posterior pharyngeal wall. It is
surrounded by three constrictor muscles, which, by contracting
Pig. 138. — Diagram of the Parts of
the Alimentary Canal, from Mouth
to. Anus. T., Tonsils; Ph.,
Pharynx; S.C., Salivary Glands;
Oc, CEsophagus ; C, Cardiac;
Py., Pyloric Portion of Stomach ;
i). , Duodenum; Li., Liver; P.,
Pancreas ; ./■., Jejunum; /., Ileum ;
v., Vermiform Appendix; Col.,
Colon ; li., Rectum,
ANNOUNCEMENT
PATHOLOGY
OF
METABOLISM
Edited by
CARL VON NOORDEN
FIRST MEDICAL CLINIC, VIENNA. LATE OF FRANKFORT.
Contributions by
ADALBERT CZERNY iBreslam, CARL DAPPER (Kissingem,
FR. KRAUS (Berlin I, OTTO LOWEI (Viennai, ADOLF
MAGNUS-LEVY (Berlin), M. MATTHES iColognei, LEO
MORH (Berlin), CARL NEUBERG (Berlin), HUGO SALOMON
(Frankfort, AD. SCHMIDT (Dresden), FRANZ STEINITZ
(Breslaui, H. STRAUSS (Berlin i, W. WEINTRAUD (Wiesbaden).
SECOND EDITION
Authorized English Translation. Edited with Additions.
By
I. \VALKER HALL, M. D.
Professor of Pathology, University College, Bristol.
THREE VOLUMES, 8vo. - - CLOTH, $16.00
Payable, $4.00 on receipt of Volume One; $6.00 on receipt
of Volume Two and $6.00 on receipt of Volume Three
W. T. KEENER & CO., CHICAGO
1906
#
PREFACE TO THE_ENGLISH EDITION.
An Ensflish Edition of von Xoorden's well-known "Lehrbuch
Stoffwechsel" does not require any sf)ecific introduction.
Although the arrangement of the sections and their contents is
the same as that of the first edition, the present text is mainly due
to the co-operation of a number of workers in this branch of
Medical Science. In his preface to the first German Edition,
von Noorden acknowledged the encouragement and assistance of
Gerhardt, von Jurgensen and Riegel ; in his introduction ^o the
second edition, he expresses his grateful thanks to the collabora-
tors, ''whose unflagging and zealous work alone has made it possi-
ble to bring out. instead of a second edition of my text-book, a
hand-book of the pathology of metabolism" worthy of the extent
and importance of the subject.
The length and style of the German original has restricted the
addition of the more recent work in detail. The additions made
to both the text and bibliography have conformed to the general
principle of the work in presenting a compilation of facts and a
critical discussion of hypothesis rather than the enunciation of
theories ; they have also been selected in harmony with the view
of von Noorden and others, that experiments upon animals should
be cited only in connection with acute conditions ; as it is so difficult
to compare them with the conditions which obtain in the chronic
diseases of human beings, these addenda have been incorporated
in the text.
It is a pleasure to express my thanks to my colleagues for
their translations, to iny friend Professor T. H. ]\Iilroy, for the
many valuable suggestions and to the University College Demon-
strator in Pathology, Dr. Carey Coombs, for his careful prepara-
tion of the indices.
CONTENTS OF THE VOLU^IES.
Volume I.
The Physiology of Metabolism.
By ADOLPH MAGNUS 'LEVY.
Volume II.
Subject. Author. Translator.
Hunger and Chronic Inanition. . v. Noorden A. Jex Blake, ]M. D.
Over Feeding v. Noorden R. W. Marsden, ]\I. D.
Subject. Author. Translator.
Fever and Infection F. Kraus J. O. Wakelin Bar-
rett, D. Sc. M. D.
Stomach and Intestinal Dis-
eases Ad. Schmidt H. French, M. D., F.
R. C. P.
Liver Diseases W. Weintraud R. W. Webster, M. D.
Respiratory and Circulator}'
Diseases M'. Matthes A. Jex Blake, M. D.
Blood Diseases H. Strauss J. A. Milroy, M. A.,
M. D.
Renal - Diseases , . v. Noorden C. Edgeworth, M. D.
Volume III.
Subject. Author. Translator.
Diabetes Carl von Noorden . . H. French, ^I. D.,
F. R. C. F.
Obesity Carl von Noorden . . D. Spence, Ph. D.
Gout Carl von Noorden . . ,R. ^^^ Webster. M'. D.
Diabetes Insipidus and Addi-
son's Disease Leo Mohr T. J. Horder, M. D.
Thyroid Gland A. ]\Iagnus Levy . . A. Jex Blake, M. D.
Carbohydraturia Carl Neuberg J. Dixon Mann, M. D.
F. R. C. P.
Cystinuria
Alcaptonuria, Oxaluria, Phos-
phaturia Carl Neuberg W. H. Hurtley, D.
Sc.
Nervous System
Muscles Leo Mohr A. Edwards
Bones
Cancerous Affections Adolf Schmidt .... W. Cramer, Ph. D.
Skin Diseases Salomen and
von Noorden .... J. A. Nixon, ]\I. B.
Childhood Czerny and
Steinitz J. Fortescue Brick-
dale, M'. D.
Influence of Drugs and Poisons. Otto Lowei J. Fortescue Brick-
dale, M. D.
Bath and Climate Matthes J. A. Nixon, 'M. B.
Phototherapeutics H. Salomen A. Edwards.
Volume I will be pulilished in the late autumn of 1906. Volumes II
and III in 1907.
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