Harry Gideon Wells.

Chemical pathology; being a discussion of general pathology from the standpoint of the chemical processes involved online

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Online LibraryHarry Gideon WellsChemical pathology; being a discussion of general pathology from the standpoint of the chemical processes involved → online text (page 1 of 86)
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Chemical Pathology



BEING A DISCUSSION OF GENERAL PATH-
OLOGY FROM THE STANDPOINT OF
THE CHEMICAL PROCESSES INVOLVED



BY

H. GIDEON WELLS, Ph.D., M.D.

PROFESSOR OF I'ATIIOLOGY IN THE UNIVERSITY OF CHICAGO ANU IN

RUSH MEDICAL COLLEGE. CHICAGO; DIRECTOR OP THE

OTHQ S. A. SPRAGOE MEMORIAL INSTITUTE



TJIIRD E Din ON, REVISED AND RESET



PHILADELPHIA AND LONDON



W. B. SAUNDERS COMPANY

1918



x:5



*^^'



Copyright, 1907, by VV. B. Saunders Company. Revised, entirely
reset, reprinted and recopyrighted, February. 1014. Revised, entirely
reset, reprinted and recopyrighted, January, igiti.

Copyright. 19 18. by W. B. Saunders Company



PRINri;i> l.\ AMERUA



TO

XuOvici Ibelitoen

THIS BOOK IS RESPECTFULLY DEDICATED. AS A

SLIGHT TOKEN OF THE GRATITUDE AND

ESTEEM OF HIS PUPIL



nSOBOl



PREFACE TO THE THIRD EDITION

Despite the war, active investigations in the chemical problems of
disease have continued, even in those countries most deeply involved
in the conflict. Although some of the later publications of foreign
countries have not been directly accessible, but few have not been avail-
able at least through abstracts, and it is believed that most of the
literature of importance, within the scope of this book, has been con-
sidered in its revision, although the rule previously followed of quot-
ing only from the original articles has of necessity been violated in
several instances. The new additions to our knowledge in the three
years since the second edition was issued have been so numerous that
it has again been necessary to reprint the entire work. Several sub-
jects have been largely rewritten, especially Gout, Specificity of Im-
munological Reactions, Anaphylaxis, Icterus, Acidosis, Diabetes and
Uremia. New sections have been added on the Abderhalden Reaction,
Specificity, Chemical Basis of Growth, Atrophy, and the Pressor
Bases, as well as many briefer additions. As previously, every effort
has been made to make the discussion of each topic as brief as con-
sistent with reasonable clearness and completeness. Where new
articles including older references have been quoted, the latter have,
in most instances, been omitted from the book.

Again I must express my indebtedness to the several colleagues
who have been so kind as to read over various sections of the book and
to help me with their suggestions; and also to the members of my
Department who have helped me so generously with the proof reading,
especially Dr. Lydia ]\I. De Witt and Miss Harriet F. Holmes.

Dr. R. T. Woodyatt has kindly revised the chapter on Diabetes,
which he contributed to the second edition. Since that edition was
printed much valuable information on the subject of carbohydrate
metabolism has been contributed from Dr. Woodyatt 's own labora-
tory, and through his new method for accurately timed and measured
intravenous injections the way has been opened for many advances in
the study of metabolism under both normal and pathological condi-
tions.

H. G. W.

Chicago, III., November, 1917.



PREFACE TO THE FIRST EDITION

DxjKiNG the past score of years the subject of biological chemistry
has attracted the attention and labors of a constantly increasing num-
ber of investigators, many of whom have, for one reason or another,
been interested in ])atlu)logical conditions. Sometimes the physiologist
has souglit for light on his problems in the evidence afforded by related
pathological conditions. Frequently clinicians have studied the meta-
bolic clianges and the composition of the products of disease processes.
Relatively seldom, unfortunately, has the pathologist attacked his
problems by chemical methods. From the above and other sources
have come scattered fragments of information concerning the chemi-
cal changes that occur in pathological phenomena. Only when bearing
upon conditions such as gout and diabetes, which concern alike the
physiologist, the clinician, and the pathologist, have the fragments
been moulded together into a homogeneous whole. For the most part
they still remain isolated, uncorrelated, frequently unconfirmed items
of information, scattered through medical, chemical, physiological, and
physical literature.

It has been the aim of the writer to collect these scattered fragments
as completely as possible, and to use them as a basis for a consideration
of General Pathology from the standpoint of the chemical processes
which occur in pathological conditions. Owing to the diffuselj^ scat-
tered conditions of the literature on which this work is based, it cannot
be claimed that all of the many contributions from which useful in-
formation might be obtained have been noticed ; but it is hoped that
a sufficiently thorough collection of material has been made to afford
a fair basis for a consideration of "Chemical Pathology." The time
seems ripe for an effort of this nature. Within the past few years
great and encouraging advances have been made in biological chem-
istry, which in many instances seem to throw light upon pathological
processes. In medicine, the use of chemical methods in the study of
clinical manifestations has become more general, and has yielded
valuable information. Pathologists have come to feel that the op-
portunities for the acquirement of knowledge by means of morphologi-
cal studies have become reduced to a mininmm, while the fields of
pathological phj^siology and chemistry lie still almost unexplored.
The development of research upon the subject of natural and acquired
immunity has presented innumerable problems, all of which are
essentialiv chemical. And perhaps most important of all is the general



8 P KEF ACE TO THE FIRST EDITION

av:akonIn^ of an appreciation of the importance of physiological chem-
it.tr> to medical science, wtiich has led to the introduction of laboratory
courses on this subject in every medical school worthy of the name.

A book on Chemical Pathology should, therefore, seek to supply
information to a varied group of readers. It sliould furnish collateral
reading to the student who for the first time goes over the subject of
General Pathology, which his text-books usually consider chiefly from
the morphological standpoint. It should exploit to the graduate in
medicine tlie advances that are being made along lines that are of
fundamental importance to clinical medicine. It should serve for the
investigator in biological chemistry or in pathology as a source of
information concerning the ground upon which the two subjects over-
lap — the "Grenzgebiete" of Pathology and Physiological Chemistry.
And, above all, it should afford a guide to the sources of our knowledge
of these subjects, since nothing but direct familiarity with the original
reports of the investigators themselves can give the student an im-
personal view of the actual status of the questions under consideration.
On account of this multiplicity of the objects in view, it has often been
necessary to consider certain topics from more than one standpoint ;
which explains, perhaps, certain apparent irregularities in the style
and manner of treatment.

It has been assumed that the reader has at least an elementary
knowledge of organic and physiological chemistry. For the benefit
of those whose studies in these subjects date back some years, it has
seemed advisable to include in an introductory chapter an epitome of
the more modern views concerning the chemistry of the protein mole-
cule, the composition of the animal cell, and the principles of physical
chemistry, in as far as they apply to biological problems. The general
consideration of ''Enzymes" in Chapter II is written with a similar
object. In discussing these fundamental topics it has seemed advis-
able to omit detailed references to the numerous original sources, —
these may be found quoted in the special text-books cited in the foot-
notes; but in presenting the more distinctly pathological topics the
attempt has been made to render all the important literature available
to the reader and investigator. To economize space, a complete bibli-
ography has not been inserted when this exists already eollected in
some readily accessible review or original article ; hence the references
cited in the foot-notes will generally be found to include only the more
recent publications. These references have been so selected, however,
that they will be found to furnish bibliogra]ihical matter sufficient to
lead the investigator to all the important litei-ature on the topics
covered in this book. As to those subjects (such as gout, diabetes, and
gastro-intestinal putrefaction) which, because of their great practical
clinical interest, have already been discussed in available monographs
at greater length than the scope of this work would })ermit, it has
seemed appropriate merely to summarize the most recent views and



PREFACE TO THE FIRST EOmON 9

advances, referring the reader to tlie ,s])eeial treatises for the general
and historical discussions.

It is with the greatest pleasure that I acknowledge my indebtedness
to many colleagues in the University of Chicago, who have kindly read
the sections of my manuscript tliat touch upon tlieir own special fields,
and whose criticism and advice have been of the greatest assistance ;
their number alone prevents my thanking them by name. Most par-
ticularly, however, must I express my debt to my former instructor,
Professor Lafayette B. jMendel, of Yale University, whose kindly
criticism and suggestions have been of inestimable value. For con-
stant assistance in the preparation of the manuscript, and for the
revision of the bibliography, I am indebted to my wife.

H. G. W.



CONTENTS

CHAPTEU i I'AGK

iMKODUCnoN 17

The ClIEMlSTKY and rilYSlCS OF THE CELL 17

Chemistry of the Essential Cell Constituents 18

Proteins It)

Fats and Lipoids (Lipins) 23

Carboliydiates 25

Inorganic iSubstances 26

The Physical Chemistry of the Cell and Its Constituents 26

Crystalloids and iheir Properties 27

Colloids 34

The (Structure of the Cell in Relation to Its Chemistry and Physics . . 43

The iS'ucleus 44

The Cytoplasm 46

The Cell-wall 49

CHAPTER II

Enzymes 53

The Nature of Enzymes and Their Actions 54

The Principles of Enzyme Action 56

The Toxicity of Enzymes 61

Anti-enzymes 63

The Intracellular Enzymes 68

Oxidizing Enzymes 68

Lipase 77

Amylase SO

CHAPTER III

Enzymes (Coniinued) 81

Intracellular Proteases (Proteolytic Enzymes), Including a Considera-
tion of Autolysis 81

Autolysis 82

Relation of Autolysis to Metabolism 87

Defense of the Cells Against Their Autolytic Enzymes 88

Autolysis in Pathological Processes 90

CHAPTER IV

The Chemistry of Bacteria and Their Products 106

Structure and Physical Properties lOti

Chemical Composition 107

Bacterial Enzymes 113

Poisonous Bacterial Products 120

Ptomains 120

Toxins 125

Endotoxins 129

Poisonous Bacterial Proteins 13]

Bacterial Pigments 132

11



12 CONtENTS

CHAPTER V PAGE

Chemistry of the Animal Parasites 134

Protozoa 135

Cestodes 137

Nematodes 140



CHAPTER VI

Phytotoxins and Zootoxins 144

Phytotoxins 144

Tlie Toxin Causing Hay-fever 147

Zootoxins 148

Snake Venoms 148

Scorpion Poison 157

Spider Poison 158

Centipedes 159

Bee Poison 160

Poisons of Dermal Glands of Toads and Salamanders 161

Poisonous Fish 162

Eel Serum 164

CHAPTER VII

Chemistry of the Immunity Reactions — Antigens, Specificity, Anti-
toxins, Agglutinins, Precipitins, Anaphylaxis or Allergy, Ab-

derhalden Reaction, Opsonins, and Related Subjects .... 165

Antigens 166

Non-Protein Antigens 167

Specificity of Immune Reactions 171

Toxins and Antitoxins 177

Chemical Nature of Antitoxins 180

Agglutinins and Agglutination 183

Precipitins 189

Anaphylaxis or Allergy 193

The Abderhalden Reaction 204

Opsonins 207

Tlie Meiostagtiiin Reaction 208

The Epiphanin Reaction 209

CHAPTER VIII

Chemistry of the Immunity Reactions (Continued) — Bacteriolysis,

Hemolysis, Complement Fixation, and Serum Cytotoxins . . 210

Scrum Bacteriolysis 210

Cytotoxins 214

Hemolysis or Erythrocytolysis 215

Hemolysis liy Known Chemical and Physical Agencies 215

Hemolysis by Serum 218

Hemolysis by ]5acteria 224

Hemolysis by Vegetable Poisons ', 225

Hemolysis 1)y Venoms 228

Hemolysis in Disease 229

Complement Fixation and Wassermann Reactions 234

Cytolysis in General 238

CHAPTER IX

Chemical Means of Defense Against Non-Antigenic Poisons .... 243

Inorganic Poisons 246

Organic Poisons 248



CONTENTS 13

CHAPTER X PAGE

Inflammation, Rkcknkkation, GIrowth 253

Ameboid Motion and Phagocytosis 254

Chemotaxis 254

Chemotaxis of Leucocytes 256

Phagocytosis 262

Theories of Chemotaxis and Phagocytosis 266

Artificial Imitations of Ameboid Movement . . .• 267

Relation of the Above Experiments to tlie Plienomena Exhibited by Leu-
cocytes in Inflammation 271

Suppuration 276

Composition of Pus 277

Sputum 280

Proliferation and Regeneration 283

Growth and Repair. "'Vitamines." 285



CHAPTER XI

Disturbances of Circut>ation and Diseases of the Blood 289

The Composition of the Blood 289

Hemorrhage 293

Hemophilia 297

Anemia and the Specific Anemias 300

Secondary Anemias 300

Chlorosis 302

Pernicious Anemia 305

Leukemia 307

Hyperemia 312

Active Hyperemia 312

Passive Hyperemia 313

Thrombosis 315

Fibrin Formation 315

The Formation of Thrombi 322

Embolism 325

Infarction 327



CHAPTER XII

Edema 330

Formation of Lymph 331

Absorption of Lymph 338

The Causes of Edema 339

Special Causes of Edema 348

Composition of Edematous Fluids 352

Varieties of Edematous Fluids 359

Chemistry of Pneumothorax 365



CHAPTER XIII

Retrogressive Changes (Necrosis, Gangrene, Rigor Mortis, Parenchy-
matous Degeneration) 367

Necrosis 36/

Causes of Necrosis 3/1

Varieties of Necrosis 381

Fat Necrosis 384

Gangrene 388

Rigor Mortis 390

Atrophy 393

Cloudv Swelling 394



14 CONTENTS

CHAPTER XIV PAGE

Retrogressive Processes (Continned), Fatty, Amyloid, Hyaline, Colloid.

AND GLYCOGf:XIC INFILTRATION AND DEGENERATION 397

Fatty Metamorpliosis 397

Physiological Formation of Fat 397

Pathological Fat Accunuilation 399

Causes of Fatty .Metamorphosis 406

Processes Related to Fatty Metamorphosis 410

Adipocere 410

Lipemia 412

Pathological Occurrence of Fatty Acids 414

Pathological Occurrence of Cholesterol 415

Amyloid Degeneration 417

The Origin of Amyloid 421

Hyaline Degeneration 423

Colloid Degeneration 425

Mucoid Degeneration 427

Glycogen in Pathological Processes 428

Physiological Occurrence 429

Pathological Occurrence 431

CHAPTER XV

Calcification, Concretions, and Incrustations 435

Calcification 435

Occurrence of Pathological Calcification 438

Chemistry of the Process of Calcification 439

Osteomalacia 443

Rickets 445

Concretions 447

Biliary Calculi 448

Urinary Calculi 454

Corpora Amylacea 400

Other Less Common Concretions 461

Pncumonokoniosis 465

CHAPTER XVI I

Pathological Pigmentation 467

Melanin 467

Lipochrome 474

Blood Pigments 476

Icterus 484

Congenital Hemolytic Icterus 489



CIL\PTER X^^I

The Chemistry of Tumors 492

A. Chemistry of Tumors in General 404

B. (licniistry of Certain Specific Tumors 50!)

(1 I Benign Tumors 50!)

(2) Malignant Tumors 515

Multiple Myelomas and ^lyclopatliic "Alliuniosuria" 51S

CHAPTER XVIII

Pathological Conditions Due to, or Associated with. Abnormalities

IN Metabolism, Including Autointoxication 523

I'remia 525

Toxemias of Pregnancy 533



COyTEMS 15

PAGE

Eclampsia 533

Acute Yellow Atrophy of the Liver 53<l

C'lieniiccil Llumges of Acute Yellow Atrophy 54:i

Acid Intoxication . ;j.}7

Diabetic Coma 5.30

Acid Intoxication in Conditions Other Than Diabetes 5.")7

Fatigue 50 1

The roisons Produced in Superficial Burns 5(;2



CHAPTER XIX

Gastro-Inti:stinal '•Autoixtoxication'" axd PvElated Metabolic Disturb-

AXCES oGG

I. The Constituents of the Digestive Fluids .... 567

II. Products of Normal Digestion 5t;8

III. Products of Putrefaction and Fermentation 57n

A. Protein Putrefaction 571

The Pressor Bases 57t)

Alkaptonuria 577

Cystine and Cystinuria 582

B. Products of Fermentation of Carbohydrates 58.3

C. Products of the Decomposition of Fats 584

Results of Gastro-intestinal Intoxication 585

Acute Intestinal Obstruction 588



CHAPTER XX

Chemical Pathology of the Ductless Glaxds 590

Diseases of the Thyroid 500

The Functions of the Thyroid . . 590

Chemistry of the Thyroid 593

The Parathyroids 597

Chemistry of Goiter 599

Myxedema and Cretinism 601

Exophthalmic Goiter 604

The Adrenals and Addison's Disease 60S

Addison's Disease 613

The Hypophysis and Acromegaly 614

Thymus and Other Ductless Glands 616



CHAPTER XXI

URic-Acin IMetaiiolism axd Gout 618

The Chemistry of Uric Acid 618

Formation of Uric Acid 621

Destruction of Uric Acid 625

The Occurrence of Uric Acid in the Blood. Tissues and Urine . . 626

Gout 628

Uric-acid Infarcts 633



CHAPTER XXII

Diabetes 635

Carbohydrate Phvsiologv . 637

The Blood Sugar ". . ' 641

The State of the Sugar in the Blood 643

Diose 645

Trioses 645



16 CONTENTS

?AGE

Tetroses ... 048

Pentoses G49

Chronic Pentosuria 650

Hexoses 650

Galactose 654

Levulose (Fructose) 655

Polysaccharides 656

Glycosurias 657

Phlorhizin Diabetes 65!)

Pancreas Diabetes and Diabetes Melitus 665



IXDEX 073



chp:]\iical pathology

CHAPTER I

INTRODUCTION

THE CHEMISTRY AND PHYSICS OF THE CELL

Since Virchow founded modem pathology the unit of all anatomical
considerations of disease has been the cell, and in physiology the same
unit has been found equally useful. When either physiological or
pathological processes are studied from a chemical standpoint, the
cell is still found occupying nearly as fundamental a position, for
we can seldom go back to molecules and atoms in investigating
biological problems. Although we know that within each cell are
many different chemical substances, and that numerous different
enzj^mes and other agencies are exerting their influences upon them,
yet we find that the reactions are all profoundly affected by the
environment in which they occur, and it is the stracture of the cell
that determines the environment of its chemical constituents. All
chemical reactions are modified by physical influences, and an enzyme
may have quite a different effect upon a substance when it acts in a
test-tube from wliat it will have when in a living cell, whose struc-
ture permits the diffusion of one substance while preventing that of
another, and where countless other substances and enzymes may
participate in the changes. The cell is the structural unit of the liv-
ing organism, and as by its physical properties it modifies chemical
processes, so it becomes practically the unit in physiological and
pathological chemistry. All consideration of the chemistry of disease
must thus refer back to the chemistry and physics of the normal cell,
and on this account a brief resume of these subjects may serve as a
fitting introduction to the strictly pathological matters to follow.^

As a])plied to the animal tissues, the tenn "cell" is entirely a mis-
nomer, for it describes accurately only such forms of "cells" as are

1 Of necessity, only so much of the vorv extensive literature on coll structure
and cell chemistry can be considered as will have direct bearing \ipon tiie subject
matter to follow, referring tlie reader for more detailed information to sucli works
as Wilson's "The Cell in Development and Inlioritance"; Mann's "Physioloirical
Histoloffy"'; Hammarsten's "Physiolofrical Cliemistry": Gurwitscli's "Morplioloeie
imd Biolo.srie der Zelle"; Hober's "Pliysikalisclie Cbemie der Zelle luid der
Clewebe"; Hamburojer's "Osmotischer Druck und Tonenlehre"; Loeb's "nviiamics
of Living Matter"; Oppenheimer's "ITandbuch der Biochemie"; and Botta-'zi,
"Handbuch der vergl. Pliysiologie," Vol. T, for general discussion, and to the most
important monographs for treatment of special points.
2 17



18 THE CHEMISTRY AXD PHYSICS OF THE CELL

found in plants, in which tlie ])r()niinent feature is tlie limiting- wall,
forming- a cell to enclose a fluid content. In most instances the
"cell" answers better to the definition, "a mass of protoplasm"; but
usage makes language, and no possible confusion can arise from the
prevailing universal use of the original term, except, perhaps, that
the term is prone to carry with it the thought of the w^alls of the
cell being much more prominent than they really are. This is not
so unfortunate a result, perhaps, for, as we shall see later, the limiting
surfaces of the cell, even when too thin to be readily demonstrable,
may play a much more important part in cell chemistry than their
appearance indicates.

The morphological division of the cell into cell wall, cytoplasm,
nucleus, and nucleolus can hardly be followed out chemically, for if
we surmount to some extent the difficulties in the way of studying the
different portions separately, we find that the differences between them
are rather quantitative than qualitative. And, furthermore, however
different the cells of one organ or tissue may appear from those of
another organ or tissue under the microscope, when analyzed by the
chemical methods at present at our disposal we find the differences
very slight indeed. Certain substances are found in every living cell,
and in quantities usuall}^ not greatly dissimilar; hence they are as-
sumed to be the most important constituents of protoplasm, and are
sometimes called the primary constituents of the cell. ]\Iany other
secondary constituents may also be present, some of which are so
nearly universal that we are not sure but that they really are primary
cell components; such are fat and glycogen. Others are characteris-
tics of certain cells, such as melanin and keratin, or specific products of
cell metabolism, such as mucin and the specific enzymes. The great
histological and chemical differences existing between different tis-
sues depend often on these secondary products, as in fat tissue and
squamous epithelium; or upon the intercellular substance, as with
connective tissue, cartilage, bone, etc., which may be looked upon as
pi'odiK'ts of cell activity.

Protoplasm, as the term is generally used, includes the various
primary constituents with the fluids permeating or dissolving them,
but does not include the more conspicuous secondary constituents,
such as fat droplets, pigment granules, etc.. nor the cell membrane
when such exists. Evidently it is a very indefinite term, to be avoided
as much as possible. ])articularly because of the confusion as to
whether it includes the nucleus or not, difrerent authors difVering in
this i'es|)ect in their usage of the word.

CHEMISTRY OF THE ESSENTIAL CELL CONSTITUENTS

To enuinei'ate the primary or essential constituents of tlu^ cell al)-
solntely is not ])ossil)le, for the rapid advances in cheiiiisti'v nuiy



PROTEINS 19

alter all classifications without warning, but practically they may be
grouped under the headings of proteins, lipins, salts, and water, and
no attempt will be made to give here more tiian the most essential
features concerning each.

PROTEINS 2

In the last few years we have obtained something approaching a
scientific understanding of the chemical nature of this great group of
the most highly C()mi)lex bodies known to chemistry, although we
are still not in a position where it can be positively said just how the
various components of the molecule are united, or in exactly what
proportion ; and we are still farther", perhaps, from the point of
synthesizing a full-fledged protein molecule. But it is certain that
the problems regarding the underlying principles of the formation
and structure of the giant protein molecule are nearing solution.
Our information has been obtained almost exclusively through studies
of the products obtained by splitting up the proteins, for as yet
relatively little has been accomplished through synthesis. Proteins
can be decomposed by the action upon them of acids or alkalies in
various concentrations, by superheated steam, by digestive ferments,
and by bacteria. The products obtained in these different ways are
not all the same, for some substances may be formed by oxidation, re-
duction, decomposition, combination, or condensation of the various
products of simple cleavage, and it is necessary to distinguish between



Online LibraryHarry Gideon WellsChemical pathology; being a discussion of general pathology from the standpoint of the chemical processes involved → online text (page 1 of 86)