Clinical pathology of the blood

Front matter

o- xO

.0^;^-

V

Preface To Second Edition

During the past two years the contributions to the knowledge of the blood in both its clinical and its pathological aspects have been very numerous^ and, in many instances, of fundamental importance. In the present edition of this work the author has endeavored to incorporate the results of these recent studies in such form as will be found available both for the medical practitioner and for the student of hematology. This undertaking has required references in the text to about four hundred new articles or monographs, which have been added to the bibliographical lists. Among the changes thus introduced are considerable additions to the chapter on Technics, the serum test for blood, and the subject of crioscopy. The discussion of the morphology of blood cells has been enlarged and a new plate added. Some noteworthy additions to the knowledge of leukemia have been included in that chapter. The essential features of Ehrlich's theories on immunity have been presented, but the proper limits of the volume do not permit full discussion of this subject. Four new plates and various other figures have been added to the illustrations.

The author acknowledges with thanks numerous valuable suggestions of his critics, and in many instances has been able to follow these suggestions in the revision.

J. E.

Preface To First Edition

The rapid advances iu the knowledge of the pathology of the blood and the multitudinous applications of this knowledge in clinical diagnosis which the last decade has witnessed have brought forth several critical treatises on hematology, and still furnish, as the writer believes, abundant reason for the preparation of another such work in English.

Although the clinical bearings of the subject have been partly or fully accessible to English readers in some recent text-books, many later contributions to the pathology of the blood and blood-forming organs have had to be sought elsewhere, often in the original articles. This omission the present work endeavors to supply.

Much "of the theoretical discussion in the volume, abstracts of special articles, and reports of cases, have been set in fine print, so as not to encumber the main text, which has been constructed for the student and general reader. The wants of the laboratory worker and special student of hematology have been partly considered in the chapter on Technics and Chemistry, and in the limited references to pathological anatomy.

There are probably always some deficiencies in a treatise closely relating to clinical medicine when that treatise emanates from a pathological laboratory. Yet a comparison of the various extant works on the so-called '' clinical '' pathology of the blood has convinced the writer that clinical pathology is pathology still, and that a wide experience at the autopsy table and in the microscopic examination of diseased tissues furnishes an absolutely essential standpoint from which to view pathological changes in the blood. The present volume aims therefore to associate changes in viii PREFACE TO FIRST EDITION.

the blood as closely as possible with lesions in the viscera, without which combination the former are very often unintelligible.

In the preparation of the work all available sources of information have been freely consulted, and the writer has profited especially by the labors of Ehrlich, Limbeck, Hayem, Lukjanow, Lowit, Grawitz, Stengel, Cabot, and many others. An endeavor has been made to discriminate between authorities, and in all details of important subjects the author has invariably consulted the original sources of information. Works without bibliography have been of little value in this task, and the considerable number of references involved have therefore been included as a feature of the present volume.

J. E.

Contents

INTRODUCTORY.

ON THE INTERPRETATION OF ANALYSES OF THE BLOOD.

Chapter I. Technics

Qualitative tests for blood

Volume of red cells and plasma

Enumeration of blood cells

Hemoglobin, Iron

Histological examination of blood

Specific gravit}" .

Alkalescence

Osmotic tension .

Crioscopy ....

Bacteriological examination .

CHAPTER 11.

CHEMISTRY OF THE BLOOD.

Red cells, Leucocytes .

Serum .....

The Whole Blood .

The Blood Ash

Urea, Uric Acid, Glucose, Glycogen.

Acetonemia, Lipacidemia, Cholemia Specific gravity ....

Osmotic tension . . . .

Alkalescence, Basic Capacity .

Bibliography ....

PAGE

75 77 78 80 83 84 88 90 93

Chapter III. Morphology And Physiology Of Red Cells

Structure and staining reactions . . . . . . . .96

Degenerative changes . . . . . . . . . .100

Numbers, Polycythemia, Oligocvthemia . ' . . . . . .104

PSEUDOLEUKEMIA.

Historical ........

Anatomical characters ......

Relation to Leukemia, Pernicious Anemia, Tuberculosis Changes in the Blood ......

Bibliography .......

254 255

258 262 266

Chapter X

AXE:\nA INFANTUM PSEUDOLEUKEMICA. SPLENECTOMY

Historical. Etiology Pathological changes in Viscera Changes in the Blood .

Significance of v. Jaksch's anemia Bibliography

Splenectomy.

Effects of Splenectomy in Animals

Splenectomy in ]\Ian BilDliography ....

268 269 269 270

274 276

PART IIL

THE ACUTE INFECTIOUS DISEASES.

INTRODUCTORY SECTION

THE BLOOD IN FEVER.

Chemical changes, Resistance of red cells , Febrile Hj^dremia . . . .

Action of Bacteria upon the Blood Bibliography . . . . ,

277 278 279 280

Chapter XX The Hemopoietic System

Liver, general considerations, special diseases . Esophagus .......

Stomach, general considerations, special diseases Intestines, absorption and depletion, special diseases Bibliography . . . . .

389 394 395 402 405

XIV

COXTEXTS.

CHAPTER XXT.

LUXGS, HEART, KIDNEYS.

Diseases of Lungs, Asphyxia .

Diseases of Heart, Malignant Endocarditis Diseases of Kidneys, Uremia .

Bibliography .....

Chapter XXII. Maligxaxt Tumoks

Carcinoma .

Sarcoma

Bibliograph}"

PAGE

. 407 . 410 . 414 . 418

421 427 428

Chapter XXIII. Malaria

Technics .....

Morphology of Parasites Plurality of species in Estivo-autumnal group Crescents, Flagellate Bodies .

Development in Mosquito Conjugation ....

Occurrence of Parasites in the Blood Malarial Anemia ....

Leucocytes in Malaria .

Bibliography ....

Morphology of Spirillum Changes in the Blood Bibliograph}'

CHAPTER XXn\

RELAPSING FEVER.

CHAPTER XXA^

MISCELLANEOUS PARASITIC DISEASES.

468 469

Trichina spiralis .......

. 470

Distoma hematobium

. 472

Ascaris lumbricoides, Anguillula stercoralis

. 473

Ankvlostoma duodenale, Bothriocephalus latus

. 474

Filariasis ........

. 478

Trypanosomiasis .......

. 480

Bibliography .......

. 481

Appendix

LIST OF PLATES.

PLATE PAGE

I. Normal blood. Triacid stain 97

IL Normal blood. Eosin and methylene blue ..... 124

III. Normal blood. Fixed in alcohol. Stained two hours by the Nocht-

Komanowskj method 127

IV. Mild chlorosis. Eosin and methylene blue 194

V. Severe chlorosis. Eosin and methylene blue 198

VI. Progressive pernicious anemia. Eosin and methylene blue . .218

VII. Secondary pernicious anemia. Eosin and methylene blue . . . 220

VIII. Myelogenous leukemia. Triacid stain 240

IX. Lymphatic leukemia. Eosin and methylene blue .... 244

X. Degenerating leucocytes in myelogenous leukemia. Triacid stain . 242

XL Mast-cells. Ehrlich's dahlia stain 248

XII. Glycogenic degeneration of leucocytes. Iodine and potassium iodide

in mucilage of acacia ......... 289

XIIL Agglutinated red cells ......... 361

XIV. Developmental cycle of benign tertian parasite . . . . . 436

XV. Cycle of quartan parasite 443

XVI. Cycles of estivo-autumnal parasite ... .... 445

XVII. Flagellating malarial parasites. Cerebral cortex in pernicious malaria 453

XVIII. Conjugating cycle of tertian malarial parasite ..... 455

INTRODUCTORY.

ON THE INTERPRETATION OF ANALYSES OF THE BLOOD.

Plethora. Although the older physicians regarded the existence of a true plethora as an important and well-established fact in pathology, this vieWj lacking proof, received a serious blow from the work of Ludwig's pupils, v. Lesser and Worm-Muller, and from the authoritative conclusion of Cohnheim. Lesser and Worm- Muller, attempting to produce artificial plethora by transfusion of blood in animals, found that when the red cells were thereby increased 28 per cent, the numbers fell to normal on the following day, and when increased 58 per cent, the blood became normal on the twenty-third day, while the total quantity of blood might be doubled without abnormal symptoms, owing to the rapid return to the normal quantity. Likewise, Hamburger was unable to produce a permanent plethora in horses, by the injection of large quantities (7 litres) of 5 per cent, soltition of sodium sulphate, finding that the isotonic power of the blood, thus increased, became normal in one-half to two hours, while nearly all traces of the salt disappeared from the blood in twenty-four hours. Instead of drawing from these data the conclusion that continuous plethora cannot be induced artificially, the unwarranted claim was advanced that a true plethora does not exist (cf. v. Eecklinghausen, Lukjanow). Against this conclusion stood the daily observation of clinicians and pathologists, at the bedside and in the dead-house, that there are extreme variations in the quantity of blood in the vessels of different subjects, in divers states of health and disease. Oertel especially strongly maintained, without being able to offer proof, that the volume of blood might be reduced in endocarditis and with good therapeutical effect. Positive data on the question were gathered by Bergmann and Heissler, pupils of Bollinger, and the fact established that there is, in general, a direct ratio between the volume of blood and size of the heart, and the muscular development of the subject, and an indirect ratio with the subject's fat deposits. Though lacking full experimental proof it is now generally accepted that the quantity of blood in the body is variable, may be increased by hygienic measures, and is diminished in many unhygienic and pathological conditions.

Anhydremia, i. e., a reduction in the volume of blood with concentration of solids, must be admitted to result from loss of body fluids, as by sweating and diarrhea, or by diminished ingestion of water.

Czerny exposed cats in a warm, dry chamber for thirty-six hours, finding that they lost 45 per cent, of their Aveight, the volume of

1 8 INTB OB UCTOB Y.

blood was greatly reduced, its viscosity increased, and the red cells rose, in one case, to ten millions per cubic millimetre.

Grawitz found that profuse sweating is followed in the majority of cases by a concentration of the blood, in one instance from specific gravity 1040 to 1051. A few subjects showed a contrary reaction and diminution in gravity (1060 to 1057.5), which Grawitz refers to nervous influences.

Limbeck examined the blood of a case of cirrhosis of the liver with extreme ascites, before and after tapping the abdomen. On the day after the removal of 18 litres of fluid the red cells had risen from 3,280,000 to 5,160,000. Stintzing and Gumprecht have made similar observations before and after the removal of large serous exudates.

Grawitz found the specific gravity of the blood at first decreased by the intravenous injection of concentrated salt solutions (absorption of water), while the administration of the salt by mouth concentrated the blood.

It therefore follows that the ingestion of water and the loss of body fluids always produces a more or less transitory effect on the volume of the blood. There can be no doubt also that the prolonged sweats of phthisis and the severe diarrhea of typhoid fever, dysentery, and cholera lead to a more or less continuous reduction in the volume of the blood and a concentration of blood cells.

A very striking illustration of this principle was frequently encountered by the writer among the soldiers at Camp Wickoff (1898). When these patients, suffering from prolonged malaria with severe anemia, were attacked by typhoid fever or acute dysentery, the ordinary watery character of the expressed blood drop disappeared, and the blood soon became thick and deep red.

Herz claims to have recognized an " acute swelling '^ of the red cells in febrile conditions, especially in typhoid fever, and v. Limbeck, finding a considerable average increase in the volume of the red cells in eight febrile cases, believes that relative oligoplasmia with increased volume of red cells is of frequent occurrence in high fevers.

The effect of nervous influences in altering the quality of the blood in the whole or a part of the circulation has been demonstrated by numerous studies.

Cohnstein and Zuntz found that section of the cord above the origin of the splanchnic nerves is followed by general dilatation of bloodvessels, and reduction in the proportion of red cells.

Grawitz and Knopfelmacher found, in general, that vasomotor paralysis is followed by local and general increase in the volume of blood, with diminished specific gravity and proportion of red cells, while the opposite effects follow vasomotor constriction of vessels.

The nervous stimulus of cold baths has been found by Leichtenstern, Wick, Knopfelmacher, Winternitz, Thayer, and Grawitz to be followed by contraction of vessels and increase in the proportion of red and white cells, while the hot pack and the inhalation of amyl nitrite have an opposite effect.

To a similar origin must be attributed the increased gravity of the blood observed by Grawitz after the injection of tuberculin, and

IXTEBPBETATIOX OF ANALYSES OF THE BLOOD. 19

cultures of the bacillus of cholera and of diphtheria, and the opposite effect produced by streptococcus and staphylococcus pyogenes and B. anthracis.

The influence of psychical emotions on the character of the blood in different regions of the body has been emphasized by Lloyd Jones, and is seen especially in the study of the blood in neurotic women, Jacobi, examining the blood of an hysterical woman, found on IN'ovember 12th 3,892,000 red cells ; on December 11th 8,084,000 red, 102,200 white cells ; on December 16th 3,393,000 red, 22,000 white. Grawitz refers to the remarkable increase seen in the specific gravity and proportion of cells in the blood of rabbits, in experiments conducted without anesthesia. The remarkable variations in the blood taken from the ears of rabbits, depending on the temperature and blood-content of the member, are a matter of common observation.

In the mechanism by which these changes are brought about there appear to be many factors. Heidenhain, Lowit, Gartner and Romer, find that many substances injected into the blood cause an increased flow of lymph. (Extract of cancerous tumors, peptone, tuberculin, toxins of B. pyocyaneus and pneumococcus, hemi-albumose, nuclein, uric acid, etc.) Heidenhain and Hamburger believe that some substances excite a secretory action of the capillary endothelium, whereby the fluids of the blood are diminished.

Grawitz explains the concentration of the blood under the influence of cold by the escape of fluids into the tissues, but the experiment of Cohnstein and Zuntz offers another explanation, since they found under the microscope that capillaries might be so reduced in calibre by irritation of vasoconstrictor nerves that no red cells, but only plasma, could pass in them. It then appears that many red cells may be caught in the contracted capillaries while the plasma passes on into the veins. Grawitz concluded from many comparative tests that the capillary blood is, in all ordinary conditions, richer in cells than that of the veins ; but Becker found no such differences in the cells of veins and capillaries, and thinks that the polycythemia of cold is referable both to the escape of fluids from the blood and to the sifting of cells by the contracted capillaries. It does not appear to have been proven that the vascular dilatation produced by heat is followed by the return of tissue fluids into the capillaries. It appears quite as likely that an irregular distribution of cells and plasma is to a larger extent responsible for such local variations in the composition of the blood (cf. Winternitz).

The law that increased blood pressure leads to transudation, authoritatively stated by Ludwig and Landois, appears to have a less important application here than in more general and more prolonged processes. It is not likely that a cold bath can be followed by much exudation of serum into the tissues.

Massage and electricity have been shown, by Mitchell and Cheron, to cause an immediate increase in the number of red cells in the blood of a part, an effect which may be explained according to the above data.

20 INTB OB UCTOR Y.

Ekgren found that ten minutes of active massage of body or abdomen increased the peripheral leucocytes, chiefly the polynuclears, from 1000 to 3000, once 7000. The increase was not marked ten minutes after the massage. Oliver was able to lower the red cells of the finger 7 per cent, by elevating the arm, while elevation of the leg for fifteen minutes lowered the red cells of the toe 14 per cent., and raised them in the finger 3 per cent. Exercise and faradism caused an increase of 5 to 8 per cent, in the peripheral blood. A Turkish bath caused an increase of 15 per cent.

The importance of the osmotic relations of the blood in controlling the volume of red cells and plasma is indicated from the discussion in Chapter II. In hydremia and anhydremia Hamburger has shown that the isotonic relations of the blood are maintained by a rapid interchange of salts and albumins between the cells and plasma, with frequent minor changes in their relative volume. From Limbeck's analyses of venous and arterial blood it appears, also, that the imbibition of CO2 causes swelling of red cells with absorption of water and salts and with relative diminution in the volume of plasma.

The foregoing considerations are dwelt upon not only because of their theoretical interest, but because they deal with fundamental facts without the knowledge of which it is impossible to properly perform or sensibly interpret the results of an examination of the blood.

To summarize the discussion, it has been shown that there are wide variations in the quantity and quality of the blood referable to diverse conditions other than disease.

1. There are considerable physiological variations in the volume and composition of the blood, according to the constitution of the individual (plethora), and the degree of muscular development. Here may be classed the variations between the sexes and between different periods of life. Such variations are permanent but usually not of extreme grade.

2. There is a great variety of physiological conditions producing marked but transitory changes in the blood, such as active digestion, muscular exertion, the ingestion of fluids, profuse perspiration, temporary cyanosis, etc.

3. The nervous system has a very striking temporary influence on the quality of the blood in local or general areas, acting through the cerebral (psychical) or medullary centres, or through local vasomotor nerves.

4. Various local influences may greatly change the quality of the blood specimen, as seen in the local and transient effects of cold, heat, massage, and electricity.

5. Many therapeutical procedures may temporarily alter the blood, as the aspiration of fluids, administration of diaphoretics, purges, vasodilators (amyl nitrite), vasoconstrictors, etc.

IXTEBPBETATIOX OF ANALYSES OF THE BLOOD. 21

6. Various pathological conditions may partly or completely obscure the real status of the blood, as the sweats of phthisis ; the diarrhea of typhoid fever, dysentery, and cholera ; general cyanosis or local stasis ; the increased arterial tension of uremia ; the polyuria of diabetes and nephritis ; antemortem cardiac failure, etc.

Having regard to the possible action of any of the above influences, one may avoid many of the local disturbances by observing special care in the manner of expressing the blood specimen.

The blood should be expressed by very slight pressure, exerted at a distance, from a liberal puncture of the finger-tip or ear-lobe. The circulation in the part should be as nearly normal as possible and should be uniform, A cold, bloodless tissue is not suitable for furnishing a blood specimen, and if artificial means are taken to correct the condition a sufficient period must elapse to allow the accelerated circulation to subside. Blood should be taken not less than four hours after a hearty meal, and when comparative tests are made the specimens should be taken at the same hour each day.

The examination having been performed, its results are to he interpreted only in the light of the fullest possible clinical information. There can be no doubt, as Grawitz has pointed out, that the numerous contradictory results of hematological studies are largely referable to hasty conclusions drawn from figures without regard to the condition of the patient or the stage of the disease under consideration. Likewise, hematological diagnosis has fallen into much discredit from the tendency to offer opinions from the isolated findings of the blood test.