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CONTEIBUTOES TO VOLUME VI
BROWN, THOMAS R., M.D.
DOCK, GEORGE, M.D.
EMERSON, CHARLES P., M.D.
GARROD, ARCHIBALD E., M.D., F.R.C.P. (Lond.),
greene, charles lyman, m.d. herrick, james b., m.d. longcope, warfield t., m.d. McCarthy, daniel j., m.d.
McCRAE, JOHN, M.B. (Tor.j, M.R.C.P. (Lond.). McCRAE, THOMAS, M.D., F.R.C.P. (Lond.). OSLER, WILLIAM, M.D., F.R.S. STEINER, WALTER R., M.D. YOUNG, HUGH HAMPTON, M.D.
MODERN MEDICINE
ITS THEORY AND PEACTICE
IN ORIGINAL CONTRIBUTIONS BY AMERICAN AND FOREIGN AUTHORS
EDITED BY
WILLIAM OSLER, M.I>.
REGIUS PROFESSOR OF MEDICINE IN OXFORD DNIVERSI't''y, ENGLAND; HONORARY PROFESSOR OF MEDICINE IN
THE JOHNS HOPKINS UNIVERSITY, BALTIMORE; FORMERLY PROFESSOR OF CLINICAL MEDICINE IN
THE UNIVERSITY OF PENNSYLVANIA, PHILADELPHIA, AND OF THE INSTITUTES OF MEDICINE
IN MC GILL UNIVERSITY, MONTREAL, CANADA
ASSISTED BY
THOMAS MCCRAE, M.D.
ASSOCIATE PROFESSOR OF MEDICINE AND CLINICAL THERAPEUTICS IN THE JOHNS HOPKINS UNIVERSITY, BALTIMORE; FELLOW OF THE ROYAL COLLEGE OF PHYSICIANS, LONDON
VOLUME VI
DISEASES OF THE URINARY SYSTEM-DISEASES OF THE
DUCTLESS GLANDS-DISEASES OF OBSCURE CAUSATION
—DISEASES OF THE MUSCLES-VASOMOTOR AND
TROPHIC DISORDERS-LIFE INSURANCE
ILLUSTRATED
PHILADELPHIA AND NEW YORK
LEA & FEBIGER
1909
Entered according to the Act of Congress, in the year 1909, by
LEA&FEBIGER in the Office of the Librarian of Congress. All rights reserved.
I
,r> \
LIBRARY OF THK
AUOMNI ASSOCIATION,
^®'-'- COLUMBIA UNlVERSnV NEW YORK
CONTRIBUTORS TO VOLUME VI.
THOMAS R. BROWN, M.D.,
Associate in Medicine in the Johns Hopkins TTniversity, Baltimore, Md.
GEORGE DOCK, M.D.,
Professor of the Theory and Practice of Medicine and Clinical Medicine, Tulane University of Louisiana; Visiting Ph^-sician to the Charity Hospital, New Orleans.
CHARLES P. EMERSON, M.D.,
Superintendent Clifton Springs Sanitarium; Late Resident Physician the Johns Hopkins Hospital, Baltimore, Md. /
ARCHIBALD E. GARROD, M.D., F.R.C.P. (Lond.),
Assistant Physician to and Lecturer on Chemical Pathology at St. Bartholo- mew's Hospital; Senior Physician to the Hospital for Sick Children, Great jOrmond Street, London, England.
CHARLES LYMAN GREENE, M.D.,
Professor of Medicine in the LTniversity of Minnesota, St. Paul, Minn.
JAMES B. HERRICK, M.D.,
Professor of Medicine in the Rush Medical College, Chicago, 111.
WARFIELD T. LONGCOPE, M.D.,
Director of the Ayer Laboratory of the Pennsylvania Hospital; Instructor in Medicine in the L'niversity of Pennsylvania, Philadelphia.
DANIEL J. McCarthy, m.d..
Professor of Medical Jurisprudence in the Medical Department of the University of Pennsvlvania; Neurologist to the Henry Phipps Institute and to the Philadelphia and St. Agnes' Hospitals, Philadelphia.
JOHN McCRAE, M.B. (Tor.), M.R.C.P. (Lond.),
Lecturer on Pathology in McGill University, Montreal; Assistant Physician, Royal Victoria Hospital, Montreal, Canada.
THOMAS McCRAE, M.D., F.R.C.P. (Lond.),
Associate Professor in Medicine and Clinical Therapeutics in the .Johns Hopkins University.
WILLIAM OSLER, M.D., F.R.S.,
Regius Prpfessor of Medicine in Oxford T'niversity, Oxford, England.
WALTER R. STEINER, M.D.,
Pathologist and Bacteriologist to the Hartford Hospital, Hartford, Conn.
HUGH HAMPTON YOUNG, M.D.,
Associate Professor of Genito-urinary Surgery in the .Tohns Hopkins T'niver- sity, Baltimore, Md.
(V)
CONTENTS OF VOLUME VI.
PART I.
DISEASES OE THE URINARY SYSTEM.
CHAPTER I.
INTRODUCTION TO THE DISEASES OF THE KIDNEY .... 17 By John McCkae, M.B. (Tor.), M.R.C.R (Lond.).
CHAPTER II.
MALFORMATIONS OF THE KIDNEY. CIRCITLATORY DISTURP.-
ANCES OF THE KIDNEY 35
By John McCrae, M.B. (Tor.), M.R.C.P. (Lond.).
CHATTER III.
ANOMALIES OF URINARY EXCRETION 40
By a. E. Garrod, M.D., F.R.C.P. (Lond.).
CHAPTER IV.
UR.^MIA 86
By a. E. Garrod, M.D., F.R.C.P. (Lond.).
CHAPTER V.
NEPHRITIS: INTRODUCTION AND ETIOLOGY 103
By James B. Herrick, M.D.
CHAPTER VL
ACUTE NEPHRITIS II9
By James B. Herrick, M.D.
CHAPTER VII.
CHRONIC PARENCHYMATOUS NEPHRITIS . , 146
By James B. Herrick, M.D.
( vii )
viii CONTENTS OF VOLUME VI
CHAPTER VIII.
CHRONIC INTERSTITIAL NEPHRITIS 158
By James B. Herrick, M.D.
^ CHAPTER IX.
AMYLOID DISEASE OF THE KIDNEY (LARDACEOUS DISEASE OF
THE KIDNEY) 211
By James B. Herrick, M.D.
CHAPTER X.
THE BACTERIOLOGY OF THE INFECTIONS OF THE URINARY
TRACT AND URINARY FINDINGS IN THESE CONDITIONS . 218 By Thomas R. Brown, M.D.
CHAPTER XL
PYOGENIC INFECTIONS OF THE KIDNEY, URETER, AND PERI- RENAL TISSUES 236
By Thomas R. Brown, M.D.
CHAPTER XII.
TUBERCULOSIS OF THE KIDNEY 273
By Thomas R. Brown, M.D.
CHAPTER XIII.
TUMORS OF THE KIDNEY 297
By Hugh Hampton Young, M.D.
CHAPTER XIV.
URINARY LITHIASIS: RENAL AND URETERAL CALCULI ... 315 By Hugh Hampton Young, M.D.
CHAPTER XV.
GENITO-URINARY DIAGNOSIS. DISEASES OF THE PROSTATE . 336 By Hugh Hampton Young, M.D.
PART II. DISEASES OF THE DUCTLESS GLANDS.
CHAPTER XVI.
DISEASES OF THE ADRENAL GLANDS 351
By George Dock, M.D.
CONTENTS OF VOLUME VI ix
CHAPTER XVII.
DISEASES OF THE THYROID GLAND 377
By George Dock, M.D.
CHAPTER XVIII.
ATHYROSIS. ATHYREA. ATHYROIDISM. HYPOTHYROIDISM.
CRETINISM. MYXCEDEMA 447
By George Dock, M.D.
CHAPTER XIX.
THE PITUITARY BODY. ACROMEGALY. PROGERIA 463
By George Dock, M.D.
PART III. DISEASES OF OBSCURE CAUSATION.
CHAPTER XX. HODGKIN'S DISEASE 475
By Warfield T. Longcope, M.D.
CHAPTER XXI. ARTHRITIS DEFORMANS 501
By Thomas McCrae, M.D., F.R.C.P. (Lond.).
CHAPTER XXII. OSTEOMALACIA 559
By George Dock, M.D.
CHAPTER XXIII.
ASTASIA-ABASIA. ADIPOSIS DOLOROSA 568
By Daniel J. McCarthy, M.D.
PART IV. DISEASES OF THE MUSCLES.
CHAPTER XXIV. MYOSITIS 575
By Walter R. Steiner, M.D.
X CONTENTS OF VOLUME VI
CHAPTER XXV.
THOMSEN'S DISEASE. MYOTONIA CONGENITA 595
By Walter R. Steiner, M.D.
i
CHAPTER XXVI.
MYASTHENIA GRAVIS. PARAMYOCLONUS MULTIPLEX. PERI- ODIC PARALYSIS 606
By Daniel J. McCarthy, M.D.
PART V. VASOMOTOR AND TROPHIC DISORDERS.
CHAPTER XXVII.
RAYNAUD'S DISEASE 625
By William Osler, M.D., F.R.S.
CHAPTER XXVIII.
ANGIONEUROTIC ffiDEMA: QUINCKE'S DISEASE 648
By William Osler, M.D., F.R.S.
CHAPTER XXIX.
DIFFUSE SCLERODERMA. ERYTHROMELALGIA 665
By William Osler, M.D., F.R.S.
CHAPTER XXX.
ACHONDROPLASIA. HYPERTROPHIC PULMONARY OSTEO- ARTHROPATHY. PAGET'S DISEASE, OSTEOGENESIS IM- PERFECTA. OSTEOPSATHYROSIS. LEONTIASIS OSSEA.
MICROCEPHALUS. FACIAL HEMIATROPHY 683
By Charles P. Emerson, M.D.
PART VI.
MEDICAL ASPECTS OF LIFE INSURANCE 733
By Charles Lyman Greene, M.D.
LIBRARY OF THE
ALUMNI ASSOCIATION
COLLEGE OF PHYSICIANS AffUSORGEO^ COLUMBIA UNIVERSITY NEW YORK
PART L DISEASES OF THE UEINAEY SYSTEM.
CHAPTER I.
INTRODUCTION TO THE DISEASES OF THE KIDNEY.
By JOHN McCRAE, M.B. (Tor.), M.R.C.P. (Lond.).
It is not the intention of the writer of this article to attempt to put forward anything new, nor yet to give in detail the knowledge that we possess of the physiology or pathology of any particular part of the kidney. So large a task as the latter would naturally fall to other hands. Nevertheless, we are in possession of a certain accumulation of fact and a greater of theory about the functions and the structure of the kidney, and the most that can be attempted in this place is to point out the general trend of these ideas.
Some investigators exalt the glomerulus, others the tubule; some believe that forces, largely mechanical, govern the excretion of urine, others that the vital powers and the selective ability of cells are more potent. While dogmatic assertion is comfortable for the student, it is not quite so just for the advanced reader, and the object here sought is to approach the subject with a mind as open as possible even though the result be that the reader is left with the idea that there is a great deal of uncertainty still prevailing with regard to the processes that go on in the kidney. This is inevitable. In the last twenty-five years there has been a great mass of work done with reference to the problems presented by urinary secretion, and one must admit that there has been no advance made in that time at all commen- surate with the energy expended, or at all comparable with the increase of knowledge concerning other apparently less important organs.
THE PHYSIOLOGY OF THE KmNEY.
Since the days of Bright the importance of the kidney as a seat of disease
has certainly not been underestimated, so that there are many diseases
with urinary manifestations in which it is difficult to keep the kidney
out of the mental picture, innocent though it be. As an excretory organ,
VOL., VI. — 2 ( 17 )
18 DISEASES OF THE KIDNEYS
while it probably stands second to the alimentary tract, it certainly sur- passes in importance the skin, whose total excretion of water it equals, and it o-reatly surpasses such subsidiary systems of excretion as the breath and the saliva. With excretion so large and so important, it is natural that it should be held responsible for much that merely goes past its portal; being dependent on other systems to a large extent, the abnormal products appear- ing in the urine are often not the product of disease of the kidney but of some other organ or system. The true view of diseases of the kidney cannot be attained until we are able rightly to estimate the variations in excretion for which it is not responsible. The kidneys excrete and put the finishing touches upon the urinary fluid; they are acting at the end of the metabolic course both as active and as passive agents. There are some modifications of the excreted products over which they have control, and some over which they have none. The limits of such control are what we endeavor to de- termine by experimental work, and there is at our disposal evidence which tends to show that while to some extent the kidneys are mere mechanical contrivances, mere filters, so to speak, they are to a far greater degree active, specific glands.^ The daily performance of the healthy kidney is no doubt a combination of these mechanical and vital processes. Yet the more one follows the conflict of evidence and the varying results that have been obtained by the use of similar experiments on kidney functions, the more must it be realized that these functions need not be absolutely hard and fast, unalterable, specific rules of procedure. Compensatory assistance of organ to organ, of one portion of an organ to another, is so widely seen that it is surely a law — and of the working of this law the kidney often avails itself. Glomerular secretion and cellular secretion undoubtedly assist and com- pensate for one another; and the history of any renal case is the sum total of successes and failures in these adaptations. Nor does it end here; the kidney, as an end Hnk in the vascular chain, is ready at all times to fall back upon the vascular system, and in time of stress throw its burden upon the vessels, which, in turn, seek the help of the adjuvant systems, the alimentary canal, the skin, and the other lesser excretory organs. Witness in nephritis the excretion of urea in the saliva, of chlorides in the faeces. It is obvious that the variations in experimental results, and the difficulty experienced in trying to lay down hard and fast rules as to kidney function arise from this very "give and take" between the different parts of the kidney, and between the kidney and its fellow-organs.
The rules of function that can be fairly considered as settled are these: The glomeruli excrete water and salts, such as sulphates, phosphates, and carbonates, especially when these are in excess; many foreign substances, such as sugar, peptone, egg albumen, and haemoglobin (Adams Bridges, Adami), if injected, are also excreted by the glomeruli; yet sugar is excreted by the tubules when the kidney is poisoned by phloridzin (Leowi and Schmid), and many pigments, when injected, have been found to be excreted by the tubules (Hober and Konigsberg). Urea is so readily diffusible that it is hard to believe that it is not excreted by the glomeruli, yet urea and uric acid are generally credited to the tubules (Stewart) ; uric acid, indeed,
' The infiltration theory was enunciated by Ludwi^, and was supported with modifications by Hans Meyer and Koranyi, while the secretory theory was upheld by Bowman, Ileidenhain, and, again, with modifications, by Bartcls.
THE PHYSIOLOGY OF THE KIDNEY 19
seems to be thrown out by the convohited tubules and the ascending loop of Henle (Sauer, Anten), while phloridzin, cantharidin, and perhaps mercury are excreted by the tubules (Henderson). Apparent discrepancies as to the place of excretion of any substance arise not from mistaken observations, but because the adaptability of the kidney causes these substances to be excreted now in one way, now in another. There is much reason to suppose that water and salts may be excreted by the tubular epithelium also; in short, it seems as if the tubules can share every glomerular labor when the need arises.
Certain it is that when, by reason of altered blood pressure, the glomeruli cease their activity the tubular epithelium has been proved to take up their function, so that excretion goes on. Nor is this assistance confined to tem- porary embarrassments of the glomeruli. Miiller^ has pointed out that in a case of diffuse nephritis with oedema and oliguria (which in turn yielded, and polyuria ensued) the convoluted tubules widened and their regenerated epithelium became quite endothelial in type. The evident meaning of this is that these tubules took up, to a greater extent than ever, the work of excreting urinary water; they doubtless lost to some degree the functions that they ordinarily possess, and adapted themselves to their new work, for which their simpler endothelium-like structure fitted them. Miiller thinks that this is an explanation, partial, at least, of the power of a kidney deprived of many glomeruli to excrete a vastly increased amount of water. In any case, it is an excellent example of what has been referred to above as the "give and take" of the one part of the kidney and another. Nor is there anything wonderful in this adaptation, for the flattened endothelium-like cells in the dilated tubule have merely asserted their relationship to the flattened epithelial cells covering the glomerular tuft, which normally possess this structure, adapted rather to the excretion of water than to the more elaborate processes which are the duty of the epithelial cell of the tubule.
Nor must we overlook the power possessed by the tubular epithelium of absorption from the fluid in its lumen ; that is, there is good reason to suppose that the action of the epithelium is not always supplementary to that of the glomeruli, but may be antagonistic or at least exerted in a contrary direction; doubtless absorption back to the blood and lymph of water already secreted by the glomeruli occurs through the tubules like other glandular cells; their absorptive power undoubtedly works in both directions. This asser- tion is not meant fully to support the old idea expressed by Ludwig, that the tubule was given its vast length to act as a corrective upon the lavish glomer- ulus, but we can well imagine that the epithelial cell is as free to act in one direction as in the other. Ludwig's idea was that the glomerulus, like a filter, passed out urinary constituents in the same degree of concentration as that in which they existed in the blood, and that subsequent alterations were the work of the tubule. It may be plainly said that his idea meets with little if any belief at the present day; yet one may insist that it is reason- able to suppose that the tubular epithelium does absorb from the lumen as well as from the blood.
Let us digress, at this point, to indicate some of the characters that the epithelium of the tuft and the epithelium of the tubules respectively possess. It has been shown that the somewhat flat epithelium of the tuft lies on the
* Verhandl. der Deutschen path. GescUschaft, 1905. p. 73.
20 DISEASES OF THE KIDNEYS
capillary directly, without the interposition of any lymph space. By its great superficial area it approximates to the endothelial cell of the capillary, and thus, in the glomerulus, where mechanical forces (e. g., blood pressure) are prominent, the urinary water has to pass through only two flat cells, the inner capillary wall, and the outer flattened epithelial cell, which latter, by its shape and its absolute juxtaposition, can allow the fluid to pass as readily as can the capillary cell. But, on the other hand, it preserves enough of its epithelial quality to remember its function. It is a kind of frontier customs officer; it possesses complete power of allowing substances to pass, but, in addition, it possesses the power of selecting and turning back the undesirable elements. This is the specific power in which it sur- passes its humbler endothelial brother. The tubule cell, on the other hand, works in an entirely different way. Between it and its capillary is a minute lymph space, and the lymph bathes it on one side and the urinary water in the lumen on the other. Here the layer of lymph exists to allow the cell to work, not in response to mechanical but to osmotic forces. The blood and the lymph make their exchanges, and the lymph and the cell make theirs; the lymph thus becomes a kind of middleman, and while breaking the con- tinuity of mechanical forces, substitutes the medium by which osmosis can proceed. This being the case, it is readily understood that the osmotic process can go on as well from the urinary water to the lymph, by way of the cell, as from the lymph to the urinary water.
The Excretion of Water. — The most easily understood function of the kidney is the excretion of urinary water, mostly a glomerular but partly a tubular function; this varies in amount directly with the rapidity of flow through the renal vessels, which rapidity may or may not be connected with a rise or fall in blood pressure; a certain minimal blood pressure is necessary, but, if this be obtained, the effect of transient rises or falls in pressure is less apparent than the results got from an increased or decreased rapidity of flow. All these, however, fail if the blood is too concentrated (Henderson^).
Thus cardiovascular influences in general have their effect upon the excretion of urinary water, but the vasomotor influences exerted upon the kidney vessels themselves must be infinitely greater. Where these vaso- motor stimuli arise and how they are conducted we do not know. Yet the results that depend upon them are at times remarkable. What is the mechanism of hysterical polyuria, and why may a cannula inserted in the ureter cause anuria? Why does moderate venous interference lessen in- stead of increase the amount of water? Again, what is to be made of the immense increase of urinary water which Rose Bradford found to follow the excision of large fractions of the kidney substance? Upon the answers to these questions we can only speculate, but, at least, they indicate how great is the elasticity of function in at least the matter of water excretion. While attention is directed to the importance of vasomotility, it must in addition be kept in mind that there is a cellular selective power in the epithelium and endothelium of the glomerular capillary, although we do not know whether the urinary water escapes through or between the cells or by both routes; whatever be the fact, the endothelium does possess a varying power of allowing fluid to pass, either by a shrinking of the cellular
' American Journal of the Medical Sciences, 1907, cxxxiv.
THE PHYSIOLOGY OF THE KIDNEY 21
bulk and a consequent increase of the intercellular space, or by a distention of the vessel producing a flattening or thinning of the cells. It may be stated, however, as a probability that the excretion of urinary water is accomplished by a combination of several forces, acting together or separately, namely, the pressure and rapidity of the blood stream, the personal power of the capsular epithelium and the endothelial cells of the capillary, and obscure influences on either or both of these brought about by nervous stimuli; all of these, again, being to a large extent under the dominance of the local vasomotor nerves. The influences which act upon the output of urinary water are thus very far reaching, and are such as will react to many physio- logical, to say nothing of morbid changes; the difficulty of telling how far the kidney itself is at fault, or how far it is merely proving an adjuvant to some other system, is apparent. The kidney may act the last-named good part for the sake of some other organ, such as the heart, and it may do this so long and so continuously that it becomes a slave, and bears the brand of its master in a physical change which is indelible.
The Excretion of Solids. — The separation of the solid substances of the urine forms the next function of the kidney, and these substances fall at once into two groups, inherently useful materials (which are in excess, such as sugar in alimentary glycosuria, or which have served their purpose, as pigments), and substances that are inherently harmful. The latter class embraces many end products of metabolism which we are accustomed to consider as the normal constituents of urine, as well as acci- dental substances introduced from without and substances produced by pathogenic agents in the body. As has been indicated above, the power of excreting solids seems to be shared by the glomeruli with the tubular epithelium; in the glomeruli there is no doubt a certain degree of extrusion by mechanical force of substances in crystalloid or soluble form in the blood which are permitted by the glomerular epithelium to pass. It seems wrong to deny to the glomerular endothelium a certain ability of selection, because we admit it for capillary walls elsewhere in the body, and, if there be no selective power in the endothelium, that of the epithehum must be excreted through the barrier of the capillary wall. The epithelium appears to be able to take up the colloidal substances from the blood. The process here must be very complex — a combination of mechanical filtration, endothelial selection, more refined epithelial selection, and perhaps osmotic exchange as well. In the tubules, on the other hand (bearing in mind what has been said previously as to the isolation of the tubular cell by an infinitesimal layer of lymph), the process is reduced to a combination of selection and osmosis. Perhaps, after all, selection is but an expression of osmotic force. If we have any force other than osmosis, we must admit that it is exerted this time across the barrier of the lymph space and the basement mem- brane. Further, the renal epithelium has the power of synthesis, and forms complex substances that are not apparent as such in the blood or lymph, such as hippuric from benzoic acid, as well as the power of analysis, breaking down other substances, as kreatin to" form kreatinin. These changes are due to the formation in the tubular cell of an enzyme, which has been called histozyme (Wells^), and it is a significant fact that it has an interchangeable action, changing benzoic acid and glycocol to hippuric
' Journal of the American Medical Association, January 25, 1902, xxxviii.
22 DISEASES OF THE KIDNEYS
acid, and the contrary. The bearing of this quality upon the supposition that the renal epithehum is free to exert its powers toward absorption as well as toward excretion is obvious.
Lastly, has the kidney an internal secretion in the sense in which we speak of the- secretion of the thyroid, the pituitary, or the adrenal? One is tempted to think' so, although it must be admitted that we have no evidence that is undeniably certain;^ unfortunately, extirpation of the kidneys is followed by death from symptoms which are explicable on other grounds than the absence of a specific secretion; but in nephrectomized animals death can be postponed for a short time, but not averted, by the adminis- tration of the juice of the fresh organ. The administration of raw kidneys in case of renal insufficiency has not yet been so successful as to enable us to deduce therefrom that a specific internal secretion exists.
In considering normal urinary excretion, it seems necessary, above all other things, to acknowledge the vast importance of the dependence of one part of the kidney mechanism on another, and the readiness with which one part takes up the work of another, remembering, at the same time, that there is a high degree of individuality in the renal cells them- selves, so that the degree of functional activity or of implication by disease may vary greatly in different parts of the same organ.
THE PATHOLOGICAL PHYSIOLOGY OF THE KIDNEY.
The Relation between the Blood and Kidney Excretion.— While
the kidney has a specific power of secretion or excretion which may be reserved for special occasions, or, on the other hand, which may be doing subsidiary work all the time, there is yet a very important, quasi-mechanical excretion going on constantly by the glomeruli. This was naturally one of the earliest facts to be observed. The glomerulus, a mere coil of capillary, was seen to have a large afferent and a small efferent vessel ; the blood pressure at the source of the renal artery is high, that at the mouth of the renal vein low; it was thought that the excretion of urine by the glomeruli was the expression of the difference of force between these, plus the amount that was excreted in the secondary system by which the tubule is supplied. It will be remembered that the arterise interlobulares carry most of the blood enter- ing the kidney directly to the glomeruli (although some of it goes to the vessels in the intertubular spaces), and that the efferent glomerular vessels are distributed to the intertubular tissue to supply the tubules after the blood has gone through the glomerulus. The kidney thus resembles a com- j)ound engine, in that most of, if not all, the blood goes to the high-pressure glomerulus, as the steam goes to the high-pressure cylinder, thence much of it goes to the low-pressure tubular capillaries, just as the steam, deprived of much of its expansive force, goes to the low-pressure cylinder; in all this the mechanical advantage is evident.
The result is that, ordinarily, the blood stream is inflicting a certain wear and tear on the glomerulus; the wear and tear depends upon the
^ R. M. Pearce (Archives of Internal Medicine, 1908, ii. No. 1) presents a strong ease astiinst the existence of a specific internal secretion by the kidney in a paper which contains rniicli useful material relating to ui'inary function.
THE PATHOLOGICAL PHYSIOLOGY OF THE KIDNEY 23
amount of work that is being extorted from the mechanism, or, expressed differently, depends upon the persistence with which blood at high pressure is supplied to the glomeruli ; the compound engine after a hard run is allowed rest, but the glomeruli have no such relief; in any middle-aged kidney, or a kidney that has experienced hard, continuous strain, there are the so- called hyaline glomeruli, which have still the form but none of the functions of glomeruli ; as the body has no means of supplying new glomeruli, the blood force is no longer expended on the high-pressure glomeruli, but falls direct, to a great extent, upon the low-pressure secondary circulation, which was never built for such high-pressure work; it is likely, then, that degeneration goes on here all the more quickly, and the stress undoubtedly leads to a rapid fibrosis; it is not difficult to imagine that a degenerated glomerulus leads soon to a damaged or quite inefficient tubule, not only from the results of this stress, but because the inefficiency of the glomerulus brings it about that the tubular cells are no longer thoroughly washed by the free flow of urinary water.
Another factor, which seems no less important, is the quality of blood that is supplied to the entire capillary system; the blood brings deleterious sub- stances which injure the structures in their passage, and the structures also have to take their nutrition from this source; the more deleterious sub- stances there are the worse is the cell food, and, therefore, the poorer the work done by the cell ; the cumulative quality of such a bad state of affairs is easily apparent. Thus it is brought to pass that the perfection of the selective power is lost, and substances that were once held back are allowed to pass through, and, on the other hand, substances whose appearance in the urine was dependent on kidney efficiency no longer appear there. In such circumstances the urinary water is excreted by skin and bowel ; salts, such as chlorides, may escape by the intestine; nitrogen may, to a great extent, escape by the same way (von Noorden^), or even by the saliva in small amounts, and the well-being of the organism no longer depends on the broken-down kidney, but on the excellence of the adjuvant systems.
Tubular Functions and Disturbances. — The Functions of the Tubiile and its Behavior when Irritated. — To the tubular epithelium we are in the habit of ascribing certain functions connected with the partial excretion of salts and other solids, as well as the synthesis of uric acid and the analysis of kreatin and other bodies; but these are doubtless but a small part of the work of so complex a structure, and our knowledge of the actual secretory power of the tubular cells is gathered from sadly uncertain modes of investigation; the convoluted tubule and the ascending loops of Henle excrete uric acid; but what is to be said for the tubular areas that as yet, like brain areas, are "silent?" What mean the modifications of epithelium in the various parts of the tubule? We can scarcely guess. One is tempted to indulge in the fancy that the tubule may some day be divided off as to function, in the same way as the alimentary tract is; that just as there is a specialized process in each part of the latter, there may be in the former; also, that the processes of absorption and re-absorption that go on repeatedly as the intestinal contents pass down may, perhaps in some less degree, be repeated in the tubule.
The convoluted parts of the tubules are those in which we mark most
' Metabolism and Practical Medicine, London, 1907, ii, 430.
24 DISEASES OF THE KIDNEYS
constantly the changes wrought by toxins; in fact, the strictly medullary parts of the tubules are as yet of but little use to us, so far as the microscopic determination of pathological change is concerned. Analogy leads us to suppose that if these last were concerned only in conduction we would have a less specialized lining for them. Experiment with pigments in the hands of Heidenhain, Adams, and many others has proved useful in the determination of functions of different parts of the tubule; various pig- ments are put into the animal body, and when the animal is killed, after a shorter or longer period the position of the pigment granules in the kidney cell is determined. The conclusions drawn therefrom are open to the ob- jection that the position of pigment in the cell is not necessarily an indica- tion of its route, but, if sufficient of such experiments be carried out, it it is safe to assume that the distance (in the cell from the lining membrane) that the pigment has progressed in animals killed at various times after injection indicates whether the pigment is taken up from the blood or from the urine. It must be admitted, of course, that experimental animals are not exactly normal, and the very "give and take" of one part of the tubule and another may perchance lead substances to be excreted in a way differ- ing from that in the normal kidney.
The tubular cell is prompt to suffer from the effect of even transitory toxicity of the blood and lymph; with reference to the lymph, indeed, we will do well to remember that the lymph which bathes the cells intercellularly probably acts precisely as does the blood with reference to excretion, save that, there being no high pressure in its current, it exchanges its constituents with the urine merely by osmotic variations of the two fluids. To toxic lymph and blood the cell quickly reacts, entering the state of cloudy swelling; this is the peculiar "ground-glass" appearance that the individual cell takes when it is damaged, and the kidney of almost every infective or toxic case shows it so distinctly that it can be determined by the naked eye. It prob- ably is often undergone by cells in the course of life, and from it the cell can recover entirely. Careful study of the cell with cloudy swelHng indicates that there is a disturbance of the osmotic relations, by which the bulk of the cell becomes much greater; the Altmann granules, instead of being arranged in definite rows, appear to be dislocated from this arrangement and are seen in apparent disorder. The cell in this state is undoubtedly less efficient, and, as was pointed out earlier in this chapter, there is at once a less perfect excretion by the cell, and its own catabolism is increased. So the vicious process continues until the individual cell has gone on to the stages of granu- lar, fatty, or hyaline degeneration, as the case may be, all of which are sup- posedly more extreme than cloudy swelling; it may well be imagined that the results upon excretion are to lessen its efficient performance. Such a condition may become the beginning of a permanent insufficiency, and the kidney tubule may not be able to regain its state of perfect health.
When considering the damage wrought upon the kidney by toxins, it is essential, however, never to lose sight of the fact that there are two widely different classes of tissue involved, the parenchyma and the connective tissue. These differ widely in the extent of their reaction to irritation. The writer is in the habit of using a fanciful illustration for this : the paren- chymatous cell represents the "professional man" in the community, specially trained, not to be replaced but by one of his own class, impressionable by even slight external stimuli, not prone to be physically hardy or overgiven
THE PATHOLOGICAL PHYSIOLOGY OF THE KIDNEY 25
to reproduction. The supportive cell, on the other hand, is its "laboring- class" brother, not trained in any high, special task, whose supportive work can be replaced by any kind of tissue, even scar tissue, not readily impres- sionable, even by powerful, external stimuli, physically strong, and ready in reproduction. These two cells lie side by side in the kidney, exposed to the same toxic influences, but reacting to them each in its own way. A toxin strong enough seriously to damage the high-class cell is only strong enough to irritate the low-class cell to reproduction. When the high-class cell is killed by toxin, it leaves no one of its kind in its stead, and its place is occu- pied, but its function is not performed, by the progeny of its laboring-class brother. If some such plan be kept in mind, one is prepared to collate the effects of toxin upon each kind of tissue, and so to form a right idea of the total result in the organ. When the condition of imperfect tubular excretion, referred to above, is prolonged, many cells die and are desquamated, and the toxins which sufficed to damage and even kill the cells are sufficiently potent to irritate the supportive structures to overgrowth; thus, hand in hand, the two processes go on until there is proliferated connective tissue where once was a tubule, and this is the process of fibrosis. The work of every destroyed tubule must be thrown on its surviving fellows, and if the kidney continue to perform its work apparently perfectly, it is done, nevertheless, at a price; the price is stress, which will have to be paid for by shortened life of the other tubules.
The Effects of Toxins. — ^What are the effective toxins? They are the toxins, so-called, of the infective diseases, products of cell catabolism throughout the body, heemoglobin (Levy^), many irritant exogenous poisons (of plant and animal origin), and perhaps many chemical products which we are accustomed to consider as the normal output of the kidney. This apparently brief narration includes a vast number of substances. The products of pathogenic bacteria are well known as having an irritant action on the kidney, but there are doubtless products of bacteria not known to be pathogenic, which also irritate; the great numbers of bacteria in the alimentary canal are constantly producing substances with which the kidney has in part to reckon; and in constipation this responsibility is doubtless increased. Every cell that breaks down in the body has to be disposed of, and in cases of extensive damage, as burns, suppurations, and necroses, the kidney has to bear its share of the excretion. With reference to exogenous substances, we have but to look at the belief that one food is better than another, that the red meats are harder on the kidneys than white meats, and a hundred other facts or fancies that make up our ideas upon diet; be they truths or errors, we have but to observe these to see that the practitioners of medicine at least have given a large place to the responsibility of the end products of ingesta with regard to the kidneys.
The Effects of Age. — The changes produced by age may be con- sidered physiological, and doubtless are, but physiological in the sense of being processes which are always occurring, which we consider hurtful, but which cannot be obviated. Every "old kidney" shows certain changes which appear to be of the nature of replacement fibrosis such as we have previously described; they appear to co-exist with changes in the arteries, and in the very old make up a well-defined entity. What, then, are the
' Deutsch. Arch.f. klin. Med., 1904, Ixxxi.
26 DISEASES OF THE KIDNEYS
causative factors here? If we knew the cause of arteriosclerosis the question would probably be answered: work, catabolism, stress, the hundred slight disturbances of all the tissues (whose catabolic effects must be disposed of), the fact that nothing lasts forever, the sudden jars, metabolic and chemical, of a blood supply no longer perfectly cushioned by elastic arteries — these, and as many more, perhaps, go to make up the factors which cause the changes of age. The constant breaking down of cells is a strain on the kidney, the greater by so much as the kidney is older; but it must be said, on the contrary side, that the very fact that the body is smaller and the cells fewer is of advantage to the kidney, because the output of such cells is less than in the body of full manhood ; there is thus a kindly compensation, even in old age, which tends relatively to lighten the renal labors.
Nevertheless, it often appears that the "old" kidney is a very efficient one; and this compensation is a virtue not to be ascribed more to the kidney than to the circulation. As the arteries become old and inelastic, the heart can no longer depend upon them for the necessary contractions which tend to raise blood-pressure in localized areas, and must perforce work harder and adopt a higher general standard of minimum blood pressure, which is accomplished by hypertrophy. From the time at which this raising of the minimum blood pressure commences, the tissues, even when most at rest, are yet exposed to a strain greater than that to which they have been accustomed ; with the increasing inelasticity the minimal blood pressure continues to rise. The kidney shares to the full degree in bearing this strain, and the constant stimulation — mechanical if no other— leads to productive processes in the supportive structures.
Parenchymatous Change in General. — Albuminuria and Casts. — As the kidney tubule is the unit of the kidney, and, so far as we can see, every tuljule is built exactly like every other one, the parenchymatous derangements of the kidney can be narrowed down to the sum of the derangements of the single tubules, derangements that vary from cloudy swelling to complete disappearance and replacement. Slight changes often pass unnoticed, so far as any urinary sign is concerned, and, on the other hand, there are slight urinary changes, such as transitory albuminuria, with which we have not yet learned to coordinate the corresponding alteration in the kidney. With- out entering into the question of albuminuria, it may be said that these transitory albuminurias must have a meaning; albumin has its place, and its place is not in the urine, so that "physiological," as a term applied to albuminuria, ought to mean not a normal process, but a process so little abnormal that experience has led us to know that certain cases of it do not habitually lead to any more serious disturbance. Albuminuria can depend, too, upon causes which are not situated in the kidney itself; anything that prevents the exit of venous blood from the kidney may cause albuminuria, experimental temporary blocking of the renal artery may cause it, the upright position in some persons seems to cause it, or, to put it in another way, the recumbent position causes its cessation, and the distribution of increased pressure in pregnancy has been held to explain the presence of albuminuria. Under these circumstances, all or most of the albumin is excreted by the glomeruli. But in its occurrence, when there is disease of the kidn(?y, the site of its output is uncertain, and may be tubular as well as glomcriilar.
Here it is in place, also, to make reference to casts. The blood cast is an
THE PATHOLOGICAL PHYSIOLOGY OF THE KIDNEY 27
evidence of rupture of a capillary or other vessel in the glandular part of the kidney. The source of the epithelial cast is equally obvious, although it is formed sometimes of the original tubular lining and sometimes of epi- thelium that has been newly generated by the tubular cells; the histological nature of the cells concerned gives no accurate information as to the site of its formation, and in all cases it must be remembered that the cast, when seen in the tissues, may be on its way out, and is not necessarily at the site of its formation; epithelial casts can be formed, too, by agglomeration of cells, so that the juxtaposition of its individual members does not always mean that they occupied that place in life, although it generally does so. Some hyaline casts are also of epithelial origin, although it is not possible to say whether the hyalinization occurred in life or after they were detached. Whenever they can be recognized as epithelial, casts mean that the kidney substance is, to this extent, destroyed. It is true that, normally, kidney cells are constantly paying their debt to nature by dying, and as such are being shed off, more or less altered. The appearance of single cells in the urine thus means nothing, but with aggregations of them it is different; if one may use a simile of a homely kind, the deaths of many men