BiSK^M**? \witf if' i frfti nl||>Hi»>l|IIJ|IUIHWM.>"*' library of JAMES P. MARSH NATIONAL LIBRARY OF MEDICINE Bethesda, Maryland Gift of The New York Academy of Medicine Trom the Jjbrary of E.LOVELL BECKER,md given by his wife, rEleanorMdcnrBecker) * \ It A TREATISE BRIGHT'S Disease of the Kidneys ITS PATHOLOGY, DIAGNOSIS, AND TREATMENT. WITH CHAPTERS ON THE ANATOMY OF THE KIDNEY, ALBU- MINURIA, AND THE URINARY SECRETION. HENRY B. MILLAKD, M.D., A.M. MEMBER OF THE N. Y. COUNTY MEDICAL SOCIETY; HONORARY MEMBER OF THE 80CE6T£ ANATOMIQUE OF PARIS ; CORRESPONDING MEMBER OF THE VEREIN DEUTSCHER AERZTE OP PRAGUE, AND OF THE SOCIETY d'HYDROLO- GIE MEDICAXE OF PARIS, ETC. SECOND EDITION. REVISED AND ENLARGED. NEW YORK: WILLIAM WOOD & COMPANY, 56 AND 58 LAFAYETTE PLACE. 1886. |SS6 COPYRIGHT, 1886, BY WILLIAM WOOD & COMPANY. @ TROWS PRINTING AND BOOKBINDINQ COMPANY, NEW YORK. TO Dr. J. M. CHARCOT PROFESSOR IN THE FACULTY OF MEDICINE, PARIS; PHYSICIAN TO THE SALPETRIERE; MEMBER OF THE ACADEMY OF MEDICINE; OFFICER OF THE LEGION OF HONOR; ETC., ETC. AND TO Dr. M. DEBOVE PHYSICIAN TO THE BICETRE AND PROFESSOR AGREGE IN THE FACULTY OF MEDICINE THIS VOLUME IS, WITH THEIR PERMISSION, DEDICATED BY THE AUTHOE AS A TRIBUTE OF RESPECT FOR THEIR PROFOUND ATTAIN- MENTS IN MEDICAL SCIENCE, AND AS A SLIGHT ACKNOWLEDGMENT OF MANY ACTS OF KINDNESS. PREFACE TO THE SECOND EDITION. I am glad that my humble labors in the department of renal affections, as presented in the first edition of this work, have proved so generally acceptable and have re- ceived so much approbation at home and abroad. The present edition contains much new matter, espe- cially relative to the nerves of the kidney ; numerous alterations have been made, and the chapter on the tests for albumin in the urine has been entirely rewritten, in accordance with many new experiments I have made relative thereto. I continue to employ the terms ursemic accidents and uraemic poisoning out of deference to usage ; though, as well known, recent experiments have shown injections of urea into the blood to be less noxious than has been supposed; the noxious element in the so-called ursBmic poisoning probably being some substance in the blood produced by imperfect formation or elimination on the part of the kidneys. H. B. MILLARD. 4 East Forty-first St. , New York. December 1, 1885. PREFACE. I have only to say of this volume that it is the result of the experience of nearly twenty-six years of hospital and extensive private practice, and of several years' study in the laboratory, of pathological and healthy kidneys of men and animals. The illustrations were all drawn by myself from kidneys, with the exception of Figures 1, 2, 7, and 8, which are taken from other authors, and 4, 5, 6, and 12, which were drawn for me from my own preparations. In perusing the works of many writers upon nephritis, I may in some instances unconsciously have incorpo- rated their ideas without according due credit. I have endeavored, however, carefully to fulfil all obligations of this kind. As I have shown in the context, the term Bright's disease, as understood by Bright himself, does not comprise every condition of nephritis, but as most of the conditions I have described are generally understood as belonging to Bright's disease, I have given my work this title, though the nomenclature is by no means exact. I have usually employed instead, throughout the book, the word nephritis. I have used exclusively the word albumin instead of vi PREFACE. albumen, although the termination en is generally used by medical writers. The word albumen, is, however, simply the Latin word meaning the "white of the egg,,f though it is applied to every variety of albumin ; the latter, however, represents the proximate princi- ple, and I believe chemists now generally distinguish the two by the terminations en and in. In Watts' "Dictionary of Chemistry," ' the most important work of the kind in English, the termination in, is exclusively used. Where, however, I have quoted from other authors, I have not felt justified in changing their spelling. My work has been, at least, conscientiously perform- ed, and with an earnest desire of adding to the knowl- edge and therapeutics of the subject of which it treats. H. B. MILLARD. 4 East Forty-first St., New York, November 1, 1883. 1 Longmans, Green & Co., London, 1870. TABLE OF CONTENTS. PART I. CHAPTEE I. PAGE General Anatomy of the Kidney.............................. 1 CHAPTER II. The Epithelia of the Urinary Tubules......................... 6 CHAPTEE III. The Endothelia of the Urinary Tubules........................ 18 CHAPTER IV. The Connective Tissue of the Kidney......................... 23 CHAPTER V. The Circulation of the Kidney................................ 25 CHAPTER VI. Nerves of the Kidney........................................ 28 CHAPTER VH. Nature and Sources of the Urinary Secretion and Extractives .... 33 viii CONTENTS. PAGE CHAPTER VIH. The Significance of the Existence or Non-existence of Albumin in the Urine, and the General Conditions of its Occurrence in Health and Disease.................................... 41 CHAPTER IX. The Tests for Albumin in the Urine........................... 54 CHAPTER X. The Importance and Significance of Urinary Casts.............. 69 CHAPTER XI. Nature and Mode of Formation of Urinary Casts............... 73 CHAPTER XII. General Directions for Examining the Urine for Casts and Kidney Epithelia............................................. 81 CHAPTER XIII. Of Nephritis................................................ 83 CHAPTER XIV. Croupous Nephritis. —Characteristics. —Acute Croupous Nephritis 87 CHAPTER XV. Chronic Croupous Nephritis ................................. 101 CHAPTER XVI. Suppurative Nephritis....................................... 124 CHAPTER XVII. Catarrhal or Interstitial Nephritis............................. 127 CONTENTS. ix PAGE CHAPTER XVIH. Acute and Chronic Interstitial Nephritis....................... 129 CHAPTER XIX. Nephritis without Albuminuria............................... 153 CHAPTER XX Chronic Interstitial Nephritis (continued)...................... 168 PART IL—Treatment. CHAPTER XXI. The Treatment of Acute Nephritis............................ 179 CHAPTER XXII. Treatment of Chronic Nephritis............................... 220 CHAPTER XXTTT. Treatment of Chronic Interstitial Nephritis.................... 222 CHAPTER XIV. Treatment of Chronic Croupous Nephritis..................... 248 CHAPTER XXV. Treatment of Suppurative Nephritis........................... 256 APPENDIX................................................ 257 INDEX..................................................... 259 t LIST OF ILLUSTRATIONS. Fig. 1.—Diagram showing the Course and Variations op the Renal Tubules.......................................... 4 Fig. 2.—Diagram op the Varieties op Epithelia................ 7 Fig. 3. —Transverse Section op the.Cortical Substance op Dog's Kidney. (500 diameters.).................................. 8 Fig. 4.—Convoluted Tubule from the Kidney of a Rabbit. (Longitudinal section—magnified 1,200 diameters.)—Nucleated columnar epithelium, showing the rods ; endothelia; interstitial connective tissue, producing the basement layer............... 13 Fig. 5.—Convoluted Tubule from a Human Kldney affected with Acute Catarrhal (Interstitial) Nephritis. (Oblique section—magnified 1,200 diameters.)—Inflammatory corpuscle, sprung from the division of an epithelium ; cluster of inflamma- tory corpuscles, sprung in the same manner; rods of cuboidal epithelia, still recognizable; endothelia, increased in size and number.................................................... 16 pIG, 6.—Convoluted Tubule prom a Human Kidney affected with Chronic Catarrhal (Desquamative) Nephritis. (Ob- lique section—magnified 1,200 diameters.)—Calibre, widened by loss of the epithelia; endothelia, increased in size and number ; interstitial fibrous connective tissue, with augmented plastids ... 20 xii LIST OF ILLUSTRATIONS. PAGE Fig. 7.—(From Heitzmann.)—Boundary Line between the Cor- tical and Pyramidal Substance op the Kidney op a Dog. Blood-vessels Injected.—Branch of renal artery ; prolonga- tion of the cortical substance ; tuft; bundle of straight tubules ; origin of the vasa recta from the capillaries of the cortical sub- stance ; bundle of vasa recta. (Magnified 100 diameters.)..... 26 Fig. 8.—(Holbrook.)—Diagram op Termination of the Nerves op the Kidney........................................... 29 Fig. 9.—Hyaline Casts. (500 diameters.)........................ 71 Fig. 10.—Mucous Casts. (500 diameters.)........................ 71 Fig. 11.—Acute Croupous Nephritis showing Exudate.—Lon- gitudinal section of tubule, showing droplets of exudate. (500 diameters.)................................................ 73 Fig. 12.—Acute Croupous Nephritis.—Longitudinal section of con- voluted tubule, showing formation of casts, endothelia, etc. (500 diameters.)................................................ 74 Fig. 13.—Convoluted Tubule from a Human Kidney affected with Acute Croupous Nephritis. (Oblique section—magni- fied 1,200 diameters.)—Hyaline cast; swollen and disintegrated epithelia participating in the formation of the cast; wreath of endothelia ; interstitial connective tissue...................... 77 Fig. 14.—Various Forms and Kinds op Casts. (Magnified 500 diameters.).................................... ........... 79 Fig. 15.—Acute Croupous Nephritis.—Transverse section of cor- tical substance, showing cloudy swelling of epithelia. (600 di- ameters.) .............,................................... 96 Fig. 16.—Convoluted Tubule from a Human Kidney affected with Acute (Interstitial) Nephritis. (1,200 diameters.) Same as Fig. 5............................................ 97 Fig. 17.—Suppurative Nephritis.—Epithelia and masses of living matter, some homogeneous and some having differentiated into LIST OF ILLUSTRATIONS. xiii inflammatory corpuscles; shining lumps of matter and inflam- matory corpuscles; epithelium dividing ; tubule, with granular matter greatly enlarged and epithelia enormously swollen; tubules, with endothelia and broken-down epithelia and granu- lar matter; tubule filled with pus corpuscles; epithelia: the nuclei, and granular matter undergoing transformation into shining lumps; thickened connective tissue. (Transverse sec- tion, magnified 500 diameters.).............................. 99 Fig. 18.—(Three illustrations.)—A, Chronic Croupous Nephritis- Straight Tubule.—Granular swelling of the epithelia, show- ing rods and reticular structure. (Magnified 1,000 diameters.) B, Fatty Degeneration of the Kidney.—Cross-section of convoluted tubule. Cloudy swelling of epithelia, showing rods and fat granules. Connective tissue thickened. (Magnified 600 diameters.) C, Chronic Croupous Nephritis with Waxy Degenera- tion, showing rods rather enlarged. Cross-section of ascend- ing tubule. A, droplets of waxy exudation. (Magnified 600 diameters.)................................................ 115 Fig. 19.—Chronic Croupous Nephritis.—Cross-section of convo- luted tubule filled with nuclei, granular matter from broken- down epithelia, and indifferent elements; granular casts sur- rounded by endothelia ; homogeneous lumps of matter formed from the nuclei of the epithelia; hyaline cast surrounded by en- dothelia ; epithelia converted into amyloid or waxy corpuscles ; widened structureless membrane ; atrophied tuft; space between capsule and tuft filled with connective tissue ; thickened cap- sule, etc. (Magnified 500 diameters.)........................116 Fig. 20.—Fatty Degeneration op the Kidney—High Degree (Large White Kidney)—Chronic Croupous Nephritis. Spaces greatly widened.— Fatty cast; broken-down epithelia, showing fat globules ; fat globules in the connective tissue ; en- dothelia ; nuclei of epithelia, some having undergone the fatty XIV LIST OF ILLUSTRATIONS. change ; inflammatory corpuscles ; tubule with granular matter ; epithelia undergoing the fatty change; epithelia partly broken down or showing fatty change. (Magnified 500 diameters.)---117 Fig. 21.—Waxy Degeneration of the Kidney—Chronic Croup- ous Nephritis. —Waxy cast; capillary with waxy walls ; medul- lary rays with incipient waxy walls ; artery, transverse section in waxy degeneration ; epithelia and nuclei, part undergoing waxy change. (Magnified 500 diameters.).......................... 120 Fig. 22.—Chronic Croupous Nephritis.—Columnar epithelia, show- ing cloudy swelling ; tuft full of shining granules ; convoluted tubule filled with a mass of hyaline and granular matter. (Mag- nified 500 diameters.)...................................... 121 ■ Fig. 23.—Suppurative Nephritis (Abscess of Kidney).—Convoluted tubule, filled with pus corpuscles and lined by endothelia; broken-down epithelia ; tubuli nearly obliterated; pus corpus- cles ; increased and greatly augmented nuclei; inflammatory cor- puscles ; tubule with nearly unchanged epithelia. (Magnified 500 diameters.)............................................. 125 Fig. 24.—Pus Corpuscles, Epithelia from the Straight and the Convoluted Tubules and the Pelvis op the Kidney. (Magnified 500 diameters.)................................. 166 Fig. 25.— Cirrhosis op the Kidney — High Degree.— Striated and hypertrophied connective tissue ; tuft striated and envel- oped in connective tissue ; tubule converted into connective tis- sue ; compressed and shrunken tuft; thickened capsule, etc. (Magnified 500 diameters.).................................. 175 BRIGHT'S DISEASE AND ALBUMINURIA. PART I. CHAPTER I. THE GENERAL ANATOMY OF THE KIDNEY. That what I have to say upon the pathology, diagnosis, and treatment of nephritis (Bright's disease) may be quite clear, I may be permitted to map out and briefly describe the region in which are situated the lesions which exist in this malady. This is necessary to the general reader, because few who do not make pathology and histology a special study, are perfectly familiar with or can call at once to mind the minute anatomy of the kidney. With the general form and position of the kidney we are familiar enough to make it unnecessary to dwell upon them, simply stating, as a guide in autopsies, the average normal weight of the organ to be between four and five ounces. It is covered by a dense, closely adherent capsule, and its bulk is constituted by masses of tubules arranged in a certain order, connective tissue, glomeruli, and blood- vessels, from one portion of which the nutrition of the kidney is derived, and from the other most of the con- stituents peculiar to the urine are eliminated. l 2 bright' s disease. The whole kidney is divided into two principal re- gions, the cortical and medullary; the latter, again, into the zone of limitation or marginal region, and the papillary region. The cortical region is most vascular, and contains many thousands of small bodies, about y^ to 2^ inch in diameter, known as the Malpighian bodies. Each of these bodies consists of a congeries of blood-vessels, from 0.02 to 0.03 mm. in diameter, and ar- ranged in two main lobes, contained in a membranous sac, known as "Bowman's capsule." This congeries of blood-vessels is composed of a number of small arteries, which are a continuation or blossoming of a small ar- tery proceeding from an interlobular artery, emptying into Bowman's capsule at a point nearly opposite the neck of the capsule, and known as a nas afferens ; the tuft is known as a Malpighian tuft or glomerulus ; it subdivides into seven or eight arteries. These reunite to form a vessel known as a vas efferens, which emerges from the capsule at a point closely adjoining that which the vas afferens enters. The convolutions of the tuft form the lobules, one be- ing slightly larger than the other; they are both covered by a very thin layer of connective tissue ; this is reflected upon and forms the lining of the capsule. The whole surface of this delicate membrane is covered by a flat epithelial layer whose functions I shall hereafter allude to. The glomerulus is not adherent to the capsule. From the blood thus introduced into Bowman's cap- sule, certain elements, mostly aqueous, are passed out into the capsule, and hence arises the necessity of another outlet than the vas efferens; this outlet is the commencement of an uriniferous tubule ; it commences as a constricted neck, which quickly dilates into a crooked tube {tubulus contortus). This, with many windings, runs toward the medulla, in reaching which it becomes suddenly attenuated, and descends straight ANATOMY OF THE KIDNEY. 3 down, forming the descending branch of a curve known as "Henle's loop." In the region of the cortex it de- flects from the medullary ray, and is known as an ir- regular tubule. It then becomes convoluted, and again forming a convoluted tubule, of the second order, its con- vexity being directed toward the surface of the kidney, it empties by the junctional part into a collecting tu- bule ; this latter runs in a straight direction toward the papilla. When several of these tubes have reached the papilla they coalesce. A number of fascicles of col- lecting tubules, constituting the medullary ray, or pyra- mid of Perrein, form a cone-like body, the base looking toward the surface of the kidney. These cone-like bod- ies are produced by the union of the tubuli uriniferi at about the beginning of the zone of limitation ; they reunite just above the papilla, forming the cone. A number of primitive cones form the pyramids, Qr ren- culi; they have a bottle-shaped appearance, owing to the space between what would represent the junction of the neck and body of the bottle. These pyramids are known as the pyramids of MalpigM, or medullary pyr- amids. There are from ten to eighteen of these, sep- arated from each other by the prolongations of the cor- tex known as the columns of Bertin ; the apex of these pyramids forms a papilla which projects into the calices, these in turn being formed by the branching and sub- divisions of the pelvis, the latter being a basin formed by the expansion of the ureter. The formation and course of an uriniferous tubule is shown by Fig. 1. The changes of an independent uriniferous tubule, from its commencement at Bowman's capsule to the time it enters into a medullary ray, are numerous, undergo- ing many variations in direction and diameter. The diameters of the tubules in an adult vary from -^ to vkj of an inch. The space between the medullary rays 4 BRIGHT'S DISEASE. Fig 1.—Diaqbam shcvwws the Course and Variations op the Ebnal Tubules. After Klein and Smith (modified).—A, Cortex limited on its free surface by the capsule; a, subscapsu- lar layer not containing Malpighian corpuscles; B, boundary layer; C, meduUary substance, or papillary layer; 1, Bowman's capsule; 2, proximal convoluted tubule; 3, descending limb of Henle's loop; 4, the loop proper ; 5, ascending limb of Henle's loop ; 6, the ^regular tu- bule, and 7, the intercalated tubule, constituting the distal convoluted tubule ; 8, junctional tubule; 9, 10, straight collecting tubule of medullary ray and boundary layer; 11, collecting tubule of papillary part. ANATOMY OF THE KIDNEY. 5 in the cortical substance is known as the labyrinth ; it is here that the Malpighian bodies and the tubuli con- torti are found. Bowman's capsule may be regarded as the commence- ment of the uriniferous tubule. The wall of each tubule is formed of a delicate membrane, or tunica propria; this is absent in the ductus papillaris. Until a comparatively recent time, this membrane has been regarded as wholly homogeneous and structure- less. Ludwig shows, however, that "though," in his own language, "this is as clear as glass, elastic, a nu- cleus can occasionally be brought to view." See Chap- ter III. CHAPTER II. THE EPITHELIA OF THE URINARY TUBULES. The membrane of Bowman's capsule and its neck is continuous; but at the commencement of the convo- luted tubule it changes. Here the epithelia are com- posed of a clouded mass of nucleated protoplasm. The epithelial pulp is only loosely attached to the basement membrane. R. Heidenhain first called attention to minute granu- lations in the epithelia in certain of the tubules of ani- mals which he called stabchen, having a long axis di- rected toward the lumen, these epithelia being known as bacillated or rod-like epithelia. As the tubules undergo various changes in their caliber, direction, and form, so do the epithelia lining them vary. The convoluted tubules of the first and second order, the ascending and descending portions of the narrow tu- bules, are lined by polyhedral or cuboidal epithelia ; as the ascending and descending portions of these become narrower, the epithelia become flat. At the commence- ment of the collecting tubules they are lined with cu- boidal epithelia which soon become columnar, and in the lower portions they are distinctly imbricated. The form and structure of the various epithelia of the kidney are shown in the following figure from Heitzmann.1 As the article is pertinent to the subject now under consideration, I subjoin here portions of a paper written 1 Microscopical Morphology of the Animal Body in Health and Disease. C. Heitzmann. New York : 1883. epithelia of the tubules. 7 by me and published in the New York Journal of Medicine, June, 1882, treating also of certain changes the result of inflammation,entitled, "Researches in the Minute Anatomy of the Kidney." ' R. Heidenhain' was the first to call attention to the presence of a peculiar rod-like or bacillated structure Fig. 2.—Diagram of the Varieties of Epithelia.—F, flat epithelia in front view; S, same in side view ; Cu. cuboidal epithelia ; Co. columnar epithelia in side view; T, columnar epithelia in top view; Ci, ciliated columnar epithelia; B, bacillated columnar epithelia. existing in the uriniferous tubules. He found this struc- ture in convoluted tubules, in the ascending portions of the looped tubules, and in the intercalated tubules of the kidneys of mammals. According to his view, the rodlets (stabchen) are plainly visible in the outer portions of the epithelia— 1 Read before the New York Medico-Chirurgical Society, May 9, 1882. 2 " Mikrosk. Beitrage zur Anat. und Physiologie der Nieren:" Max Schultze's Arch. f. mikr. Anat., 10 Bd., 1874. 8 BRIGHT'S DISEASE. that is, in those portions lying next the connective tis- sue, and he sometimes saw in torn epithelia the rods isolated. The same observer1 also first demonstrated with accuracy that the secretion of the salts is per- formed only in the tubules, in accordance with the views maintained by Bowman. Char- cot 2 deduces from the experiments of Heidenhain with indigo-blue the conclusion that the secretion or elimination of this coloring matter takes place only in those portions of the tubuli uriniferi which are covered by the epithelia having the rods (epithelium a batonnets). Whether the secre- Fra. 3.-Cortical Substance op tion of the Specific principles of Dog's Kidnet—Transverse Sec- . . r tion—Blood Vessels Injected.— the Urine takes place in precisely A, tuft; B, capsule; C, flat epi- r ^ J theiia; d, convoluted tubuie; e, the same fashion as the elimination straight collecting tubule; F, as- cending limb of narrow tubuie; g, of coloring matters, he regards as descending limb of narrow tubule; ° ' ° h,irregular-tubuie: i,vasa reaa. impossible of demonstration ex- Magmfied 500 diameters. 1 perimentally. In a late monograph by Charcot, Legons sur les Con- ditions Pathogeniques de VAlbuminuric, Paris, 1881, he regards the tubuli contorti and the loops of Henle, particularly the ascending branches of the loops, as the real glandular part of the kidney. "They are," he says, "lined by an epithelium, thick, granulated, cloudy—in a word, glandular. They are enveloped in all parts by a dense capillary network, bathed, like themselves, in a lymphatic fluid." " These parts seem, then, in some respects, designed for the selection and concentration of the specific principles of the urine, 1 " Versucbe iiber den Vorgang der Harnabsonderung : " Pfltiger's Archiv, 9 Bd., p. 1., 1874. 2 Charcot on Bright's Disease, translated by Millard, p. 23, New York, 1878. EPITHELIA OF THE TUBULES. 9 urea, and uric acid; it is in these parts, no doubt, that is formed the hippuric acid, which does not pre-exist in the blood." Heidenhain, however, did not associate the rods with the process of secretion, for he observed a similar struc- ture also in the smaller ducts of the parotid and sub- maxillary glands, the same formation in the latter structure being already known to Henle and Pfluger. In the acini of the glandula submaxillaris and in the other acinous glands he could not discern them. E. Klein1 asserts that he has observed that the rods or fibrils of Heidenhain, when looked at from the surface, are connected into a network, so that they are more probably septa of a honey-combed network seen in pro- file. What the intimate nature of these formations is neither of the above-named authors attempts to explain. My own researches, I hope, will prove their nature, though as to their significance I have only suggestions to make. Since the reticular structure of all protoplas- mic formations, including, therefore, epithelium, was demonstrated by C. Heitzmann,2 the question has been what the reticulum present in the protoplasm is. Un- questionably the two main properties of living matter are motion and production of its own kind. Both these properties are attributes of the reticulum within the protoplasm. As long as a protoplasmic body is alive and endowed with the property of amoeboid motion and locomotion, the reticulum in it is never in a state of per- fect rest. We constantly see changes in the configura- tion of the reticulum. We see that in a portion of the protoplasmic body the reticulum becomes very narrow, while in an opposite portion it is simultaneously wi- dened, especially so when a prolongation of the body, a 1 Atlas of Histology, London, 1880. * " Untersuchungen iiber das Protoplasma: " Sitzungsberichte d. kaiserl. Akad. d. Wissensch. in Wien., 1873. 10 BRIGHT'S DISEASE. pseudopodium, is pushed out. In such a flat offshoot, or false leg, the reticulum may be stretched to such a degree that the projection looks homogeneous, as if des- titute of any structure. The writer above quoted claims that the narrowing of the reticulum is the state of contraction which is an ac- tive property belonging to it. The stretching, on the contrary, represents the state of extension which is merely passive, due to the pressure of the liquid pushed out from the contracted portion into that at compara- tive rest, this contracted portion being immediately after extended. The foregoing is tenable only if we admit the presence of an investing layer around the protoplasmic body which prevents the liquid filling the meshes from escap- ing outward. The flat investing layer is claimed to be identical in its nature with the mass composing the re- ticulum proper. It is maintained, also, that the reticu- lum at any time, and almost instantaneously, may be transformed into a flat layer, as is the case in the for- mation of an investing layer around a vacuole. Vice versa, the flat'layer almost instantaneously may fall back into the reticular structure at the moment of dis- appearance of the vacuole. This continuous change of shape and place of the reticulum is a positive proof of its being living matter. S. Strieker,1 among the most recent observers, describes the reticular structure and its changes as follows : "The interior of the cell-bodies undergoes manifold visible variations. One of the most remarkable instances is furnished in the saliva corpuscles. The assumption that a so-called molecular motion takes place in the saliva corpuscles is erroneous. The granules seen with insufficient amplifications are transverse sections of tra- 1 " Mittheilung iiber Zellen und Grundsubstanzen:" Med. Jahrbiicher, 1880. EPITHELIA OF THE TUBULES. 11 beculse. The saliva corpuscle is traversed by a sharply marked trabecular structure, which, so long as the cor- puscle is fresh, executes lively wavy motions. The waving gradually ceases on addition of solutions of salts in certain concentration, and the reticular structure dis- appears. The waving is now replaced by very slowly formed changes in the interior mass." A second proof of the reticulum being the living mat- ter proper rests upon the fact that, both in normal and in morbid processes, the new formation of corpuscular elements starts from the points of intersection in the reticulum. This so-called endogenous new formation of living matter is especially plain in the inflammatory process invading epithelial formations. Here, it is im- portant to note, the reticulum at first becomes coarse, next it coalesces into lumps, which, being at first homo- geneous, in turn assume a reticular structure themselves, and now represent so-called inflammatory or pus cor- puscles. These corpuscles at first remain in connection with the neighboring reticulum by means of delicate filaments, which are portion and part of the reticulum. Later, when the pus corpuscles which have originated in the interior of an epithelium become extruded from its interior, the newly formed corpuscles represent pus corpuscles. In conducting my researches, I have studied the kid- neys of the rabbit, pig, dog, and man, all of them being preserved and hardened in a solution of chromic acid. I have, therefore, no observations to report upon the form-changes of the epithelia, but have studied the changes in the interior structure-of the epithelia in the inflamed human kidney as they appear in chronic croupous, in chronic interstitial nephritis, in waxy de- generation of the kidney, in fatty degeneration, and in chronic interstitial nephritis with acute recurrence. These investigations enable me to maintain that the re- 12 BRIGHT'S DISEASE. ticular structure of the epithelium of the kidney is really a formation of living matter. Upon closely examining the epithelia of the tubuli uriniferi in the kidneys of the above-named animals, we readily perceive, with comparatively low powers of the microscope (400 or 500 is sufficient), the presence of rod-like formations in the epithelia of the tubuli con- torti, in the irregular tubules, in the ascending branch of the looped tubules, and in the intercalated tubules, entirely in accordance with Heidenhain's assertions, al- though he does not include the kidneys of the pig. The drawings of the rodlets, as given by Heidenhain in Max Schultze's " Archiv," and copied by Klein and other writers, give an exaggerated idea of the real ap- pearance of the rods. Even under a high power they are never so large as in the drawings, and seldom pre- sent the straight, regular, and symmetrical appearance there represented. The accompanying drawing (Fig. 4) more nearly represents their average appearance under a power of 1,200. I have found them in the healthy kidney as follows : In man, in the ascending tubules, power 1,200. In the rabbit, power 500 to 600, in convoluted, in ascending, and in irregular tubules. Also (never before mentioned) in a portion of the descending tubules. In the pig, in the convoluted and irregular tubules; and in the same tubules, and narrow tubules, in which the rods are very faintly shown, of the pup. The pale, flat epithelia of the looped tubule proper do not, as a rule, exhibit the rods. The columnar epithelia of the collecting tubules, on the contrary, which are distinctly imbricated, especially in the kidney of the dog, exhibit the rods more or less plainly. The colum- nar epithelium of the rabbit does, however, show them. High powers (1,000 to 1,200) of the microscope corrob- orated the views of Klein—namely, that the rods are RODLIKE STRUCTURE OF THE EPITHELIA. connected with a reticulum by means of delicate fila- ments inosculating both with the wall of the nucleus around which the rods are located, and also with the delicate reticulum in the inner portion of the epithelia, next to the caliber, where the rods are usually absent. It is striking how the thickness of the rods differs in the different epithelia of the same animal's kidney. producing Sometimes they are very thin, beaded poles, with quite distinctly marked interstices between them. In this case the connecting filaments, running almost at right angles from rod to rod, are easily discernible At other times the rods are rather bulky formations, having but extremely narrow interstices between them. In this in stance the connecting filaments, as a matter of course, are very short, and not easily seen. In a third instance the outermost portion of the epithelium is a compact or 14 BRIGHT'S DISEASE. homogeneous mass, in which no rods can be observed at all. Another striking feature is the great variety of ap- pearances exhibited by the cement-substance. Some- times this is plainly marked at regular intervals between the epithelia. Then the transverse connecting filaments, the formerly so-called thorns, are plainly visible. At other times hardly any trace of cement-substance is seen, but the reticular structure is present in a nearly uniform distribution throughout the epithelial layer. S. Strieker (loc. cit.) was the first who observed these same varieties in the appearance of the cement-sub- stance in the epithelial layer of the cornea ; also, that the nucleus varies greatly in the degree of distinctness in which it comes to observation. Where the rods are slender, the nucleus, as a rule, is well defined; where, on the contrary, they are bulky, the nucleus is, on an average, not very plainly marked. The sharpest defi- nition of the nucleus is furnished by the flat epithelia of the looped tubules in which the rods, as before men- tioned, are absent. In inflamed kidneys of man I have repeatedly found the rods as follows: 1. In chronic interstitial nephritis : a. In the convoluted tubules. b. In the straight tubules. 2. In acute croupous nephritis : a. In ascending tubules. 3. In chronic croupous nephritis, in the straight tu- bules. 4. In chronic croupous nephritis with waxy degenera- tion, cross-sections of ascending tubules show the rods rather enlarged. Also in straight tubules in the pyra- mid of the same kidney. 5. In chronic croupous nephritis with acute recur- rence, in cross-sections of the convoluted tubules. RODLIKE STRUCTURE OF THE EPITHELIA. 15 6. In fatty degeneration of the kidney, in cross-sec- tions of the convoluted tubules. The rods here showed fat globules. The connective tissue was thickened. In these specimens the rods of the epithelia through- out the tubules are clumsy and bulky, the whole reticu- lum being enlarged, rendering the epithelium, with low powers of the microscope, coarsely granular. In many instances the rods are not discernible, as, in their place, a coarsely granular mass is present, pervading the whole epithelial body; or else the innermost portion of the epithelium looks coarsely granular, the outermost por- tion, on the contrary, being homogeneous and shining. I have repeatedly seen in acute interstitial nephritis even the looped tubules, which in this situation were consid- erably increased in bulk, provided with a coarsely gran- ular reticulum—nay, even with an indistinct rod-like structure. All these features become still more promi- nent by staining the specimens with the chloride of gold after they have been soaked and washed for several days in distilled water. This reagent, in a half-per- cent, solution, brought in contact with the specimens for forty minutes, renders sections from the normal kidney of a brown violet hue, slightly increasing the distinct- ness of the reticular structure of the epithelia. In the inflamed kidneys of man, the epithelia of a great many of the ascending, irregular, and convoluted tubules, upon being stained with the chloride of gold, as above de- scribed, became dark violet. With higher powers of the microscope we can ascertain that it is the coarse re- ticulum, the bulky rods, and the homogeneous masses sprung from coalescence, as it were, of the rods, which exhibit the deepest gold stain. As it is the tubuli uriniferi which have the rod-like structure, which in Heidenhain's experiments with in- digo sulphate are the only ones which are colored by it, so in the inflamed kidney it is only these tubules that 16 BRIGHT'S DISEASE. become colored by the gold. It seems reasonable to suppose, from the effect of these reagents, that the epithelia with rods, perhaps by virtue of their having more living matter and a more bulky reticulum, are of most importance in secreting or forming the extractive matter of the urine. Numerous attempts to produce the stain with the gold in the healthy kidney of the dog, pup, rabbit, and pig Fig. 5.—Convoluted Tubule fhom a Human Kidney affected with Acute Catab- rhal (Interstitial) Nephritis. (Oblique section—magnified 1,200 diameters.)—P, inflam- matory corpuscle, sprung from the division of an epithelium ; D, cluster of inflammatory corpuscles, sprung in the same manner; B, rods of cuboidal epithelia, still recognizable; Es endothelia, increased in size and number. were ineffectual in rendering the rods plainer than in the unstained condition. In the inflamed kidneys, in which the violet coloration was produced, no doubt the reticulum of the epithelia, owing to the inflammatory process, was considerably increased in bulk. The most marked violet stain was exhibited by a number of the convoluted tubules and by irregular and ascending tubules. We know that living RODLIKE STRUCTURE OF THE EPITHELIA. 17 matter is considerably increased in amount in the in- flammatory process, and are justified, consequently, in maintaining that the reticulum and rod-like formations within the epithelium, being part of the reticulum, are formations of living matter. As to the significance of the rods, it may be inferred from the statements I have made that they are in close relation with the process of secretion. Obviously, the stream of liquid running from the neighboring blood- vessels through the epithelia toward the liquids con- tained in the caliber, and vice versa, will be facilitated by an elongated arrangement of the reticulum—i.e., the rods. In a state of comparative rest the rods lie close to each other—nay, are coalesced into homogeneous masses. In this condition the cement-substance between the epithelia is best marked. In full activity of the epithelium, on the contrary, the rods will be very dis- tinct, will stand further apart, and the cement-sub- stance between the epithelia will in consequence become indistinct. 2 CHAPTER III. THE ENDOTHELIA OF THE URINARY TUBULES. While investigating the peculiarities in the structure of epithelia of tubuli uriniferi in their normal condi- tion, I often observed the presence of flat, spindle-shaped bodies between the basis of the epithelia and the adja- cent so-called structureless membrane of the tubule. These spindle-shaped bodies doubtless correspond to those flat, nucleated formations which cover the inner surface of the structureless layer in nearly all epithelial —i.e., glandular—formations. By most observers they are regarded as endothelia belonging to the connective tissue subjacent to the epithelial layers. V. Czerny was the first one to bring them to view in other tissues, which he did by staining the specimens with the nitrate of silver ; and C. Ludwig,1 also by the silver stain, first indicated their presence in the urinary tubules. He does not fully describe them, but alludes to them as follows. Speaking of the basement membrane of the tubuli uriniferi, he says: "In general the basement membrane appears to be homogeneous, and cannot be further divided; but occasionally a nucleus can be brought into view in the substance by carmine ; and in some instances, and for short distances, the same ap- pearances occur in the tortuous canals, when treated with nitrate of silver, as are presented by the blood and lymph capillaries under the same condition." "The basement membrane is as clear as glass, elastic." " The 1 Hand-book of Histology, by S. Strieker. London, 1874. ENDOTHELIA OF THE TUBULES. 19 shape of the nucleus is usually the same in all instances, being spherical, sharply defined, and with numerous granules scattered through its substance." Such an endothelial layer, present in all varieties of the urinary tubules, is best visible in the front view of the structureless membrane, where the epithelium is stripped off. Here the endothelia are comparatively large, irregularly polyhedral bodies, with distinct cen- tral nuclei. The nucleus has a plainly marked shell, containing in its interior a few small nucleoli, the nuclei being mostly of oblong shape. In the body of the en- dothelium a delicate reticulum is seen with very minute nodulations. Each body is separated from all its neigh- bors by a delicate light rim of cement-substance, which is traversed at right angles by extremely minute fila- ments or thorns. In side view, obviously, these bodies will exhibit a spindle-shape, the broadest portion of the spindle corresponding to the central nucleus. If the views of recent observers are correct—namely, that the structureless layer, synonymous with the hya- line or basement layer, is an aggregation of endothelia infiltrated with elastic substance—this view may also be applied to the structureless membrane of the urinary tubules. In normal kidneys I failed to discover nu- clei in the structureless layer proper, which would indicate their construction of former endothelia. In inflamed kidneys, on the contrary, no doubt was left as to the fact that the structureless layer is composed by a number of closely attached, in part nucleated, en- dothelia. I have found the endothelia repeatedly in the inflamed kidney in chronic croupous and in chronic interstitial nephritis, in acute interstitial and in acute croupous nephritis, and in fatty and waxy degeneration of the kidney. I have found them most frequently in the ascending, descending, and convoluted tubules. I am 20 BRIGHT'S DISEASE. not aware that any observer has heretofore recognized their existence as having a pathological significance. In the inflamed kidney the endothelial layer beneath the epithelial is always more marked than in the nor- mal kidney. In chronic catarrhal (interstitial or des- quamative) nephritis, all the tubules that have lost their epithelial investment invariably show an invest- ment of endothelia. Fig. 6.—Convoluted Tubul'e from a Human Kidney affected with Chronic Ca- tarrhal (Desquamative) Nephritis. (Oblique section—magnified 1,200 diameters.)—C, caliber, widened by loss of the epithelia; E, endothelia, increased in size and number; F, in- terstitial fibrous connective tissue, with augmented plastids. This, in the transverse section of the tubule, is char- acterized by the presence of flat, irregularly spindle- shaped bodies, which are always more coarsely granular than in the physiological condition. Their nuclei are also more coarsely granular, sometimes homogeneous. The flat shape, the large size in the frontal diameter, and the construction of the nuclei serve for an accurate contradistinction to epithelia. I have failed in obtain- ENDOTHELIA OF THE TUBULES. 21 ing specimens indicative of a new formation of epithelia after the loss of the original epithelial investment. It may be admissible to assume that the enlarged en- dothelial layer serves (at least to some extent) as a substitute for the lost epithelia. In tubules whose epi- thelia, as in chronic catarrhal nephritis, are transformed into inflammatory or medullary corpuscles, the new formation also starts from the endothelia. The final result in this instance is known to be the destruction of the tubule and its replacement by newly formed con- nective tissue—a condition which is known by patholo- gists as cirrhosis of the kidney. [Since writing the rough outlines of this article, I have recognized for the first time well-marked endo- thelia in the urine in a case of advanced chronic croup- ous nephritis with fatty degeneration. I found a clus- ter of three or four of these surrounded by free fat granules.] Still more plainly marked are the endothelia in croupous (parenchymatous) nephritis. In fact, the ap- pearances seen in urinary tubules where casts have just formed could not be explained unless by the presence of endothelia. The results of my researches may be summed up in the following statements : 1. The rods discovered by Heidenhain in some varie- ties of the tubuli uriniferi are part and parcel of a retic- ulum present within every epithelium. 2. The reticulum, including its elongated rodlike for- mations, is the living matter proper. 3 The relation of the rods to the rest of the reticulum of an epithelial body varies greatly, the variation prob- ably being due to different stages or degrees of secretion. 4 The reticulum, including the rodlike formations, in the inflammatory process, both in catarrhal and croupous nephritis, gives rise, to a new formation of 22 BRIGHT'S DISEASE. living matter, which results in the new formation of medullary corpuscles or pus corpuscles. 5. The structureless membrane is lined by flat endo- thelia lying between it and the basis of the epithelia of the urinary tubules. 6. In nephritis the endothelia become considerably enlarged, and in catarrhal, as well as in croupous ne- phritis, they line the urinary tubules after the epithelia have been shed or lost; they surround the cast in croupous nephritis after the epithelia have perished in the formation of the cast. CHAPTER IV. THE CONNECTIVE TISSUE OF THE KIDNEY. The importance of this tissue will be readily understood when we consider that to its lesions is due one of the most common forms of Bright's disease, namely, inter- stitial nephritis. According to G. Johnson (" Lectures on Bright's Dis- ease") this connective tissue does not exist in the laby- rinth, but I have repeatedly recognized it in healthy kidneys of man, of the rabbit, dog, and pig. No fibril- lated connective tissue exists between the tubuli con- tort i. It is found, however, in the tissue immediately surrounding the Malpighian corpuscles, and especially those lying close to the medulla. These are often en- closed by fibrous connective tissue. Elsewhere, only isolated small fusiform cells lie be- tween the blood capillaries and the urinary tubules of the labyrinth. They do not, however, in any way bind the convolutions of the tubuli uriniferi either to one another or to the blood-vessels. The spaces between the tubules of the medulla in the immediate neighbor- hood of the papilla are filled with a distinctive fibrillated connective tissue surrounding the urinary tubules in a concentric manner. The nearer we approach the limit- ing layer the more delicate becomes the fibrillation and the more abundant the cellular elements. (Ludwig, in Strieker's "Histology.") The capillaries forming the glomerulus are covered by delicate connective tissue. This delicate layer also lines 24 BRIGHT'S DISEASE. the capsule, both layers being covered with epithelia; according to Heitzmann that upon the glomerulus be- ing cuboid in the fcetus and flat in the adult, while that upon the parietal portion is flat. In scarlatina, in the case of patients who succumbed rapidly from anuria, Mr. Klebs states that he found the only lesion in the kidney to be an excessive multiplication of the cells (or epithelia) of the connective tissue of the glomerulus, naturally producing compression of its blood-vessels. There is no doubt, however, that inflammation of the glomerulus could not exist without inflammations of other portions of this organ. The convoluted tissue of the glomerulus is often thickened, but not indepen- dently of other inflammation. CHAPTER V. THE CIRCULATION OF THE KIDNEY. The greater part of the renal arteries run into the cor- tex, forming arterise interlobulares. A small portion of these penetrate to the fibrous capsule, and each arte- ria interlobularis sends to a Malpighian body a small trunklet called a vas afferens ; a few of these vasa affer- entia give off fine branches which break up into capilla- ries through which the blood passes into the capillary plexuses surrounding the urinary tubules. The vas efferens, which contains arterial blood, after leaving the capsule of Bowman runs immediately to th(J medullary ray, subdividing, as it extends, into a capil- lary network and running in part to the cortical sub- stance. From the capillaries of the cortical substance thus formed, descend straight branches, supplying the medullary rays. These are the true vasa recta. The labyrinth derives its supply of blood from the capillaries running upward from the efferent vessel. The capillaries, composing a plexus surrounding a medullary ray, are never closely adherent to the urinary tubules, lacuniform spaces, frequently filled with fluid, intervening between the walls of the blood and the uri- nary vessels. Both these varieties run immediately toward the fis- sure-like space in the marginal layer of the medulla, between the fasciculi of the tubuli uriniferi. They break up into capillaries that form looped plexuses about the tubules. The circulation of the medullary 26 bright' s disease. portion is therefore derived from the capillaries di- rectly arising from the vasa efferentia and from the vasa recta descending from the cortical plexus. "The veins arise from the capillaries of the cortical substance, es- Fig. 7. (From Heitzmann.)—Boundaby Line between the Cortical and Pyramidal Substance of the Kidney or a Dog. Blood-vessels Injected.— A, branch of renal ar- tery ; Co, prolongation of the cortical substance; T, tuft; S, bundle of straight tubules; O, origin of the vasa recta from the capillaries of the cortical substance ; B, bundle of vasa recta, magnified 100 diameters. pecially those of the labyrinth, and their confluence is often marked on the surface of the kidney in the form of stars. As the medullary rays are lost near the sur- face of the kidney and the outermost portion of the cor- tex has no tufts, obviously the veins arise from the CIRCULATION of the kidney. 27 capillary system surrounding the convoluted tubules. The veins accompany the arteries, and empty into the venous plexus at the boundary zone between the cortex and the pyramis. The latter furnishes veins derived both from the capillaries of the collecting tubules and from the vasa recta, the ascending loops of which empty directly into the inter-zonal venous plexus." (Heitzmann, loc. cit, p. 738.) CHAPTER VI. the nerves of the kidney Have not by histologists received the attention they merit. Among the most valuable investigations are those made by Dr. Holbrook, of New York, and con- tained in a paper on "The Termination of the Nerves of the Kidney," read before the American Society of Mi- croscopists, in 1883, a resume of which is herewith pre- sented : The nerves supplying the kidneys are mainly of the non-medullated variety. They accompany the larger arteries of this organ, either in bundles or in flat ex- panded layers, and the latter features I found more common than the former. Sometimes an artery would be found encircled by a network of non-medullated nerves of a bewildering number. Hundreds of such nucleated bundles of fibres could be traced around, above, and below an artery, freely branching, bifurcating and supplying all the neighboring formations with a large number of delicate fibrillse. In such a case the single non-medullated nerve-fibres lay apart and were separated by an ex- tremely delicate layer of fibrous tissue, the perineu- rium internum. The cortical substance undoubtedly derives all of its nerves from such bundles accompany- ing arteries. The pyramidal substance is supplied with bundles of non-medullated nerves, apparently indepen- dent of the arteries ; at all events such formations are exceedingly scanty here. The bundles of non-medul' THE NERVES OF THE KIDNEY. 29 lated nerve-fibres are marked by a large number of nuclei. True ganglions I have seen only in small numbers. The bundles of nerve-fibres give off delicate ramules to the afferent vessels by which they enter the tuft, Fig. 8. (Holbrook.)—Diagram of the Termination op thk Nebveb of the Kidney.— JV Bundle of non-medullated nerve-fibres accompanying an artery ; T, tuft; A, afferent vessel; G ganglionic enlargement along a nerve-fibre going to a convoluted tubule; C L, convoluted tubule in longitudinal section; C C, convoluted tubule in cross section; WA, ascending branch of narrow tubule; JV, narrow looped tubule; C, capillary blood-vessel; -S L, straight collecting tubule in longitudinal section; .*s^-%K