Structural and Functional Transformations in the Tubular Epithelium of the Dog's Kidney in Chronic Bright's Disease and Their Relation to Mechanisms of Renal Compensation and Failure

Abstract

Although it has been generally recognized since the work of Jores (1) that a profound transformation of the normal architecture of the kidney must result from the intermingling of retrogressive and reparative processes that make up the protracted course of chronic Bright's disease, the full degree of the complexity of these alterations only becomes evident when the constituent parenchymal units are examined by a technique, such as microdissection, which allows an appreciation of continuity of structure and an exact localization of parenchymal distortions. A topographical reconstruction of the altered organ thus becomes possible (2).Appreciation of such detail in the form of an organ is necessary as a first step in the understanding of its activity; yet these architectural data are obviously inadequate in any exact correlation of the two aspects, functional and structural, of the renal lesion, for it is at the interface of cell, capillary, and tubule lumen that the essential disturbances occur. The structure of the tubular epithelium of the altered nephrons must therefore be known and for this problem the method of the histological section is proper.A priori consideration of the nature of the epithelial wall of the nephron shows at once how complicated the study of its structure may become in a kidney that has been affected for a considerable period of time. The following categories of epithelia might be expected.

Pathophysiology of Experimental Glomerulonephritis in Rats

“…Impressive overall functional renal adaptation accompanies these marked structural changes (8)(9)(10)(11). Information on the function of individual structurally altered nephrons, however, is sparse and apparently contradictory (12)(13)(14)(15)(16)(17).…”

Cellular Mechanisms of Protein Metabolism in the Nephron

“…In these hypertrophied proximal convolutions of the failing kidney there was, as in the case of vital staining with the large molecular complexes of the dye trypan blue (15), visible evidence of both increased reabsorption and cellular inadequacy. In the case of vital staining with trypan blue, the latter took the form of a diffusion of dye throughout the cell cytoplasm and in the experiments with protein of droplet formation, a dissimilarity explicable by the differing physical properties of the two materials, dye and protein, which were being handled by renal cells.…”

“…Though the mechanisms of reabsorption and transport are presumably different in the two cases, a "threshold" of protein excretion with its implication of tubular reabsorption has been observed (39), and the "negative intercept" (40) resulting when its urinary output is plotted against its plasma concentration in the normal dog (41) has been advanced as a measure of this reabsorpfion. The application of clearance studies to the measurement of the relative filtration and reabsorption of protein in the nephrotic syndrome (42,43) has encountered the difficulties of interpretation which are not infrequently met when these techniques are applied to the examination of abnormal nephrons which are no longer working by the basic mechanisms on which the interpretations of the clearance is predicated; in fact, the first doubts as to the meaning of clearances in such situations was illustrated by the anomalies occurring in the reabsorption of large molecular complexes (15). Moreover, in the case of protein clearances, the procedure itself introduces the disturbing factor of an increasing blood volume and glomerular filtration (44,45) which may obscure whatever part tubular reabsorption, itself demonstrably (15) altered, may be playing in that final resultant which is termed a "clearance.…”

“…It has been shown that droplets do not form in the cells of an area of localized tubular damage caugecl by heavy metal (Hg) poisoning even when foreign egg white is administered in an amount which fills the cells of the remaining normal parts of the same convolution (1). Atypical regenerated tubule cells which are deficient in mitochondrial organelles (13) and enzyme content (14) and which do not reabsorb vital dyes (15) from the tubule lumen also show no evidence of droplet formation after an injection of egg white (1).…”

“…The maintenance of filtration in the progressively failing kidney requires no increased energy output of a surviving nephron, but the increased work of its tubule in all its multiform aspects increases progressively to an ever higher and ultimately impossible level. The structural changes that accompany this increase and final collapse in tubular activity, in so far as they affect tubular reabsorption and intracellular accumulation of large molecular complexes other than protein, have been examined by vital staining of the nephrons with trypan blue in the chronic renal failure of spontaneous canine nephritis (15). In brief, there is observed an increased vital staining of the persisting and now hypertrophic proximal convolutions so that the concentration of reabsorbed dye per nephros is greatly increased.…”