Dimensional Interrelationships of the Proximal and Distal Tubules of the Nephrons in the Dog

Abstract

The structural organization of the nephron is consistent with a progressive change in the volume and composition of glomerular filtrate as it passes down the tubule. Reabsorption of solute and water seems to begin as soon as filtrate enters the proximal convoluted tubule and continues thereafter in proportion to the load. Since the TF/P ratio of inulin remains relatively constant at any point over a wide range of GFR it has been inferred that a functional "glomerulotubular balance" arises actively from appropriate changes in reabsorption in response to alterations in filtered load. By this mechanism, which is not yet understood nor clearly defined ( l ) , an inherent variation in nephron function is minimized. If the remarkable diversity of the nephron population evident in a two-to fourfold range in glomerular and tubular dimensions ( 2, 3 ) were coupled with an equal diversity in nephron activity, precise and predictable control of overall activity by neural and humoral mechanisms would be greatly impaired. Non-uniform distribution of the excretory load might also have deleterious effects. This potential variance appears to be modulated by anatomic as well as physiologic integration. Glomerular size has !been found (2, 3 ) to be correlated in dog and man with volume of the attached proximal convoluted tubules, suggesting that the tubular cell mass is approximately geared to the filtered load imposed upon it. Since function of the proximal tubule, in turn, determines the volume and composition of the residual filtrate entering the distal tubule, it may be inferred that the volumes of the prox-1 This work was supported by a Program-Project Grant (HE 05'141) from the National Heart Institute, Bethesda, Maryland.imal and distal convoluted tubules are correlated in the same manner. This inference has been borne out by the study reported herewith.Methods. Measurements of the dimensions of proximal and distal tubules were made on nephrons obtained by microdissection (2, 3) from the kidneys of three female dogs (Q, P, and E), weighing 16, 14, and 15 kg, respectively. All were in good heaath and renal function studies had yielded normal results sl~ortly before sacrifice. I n each instance the hidrieys (weighing 28, 28, and 36 g, respectively) were removed, bisected, and fixed in 10% formalin for a t least 4 weeks. I n none was there any evidence of renal or urinary tract pathology on gross and microscopic examination.Small thin wedges of tissue which included cortex and medulla were taken from one of each pair of kidneys a t uniformly distributed points from the polar, equatorial, and intermediate zones. The tissue was macerated for 5 hr in concentrated hydrochloric acid a t 3 7 5-0.5", washed with distilled water or isotonic saline solution, and then allowed to stand approximately 20 hr in water or saline a t 4-7'. A small portion of the tissue block was then teased apart in distilled water or saline and the nephrons separated under a binocular dissecting microscope. Complete proximal and distal tubules with their atta...