Glomerular Dynamics in the Normal Human Kidney 1

Abstract

One of the most interesting facts about the renal circulation is that during marked changes in renal blood flow (adrenalin ischemia and pyrogenic hyperemia) the rate of glomerular filtration typically remains unchanged. This fact has been attributed to the circumstance that the changes in renal blood flow are mediated primarily by changes in the tonus of the efferent arterioles; consequently, any increase or decrease in blood flow is accompanied by a reciprocal change in glomerular filtration pressure, with the result that the filtration rate remains unchanged (3).Beyond the fact that this emphasis upon the efferent arteriole is to some extent contrary to the importance which has hitherto, chiefly for anatomical reasons, been attached to the afferent vessel, this description of the glomerular circulation presents several interesting implications. It assumes that the rate of glomerular filtration is determined solely by glomerular pressure factors, exclusive of any limitation imposed by the permeability of the glomerular membranes. There logically issues from this assumption the question whether or not filtration pressure equilibrium is normally reached in the glomerulus. The answer to this question is of practical importance in two respects. If filtration equilibrium is reached in the glomerular circulation, then this fact must set the upper limit to the hydrostatic pressure available to propel blood through the efferent arterioles and the postglomerular circulation. And in the face of a demonstration of filtration equilibrium in the normal kidney, a decrease in filtration rate in renal disease cannot logically be attributed to reduced permeability of the glomerular capillaries, in contradistinction to a decrease in filtration pressure or in total filtering 1This investigation has been supported in part by aid from the William Gibbs Memorial Prize Fund, granted especially for the study of renal hyperemia, and in part by the Commonwealth Fund.surface, without evidence that glomerular permeability is actually reduced.These and other considerations lead us to a further analysis of this problem. It has recently been shown that the inulin and diodrast clearances in different subjects are closely correlated with differences in the tubular excretory mass (diodrast Tm), it being presumed that the last term varies with the total quantity of renal parenchyma (8). It is advantageous to utilize this correlation in examining the relations which exist in various subjects between the inulin and diodrast clearances; i.e., to make this comparison in terms of the ratios, CINITmD and CDITmD (where CIN and CD are the inulin and diodrast clearances, respectively, and TmD is diodrast Tm). Such an analysis is, in the first approximation, equivalent to comparing the filtration rate and renal plasma flow of various subjects on the basis of their actual renal weights.Furthermore, we now have in our records numerous data, not available when the previous paper was published, on the diodrast and inulin clearances in normal subjects under va...

Effective Renal Blood Flow in Subjects With Essential Hypertension 12

“…Normal subjects vary considerably in sensitivity to pyrogen and this is doubtless true of hypertensive subjects. In the latter, CD/TmD during hyperemia ranges from 17.5 to 34.7 and averages 22.8, figures which are comparable with those shown in Figure 2 of our previous paper (14) on a smaller series of normals in which hyperemia was induced; consequently, we feel that the magnitude of hyperemia obtained in the hypertensive subjects is equal to that obtained in normals.…”

“…3. Locus of increased renal resistance The question whether the increased renal resistance deduced above involves obstruction on the afferent or efferent side of the glomerular bed can be examined by reference to the filtration In normal subjects the filtration rate tends to remain constant when the renal blood flow is increased during pyrogenic hyperemia or decreased by adrenalin, a circumstance which indicates that the locus of changing resistance is at the efferent glomerular arteriole (3,14 hyperemia. (The data on experimentally induced hyperemia will be discussed in the next section.…”

“…by amidopyrine to reduce or eliminate the general autonomic disturbances of the pyrogenic reaction, produce in normal subjects a moderate to very marked renal hyperemia by efferent dilatation (3,13,14). Since this is the only method known to us to induce renal hyperemia, we have utilized it in the examination of the vascular responses of the kidney in hypertensive subjects.…”

“…Three factors might operate to maintain a relatively high filtration rate in functional glomeruli: (a) increased mean systemic pressure, (b) dilatation of the afferent glomerular arterioles, and (c) the formation of impotent nephrons (12). (In the view that filtration equilibrium is approximately reached in the normal glomerulus (14), it is improbable that increased permeability of the glomerular membranes could significantly increase the filtration rate.) Again, we cannot immediately distinguish between these alterna-200 tive possibilities, but for our present purposes this fact is not important since the net result upon the blood flow to the residual functional tissue will be the same; namely, elevated mean systemic pressure or afferent dilatation will, by increasing glomerular pressure, increase the postglomerular blood flow, thus producing an active hyperemia; while impotent nephrons will produce a vicarious hyperemia in such functional tissue as may be perfused by the vestigial vascular channels related to the now defunct tissue.…”

Note on the Interpretation of Clearance Methods in the Diseased Kidney

“…The use of inulin as the standard of reference for the measurement of the rate of filtration of plasma water rests upon good experimental evidence, so far as the normal human kidney is concerned (13). 1 In the diseased kidney, however, an increase in permeability of the tubule may permit the escape of water from the tubular urine without permitting the escape of inulin; and, conversely, a decrease in permeability of the glomerular membranes may retard the filtration of inulin without proportionally retarding the filtration of water; 2 (11). 3 The parallel behavior of urea and inulin in all stages of diffuse glomerular nephritis indicates that the reduced excretion of both substances is primarily attributable to the obliteration of the filtering bed rather than increased back-diffusion of urea (1).…”