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Biomedical subjects

B M Brenner

Publications and source records attributed to B M Brenner.

At least 325 records · Page 18Linked to original sources
PubMed1975

Control of proximal tubule fluid reabsorption in experimental glomerulonephritis.

We have recently shown that in the early autologous phase of nephrotoxic serum nephritis (NSN) single nephron glomerular filtration rate is unchanged from values in normal hydropenic control rats, but that single nephron filtration fraction and efferent arteriolar oncotic pressure (piE) are reduced because of a marked reduction in the glomerular capillary ultrafiltration coefficient. The present study was undertaken to examine the influence of this decline in piE as well as the other known determinants of peritubular capillary fluid exchange on absolute proximal fluid reabsorption (APR) in NSN. The findings indicate that APR and proximal fractional reabsorption are reduced significantly in NSN, relative to values in a separate group of age and weight-matched normal hydropenic control rats studied concurrently. In addition to the measured decline in piE, efferent arteriolar plasma flow (Qe) and peritubular capillary hydraulic pressure (Pc) were found to increase significantly, while interstitial oncotic pressure, estimated from hilar lymph, was not significantly different from values in control rats. Using a mathematical model of peritubular capillary fluid uptake we found that, assuming that the capillary permeability-surface area product and interstitial hydraulic pressure are unchanged in NSN, the observed changes in piE and Pc are sufficient to offset the effect of the increase in QE, yielding a calculated reduction in APR of approximately 4 nl/min, in excellent agreement with the observed mean decline of 4.1 nl/min. These findings suggest that control of APR in NSN is mediated by the same factors that regulate APR under normal physiological conditions, namely, the imbalance of forces governing peritubular capillary uptake of isotonic reabsorbate.

Animals↗
PubMed1974

Concentration polarization in an ultrafiltering capillary.

Concentration polarization, the accumulation of retained solute next to an ultrafiltering membrane, elevates osmotic pressure above that which would exist in the absence of polarization. For ultrafiltration in a cylindrical tube, use of the radially averaged solute concentration results in an underestimate of osmotic pressure, yielding an effective hydraulic permeability (k) less than the actual membrane hydraulic permeability (k(m)). The extent to which k and k(m) might differ in an ultrafiltering capillary has been examined theoretically by solution of the momentum and species transport equations for idealized capillaries with and without erythrocytes. For diameters, flow velocities, protein concentrations and diffusivities, and ultrafiltration pressures representative of the rat glomerular capillary network, results indicate that the effects of polarization are substantial without erythrocytes (k/k(m) = 0.7) and persist, but to a lesser extent, with erythrocytes (k/k(m) = 0.9), the reduction in polarization in the latter case being due to enhanced plasma mixing. In accord with recent experimental findings in rats, k is found to be relatively insensitive to changes in glomerular plasma flow rate.

Blood Proteins↗
PubMed1974

Dynamics of glomerular ultrafiltration in the rat. V. Response to ischemic injury.

An experimental model of postischemic, acute renal failure has been developed in Wistar rats with surface glomeruli, thereby making possible a direct assessment of the mechanisms responsible for the fall in glomerular filtration rate that characterizes this disorder. Whole kidney and cortical single nephron filtration rates were reduced proportionately, on average by approximately 40%, after 3 h of nearly complete occlusion of the ipsilateral renal artery. The possibility of a significant transtubular leak of inulin was excluded. This decline in filtration rate occurred in the absence of measured changes in mean arterial pressure, mean glomerular transcapillary hydrostatic pressure, or net ultrafiltration pressure at afferent and efferent ends of the glomerular capillary. Net ultrafiltration pressure at the efferent end of the capillary approached zero both before and after ischemic injury, demonstrating that filtration pressure equilibrium was achieved throughout this study. Single nephron filtration fraction remained unchanged, indicating that the fall in filtration rate was accompanied by a proportional decline in glomerular plasma flow. The results indicate that the fall in filtration rate was solely the consequence of this fall in glomerular plasma flow. Since filtration rate per nephron is equal to the product of the ultrafiltration coefficient and mean ultrafiltration pressure, this product must also have fallen in proportion to the decline in glomerular plasma flow. Evidence is presented to indicate that a change in ultrafiltration coefficient is not required to account for the observed fall in filtration rate. The reduction in glomerular plasma flow, occuring in the absence of a concomitant decline in mean glomerular capillary hydrostatic pressure, resulted from large and proportional increases in afferent and efferent arteriolar resistances. These resistance changes appear to play a fundamental role in the pathogenesis of this form of acute renal failure.

Acute Kidney Injury↗
PubMed1974

Current concepts of sodium chloride and water transport by the mammalian nephron.

The decision of the editors to solicit a review for the Medical Progress series of this journal devoted to current concepts of the renal handling of salt and water is sound in that this important topic in kidney physiology has recently been the object of a number of new, exciting and, in some instances, quite unexpected insights into the mechanisms governing sodium excretion. These developments have come about largely as a consequence of the fact that segments of nephrons previously inaccessible to direct study are now readily accessible. Many of the findings to be discussed argue for extensive revision of a number of our current widely held views concerning the renal handling of sodium chloride and water. In the opinion of the authors, the strength of this argument rests in the fact that many of these new findings were obtained under circumstances that enabled workers to gain more direct access to the nephron than has been possible heretofore. This is not to say that areas of controversy and disagreement no longer exist. Wherever possible, these have been identified. In attempting to provide a comprehensive review of this topic, it has been necessary at times to overgeneralize and to disregard minor deficiencies in some of the studies cited. Finally, we wish to emphasize that a considerable portion of the information contained herein derives from work still under active investigation. Much of this contemporary work will undoubtedly withstand the rigors of future experimental scrutiny. It is inevitable, however, as William James so aptly noted in the quotation cited below, that some of our present ideas will need to be abandoned or revised in favor of newer, more convincing evidence. Seen in this light, the present effort is intended as nothing more than a timely survey of this active and fertile topic in renal physiology.

Animals↗
PubMed1973

A model of peritubular capillary control of isotonic fluid reabsorption by the renal proximal tubule.

A mathematical model of peritubular transcapillary fluid exchange has been developed to investigate the role of the peritubular environment in the regulation of net isotonic fluid transport across the mammalian renal proximal tubule. The model, derived from conservation of mass and the Starling transcapillary driving forces, has been used to examine the quantitative effects on proximal reabsorption of changes in efferent arteriolar protein concentration and plasma flow rate. Under normal physiological conditions, relatively small perturbations in protein concentration are predicted to influence reabsorption more than even large variations in plasma flow, a prediction in close accord with recent experimental observations in the rat and dog. Changes either in protein concentration or plasma flow have their most pronounced effects when the opposing transcapillary hydrostatic and osmotic pressure differences are closest to equilibrium. Comparison of these theoretical results with variations in reabsorption observed in micropuncture studies makes it possible to place upper and lower bounds on the difference between interstitial oncotic and hydrostatic pressures in the renal cortex of the rat.

Animals↗
PubMed1973

Quantitative importance of changes in postglomerular colloid osmotic pressure in mediating glomerulotubular balance in the rat.

In recent studies in this laboratory employing normal hydropenic rats we have demonstrated that the reduction in absolute proximal reabsorption that attends the experimental reduction of single nephron glomerular filtration rate (SNGFR) (glomerulotubular balance) is mediated, at least in part, by the accompanying decline in postglomerular vascular protein concentration, and therefore, postglomerular colloid osmotic pressure (piEA). The present study was undertaken to define the quantitative contribution of these changes in piEA to the changes in absolute proximal reabsorption measured under these conditions. A protocol was employed which enabled us to examine the effects on absolute proximal reabsorption of reductions in filtered load brought about under conditions in which piEA remained essentially unchanged. Thus, after partial aortic constriction in 16 plasma-loaded rats, near constancy of piEA was observed in 10 (a change in efferent arteriolar protein concentration of 0.4 g/100 ml or less) and in these, uniform reductions in SNGFR averaging 16.7 nl/min were attended by reductions in absolute proximal reabsorption averaging only 1.7 nl/min, or 7% of preconstriction values. These findings, taken together with previous observations from this laboratory, suggest that the proximal reabsorptive adjustment that characterizes glomerulotubular balance in the rat is markedly blunted when changes in piEA are prevented. In the remaining six rats, a mean reduction in filtered load comparable to that observed in the above group was attended by slightly to moderately greater reductions in efferent arteriolar protein concentration, thereby fulfilling less well the stated aim of this study. Nevertheless, in accord with the above conclusion, these relatively greater reductions in piEA were accompanied by correspondingly greater reductions in absolute proximal reabsorption.

Animals↗
PubMed1973

Renal response to chronic intravenous salt loading in the rat.

The natriuresis of acute Ringer's loading is associated with a rise in the rate of delivery of fluid beyond the proximal tubule due both to a rise in glomerular filtration and a fall in absolute reabsorption, the latter being causally mediated, at least in part, by the accompanying fall in postglomerular vascular [protein]. To determine whether these factors also contribute to the renal response to chronic Ringer's loading, nine rats given continuous infusions, 30% body weight/day over 5-14 days, were studied using free-flow micro-puncture techniques. Results were compared with data from 10 chronic control rats given less than 1.5% body wt/day. Late proximal tubule fluid-to-plasma [inulin] ratios, (TF/P)(IN), single nephron glomerular filtration rate (SNGFR), absolute proximal reabsorption, and postglomerular vascular [protein] in chronic control rats and chronically loaded rats averaged 2.2+/-SE 0.1 (n = 35) and 1.5+/-0 (35), P<0.001; 37+/-2 (35) and 47+/-4 nl/min (35), P<0.05; 19+/-1 (35) and 16+/-2 nl/min (35), P>0.2; and 9.5+/-0.3 (8) and 8.6+/-0.3 g/100 ml (8), P>0.05, respectively. Thus the fall in (TF/P)(IN) and the rise in distal delivery during chronic Ringer's loading were due almost entirely to the rise in SNGFR, and not to any large fall in absolute reabsorption. Hence chronic and acute Ringer's loading increase delivery of proximal tubule fluid by different mechanisms, with chronic sodium homeostasis being governed overwhelmingly by adjustments in GFR. When, however, an acute Ringer's load was infused into chronically loaded rats, we observed significant and parallel reductions in absolute proximal reabsorption and postglomerular vascular [protein]. These findings suggest that the difference between the effects of chronic vs. acute Ringer's loading on absolute proximal reabsorption may have been due, at least in part, to the corresponding difference in the effects these two loading procedures have on postglomerular vascular [protein].

Aminohippuric Acids↗
PubMed1973

Dynamics of glomerular ultrafiltration in the rat. IV. Determination of the ultrafiltration coefficient.

Pressures and flow rates were measured in accessible surface glomeruli of mutant Wistar rats under conditions deliberately designed to prevent achievement of filtration pressure equilibrium, that is, the equalization of transcapillary hydrostatic and oncotic pressures by the efferent end of the glomerulus as typically observed in the normal hydropenic rat. Disequilibrium was obtained at elevated levels of glomerular plasma flow (GPF) brought about by acute expansion of plasma volume with a volume of rat plasma equal to 5% of body weight. Glomerular hydrostatic and oncotic pressures measured at high GPF were used to calculate the ultrafiltration coefficient, K(f), the product of effective hydraulic permeability and surface area. GPF was then either lowered (by aortic constriction) or raised (by carotid occlusion) in order to examine the dependence of K(f) on GPF. The value of K(f) per glomerulus, 0.08 nl/(s.mm Hg), was found not to vary over an approximately twofold range of GPF. This finding, taken together with data from previous studies from this laboratory, leads us to conclude that plasma-flow dependence of glomerular filtration rate (GFR) results primarily from flow-induced changes in mean ultrafiltration pressure, rather than large changes in K(f).

Animals↗