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Biomedical subjects

C R Robertson

Publications and source records attributed to C R Robertson.

At least 73 records · Page 4Linked to original sources
PubMed1976

Permselectivity of of the glomerular capillary wall. Studies of experimental glomerulonephritis in the rat using neutral dextran.

Polydisperse [3h] dextran was infused into eight Munich-Wistar rats in the early autologous phase of nephrotoxic serum nephritis (NSN), thereby permitting direct measurements of pressures and flows in surface glomeruli and fractional clearances for dextrans [(U/P) dextran/(U/P) inulin] ranging in radius from 18 to 42 A. Despite glomerular injury, evidenced morphologically and by a marked reduction in the glomerular capillary ultrafiltration coefficient, the glomerular filtration rate remained normal because of a compensating increase in the mean net ultrafiltration pressure. In NSN rats, as in normal controls, inulin was found to permeate the glomerular capillary wall without measurable restriction, and dextrans were shown to be neither secreted nor reabsorbed. For dextran radii of 18, 22, 26, 30, 34, 38, and 42 A, (U/P) dextran/(U/P) inulin in NSN and control rats, respectively, averaged 0.90 vs. 0.99, 0.81 vs. 0.97, 0.63 vs. 0.83, 0.38 vs 0.55, 0.20 vs. 0.30, 0.08 vs. 0.11, and 0.02 vs. 0.03. Using a theory based on macromolecular transport through pores, the results indicate that in NSN rats, effective pore radius is the same as in controls, approximately 50 A. In NSN, however, the ratio of total pore surface area to pore length, a measure of the number of pores, is reduced to approximately 1/3 that of control, probably due to a reduction in capillary surface area. These results suggest that proteinuria in glomerular disease is not due simply to increases in effective pore radius or number of pores, as previously believed. Using a second theoretical approach, based on the Kedem-Katchalsky flux equations, dextran permeability across glomerular capillaries was found to be slightly lower, and reflection coefficient slightly higher in NSN than in control rats.

Animals↗
PubMed1976

Permselectivity of the glomerular capillary wall. Studies of experimental glomerulonephritis in the rat using dextran sulfate.

To determine whether the increased filtration of serum proteins after glomerular injury is the consequence of altered electrostatic properties of the glomerular capillary wall, we measured fractional clearances of the anionic polymer, dextran sulfate, in nine Munich-Wistar rats in the early autologous phase of nephrotoxic serum nephritis (NSN). In agreement with previous studied from this laboratory, whole kidney and single nephron glomerular filtration rates were normal in NSN rats despite histological evidence of glomerular injury, and despite a marked reduction in the glomerular capillary ultrafiltration coefficient to approximately one-third of normal. In the companion study (9), it was shown that in NSN rats the mean fractional clearances of neutral dextrans over the range of effective molecular radii from 18 to 42 A were reduced, compared to normla. In contrast, in the present study the mean fractional clearances for dextran sulfate over the same range of molecular radii were significantly greater than those found previously for normal Munich-Wistar rats. The fractional clearance of dextran sulfate molecules of the same molecular radius as serum albumin (approximately 36 A) was increased markedly, from 0.015 +/- 0.005 (SEM) in nonnephritic controls to 0.24 +/- 0.03 in NSN (P less than 0.001). The sialoprotein content of glomeruli, estimated by the colloidal iron reaction, was reduced in NSN rats as compared to normal controls. It is concluded that the abnormal filtration of anionic serum proteins, such as albumin, seen in glomerulopathies is, at least in part, the consequence of loss of fixed negative charges from the glomerular capillary wall.

Animals↗
PubMed1975

Effect of ionic polarizability on electrodiffusion in lipid bilayer membranes.

Ion-carrier complexes and organic ions of similar size and shape have mobilities in lipid bilayer membranes which span several orders of magnitude. In this communication, an examination is made of the hypothesis that the basis for this unusually wide range of ionic mobilities is the potential energy barrier arising from image forces which selectively act on ions according to their polarizability. Using Poisson's equation to evaluate the electrostatic interaction between an ion and its surroundings, the potential energy barrier to ion transport due to image effects is computed, with the result that the potential energy barrier height depends strongly on ionic polarizability. Theoretical membrane potential energy profile calculations are used in conjunction with Nernst-Planck electrodiffusion equation to analyze the available mobility data for several ion-carrier complexes and lipid-soluble ions in lipid bilayer membranes. The variation among the mobilities of different ions is shown to be in agreement with theoretical predictions based on ionic polarizability and size. Furthermore, the important influence exerted by image forces on ion transport in lipid bilayer membranes compared to the frictional effect of membrane viscosity is established by contrasting available data on the activation energy of ionic conductivity with that for membrane fluidity.

Diffusion↗
PubMed1975

Permselectivity of the glomerular capillary wall to macromolecules. I. Theoretical considerations.

The transport of macromolecules across the renal glomerular capillary wall has been described theoretically using flux equations based on (a) restricted transport through small pores, and (b) the Kedem-Katchalsky formulation. The various assumptions and limitations inherent in these two approaches are discussed. To examine the coupling between macromolecular solute transport and the determinants of glomerular filtration rate, these flux equations were combined with mass balance relations which allow for variations in the transmembrane driving forces along a glomerular capillary. It was predicted, using both pore theory and the Kedem-Katchalsky equations, that fractional solute clearance should be strongly dependent on the determinants of glomerular filtration rate when convection and diffusion both contribute to solute transport. When convection becomes the sole mechanism for transcapillary solute transport, however, fractional solute clearance is essentially independent of changes in the determinants of glomerular filtration rate. Consequently, unless diffusion is absent, fractional solute clearances alone are insufficient to characterize the permselective properties of the glomerular capillary wall, since these values may be altered by changes in glomerular pressures and flows as well as changes in the properties of the capillary wall per se.

Animals↗
PubMed1975

Permselectivity of the glomerular capillary wall to macromolecules. II. Experimental studies in rats using neutral dextran.

To determine the permselectivity characteristics of the glomerular capillary wall, known molecular size fractions of [3H]dextran, prepared by gel chromatography, were infused into normally hydrated Wistar rats, thus permitting simultaneous measurement of Bowman's space/plasma water (BS/P) and urine/plasma water (U/P) concentration ratios, along with glomerular pressures and flows. Since (BS/P)inulin = 1.01 +/- 0.01 SE(n = 34, radius = approximately 14 A) and since (BS/P)dextran/(BS/P)inulin equaled (U/P)dextran/(U/P)inulin for dextrans ranging in molecular radius from 21 to 35 A, these findings validate that dextrans are neither secreted nor reabsorbed. For dextran radii of 20, 24, 28, 32, 36, 40, and 44 A, (U/P)dextran/(U/P)inulin averaged 0.99, 0.92, 0.69, 0.42, 0.19, 0.06, and 0.01, respectively. In accord with theoretical predictions that these fractional dextran clearances should vary appreciably with changes in glomerular transcapillary pressures and flows, an increase in glomerular plasma flow rate, induced in these same rats by plasma volume expansion, resulted in a highly significant lowering of fractional clearance of all but the smallest and largest dextrans studied. These findings emphasize that fractional solute clearances alone are inadequate to describe the permselective properties of the glomerular capillary wall unless glomerular pressures and flows are also known. This sensitivity of fractional dextran clearance to changes in plasma flow indicates that dextrans are transported across the capillary not only by bulk flow but also to an important extent by diffusion.

Animals↗
PubMed1975

Permselectivity of the glomerular capillary wall: III. Restricted transport of polyanions.

The clearance of albumin relative to that of inulin is greatly exceeded by that of uncharged dextrans of the same effective molecular radius (approximately 36A), less than 0.01 vs. 0.20 in normal hydropenic rats. This marked difference in fractional clearances of albumin and neutral dextran suggests that some factor in addition to molecular size retards the transglomerular passage of albumin. Since albumin is a polyanion in physiological solution, we tested the effect of charge on macromolecular permeability by infusing the anionic polymer, dextran sulfate (approximately 2.3 sulfate groups per glycosyl residue), into seven normal hypropenic Munich-Wistar rats. For dextran sulfate with an effective radius of approximately 36A, the fractional clearance was reduced essentially to that found for albumin (approximately 0.01). This enhanced restriction of dextran sulfate, relative to neutral dextran, was also noted for smaller and larger dextran sulfate molecules. These differences in the transport of dextran sulfate vs. dextran suggest electrostatic repulsion of charged macromolecules by some component of the glomerular capillary wall, perhaps the negatively charged sialoprotein which coats glomerular epithelial cells. Loss of this polyanionic coat, as has been reported to occur in proteinuric disorders, might thereby account for the enhanced transmural passage of albumin.

Animals↗
PubMed1975

Hydraulic and oncotic pressure measurements in inner medulla of mammalian kidney.

The vasa recta are thought to play an important role in the transfer of water andsolutes within the renal medulla. Hydraulic pressures were measured in vasa recta onthe surface of the exposed papilla in young Munich Wistar rats, and blood was collected from these microvessels for determination of total protein concentration and calculation of colloid oncotic pressure. In descending vasa recta at the base of the exposed papilla, mean hydraulic pressure was 9.2 plus or minus 0.4 (SE) mmHg and plasma protein concentration averaged 7.1 plus or minus 0.4 g/100 ml. Corresponding valuesin ascending vasa recta at the same level were 7.8 plus or minus 0.4 mmHg and 5.6 plusor minus 0.3 g/100 ml. respectively. The protein concentrations correspond to calculated oncotic pressures of 26 and 18 mmHg in descending and ascending vasa recta, respectively. We interpret these findings as evidence for net water uptake by the vasa recta in the renal inner medulla for which the driving forces are the transcapillary hydraulic and oncotic pressure differences.

Animals↗
PubMed1975

Dynamics of glomerular ultrafiltration in the rat. VIII. Effects of hematocrit.

This study was undertaken in an effort to examine the effects of selective variations in systemic hematocrit on the preglomerular, glomerular, and postglomerular micocirculation in the rat. By isovolemic exchange transfusions, systemic hematocrit (control 51 ml/100 ml) was either reduced (21 ml/100 ml, N equal 7 rats) or elevated (62 ml/100 ml, N equal 7). Single nephron glomerular filtration rate varied inversely and filtration fraction varied directly with the changes in hematocrit. The fall in filtration fraction with decreased hematocrit was due to a decline in the measured glomerular transcapillary hydraulic pressure difference and to a marked increased in the initial glomerular plasma flow rate. Afferent (RA)and efferent (RE) arteriolar resistance declined with the fall in hematocrit; RA fell proportionately more than did RE. The rise in filtration fraction with the elevation in hematocrit was due to a marked increase in in part due to a relatively greater rise in RE than in RA. These findings provide an attractive explanation for the general tendency for filtration fraction to vary directly with hematocrit in anemic and polycythemic states in man.

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↗
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

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↗