Measurement of the Permeability of Biological Membranes Application to the glomerular wall

Abstract

The transport equation describing the flow of solute across a membrane has been modified on the basis of theoretical studies calculating the drag of a sphere moving in a viscous liquid undergoing Poiseuille flow inside a cylinder. It is shown that different frictional resistance terms should be introduced to calculate the contributions of diffusion and convection. New sieving equations are derived to calculate r and A,/Ax (respectively, the pore radius and the total area of the pores per unit of path length). These equations provide a better agreement than the older formulas between the calculated and the experimental glomerular sieving coefficients for [6I]polyvinylpyrrolidone (PVP) fractions with a mean equivalent radius between 19 and 37 A. From r and A,/Ax, the mean effective glomerular filtration pressure has been calculated, applying Poiseuille's law. A value of 15.4 mm Hg has been derived from the mean sieving curve obtained from 23 experiments performed on normal anesthetized dogs.In 1951, Pappenheimer et al. developed the so-called "pore theory" to account for the transcapillary transport of uncharged, lipid-insoluble solutes in mammalian muscles (24). According to this theory, convective flow and net diffusion contribute to solute flow across the membrane, in this case the capillary walls, both processes being impeded by the steric hindrance at the entrance of the "pores" (supposed to exist between the cells) and by frictional forces within the pores (20,22,23,25).The solute flow due to diffusion was calculated as D(c -c 2 )AW/Ax X A,/A, where D is the free diffusion coefficient, cl and c 2 , respectively, the solute concentrations in filtrand and filtrate and A,/Ax the pore area freely available to water per unit of length. The term A,/A, describes the restriction to the motion and can be calculated as 1/K 1 X SD where SD = [1 -(a,/r)]2 is the steric hindrance term (a, is the radius of the solute molecules

Mechanisms of the Puromycin-Induced Defects in the Transglomerular Passage of Water and Macromolecules

“…It is evident that fractional D or DS clearances obtained for five single superficial glomeruli from four PAN-treated rats were essentially the same as fractional clearances measured for the kidney as a whole. These data were obtained for dextrans ranging in molecular radii from 22 These findings demonstrate that in these MunichWistar rats treated with PAN, D and DS molecules appear to be neither secreted nor reabsorbed by the renal tubules, in accord with our previous findings in this same strain of rats during normal hydropenia (23,25), after induction of nephrotoxic serum nephritis (29,31), and in response to angiotensin II infusion (30). The results further suggest that fractional clearances of D and DS are homogeneous from glomerulus to glomerulus within a single kidney under the conditions of the present experiments.…”

“…Such functional studies would seem to be of paramount importance in that much experimental and theoretical evidence exists to indicate that the passage of macromolecules across the glomerular capillary wall is influenced by a variety of factors (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31). These not only include macromolecular size but also net macromolecular charge, and the hemodynamic determinants of the glomerular filtration rate of water (GFR) as well.…”

Glomerular permeability of macromolecules. Effect of molecular configuration on the fractional clearance of uncharged dextran and neutral horseradish peroxidase in the rat.

“…INTRODUCTION The filtration of macromolecules across the glomerular capillary wall is determined by the structural characteristics of the filter (1-12), glomerular hemodynamics (13)(14)(15)(16)(17)(18)(19)(20)(21), and molecular parameters of the solute. Molecular determinants include the molecular radius (22)(23)(24)(25) and the net molecular charge (26-30). The fractional clearance of macromolecules decreases with increasing molecular radii but for the same molecular size, polyanions are selectively restricted and the filtration of polycations is enhanced.…”

Permselectivity of the Glomerular Capillary Wall

“…In mammals the transglomerular passage of macromolecules is known to be influenced by molecular size as well as by the hemodynamic forces operating across the glomerular capillary wall (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). Recently, studies by the authors (13) and others (14)(15)(16) have provided clear evidence for a third determinant of macromolecular filtration, that resulting from the operation of the glomerular capillary wall as an electrostatic barrier.…”