Biomedical subjects

M C Drumond

Publications and source records attributed to M C Drumond.

5 recordsLinked to original sources

PubMed1995

Hindered transport of macromolecules through a single row of cylinders: application to glomerular filtration.

The slit diaphragms of renal glomerular capillaries form an ultrafiltration barrier which may be approximated as a row of cylindrical fibers of macromolecular dimensions. To describe the hindered transport of plasma proteins and other macromolecules through this barrier, we developed an approximate hydrodynamic model for spherical, Brownian particles passing through a row of infinitely long cylinders. The selectivity of the slit diaphragm was assessed by computing concentration profiles for a wide range of molecular sizes for Pe < or = 1, where Pe is a Peclet number based on the cylinder radius. The sieving coefficient for the slit diaphragm was computed as theta SD = CB/CO, where CO was the average concentration at a specified distance upstream from the cylinders (corresponding to the location of the basement membrane), and CB was the concentration far downstream (corresponding to Bowman's space). The results of previous experimental sieving studies using rats could be accounted for approximately by postulating a wide distribution of spacings between the fibers of the slit diaphragm. Comparing the results for theta SD with calculations for a model of the glomerular basement membrane suggests that the slit diaphragm is by far the more size-restrictive part of the overall barrier.

Animals↗

PubMed1994

Stokes flow through a row of cylinders between parallel walls: model for the glomerular slit diaphragm.

As a model for flow through the slit diaphragms which connect the epithelial foot processes of renal glomerular capillaries, finite element solutions of Stokes equations were obtained for flow perpendicular to a row of cylinders confined between parallel walls. A dimensionless "additional resistance" (f), defined as the increment in resistance above the Poiseuille flow value, was computed for L/W < or = 4 and 0.1 < or = R/L < or = 0.9, where L is half the distance between cylinder centers, W is half the distance between walls and R is the cylinder radius. Two factors contributed to f: the drag on the cylinders, and the incremental shear stresses on the walls of the channel. Of these two factors, the drag on the cylinders tended to be dominant. A more complex representation of the slit diaphragm, suggested in the literature, was also considered. The predicted hydraulic permeability of the slit diaphragm was compared with experimental values of the overall hydraulic permeability of the glomerular capillary wall.

Capillary Permeability↗

PubMed1994

Structural determinants of glomerular hydraulic permeability.

To elucidate which structures determine the resistance to water movement, we used a computational fluid dynamics approach to determine velocity and pressure fields within the glomerular capillary wall. The model included representations of the endothelial fenestrae, basement membrane, and epithelial filtration slits with slit diaphragms. The input data included dimensions of the various structures from previous electron microscopy studies, as well as the hydraulic permeability recently measured for isolated films of glomerular basement membrane in vitro. The hydraulic resistance of the endothelium was predicted to be small, whereas the basement membrane and filtration slits were each found to contribute roughly one-half of the total hydraulic resistance of the capillary wall. It was calculated that, for a given filtrate flux, the pressure drop within basement membrane in vivo is roughly twice that of "bare" or isolated basement membrane, because of the small fraction of basement membrane area exposed. The dominant resistance in the filtration slit was found to be the slit diaphragm. Predicted values for the overall hydraulic permeability of the capillary wall were within the experimental range derived from micropuncture measurements in normal rats. The model should be a useful tool for analyzing the effects of various structural changes on glomerular hydraulic permeability. This is illustrated by applying the model to recent physiological and morphometric data in nephrotic rats.

Animals↗

PubMed1994

Structural basis for reduced glomerular filtration capacity in nephrotic humans.

Previous studies have established that in a variety of human glomerulopathies the reduced glomerular filtration rate (GFR) is due to a marked lowering of the ultrafiltration coefficient (Kf). To identify the factors which lower Kf, we measured the filtering surface area per glomerulus, filtration slit frequency, basement membrane thickness, and GFR and its determinants in patients with minimal change and membraneous nephropathies and in age-matched healthy controls. Overall values of Kf for the two kidneys were calculated from GFR, renal plasma flow rate, systemic colloid osmotic pressure, and three assumed values for the transcapillary pressure difference. "Experimental" values of the glomerular hydraulic permeability (kexp) were then calculated from Kf, glomerular filtering surface area, and estimates of the total number of nephrons of the two kidneys. Independent estimates of the glomerular hydraulic permeability (kmodel) were obtained using a recent mathematical model that is based on analyses of viscous flow through the various structural components of the glomerular capillary wall. Individual values of basement membrane thickness and filtration slit frequency were used as inputs in this model. The results indicate that the reductions of Kf in both nephropathies can be attributed entirely to reduced glomerular hydraulic permeability. The mean values of kexp and kmodel were very similar in both disorders and much smaller in the nephrotic groups than in healthy controls. There was good agreement between kexp and kmodel for any given group of subjects. It was shown that, in both groups of nephrotics, filtration slit frequency was a more important determinant of the water flow resistance than was basement membrane thickness. The decrease in filtration slit frequency observed in both disorders caused the average path length for the filtrate to increase, thereby explaining the decreased hydraulic permeability.

Adolescent↗

PubMed1991

Analysis of pulsatile pressures and flows in glomerular filtration.

Previous mathematical models of glomerular filtration have ignored the pulsatility of the glomerular capillary pressure, using only steady-state equations and time-averaged pressures and flows. Because the actual pressure pulses are rapid and of large amplitude and because the governing equations are nonlinear, it is questionable whether the effects of the pressure pulses average out in the manner that has been assumed. We have developed a model that includes sinusoidal variations in the glomerular transcapillary hydraulic pressure (delta P) and the afferent arteriolar plasma flow rate over each cardiac cycle. The analysis suggests that the previously ignored time derivatives in the luminal mass balance equations are not negligible. The amplitude of the oscillations in delta P was found to be sufficient to reverse the direction of the transmural fluxes over part of each cardiac cycle, at the more efferent locations in a capillary. However, the time-averaged values of single-nephron glomerular filtration rate and sieving coefficients for macro-molecules from the pulsatile model differed from that for a steady-state formulation by less than 0.1 and less than or equal to 10%, respectively. We conclude that use of the usual steady-state assumption introduces negligible errors in calculating glomerular membrane parameters from experimental data.

Animals↗