STRUCTURAL DETERMINANTS OF GLOMERULAR HYDRAULIC PERMEABILITY

To elucidate which structures determine the resistance to water moveme nt, we used a computational fluid dynamics approach to determine veloc ity and pressure fields within the glomerular capillary wall. The mode l included representations of the endothelial fenestrae, basement memb rane, and epithelial filtration slits with slit diaphragms. The input data included dimensions of the various structures from previous elect ron 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 t o contribute roughly one-half of the total hydraulic resistance of the capillary wall. It was calculated that, for a given filtrate flux, th e pressure drop within basement membrane in vivo is roughly twice that of ''bare'' or isolated basement membrane, because of the small fract ion of basement membrane area exposed. The dominant resistance in the filtration slit was found to be the slit diaphragm. Predicted values f or the overall hydraulic permeability of the capillary wall were withi n the experimental range derived from micropuncture measurements in no rmal rats, The model should be a useful tool for analyzing the effects of various structural changes on glomerular hydraulic permeability. T his is illustrated by applying the model to recent physiological and m orphometric data in nephrotic rats.