A network thermodynamic model of glomerular dynamics: Application in the rat

Abstract

A model of glomerular dynamics has been developed by using network thermodynamics and the SPICE 2 computer program to further explore the determinants of glomerular filtration. The model is designed to be holistic and self-adjusting, taking cognizance of and permitting quantitation of the secondary alterations in individual effective glomerular resistances, glomerular blood and plasma flow, capillary oncotic pressure and glomerular capillary pressure, which inevitably result when any parameter affecting glomerular dynamics changes. Such automatic adjustment adds to the precision of computation and is unique to the present model. Few assumptions are introduced, independent variables (arterial pressure, individual resistances, hydraulic conductivity, hematocrit, and serum protein concentration) being entered whereas values for the dependent variables are determined by the computer. In rats, filtration pressure equilibrium is seen not to obtain either under physiologic conditions or with reasonably large changes in any of the independent variables. Capillary pressure is shown to be affected by any maneuver that modulates single nephron GFR (SNGFR) and flow across the efferent arteriole (for example, tubule pressure, serum protein concentration) even when arteriolar caliber is held constant. The axial rise in colloid oncotic pressure and serum protein concentration along the capillary is found to be neither linear nor semilogarithmic, a characteristic that reflects on equations used to determine capillary hydraulic conductivity. Isolated change in afferent arteriolar resistance is shown by the model to produce a linear relationship between glomerular plasma flow and capillary pressure, and thus between the former parameter and filtration. Large solitary increases in efferent arteriolar resistance raise SNGFR and a 60% fall in resistance virtually abolishes filtration while exerting little change in blood flow. Concomitant and equal alterations of afferent and efferent arteriolar resistances cause filtration to rise linearly with blood flow but to produce minor change in glomerular capillary pressure, an example of true plasma flow dependence. Plasma flow dependence is, however, found to be unique to this particular circumstance under physiologic conditions. Adding an optional element that automatically adjusts effective efferent arteriolar resistance as a function of Hct2 has but modest effects on glomerular dynamics except when systemic hematocrit is substantially altered. The data and conclusions derived in this study are based on typical values for resistances, hydraulic conductivity, systemic protein concentration, hematocrit, and arterial and tubular pressures reported for normal hydropenic rats. They will not necessarily hold in other species in which these values may be distinctly different.