A model of osmotic and hydrostatic pressure effects on volume absorption in the proximal tubule.

Abstract

A computer model of the proximal tubule of the rabbit is described in which the tubule is treated as a single cylindrical barrier to the flow of solute and water between lumen and bath, and volume absorption is assumed to be driven exclusively by hydrostatic and osmotic pressure differences across this barrier. The model mimics the function of the tubule in two in vitro preparations: in simulations of the isolated tubule perfused under oil, the model correctly describes the solute concentration gradients that exist between the perfusate and absorbate and predicts differences in solute concentrations among absorbate droplets on the same tubule if luminal concentration becomes limiting. This prediction was tested experimentally with glucose and found to be correct. In simulations of the tubule perfused in an aqueous bath, the role of transmural hydrostatic pressure was explored; it is predicted that, at normal rates of in vitro perfusion (approximately 10 nl/min), increases in pressure have very little effect on volume absorption but can greatly alter the osmotic differences present across the wall of the tubule, especially with high values of osmotic water permeability. At high rates of perfusion, the ability of the tubule to produce a lumen hypotonic to the bath is reduced, but the direct effects of pressure on volume absorption become more apparent, resulting in relatively little effect of perfusion rate on volume absorption if the osmotic water permeability is sufficiently high. A similar relationship was seen experimentally. In all, this simple model provides a good prediction of function in isolated perfused tubules without any assumptions of hypertonic compartments within the epithelium.