Osmotic diuresis in a mathematical model of the rat proximal tubule

Solute reabsorption in the presence of an osmotic load has been examined in a model of the rat proximal convoluted tubule. The model is a computer simulation of a 0.5-cm segment of tubule comprised of compliant cellular and paracellular compartments, which tracks the luminal profiles of Na, K, Cl, HCO3, phosphate, glucose, and urea. In one series of calculations, the peritubular and initial luminal glucose concentrations are varied from 1.0 to 50 mmol/liter. The resulting proximal reabsorption of glucose increases monotonically to 1.5 nmol X s-1 X cm-2. Sodium reabsorption increases with glucose perfusion concentrations between 1.0 and 10 mmol/liter and then declines with greater glucose loads. Above 10 mmol/liter glucose, there is progressive decline in mean luminal Na concentration so that diffusive paracellular backflux, as well as decreased convective reabsorption, are responsible for the natriuresis. Diuresis per se blunts reabsorption of species requiring the development of lumen-to-bath concentration gradients (i.e., K, Cl, and urea). Diminished bicarbonate reabsorption is also predicted with large glucose loads due to intraepithelial alkalinization. This derives both from cellular depolarization and bicarbonate trapping (interspace closure). It is also observed that when interspace closure occurs, a region of intraepithelial K depletion may be formed, promoting diffusive reabsorption of potassium across the tight junction. Thus a 'middle compartment model' for potassium may provide a means of achieving tubule fluid-to-plasma K ratios less than 1.0, in the absence of specific cellular uptake mechanisms.