A numerical model of acid-base transport in rat distal tubule

Abstract

The purpose of this study is to develop a numerical model that simulates acid-base transport in rat distal tubule. We have previously reported a model that deals with transport of Na+, K+, Cl−, and water in this nephron segment (Chang H and Fujita T. Am J Physiol Renal Physiol 276: F931–F951, 1999). In this study, we extend our previous model by incorporating buffer systems, new cell types, and new transport mechanisms. Specifically, the model incorporates bicarbonate, ammonium, and phosphate buffer systems; has cell types corresponding to intercalated cells; and includes the Na/H exchanger, H-ATPase, and anion exchanger. Incorporation of buffer systems has required the following modifications of model equations: new model equations are introduced to represent chemical equilibria of buffer partners [e.g., pH = p K a + log10(NH3/NH4)], and the formulation of mass conservation is extended to take into account interconversion of buffer partners. Furthermore, finite rates of H2CO3-CO2 interconversion (i.e., H2CO3 ⇌ CO2 + H2O) are taken into account in modeling the bicarbonate buffer system. Owing to this treatment, the model can simulate the development of disequilibrium pH in the distal tubular fluid. For each new transporter, a state diagram has been constructed to simulate its transport kinetics. With appropriate assignment of maximal transport rates for individual transporters, the model predictions are in agreement with free-flow micropuncture experiments in terms of HCO[Formula: see text] reabsorption rate in the normal state as well as under the high bicarbonate load. Although the model cannot simulate all of the microperfusion experiments, especially those that showed a flow-dependent increase in HCO[Formula: see text] reabsorption, the model is consistent with those microperfusion experiments that showed HCO[Formula: see text] reabsorption rates similar to those in the free-flow micropuncture experiments. We conclude that it is possible to develop a numerical model of the rat distal tubule that simulates acid-base transport, as well as basic solute and water transport, on the basis of tubular geometry, physical principles, and transporter kinetics. Such a model would provide a useful means of integrating detailed kinetic properties of transporters and predicting macroscopic transport characteristics of this nephron segment under physiological and pathophysiological settings.