A mathematical model of rat collecting duct. II. Effect of buffer delivery on urinary acidification.

Abstract

A mathematical model of the rat collecting duct (CD) is used to examine the effect of delivered load of bicarbonate and nonbicarbonate buffer on urinary acidification. Increasing the delivered load of HCO(3)(-) produces bicarbonaturia, and, with luminal carbonic anhydrase absent, induces a disequilibrium luminal pH and a postequilibration increase in urinary PCO2. At baseline flows, this disequilibrium disappears when luminal carbonic anhydrase rate coefficients reach 1% of full catalysis. The magnitude of the equilibration PCO2 depends on the product of urinary acid phosphate concentration and the disequilibrium pH. Thus, although increasing phosphate delivery to the CD decreases the disequilibrium pH, the increase in urinary phosphate concentration yields an overall increase in postequilibration PCO2. In simulations of experimental HCO(3)(-) loading in the rat, model predictions of urinary PCO2 exceed the measured PCO2 of bladder urine. In part, the higher model predictions for urinary PCO2 may reflect higher urinary flow rates and lower urinary phosphate concentrations in the experimental preparations. However, when simulation of CD function during HCO(3)(-) loading acknowledges the high ambient renal medullary PCO2 (5), the predicted urinary PCO2 of the model CD is yet that much greater. This discrepancy cannot be resolved within the model but requires additional experimental data, namely, concomitant determination of urinary buffer concentrations within the tubule fluid sampled for PCO2 and pH. This model should provide a means for simulating formal testing of urinary acidification and thus for examining hypotheses regarding transport defects underlying distal renal tubular acidosis.