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[Formula: see text] produces bicarbonaturia, and, with luminal carbonic anhydrase absent, induces a disequilibrium luminal pH and a postequilibration increase in urinary Pco 2. At baseline flows, this disequilibrium disappears when luminal carbonic anhydrase rate coefficients reach 1% of full catalysis. The magnitude of the equilibration Pco 2 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 Pco 2. In simulations of experimental HCO[Formula: see text] loading in the rat, model predictions of urinary Pco 2 exceed the measured Pco 2 of bladder urine. In part, the higher model predictions for urinary Pco 2 may reflect higher urinary flow rates and lower urinary phosphate concentrations in the experimental preparations. However, when simulation of CD function during HCO[Formula: see text] loading acknowledges the high ambient renal medullary Pco 2 (5), the predicted urinary Pco 2 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 Pco 2 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.