Effect of extracellular fluid volume depletion on renal regulation of acid-base and potassium equilibrium during prolonged mineral acid administration.

Previous studies of the renal and systemic acid-base response to prolonged administration of mineral acids in dogs have suggested that during the steady state of acidosis, the level at which plasma bicarbonate concentration is regulated by the kidney is dependent on the degree of augmentation of "distal delivery" of sodium imposed by the increased filtered load of administered mineral acid anion with filtered sodium, and on the degree of augmentation of "distal avidity" for sodium reabsorption imposed by ECF volume ( ECFV ) contraction secondary to renal sodium losses accompanying the administered mineral acid anion. This formulation, however, fails to predict the level at which plasma bicarbonate concentration would be regulated under conditions of preexisting ECFV depletion, which would simultaneously limit distal delivery of sodium salts and yet increase distal avidity for sodium reabsorption. Our studies assessed the renal and systemic acid-base responses to prolonged daily administration of 5.0 mEq/kg of H+ as HCl (groups 1 and 2) or H2SO4 (groups 3 and 4) in dogs with normal ECFV (groups 1 and 3) vs. preexisting ECFV depletion (groups 2 and 4) induced by administration of ethacrynic acid. In response to HCl administration, dogs with depleted ECFV developed more severe acidosis than ECFV -replete dogs (delta[HCO-3,]p, -5.0 +/- 0.6 mEq/L, group 2 vs. -2.7 +/- 0.5 mEq/L, group 1, p less than 0.02). The exacerbated metabolic acidosis in group 2 persisted in the steady state, even though the steady-state net systemic acid load was not greater than in group 1. No exacerbation of acidosis was observed in H2SO4-fed dogs with depleted ECFV . In response to either HCl or H2SO4, persistent hypokalemia caused by increased renal potassium clearance occurred in ECFV -replete dogs but not in ECFV -depleted dogs. Our results indicate that preexisting ECFV depletion results in impaired renal hydrogen ion secretion during prolonged HCl feeding, but not during H2SO4 feeding. These results suggest that during prolonged HCl loading under conditions of preexisting ECFV depletion, hypovolemia-mediated restriction of the normal augmentation of distal delivery of sodium salts overrides the effects of enhanced distal cation secretory capacity that attends hypovolemia-mediated augmentation of distal avidity for sodium reabsorption.