The maladaptive renal response to secondary hypocapnia during chronic HCl acidosis in the dog.
It has generally been thought that homeostatic mechanisms of renal origin are responsible for minimizing the alkalemia produced by chronic hypocapnia. Recent observations from this laboratory have demonstrated, however, that the decrement in [HCO(-) (3)], which "protects" extracellular pH in normal dogs, is simply the by-product of a nonspecific effect of Paco(2) on renal hydrogen ion secretion; chronic primary hypocapnia produces virtually the same decrement in plasma [HCO(-) (3)] in dogs with chronic HCl acidosis as in normal dogs (Delta[HCO(-) (3)]/DeltaPaco(2) = 0.5), with the result that plasma [H(+)] in animals with severe acidosis rises rather than falls during superimposed forced hyperventilation. This observation raised the possibility that the secondary hypocapnia which normally accompanies metabolic acidosis, if persistent, might induce an analogous renal response and thereby contribute to the steady-state decrement in plasma [HCO(-) (3)] observed during HCl feeding. We reasoned that if sustained secondary hypocapnia provoked the kidney to depress renal bicarbonate reabsorption, the acute salutary effect of hypocapnia on plasma acidity might be seriously undermined. To isolate the possible effects of secondary hypocapnia from those of the hydrogen ion load, per se, animals were maintained in an atmosphere of 2.6% CO(2) during an initial 8-day period of acid feeding (7 mmol/kg per day); this maneuver allowed Paco(2) to be held constant at the control level of 36 mm Hg despite the hyperventilation induced by the acidemia. Steady-state bicarbonate concentration during the period of eucapnia fell from 20.8 to 16.0 meq/liter, while [H(+)] rose from 42 to 55 neq/liter. During the second phase of the study, acid feeding was continued but CO(2) was removed from the inspired air, permitting Paco(2) to fall by 6 mm Hg. In response to this secondary hypocapnia, bicarbonate concentration fell by an additional 3.0 meq/liter to a new steady-state level of 13.0 meq/liter. This reduction in bicarbonate was of sufficient magnitude to more than offset the acute salutary effect of the hypocapnia on plasma hydrogen ion concentration; in fact, steady-state [H(+)] rose as a function of the adaptive fall in Paco(2), Delta[H(+)]/Delta Paco(2) = -0.44. That the fall in bicarbonate observed in response to chronic secondary hypocapnia was the result of the change in Paco(2) was confirmed by the observation that plasma bicarbonate returned to its eucapnic level in a subgroup of animals re-exposed to 2.6% CO(2). These data indicate that the decrement in plasma [HCO(-) (3)] seen in chronic HCl acidosis is a composite function of (a) the acid load itself and (b) the renal response to the associated hyperventilation. We conclude that this renal response is maladaptive because it clearly diminishes the degree to which plasma acidity is protected by secondary hypocapnia acutely. Moreover, under some circumstances, this maladaptation actually results in more severe acidemia than would occur in the complete absence of secondary hypocapnia.
The maladaptive renal response to secondary hypocapnia during chronic HCl acidosis in the dog. It has generally been thought that homeostatic mechanisms of renal origin are responsible for minimizing the alkalemia produced by chronic hypocapnia. Recent observations from this laboratory have demonstrated, however, that the decrement in [HCO(-) (3)], which "protects" extracellular pH in normal dogs, is simply the by-product of a nonspecific effect of Paco(2) on renal hydrogen ion secretion; chronic primary hypocapnia produces virtually the same decrement in plasma [HCO(-) (3)] in dogs with chronic HCl acidosis as in normal dogs (Delta[HCO(-) (3)]/DeltaPaco(2) = 0.5), with the result that plasma [H(+)] in animals with severe acidosis rises rather than falls during superimposed forced hyperventilation. This observation raised the possibility that the secondary hypocapnia which normally accompanies metabolic acidosis, if persistent, might induce an analogous renal response and thereby contribute to the steady-state decrement in plasma [HCO(-) (3)] observed during HCl feeding. We reasoned that if sustained secondary hypocapnia provoked the kidney to depress renal bicarbonate reabsorption, the acute salutary effect of hypocapnia on plasma acidity might be seriously undermined. To isolate the possible effects of secondary hypocapnia from those of the hydrogen ion load, per se, animals were maintained in an atmosphere of 2.6% CO(2) during an initial 8-day period of acid feeding (7 mmol/kg per day); this maneuver allowed Paco(2) to be held constant at the control level of 36 mm Hg despite the hyperventilation induced by the acidemia. Steady-state bicarbonate concentration during the period of eucapnia fell from 20.8 to 16.0 meq/liter, while [H(+)] rose from 42 to 55 neq/liter. During the second phase of the study, acid feeding was continued but CO(2) was removed from the inspired air, permitting Paco(2) to fall by 6 mm Hg. In response to this secondary hypocapnia, bicarbonate concentration fell by an additional 3.0 meq/liter to a new steady-state level of 13.0 meq/liter. This reduction in bicarbonate was of sufficient magnitude to more than offset the acute salutary effect of the hypocapnia on plasma hydrogen ion concentration; in fact, steady-state [H(+)] rose as a function of the adaptive fall in Paco(2), Delta[H(+)]/Delta Paco(2) = -0.44. That the fall in bicarbonate observed in response to chronic secondary hypocapnia was the result of the change in Paco(2) was confirmed by the observation that plasma bicarbonate returned to its eucapnic level in a subgroup of animals re-exposed to 2.6% CO(2). These data indicate that the decrement in plasma [HCO(-) (3)] seen in chronic HCl acidosis is a composite function of (a) the acid load itself and (b) the renal response to the associated hyperventilation. We conclude that this renal response is maladaptive because it clearly diminishes the degree to which plasma acidity is protected by secondary hypocapnia acutely. Moreover, under some circumstances, this maladaptation actually results in more severe acidemia than would occur in the complete absence of secondary hypocapnia.