Maladaptive renal response to secondary hypercapnia in chronic metabolic alkalosis
Madias, N.E.; Adrogué, H.J.; Cohen, J.J.
American Journal of Physiology 238(4): F283-F289
1980
ISSN/ISBN: 0002-9513 PMID: 7377300 Document Number: 158895
The secondary hypocapnic accompanying chronic HCl acidosis has recently been shown to elicit a renal response that contributes significantly to the overall decrement in plasma [HCO3-]; because of its unfavorable effect on the bicarbonate/carbonic acid ratio, this hypocapnia-induced decrement in plasma [HCO3-] mitigates against the otherwise protective effect of the ventilatory adaptation on plasma acidity. The secondary hypercapnia of chronic metabolic alkalosis elicits an analogous renal response. Dogs (7) were made alkalotic by the repeated administration of ethacrynic acid and the provision of a chloride-deficient diet. The secondary hypercapnia (.DELTA.PaCO2 = 5 mmHg) that developed was subsequently eradicated by forcing the animals to breathe 13% O2 in an environmental chamber. Steady-state PaCO2 was returned to the control level of 36 mmHg and plasma [HCO3-] fell from 30.8 to 27.6 meq/l (P < 0.01). That this fall in plasma [HCO3-] was the consequence of the restoration of normal PaCO2 was confirmed when secondary hypercapnia was allowed to reemerge by returning the animals to room air; plasma [HCO3-] rose to 31.4 meq/l, a level indistinguishable from that present in the initial period of metabolic alkalosis. The increment in plasma [HCO3-] during chronic diuretic-induced metabolic alkalosis is a composite function; one component stems from a renal response to the associated chloride and volume deficits and another from a renal response to the accompanying secondary hypercapnia. The latter renal response is clearly maladaptive because it undermines the salutary effect of the ventilatory adjustment on plasma hydrogen ion concentration.