pH regulation of endogenous acid production in subjects with chronic ketoacidosis

Abstract

In a previous study of starvation-induced acute ketoacidosis, net ketoacid production was inhibited by acid and facilitated by base ingestion. To determine whether hydrogen ion modifies net ketoacid production during chronic ketoacidosis, six over-weight volunteers ingested NaHCO3, NaCl, or NH4Cl (2 mmol X kg-1 X day-1), each for 7 days, during weeks 6-8 of ketogenic dieting. During days 4-7 of each phase, blood bicarbonate was stable but lower in the NH4Cl (19.6 +/- 0.7 mM) than the NaHCO3 (23.7 +/- 0.7 mM) phases. Throughout these periods, acid intake differed by 216 mmol/day, whereas acid output differed by 129 mmol/day between the NaHCO3 and the NH4Cl phases. The major contribution to this difference in acid balance was a difference in net organic acid (ketoacid) production. Although blood ketones were stable, ketoacid excretion, reflecting net ketoacid production, was decreased by 59% with acid and increased by 66% with base compared with NaCl (control) ingestion. Thus, in this state of chronic ketoacidosis, challenges to acid-base balance were countered by a rapidly occurring, sustained, reversible, and quantitatively significant modification of net acid production which acted as an effective mechanism for acid-base regulation.