Removal of an inorganic acid load in subjects with ketoacidosis of chronic fasting

Abstract

When a large inorganic acid load is ingested by normals, the proton load is eliminated because the rate of excretion of ammonium can rise to 200 to 300 mmol/day. In subjects with ketoacidosis of chronic fasting, such a large increase in the rate of excretion of ammonium might not be possible because of ATP balance considerations in proximal cells. Subjects with ketoacidosis of chronic fasting excreted less net acid as defined in the conventional way when they consumed a large inorganic acid load (136 ± 6 vs. 176 ± 26 mmol/day in control fasted subjects). Nevertheless, the vast majority of this inorganic acid load was eliminated because they were in steady state and had only a slightly lower concentration of bicarbonate (13 ± 0.6 vs. 15 ± 0.5 mmol/liter) and ketoacid anions (3.3 ± 0.2 vs. 5.5 ± 0.2 mmol/liter) in their blood. Using a definition of net acid excretion where the component of bicarbonate loss was expanded to include "potential bicarbonate" (ketoacid anions) in the urine, the rate of excretion of net acid was higher in subjects who ingested the inorganic acid load, owing to a much lower rate of excretion of ketoacid anions (9 ± 2 vs. 120 ± 7 mmol/day). This lower rate of excretion was not only due to a lower filtered load, but also to a higher fractional reabsorption of ketoacid anions during acidosis (97 ± 0.1 vs. 77 ± 0.2%). This higher fractional reabsorption could not be explained by a lower filtered load of ketoacid anions or to a restricted intake of sodium. We conclude that an enhanced rate of reabsorption leads to a reduced rate of excretion of "potential bicarbonate" in the urine, and this is part of the response to eliminate an inorganic acid load during chronic ketoacidosis.