Effect of acute pH change on serum anion gap

The serum anion gap is decreased in hyperchloremic (HCl) acidosis and increased in diuretic-induced alkalosis. These anion gap changes have been largely attributed to titration-induced variations in the net negative charge of the serum proteins, which are the predominant non-HCO₃ buffers of serum. It has recently been shown, however, that albumin has all of the net protein charge, and titration-induced changes in charge are smaller than have been widely believed. Because the non-HCO₃ buffers are also titrated in acute hypocapnia and hypercapnia, these disorders were induced in 16 anesthetized dogs for 10 min in order to assess the effect of acute changes in pH on the anion gap. Although the mean arterial pH varied from 7.04 to 7.65, the calculated mean albumin charge only varied from 6.8 to 9.0 mEq/L. When the anion gap was computed with HCO₃ (AG(HCO3) = Na + K - Cl - HCO₃), the change in AG(HCO3) per 0.1 change in pH (ΔAG(HCO3)/ΔpH) was only 0.15 mEq/L per 0.1 pH. When the anion gap was computed with total CO₂ content (AG(TCO2) = Na + K - Cl - TCO₂), ΔAG(TCO2)/ΔpH was larger (0.51 mEq/L per 0.1 pH) because of the effect of variable PCO₂ levels on TCO₂. In a review of 22 previous studies in humans and dogs, similar estimates of ΔAG/ΔpH were obtained (after adjusting for the lower albumin level in dogs). These results show that simple titration processes that occur within 10 min of a change in pH cause minimal changes in the anion gap. Titration of the known non-HCO₃ buffers of serum does not explain the much larger anion gap changes of HCl acidosis and diuretic alkalosis.