Fixed Acid Uptake by Visceral Organs During Early Endotoxemia

Abstract

Metabolic acidosis commonly occurs in patients with the sepsis syndrome (1). Acidosis correlates with increased mortality even in the absence of increased lactate levels and is a more reliable predictor of outcome (2). Although many studies have focused on the pathophysiology, clinical significance, and treatment of lactic acidosis (3–9), relatively few have investigated other sources of metabolic acidosis in sepsis. This is surprising because lactate ion accounts for less than 50% of the “unmeasured” anions present in patients with sepsis and metabolic acidosis (10). We have previously demonstrated that during normal physiologic conditions the liver takes up some of these other anions. However, following administration of endotoxin the liver switches to release of unexplained anions (11). This might account for the appearance of unexplained anions in the circulation of patients with sepsis (10) and liver disease (12) and may result in systemic acidosis if these anions accumulate in excess of strong cations. However, a non-anion gap metabolic acidosis occurs within several minutes of the administration of endotoxin to healthy animals (13). In addition, patients with sepsis frequently exhibit an acidosis which has a significant non-anion gap component (14). This acidosis cannot be explained by the release of anions by the liver. Accordingly, we reanalyzed the data from our original study (11) and included analysis of net acid flux in order to determine the sites of fixed acid production and clearance in acute endotoxemia.