These unmeasured anions are generated as the result of the consumption of HCO3− by endogenous organic
acids such as lactic acid, acetoacetic acid, or βhydroxybutyric
acid or from the ingestion of toxins such as
methanol or ethylene glycol. The degree of elevation in the SAG is dependent on the clearance of the anion, as
well as the multiple factors that influence HCO3− concentrations. Thus, the SAG is a relative rather than an
absolute indication of the cause of metabolic acidosis. The SAG can also be elevated in the metabolic acidosis
because of renal failure, as the result of the accumulation of various organic anions, phosphates, and sulfates.