Cause | Comments |
Laboratory error | Spuriously low serum Na+ or spuriously elevated serum Cl– or HCO3–; laboratory error is the most common cause of low anion gap |
Hypoalbuminemia | Second most common cause of low serum anion gap (after laboratory error); albumin is anionic, and reduced levels decrease the concentration of unmeasured anions |
Salicylate poisoning or use of thiosulfate | Increased concentration of unmeasured anions |
Monoclonal or polyclonal gammopathy | Immunoglobulins are usually cationic, and elevated levels increase the concentration of unmeasured cations (especially IgG and IgM) |
Hypercalcemia or hypermagnesemia | Increased concentration of unmeasured cations |
Severe hyperkalemia | Increased concentration of unmeasured cations |
Lithium intoxication | Lithium is an unmeasured cation, and a low anion gap can occur with lithium >4 mEq/L |
Polymyxin B | Polymyxin B is polycationic at physiologic pH |
Psuedohyponatremia | Measurement of serum Na+ with indirect ion-selective electrode in the setting of marked hypertriglyceridemia, hypercholesterolemia, or hyperproteinemia |
Pseudohyperchloremia | Can occur in the setting of bromide or iodide intoxication |
Pseudohyperbicarbonatemia | Rare, but can be present if there are markedly elevated levels of lactate dehydrogenase |
Adapted from: Kraut JA, Madias NE. Serum anion gap: Its uses and limitations in clinical medicine. Clin J Am Soc Nephrol 2007; 2:162.