the difference between the concentrations of serum or plasma cations and anions, determined by measuring the concentrations of sodium cations and chloride and bicarbonate anions. It is helpful in the diagnosis and treatment of acidosis, and it is estimated by subtracting the sum of chloride and bicarbonate concentrations in the plasma from that of sodium. It is normally about 8 to 14 mEq/L and represents the negative charges contributed to plasma by unmeasured ions or ions other than those of chloride and bicarbonate, mainly phosphate, sulfate, organic acids, and plasma proteins. Anions other than chloride and bicarbonate normally constitute about 12 mEq/L of the total anion concentration in plasma. Acidosis can develop with or without an associated anion increase. An increase in the anion gap often suggests diabetic ketoacidosis, drug poisoning, renal failure, or lactic acidosis and usually warrants further laboratory tests.