What is the role of the anion gap (AG) in the diagnosis of metabolic acidosis?

Updated: Oct 05, 2018
  • Author: Antonia Quinn, DO; Chief Editor: Romesh Khardori, MD, PhD, FACP  more...
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Calculation of the AG is often helpful in the differential diagnosis of metabolic acidosis. [3] The AG is equal to the difference between the plasma concentrations of the measured plasma cation (ie, Na+) and the measured anions (ie, chloride [Cl-], HCO3-). It exists because standard electrolyte panels do not measure all the anions present in the serum.

AG calculation = (Na+) - ([Cl-] + [HCO3-])

A normal AG is traditionally listed as 8-16 mEq/L, with an average value of 12. This value may vary, depending on the instrumentation used to measure electrolyte levels, and recent data suggest a normal range of 5-11 mEq/L. Some authors add K+ to measured cations; then, the traditional normal range is 12-20 mEq/L. The anion gap allows for the differentiation of 2 groups of metabolic acidosis. Metabolic acidosis with a high AG is associated with the addition of endogenously or exogenously generated acids. Metabolic acidosis with a normal AG is associated with the loss of HCO3 or the failure to excrete H+ from the body.

High AG warrants the following:

  • Lactic acidosis - Lactate, D-lactate

  • Ketoacidosis - Beta-hydroxybutyrate, acetoacetate

  • Renal failure - Sulfate, phosphate, urate, and hippurate

  • Ingestions - Salicylate, methanol or formaldehyde (formate), ethylene glycol (glycolate, oxalate), paraldehyde (organic anions), sulfur (SO4-), phenformin/metformin

  • Pyroglutamic acidemia (5-oxoprolinemia)

  • Massive rhabdomyolysis (release of H+ and organic anions from damaged muscle)

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