• Anion gap (AG) is routinely calculated during the workup of metabolic acidosis because it estimates the level of unmeasured anions that often rise in anion gap metabolic acidosis (AGMA) but not non-anion gap metabolic acidosis (NAGMA).
• AG is the difference between measured cations (Na and K, but K is often not included in the calculation) and measured anions (Cl, HCO3) (shown in right figure below).
• In normal state, unmeasured anions (e.g. albumin, urate, sulfate, phosphate) account for the normal level of AG (~ 12).
• In AGMA, AG rises due to a rise in unmeasured anions from strong acids such as lactate and ketoacetate. In the meantime, H+ ions release from strong acids bind with HCO3 and effectively decrease their concentrations.
• In NAGMA, AG remains at baseline because there is no additional unmeasured anions introduced, but rather HCO3 ions are lost in the urine or gut lumen and those are replaced by Cl- ions. As a result, [HCO3] decreases and [Cl] increases while AG is within normal range.
• Note that the level of total anions (unmeasured + measured) is maintained by the body to be equal to the level of total cations (unmeasured + measured) and there are many other anions and cations in the body that are either “unmeasured” during routine lab or not included in the AG formula (e.g. K, Ca, Mg cations and albumin, phosphate, sulfate, urate anions). Therefore, AG is also an estimate of the difference between unmeasured cations and anions (shown in left figure below).
• Because anion gap (AG) value changes from baseline when there is any change in the level of of anions or cations (unmeasured or measured), an abnormally low or high AG might suggest certain diagnoses including those other than metabolic acidosis.
• AG increases when there is a(n)-
Increase in unmeasured anions such as strong acids’ anions in anion gap metabolic acidosis and negatively charged compounds such as albumin, phosphate, IgA
Increase in measured cations/ decrease in measured anions: often caused by erroneous lab measurement of Na, K, Cl, and/or HCO3.
• AG decreases when there is a(n)-
Decrease in unmeasured anions such as albumin in hypoalbuminemia or severe non-anion gap metabolic acidosis (H+ ions bind with albumin)
Increase in unmeasured cations such as K, Ca, Mg, and IgG (in multiple myeloma)
Decrease in measured cations/ increase in measured anions: often caused by erroneous lab measurement of Na, K, Cl, and/or HCO3. or less commonly seen in other conditions listed below.
