Serum Anion Gap

Serum must be electrically neutral, so all the cations and all the anions balance exactly. A chemistry panel measures only some of them: sodium among the cations, chloride and bicarbonate among the anions. Subtract what you can see and you get a positive residue, the anion gap, which is the excess of unmeasured anions such as albumin, phosphate, sulphate and organic acids over unmeasured cations like potassium, calcium and magnesium. A normal panel of 140, 104 and 24 gives $140 - 128 = 12$ mmol/L.

The gap earns its place because it splits a metabolic acidosis into two families. A high gap means an acid has been added and its anion is sitting in the residue: ketoacids, lactate, salicylate, methanol and ethylene glycol metabolites, and the retained acids of renal failure. A normal gap means bicarbonate was lost and chloride came in to replace it, as in diarrhoea or renal tubular acidosis. In diabetic ketoacidosis a panel of 138, 100 and 10 gives a gap of 28, and the elevation is the ketoacid anion made visible.

Two corrections matter. Albumin is the largest single unmeasured anion, so a hypoalbuminaemic patient has a low baseline gap and can hide a significant acidosis; the usual adjustment adds about 2.5 mmol/L to the gap for each 1 g/dL the albumin falls below 4.0. And the reference range depends on the laboratory, because analysers that measure bicarbonate directly and those that calculate it from CO₂ differ, and older methods gave a normal range of 8 to 16 where modern ones often give 3 to 11. Compare a gap against your own laboratory's range, not against a remembered number.