How the Anion Gap is calculated
The anion gap represents the "unmeasured" anions in serum — mostly albumin, plus phosphate, sulfate and organic acids — inferred from the difference between routinely measured cations and anions.
Because albumin accounts for most of the normal gap, hypoalbuminemia falsely lowers it. A correction is applied when albumin is low:
Normal values
| Anion gap (mEq/L) | Interpretation |
|---|---|
| < 8 | Low anion gap (rare; consider paraproteinaemia, hypoalbuminaemia, lab error) |
| 8 – 16 | Normal anion gap |
| > 16 | High anion gap metabolic acidosis |
Reference ranges vary somewhat by lab and assay method (some modern ion-selective electrode labs quote 6–12 mEq/L) — always check the local reference range alongside this general guide.
Clinical use
The anion gap is the first step in classifying a metabolic acidosis. A raised gap points toward an accumulation of unmeasured acid — remembered by the mnemonic MUDPILES (Methanol, Uraemia, Diabetic ketoacidosis, Propylene glycol/Paraldehyde, Iron/Isoniazid, Lactic acidosis, Ethylene glycol, Salicylates). A normal-gap acidosis instead suggests bicarbonate loss (e.g. diarrhoea, renal tubular acidosis) with a compensatory rise in chloride (hyperchloraemic acidosis).
Frequently asked questions
What is the anion gap?
It's the calculated difference between measured cations (sodium) and anions (chloride, bicarbonate) in serum, used as the first step in classifying the cause of a metabolic acidosis.
What causes a high anion gap?
Accumulation of an unmeasured acid — common causes are remembered by the mnemonic MUDPILES (methanol, uraemia, diabetic ketoacidosis, propylene glycol/paraldehyde, iron/isoniazid, lactic acidosis, ethylene glycol, salicylates).
What is a normal anion gap?
Roughly 8–16 mEq/L, though exact reference ranges vary by lab and assay method — some modern ion-selective electrode labs cite a slightly lower range (around 6–12 mEq/L).
What is the MUDPILES mnemonic?
A memory aid for causes of a high anion gap metabolic acidosis: Methanol, Uraemia, Diabetic ketoacidosis, Propylene glycol/Paraldehyde, Iron/Isoniazid, Lactic acidosis, Ethylene glycol, Salicylates.
References
- Emmett M, Narins RG. Clinical use of the anion gap. Medicine (Baltimore). 1977;56:38–54.
- Kraut JA, Madias NE. Metabolic acidosis: pathophysiology, diagnosis and management. Nat Rev Nephrol. 2010;6:274–285.