What the anion gap measures
The anion gap estimates unmeasured anions in plasma. Because the body is electrically neutral, measured cations minus measured anions leaves a "gap" made up largely of albumin and other unmeasured anions.
Anion gap = (Na⁺ + K⁺) − (Cl⁻ + HCO₃⁻) (potassium is sometimes omitted). A normal value is approximately 8–14 mmol/L.
Its main use is to split a metabolic acidosis into two mechanistic groups.
Raised anion gap metabolic acidosis
An unmeasured acid accumulates, consuming bicarbonate. Causes (MUDPILES):
- Methanol
- Uraemia (renal failure)
- Diabetic (and other) ketoacidosis
- Propylene glycol / Paraldehyde
- Isoniazid / Iron
- Lactic acidosis
- Ethylene glycol
- Salicylates
Normal anion gap (hyperchloraemic) metabolic acidosis
Bicarbonate is lost (and replaced by chloride), or chloride is added. Causes:
- Gastrointestinal bicarbonate loss: diarrhoea, ileostomy, pancreatic/biliary fistula
- Renal tubular acidosis (types 1, 2 and 4)
- Carbonic anhydrase inhibitors (acetazolamide)
- Ammonium chloride ingestion; large-volume saline resuscitation
MRCP-specific traps
- Correct for albumin: hypoalbuminaemia lowers the measured gap, potentially masking a raised-gap acidosis (add ~2.5 mmol/L per 10 g/L fall in albumin).
- In a raised-gap acidosis of uncertain cause, calculate the osmolar gap — a raised osmolar gap suggests toxic alcohols (methanol, ethylene glycol).
- Diarrhoea gives a normal gap; DKA and lactic acidosis give a raised gap.
Summary
The anion gap = (Na + K) − (Cl + HCO₃). A raised gap means an unmeasured acid has accumulated (MUDPILES); a normal gap means bicarbonate has been lost (GI losses or renal tubular acidosis). Correct for albumin before interpreting.