nephrology & metabolismformula

Anion Gap

The anion gap measures the difference between measured cations (Na⁺) and measured anions (Cl⁻ + HCO₃⁻) in serum. It identifies unmeasured anions and is essential for characterising metabolic acidosis as either high anion gap (HAGMA) or normal anion gap (NAGMA).

inputs

mmol/L
mmol/L
mmol/L

✓ when to use

Calculate in any patient with metabolic acidosis (low bicarbonate or low pH). Also useful as a screening tool in poisoning, DKA monitoring, unexplained metabolic derangement, or any critically ill patient. Should be calculated alongside the delta ratio (delta-delta) in mixed acid-base disorders.

✗ when not to use

The anion gap must be corrected for albumin — for every 10 g/L decrease in albumin below 40 g/L, the expected AG decreases by approximately 2.5 mmol/L. An uncorrected AG can mask a HAGMA in hypoalbuminaemic patients (common in critical illness, liver disease, nephrotic syndrome). The AG is also affected by the laboratory analyser used — modern ion-selective electrode analysers produce lower 'normal' ranges than older methods.

clinical pearls

  • Always correct the AG for albumin. The corrected AG = calculated AG + 2.5 × (40 − measured albumin in g/L). A patient with albumin 20 g/L and a 'normal' AG of 10 actually has a corrected AG of 15 — a hidden HAGMA.
  • MUDPILES is the classic mnemonic for HAGMA causes: Methanol, Uraemia, DKA (and starvation/alcoholic ketoacidosis), Propylene glycol, Isoniazid/Iron, Lactic acidosis, Ethylene glycol, Salicylates.
  • A low anion gap (<4) is often overlooked but clinically significant. The most common cause is hypoalbuminaemia. Other causes include paraproteinaemia (myeloma, Waldenström), lithium toxicity, and bromide interference.
  • In mixed acid-base disorders, calculate the delta ratio: (AG − 12) / (24 − HCO₃⁻). A ratio <1 suggests concurrent NAGMA; >2 suggests concurrent metabolic alkalosis.
  • In DKA monitoring, the AG is more reliable than blood glucose for tracking resolution. Glucose normalises before ketoacidosis resolves — premature insulin cessation based on glucose alone is a common error.

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