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Anion Gap

Serum anion gap calculation for metabolic acidosis differential

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Why use it

Essential for metabolic acidosis differential diagnosis. Guides workup: elevated AG prompts evaluation for lactate, ketones, toxins, renal failure. Albumin correction prevents false normals in ICU patients.

About

The serum anion gap (AG) helps differentiate causes of metabolic acidosis. An elevated AG (> 12) suggests accumulation of unmeasured anions (lactic acid, ketoacids, uremic toxins, toxic alcohols). Normal AG acidosis (hyperchloremic) suggests bicarbonate loss (diarrhea, RTA). Albumin-corrected AG improves accuracy in hypoalbuminemic patients.

When to use

  • Metabolic acidosis (low bicarbonate) on arterial blood gas or BMP
  • Suspected poisoning or toxic ingestion
  • DKA or lactic acidosis evaluation
  • Acid-base disturbance workup

Formula

AG = Na - (Cl + HCO₃) Albumin-corrected AG = AG + 2.5 × (4.0 - Albumin) Normal AG: 8-12 mEq/L

Pearls & pitfalls

  • Normal AG is ~12 ± 4 (or 8-12 without potassium in formula).
  • MUDPILES mnemonic for elevated AG: Methanol, Uremia, DKA, Propylene glycol, INH/Iron, Lactic acidosis, Ethylene glycol, Salicylates.
  • Correct AG for albumin: for every 1 g/dL decrease in albumin below 4.0, AG decreases by ~2.5.
  • Normal AG acidosis (HARDUPS): Hyperalimentation, Addison, RTA, Diarrhea, Uretero-pelvic, Pancreatic fistula, Saline infusion.
  • Delta-delta ratio = (AG - 12) / (24 - HCO3): < 1 = mixed NAGMA; 1-2 = pure AGMA; > 2 = concurrent metabolic alkalosis.

Next steps

Elevated AG: Check lactate, ketones, BUN/Cr, osmolar gap (if toxic alcohol suspected). Normal AG: Check urine anion gap, consider RTA or GI bicarbonate loss. Calculate delta-delta ratio to check for mixed disorders.

Evidence

Classic clinical tool described by Emmett and Narins (Medicine, 1977). Albumin-corrected AG described by Figge et al. (Crit Care Med, 1998). Universally used in acid-base physiology and critical care.

References

  1. Emmett M, Narins RG. Clinical use of the anion gap. Medicine (Baltimore). 1977;56(1):38-54. — link
  2. Figge J et al. Anion gap and hypoalbuminemia. Crit Care Med. 1998;26(11):1807-1810. — link