normal anion gap
Summary
Normal anion gap (typically 8-12 mEq/L) is calculated as Na+ - (Cl- + HCO3-). A normal anion gap metabolic acidosis (NAGMA) occurs due to bicarbonate loss or impaired renal acid excretion, with chloride rising to compensate (hyperchloremic metabolic acidosis).
Detail
The anion gap represents unmeasured anions in serum, primarily albumin, and is calculated as Na+ - (Cl- + HCO3-), normally 8-12 mEq/L (adjust for hypoalbuminemia: gap decreases ~2.5 mEq/L per 1 g/dL drop in albumin below normal).
Normal anion gap metabolic acidosis (NAGMA), also called hyperchloremic metabolic acidosis, occurs when HCO3- is lost or H+ is retained without generation of new unmeasured anions—chloride rises reciprocally to maintain electroneutrality.
Key causes (mnemonic: HARDUP or diarrhea-focused mnemonics): - GI bicarbonate loss: Diarrhea, pancreatic fistulas, ileostomy - Renal tubular acidosis (RTA): - Type 1 (distal): impaired H+ secretion, low urine pH, associated with nephrocalcinosis, hypokalemia - Type 2 (proximal): impaired HCO3- reabsorption, Fanconi syndrome - Type 4: aldosterone deficiency/resistance, hyperkalemia - Early renal failure (before uremic anions accumulate) - Carbonic anhydrase inhibitors (acetazolamide) - Ammonium chloride ingestion - Ureteral diversion (ureterosigmoidostomy) - Post-hyperventilation - Saline/NaCl infusion (dilutional acidosis)
Clinical utility: Distinguishing NAGMA from high anion gap metabolic acidosis (HAGMA) narrows differential diagnosis significantly. Urine anion gap (Na+ + K+ - Cl-) helps differentiate GI losses (negative UAG, appropriate renal ammonium excretion) from RTA (positive UAG, impaired ammonium excretion).
Boards frequently test RTA subtypes with their associated findings, and diarrhea as the classic NAGMA cause vs. DKA/lactic acidosis/toxic ingestions as HAGMA causes.
Sources
- First Aid for the USMLE Step 1
- Harrison's Principles of Internal Medicine
- UpToDate: Approach to the adult with metabolic acidosis
- Guyton and Hall Textbook of Medical Physiology
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