How to Calculate the Anion Gap
The anion gap is calculated using the formula: Na⁺ + K⁺ - Cl⁻ - HCO₃⁻, though potassium is often omitted in clinical practice 1.
Standard Calculation Formula
The most commonly used formula is: Anion Gap = Na⁺ - (Cl⁻ + HCO₃⁻) 2, 3.
Alternative Formulas and Adjustments
When potassium is included in the calculation, use: Na⁺ + K⁺ - Cl⁻ - HCO₃⁻ 1.
If the anion gap was calculated without K⁺, add 4 mmol/L to convert it to the formula that includes potassium 1.
If the method of calculation is unclear, add 2 mmol/L as a standardization adjustment 1.
Normal Reference Ranges
The modern reference range using ion-selective electrode methods is 3-11 mmol/L (when calculated without potassium) 4.
Using the traditional formula without potassium, the reference range is 5-12 mmol/L 4.
The older reference range of 8-16 mmol/L is outdated and should not be used with current laboratory techniques, as this can lead to misinterpretation 4.
When calculated with potassium included, the normal range is approximately 8-12 mEq/L 5.
Important Clinical Considerations
The anion gap represents the difference between unmeasured anions (primarily albumin) and unmeasured cations 2, 3.
Hypoalbuminemia falsely lowers the anion gap, requiring correction: for every 1 g/dL decrease in albumin below 4 g/dL, add approximately 2.5 mmol/L to the calculated anion gap 6, 2.
An anion gap >24 mmol/L strongly suggests metabolic acidosis and warrants immediate investigation 4.
In ethylene glycol poisoning specifically, an anion gap >27-28 mmol/L is associated with significantly higher mortality (20.4%) and requires immediate hemodialysis 1, 6.
Quality Control Applications
The anion gap serves as an internal quality control check for electrolyte measurements - values exceeding 24 mmol/L or below 2 mmol/L should prompt verification of laboratory results 4, 7.
Most analytical variability in the anion gap comes from laboratory measurement error rather than physiological variation 7.