Anion Gap Calculation Formula
The anion gap is calculated as: Na⁺ + K⁺ - Cl⁻ - HCO₃⁻, though in clinical practice it is commonly calculated without potassium as: Na⁺ - (Cl⁻ + HCO₃⁻). 1
Standard Calculation Methods
The most comprehensive formula includes potassium: Na⁺ + K⁺ - Cl⁻ - HCO₃⁻ 2, 1
The simplified formula (most commonly used in practice) omits potassium: Na⁺ - (Cl⁻ + HCO₃⁻) 3, 4, 5
When converting between formulas, if potassium is not included in the calculation, add 4 mmol/L to the result to approximate the value that would be obtained with potassium included 2
Normal Reference Range
The modern reference range for anion gap is 3-11 mmol/L when using ion-selective electrode methodology, which is significantly lower than the outdated range of 8-16 mmol/L that many clinicians still incorrectly reference 3
More recent data suggests a reference range of 5-12 mmol/L, with the normal gap primarily representing negatively charged albumin 3, 5
Using the outdated reference range of 8-16 mmol/L can lead to misinterpretation and missed diagnoses 3
Clinical Interpretation Thresholds
An anion gap >12 mmol/L suggests metabolic acidosis in diabetic ketoacidosis (mild severity) 2
An anion gap >24 mmol/L is rare and strongly suggests significant metabolic acidosis requiring immediate investigation 3
For ethylene glycol poisoning specifically, an anion gap >28 mmol/L defines "late" poisoning with significantly higher mortality (20.4%) 2, 1
An anion gap >27 mmol/L in suspected ethylene glycol poisoning warrants immediate hemodialysis 1
Important Adjustments and Pitfalls
Correct for hypoalbuminemia: The anion gap decreases by approximately 2.5 mmol/L for every 1 g/dL decrease in albumin below normal, as low albumin reduces unmeasured anions 4, 5
Negative or very low anion gap (<2 mmol/L) is rare and should prompt investigation for IgG multiple myeloma, severe hypoalbuminemia, or laboratory error 3
The anion gap may overestimate acidosis severity in patients with acute kidney injury or ketoacidosis, and underestimate it in hypoalbuminemia 1
If your institution reports high incidence of anion gaps >24 mmol/L or <2 mmol/L, check electrolyte quality control and assess for hypoalbuminemia or hyperglobulinemia 3