What is the formula to calculate the anion gap?

How to Calculate the Anion Gap

The anion gap is calculated using the formula: Na⁺ - (Cl⁻ + HCO₃⁻), though some laboratories include potassium in the calculation as: Na⁺ + K⁺ - (Cl⁻ + HCO₃⁻). 1

Standard Calculation Methods

Primary Formula (Most Common)

• Anion Gap = Na⁺ - (Cl⁻ + HCO₃⁻) 1, 2
• This is the most widely used formula in clinical practice 3

Alternative Formula (With Potassium)

• Anion Gap = Na⁺ + K⁺ - (Cl⁻ + HCO₃⁻) 1
• When converting between formulas: if calculated without K⁺, add 4 mmol/L; if potassium status is unknown, add 2 mmol/L 1

Normal Reference Ranges

Modern Ion-Selective Electrode Method

• Normal range: 3-11 mmol/L (without potassium) 4
• Updated range: 5-12 mmol/L in some laboratories 4
• The reference range has been lowered from the historical 8-16 mmol/L due to changes in electrolyte measurement techniques 4

Clinical Interpretation Thresholds

• Normal anion gap: 59.5% of hospitalized patients 4
• Increased anion gap: 37.6% of hospitalized patients 4
• Decreased anion gap: 2.9% of hospitalized patients 4

Critical Clinical Cutoffs

High Anion Gap Thresholds

• Anion gap >27 mmol/L: Strong indication for urgent intervention in toxic ingestions 1
• Anion gap 23-27 mmol/L: Moderate elevation warranting investigation 1
• Anion gap >24 mmol/L: Rare finding that strongly suggests metabolic acidosis 4

Low Anion Gap Thresholds

• Anion gap <2 mmol/L: Very rare finding requiring investigation 4
• Negative anion gap (-1 or less): Suggests laboratory error, specimen contamination, hypoalbuminemia, extreme hyperkalemia, bromism, or paraproteins 5

Important Corrections and Adjustments

Hypoalbuminemia Correction

• Recalculate using: Na⁺ + K⁺ - Cl⁻ - HCO₃⁻ to confirm the value 6
• Severe hypoalbuminemia significantly lowers the anion gap since albumin is a major unmeasured anion 6
• Check arterial blood gas to assess actual acid-base status when baseline anion gap is low, as it can mask concurrent high anion gap metabolic acidosis 6

Clinical Pitfalls to Avoid

• The anion gap may overestimate glycolate/toxin concentrations in concomitant AKI or ketoacidosis 1
• The anion gap may underestimate toxin concentrations in hypoalbuminemia or co-ingestions of lithium or barium 1, 6
• Clinicians still commonly use the outdated reference range of 8-16 mmol/L, which can lead to misinterpretation 4

Quality Control Applications

Laboratory Verification

• Use anion gap as an internal quality control check for electrolyte measurements 4, 7
• High incidence of anion gap >24 mmol/L or <2 mmol/L should prompt verification of electrolyte quality control and assessment for hypoalbuminemia or hyperglobulinemia 4
• Most variability in anion gap measurements is due to analytical rather than physiological variation 7

Delta Gap Calculation

• Δ anion gap = observed anion gap - normal anion gap 3
• Δ HCO₃⁻ = normal HCO₃⁻ - observed HCO₃⁻ 3
• Ratio of 1 suggests simple anion gap acidosis 3
• Ratio <1 indicates superimposed non-gap acidosis 3
• Ratio >1 suggests superimposed metabolic alkalosis 3