How to Calculate the Anion Gap in DKA
The anion gap is calculated as: [Na+] - ([Cl-] + [HCO3-]), with a normal range of 8-12 mEq/L. 1, 2
The Basic Formula
The anion gap represents the difference between measured cations and measured anions in serum, reflecting unmeasured anions (primarily negatively charged albumin under normal conditions, and ketoacids in DKA). 1
- Standard calculation: Serum Sodium - (Serum Chloride + Serum Bicarbonate) 1, 3
- Normal range: 8-12 mEq/L 1, 2
- In DKA: The anion gap is elevated due to accumulation of ketoacids (primarily beta-hydroxybutyrate and acetoacetate) 4
Anion Gap Values in DKA Severity Classification
The elevation in anion gap directly correlates with DKA severity:
- Mild DKA: Anion gap >10 mEq/L 4
- Moderate DKA: Anion gap >12 mEq/L 4
- Severe DKA: Anion gap >12 mEq/L with more profound acidosis 4
Resolution of DKA requires normalization of the anion gap to ≤12 mEq/L (along with glucose <200 mg/dL, serum bicarbonate ≥18 mEq/L, and venous pH >7.3). 5, 4
Monitoring During DKA Treatment
The anion gap should be monitored every 2-4 hours during active DKA treatment to track resolution of acidosis. 5
- Venous pH and anion gap can be followed together, avoiding the need for repeated arterial blood gases 5
- The anion gap provides the most reliable marker of treatment response, as it reflects total unmeasured anion burden regardless of specific ketone species 6
- Continue monitoring until anion gap normalizes to ≤12 mEq/L 4, 6
Important Corrections and Considerations
Albumin Correction
The normal anion gap is primarily due to negatively charged albumin. 1 In hypoalbuminemia, the anion gap should be corrected, as low albumin artificially lowers the calculated gap. 3, 7 The Figge-Fencl-Watson model justifies correcting the anion gap for net protein charge in clinical practice. 7
Delta Gap Calculation
To identify mixed acid-base disorders, calculate the delta gap: Δ anion gap - Δ HCO3- 1, 8
- Δ anion gap = observed anion gap - normal anion gap (typically 12) 1
- Δ HCO3- = normal HCO3- (typically 24) - observed HCO3- 1
- Ratio of 1:1 suggests simple anion gap acidosis 1
- Ratio <1 indicates superimposed non-gap (hyperchloremic) acidosis 1, 8
- Ratio >1 suggests superimposed metabolic alkalosis 1, 8
- Delta gap significantly positive (>+6): metabolic alkalosis present 8
- Delta gap significantly negative (<-6): hyperchloremic acidosis present 8
Clinical Pitfalls
Do not rely on nitroprusside ketone measurements to track DKA resolution, as this method only measures acetoacetic acid and acetone, not beta-hydroxybutyrate (the predominant ketoacid in DKA). 5 During therapy, beta-hydroxybutyrate converts to acetoacetic acid, which may falsely suggest worsening ketosis. 5
The anion gap serves as an inexpensive quality control measure for electrolyte measurements—abnormal values should prompt verification of laboratory data. 2