What is the formula to calculate the anion gap?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: August 26, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

How to Calculate Anion Gap

The anion gap is calculated using the formula: Anion Gap = [Na+] - ([Cl-] + [HCO3-]) 1, 2.

Understanding the Anion Gap

The anion gap (AG) is a mathematical construct that compares the blood sodium concentration with the sum of the chloride and bicarbonate concentrations. It represents the difference between measured cations and measured anions in the blood and helps categorize metabolic acidosis into:

  • High anion gap metabolic acidosis (HAGMA)
  • Normal anion gap (hyperchloremic) metabolic acidosis

Normal Values

The normal anion gap typically ranges from:

  • 8-12 mEq/L 3
  • 7-16 mEq/L (90% range in plasma donors) 4

Clinical Applications

The anion gap calculation serves several important clinical purposes:

  1. Categorizing metabolic acidosis: Divides acidosis into high anion gap and normal anion gap types, narrowing differential diagnosis 3

  2. Identifying mixed acid-base disorders: When comparing the rise in anion gap (delta AG) with the fall in bicarbonate (delta HCO3-), additional acid-base disorders can be detected 5

  3. Quality control: Serves as an additional check for electrolyte measurements 4

Important Considerations

Correcting for Albumin

Since albumin is a major contributor to the normal anion gap, hypoalbuminemia can falsely lower the calculated anion gap. For accurate clinical interpretation, the anion gap should be corrected for low albumin levels 6, 7.

Delta Gap Analysis

For more complex acid-base disorders, calculating the delta gap can be helpful:

  • Delta gap = Delta AG - Delta HCO3-
  • If delta gap > +6: Suggests concurrent metabolic alkalosis
  • If delta gap < -6: Suggests concurrent hyperchloremic acidosis 5

Potential Pitfalls

  • Negative anion gaps: May indicate laboratory error, specimen contamination, extreme hyperkalemia, or paraproteins from conditions like multiple myeloma 7
  • Falsely normal anion gap: Can occur in hypoalbuminemia despite presence of high anion gap acidosis

Clinical Context

The anion gap calculation is particularly useful in:

  • Evaluating unexplained metabolic acidosis
  • Diagnosing conditions like diabetic ketoacidosis (DKA), where anion gap >10-12 is diagnostic 1
  • Distinguishing DKA from other causes of high anion gap acidosis like lactic acidosis, salicylate toxicity, methanol or ethylene glycol ingestion 1, 2

Remember that the anion gap should always be interpreted in the context of the patient's clinical presentation and other laboratory values for optimal diagnostic utility.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Metabolic Acidosis and Medication-Associated Risks

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Anion-gap metabolic acidemia: case-based analyses.

European journal of clinical nutrition, 2020

Research

The anion gap: its use in quality control.

Clinical chemistry, 1976

Research

Approach to Patients With High Anion Gap Metabolic Acidosis: Core Curriculum 2021.

American journal of kidney diseases : the official journal of the National Kidney Foundation, 2021

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.