What is the anion gap (electrolyte imbalance) formula?

Anion Gap Formula

The anion gap (AG) is calculated as Na+ + K - Cl- - HCO3- 1. This is the most comprehensive formula that includes potassium in the calculation.

Standard Formulas and Variations

There are two main variations of the anion gap formula:

1. With potassium (comprehensive formula):

   • AG = Na+ + K+ - Cl- - HCO3-

2. Without potassium (simplified formula):

   • AG = Na+ - (Cl- + HCO3-)

When potassium is not included in the calculation, the normal range is typically adjusted downward by approximately 4 mEq/L 1, 2.

Normal Ranges

The normal anion gap varies depending on the formula used:

• With potassium: 12-16 mEq/L
• Without potassium: 8-12 mEq/L 3

These ranges may vary slightly between laboratories based on their specific measurement methods.

Clinical Applications

The anion gap calculation is primarily used to:

1. Categorize metabolic acidosis:

   • High anion gap metabolic acidosis (HAGMA): Caused by accumulation of acids other than HCl
   • Normal anion gap (hyperchloremic) metabolic acidosis: Caused by bicarbonate loss or failure to excrete acid

2. Detect mixed acid-base disorders using the delta gap:

   • Delta gap = Delta AG - Delta HCO3-
   • Delta AG = Observed AG - Normal AG
   • Delta HCO3- = Normal HCO3- - Observed HCO3-
   • If delta gap > +6: Suggests concurrent metabolic alkalosis
   • If delta gap < -6: Suggests concurrent hyperchloremic acidosis 4

3. Guide treatment decisions in toxicology:

   • In ethylene glycol poisoning, an anion gap > 27 mmol/L is a strong indication for extracorporeal treatment 1
   • An anion gap of 23-27 mmol/L suggests consideration of extracorporeal treatment in ethylene glycol poisoning 1

Important Considerations

• Hypoalbuminemia adjustment: Since albumin is a major unmeasured anion, the anion gap should be adjusted in hypoalbuminemia by adding 2.5 mEq/L for every 1 g/dL decrease in albumin below normal 2

• Potassium inclusion: When reviewing literature or guidelines, always note whether potassium was included in the calculation. If not specified, some experts recommend adding 2-4 mmol/L to standardize results 1

• Limitations: The anion gap can be affected by:

  • Laboratory measurement errors
  • Severe hyperglycemia
  • Paraproteinemia
  • Lithium or bromide intoxication
  • Severe hypermagnesemia (though evidence for this is limited) 5

Clinical Pitfalls to Avoid

• Not adjusting for hypoalbuminemia: This can lead to underestimation of the anion gap in critically ill patients
• Ignoring mixed disorders: A normal anion gap doesn't rule out the presence of a high anion gap acidosis with concurrent metabolic alkalosis
• Using the wrong reference range: Always confirm the laboratory's specific reference range and whether potassium is included in their calculation
• Relying solely on the anion gap: The anion gap should be interpreted in conjunction with other laboratory values and clinical findings

The anion gap remains one of the most valuable calculations in evaluating acid-base disorders and guiding critical treatment decisions, particularly in toxicology and critical care settings.