Chemistry
Anion Gap
Serum anion gap for metabolic acidosis.
Education and reference only. Not a substitute for clinical judgement, local policy or product labelling. Always verify before clinical use. Values are calculated in your browser and never stored.
Background
The serum anion gap is a calculated value used to investigate metabolic acidosis, derived as sodium minus the sum of chloride and bicarbonate. It represents the unmeasured anions in plasma and helps separate acidoses into high-anion-gap and normal-anion-gap categories. By doing so it rapidly narrows the differential diagnosis in a patient with a low bicarbonate. The reference range is laboratory-dependent, typically around 8–12 mmol/L.
Interpreting the result
A value within the laboratory's typical range (about 8–12 mmol/L) suggests a normal anion gap, while a raised value (commonly above 12) indicates a high-anion-gap metabolic acidosis (HAGMA). High-anion-gap causes include lactic acidosis, ketoacidosis, renal failure and certain ingestions, whereas a normal gap points to causes such as gastrointestinal bicarbonate loss or renal tubular acidosis. The threshold is approximate and lab-specific, so interpret the number against the local reference range.
Worked example
A patient with sodium 140, chloride 100 and bicarbonate 14 mmol/L has an anion gap of 140 − (100 + 14) = 26 mmol/L. This is clearly raised and indicates a high-anion-gap metabolic acidosis warranting a search for an underlying cause such as ketoacidosis or lactic acidosis.
Critical actions
Reference range is lab-dependent (≈8–12). Correct for albumin in hypoalbuminaemia (a low albumin lowers the apparent gap).
Pearls / pitfalls
- The reference range is laboratory-dependent (around 8–12), so always compare against the local range rather than a fixed cut-off.
- Hypoalbuminaemia lowers the apparent gap — correct for albumin, otherwise a true high-gap acidosis can be masked.
- Whether potassium is included varies between formulae and laboratories; be consistent with your local method.
- The anion gap narrows the differential but does not identify the specific cause — pair it with history, lactate, ketones and renal function.
Evidence & validation
The anion gap is a long-standing component of acid-base assessment described in clinical biochemistry and acid-base physiology literature, and remains a routine first step in evaluating metabolic acidosis.
Frequently asked questions
What is a normal anion gap?
It is laboratory-dependent but typically around 8–12 mmol/L. Values above this generally indicate a high-anion-gap metabolic acidosis.
Why does a high anion gap matter?
It points towards causes such as lactic acidosis, ketoacidosis, renal failure or certain ingestions. This narrows the differential and directs urgent investigation.
Does low albumin affect the anion gap?
Yes. Albumin is a major unmeasured anion, so hypoalbuminaemia lowers the apparent gap. The gap should be corrected for albumin to avoid missing a true high-gap acidosis.
Is potassium included in the calculation?
It depends on the formula. Some include potassium and some do not; the reference range shifts accordingly. Use your local laboratory's convention consistently.
Does the anion gap tell me the cause of the acidosis?
No. It only categorises the acidosis as high or normal gap. The specific cause is found by combining it with the history, lactate, ketones and renal function.
References
- Emmett M, Narins RG. Clinical use of the anion gap. Medicine (Baltimore). 1977;56(1):38–54.
- Kraut JA, Madias NE. Serum anion gap: its uses and limitations in clinical medicine. Clin J Am Soc Nephrol. 2007;2(1):162–174.
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