Anion Gap
The calculated gap between measured cations and anions, used to narrow the differential for a metabolic acidosis.
Definition
The anion gap is the difference between the major measured cation and the major measured anions: AG = Na − (Cl + HCO3). It's a calculated proxy for the concentration of unmeasured anions in the plasma (normally proteins, phosphate, and sulfate), not a directly measured value.
Mechanism
Plasma must remain electrically neutral, so the total concentration of cations always equals the total concentration of anions — the 'gap' only exists because routine labs don't measure every ion. A rising anion gap during a metabolic acidosis means an unmeasured anion (lactate, ketoacids, or a toxic metabolite) is accumulating and displacing bicarbonate as it's consumed in buffering. A normal-anion-gap acidosis, by contrast, means bicarbonate is being lost directly and replaced by chloride, keeping the calculated gap unchanged.
Visual Physiology — Anion Gap Physiology & Albumin Correction
Anion gap physiology: electroneutrality, unmeasured anions, and the value of considering albumin correction when hypoalbuminemia may mask an elevated gap (commonly AG_corr ≈ AG + 2.5 × [4.0 - albumin in g/dL]).
Key Visual Takeaways
- Anion gap represents the concentration of unmeasured plasma anions (primarily albumin, phosphate, sulfate, and organic acids).
- Hypoalbuminemia drastically lowers baseline anion gap (2.5 mEq/L drop per 1 g/dL drop in albumin below 4.0), masking high anion gap acidosis if uncorrected.
- Elevated corrected anion gap (> 12-14 mEq/L) confirms the pathological accumulation of fixed organic acids (lactic acidosis, ketoacidosis, toxic alcohols, uremia).
Interactive visual
Anion gap = Na − (Cl + HCO3) = 140 − (104 + 16) = 20
Winter's expected PaCO2 = 1.5 × HCO3 + 8 ± 2 = 30–34
Within the expected range — appropriate respiratory compensation for a simple metabolic acidosis.
Delta ratio = (AG − 12) / (24 − HCO3) = 1
Consistent with a pure high-anion-gap metabolic acidosis.
pH is shown for reference and isn't used in these particular calculations.
An educational visualization for exploring the relationship between values, not a patient simulation.
Clinical significance
The anion gap is the single most useful branch point in working up a metabolic acidosis, splitting a broad differential into two much narrower ones — production/accumulation of an unmeasured acid versus direct bicarbonate loss — that point toward very different causes and workups.
Common ICU applications
- A high anion gap in a critically ill patient should prompt an immediate lactate — the most common ICU cause — before considering ketoacidosis, uremia, or toxic ingestion.
- Correcting the anion gap for a low albumin (each 1 g/dL drop in albumin lowers the expected gap by about 2.5) prevents missing a clinically significant HAGMA in a hypoalbuminemic critically ill patient.
- Trending the anion gap over time is used to track resolution of the underlying process (e.g. clearing lactate, resolving ketoacidosis) alongside the primary lab values.
Related concepts
Related topics