What it is
The anion gap (AG) estimates unmeasured anions in plasma to classify metabolic acidosis. It is calculated from routine electrolytes:
$$ AG = Na^+ - (Cl^- + HCO_3^-) $$
A high anion gap metabolic acidosis (HAGMA) reflects added unmeasured acid (lactate, ketoacids, toxins, uremic anions). A normal anion gap metabolic acidosis (NAGMA) reflects bicarbonate loss with chloride retention (diarrhea, renal tubular acidosis, carbonic anhydrase inhibitors). The split is the first fork in any acidosis workup.
Method
Normal AG is roughly 8–12 mmol/L (lab- and method-dependent; this tool flags >16 as high). Two adjustments make it reliable:
Albumin correction. Albumin is the dominant unmeasured anion, so hypoalbuminemia — common in sick children — lowers the baseline gap and can mask a true HAGMA. Correct by +2.5 mmol/L for every 1 g/dL the albumin sits below 4 g/dL:
$$ AG_{corr} = AG + 2.5 \times (4.0 - albumin,[g/dL]) $$
Delta-delta (delta ratio). In a pure HAGMA the rise in AG should mirror the fall in bicarbonate. Compare them:
$$ \frac{\Delta AG}{\Delta HCO_3} = \frac{AG - 12}{24 - HCO_3} $$
- <0.4–0.8 → a concurrent NAGMA is also present.
- ~1–2 → pure HAGMA.
- >2 → a coexisting metabolic alkalosis or chronic respiratory acidosis is propping up the bicarbonate.
When to use
Any metabolic acidosis, to separate HAGMA from NAGMA and — via the delta ratio — to detect a second hidden disorder the bicarbonate alone would not reveal.
Worked example
Na 140, Cl 100, HCO₃ 14, albumin 2.0 g/dL. Raw AG = 140 − (100 + 14) = 26 mmol/L — already high. Corrected: 26 + 2.5 × (4.0 − 2.0) = 31 mmol/L, even more striking. Delta ratio = (26 − 12) / (24 − 14) = 14/10 = 1.4 → consistent with a pure HAGMA.
Pitfalls
- Always albumin-correct in the critically ill. A “normal” gap of 10 in a child with albumin 2.0 corrects to ~15 — a missed HAGMA.
- The delta ratio is interpretive, not absolute — bands overlap and it assumes a normal starting bicarbonate; use it to prompt a search for a second process, not to diagnose one.
- Watch for AG-lowering states (hypoalbuminemia, lithium, bromide, severe hypercalcemia) and lab artefacts.
- The gap is a screen — confirm the acid with lactate, ketones, osmolar gap, and renal function as the history directs.
Run it: Anion Gap
Decision support for qualified clinicians only — verify against current primary guidelines and your clinical judgement.