Anion Gap Calculator

Anion Gap Calculator

Calculate the serum anion gap from sodium, chloride and bicarbonate — with the interval that belongs to this formula, not the one the textbooks printed before ion-selective electrodes.

Anion Gap

Na⁺ − (Cl⁻ + HCO₃⁻)
11.0mmol/LExample

Na⁺ 140, Cl⁻ 105, HCO₃⁻ 24 mmol/L

Formula

Anion gap = Na⁺ − (Cl⁻ + HCO₃⁻)
Potassium-inclusive form: AG = (Na⁺ + K⁺) − (Cl⁻ + HCO₃⁻)
Na⁺ − (Cl⁻ + HCO₃⁻)
the form used here; reference interval 8–12 mmol/L
+ K⁺
some laboratories include potassium, which adds a whole normal serum potassium — about 4 mmol/L — and shifts the interval to roughly 12–16. The two forms are not interchangeable
8–12, not 12–16
ion-selective-electrode chloride methods read higher than the older colorimetric ones, which lowered the gap. The textbook 12–16 predates them
albumin
the largest unmeasured anion. The gap falls about 2.5 mmol/L for every 10 g/L (1 g/dL) fall in albumin, so correct before interpreting

Worked example

Na⁺ 140, Cl⁻ 105, HCO₃⁻ 24 mmol/L
105 + 24 = 129 mmol/L of measured anions
140 − 129 = 11.0 mmol/L
Within the 8–12 mmol/L interval for this formula — but only 1 mmol/L below its upper limit
On the potassium-inclusive formula with a potassium of 4.0, the same patient would read 15.0, which is also normal for that formula

Which formula, which interval

FormulaReference intervalNote
Na⁺ − (Cl⁻ + HCO₃⁻)8 – 12 mmol/LThe form on this page, and the commoner one in UK practice
(Na⁺ + K⁺) − (Cl⁻ + HCO₃⁻)12 – 16 mmol/LRuns about 4 mmol/L higher — the whole of a normal serum potassium
Older textbook figure, either formula12 – 16 mmol/LPredates ion-selective-electrode chloride; do not apply it to a modern analyser
A gap of 14 is entirely normal on the potassium-inclusive formula and clearly raised on the potassium-free one. Know which your laboratory reports before comparing a result against any published interval.

Causes by direction

Raised gapNormal gap (hyperchloraemic)Low gap
Lactic acidosis — sepsis, ischaemia, metforminDiarrhoea and other gastrointestinal bicarbonate lossHypoalbuminaemia, much the commonest cause
Diabetic, alcoholic and starvation ketoacidosisRenal tubular acidosis, types 1, 2 and 4Cationic paraprotein, typically IgG myeloma
Renal failure — retained urate, phosphate and sulfateLarge-volume 0.9% sodium chlorideLithium or bromide intoxication
Toxic alcohols, salicylate, pyroglutamic acidCarbonic anhydrase inhibitors, ureterosigmoidostomySevere hypercalcaemia or hypermagnesaemia
RhabdomyolysisEarly chronic kidney diseaseLaboratory error — repeat before believing it
GOLDMARK — glycols, oxoproline, L-lactate, D-lactate, methanol, aspirin, renal failure, ketoacidosis — has largely replaced MUDPILES for the raised-gap column, because it drops causes that no longer occur and adds ones that do.

An interval that moved, and a formula that has two versions

Plasma is electrically neutral, so the measured cations and the measured anions must be balanced by everything that is not measured. The anion gap makes that difference visible: subtract chloride and bicarbonate from sodium and what is left is the unmeasured anions, chiefly albumin, with smaller contributions from phosphate, sulfate and organic acids. A gap that opens means an acid has been added whose anion the analyser does not see.

Two things about the reference interval trip people up. First, some laboratories include potassium, reporting (Na⁺ + K⁺) − (Cl⁻ + HCO₃⁻), which adds a whole normal serum potassium and lifts the interval by roughly 4 mmol/L to 12–16. A gap of 14 is unremarkable on that formula and clearly raised on this one, so the two are not interchangeable and a result should never be compared against the wrong interval. Second, the familiar 12–16 figure belongs to older colorimetric chloride methods. Ion-selective electrodes read chloride higher, which lowered the gap, and 8–12 has been the interval for the potassium-free formula for over thirty years. A gap of 12 on a modern analyser is at the top of the range, not in the middle.

The third correction is albumin. Albumin is negatively charged at physiological pH and is the single largest unmeasured anion, so the gap falls by about 2.5 mmol/L for every 10 g/L — one g/dL — that albumin falls below normal. In a critically ill patient with an albumin of 20 g/L, a measured gap of 11 is a corrected gap of about 16, and a significant high-anion-gap acidosis has been reported as normal. The albumin-corrected anion gap calculator does that arithmetic.

Used properly, the gap sorts a metabolic acidosis into two families and points at the next test. A raised gap sends you to lactate, ketones, renal function and the osmolal gap; a normal gap sends you to gastrointestinal losses, saline, and renal tubular acidosis, where the urine anion gap distinguishes them. The delta ratio then asks whether a second disorder is hiding behind the first.

Frequently asked questions

What is a normal anion gap?

For the Na⁺ − (Cl⁻ + HCO₃⁻) formula used here, 8 to 12 mmol/L on a modern ion-selective-electrode analyser. If your laboratory includes potassium, the interval is about 4 mmol/L higher, roughly 12 to 16, because a whole normal serum potassium has been added.

Why do textbooks say 12 to 16?

That interval belongs to the older colorimetric chloride methods. Ion-selective electrodes read chloride higher, which lowers the calculated gap, and the interval for the potassium-free formula fell to 8 to 12. Applying the old figure to a modern analyser under-calls raised gaps.

Should potassium be included in the formula?

Either form is valid, but they are not interchangeable and each has its own interval. The potassium-free version is commoner in UK practice and has an interval of 8 to 12; the potassium-inclusive version runs about 4 mmol/L higher. Use whichever your laboratory reports, with its matching interval.

Why must the anion gap be corrected for albumin?

Albumin is the largest unmeasured anion, so a low albumin lowers the measured gap by about 2.5 mmol/L for every 10 g/L it falls. In hypoalbuminaemic patients this can hide a genuine high-anion-gap acidosis, which is why the corrected gap should be used in critical illness.

What causes a low anion gap?

Hypoalbuminaemia is much the commonest. Others are a cationic paraprotein in myeloma, lithium or bromide intoxication, severe hypercalcaemia or hypermagnesaemia, and laboratory error. A genuinely low gap is unusual enough to be worth repeating before it is explained.

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References

  1. Kraut JA, Madias NE. Serum anion gap: its uses and limitations in clinical medicine. Clin J Am Soc Nephrol. 2007;2(1):162–174.
  2. Winter SD, Pearson JR, Gabow PA, Schultz AL, Lepoff RB. The fall of the serum anion gap. Arch Intern Med. 1990;150(2):311–313.
  3. Figge J, Jabor A, Kazda A, Fencl V. Anion gap and hypoalbuminemia. Crit Care Med. 1998;26(11):1807–1810.