Anion Gap Calculator

The anion gap is a piece of arithmetic on an ordinary electrolyte panel. Blood is electrically neutral, so the positive and negative charges have to balance. A routine panel measures one big cation (sodium) and two big anions (chloride and bicarbonate), and the cations come out ahead. That leftover is the “gap”: negative charge carried by things nobody measured, mostly albumin, plus phosphate, sulphate and small amounts of organic acid.

When an acid the body should not hold in quantity builds up (lactate, ketones, the breakdown products of a toxic alcohol), it uses up bicarbonate and leaves its own anion behind. Bicarbonate falls, chloride stays put, and the gap widens. That is the whole reason anyone calculates it.

The formula

AG = Na⁺ − (Cl⁻ + HCO₃⁻)
All three are serum values in mEq/L, which for these ions is the same number as mmol/L.

The normal range moved, and plenty of references never noticed

Older textbooks give 8 to 16 mEq/L, or “12 plus or minus 4”. That range came from flame photometry. Modern analyzers use ion-selective electrodes, which read chloride a few points higher, and the gap fell with it. Winter and colleagues showed this in 1990: one of their labs had a normal range of 3 to 11, and most healthy people sat at 6 or below.

The difference is not academic. Against the old range a gap of 14 looks fine. On a modern analyzer it is three points high. This calculator uses 3 to 11 unless you type in the range printed on your own lab report, and you should, because labs differ.

Correcting for albumin

Albumin is the biggest unmeasured anion, so when albumin falls the gap falls with it and can hide an acidosis. Figge and colleagues (1998) put the effect at about 2.5 mEq/L for every 1 g/dL that albumin sits below a normal of about 4.0. A hospital patient with an albumin of 2.0 and a gap of 10 has a corrected gap of 15, which is high. Enter albumin and the calculator applies the correction. It takes g/dL (3.5 to 5.0 is normal) or g/L (35 to 50).

Skipping this step is the most common way a raised gap gets missed on a ward, where low albumin is the rule rather than the exception.

What a high gap points to

For decades students learned MUDPILES. In 2008 Mehta, Emmett and Emmett proposed GOLD MARK in The Lancet as a replacement, dropping causes that had become rare (paraldehyde, iron, isoniazid) and adding three the old list missed:

• Glycols: ethylene glycol (antifreeze), and propylene glycol, the solvent in some intravenous drugs such as lorazepam
• Oxoproline (pyroglutamic acid), usually from long-term paracetamol (acetaminophen) use in someone malnourished or very ill
• L-lactate: shock, sepsis, seizures, metformin with failing kidneys
• D-lactate, made by gut bacteria after short-bowel surgery
• Methanol
• Aspirin in overdose
• Renal failure
• Ketoacidosis: diabetic, alcoholic or starvation

The big three, lactate, ketones and kidney failure, cover most of what any hospital sees. The toxic alcohols are rarer but time-critical, and a raised osmolar gap next to a raised anion gap points hard at them.

A normal or low gap

A normal gap with a low bicarbonate is a different problem: the body has lost bicarbonate rather than gained an acid, and chloride rises to take its place. Diarrhoea, renal tubular acidosis, large volumes of saline and acetazolamide are the usual causes.

A gap below the range is uncommon. Kraut and Madias, in their 2007 review, name laboratory error and low albumin as the usual explanations. The rarer ones are an IgG paraprotein in myeloma, bromide or iodide (which many analyzers read as chloride), and very high lithium, calcium or magnesium.

The delta ratio

When the gap is high, the delta ratio asks whether the rise in the gap matches the fall in bicarbonate:
Delta ratio = (AG − normal AG) ÷ (24 − HCO₃⁻)

Between about 0.8 and 2, a high-gap acidosis explains the whole picture. Under 0.4, a normal-gap acidosis is doing most of the work, and 0.4 to 0.8 suggests both at once. Above 2, bicarbonate fell less than the gap rose, which usually means a metabolic alkalosis alongside (vomiting, diuretics) or a long-standing respiratory acidosis that had pushed bicarbonate up beforehand. The calculator takes the normal gap as the middle of your reference range. Read the bands loosely: Kraut and Madias found the ratio varies too much between patients to diagnose a mixed disorder on its own.

Worked example: a healthy panel

Na⁺ 140, Cl⁻ 106, HCO₃⁻ 26.
AG = 140 − (106 + 26) = 8 mEq/L, inside 3 to 11.

Worked example: diabetic ketoacidosis

Na⁺ 138, Cl⁻ 98, HCO₃⁻ 14.
AG = 138 − (98 + 14) = 26 mEq/L, fifteen above the top of the range.
Delta ratio = (26 − 7) ÷ (24 − 14) = 1.9, a high-gap acidosis on its own.

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