Anion Gap Calculator

How do you calculate the anion gap?

The anion gap is sodium minus the sum of chloride and bicarbonate: AG = Na − (Cl + HCO₃), with each value in mEq/L or mmol/L, the same number for these ions. To correct it for a low albumin, add 2.5 for each g/dL that albumin falls below 4.0 g/dL. Judge the result against the range on the laboratory’s own report.

What the gap is counting

Plasma carries equal positive and negative charge. A routine chemistry panel reports most of the positive side, as sodium, but only part of the negative side, as chloride and bicarbonate. The difference is the anions the panel leaves out, less the cations it leaves out. Albumin is the largest of the unreported anions, with phosphate, sulfate and organic anions such as lactate making up the rest, while potassium, calcium and magnesium are the unreported cations.

An acid whose anion is not on the panel raises the gap. Bicarbonate buffers the hydrogen ion and falls, and the new anion takes its place unseen. If bicarbonate is lost instead, from the gut in diarrhea or through the kidney in a renal tubular acidosis, or diluted by large volumes of 0.9 percent saline, chloride takes its place and the gap stays where it was. That split, a raised gap or a normal one, is the first branch in working up a metabolic acidosis, and the normal-gap kind is called hyperchloremic for that reason.

On a US basic metabolic panel the bicarbonate figure is the line marked CO2 or total CO2. It measures all the carbon dioxide the sample releases, which is mostly bicarbonate, while a blood gas report gives a bicarbonate calculated from pH and pCO2. Use whichever the laboratory calculated its own gap from.

Why no single normal range fits

Each laboratory sets the reference interval for its own method. About 8 to 12 mmol/L is the range long taught, and many laboratories on current methods print about 3 to 11 mmol/L, both calculated without potassium. Intervals have moved as measurement methods changed, which Kraut and Madias review in their 2007 account of the gap. A laboratory that adds potassium to the sum reports a gap higher by the potassium concentration and sets its range to match.

The calculator places the corrected gap against both common ranges and says where it falls in each, calling neither one normal.

Correcting the gap for albumin

Albumin carries a net negative charge at the pH of blood, so it supplies much of the normal gap. It falls in critical illness, liver disease, nephrotic syndrome and malnutrition, and the baseline gap falls with it, so an added acid can lift the gap only as far as a value that looks normal. Figge and colleagues put the size of the effect in 1998 at about 2.5 mmol/L of gap per g/dL of albumin, which is 0.25 per g/L.

The correction adds that back for every g/dL below 4.0 g/dL, the conventional normal albumin and the one this site uses throughout. Above 4.0 it turns negative, and the corrected gap is smaller than the measured one. US reports give albumin in g/dL, while UK, Canadian and Australian reports give g/L, ten times the number, so choose the unit in the albumin field instead of converting by hand.

What raises the gap

A raised gap means an unmeasured acid anion has accumulated. Mehta and colleagues grouped the causes under the mnemonic GOLD MARK in 2008: glycols (ethylene and propylene glycol), 5-oxoproline (pyroglutamic acid, linked to long-term acetaminophen use), L-lactate, D-lactate, methanol, aspirin, renal failure and ketoacidosis, whether diabetic, alcoholic or from starvation.

Methanol and ethylene glycol also raise the measured osmolality. The parent alcohols do so before they are broken down into the acids that raise the gap, so an unexplained osmolar gap beside a raised anion gap points at them. The serum osmolality calculator works out that second gap.

The delta ratio, and when to leave it alone

Once the gap is raised, use the delta ratio to check whether one process explains the whole fall in bicarbonate. It divides the rise in the corrected gap above 12 by the fall in bicarbonate below 24, the comparison Wrenn described in 1990 as the delta gap. In a single raised-gap acidosis each unit of acid adds about one unit of unmeasured anion and removes one unit of bicarbonate, so the ratio sits near 1.

• Under 0.8. Bicarbonate has fallen further than the gap has risen, so a normal-gap acidosis is running alongside the raised-gap one.
• 0.8 to 2. Consistent with a raised-gap acidosis on its own.
• Over 2. The gap has risen further than bicarbonate has fallen, which needs something holding bicarbonate up: a metabolic alkalosis, from vomiting for example, or the renal compensation for chronic CO2 retention.

These are teaching bands, the same ones the acid base interpreter applies, not guideline cut-offs. The calculator reads the ratio only when the corrected gap is above 12 and bicarbonate has fallen by at least 4, because near 24 the divisor is so small that a 1 mmol/L change in bicarbonate can double the ratio. It also measures the rise from a gap of 12, so on a method whose normal gap is lower the ratio is understated. In diabetic ketoacidosis, ketoanions lost in the urine stop counting towards the gap while bicarbonate stays low, so the ratio often runs near or below 1, more so once fluids restore urine flow.

Common mistakes

• Reading the uncorrected gap when albumin is low. Hypoalbuminemia is common in critical illness, where lactic acidosis is common too, and it is the usual way a raised gap hides inside the reference range.
• Typing a g/L albumin against g/dL. The number is ten times too large: in the bare formula, 35 g/L read as g/dL gives a correction of 2.5 × (4.0 − 35) = −77.5 mmol/L. This field refuses it, so switch the unit to g/L instead.
• Judging against someone else’s range. Read a gap from a method whose interval is 3 to 11 against 3 to 11, not 8 to 12, and a gap that includes potassium against a range that includes it too.
• Reading a delta ratio when bicarbonate is near normal. A fall of 1 or 2 mmol/L makes the ratio meaningless, and the calculator gives none for a fall under 4.
• Treating the gap as a diagnosis. It narrows a differential and says nothing about compensation. The acid base interpreter works a full blood gas through in order, including the step where a second disorder shows itself.