Anion Gap Calculator

Accounting for unmeasured ions

Blood is electrically neutral, so measured cations and anions should balance. They do not, because routine panels measure sodium but not all the anions.

The anion gap is sodium minus the sum of chloride and bicarbonate, and it represents the unmeasured anions: albumin mostly, plus phosphate, sulphate and organic acids.

Some laboratories include potassium in the calculation, which raises the normal range by roughly the potassium concentration. Knowing which convention a result used is necessary to interpret it against a reference range.

The normal range and why it moved

The classically taught normal range of 8 to 16 was derived using older analytical methods. Modern ion-selective electrodes measure chloride differently, and the contemporary normal range is lower, commonly around 3 to 11.

Which means a gap of 14 is elevated by modern standards and normal by the range many clinicians learned. That discrepancy has been the subject of a good deal of published comment.

Local laboratory reference ranges account for the local assay and should be used in preference to any remembered figure.

Correcting for albumin

Albumin is the largest contributor to the anion gap, so hypoalbuminaemia lowers the gap and can mask a genuine high anion gap acidosis.

The correction adds roughly 2.5 to the gap for each gram per decilitre that albumin falls below 4, or approximately 0.25 for each gram per litre below 40 in SI units.

This matters because hypoalbuminaemia is common in exactly the critically ill patients most likely to have a metabolic acidosis. An uncorrected gap in a patient with an albumin of 20 can appear normal while a substantial acidosis is present.

What a raised gap indicates

The traditional mnemonic MUDPILES covers methanol, uraemia, diabetic ketoacidosis, propylene glycol, isoniazid or iron, lactic acidosis, ethylene glycol and salicylates.

GOLDMARK is a more contemporary version reflecting current epidemiology: glycols, oxoproline, L-lactate, D-lactate, methanol, aspirin, renal failure and ketoacidosis.

Lactic acidosis, ketoacidosis and renal failure account for the overwhelming majority in practice. The toxic alcohols are rare, dangerous and time-critical, which is why they retain a place in the mnemonic despite their frequency.

The delta gap

In a pure high anion gap acidosis, the rise in the gap should approximately match the fall in bicarbonate. When it does not, a second acid-base disorder is present.

A rise in the gap substantially exceeding the bicarbonate fall suggests a coexisting metabolic alkalosis. A bicarbonate fall exceeding the gap rise suggests a coexisting normal anion gap acidosis.

That analysis identifies mixed disorders that would otherwise be missed, and it is a genuinely useful piece of bedside reasoning. It is also exactly the kind of interpretation that requires the whole clinical picture, which is why this page calculates a number and stops there.

The osmolar gap deserves a mention alongside it, because the two are read together when a toxic alcohol is suspected. Measured serum osmolality minus calculated osmolality gives the osmolar gap, and a raised gap alongside a raised anion gap points strongly towards methanol or ethylene glycol. Early in a poisoning the osmolar gap can be raised before the anion gap has risen, since the parent alcohol is osmotically active before it is metabolised to acid, which is a genuinely time-critical distinction.