Anion gap blood test: how it's calculated and what it means

How the anion gap is calculated

Blood always has equal positive and negative charges. Labs measure the main positive ion (sodium) and the main negative ones (chloride and bicarbonate). The rest of the negative charge comes from things not on the panel, mostly albumin. The gap is an estimate of those unmeasured negative charges:

Anion gap = sodium minus (chloride plus bicarbonate), in mEq/L or mmol/L. Potassium is often left out because it adds little; some labs include it, which makes the number a few points higher.

All three inputs come from an electrolyte panel or a CMP, so you don't need an extra blood draw.

Why normal ranges differ so much

The normal range depends on the lab's formula and analyzer. Before the 1980s the usual range was about 8 to 16 mEq/L. When newer analyzers arrived, some labs revised it to about 3 to 9 mEq/L. Your lab's printed range is the one that counts.

Gabriel's optimal band (11 to 16 mmol/L) fits labs that include potassium in the calculation. If your lab's printed upper limit is 16 or lower, your lab uses a different method, so go by your lab's range rather than the optimal band.

What a high anion gap can mean

A high gap usually means an acid the panel doesn't measure has built up (a high anion gap metabolic acidosis). Causes include:

• Ketoacidosis, from uncontrolled diabetes, heavy alcohol use or starvation.
• Lactic acidosis, for example from shock, severe infection or very low oxygen.
• Kidney failure, when the kidneys can't clear acids.
• Poisonings, such as aspirin (salicylate) overdose, antifreeze (ethylene glycol) or methanol.
• Dehydration, which concentrates everything in the blood.

A normal gap does not rule out acidosis. Some causes, such as long-lasting diarrhea, lower bicarbonate and raise chloride at the same time, so the gap stays normal. See chloride.

What a low anion gap can mean

• A lab or sample error. The most common cause. A repeat test is the usual first step.
• Low albumin. Albumin carries much of the unmeasured negative charge. The gap falls about 2.5 mEq/L for every 1 g/dL drop in albumin, which can also hide a real high gap. See albumin.
• Extra antibody proteins, as in multiple myeloma and related conditions. See globulin.
• Lithium at high levels, and bromide or iodide, which some analyzers read as chloride.
• High calcium or magnesium.

What to do with an abnormal result

1. Check it against your lab's range, not a number from the internet.
2. Look at CO2, chloride, glucose, kidney tests and albumin on the same report. The pattern matters more than the gap alone.
3. Ask whether a repeat test is needed, especially for a low gap.
4. Tell your clinician about medications and supplements, including aspirin, metformin and lithium.

Get emergency care if a high anion gap comes with confusion, fast or deep breathing, vomiting, severe belly pain, fruity-smelling breath, or a possible swallowed poison or medication overdose.