Anion gap in cats and dogs

What it shows

Blood carries as many positive charges as negative ones. A chemistry analyser measures only some of them: sodium and potassium make up about 95% of the positive ions, chloride and bicarbonate about 85% of the negative ones. The anion gap is the difference between these measured values:

anion gap = (sodium + potassium) − (chloride + bicarbonate)

Some labs leave potassium out of the formula; this is not recommended, and results calculated with and without potassium cannot be compared directly. The gap is usually positive, because the uncounted negative particles outnumber the uncounted positive ones. In a healthy animal the largest share comes from albumin; the rest are acids — lactate, phosphate, sulphate, ketones — and, in poisoning, toxins and their products. Uncounted positive particles include gamma-globulins (a group of blood proteins that includes antibodies), while ionised calcium and magnesium matter little.

Higher than reference — what it may be a sign of

• Extra acids in the blood (high anion gap acidosis: acids are added and use up bicarbonate) — the main cause: lactate from poor circulation, ketones in diabetic ketoacidosis, acids that build up in kidney failure, and toxins such as ethylene glycol (antifreeze), salicylate and methanol. Within 3 hours of swallowing a toxic amount of ethylene glycol, dogs and cats have metabolic acidosis and an increased anion gap; this is an emergency, and the vet decides what to do.
• Dehydration — albumin rises, and with it the gap, mildly.
• Alkalosis — usually a mild rise, under 3 mEq/L.
• Medicines that contain sodium, such as sodium salts and penicillin, which raise measured sodium.
• Sample artefact — uncommon: in stored blood, cells keep making lactate, which uses up bicarbonate.

Lower than reference

A low anion gap is usually a laboratory artefact or low albumin. A fall in albumin of 1 g/dL (10 g/L) may lower the gap by 2.5–3 mEq/L. Bromide, a seizure medicine, is read by the analyser as chloride, so chloride comes out falsely high and the gap low. Fluids that contain bicarbonate can lower it too; rarely, severe muscle injury falsely raises the bicarbonate reading.

Look at together with

• Bicarbonate — the key partner. High gap with low bicarbonate means extra acids. Normal gap with low bicarbonate means bicarbonate has been lost or chloride retained (hyperchloraemic acidosis, meaning acidosis with high chloride) — for example renal tubular acidosis, a defect of the kidney tubules in dogs and cats.
• Chloride and sodium — read together, they help spot a second disturbance hidden behind the first.
• Albumin — low albumin can hide a raised gap.
• Lactate, glucose with urine ketones, and creatinine — the usual places to look for the acid behind a high gap.

Units and conversion

The anion gap is reported in mmol/L or mEq/L — for these ions the same number. It is not measured but calculated from the four electrolytes on the same form, so any error in one of them carries into the gap. In the app each row keeps the unit printed on the form.

Reference range

The reference range is on your lab’s form, and it depends on the formula — with or without potassium — and on the analyser. The gap is read together with bicarbonate and albumin, not on its own. Dehydration can mask low albumin, and when two disturbances pull in opposite directions bicarbonate may look normal while the gap is high — that is why vets look at the gap even when bicarbonate is within range. A high gap is a reason to look for the cause, not a diagnosis by itself.

Cats and dogs

Sources

1. eClinPath (Cornell University) — Anion gap
2. eClinPath (Cornell University) — Acid-base: laboratory detection (TCO2, anion gap)
3. eClinPath (Cornell University) — Chloride
4. Regehr T. Ethylene Glycol Toxicosis in Animals. Merck Veterinary Manual
5. Van Vertloo L. Renal Tubular Defects in Dogs and Cats. Merck Veterinary Manual