Anion Gap Acidosis Cause Identifier
Anion Gap Acidosis Cause Identifier
Screen a raised anion gap against lactate, ketones and the osmolal gap to narrow the cause using the GOLDMARK framework.
Anion Gap Acidosis Cause Identifier
GOLDMARK screenAnion gap 26 mmol/L, lactate 1.4, ketones 0.3, osmolal gap 22
How this identifier reasons through the gap
- albumin correction
- add roughly 2.5 mmol/L to the measured gap for every 1 g/dL that albumin is below 4 g/dL
- osmolal gap
- measured osmolality minus calculated osmolality; a gap above about 10 mOsm/kg suggests an unmeasured osmotically active substance such as a toxic alcohol
- pyroglutamic acidosis
- an under-recognised cause from chronic therapeutic paracetamol, typically in a malnourished or unwell patient
Worked example
Anion gap 26 mmol/L, lactate 1.4, ketones 0.3, osmolal gap 22
Anion gap 26 > 12 → high anion gap acidosis present
Lactate 1.4 < 4 and ketones 0.3 < 3 → not lactic or keto-acidosis
Osmolal gap 22 > 10 → toxic alcohol likely
GOLDMARK causes of a high anion gap acidosis
| Letter | Cause |
|---|---|
| G | Glycols — ethylene glycol, propylene glycol |
| O | Oxoproline — pyroglutamic acidosis, chronic paracetamol |
| L | L-lactate — the common lactic acidosis |
| D | D-lactate — short bowel syndrome, gut bacterial production |
| M | Methanol |
| A | Aspirin (salicylate) |
| R | Renal failure — retained anions |
| K | Ketoacidosis — diabetic, alcoholic, starvation |
Working through a raised anion gap
A raised anion gap means an unmeasured anion is accumulating, and the differential is usefully organised by the mnemonic GOLDMARK — Glycols (ethylene and propylene), Oxoproline (pyroglutamic acid, from chronic therapeutic paracetamol), L-lactate, D-lactate, Methanol, Aspirin, Renal failure, and Ketoacidosis. It replaced the older MUDPILES mnemonic because it better reflects the causes seen in current practice and drops several that are now rare or reclassified.
The albumin correction is easy to miss and changes the answer. Hypoalbuminaemia lowers the measured anion gap by roughly 2.5 mmol/L for every 1 g/dL that albumin sits below 4 g/dL, because albumin itself is an unmeasured anion. A critically ill patient with an albumin of 2 g/dL and a calculated gap of 12 — apparently normal — actually has a corrected gap of about 17, and a real high anion gap acidosis that a normal-looking number would otherwise conceal.
Lactate and ketones are checked first because they are the commonest causes and the fastest to confirm. When both are unremarkable and the anion gap remains unexplained, the osmolal gap becomes the key discriminator: a gap above roughly 10 mOsm/kg points to an unmeasured osmotically active substance, most urgently a toxic alcohol, which needs treatment while confirmatory levels are awaited.
Pyroglutamic acidosis is genuinely under-recognised. It arises from chronic therapeutic-dose paracetamol, typically in a malnourished, unwell or glutathione-depleted patient, often female, presenting with a large unexplained anion gap and no other obvious cause — a diagnosis that is easy to miss unless specifically considered.
Frequently asked questions
What does GOLDMARK stand for?
Glycols, Oxoproline, L-lactate, D-lactate, Methanol, Aspirin, Renal failure, Ketoacidosis — the current framework for a high anion gap metabolic acidosis, which replaced the older MUDPILES mnemonic.
How do I correct the anion gap for a low albumin?
Add about 2.5 mmol/L to the measured gap for every 1 g/dL that albumin sits below 4 g/dL. A critically ill patient with hypoalbuminaemia can have a genuinely raised gap that reads as normal until corrected.
What does a raised osmolal gap mean?
An unmeasured osmotically active substance is present, most urgently a toxic alcohol such as ethylene glycol or methanol. It is the key discriminator once lactate and ketones have been excluded.
What is pyroglutamic acidosis?
An under-recognised cause of a high anion gap from chronic therapeutic paracetamol use, typically in a malnourished or unwell patient. It should be considered when the gap is large and otherwise unexplained.
Related calculators
References
- Mehta AN, Emmett JB, Emmett M. GOLD MARK: an anion gap mnemonic for the 21st century. Lancet. 2008;372(9642):892.
- Kraut JA, Madias NE. Serum anion gap: its uses and limitations in clinical medicine. Clin J Am Soc Nephrol. 2007;2(1):162–174.