Measured minus calculated osmolality, raised by unmeasured osmoles
Expansion
Calculated osmolality = 2 x sodium + urea + glucose (all mmol/l)
Osmolar gap = measured - calculated, normally under 10 mOsm/kg.
A raised gap indicates unmeasured osmoles:
- Ethanol (the commonest cause by far)
- Methanol, ethylene glycol, isopropanol, propylene glycol
- Mannitol, glycine irrigation fluid
- Severe hyperlipidaemia or hyperproteinaemia (pseudohyponatraemia)
- Ketoacidosis and lactic acidosis contribute modestly
The combination that matters is a high osmolar gap with a high anion gap metabolic acidosis, which points to methanol or ethylene glycol. The parent alcohols create the osmolar gap; their metabolites (formic acid, and glycolic then oxalic acid) create the acidosis. Early on the gap is high and the acidosis mild; later the reverse, as the parent compound is metabolised.
Clues to each: methanol causes visual loss and optic disc oedema; ethylene glycol causes calcium oxalate crystalluria, hypocalcaemia and renal failure.
Treatment is fomepizole or ethanol to block alcohol dehydrogenase, plus haemodialysis.