Osmolal gap

Measured minus calculated serum osmolality — screens for unmeasured osmoles

Sources last checked: 2026-11-03

Osmolal gap

Measured minus calculated serum osmolality — screens for unmeasured osmoles

Measured serum osmolality (mOsm/kg)Freezing-point osmometer value from the same sample.Sodium (mmol/L)Glucose (mmol/L or mg/dL)mg/dL × 0.0555 = mmol/L. Pick the matching unit below.Urea / BUN (mmol/L or mg/dL)Urea and BUN are not the same in mg/dL: urea (mg/dL) ≈ BUN (mg/dL) × 2.14. Pick the matching unit below.

Unit of glucose and urea

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Uses the same calculated-osmolality formula as the serum osmolality calculator; other equations (e.g. with an ethanol term or different coefficients) give different gaps. Measured and calculated values must come from the same sample, and osmolality must be measured by freezing-point depression — vapour-pressure osmometers miss volatile alcohols.

Source: Smithline N, Gardner KD Jr. Gaps — anionic and osmolal. JAMA 1976;236(14):1594-1597.Open

Interpretation

≤ 10 — not raised	Within the range Smithline and Gardner regarded as normal. A normal gap does not exclude toxic alcohol ingestion: the normal range is wide and the parent alcohol is metabolised over time.
> 10 — raised	Smithline and Gardner regarded a gap above about 10 mOsm/kg as abnormal: unmeasured osmoles (ethanol, methanol, ethylene glycol, isopropanol, mannitol, glycine), pseudohyponatraemia from severe hyperlipidaemia or hyperproteinaemia, or laboratory error.

What is the Osmolal gap?

The osmolal gap is the difference between serum osmolality measured by freezing-point depression and the value calculated from sodium, glucose and urea. A raised gap means osmotically active substances are present that the calculation does not include — classically toxic alcohols. Smithline and Gardner described the concept in 1976 together with the anion gap.

When to use it

Suspected methanol, ethylene glycol or isopropanol ingestion
Unexplained high anion gap metabolic acidosis
Hyponatraemia with suspected pseudohyponatraemia (severe hyperlipidaemia or hyperproteinaemia)
Monitoring after mannitol or hypertonic glycine exposure

When not to use it

To rule out toxic alcohol ingestion on its own — a normal gap does not exclude it
When osmolality was measured by a vapour-pressure osmometer, which misses volatile alcohols

How it is calculated

Calculated osmolality = 2 × Na + glucose + urea (mmol/L) Osmolal gap = measured osmolality − calculated osmolality

Clinical pearls and limitations

Uses the same calculated-osmolality formula as the serum osmolality calculator; other equations (e.g. with an ethanol term or different coefficients) give different gaps. Measured and calculated values must come from the same sample, and osmolality must be measured by freezing-point depression — vapour-pressure osmometers miss volatile alcohols.
Ethanol is the most common cause of a raised gap; account for a measured ethanol level before blaming another alcohol.
Early after ingestion the gap is high and the anion gap normal; later, as the alcohol is metabolised to acids, the osmolal gap falls and the anion gap rises.
The baseline gap varies between individuals, so a value within the 'normal' range may still hide a substantial toxic alcohol level.
Measured and calculated osmolality must come from the same sample.

Frequently asked questions

What is a normal osmolal gap?

Smithline and Gardner considered a gap above about 10 mOsm/kg abnormal; the normal range is wide and differs with the equation used.

What causes a high osmolal gap?

Unmeasured osmoles such as ethanol, methanol, ethylene glycol, isopropanol, mannitol or glycine; pseudohyponatraemia from high lipids or protein; or laboratory error.

Osmolal gap and anion gap — what is the difference?

The osmolal gap detects uncharged osmoles such as the parent alcohol; the anion gap detects unmeasured anions such as the organic acid metabolites. Both are often raised in toxic alcohol poisoning, at different times.

Evidence and guidelines

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For healthcare professionals and medical students. These tools support, and do not replace, clinical judgement. Always check results against the original source and your local protocols.