Serum osmolality (calculated)

Calculated serum osmolality from sodium, glucose and urea

Sources last checked: 2026-10-27

Serum osmolality (calculated)

Calculated serum osmolality from sodium, glucose and urea

Unit of glucose and urea
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A calculated value, not a measurement: it does not detect unmeasured osmoles (ethanol, methanol, ethylene glycol, mannitol), which is why the osmolal gap against a measured value matters. Urea crosses cell membranes freely, so the calculated value is total, not effective (tonicity) osmolality.

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

What is the Serum osmolality (calculated)?

Calculated serum osmolality estimates the concentration of osmotically active particles from the main measured solutes: sodium (counted twice for its accompanying anions), glucose and urea. The formula was popularised by Smithline and Gardner (1976) together with the concept of the osmolal gap — the difference between measured and calculated osmolality that points to unmeasured osmoles.

When to use it

  • Work-up of hyponatraemia or hypernatraemia alongside a measured osmolality
  • Suspected toxic alcohol ingestion (methanol, ethylene glycol) — to compute the osmolal gap
  • Hyperglycaemic crises, where glucose contributes substantially to osmolality

When not to use it

  • As a replacement for measured osmolality when the distinction matters (e.g. pseudohyponatraemia, toxic alcohols)
  • Severe hyperlipidaemia or hyperproteinaemia with indirect sodium measurement, which underestimates sodium

How it is calculated

Calculated osmolality = 2 × Na + glucose + urea (all in mmol/L) Conventional units: 2 × Na + glucose (mg/dL)/18 + BUN (mg/dL)/2.8 Osmolal gap = measured − calculated osmolality

Clinical pearls and limitations

  • A calculated value, not a measurement: it does not detect unmeasured osmoles (ethanol, methanol, ethylene glycol, mannitol), which is why the osmolal gap against a measured value matters. Urea crosses cell membranes freely, so the calculated value is total, not effective (tonicity) osmolality.
  • Osmolal gap = measured − calculated osmolality; Smithline and Gardner considered a gap above about 10 mOsm/kg abnormal, but the normal range is wide and a normal gap does not exclude toxic alcohol ingestion.
  • Ethanol is the most common cause of a raised gap; some formulas add ethanol (mmol/L) to the calculation.
  • Urea is an ineffective osmole: effective osmolality (tonicity) = 2 × Na + glucose.
  • In mg/dL, glucose/18 and BUN/2.8 convert to mmol/L; German and Turkish labs often report urea rather than BUN, which is why a separate urea option is offered.

Frequently asked questions

What is the formula for calculated serum osmolality?

2 × Na + glucose + urea, all in mmol/L. In US units: 2 × Na + glucose/18 + BUN/2.8.

How do I calculate the osmolal gap?

Subtract the calculated value from the measured osmolality (freezing-point osmometer). A gap well above 10 mOsm/kg suggests unmeasured osmoles such as ethanol, methanol, ethylene glycol or mannitol.

Osmolality or osmolarity?

Osmolality is per kg of water and is what the laboratory measures; the calculated formula gives an osmolarity-like estimate that is compared with it directly in practice.

Evidence and guidelines

  1. Primary source: Smithline N, Gardner KD Jr. Gaps — anionic and osmolal. JAMA 1976;236(14):1594-1597.
  2. Spasovski G, Vanholder R, Allolio B et al. Clinical practice guideline on diagnosis and treatment of hyponatraemia. Eur J Endocrinol 2014;170(3):G1-G47 (ESE, ESICM, ERBP).

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