Biochemistry · Topic
Serum osmolality and osmolar gap !
The difference between measured and calculated osmolality reveals extra substances in the blood, such as methanol.
Updated 2026-11-01
Key facts
- Calculated osmolality = 2 × Na⁺ + glucose/18 + BUN/2.8 (glucose and BUN in mg/dL); in mmol/L: 2 × Na⁺ + glucose + urea.
- Osmolar gap = measured osmolality (by freezing-point depression) − calculated osmolality.
- A raised gap means unmeasured osmoles: methanol, ethylene glycol, ethanol, isopropanol, mannitol, glycerol.
- Methanol and ethylene glycol give a high osmolar gap early and a high anion gap later, as their acids form.
- Sodium is the main determinant of tonicity; urea counts in osmolality but not tonicity because it crosses membranes.
In detail
- The laboratory measures osmolality by cryoscopy; the reference value and the cut-off for a 'raised' gap vary by laboratory.
- The intact toxic alcohol is osmotically active and raises the osmolar gap without acidosis; once alcohol dehydrogenase metabolises it, it yields formic acid (methanol) or glycolic and oxalic acid (ethylene glycol), which open the anion gap.
- So a normal osmolar gap does not rule out a late poisoning: the alcohol may already have become acids.
- Ethanol raises the osmolar gap; some formulas add ethanol/4.6 (mg/dL) to correct for it.
- Calculated osmolality also helps in hyponatraemia: if the measured value is normal or high, it is pseudohyponatraemia or hyponatraemia from glucose or mannitol.
- Also called
- Osmolal gap, Calculated osmolality
Clinical notes
- With a high-AG acidosis, visual disturbance (methanol) or calcium oxalate crystals in the urine with kidney injury (ethylene glycol), the osmolar gap guides care while specific levels are awaited.
- Treatment of these poisonings blocks alcohol dehydrogenase (fomepizole or ethanol) and may need haemodialysis.
- Methanol poisoning from adulterated drinks causes outbreaks in Latin America.
Related conditions
Related
Test yourself
Think of the answer, then tap the question to see it.
How is serum osmolality calculated?
2 × Na⁺ + glucose/18 + BUN/2.8 with glucose and BUN in mg/dL (in mmol/L: 2 × Na⁺ + glucose + urea).
What does a raised osmolar gap indicate?
Osmoles not in the formula: toxic alcohols (methanol, ethylene glycol), ethanol, isopropanol, mannitol.
Why can a patient with ethylene glycol poisoning have a normal osmolar gap?
If seen late, the ethylene glycol has become glycolic and oxalic acids: the osmolar gap falls and the anion gap rises.
Why does urea not shift water between compartments?
It crosses cell membranes freely: it adds to osmolality but not to effective tonicity.
Educational information, not medical advice. For any symptom, see a health professional.
Sources: Osmolality Tests: MedlinePlus Medical Test (MedlinePlus, US National Library of Medicine, 2026); Osmolality blood test: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).
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Representative model, for educational purposes only.