[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Biochemistry](https://durgical.com/en/biochemistry/) › Serum osmolality and osmolar gap [Biochemistry](https://durgical.com/en/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 - [High anion gap metabolic acidosis](https://durgical.com/en/conditions/high-anion-gap-metabolic-acidosis/) - [Hyponatraemia](https://durgical.com/en/conditions/hyponatraemia/) - [Hypernatraemia](https://durgical.com/en/conditions/hypernatraemia/) ## Related - [Anion gap and delta ratio](https://durgical.com/en/biochemistry/topics/anion-gap-and-delta-ratio/) - [Acid–base interpretation (step by step)](https://durgical.com/en/biochemistry/topics/acid-base-interpretation/) - [Glucose](https://durgical.com/en/biochemistry/molecules/glucose/) - [Urea](https://durgical.com/en/biochemistry/molecules/urea/) ## 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. [Add to my cards (4)](https://durgical.app/estudiar/?add=/en/biochemistry/topics/serum-osmolality-and-osmolar-gap/) Educational information, not medical advice. For any symptom, see a health professional. Sources: [Osmolality Tests: MedlinePlus Medical Test](https://medlineplus.gov/lab-tests/osmolality-tests/) (MedlinePlus, US National Library of Medicine, 2026); [Osmolality blood test: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/003463.htm) (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). [← All of biochemistry](https://durgical.com/en/biochemistry/) ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/biochemistry/topics/serum-osmolality-and-osmolar-gap/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/biochemistry/topics/serum-osmolality-and-osmolar-gap/