1Osmolality Formula & Osmol Gap
Normal range: 275–295 mOsm/kg
Osmol Gap = Measured Osmolality − Calculated Osmolality
Normal osmol gap: <10 mOsm/kg (some labs <15)
Causes of Elevated Osmol Gap (>10 mOsm/kg)
- Toxic alcohols: Methanol, ethylene glycol, isopropanol, propylene glycol — most important cause to exclude
- Ketoacidosis: DKA, alcoholic ketoacidosis — acetone is osmotically active
- Renal failure: Accumulation of unmeasured solutes
- Mannitol infusion: Common in neurosurgery/neurology
- Severe hyperlipidaemia or hyperproteinaemia: Pseudohyponatraemia
- Glycine, sorbitol: Irrigation fluid absorption (TURP syndrome)
High Osmol Gap + High Anion Gap Metabolic Acidosis
The combination of elevated osmol gap AND elevated anion gap metabolic acidosis should immediately raise suspicion for methanol or ethylene glycol poisoning. Both are initially osmotically active (elevating osmol gap) but are subsequently metabolised to toxic acids (formate from methanol → anion gap acidosis; oxalate from ethylene glycol → anion gap acidosis). The osmol gap may normalise as the parent alcohol is metabolised — leaving only the anion gap acidosis. Do not be falsely reassured by a normal osmol gap late in the course.
Causes of Hyperosmolality (>295 mOsm/kg)
- Hypernatraemia (most common) — water deficit, diabetes insipidus
- Hyperglycaemia — hyperosmolar hyperglycaemic state (HHS)
- Uraemia — elevated BUN in acute/chronic kidney failure
- Toxic alcohol ingestion
- Mannitol infusion
2Frequently asked questions
What is serum osmolality and how is it calculated?
Serum osmolality estimates the concentration of all osmotically active particles in plasma. Calculated formula: Osmolality (mOsm/kg) = 2 × Na + Glucose (mg/dL)/18 + BUN (mg/dL)/2.8. In SI units: 2 × Na + Glucose (mmol/L) + Urea (mmol/L). Normal range: 275–295 mOsm/kg. Measured osmolality by freezing-point depression is the gold standard.
What is the osmol gap and what causes it?
Osmol gap = Measured osmolality − Calculated osmolality. Normal osmol gap: <10 mOsm/kg. An elevated osmol gap (>10–15) indicates unmeasured osmoles in plasma — caused by: toxic alcohols (methanol, ethylene glycol, isopropanol — most important causes), severe lactic acidosis, ketoacidosis (acetone), mannitol infusion, or propylene glycol toxicity. A high osmol gap in a comatose patient should immediately raise suspicion for toxic alcohol ingestion.
What causes hyperosmolaemia?
Hyperosmolaemia (>295 mOsm/kg): hypernatraemia (sodium is the main determinant), severe hyperglycaemia (diabetic hyperosmolar state — serum osmolality can exceed 320–340 mOsm/kg), uraemia (BUN contributes but is an ineffective osmole — crosses cell membranes freely), toxic alcohol ingestion (effective osmoles — cause cellular dehydration). Hyperosmolar hyperglycaemic state (HHS): osmolality >320, glucose >600 mg/dL, no significant ketosis.
What is effective vs ineffective osmolality?
Effective osmolality (tonicity) = 2 × Na + Glucose/18. It excludes BUN because urea freely crosses cell membranes and does not cause osmotic water shifts between compartments. Tonicity determines cellular hydration status and is clinically more relevant than total osmolality. Normal tonicity: 275–290 mOsm/kg. Hypertonicity causes cellular dehydration (brain shrinkage, cerebral haemorrhage risk).
How is hyperosmolar hyperglycaemic state managed?
HHS management: IV fluid resuscitation (0.9% saline initially — typically 1–2L in first hour, then 0.45% saline if Na corrected or normal), low-dose insulin infusion (only after adequate hydration — insulin without fluids worsens hypotension), potassium replacement (severe hypokalaemia risk as glucose normalises), VTE prophylaxis (high thrombosis risk), treat precipitant (infection most common). Target: gradual glucose reduction ~50–70 mg/dL/hour, osmolality reduction <3 mOsm/kg/hour.
What is SIADH and how does serum osmolality help diagnose it?
SIADH (Syndrome of Inappropriate ADH secretion) causes euvolaemic hyponatraemia with: serum osmolality <275 mOsm/kg, urine osmolality >100 mOsm/kg (inappropriately concentrated), urine sodium >20–40 mEq/L (sodium-wasting despite hyponatraemia), normal renal, adrenal, and thyroid function. Causes: CNS disease, pulmonary disease, malignancy (ectopic ADH), drugs (SSRIs, carbamazepine, cyclophosphamide, NSAIDs). Treatment: fluid restriction ±salt tablets; tolvaptan for severe/refractory cases.
Medical disclaimer: This calculator is for educational and clinical decision-support purposes only. It does not replace clinical judgment or specialist consultation. RxMedCalc is not liable for clinical decisions made solely on this tool.