What Osmolality Measures
Osmolality measures the concentration of solute particles (osmoles) per kilogram of water in a solution, expressed as mOsm/kg, and serves as an indicator of the osmotic pressure of plasma or other biological fluids. 1, 2
Core Definition and Measurement
- Osmolality quantifies the number of milliosmoles of solutes per kilogram of water in a solution, distinguishing it from osmolarity (which measures per liter of solution rather than per kilogram of water) 3
- The measurement reflects the total concentration of all dissolved particles that contribute to osmotic pressure, regardless of their molecular weight or charge 3
- Direct measurement via freezing point depression or vapor pressure osmometry is the gold standard method, though calculated values are acceptable for screening purposes 1
Major Contributors to Plasma Osmolality
Sodium and its associated anions (chloride and bicarbonate) are the primary determinants of serum osmolality under normal conditions, accounting for the majority of total osmotic load 2
- Glucose contributes significantly to osmolality, particularly in hyperglycemic states 1
- Blood urea nitrogen (BUN) affects measured osmolality but not tonicity, as urea freely crosses cell membranes 1
- Potassium contributes to a lesser extent than sodium, with normal ranges of 3.5-5.3 mEq/L 2
Standard Calculation Formula
The most widely accepted formula for calculating serum osmolality is: 2 × [Na (mEq/L)] + glucose (mg/dL)/18 + BUN (mg/dL)/2.8 1, 3
- This formula provides rapid clinical estimation with high evidence support across multiple professional societies 1
- For effective osmolality (tonicity), which excludes urea: Effective Osmolality = 2 × [Na] + (Glucose/18) 1
- An alternative formula for geriatric populations: Osmolarity = 1.86 × (Na + K) + 1.15 × glucose + urea + 14 (all in mmol/L) 1, 2
Normal Reference Ranges
- Normal plasma osmolality: 275-295 mOsm/kg 1, 2
- Normal plasma osmolarity: approximately 308 mOsm/L 2, 4
- The osmolal gap (difference between measured and calculated osmolality) should be 0 ± 2 mOsm/L under normal conditions 1
Clinical Applications
Osmolality assessment is vital for evaluating hydration status, electrolyte disorders, and various metabolic derangements:
- >295 mmol/L: Action threshold for intervention in older adults 1
- >300 mOsm/kg: Indicates low-intake dehydration requiring intervention 1
- >320 mOsm/kg: Diagnostic criterion for Hyperosmolar Hyperglycemic State (HHS) 1
- Losing 2% of body water relative to body mass reduces physical efficiency by approximately 20% 5
Important Clinical Caveats
- Calculated osmolality may miss unmeasured osmoles (such as alcohols, mannitol, or toxic ingestions), making direct measurement preferable when available 1
- When interpreting elevated osmolality, verify that glucose and urea are within normal ranges before attributing hyperosmolality to dehydration alone 2
- Clinical signs like skin turgor, dry mouth, and urine color are unreliable for assessing osmolality, especially in older adults 1
- An elevated osmolal gap (>10 mOsm/L) suggests the presence of unmeasured osmotically active substances 1