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Osmolality is a colligative property and is a measure of the total number of particles in a solution. Colligative properties affect the freezing point, boiling point, and vapor pressure of any solution. Increasing the osmolality reduces the temperature at which the solution freezes, reduces the solution's vapor pressure, and raises the boiling point temperature. The osmolality of any aqueous solution can be determined by measuring any of these colligative properties. Freezing point depression osmometry is the preferred method for measuring osmolality in the clinical laboratory because it is not influenced by atmospheric temperature.

Osmotically active solutes include sodium, chloride, potassium, urea and glucose. Osmolality is actually a measurement not of the solute, but of the chemical activity of water in an aqueous solution. Solute dilutes the solvent water and increases entropy, causing the water to have a greater tendency to remain in liquid phase. The freezing point of water is decreased.

Solute-free water freezes at 0ºC. Osmometers derive osmolality from the relationship that 1 mole (1000 mosmol) of small particles per kilogram of water depresses the freezing point by 1.86oC. This relationship can be used to calculate the osmotic concentration of a solution. The freezing point of plasma water is normally approximately -0.521ºC. This represents an osmolality of 0.280 osmol/kg (0.521 ÷ 1.86) or 280 mosmol/kg.

Patients who are adequately hydrated have plasma osmolality values between 280 and 300 mOsm/kg, while patients who are dehydrated have values >300 mOsm/kg. The principle determinants of plasma osmolality are sodium, chloride, glucose and urea. The classical formula for calculating plasma osmolality is: Serum osmolality = 1.86 x sodium + Glucose/18 + BUN/2.8. A more recent publication reported that a formula, which included sodium, potassium, glucose and urea, correlated most closely with measured osmolality. The Khajuria & Krahn formula is plasma osmolality = 1.86 (sodium + potassium) + (1.15 x glucose) + urea + 14 (BMJ Open 2015;5:e008846). Calculated osmolality using this formula compared within 2% of measured osmolality. A simplified formula with excellent clinical utility is: Plasma osmolality = 2 x Sodium + Glucose/20 + BUN/3. BUN and glucose are reported in mg/dL for both formulas.

Urine osmolality depends on an individual’s hydration status. With normal fluid intake, urine osmolality varies from 400 to 800 mOsm/kg. Urine osmolality falls below 100 mOsm/kg with excessive fluid intake and increases above 1100 mOsm/kg with markedly decreased fluid intake. Urine osmolality is significantly decreased in patients with acute tubular necrosis because the kidneys are unable to concentrate the urine.

Serum and urine osmolality are used for the diagnostic workup of sodium disturbances and polyuria. Serum osmolality is also used to screen for poisoning by low molecular weight volatile substances.

The simultaneous measurement of plasma and urine osmolality is clinically significant in diagnosing the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). The typical patient with SIADH has a plasma osmolality of less than 270 mOsm/kg and a urine osmolality that is higher than the plasma.

In contrast, a patient with diabetes insipidus has a plasma osmolality greater than 320 mOsm/kg and a urine osmolality less than 100 mOsm/kg. The ratio of urine to plasma osmolality is normally between 1.0 and 3.0. Simultaneous determination of urine and plasma osmolality after three hours of water deprivation is useful in the differentiation of diabetes insipidus, nephrogenic diabetes insipidus, and psychogenic polydypsia.

Disorder Ratio w/o water Ratio after ADH
Diabetes insipidus <1 >1
Nephrogenic Diabetes insipidus <1 <1
Psychogenic polydypsia >1 >1


The ratio of urine to plasma osmolality is less than one in the patient with diabetes insipidus and greater than one in psychogenic polydypsia. After ADH administration, the patient with diabetes insipidus will have a ratio greater than one, but the ratio remains less than one in patient with nephrogenic diabetes insipidus.

In addition to assessing the presence of SIADH or diabetes insipidus, calculation of the osmolal gap can be used to screen for low molecular volatile toxins. The gap is calculated by subtracting the calculated osmolality from the measured osmolality.

Osmolal Gap = Measured osmolality – Calculated osmolality

Generally, the calculated and measured values are within 10 units of each other. If the measured value exceeds the calculated value by more than 10 units, other osmotically substances are present. In an emergency room setting, the most commonly ingested substances that produce a significant osmolal gap are; ethanol, methanol, isopropanol, ethylene glycol, propylene glycol, acetone, diethyl ether, paraldehyde, trichloroethane, and dimethyl sulfoxide.

Reference range for adults is 280 ‑ 300 mOsm/kg for serum and 150 - 1150 mOsm/kg for urine.  

Specimen requirement is one SST tube of blood and 1 mL of a random urine collection. Blood and urine specimens should be obtained within one hour of each other. Urine specimens should be refrigerated after collection.

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