Osmolality is a colligative property and is a measure of the total number of particles in a solution. 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. Osmometers derive osmolality from the relationship that 1 mole of particles per kilogram of water depresses the freezing point by 1.86oC.  Measurement of osmolality has two specific clinical uses. The first is to determine whether plasma water content deviates from normal and the second is to screen for poisoning by low molecular weight volatile substances.

Plasma osmolality is an indicator of total body water osmolality. Plasma osmolality ranges between 280 and 300 mOsm per kg of water. The principle determinants of plasma osmolality are sodium, chloride, glucose and urea. The classical formula for calculating plasma osmolality is: Plasma osmolality = 1.86 x sodium + Glucose/18 + BUN/2.8.  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 of these formulas. 

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.

Patients who are adequately hydrated have plasma osmolality values between 275 and 295 mOsm/kg, while patients who are dehydrated have values >300 mOsm/kg.

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. 

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. 



Ratio w/o water

Ratio after ADH

Diabetes insipidus



Nephrogenic Diabetes insipidus



Psychogenic polydypsia



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 is 280 to 300 mOsm/kg for serum and 50 to 1050 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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