Serum Osmolality

The serum or plasma osmolality is a measure of the different solutes in plasma. Among other applications, serum osmolality is indicated to evaluate the etiology of hyponatremia and may be used to screen for alcohol intoxication by means of the osmolal gap.

The reference ranges for serum osmolality are as follows ^[1] :

• Adult/elderly: 285-295 mOsm/kg H ₂O or 285-295 mmol/kg (SI units)
• Child: 275-290 mOsm/kg H ₂O

Possible critical values are as follows ^[1] :

• < 265 mOsm/kg H ₂O
• >320 mOsm/kg H ₂O

Various conditions are associated with abnormal serum osmolality.

Conditions associated with increased serum osmolality include the following:

• Marked hyperglycemia, including diabetic ketoacidosis and nonketotic hyperosmolar hyperglycemic coma

• Diabetes insipidus (central and nephrogenic)

• Hypernatremia due to dehydration ^[2]

• Hypernatremia due to iatrogenic or accidental excessive sodium chloride (NaCl) or sodium bicarbonate (NaHCO₃) intake

• Alcohol ingestion (eg, ethanol, methanol, ethylene glycol, polyethylene glycol)

Conditions associated with decreased serum osmolality include the following:

• Hyponatremia with euvolemia (eg, psychogenic polydipsia, syndrome of inappropriate antidiuretic hormone (SIADH), hypothyroidism, adrenal insufficiency)

• Hyponatremia with hypervolemia (eg, cirrhosis, congestive heart failure, nephrotic syndrome)

It is important to note that the osmolal gap should be used only as a screening test or a surrogate marker for the diagnosis of toxic alcohol ingestion. The osmolal gap must be interpreted in conjunction with clinical history and physical examination. Clinicians should be aware of the common causes of elevated osmolal gap other than toxic alcohols, including alcoholic ketoacidosis, renal failure, shock, diabetic ketoacidosis, and recent mannitol administration. ^[3]

It is not necessary to draw blood in a fasting state, and no special preparations are required prior to the test.

A blood sample is obtained by routine venipuncture and collected in a red-top tube or serum separator tube (SST).

Description

The serum or plasma osmolality is a measure of the different solutes in plasma. It is primarily determined by sodium and its corresponding anions (chloride and bicarbonate), glucose, and urea. Osmoles per kilogram of water defines osmolality, while osmoles per liter of solution defines osmolarity .

Osmolality is a technically more precise expression because solute concentrations expressed on a weight basis are temperature independent, while those based on volume vary with temperature, dependent on the thermal expansion of the solution. ^[4] However, at physiologic solute concentrations, these two measurements are clinically interchangeable.

Serum osmolality is measured using a technique called osmometry. The most widely used method of osmometry is freezing-point depression, for which a value is obtained based on the temperature at which the serum sample freezes. Another method used to measure serum osmolality is vapor pressure osmometry. However, this method does not accurately detect the presence of volatile solutes such as alcohols; hence, is not suitable when toxic alcohol ingestion is suspected. ^{[5, 6]}

Serum osmolality can be calculated using the following formula:

Calculated serum osmolality = (2 X serum [Na]) + [glucose, in mg/dL]/18 + [blood urea nitrogen, in mg/dL]/2.8

Using SI units (mmol/L), serum osmolality can be calculated as follows:

Calculated serum osmolality = (2 X serum [Na]) + [glucose, in mmol/L] + [urea, in mmol/L]

Sodium is multiplied by two to take into account the accompanying anions, chloride and bicarbonate. Glucose and blood urea nitrogen are divided by 18 and 2.8, respectively, to convert units of mg/dL into mmol/kg.

The presence of ethanol in the blood contributes to calculated serum osmolality. Theoretically, the osmolal contribution of ethanol to serum osmolality would be equal to its molar concentration, which is 46. Hence, when measured in mg/dL, it would be assumed that the serum ethanol level should be divided by 4.6. It is believed, however, that ethanol is not an ideal osmole. As such, 1 mmol/L of the compound will not account for 1 mosm/L of osmolarity. ^[7] The exact contribution of ethanol to serum osmolality remains controversial, with multiple formulas proposed. ^{[7, 3, 8]} Data from Purssell et al (2001) suggest that the best formula for the calculation of the contribution of ethanol to osmolality is as follows ^[7] :

Calculated serum osmolality = (2 X serum [Na]) + [glucose, in mg/dL]/18 + [blood urea nitrogen, in mg/dL]/2.8 + [ethanol, in mg/dL]/3.7

The disparity between measured serum osmolality and calculated serum osmolality is termed osmolal gap. An osmolal gap of greater than 10 is considered abnormal and may suggest the presence of toxic alcohols such as methanol, isopropyl alcohol, ethylene glycol, or polyethylene glycol in the appropriate clinical context. ^[9]

Indications/Applications

Hyponatremia

Serum osmolality is indicated to evaluate the etiology of hyponatremia. ^{[2, 10, 11]}

Hyponatremia in the setting of an elevated serum osmolarity (hypertonic hyponatremia) may result from marked hyperglycemia or the presence of hyperosmolar substances such as mannitol, maltose, or sucrose incorporated in intravenous immunoglobulin. Such hypertonic substances draw water out of the cells, thereby lowering sodium concentration in the serum (dilution effect).

Hyponatremia associated with a low serum osmolality (hypotonic hyponatremia), sometimes termed true hyponatremia, represents true excess of free water relative to sodium. Possible causes of hypotonic hyponatremia include psychogenic polydipsia, SIADH, hypothyroidism, or states of volume overload (congestive heart failure, cirrhosis, nephrotic syndrome).

Hyponatremia with normal serum osmolarity (pseudohyponatremia) may be seen in cases of severe hyperlipidemia or hyperproteinemia. In these settings, the aqueous volume of serum containing sodium is reduced by displacement by lipids and proteins, thus falsely lowering serum sodium levels. Pseudohyponatremia can be avoided by using a method called direct potentiometry. ^[12]

Alcohol intoxication

Serum osmolality may be used to screen for alcohol intoxication by means of the osmolal gap.

A significant disparity (>10) between measured and calculated serum osmolality may corroborate the diagnosis of toxic alcohol ingestion. The ingestion of toxic alcohols, commonly methanol, ethylene glycol, and isopropyl alcohol, are life threatening, so immediate diagnosis and intervention is warranted. Gas chromatography, which is the definitive diagnostic test for toxic alcohol ingestion, is labor-intensive, expensive, and, most importantly, not widely available in small centers. ^[13]

Considerations

It is important to note that the osmolal gap should be used only as a screening test or a surrogate marker for the diagnosis of toxic alcohol ingestion. The osmolal gap must be interpreted in conjunction with clinical history and physical examination. Clinicians should be aware of the common causes of elevated osmolal gap other than toxic alcohols, including alcoholic ketoacidosis, renal failure, shock, diabetic ketoacidosis, and recent mannitol administration. ^[3]