Serum Osmolality

What calculated serum osmolality is

Serum osmolality is the amount of dissolved particles per kilogram of serum water. It can be measured directly with an osmometer, usually by freezing point depression, or estimated from the solutes that contribute most to it: sodium and its accompanying anions, glucose and urea.

The estimate is used to:

• evaluate hyponatremia and separate the forms with low, normal or high osmolality;
• monitor hyperosmolar states, as in severe hyperglycemia;
• calculate the osmolal gap, the difference between measured and calculated osmolality, used as a screen for unmeasured solutes such as methanol and ethylene glycol, according to the review by Purssell, Lynd and Koga (2004).

In hyperglycemia, osmolality is read together with sodium corrected for glucose. When poisoning with acidosis is suspected, the anion gap completes the assessment.

How to calculate osmolality: inputs, urea or BUN, and units

The calculator asks for four pieces of information:

• Sodium (Na⁺), in mEq/L, between 100 and 200. Example: 140.
• Glucose, in mg/dL, greater than 0 and up to 3,000. Example: 100.
• Use urea or BUN? Choose Urea (mg/dL), the default, or BUN, blood urea nitrogen (mg/dL).
• Urea or BUN, in mg/dL, according to the choice, greater than 0 and up to 600 (urea) or 280 (BUN). Example: 40 for urea or 18 for BUN.

The tool calculates as follows:

1. Doubles the sodium, to account for the anions that accompany it.
2. Divides the glucose by 18.
3. Divides the urea by 6, or the BUN by 2.8.
4. Adds the three terms.

The result appears with one decimal place, in mOsm/kg, with the formula used and a note to compare with the laboratory's range. Zero, negative values and numbers outside the ranges produce an error message. With the example values in the fields (140, 100 and urea 40), the result is 292.2 mOsm/kg. In Brazil, most reports give urea; BUN is more common in North American reports and articles.

Calculated osmolality formula and origin of the divisors

The tool uses the most widespread form of calculated osmolality. The urea term has two variants:

Osm (mOsm/kg) = 2 × Na + Glucose ÷ 18 + Urea ÷ 6
Osm (mOsm/kg) = 2 × Na + Glucose ÷ 18 + BUN ÷ 2.8

• 2 × Na: sodium in mEq/L multiplied by 2, to include chloride and bicarbonate.
• Glucose ÷ 18: converts mg/dL to mmol/L, because the molar mass of glucose is about 180 g/mol.
• Urea ÷ 6: converts mg/dL to mmol/L; the molar mass of urea is about 60 g/mol.
• BUN ÷ 2.8: BUN measures only the nitrogen in urea, two atoms totaling about 28 g/mol.

Both variants give the same result, because urea (mg/dL) = BUN (mg/dL) × 2.14 (60 ÷ 28). Dorwart and Chalmers (1975) compared 13 formulas in 715 sera, and several performed similarly; the best fit in their data was 1.86 × Na + glucose/18 + BUN/2.8 + 9.

Worked example of calculated osmolality

With sodium of 140 mEq/L, glucose of 90 mg/dL and urea of 30 mg/dL, the calculated osmolality is 290.0 mOsm/kg. The terms:

1. Sodium: 2 × 140 = 280.
2. Glucose: 90 ÷ 18 = 5.
3. Urea: 30 ÷ 6 = 5.
4. Total: 280 + 5 + 5 = 290.0 mOsm/kg.

The same sample expressed with a BUN of 14 mg/dL gives 14 ÷ 2.8 = 5 and, therefore, the same total of 290.0 mOsm/kg.

If the urea of 30 mg/dL is entered with the BUN option selected by mistake, the tool calculates 280 + 5 + 30 ÷ 2.8 = 295.7 mOsm/kg. The example shows how the wrong choice in the selector changes the result by almost 6 mOsm/kg.

The numbers are didactic and do not represent a real patient.

How to understand the result and the osmolal gap

The tool does not classify calculated osmolality as low, normal or high. We did not find a published source for a single range for the calculated value, and the valid reference range for measured osmolality is the laboratory's.

Calculated osmolality becomes meaningful when compared with the measured value:

Osmolal gap = Measured osmolality − Calculated osmolality

An increased osmolal gap suggests the presence of solutes that the formula does not include, such as ethanol, methanol, ethylene glycol, mannitol or isopropanol. Purssell, Lynd and Koga (2004) show, however, that the gap has low sensitivity as a screen for toxic alcohols and that the value considered normal varies with the formula used; a normal gap does not exclude poisoning.

In hyponatremia, a low measured osmolality confirms the hypotonic form, while a high osmolality with elevated glucose points to the dilutional effect of glucose. Clinical interpretation, including the decision to investigate poisoning, is the responsibility of the professional caring for the patient.

Common errors, SI units and verification checklist

The most common error is selecting BUN and entering urea, or the reverse. Since urea is about 2.14 times BUN, the mix-up changes the urea term by more than double.

• Correct selector: Urea for Brazilian reports; BUN only if the report gives urea nitrogen.
• Glucose in mg/dL: if it is in mmol/L, multiply by 18.
• Report in SI units: with sodium, glucose and urea in mmol/L, the formula becomes 2 × Na + glucose + urea, without divisors. Convert to mg/dL before using this calculator.
• Same sample: sodium, glucose and urea from the same collection, and the measured osmolality too, if you are calculating the gap.
• Impossible values: zero, negatives and numbers outside the field ranges produce an error message; check your typing.
• Pseudohyponatremia: lipemia or very high proteins lower sodium measured by an indirect method and, with it, the calculated osmolality, without changing the measured value.

Elevated urea usually reflects reduced kidney function; CKD-EPI estimates the glomerular filtration rate.

Limitations and comparison between osmolality formulas

No formula exactly reproduces measured osmolality. Fazekas and colleagues (2013) evaluated 36 published formulas in 236 patients and found mean differences of up to 35 mOsm/kg between calculated and measured osmolality; only 4 of the 36 had a mean difference below 1 mOsm/kg.

The tool's result appears in mOsm/kg, but the inputs are concentrations per volume. In practice, the formula estimates osmolality without correcting for the water fraction of plasma. For renal urea excretion, see the fractional excretion of urea.

Frequently asked questions about calculated serum osmolality

References

1. Dorwart WV, Chalmers L. Comparison of methods for calculating serum osmolality from chemical concentrations, and the prognostic value of such calculations. Clin Chem. 1975;21(2):190-4. View
2. Fazekas AS, Funk GC, Klobassa DS, Rüther H, Ziegler I, Zander R, et al. Evaluation of 36 formulas for calculating plasma osmolality. Intensive Care Med. 2013;39(2):302-8. doi:10.1007/s00134-012-2691-0. View
3. Purssell RA, Lynd LD, Koga Y. The use of the osmole gap as a screening test for the presence of exogenous substances. Toxicol Rev. 2004;23(3):189-202. doi:10.2165/00139709-200423030-00005. View