Osmolality vs osmolarity
Per kilogram of water or per litre of solution: why the distinction matters and when it does not.
Short answer: Osmolarity counts osmotically active particles per liter of solution (mOsm/L). Osmolality counts them per kilogram of solvent water (mOsm/kg; SI: mmol/kg). Clinical laboratories measure osmolality. Formulas, IV-bag labels and textbook calculations give a calculated osmolarity, often used as an estimate of osmolality. In dilute body fluids the two numbers are close, but they are not the same quantity. The difference matters when you compare solutions with different water content, read a lab report, or calculate an osmolar gap.
Units on this page. US conventional units come first (glucose and BUN in mg/dL), with SI in brackets (mmol/L). Sodium in mEq/L equals mmol/L. For osmolality, 1 mOsm/kg = 1 mmol/kg. BUN and urea are not the same measurement. See the box in Section 3.
1. Definitions
Osmolarity (mOsm/L)
Osmolarity is the number of milliosmoles of solute per liter of solution. For an ideal solute it is:
Osmolarity (mOsm/L) = molarity (mmol/L) × n
where n (often written i, the van ‘t Hoff factor) is the number of particles each formula unit releases on full dissociation: glucose 1, urea 1, NaCl 2, KCl 2, CaCl₂ 3 [1]. For a mixture, add the milliosmoles of every component and divide by the total volume. Never average osmolarities without weighting them by volume.
Osmolarity is the number you get by calculation. That is why US IV labels print values such as “308 mOsmol/L (calc.)” for 0.9% sodium chloride [22].
Osmolality (mOsm/kg H₂O)
Osmolality is the number of milliosmoles of solute per kilogram of solvent (water) [1, 2]. Mass does not change with temperature, so osmolality is thermodynamically sounder than osmolarity, whose denominator (volume) does [2]. Osmometers measure a colligative property, usually freezing-point depression. What they report is osmolality [2, 3, 7].
Osmole vs mole
One osmole is the amount of substance that behaves as one mole of independent, osmotically active particles. One mole of a non-ionized solute is one osmole [1]. In real solutions, interactions between ions mean a salt behaves as if it releases somewhat fewer particles than the ideal n. This is corrected with the osmotic coefficient (φ), covered in Worked Example 1 [1, 7].
| Osmolarity | Osmolality | |
|---|---|---|
| Denominator | 1 L of solution | 1 kg of water |
| Unit | mOsm/L | mOsm/kg H₂O (SI mmol/kg) |
| Temperature-dependent? | Yes (volume changes) | No (mass does not) |
| How you usually get it | Calculated (recipe, label, formula) | Measured (osmometer) |
| Typical uses | IV bag labels, PN/TPN compounding, textbook problems | Serum and urine lab results, osmolar gap |
2. Why the two numbers differ
There are two separate reasons. Students often merge them.
Reason 1: Solution volume vs solvent mass (water content)
A liter of solution is not a kilogram of water. Part of every liter of plasma is taken up by proteins and lipids rather than water. Clinical chemistry conventionally takes plasma (or serum) to be about 93% water by volume, with about 7% occupied by proteins and lipids [9, 10]. This page uses 93% as its default. Zander et al. use about 94% inside their own equation [7]. Electrolytes are dissolved only in the water phase [9, 10].
That gap is large. A plasma sodium of 143 mEq/L, expressed per liter of whole plasma, corresponds to about 154 mEq/L in plasma water (143 ÷ 0.93 ≈ 154) [9]. That is the sodium concentration of 0.9% saline [9].
So to convert an osmolarity (per liter of solution) to an osmolality (per kg of water), divide by the water fraction [1]:
Osmolality ≈ osmolarity ÷ water fraction (kg water per L of solution)
For pure water and very dilute solutions, 1 L ≈ 1 kg of water, so the two values almost coincide. This is why Merck notes they are “similar in water-based body fluids” [4].
Clinical spin-off: pseudohyponatremia. Most automated analyzers measure sodium by indirect ion-selective electrode (ISE). The sample is diluted first, and the result assumes plasma is about 93% water [10]. In severe hyperlipidemia or hyperproteinemia the water fraction is lower, so the reported sodium is falsely low while the measured osmolality stays normal [3, 9]. Direct ISE, which measures undiluted sample, is not affected in this way [9, 10].
Reason 2: Non-ideal behavior (osmotic coefficient)
Even in pure water, 1 mmol of NaCl does not act as exactly 2 mOsm. Ion interactions lower its effective particle count. The osmotic coefficient φ corrects for this [1, 7]. For NaCl at physiological ionic strength, Zander et al. use φ = 0.926 [7].
Putting both corrections together [7]:
Actual osmolality (mOsm/kg H₂O) = theoretical osmolarity (mOsm/L) × φ ÷ water fraction
The two corrections pull in opposite directions in plasma. φ < 1 lowers the value, and a water fraction < 1 raises it. Zander et al. calculate a theoretical plasma osmolarity of about 291 mOsm/L and an actual osmolality of about 287 mOsm/kg H₂O (using φ 0.926 and a water content of 0.94) [7]. Both are close to the measured normal mean of about 288 mOsm/kg H₂O, and the authors call this “purely by coincidence” a likely source of confusion in the literature [7].
3. Measured vs calculated osmolality
Measured
The lab measures serum or urine osmolality with an osmometer, most often by freezing-point depression. Results are reported in mOsm/kg [2, 3, 7]. For osmolar-gap work, the measured value should come from freezing-point-depression osmometry [17]. See How osmometers work.
Calculated (serum)
Serum osmolality can be estimated from the dominant plasma osmoles: sodium (with its accompanying anions, hence ×2), glucose and urea [1, 2, 4].
US conventional units:
Calculated osmolality = 2 × Na (mEq/L) + glucose (mg/dL) ÷ 18 + BUN (mg/dL) ÷ 2.8 [1, 4, 12]
SI units (all mmol/L):
Calculated osmolality = 2 × Na + glucose + urea [6, 12, 13]
By convention, the result is reported in mOsm/kg. Strictly, the inputs are per liter of serum, so the formula yields a calculated osmolarity that is used as an estimate of osmolality [16, 17]. The literature labels it either way.
BUN vs urea: get the unit right
Lab reports… Convert to urea mmol/L Note BUN, mg/dL (US) BUN ÷ 2.8 BUN measures only urea’s nitrogen: 2 N atoms × 14 g/mol = 28 g N per mol urea, so 1 mmol/L urea = 2.8 mg/dL BUN Urea, mg/dL (whole molecule) urea ÷ 6.0 Urea molar mass 60.06 g/mol. Urea mg/dL ≈ BUN mg/dL × 2.14 Urea, mmol/L (SI; most EU labs) use as is Never put a urea mg/dL value into a ”÷ 2.8” BUN formula. It inflates the urea term about 2.14-fold. Urea 30 mg/dL is 5.0 mmol/L (30 ÷ 6.0). Treating it as BUN gives 10.7.
Where the glucose divisor comes from: glucose has a molar mass of 180.16 g/mol, so 1 mmol/L = 180 mg/L ≈ 18 mg/dL. Dividing mg/dL by 18 gives mmol/L.
Formula history. The 2·Na + glucose + urea form is attributed to Smithline and Gardner (1976) [11]. The 1976 paper’s abstract does not print the equation. Lynd et al. (2008) give it explicitly as the “Smithline and Gardner equation” [12]. Worthley et al. (1987) found that this simplest formula agreed best with measured osmolality [13]. Dorwart and Chalmers (1975) proposed 1.86 × Na + glucose/18 + BUN/2.8 + 9 [14]. Later reviews recommend the simple 2·Na + glucose + urea formula instead. Rasouli calls for Dorwart–Chalmers to be withdrawn from textbooks and analyzers [1], and an Australasian harmonisation review proposes 2·Na + glucose + urea as the common formula [6]. Many other formulas exist [6, 17]. When a calculated result is printed, check which equation was used. Our serum osmolality calculator names its equation and lists the alternatives.
Adding ethanol
When serum ethanol is known, it is often added to the calculation so that it does not inflate the osmolar gap:
Ethanol-adjusted calculated osmolality = (standard formula) + ethanol (mg/dL) ÷ 3.7 [SI: + 1.25 × ethanol (mmol/L)] [15]
Purssell et al. derived the ÷ 3.7 factor by regression and validated it prospectively. The 95% CI for the factor was 1/3.58 to 1/3.80 (1.21–1.28 in SI) [15]. In Lynd et al.’s toxic-alcohol screening study, the 1.25 coefficient gave higher specificity and positive predictive value than 1.0, without loss of sensitivity [12].
The theoretical alternative is ethanol (mg/dL) ÷ 4.6 (SI: + 1.0 × ethanol mmol/L, since ethanol’s molar mass is 46.07 g/mol). It assumes 1 mOsm per mmol and is used, for example, by Hoffman et al. [16]. The two are not interchangeable: 1.25 × mmol/L corresponds to ÷ 3.7, not ÷ 4.6. Always state which factor you used.
4. The osmolar gap (introduction)
Osmolar gap = measured osmolality − calculated osmolality [4, 12, 17]
A positive gap means there are osmotically active particles in the sample that the formula does not count. Classic examples are methanol, ethylene glycol and isopropanol, ethanol if it is not included in the formula, and administered solutes such as mannitol [4, 18]. A gap can also come from a falsely low measured sodium (pseudohyponatremia, Section 2) [3, 11].
How to read the number:
- A gap of 10 or more (Merck ≥10) is a commonly used threshold. It is a convention, not a sharp boundary [4, 12].
- The “normal” gap is wide and depends on the equation. Hoffman et al. found a mean gap of −2 ± 6 mOsm in 305 patients. Different equations gave mean gaps ranging from −5 to +15 [16]. In Purssell’s validation cohort, residual gaps ranged from −18.4 to +17.9 [15].
- A normal or small gap does not exclude toxic-alcohol ingestion. Hoffman et al. concluded that small osmol gaps “should not be used to eliminate the possibility of toxic alcohol ingestion” [16]. The gap is highest soon after ingestion. As methanol or ethylene glycol is metabolized to toxic acids, the osmolar gap falls while the anion gap rises, so a patient who presents late can have a normal osmolar gap [6, 26, 27]. Purssell et al.’s 2004 review found the gap’s diagnostic utility had not been properly validated [17].
- Formula and threshold must match. A gap is interpretable only against a reference range derived with the same calculation equation [16, 17].
Suspected poisoning is an emergency. Contact poison control or emergency services rather than relying on a calculated gap. The full explainer and calculator are on the osmolar gap page.
5. Tonicity and effective osmolality
Osmolality counts all solutes. Tonicity (effective osmolality) counts only solutes that do not freely cross cell membranes and therefore pull water between compartments [1, 4, 19].
- Urea crosses cell membranes freely. It raises osmolality but not tonicity [1, 19].
- Sodium (with its anions) is the main effective osmole of extracellular fluid [1, 4].
- Glucose acts as an effective osmole when it cannot enter cells, as in insulin deficiency [20].
Effective osmolality (US) = 2 × Na + glucose (mg/dL) ÷ 18 [1, 19] Effective osmolality (SI) = 2 × Na + glucose (mmol/L)
BUN and urea are left out of both forms.
So a patient can be hyperosmolal but not hypertonic. Uremia is the classic case (see Worked Example 4). Tonicity is what determines whether cells swell or shrink, and it is the basis of iso-, hypo- and hypertonic fluids. See Isotonic vs hypotonic vs hypertonic.
Tonicity also changes after infusion. Once dextrose is metabolized, the water it was dissolved in remains, so the in-vivo osmolality of plain 5% dextrose is effectively 0. D5W behaves like free water in the body [7].
6. Normal ranges
| Quantity | Reference values reported in sources | Source |
|---|---|---|
| Serum osmolality (adult) | 275–295 mOsm/kg (275–295 mmol/kg) | MedlinePlus [5]; StatPearls [2] |
| Serum osmolality (variant) | 275–290 mOsm/kg | Merck Manual [4] |
| Plasma osmolality, freezing-point depression | mean ≈ 288 mOsm/kg H₂O (study SDs 0.9–5.1) | Zander et al. review [7] |
| Osmolar gap | 10 or more (Merck ≥10) commonly used as the threshold; observed mean −2 ± 6 (equation-dependent) | [4, 12, 16] |
Reference ranges vary by laboratory and method. Interpret results against the reporting lab’s range. Ranges with context, including urine, are on Normal osmolality range and Urine osmolality.
7. Worked examples
Worked Example 1: 0.9% sodium chloride, from grams to mOsm/L to mOsm/kg
Given: 0.9% w/v NaCl = 0.9 g per 100 mL = 9 g/L. Molar mass of NaCl = 58.44 g/mol.
Step 1. Molarity. 9 g/L ÷ 58.44 g/mol = 0.154 mol/L = 154 mmol/L (154 mmol Na⁺ + 154 mmol Cl⁻ per liter).
Step 2. Ideal osmolarity (molarity × n). 154 mmol/L × 2 = 308 mOsm/L. This matches the label value, “308 mOsmol/L (calc.)” [22].
Step 3. Correct for non-ideal behavior (osmotic coefficient). 308 × 0.926 = 285.2
Step 4. Correct for water content. The solution is about 99.7% water [7]: 285.2 ÷ 0.997 = ≈ 286 mOsm/kg H₂O.
Result: 308 mOsm/L (calculated, ideal osmolarity) vs ≈ 286 mOsm/kg H₂O (actual osmolality). Freezing-point osmometry of 0.9% NaCl has measured 286 mOsm/kg [8], matching the calculation. So normal saline is close to plasma (≈ 288 mOsm/kg H₂O), even though its label value of 308 looks “hyperosmolar” [7].
Osmotic coefficient note. Ideal n = 2 for NaCl is an upper bound. At physiological strength, NaCl behaves as roughly 2 × 0.93 ≈ 1.86 particles per formula unit [1, 7]. This corresponds to the 1.86 coefficient in the Dorwart–Chalmers formula [6, 14]. Labels print the ideal “calc” value. In exam questions, use n = 2 unless the question gives φ.
Worked Example 2: 5% dextrose (D5W). Which molar mass?
Given: 5% w/v dextrose = 50 g/L.
US IV label basis (dextrose monohydrate, “hydrous”, 198.17 g/mol): Step 1. 50 ÷ 198.17 = 0.2523 mol/L = 252.3 mmol/L Step 2. n = 1, so ≈ 252 mOsm/L. This matches the label value, “252 mOsmol/L (calc)” [23].
Chemistry-textbook basis (anhydrous glucose, 180.16 g/mol): 50 ÷ 180.16 = 277.5 mmol/L → ≈ 278 mOsm/L. Zander et al.’s figure of 278 mOsm/L uses this basis [7].
In the body: once glucose is metabolized, the effective (in-vivo) osmolality is ≈ 0, so D5W acts as free water [7].
Lesson: state which molar mass you used. US ”% dextrose” products are labeled on the hydrous basis. Also, the osmolarity on the bag and the tonicity in the body can differ. For more fluids, see IV fluid osmolarity.
Worked Example 3: Calculated serum osmolality, same patient in both unit systems
US conventional: Na 140 mEq/L, glucose 90 mg/dL, BUN 14 mg/dL
| Step | Arithmetic | Contribution |
|---|---|---|
| 2 × Na | 2 × 140 | 280 |
| Glucose ÷ 18 | 90 ÷ 18 | 5.0 |
| BUN ÷ 2.8 | 14 ÷ 2.8 | 5.0 |
| Total | 280 + 5 + 5 | 290 mOsm/kg |
SI: Na 140 mmol/L, glucose 5.0 mmol/L, urea 5.0 mmol/L
| Step | Arithmetic | Contribution |
|---|---|---|
| 2 × Na | 2 × 140 | 280 |
| Glucose | 5.0 | 5.0 |
| Urea | 5.0 | 5.0 |
| Total | 280 + 5 + 5 | 290 mmol/kg |
Cross-checks:
- 90 mg/dL ÷ 18 = 5.0 mmol/L glucose.
- BUN 14 mg/dL ÷ 2.8 = 5.0 mmol/L urea.
- The same urea reported as urea 30 mg/dL gives 30 ÷ 6.0 = 5.0 mmol/L.
- Sodium contributes about 97% of the total (280/290).
Worked Example 4: Total vs effective osmolality (uremia)
Given (US): Na 142 mEq/L, glucose 108 mg/dL, BUN 112 mg/dL (SI equivalents: glucose 6.0 mmol/L, urea 40 mmol/L)
Step 1. Total calculated osmolality. 2 × 142 = 284 108 ÷ 18 = 6.0 112 ÷ 2.8 = 40.0 284 + 6 + 40 = 330 mOsm/kg
Step 2. Effective osmolality (exclude urea). 284 + 6 = 290 mOsm/kg
Interpretation: the total is above the usual reference interval, but the effective osmolality (290) is within it. That holds under both the 275–295 serum range [2, 5] and the 285–295 tonicity range cited by StatPearls [19]. Urea crosses cell membranes, so this patient is hyperosmolal but not hypertonic [1, 19].
Worked Example 5: Osmolar gap with ethanol (arithmetic only)
Given: measured osmolality 350 mOsm/kg. Na 140 mEq/L, glucose 90 mg/dL, BUN 14 mg/dL, ethanol 100 mg/dL (≈ 21.7 mmol/L).
Step 1. Standard calculated osmolality: 280 + 5 + 5 = 290 (as in Example 3)
Step 2. Add ethanol (default ÷ 3.7): 100 ÷ 3.7 = 27.03, so the calculated value is 317.03 SI check: 1.25 × 21.7 = 27.1, giving 317.1
Step 3. Gap: 350 − 317.03 = 32.97 → 33 mOsm/kg
Alternative (÷ 4.6): 100 ÷ 4.6 = 21.74. Calculated 311.74, gap 38.26 → 38 mOsm/kg
Rounding: keep the unrounded calculated value when you subtract, and round only the final gap.
The ethanol factor alone moves the gap by about 5 mOsm/kg. This is why every gap must state its equation [16]. A gap above the commonly used threshold suggests unmeasured osmoles or an artifact. Conversely, a gap under the threshold would not exclude a toxic alcohol (Section 4). Interpretation is a clinical decision. See the osmolar gap page.
8. When the distinction actually matters
- IV fluids. US labels state the calculated (ideal) osmolarity in mOsmol/L, not a measured osmolality [22, 23, 24]. That is why 0.9% NaCl reads 308 yet measures about 286 mOsm/kg [8, 22]. Lactated Ringer’s is labeled 273 mOsmol/L (calc) by Baxter [24]. Zander et al. estimate its actual osmolality at about 256 mOsm/kg H₂O (hypotonic), using a slightly different composition basis (276 mOsm/L theoretical) [7]. Freezing-point osmometry measured LR at 254 mOsm/kg [28], consistent with that estimate. Compare fluids with the IV fluid osmolarity tool.
- Parenteral nutrition (PN/TPN). Compounding works in calculated mOsm/L, and the commonly quoted peripheral-vein figure is 900 mOsm/L. Treat it as a weakly graded convention, not a safety line:
- ASPEN’s 2014 guideline suggests PN up to 900 mOsm/L for peripheral infusion. It states that “the evidence to support a safe limit is lacking”, and the recommendation is graded weak [21].
- FDA labeling for lipid emulsions states that admixtures ≥ 900 mOsm/L must go through a central vein [25]. Dextrose labeling advises considering a central vein at ≥ 900 mOsm/L [23].
- Other sources use different cut-offs. ASHP teaching material, for example, gives a peripheral maximum of 900–1000 mOsm/L for adults and children [29].
- Calculated PN osmolarity is itself an estimate.
- Institutional thresholds vary, so follow local protocols and your pharmacist.
- Try the TPN osmolarity calculator.
- Enteral feeds and oral fluids. Product data for formulas, ORS and drinks may be given in either unit, so check which one before you compare products. See Enteral formula osmolality and ORS vs sports drinks.
- Lab reports. A measured result in mOsm/kg comes from an osmometer. A calculated value, when printed, comes from a formula, and which formula varies by lab [6]. Gap reference limits are specific to the formula, so a gap built from one equation should not be judged against a cutoff derived for another [16].
- Hyponatremia work-up. Measured serum osmolality separates hypotonic hyponatremia from pseudohyponatremia (normal osmolality) and from hyperosmolar states such as hyperglycemia or mannitol [3]. For related calculations, see the sodium correction calculator and the free water deficit calculator.
9. Practice questions
Q1. What is the ideal (calculated) osmolarity of 3% NaCl? (NaCl molar mass 58.44 g/mol)
Answer
≈ 1027 mOsm/L. 3% = 30 g/L. 30 ÷ 58.44 = 0.513 mol/L = 513 mmol/L. × 2 (n) = 1026.7 → 1027 mOsm/L. US 3% Sodium Chloride Injection labels print the same figure, “1,027 mOsmol/L (calc)” [30]. This is an ideal value. The actual osmolality would be lower because of the osmotic coefficient, and φ itself changes with concentration, so don’t reuse 0.926 outside the physiological range without a source.
Q2. A report gives Na 140 mmol/L, glucose 90 mg/dL and urea 30 mg/dL (urea, not BUN). Calculate serum osmolality. What happens if you plug the urea value into the BUN ÷ 2.8 term?
Answer
290 mOsm/kg. Urea 30 mg/dL ÷ 6.0 = 5.0 mmol/L. 2 × 140 + 90 ÷ 18 + 5.0 = 280 + 5 + 5 = 290. The wrong way: 30 ÷ 2.8 = 10.7, giving 295.7. That is a 5.7 mOsm/kg error, enough to distort an osmolar gap. The ÷ 2.8 divisor applies only to BUN.
Q3. US units: Na 125 mEq/L, glucose 360 mg/dL, BUN 42 mg/dL. Calculate (a) total and (b) effective osmolality.
Answer
(a) 2 × 125 = 250; 360 ÷ 18 = 20; 42 ÷ 2.8 = 15; total = 285 mOsm/kg. (b) Effective = 250 + 20 = 270 mOsm/kg. The total falls inside the usual reference interval, but the effective osmolality is low. The patient is hypotonic despite a “normal-looking” total, because urea contributes to osmolality but not tonicity [1, 19].
Q4. A lab reports a measured serum osmolality of 288 mOsm/kg. Why is it reported per kg and not per L?
Answer
Osmometers measure a colligative property of the solvent (usually freezing-point depression), which depends on particles per mass of water. That makes the result an osmolality [2, 3, 7]. Mass-based concentrations also do not change with temperature, while volume-based ones do [2].
Q5. Why does 0.9% saline, labeled 308 mOsmol/L (calc), behave as roughly isotonic with plasma (≈ 288 mOsm/kg H₂O)?
Answer
Because 308 is an ideal osmolarity. Na⁺ and Cl⁻ are not fully osmotically independent (φ ≈ 0.926), so the actual osmolality is 308 × 0.926 ÷ 0.997 ≈ 286 mOsm/kg H₂O [7]. That matches the freezing-point measurement [8] and is close to plasma.
Key takeaways
- Osmolarity = per liter of solution. Osmolality = per kg of water. Labs measure osmolality, and labels and formulas give calculated osmolarity.
- They differ because of water content (plasma is about 93% water) and non-ideal behavior (φ ≈ 0.93 for NaCl).
- Calculated serum osmolality: 2·Na + glucose/18 + BUN/2.8 (US), or 2·Na + glucose + urea (SI, mmol/L). Urea mg/dL ÷ 6.0, not ÷ 2.8.
- Ethanol: add ethanol (mg/dL) ÷ 3.7 (SI × 1.25). The ÷ 4.6 form is a theoretical alternative. State which you used.
- Effective osmolality (tonicity) leaves out urea. Tonicity is what moves water across cell membranes.
- Osmolar gap = measured − calculated. A gap of 10 or more (Merck ≥10) is a convention, the formula must match the threshold, and a normal gap does not exclude a toxic alcohol.
Educational content, not medical advice. The numbers on this page are calculation aids for learning, not dosing or treatment decisions. Verify against your institution’s protocols, your laboratory’s reference ranges, and your pharmacist or physician. In a suspected poisoning, contact poison control or emergency services. See our disclaimer and how we check content.
Related: Osmolarity calculator · Serum osmolality calculator · Osmolar gap · Isotonic, hypotonic, hypertonic · Normal osmolality range
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