Osmolar

Isotonic, hypotonic and hypertonic

Tonicity explained visually, with 10 practice questions for NCLEX and pharmacy exams.

Short answer: Tonicity describes what a solution does to cell volume once it reaches equilibrium. An isotonic solution leaves cell volume unchanged. A hypotonic solution makes cells swell. A hypertonic solution makes cells shrink. Tonicity depends only on non-penetrating (“effective”) solutes, the ones that cannot cross the cell membrane. Osmolality and osmolarity count all dissolved particles. That is why a solution can be iso-osmotic or even hyperosmotic and still be hypotonic. 5% dextrose (D5W) is the classic clinical example [1, 2].

Units on this page. US conventional units come first (mg/dL, mEq/L), with SI in brackets (mmol/L). IV bag labels state calculated osmolarity in mOsm/L. Laboratories measure osmolality in mOsm/kg (SI: mmol/kg). See Osmolality vs Osmolarity for the difference.

1. Tonicity is not the same as osmolality

TermWhat it describesUnitsMeasured how?
OsmolarityAll solute particles per liter of solutionmOsm/LCalculated from composition
OsmolalityAll solute particles per kg of watermOsm/kg (mmol/kg)Osmometer (e.g., freezing-point depression)
TonicityEffect of a solution on cell volume at equilibriumNo unitsCannot be read from an osmometer; tonicity can only be predicted, not measured directly. It depends on which solutes penetrate the cell

Silverthorn’s summary for physiology teaching sets out three rules [1]:

  • Tonicity is a behavioral term. It tells you what a cell placed in the solution will do: swell (hypotonic), shrink (hypertonic), or stay the same (isotonic).
  • Tonicity cannot be measured on an osmometer and has no units.
  • In Silverthorn’s words: “isosmotic solutions are not always isotonic. Hyperosmotic solutions are not always hypertonic. But hyposmotic solutions are always hypotonic.”

The deciding factor is the reflection coefficient of each solute. It runs from 1 (impermeant, so the solute exerts its full osmotic effect across the membrane) to 0 (freely permeant, so the solute exerts no sustained osmotic effect) [3]. Na⁺ and Cl⁻ behave as effectively non-penetrating across cell membranes. Glucose (once it is taken up and metabolized) and urea do not [1, 2, 4].

Why urea counts for osmolality but not tonicity

Urea crosses cell membranes, so an isosmotic urea solution is hypotonic. Red blood cells placed in it swell and lyse [4]. Clinically, a high BUN raises the measured serum osmolality, but it does not by itself pull water out of cells. Worked example 3 below quantifies this.

2. What red blood cells do

RBCs are the standard teaching model because their volume change is easy to see and to measure (for example as hemolysis) [4].

Solution relative to the RBC interiorNet water movementRBC appearance
Isotonic (e.g., 0.9% NaCl)None at equilibriumNormal biconcave disc
Hypotonic (e.g., 0.45% NaCl, water, isosmotic urea)Into the cellSwells, and may hemolyze (burst)
Hypertonic (e.g., 3% NaCl)Out of the cellShrinks (crenation)

StatPearls uses the general terms for cells: swelling to rupture in hypotonic solution and shrinking in hypertonic solution [3]. (“Plasmolysis” strictly refers to plant cells with walls. For RBCs, use crenation.)

3. Common IV fluids by osmolarity and tonicity

Values are calculated osmolarities from US product labels or StatPearls. Normal plasma osmolality is about 275–295 mOsm/kg [5, 6].

FluidKey contents per literCalculated osmolarity (mOsm/L)Tonicity in the body
0.9% NaCl (“normal saline”, NS)Na⁺ 154, Cl⁻ 154 mEq308 [6, 7]Isotonic (308 calculated (label) / ~286 mOsm/kg measured [8]; see Example 1)
0.45% NaCl (½NS)Na⁺ 77, Cl⁻ 77 mEq154 [6, 7]Hypotonic [7]
Lactated Ringer’s (LR)Na⁺ 130, K⁺ 4, Ca²⁺ 2.7 mEq (1.35 mmol), Cl⁻ 109, lactate 28273 [6, 9]Treated as isotonic. It is slightly hypo-osmolar on paper [6]
Plasma-Lyte ANa⁺ 140, K⁺ 5, Mg²⁺ 3, Cl⁻ 98, acetate 27, gluconate 23 mEq294 [10]Isotonic [10, 11]
5% dextrose in water (D5W)Dextrose (hydrous) 50 g252 (Baxter label; B. Braun label prints 250) [12, 13]Hypotonic in the body. Near iso-osmolar in the bag (one label, an HF Acquisition relabel of a 5%/10% dextrose label, calls it “slightly hypotonic” in osmolar terms [19])
D5 ½NSDextrose 50 g, Na⁺ 77, Cl⁻ 77 mEq406 [14]Hyperosmolar in the bag (labels call it “hypertonic”), hypotonic once the dextrose is metabolized
D5NSDextrose 50 g, Na⁺ 154, Cl⁻ 154 mEq560 [14]Hyperosmolar in the bag, roughly isotonic after the dextrose is metabolized (the NaCl component remains)
3% NaClNa⁺ 513, Cl⁻ 513 mEq1026–1030 (label-dependent) [6, 15]Hypertonic

Values are calculated (ideal) osmolarities from labels, not measured osmolality. LR calcium is 2.7 mEq/L (≈1.35–1.4 mmol/L) on the Baxter label [9]. Some sources print 1.5 mmol/L (3 mEq/L), which matches other manufacturers’ rounded labels (e.g., B. Braun LR: Ca 3 mEq/L, 274 mOsm/L [18]). Check your product’s label.

ACEP’s critical-care section summarizes the tonicity groups as hypotonic (0.45% NS, 5% dextrose), isotonic (0.9% NS, LR, Plasma-Lyte) and hypertonic (3% NS) [11]. Hypotonic and hypertonic fluids shift water across cell membranes and are reserved for specific indications, such as selected hypo- or hypernatremia. Isotonic crystalloids are the default for volume resuscitation [11].

For the full fluid library and a calculator, see IV Fluid Osmolarity.

D5W: iso-osmolar in the bag, hypotonic in the patient

A liter of D5W contains 50 g of dextrose monohydrate (hydrous), about 252 mOsm/L [12]. Both labels describe the same 50 g/L of dextrose monohydrate (ideal 252.3 mOsm/L). The 250 vs 252 difference is the manufacturer’s rounding or calculation convention, not a different formulation [12, 13]. In the bag, that is close to plasma. After infusion, cells take up and metabolize the glucose. Silverthorn puts it plainly: “A solution of 5% dextrose has zero nonpenetrating solutes, and therefore, it is hypotonic” [1]. Physiologically, D5W behaves as free water, which is why it is described as a free-water source; choice of fluid is a clinical decision. Used inappropriately, it can worsen hyponatremia or cerebral edema. Hyperosmotic dextrose solutions (D10W, 505 mOsm/L calculated, B. Braun label [13]) are still hypotonic for the same reason. A cell placed in 10% dextrose first shrinks (water leaves faster than glucose enters) and then re-swells as glucose and water move in [1].

3% saline

3% NaCl (about 513 mEq/L each of Na⁺ and Cl⁻) is genuinely hypertonic, because Na⁺ and Cl⁻ are effective osmoles. Its main uses are severe symptomatic hyponatremia and cerebral edema or raised intracranial pressure [16]. Whether it is given through a peripheral or a central line is set by the product label and by institutional policy, which vary. This page does not cover how it is given. Follow your local protocol.

4. Worked examples

Example 1: Calculate the osmolarity of 0.9% NaCl, and see why “308” is still isotonic

Step 1. Grams per liter. 0.9% w/v = 0.9 g per 100 mL = 9 g/L.

Step 2. Moles per liter. Molar mass of NaCl = 58.44 g/mol. 9 ÷ 58.44 = 0.154 mol/L = 154 mmol/L.

Step 3. Apply dissociation (i = 2 for an ideal solution). 154 × 2 = 308 mOsm/L. This matches the label value [6, 7].

Step 4. Compare with measurement. NaCl does not behave ideally (its osmotic coefficient is below 1). The measured osmolality of 0.9% saline is about 286 mOsm/kg [8], which lies inside the plasma range of 275–295 [5]. So NS is effectively isotonic, even though the calculated 308 sits above that range.

Example 2: Why D5W is hypotonic

Step 1. Bag osmolarity. D5W = 50 g/L of dextrose monohydrate (molar mass about 198.17 g/mol). 50 ÷ 198.17 = 0.252 mol/L → 252 mOsm/L calculated (Baxter label: 252) [12].

Step 2. Effective (non-penetrating) solutes after infusion. Glucose is taken up by cells and metabolized, so the effective osmoles left behind are 0 mOsm/L [1].

Step 3. Conclusion. The bag is near iso-osmolar (252 vs about 285), but tonicity is set by effective osmoles, so the fluid is hypotonic. In effect, 1 L of D5W delivers about 1 L of free water.

Example 3: Urea raises osmolality but not tonicity

A patient’s BUN rises from 14 mg/dL to 84 mg/dL. Sodium and glucose are unchanged.

Step 1. Urea’s osmolar contribution = BUN (mg/dL) ÷ 2.8 [17]. (If the lab reports urea in mg/dL, divide by 6.0 instead. The ÷2.8 divisor is only for BUN.)

  • Before: 14 ÷ 2.8 = 5 mOsm/kg
  • After: 84 ÷ 2.8 = 30 mOsm/kg [SI: urea 5 → 30 mmol/L]

Step 2. Change in osmolality. 30 − 5 = +25 mOsm/kg.

Step 3. Change in tonicity. Urea is a penetrating solute [4], so the effective osmolality (and cell volume) is essentially unchanged in steady state. A hyperosmolar state from uremia is therefore not the same as a hypertonic state from hypernatremia or hyperglycemia.

Example 4: ½NS as “half saline, half free water”

Step 1. 0.45% NaCl = 4.5 g/L ÷ 58.44 = 77 mmol/L → 77 × 2 = 154 mOsm/L [7].

Step 2. 1 L of ½NS contains the same Na⁺ and Cl⁻ as 0.5 L of NS (77 mEq each).

Step 3. So 1 L of ½NS ≈ 0.5 L of isotonic saline + 0.5 L of electrolyte-free water. This explains why it is hypotonic.

5. Practice questions

Q1. A solution has an osmolarity of 300 mOsm/L, and all of its solute is urea. RBCs are placed in it. What happens?

Answer

The RBCs swell and may hemolyze. The solution is isosmotic, but urea penetrates the membrane, so the effective osmolarity is about 0 and the solution is hypotonic [1, 4]. Osmolarity alone does not predict tonicity.

Q2. Rank NS, ½NS, D5W, LR and 3% NaCl from lowest to highest calculated osmolarity.

Answer

½NS (154) < D5W (252) < LR (273) < NS (308) < 3% NaCl (about 1027) mOsm/L [6, 7, 9, 12, 15]. Note that D5W ranks above ½NS by osmolarity but behaves as more hypotonic in the body, because its effective osmolarity after metabolism is about 0.

Q3. True or false: “Because 10% dextrose is hyperosmotic (505 mOsm/L), it is hypertonic.”

Answer

False, in the physiological sense. Glucose is a penetrating solute (it is taken up and metabolized), so once infused a pure dextrose solution adds no lasting effective osmoles and behaves as hypotonic, whatever its osmolarity [1]. A cell in 10% dextrose first shrinks briefly, then swells [1]. Note the terminology clash: IV product labels often describe D10W or D5½NS as “hypertonic”, because labels use the word to mean hyperosmolar relative to plasma in the bag, not the effect on cells after infusion.

Q4. Calculate the osmolarity of D5 ½NS from its parts, and say whether it is hypotonic or hypertonic once infused.

Answer

Dextrose: 252 mOsm/L. 0.45% NaCl: 154 mOsm/L. Sum: 252 + 154 = 406 mOsm/L, which matches the label [14]. Once the dextrose is metabolized, only the 154 mOsm/L of NaCl remains as effective osmoles, so it is hypotonic in the body.

Q5. Why is normal saline called isotonic when its label osmolarity (308 mOsm/L) is above the plasma range (275–295)?

Answer

The 308 figure is an ideal calculation that assumes complete dissociation with no interionic interaction. The measured osmolality is about 286 mOsm/kg [8], within the plasma range, and both Na⁺ and Cl⁻ are effective osmoles. Some sources still describe NS as “slightly hypertonic” on the basis of the calculated figure [11].

Educational content, not medical advice. This page explains physiology and arithmetic for students and clinicians. It is not a guide to choosing, ordering or administering IV fluids. Verify all decisions with your institution’s protocols, product labeling and pharmacist.

References

  1. Silverthorn DU. Isosmotic is not always isotonic: the five-minute version. Adv Physiol Educ. 2016;40:499–500. https://journals.physiology.org/doi/full/10.1152/advan.00080.2016
  2. Vujovic P, Chirillo M, Silverthorn DU. Learning (by) osmosis: an approach to teaching osmolarity and tonicity. Adv Physiol Educ. 2018;42:626–635. https://journals.physiology.org/doi/full/10.1152/advan.00094.2018
  3. StatPearls. Physiology, Osmosis. NCBI Bookshelf NBK557609. https://www.ncbi.nlm.nih.gov/books/NBK557609/
  4. Goodhead LK, MacMillan FM. Measuring osmosis and hemolysis of red blood cells. Adv Physiol Educ. 2017;41:298–305. https://journals.physiology.org/doi/full/10.1152/advan.00083.2016
  5. StatPearls. Serum Osmolality. NCBI Bookshelf NBK567764. https://www.ncbi.nlm.nih.gov/books/NBK567764/
  6. StatPearls. Crystalloid Solutions in Intravenous Fluid Therapy (Table: Commonly Used Intravenous Fluids and Their Components). NCBI Bookshelf NBK500033. https://www.ncbi.nlm.nih.gov/books/NBK500033/
  7. StatPearls. Normal Saline. NCBI Bookshelf NBK545210. https://www.ncbi.nlm.nih.gov/books/NBK545210/
  8. Finfer S, Myburgh J, Bellomo R. Intravenous fluid therapy in critically ill adults. Nat Rev Nephrol. 2018;14:541–557 (Table 1). https://www.nature.com/articles/s41581-018-0044-0/tables/1
  9. Lactated Ringer’s Injection, USP (Baxter). DailyMed, accessed 2026-10-17 (label text: “Revised: 10/2025”). https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=dad7735c-709b-40ea-ab7a-15577e24a966
  10. Plasma-Lyte A Injection pH 7.4 (Baxter). DailyMed, accessed 2026-10-17 (label text: “Rev. August 2019”). https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6ec9e61c-2c26-402f-8604-f446b2e34058
  11. ACEP Critical Care Medicine Section. Updated Considerations for Intravenous Fluid Resuscitation. December 2024. https://www.acep.org/criticalcare/newsroom/newsroom-articles/december-2024/updated-considerations-for-intravenous-fluid-resuscitation
  12. 5% Dextrose Injection, USP (Baxter). DailyMed, accessed 2026-10-18. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=36e9478c-5df0-4b47-b97d-de3626d7cb29
  13. Dextrose Injections USP (B. Braun). DailyMed, accessed 2026-10-17 (label text: “Revised: May 2019”). https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=085614c7-ada4-4e2c-87c0-c9bc2f18365a
  14. Dextrose and Sodium Chloride Injection, USP (ICU Medical). DailyMed, accessed 2026-10-17 (label text: “Revised: August, 2020”). https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4555b1bf-6d97-4798-a63d-6d34291c85ce
  15. 3% and 5% Sodium Chloride Injections USP (Hypertonic) (B. Braun). DailyMed, accessed 2026-10-17 (label text: “Revised: September 2016”). https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f2475fa3-ab1d-4b81-8127-b58cd0790a54
  16. StatPearls. Hypertonic Fluids. NCBI Bookshelf NBK542194. https://www.ncbi.nlm.nih.gov/books/NBK542194/
  17. Kraut JA, Kurtz I. Toxic alcohol ingestions: clinical features, diagnosis, and management. Clin J Am Soc Nephrol. 2008;3:208–225. https://doi.org/10.2215/CJN.03220807
  18. Lactated Ringer’s Injection, USP (B. Braun). DailyMed, accessed 2026-10-18 (label text: “Revised: 10/2025”). https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=aad6e18f-04f8-4799-b366-873ec5a50317
  19. Dextrose Injection, USP 5% and 10% (HF Acquisition Co./HealthFirst relabel). DailyMed, accessed 2026-10-17 (label text: “Revised: June, 2010”). https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7790c2ce-2f46-7c4d-e053-2991aa0a7eda

Sources

Numbered references are listed in the article above.