All courses > Health > Physiology ::

Osmosis and Tonicity: Predicting Water Movement in Cells and Tissues

Capítulo 4

Estimated reading time: 7 minutes

Water movement is driven by effective solute differences

Across a semipermeable membrane (one that allows water to move more easily than at least some solutes), water shifts in the direction that reduces the effective difference in solute concentration between the two sides. In physiology, the key idea is not “water seeks salt,” but “water moves to equalize the concentration of solutes that cannot cross as quickly as water can.” Those solutes create a persistent osmotic pull, so water redistributes until the effective gradient is reduced or balanced by opposing forces (for example, pressure in some tissues).

Separate the terms: osmosis vs osmolarity vs tonicity

Osmosis (the process)

Osmosis is the net movement of water across a semipermeable membrane due to differences in solute concentration. It is about direction of water flow, not about how much solute is present in total.

Osmolarity (a concentration measure)

Osmolarity is the total concentration of osmotically active particles in a solution, expressed as osmoles per liter (Osm/L) or milliosmoles per liter (mOsm/L). It counts all dissolved particles, whether or not they can cross the membrane.

Example: 150 mM NaCl dissociates into ~300 mOsm/L (Na⁺ + Cl⁻).
Example: 300 mM glucose is ~300 mOsm/L (does not dissociate).

Tonicity (the effect on cell volume)

Tonicity predicts the change in cell volume when a cell is placed in a solution. Tonicity depends only on non-penetrating (effectively impermeant) solutes, because only those maintain a lasting osmotic gradient that water must respond to.

Isotonic: no net water movement; cell volume stays the same.
Hypotonic: water enters the cell; cell swells.
Hypertonic: water leaves the cell; cell shrinks (crenates in RBCs).

Key warning: A solution can be iso-osmotic (same total osmolarity) but not isotonic if much of its osmolarity comes from penetrating solutes.

Continue in our app.

Listen to the audio with the screen off.
Earn a certificate upon completion.
Over 5000 courses for you to explore!

Or continue reading below...

Download the app

Penetrating vs non-penetrating solutes: what matters for tonicity

To use tonicity correctly, classify solutes by whether they cross the membrane on the relevant time scale.

Non-penetrating solutes: do not cross (or cross very slowly). They exert a sustained osmotic effect. Examples for many cells: Na⁺, Cl⁻ (because membranes are not freely permeable to ions without channels and transporters), large proteins.
Penetrating solutes: cross relatively easily (or are transported in a way that allows equilibration). Their osmotic effect is often transient because they redistribute. Examples: urea (often), glycerol (variable), ethanol. Glucose can be functionally penetrating in cells with glucose transporters (time scale matters).

Because different cell types have different transporters, always interpret “penetrating” in context. For red blood cells (RBCs), urea is relatively penetrating; NaCl is effectively non-penetrating over short time frames.

A structured method to predict water movement and cell volume

Use this sequence every time. It prevents the common mistake of using total osmolarity when you should use effective (non-penetrating) osmolarity.

Step 1: List solutes on each side of the membrane

Write down the extracellular and intracellular solutes and their concentrations (or the solution composition you are given).

Step 2: Classify each solute as penetrating or non-penetrating

Decide which solutes can cross the membrane on the time scale of the question.

Step 3: Compute the effective osmolarity (non-penetrating osmolarity) on each side

Add up only the contributions from non-penetrating solutes. This is the value that determines tonicity.

If you are given a single extracellular solution and asked what happens to a cell, you typically compare:

Extracellular effective osmolarity (non-penetrating solutes in the solution)
Intracellular effective osmolarity (often approximated as ~300 mOsm of non-penetrating solutes for many mammalian cells, unless specified otherwise)

Step 4: Predict net water direction

Water moves from lower effective osmolarity to higher effective osmolarity (toward the side with more non-penetrating solute particles).

Step 5: Predict cell volume change

Water enters cell → cell swells (risk of lysis in RBCs).
Water leaves cell → cell shrinks (crenation in RBCs).
No net water movement → volume unchanged.

Worked examples: red blood cells in hypotonic, isotonic, and hypertonic solutions

Assume an RBC has an effective intracellular osmolarity of ~300 mOsm due to non-penetrating solutes (hemoglobin and other intracellular solutes that do not rapidly leave). Also assume NaCl is non-penetrating over the time frame, while water moves freely.

Example 1: RBC in isotonic saline (0.9% NaCl)

Given: 0.9% NaCl is about 154 mM NaCl. Because NaCl dissociates into two particles, osmolarity is ~308 mOsm/L.

Step 1–2: Extracellular solute is NaCl (non-penetrating).
Step 3: Extracellular effective osmolarity ≈ 308 mOsm. Intracellular effective osmolarity ≈ 300 mOsm.
Step 4: Nearly equal → no meaningful net water movement.
Step 5: RBC volume stays ~constant (isotonic).

What you would observe: Normal biconcave RBC shape maintained.

Example 2: RBC in hypotonic solution (e.g., 0.45% NaCl)

Given: 0.45% NaCl is about 77 mM NaCl → ~154 mOsm/L.

Step 1–2: Extracellular NaCl is non-penetrating.
Step 3: Extracellular effective osmolarity ≈ 154 mOsm. Intracellular effective osmolarity ≈ 300 mOsm.
Step 4: Water moves into the cell (toward higher effective osmolarity inside).
Step 5: RBC swells; if sufficiently hypotonic, it can lyse (hemolysis).

What you would observe: Cells become more spherical; in extreme hypotonicity, membranes rupture.

Example 3: RBC in hypertonic solution (e.g., 3% NaCl)

Given: 3% NaCl is about 513 mM NaCl → ~1026 mOsm/L.

Step 1–2: Extracellular NaCl is non-penetrating.
Step 3: Extracellular effective osmolarity ≈ 1026 mOsm. Intracellular effective osmolarity ≈ 300 mOsm.
Step 4: Water moves out of the cell (toward higher effective osmolarity outside).
Step 5: RBC shrinks (crenates).

What you would observe: Spiky, shrunken RBCs due to water loss.

Common trap: iso-osmotic does not always mean isotonic

Consider an extracellular solution that is 300 mOsm total, but made of a solute that can enter the cell.

Example: RBC in 300 mOsm urea (conceptual)

Total osmolarity: 300 mOsm (iso-osmotic with the cell).
Tonicity: often hypotonic over time if urea is penetrating, because urea enters the RBC, reducing the extracellular effective osmolarity while increasing intracellular solute load; water follows into the cell.

Takeaway: For tonicity, count only the solutes that stay put across the membrane on the time scale of interest.

Everyday physiology connections

Why IV fluids must be isotonic (most of the time)

When fluids are infused into the bloodstream, they mix with plasma and immediately contact RBCs and vascular endothelium. If the infused solution is markedly hypotonic, water enters RBCs and can cause hemolysis; if markedly hypertonic, RBCs crenate and water is pulled out of cells, potentially disturbing tissue hydration.

0.9% NaCl and lactated Ringer’s are designed to be approximately isotonic with plasma, minimizing rapid water shifts across cell membranes.
Some fluids may be iso-osmotic but behave differently depending on solute permeability and metabolism; clinically, selection depends on where you want water to distribute (intravascular vs interstitial vs intracellular compartments).

How dehydration raises extracellular osmolarity and draws water out of cells

In dehydration, the body loses more water than solute (common with sweating without adequate water replacement). This increases extracellular osmolarity, largely due to non-penetrating ions like Na⁺ and accompanying anions. The extracellular fluid becomes effectively hypertonic relative to cells, so:

Water shifts from intracellular to extracellular space.
Cells shrink as they lose water.
In the nervous system, cellular dehydration can contribute to symptoms such as irritability, lethargy, or confusion (severity depends on magnitude and rate of change).

This is also why correcting severe hypertonic dehydration must be done carefully: a rapid drop in extracellular effective osmolarity can drive water into brain cells too quickly.

Practice items: label the solution and predict outcomes

For each item, assume the cell’s effective intracellular osmolarity is 300 mOsm from non-penetrating solutes. State: (1) penetrating vs non-penetrating solutes, (2) effective extracellular osmolarity, (3) tonicity (hypo/iso/hypertonic), (4) water movement direction, (5) cell volume change.

Solution A: 0.9% NaCl (~308 mOsm, non-penetrating). What happens to an RBC?
Solution B: 0.45% NaCl (~154 mOsm, non-penetrating). What happens to an RBC?
Solution C: 3% NaCl (~1026 mOsm, non-penetrating). What happens to an RBC?
Solution D: 300 mOsm of a solute that is fully penetrating on this time scale. Is it isotonic? What happens to cell volume over time?
Solution E: Mixture: 150 mOsm non-penetrating solute + 150 mOsm penetrating solute. What is the effective extracellular osmolarity? Predict tonicity and cell volume change.
Solution F: Extracellular effective osmolarity rises from 300 to 330 mOsm due to water loss (dehydration). Predict water movement and cell volume change.

Now answer the exercise about the content:

A cell has an effective intracellular osmolarity of 300 mOsm from non-penetrating solutes. It is placed in an extracellular solution containing 150 mOsm non-penetrating solute plus 150 mOsm fully penetrating solute. What happens to water movement and cell volume over time?

You are right! Congratulations, now go to the next page

You missed! Try again.

Tonicity depends only on non-penetrating solutes. Here the effective extracellular osmolarity is 150 mOsm (not 300), which is lower than the cell’s 300 mOsm, so water moves into the cell and it swells over time.