Physiology

Osmosis

Water movement across semipermeable membranes — driven by solute concentration gradients

Osmosis is the passive movement of water across a semipermeable membrane from a region of low solute concentration to high solute concentration, driven by osmotic pressure. Tonicity describes how a solution affects cell volume — isotonic (no change), hypotonic (cell swells, lyses), hypertonic (cell shrinks, crenates). Normal plasma osmolality is 285-295 mOsm/kg. Clinically critical for IV fluids: 0.9% NaCl (normal saline) is isotonic; D5W becomes hypotonic after glucose metabolism; 3% NaCl is hypertonic. Aquaporins are water channels that accelerate transmembrane flux. Disorders of osmolality cause cellular damage — rapid correction of hyponatremia risks central pontine myelinolysis.

  • Driving forceSolute concentration gradient (osmotic pressure)
  • Plasma osmolality285-295 mOsm/kg
  • Water channelsAquaporins (AQP1-AQP12)
  • Isotonic IV0.9% NaCl, lactated Ringer's
  • Hypertonic IV3% NaCl, mannitol, D50W
  • Correction limitSodium ≤ 8-10 mEq/L per 24 hours

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Why osmosis matters

  • IV fluids. Choosing tonicity drives volume distribution between compartments.
  • Hyponatremia. Osmotic shifts cause brain swelling and seizures.
  • Diabetes. Glucose-induced osmotic diuresis causes polyuria and dehydration.
  • Renal physiology. Aquaporins and ADH regulate water reabsorption.
  • Cerebral edema. Mannitol and hypertonic saline shrink brain volume.
  • Dialysis. Peritoneal dialysis uses hypertonic glucose to remove fluid.
  • Cell biology. Tonicity determines cell volume in any storage or transfusion.

Common misconceptions

  • Osmolality equals tonicity. Only impermeant solutes (Na, glucose, mannitol) drive tonicity.
  • D5W is isotonic. It's isotonic in the bag, but glucose is metabolized leaving free water.
  • Saline can be given fast. Rapid correction of chronic hyponatremia causes pontine myelinolysis.
  • Water moves toward water. Water moves toward higher solute concentration, not lower.
  • Membranes block all water. Lipid bilayers allow some passive flux; aquaporins accelerate it.
  • Osmosis requires energy. It's passive — driven by entropy, no ATP needed.

Frequently asked questions

What's the difference between osmolality and tonicity?

Osmolality measures total solute particles per kg water (mOsm/kg) including urea and glucose. Tonicity is effective osmolality — only solutes that don't cross the membrane (impermeant) contribute. Urea crosses cell membranes freely, so it raises osmolality but not tonicity. A urea-rich solution can be hyperosmolar yet isotonic, causing no net water shift across cell membranes.

Why does normal saline contain 0.9% NaCl?

At 0.9%, NaCl provides ~308 mOsm/L — slightly higher than plasma (285-295) but isotonic in practice because Na and Cl distribute through extracellular fluid without entering cells. It expands intravascular volume without lysing red cells. Half-normal saline (0.45%) is hypotonic and causes cell swelling; 3% saline is hypertonic and used for severe hyponatremia or cerebral edema.

How do aquaporins work?

Aquaporins are tetrameric membrane proteins forming water-selective channels. Each monomer has a narrow pore (~3 Å) with conserved NPA motifs that exclude protons via electrostatic repulsion while allowing single-file water passage. AQP2 in collecting duct principal cells inserts into the apical membrane in response to ADH (vasopressin), enabling water reabsorption. Mutations cause nephrogenic diabetes insipidus.

Why is rapid correction of hyponatremia dangerous?

Chronic hyponatremia (Na < 135 mEq/L for > 48 hours) allows brain cells to extrude osmolytes to reach equilibrium. Rapid correction causes water to rush out of brain cells, triggering osmotic demyelination — central pontine myelinolysis. Symptoms appear days later: dysarthria, dysphagia, quadriparesis, locked-in syndrome. Limit correction to 8-10 mEq/L per 24 hours.

What causes osmotic diuresis?

Filtered solute the kidney can't fully reabsorb obligates water excretion. Classic cause: hyperglycemia in diabetic ketoacidosis. When plasma glucose exceeds the renal threshold (~180 mg/dL), glucose spills into urine carrying water. Also caused by mannitol (used to treat cerebral edema), urea in high-protein states, and contrast dye. Result: polyuria, dehydration, electrolyte loss.

How does osmosis cause red cell lysis?

In hypotonic solution, water flows into RBCs along the osmotic gradient. The cell swells until membrane tension exceeds tolerance and ruptures (hemolysis), releasing hemoglobin. Distilled water causes immediate lysis. Hypertonic solution causes the opposite — water exits, cells shrivel (crenation). The osmotic fragility test diagnoses hereditary spherocytosis by measuring lysis at varying NaCl concentrations.

What's the role of mannitol clinically?

Mannitol is a non-metabolized sugar alcohol given IV to draw water osmotically. Used for elevated intracranial pressure (cerebral edema) — the intact blood-brain barrier excludes mannitol, so water shifts from brain interstitium into plasma. Also for acute glaucoma and oliguric acute kidney injury. Dose 0.25-1 g/kg. Side effects: rebound edema if BBB compromised, hypovolemia, electrolyte disturbances.