Category 1
Passive transport — no energy required, movement down the gradient
Passive transport moves molecules from high concentration to low concentration — down the gradient. No ATP is consumed. The gradient itself provides the driving force, like water flowing downhill. Three types:
SD
Simple diffusion — molecules dissolve directly through the bilayer
Small nonpolar molecules dissolve into the lipid bilayer on the high-concentration side and diffuse out on the low-concentration side. No protein required. Rate depends on concentration gradient, temperature, surface area, and lipid solubility.
Molecules using simple diffusion: O₂ and CO₂ (gas exchange in lungs and tissues), steroid hormones (cross freely → intracellular receptors), fat-soluble vitamins (A, D, E, K), most lipid-soluble drugs, ethanol (crosses the blood-brain barrier rapidly — explains fast CNS effects), and small uncharged polar molecules like water (slowly) and urea.
Clinical application: O₂ crosses from alveoli (high O₂) into pulmonary capillary blood (low O₂) entirely by simple diffusion. No transporter needed. CO₂ moves in reverse by the same mechanism.
FD
Facilitated diffusion — through protein channels or carriers
Polar molecules and ions cannot dissolve in the bilayer but cross through specific membrane proteins — still passive (no ATP, still down the gradient).
Ion channels: water-filled pores that open and close (gating). Ligand-gated (open in response to neurotransmitter binding — acetylcholine receptor). Voltage-gated (open in response to membrane voltage change — Na⁺ channels in action potentials). Mechanically gated (auditory hair cells). Aquaporins: always-open water channels.
Carrier proteins: bind specific molecules, change conformation, release on the other side. GLUT1-4 transporters carry glucose into cells. GLUT4 is insulin-sensitive — insulin causes GLUT4 vesicles to fuse with the plasma membrane, rapidly increasing glucose uptake in muscle and fat cells (basis of type 2 diabetes treatment).
Memory trick: Facilitated = getting help going downhill. The protein is the helper. The concentration gradient still does the work. No ATP = passive.
Osm
Osmosis — water follows its concentration gradient
Osmosis is the diffusion of water across a semipermeable membrane from lower solute concentration (higher water concentration) to higher solute concentration (lower water concentration). Water moves toward where there is relatively less of it — toward the more concentrated solution.
Isotonic solution: same osmolarity as the cell → no net water movement → cells maintain shape. (0.9% NaCl = normal saline = isotonic for RBCs.)
Hypotonic solution: lower solute than the cell → water moves IN → animal cells swell → may lyse (hemolysis). Plant cells develop beneficial turgor pressure.
Hypertonic solution: higher solute than the cell → water moves OUT → animal cells shrink (crenate). Plant cells lose turgor (plasmolysis).
Memory trick: HYPO = low solute = water floods IN (cell swells like a water balloon). HYPER = high solute = water flows OUT (cell shrinks like a raisin). ISO = equal = no change.
Category 2
Active transport — ATP required, movement against the gradient
Active transport moves molecules from low to high concentration — uphill against the gradient. Energy (ATP) is required because this is thermodynamically unfavorable. Active transport creates concentration differences that power all cellular function.
NaK
Na⁺/K⁺ ATPase pump — the most important pump in the body
The Na⁺/K⁺ pump hydrolyzes 1 ATP to pump 3 Na⁺ OUT and 2 K⁺ IN — both against their concentration gradients. This creates the ionic asymmetry that underlies all electrical signaling: intracellular Na⁺ is low (~12 mM vs ~145 mM outside) and intracellular K⁺ is high (~140 mM vs ~5 mM outside).
The pump is electrogenic — 3 positive charges out, 2 in — making the inside more negative with each cycle, directly contributing to the resting membrane potential (−70 mV in neurons). The pump consumes ~30% of the cell's total ATP. In the brain, over 70% of ATP goes to this pump — explaining why the brain is so sensitive to hypoxia (no O₂ → no ATP → pump fails → gradients collapse → neurons die within minutes).
Clinical application: Digoxin (cardiac glycoside) inhibits the Na⁺/K⁺ pump → intracellular Na⁺ rises → Na⁺/Ca²⁺ exchanger driven in reverse → intracellular Ca²⁺ rises → stronger heart contractions (positive inotropy). Used in heart failure and atrial fibrillation.
Memory trick: 3 Sodium OUT, 2 Potassium IN, 1 ATP used. '3 out, 2 in, 1 cost.' Electrogenic — the pump itself helps maintain the negative interior.
Cot
Secondary active transport — riding the Na⁺ gradient
Secondary active transport uses the electrochemical gradient created by the Na⁺/K⁺ pump to move other molecules against their gradients — without directly consuming ATP. The Na⁺ gradient is stored energy that powers co-transporters.
Symporters move Na⁺ and a co-molecule in the same direction. The Na⁺/glucose cotransporter (SGLT) in intestinal cells: Na⁺ flows in down its gradient → glucose dragged along even when intracellular glucose is already high. This is how the gut absorbs glucose from food. SGLT2 inhibitors (empagliflozin/Jardiance, dapagliflozin/Farxiga) block the kidney SGLT2 cotransporter → glucose excreted in urine → blood glucose falls → used to treat type 2 diabetes and reduce cardiovascular events.
Antiporters move Na⁺ and a co-molecule in opposite directions. Na⁺/H⁺ exchanger: Na⁺ in, H⁺ out — important in pH regulation.
Memory trick: Secondary active = using someone else's stored energy (the Na⁺ gradient). Symport = same direction. Antiport = opposite directions.
Category 3
Bulk transport — vesicles move large cargo
Materials too large for any protein channel are moved by membrane-bounded vesicles — endocytosis (in) and exocytosis (out).
Endo
Endocytosis — importing large materials
Phagocytosis ('cell eating'): macrophages and neutrophils extend pseudopods around bacteria or debris → phagosome → fuses with lysosome → contents digested. The primary mechanism of innate immune cell killing.
Pinocytosis ('cell drinking'): small vesicles pinch off containing extracellular fluid. Nonspecific bulk uptake.
Receptor-mediated endocytosis: specific ligands bind receptor proteins in clathrin-coated pits → membrane invaginates → clathrin-coated vesicle → receptor recycled, cargo delivered to lysosome. Used by LDL cholesterol, transferrin (iron), growth factors, insulin, and many viruses (HIV, influenza use this to enter cells).
Clinical connection: Familial hypercholesterolemia — LDL receptor mutations → LDL cannot be endocytosed → LDL accumulates in blood → severe atherosclerosis in childhood (homozygotes). Statins reduce LDL partly by upregulating LDL receptor expression, increasing uptake.
Exo
Exocytosis — secreting large materials
Secretory vesicles travel along microtubule tracks, dock via SNARE proteins, and fuse with the plasma membrane → contents released outside. Used for: neurotransmitter release at synapses, insulin secretion from pancreatic beta cells, mucus secretion from goblet cells, digestive enzyme release from pancreatic acinar cells, collagen secretion by fibroblasts.
Botulinum toxin (Botox) cleaves SNARE proteins → vesicles cannot fuse → acetylcholine cannot be released at neuromuscular junctions → flaccid paralysis. Cosmetically used to prevent muscle contraction in facial wrinkles.
Memory trick: Exo = exit (materials leave the cell). Endo = enter. SNARE proteins dock the vesicle to the membrane — Botox destroys SNAREs.
🔬 Clinical Scenario — IV Fluids and Osmosis in Practice
The life-or-death importance of osmosis in clinical fluid management:
A
Normal saline (0.9% NaCl) is isotonic — same osmolarity as blood plasma (~290 mOsm/L). No net water movement across membranes. Red blood cells maintain shape. Used for routine IV hydration and resuscitation.
B
D5W (5% dextrose in water) becomes hypotonic once glucose is metabolized, leaving free water. Can worsen hyponatremia. Not used for resuscitation — only for specific indications.
C
3% hypertonic saline draws water out of cells → used for severe hyponatremia and cerebral edema. Must be corrected slowly — correcting hyponatremia too rapidly causes osmotic demyelination syndrome (central pontine myelinolysis) — myelin shrinks too fast → irreversible brainstem damage.
D
Oral rehydration solution (ORS) exploits the Na⁺/glucose cotransporter. Glucose + Na⁺ → cotransporter absorbs both → water follows osmotically. Works better than plain water for diarrhea dehydration — the cotransporter pulls Na⁺ and water into blood even while the gut is secreting fluid. WHO ORS is one of the most important medical discoveries of the 20th century, saving tens of millions of lives.
📌 Exam Application
The highest-yield transport topics:
1. Na⁺/K⁺ pump: 3 Na⁺ OUT, 2 K⁺ IN, 1 ATP. Electrogenic. Inhibited by digoxin → increased cardiac inotropy. Consumes 30% of cell ATP.
2. Passive vs facilitated vs active: Passive = no ATP (simple diffusion). Facilitated = protein + no ATP (down gradient). Active = protein + ATP (against gradient).
3. Osmosis terms: Hypo = swell. Hyper = shrink. Iso = no change. Correcting hyponatremia too fast = osmotic demyelination.
4. Secondary active transport: Na⁺ gradient drives SGLT cotransporter. SGLT2 inhibitors = diabetes treatment (glycosuria).
5. Receptor-mediated endocytosis: LDL, transferrin, viral entry. Familial hypercholesterolemia = defective LDL receptor.
⚠️ The Transport Traps
Facilitated diffusion is passive. Students see 'protein involved' and classify it as active transport. No — facilitated diffusion uses proteins but requires NO ATP and moves DOWN the gradient. Active transport moves AGAINST the gradient and requires ATP. The presence of a protein does not make transport active.
Osmosis direction: Water moves from LOW solute (HIGH water concentration) to HIGH solute (LOW water concentration). Water moves TOWARD more dissolved solute. Students say 'water moves from high solute to low solute' — wrong.
Na⁺/K⁺ pump ratio is 3:2, not 2:2 or 3:3. Three Na⁺ out, two K⁺ in. This unequal ratio makes the pump electrogenic. Both the 3 and the 2 are tested constantly.
✓ Quick Self-Test
1. What is the difference between simple diffusion and facilitated diffusion?
2. What does the Na⁺/K⁺ pump do and how is it clinically exploited?
3. What happens to a red blood cell in a hypotonic solution? A hypertonic solution?
4. What is secondary active transport? Give an example with a clinical application.
5. Describe receptor-mediated endocytosis and the disease caused by a defective LDL receptor.
Answers:
1. Simple diffusion: small nonpolar molecules dissolve directly through the bilayer — no protein, no ATP, down the gradient. Facilitated diffusion: polar or charged molecules move through specific protein channels or carriers — protein required, no ATP, still down the gradient. Both are passive.
2. The pump uses 1 ATP to move 3 Na⁺ out and 2 K⁺ in — maintaining the electrochemical gradients essential for nerve and muscle function. Clinically: digoxin inhibits the pump → intracellular Na⁺ rises → Na⁺/Ca²⁺ exchanger reverses → intracellular Ca²⁺ rises → stronger heart contractions (positive inotropy).
3. Hypotonic: water rushes in → cell swells → may lyse (hemolysis). Hypertonic: water leaves → cell shrinks and crenates.
4. Secondary active transport uses the Na⁺ gradient (created by the Na⁺/K⁺ pump) to move another molecule against its own gradient without directly using ATP. Example: SGLT cotransporter moves Na⁺ and glucose together into intestinal and kidney tubule cells. SGLT2 inhibitors (empagliflozin) block kidney glucose reabsorption → glycosuria → lower blood glucose → diabetes treatment.
5. Ligands bind receptors in clathrin-coated pits → membrane invaginates → clathrin vesicle formed → receptor recycled, cargo to lysosome. Familial hypercholesterolemia: LDL receptor mutations → LDL cannot be taken up → LDL accumulates in blood → premature severe atherosclerosis.