Transport across epithelial sheets
- Mechanism
- Exam priority: medium
Epithelia move salt and water in one direction because their two faces carry different transporters; the Na⁺/K⁺ pump at the base powers it all.
Also called: Apical and basolateral membranes, Paracellular transport, Tight junctions
What it is
An epithelium is a sheet of polarized cells joined by tight junctions. The apical (lumen) and basolateral (blood) membranes carry different transporters, so solutes cross the cell in one direction. The basolateral Na⁺/K⁺-ATPase keeps cell Na⁺ low, which pulls Na⁺ in at the apex; Cl⁻ and water follow by transcellular and paracellular routes. This model explains the gut, kidney tubule, sweat glands, airways and the defect in cystic fibrosis.
How it works, step by step
- The basolateral Na⁺/K⁺-ATPase pumps 3 Na⁺ out and 2 K⁺ in, keeping cell Na⁺ low (≈ 10–15 mmol/L) and the cell interior negative.
- K⁺ leaks back out through basolateral K⁺ channels, which keeps the pump supplied and the membrane potential negative.
- Na⁺ enters across the apical membrane down its gradient, through ENaC channels or with glucose, amino acids or Cl⁻ on cotransporters.
- Na⁺ moved to the interstitium makes the lumen negative relative to blood; Cl⁻ follows through channels or between cells.
- Salt in the lateral spaces makes them slightly hypertonic; water follows through aquaporins and tight junctions.
- Raised interstitial pressure pushes the absorbed fluid into peritubular or villous capillaries.
- For secretion the polarity is reversed for Cl⁻: NKCC1 brings it in at the base, cAMP opens apical CFTR, and Na⁺ and water follow into the lumen.
The nephron: segments, transporters and diuretics
Na⁺ reabsorbed ≈ 65–70%Water reabsorbed ≈ 65–70%
Proximal tubule
- What it does: Reabsorbs ≈ 65–70% of filtered Na⁺ and water (isosmotically), nearly all glucose and amino acids, ≈ 80% of HCO₃⁻ and most K⁺ and phosphate. Secretes organic acids and bases (many drugs) and makes NH₄⁺ from glutamine.
- Transporters: NHE3 (Na⁺/H⁺) with carbonic anhydrase; SGLT2 (early segment, ≈ 90% of glucose) and SGLT1; NaPi-2a (phosphate); basolateral Na⁺/K⁺-ATPase.
- Hormones: Ang II stimulates NHE3 (more Na⁺ and HCO₃⁻: contraction alkalosis); PTH inhibits NaPi-2a (phosphaturia) and activates 1α-hydroxylase (active vitamin D).
- Drugs: Carbonic anhydrase inhibitors (1), SGLT2 inhibitors (2) and osmotic diuretics (3, with the thin descending limb).
- Disorders: Fanconi syndrome (loses glucose, amino acids, phosphate and HCO₃⁻); type 2 (proximal) renal tubular acidosis; familial renal glucosuria (SGLT2).
- Glomerulus and arterioles
- Proximal tubule
- Thin descending limb
- Thin ascending limb
- Thick ascending limb
- Distal convoluted tubule
- Collecting tubule and duct
- Juxtaglomerular apparatus (macula densa)
- Cortex
- Medulla
- Interstitial osmolality (≈ 300 → 1200 mOsm/kg)
Leaky and tight epithelia
| Feature | Leaky | Tight |
|---|---|---|
| Examples | Proximal tubule, small intestine, gallbladder | Collecting duct, distal colon, sweat duct, urinary bladder |
| Paracellular route | Large; water and ions cross easily | Small; little backflow |
| Gradient it can build | Small; fluid stays near isosmotic | Large; e.g. very dilute or concentrated urine |
| Volume moved | Large | Small, fine-tuned |
| Hormonal control | Little | Strong (aldosterone, ADH) |
Clinical notes
- Cholera: toxin keeps cAMP high, CFTR stays open and the crypts secrete large volumes of Cl⁻ and water; SGLT1 still works, so glucose with salt by mouth is absorbed.
- Cystic fibrosis: defective CFTR thickens airway, pancreatic and biliary secretions; in the sweat duct Cl⁻ cannot be reabsorbed, so sweat Cl⁻ is high (sweat test).
- Aldosterone excess adds apical ENaC and basolateral pumps in the collecting duct: Na⁺ retention, K⁺ loss and hypertension.
Test yourself
Think of the answer, then tap the question to see it.
Why must the Na⁺/K⁺-ATPase be on the basolateral and not the apical membrane in an absorbing epithelium?
Pumping Na⁺ out at the base keeps cell Na⁺ low, which pulls Na⁺ in from the lumen; the result is net movement from lumen to blood.
Why does oral rehydration solution contain glucose as well as salt?
SGLT1 carries Na⁺ and glucose together into enterocytes; this pathway still works in secretory diarrhea, and water follows the absorbed solutes.
Why is sweat salty in cystic fibrosis?
The sweat duct reabsorbs Cl⁻ through CFTR (and Na⁺ with it); with defective CFTR, NaCl stays in the sweat.
What distinguishes a tight epithelium from a leaky one, and where is each found?
Tight epithelia have low paracellular permeability and build large gradients under hormones (collecting duct, colon); leaky ones move large isosmotic volumes (proximal tubule, small intestine).
Connections
In Biochemistry2
In Pharmacology2
Educational physiology content; not a diagnostic or treatment guide and no substitute for a health professional's advice. Values are approximate references. No doses are given.
Sources: Cystic fibrosis: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2025); Cholera (World Health Organization, 2024); Anatomy, Abdomen and Pelvis: Kidneys (StatPearls (NCBI Bookshelf), 2025).
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Representative model, for educational purposes only.