Physiology chapters
Tubular transport: proximal tubule to collecting duct
What each part of the nephron reabsorbs and secretes, the transporters involved, how the loop of Henle and urea build the medullary gradient, the cells of the collecting duct, and how aldosterone, ADH, ANP and PTH act on the tubule.
- The proximal tubule reabsorbs about 65% of filtered Na+ and water, and all glucose and amino acids, mostly by Na+-coupled secondary active transport.
- The loop of Henle builds a concentrated medulla: the descending limb lets water out; the thick ascending limb pumps NaCl out (Na-K-2Cl) but is impermeable to water; urea recycling adds to the gradient.
- The distal tubule and collecting duct fine-tune: aldosterone (principal cells) keeps Na+ and loses K+; ADH inserts aquaporin-2 for water; intercalated cells handle H+.
On this page
Overview
About 180 litres of filtrate are made each day, but only about 1.5 litres of urine are passed. The tubules reabsorb almost everything useful and secrete some unwanted substances.
Each segment has its own job and its own transporters. This explains how the kidney controls salt, water, potassium, acid and calcium, and where diuretics act.
Modes of transport
- Primary active transport: uses ATP directly. The Na+/K+-ATPase on the basolateral membrane of every tubular cell pumps Na+ out into the blood, keeping cell Na+ low.
- Secondary active transport: the Na+ gradient made by the pump drives other substances. Cotransport (same direction): Na+ with glucose, amino acids, phosphate. Countertransport (opposite): Na+ in, H+ out.
- Passive diffusion: water (by osmosis), urea, Cl−.
- Transcellular (through cells) and paracellular (between cells, across tight junctions) routes.
- Endocytosis: small filtered proteins in the proximal tubule.
Almost all tubular transport depends, directly or indirectly, on the basolateral Na+/K+-ATPase.
Proximal tubule
The "workhorse" of the nephron. Its cells have a brush border and many mitochondria.
| Substance | Share reabsorbed here (approx.) |
|---|---|
| Na+, water, K+, Cl− | About 65% |
| Glucose, amino acids | About 100% (normally) |
| Bicarbonate | About 80–90% |
| Phosphate | Most (reduced by PTH) |
- Reabsorption is isosmotic: water follows solute, so the fluid leaving is still about 300 mOsm/L.
- Glucose uses SGLT2 (early) and SGLT1 (later), then leaves the cell by GLUT transporters.
- Bicarbonate reclaim needs carbonic anhydrase (the site of acetazolamide).
- The proximal tubule secretes organic acids and bases: PAH, uric acid, penicillin, many drugs.
Loop of Henle
| Segment | Water | Solutes |
|---|---|---|
| Thin descending limb | Highly permeable (water leaves into the salty medulla) | Little NaCl movement |
| Thin ascending limb | Impermeable | NaCl leaves passively |
| Thick ascending limb | Impermeable | Active NaCl reabsorption by Na-K-2Cl (NKCC2); also Ca2+ and Mg2+ (paracellular) |
The loop reabsorbs about 25% of filtered Na+. Loop diuretics (furosemide) block NKCC2.
The thick ascending limb pumps out NaCl but not water, so the fluid leaving it is dilute (about 100 mOsm/L): the diluting segment.
The countercurrent multiplier
- The thick ascending limb pumps NaCl into the medullary interstitium.
- The interstitium becomes salty.
- Water leaves the descending limb, concentrating the fluid inside it.
- This concentrated fluid flows round to the ascending limb, where more NaCl is pumped out.
- Repeated, this builds a gradient from about 300 mOsm/L in the cortex to about 1,200 mOsm/L at the tip of the papilla.
Juxtamedullary nephrons with long loops are essential for this.
The vasa recta (countercurrent exchanger)
The hairpin capillaries of the medulla run alongside the loops. Their slow flow and hairpin shape let them supply the medulla without washing away the gradient.
Role of urea
- In the inner medullary collecting duct, ADH increases urea permeability (UT-A transporters).
- Urea diffuses into the inner medulla and adds to the gradient (it makes up a large part of inner medullary osmolarity).
- Some urea re-enters the thin limb and is recycled.
Urea contributes about 40–50% of the osmolarity of the inner medulla when ADH is high, helping to make concentrated urine. People on very low-protein diets concentrate urine less well.
Distal convoluted tubule
- Reabsorbs about 5% of filtered Na+ by the Na-Cl cotransporter (NCC), the target of thiazide diuretics.
- Impermeable to water, so it dilutes the fluid further.
- Parathyroid hormone increases Ca2+ reabsorption here.
Thiazides increase calcium reabsorption, so they are used to prevent calcium kidney stones; loop diuretics increase calcium loss.
Collecting duct
Principal cells
- Reabsorb Na+ through epithelial Na+ channels (ENaC) and secrete K+.
- Controlled by aldosterone, which increases ENaC, Na+/K+-ATPase and K+ channels.
- Reabsorb water when ADH is present.
Potassium-sparing diuretics: spironolactone blocks the aldosterone receptor; amiloride blocks ENaC.
Intercalated cells
- Type A: secrete H+ (H+-ATPase and H+/K+-ATPase) and reabsorb HCO3− and K+. Important in acidosis.
- Type B: secrete HCO3−. Important in alkalosis.
ADH (vasopressin)
ADH acts on V2 receptors on principal cells, inserting aquaporin-2 water channels into the luminal membrane. Water then moves out into the concentrated medulla, and concentrated urine forms (up to about 1,200 mOsm/L).
Without ADH, the collecting duct stays impermeable to water, and large volumes of dilute urine (as low as about 50 mOsm/L) are passed.
Summary of hormone actions
| Hormone | Main site | Effect |
|---|---|---|
| Aldosterone | Distal tubule and collecting duct (principal cells) | ↑ Na+ reabsorption, ↑ K+ secretion, ↑ H+ secretion |
| ADH | Collecting duct | ↑ water reabsorption (aquaporin-2); ↑ urea permeability |
| Angiotensin II | Proximal tubule | ↑ Na+ and HCO3− reabsorption (Na+/H+ exchange) |
| ANP (from stretched atria) | Collecting duct; glomerulus | ↓ Na+ reabsorption, ↑ GFR: natriuresis |
| PTH | Distal tubule; proximal tubule | ↑ Ca2+ reabsorption; ↓ phosphate reabsorption |
Clinical relevance
Diuretics
| Diuretic | Site | Transporter |
|---|---|---|
| Acetazolamide | Proximal tubule | Carbonic anhydrase |
| Furosemide (loop) | Thick ascending limb | Na-K-2Cl |
| Thiazides | Distal convoluted tubule | Na-Cl |
| Spironolactone, amiloride | Collecting duct | Aldosterone receptor; ENaC |
Loop and thiazide diuretics deliver more Na+ to the collecting duct, increasing K+ loss (hypokalaemia).
Diabetes insipidus
How it happens: no ADH (central) or the kidney does not respond to it (nephrogenic).
What you see: large volumes of dilute urine and thirst.
Fanconi syndrome
How it happens: generalised failure of the proximal tubule.
What you see: glucose, amino acids, phosphate and bicarbonate lost in urine.
Expect: the percentage reabsorbed in the proximal tubule and what is reabsorbed completely, the modes of transport, permeability of each loop segment, the diluting segment, countercurrent multiplication and the vasa recta, the role of urea, principal vs intercalated cells, hormone actions, and the site of each diuretic.
Quick revision
- Proximal tubule: 65% Na+ and water; all glucose and amino acids; isosmotic.
- Descending limb: water out. Thick ascending limb: NaCl out by NKCC2, no water.
- Countercurrent multiplier builds 300 → 1,200 mOsm/L; vasa recta preserve it.
- Urea recycling adds to the inner medullary gradient.
- DCT: NCC (thiazides); PTH increases Ca2+ reabsorption.
- Principal cells: aldosterone (Na+ in, K+ out), ADH (aquaporin-2).
- Intercalated cells: type A secrete H+; type B secrete HCO3−.
Written by The House Job from standard physiology references (Guyton and Hall Textbook of Medical Physiology; BRS Physiology).
FAQ
Which part of the nephron reabsorbs the most sodium and water?
The proximal tubule, about 65% of the filtered load.
Why is the thick ascending limb called the diluting segment?
It actively removes NaCl but is impermeable to water, so the fluid inside becomes dilute.
How does ADH concentrate urine?
It inserts aquaporin-2 water channels into the collecting duct cells, letting water move out into the concentrated medulla.
Where does aldosterone act?
Mainly on the principal cells of the late distal tubule and collecting duct, increasing sodium reabsorption and potassium secretion.