Physiology · Renal, fluids and acid–base
Distal tubule and collecting duct !
- Mechanism
- Exam priority: high
The end of the nephron does the fine tuning: how much salt, water, potassium and acid leaves in urine, under hormone control.
Updated 2026-11-01
Also called: Distal nephron, Principal and intercalated cells
See it in 3D: Kidneys · Left adrenal gland · Right adrenal gland
What it is
The distal convoluted tubule and collecting duct reabsorb only ≈ 5–10% of filtered sodium, but this is the stretch hormones regulate. Aldosterone sets how much Na⁺ is reabsorbed and how much K⁺ and H⁺ are secreted; ADH sets how much water returns; PTH sets how much calcium. The final composition of urine is decided here.
How it works, step by step
- In the distal tubule, NCC brings in Na⁺ and Cl⁻; low intracellular Na⁺ favours Ca²⁺ exit across the basolateral side (Na⁺/Ca²⁺ exchanger).
- Aldosterone enters the principal cell, binds the mineralocorticoid receptor and increases ENaC, ROMK and Na⁺/K⁺-ATPase.
- Na⁺ enters through ENaC without an accompanying anion and leaves the lumen negative (≈ −40 mV).
- That voltage and high intracellular K⁺ push K⁺ into the lumen through ROMK and BK.
- In the α-intercalated cell, H⁺-ATPase secretes H⁺, buffered by phosphate and ammonia; the new HCO₃⁻ returns to blood.
- ADH, through the V2 receptor and cAMP, inserts aquaporin 2 into the luminal membrane and water leaves toward the hypertonic medulla.
The nephron: segments, transporters and diuretics
Na⁺ reabsorbed ≈ 5%Water reabsorbed 0%
Distal convoluted tubule
- What it does: Reabsorbs ≈ 5% of Na⁺; impermeable to water (keeps diluting). Actively reabsorbs Ca²⁺, under PTH control, and Mg²⁺.
- Transporters: NCC (Na⁺-Cl⁻ cotransporter); TRPV5 (Ca²⁺) with the basolateral Na⁺/Ca²⁺ exchanger; TRPM6 (Mg²⁺).
- Hormones: PTH (more Ca²⁺ reabsorption); aldosterone and Ang II in the late part.
- Drugs: Thiazides (5): block NCC; lower Ca²⁺ excretion (hypocalciuria) and cause hypokalemia and hyponatremia.
- Disorders: Gitelman syndrome (like a thiazide: hypokalemic alkalosis, hypomagnesemia, hypocalciuria). Gordon syndrome (pseudohypoaldosteronism type 2): the opposite, hypertension with hyperkalemia.
- 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)
The nephron: segments, transporters and diuretics
Na⁺ reabsorbed ≈ 2–5%Water reabsorbed variable (ADH)
Collecting tubule and duct
- What it does: Fine tuning: reabsorbs ≈ 2–5% of Na⁺, secretes K⁺ and H⁺ and reabsorbs water as ADH allows (urine from ≈ 50 to ≈ 1200 mOsm/kg). Principal cells handle Na⁺, K⁺ and water; intercalated cells handle acid–base.
- Transporters: Principal: ENaC, ROMK and BK (K⁺ secretion; BK is flow-driven), apical AQP2 (ADH) and basolateral AQP3/4. α-intercalated: H⁺-ATPase and H⁺/K⁺-ATPase (secrete acid). β-intercalated: pendrin (secrete HCO₃⁻). Inner medulla: urea transporters (ADH).
- Hormones: Aldosterone (more ENaC, ROMK, Na⁺/K⁺-ATPase and H⁺-ATPase); ADH via the V2 receptor → cAMP → AQP2 insertion; atrial natriuretic peptide curbs Na⁺ reabsorption.
- Drugs: ENaC blockers (6) and mineralocorticoid receptor antagonists (7): K⁺-sparing (risk of hyperkalemia). V2 receptor antagonists (8, vaptans): aquaretics.
- Disorders: Liddle syndrome (overactive ENaC: hypertension, hypokalemia, low renin and aldosterone); nephrogenic diabetes insipidus (V2 or AQP2, lithium); type 1 distal renal tubular acidosis (H⁺ secretion fails: urine pH > 5.5, hypokalemia, stones) and type 4 (hypoaldosteronism: hyperkalemia); SIADH (excess ADH).
- 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)
Regulation
- +Aldosterone: More ENaC and Na⁺/K⁺-ATPase: retains Na⁺, secretes K⁺ and H⁺.
- +ADH (V2 receptor): Inserts AQP2 in the collecting duct: reabsorbs water and concentrates urine.
- +PTH: Increases Ca²⁺ reabsorption in the distal tubule.
- −Natriuretic peptides: Inhibit Na⁺ reabsorption in the medullary collecting duct: natriuresis.
- +High tubular flow: Activates BK channels and increases K⁺ secretion.
Collecting duct cells
| Cell | Transporters | Does | Hormone |
|---|---|---|---|
| Principal | ENaC, ROMK/BK, AQP2 | Reabsorbs Na⁺ and water; secretes K⁺ | Aldosterone, ADH |
| α-intercalated | H⁺-ATPase, H⁺/K⁺-ATPase, AE1 | Secretes H⁺; reabsorbs HCO₃⁻ and K⁺ | Aldosterone |
| β-intercalated | Pendrin | Secretes HCO₃⁻ | Increases in alkalosis |
Clinical notes
- Primary hyperaldosteronism: hypertension, hypokalemia and metabolic alkalosis with low renin.
- Adrenal insufficiency (no aldosterone): sodium is lost, K⁺ and H⁺ retained: hyponatremia, hyperkalemia and acidosis.
- Gitelman syndrome (NCC): like a thiazide, with hypokalemia, hypomagnesemia and hypocalciuria.
- Liddle syndrome (ENaC always on): hypertension and hypokalemia with low aldosterone.
Test yourself
Think of the answer, then tap the question to see it.
Why does excess aldosterone cause both hypokalemia and metabolic alkalosis?
It increases Na⁺ entry through ENaC; the lumen becomes more negative and drives K⁺ secretion (principal cells) and H⁺ secretion (α-intercalated cells).
Why do thiazides reduce urinary calcium while loop diuretics increase it?
Blocking NCC lowers Na⁺ inside the distal cell; the Na⁺/Ca²⁺ exchanger moves more Ca²⁺ into blood, so more is reabsorbed. Loop diuretics instead abolish the voltage that reabsorbs Ca²⁺.
What does ADH do in the principal cell, and why does it need a hypertonic medulla?
Through the V2 receptor and cAMP it inserts AQP2 into the luminal membrane. Water only leaves if the medullary interstitium is more concentrated than the lumen.
Why does a patient on a loop diuretic lose more potassium even though the drug acts before the collecting duct?
More flow and Na⁺ reach the collecting duct: more ENaC Na⁺ uptake, a more negative lumen and washout of secreted K⁺, plus aldosterone activated by hypovolemia.
See it in 3D
The structures of Durgical's 3D anatomy where it happens.
Related topics
- Potassium balance
- ADH, thirst and water balance
- Where and how diuretics act
- Aldosterone: actions and control
- Renal handling of H⁺ and bicarbonate
- The renin–angiotensin–aldosterone system
- Transport in the loop of Henle
Related conditions
In Biochemistry
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: 25.6 Tubular Reabsorption (OpenStax (Rice University), 2022); 25.8 Endocrine Regulation of Kidney Function (OpenStax (Rice University), 2022); High potassium level: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); Hall JE. Guyton and Hall Textbook of Medical Physiology, 13th ed. (ch. 28). Reference book used to check facts; its text and figures are not reproduced (Elsevier, 2016).
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Representative model, for educational purposes only.