Physiology · Renal, fluids and acid–base
Transport in the loop of Henle !
- Mechanism
- Exam priority: high
The loop of Henle separates salt from water: one limb lets water out and the other pumps salt out. This dilutes urine and builds a salty medulla.
Updated 2026-11-01
Also called: Thick ascending limb, NKCC2
See it in 3D: Kidneys
What it is
The loop of Henle has a water-permeable descending limb and a water-tight ascending limb that removes NaCl. The thick ascending limb reabsorbs ≈ 25% of filtered sodium through the NKCC2 cotransporter and delivers dilute fluid to the distal tubule. That separation of salt from water underlies both concentration and dilution of urine.
How it works, step by step
- The basolateral Na⁺/K⁺-ATPase keeps intracellular Na⁺ low in the thick limb cell.
- Using that gradient, luminal NKCC2 brings in 1 Na⁺, 1 K⁺ and 2 Cl⁻ together.
- K⁺ returns to the lumen through ROMK; without that recycling, NKCC2 would run out of K⁺ and stop.
- Cl⁻ exits basolaterally (ClC-Kb channels with barttin) and the lumen becomes positive (≈ +8 mV).
- That voltage pushes Na⁺, Ca²⁺ and Mg²⁺ between the cells (claudins 16 and 19).
- Water cannot follow the salt, so luminal fluid is diluted and the medullary interstitium becomes hypertonic.
- The macula densa, at the end of the thick limb, senses delivered NaCl (via NKCC2) and signals the glomerulus.
The nephron: segments, transporters and diuretics
Na⁺ reabsorbed ≈ 25%Water reabsorbed 0%
Thick ascending limb of the loop of Henle
- What it does: Reabsorbs ≈ 25% of filtered Na⁺ but is impermeable to water: the diluting segment (fluid leaves at ≈ 100 mOsm/kg) and the engine of the medullary gradient. The lumen-positive potential drives paracellular Ca²⁺ and Mg²⁺ reabsorption.
- Transporters: Apical NKCC2 (Na⁺-K⁺-2Cl⁻); ROMK recycles K⁺ to the lumen; basolateral ClC-Kb with barttin; claudins 16 and 19 (paracellular path); Ca²⁺-sensing receptor.
- Hormones: ADH (V2) increases NaCl reabsorption; PTH increases Ca²⁺ reabsorption.
- Drugs: Loop diuretics (4): block NKCC2; Na⁺, K⁺, Ca²⁺ and Mg²⁺ are lost (hypokalemia, metabolic alkalosis, hypercalciuria).
- Disorders: Bartter syndrome (like a loop diuretic: hypokalemic alkalosis, hypercalciuria, high renin and aldosterone).
- 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 almost noneWater reabsorbed ≈ 15%
Thin descending limb of the loop of Henle
- What it does: Permeable to water, barely to solutes: water leaves into the hyperosmotic interstitium (≈ 15% of filtered water) and the fluid concentrates to ≈ 1200 mOsm/kg at the hairpin.
- Transporters: Aquaporin 1 (AQP1), always present: it does not depend on ADH.
- Drugs: Osmotic diuretics (3): keep water in the lumen here and in the proximal tubule.
- Disorders: Losing the medullary gradient (medullary washout) lowers the ability to concentrate urine.
- 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)
Approximate values
| Parameter | Value |
|---|---|
| Filtered Na⁺ reabsorbed in the thick limb | ≈ 25% |
| Filtered water leaving in the descending limb | ≈ 15–20% |
| Osmolality leaving the thick limb | ≈ 100 mOsm/kg |
| Thick limb lumen voltage | ≈ +8 mV |
Approximate values for a healthy adult at rest; each laboratory sets its own ranges.
The limbs of the loop
| Segment | Water | NaCl | Result |
|---|---|---|---|
| Thin descending | Leaves (AQP1) | Barely moves | Fluid concentrates (up to ≈ 1200 mOsm/kg) |
| Thin ascending | Impermeable | Leaves passively | Begins to dilute |
| Thick ascending | Impermeable | Leaves actively (NKCC2) | Exits at ≈ 100 mOsm/kg |
Clinical notes
- Bartter syndrome (mutations in NKCC2, ROMK, ClC-Kb or barttin): hypokalemia, metabolic alkalosis, hypercalciuria and high renin, with normal blood pressure.
- By abolishing the positive voltage, loop diuretics increase urinary Ca²⁺ loss: they are used to lower calcium and can cause stones.
- Blocking NKCC2 at the macula densa makes the kidney 'think' little NaCl arrives, so it releases more renin.
Test yourself
Think of the answer, then tap the question to see it.
Why does a loop diuretic increase urinary calcium and magnesium loss?
Blocking NKCC2 stops K⁺ recycling through ROMK and abolishes the lumen-positive voltage, the force that reabsorbs Ca²⁺ and Mg²⁺ between cells.
Why is the thick ascending limb called the diluting segment?
It actively removes NaCl but is impermeable to water, so the fluid leaving it is hypotonic (≈ 100 mOsm/kg) even when ADH is present.
What would happen to NKCC2 if ROMK failed?
The lumen would lack enough K⁺ for cotransport and NKCC2 would slow, which is why ROMK mutations cause a Bartter syndrome.
Why do loop diuretics tend to cause metabolic alkalosis?
More Na⁺ reaches the collecting duct, which secretes more K⁺ and H⁺, and volume contraction activates aldosterone, which strengthens that secretion.
See it in 3D
The structures of Durgical's 3D anatomy where it happens.
Related topics
- The countercurrent mechanism, urea recycling and urine concentration
- Where and how diuretics act
- Distal tubule and collecting duct
- Renal blood flow, autoregulation and tubuloglomerular feedback
- Renal handling of calcium, phosphate and magnesium
- Urine dilution, free water and osmotic diuresis
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); Low blood potassium: 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.