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[Physiology](https://durgical.com/en/physiology/) · [Renal, fluids and acid–base](https://durgical.com/en/physiology/#s-renal)

# 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](https://durgical.com/en/anatomy/kidney/)

## Key points

- Thin descending limb: permeable to water (AQP1), little to solute; fluid concentrates as it descends.
- Thick ascending limb: water-tight; NKCC2 (1 Na⁺, 1 K⁺, 2 Cl⁻) reabsorbs ≈ 25% of filtered Na⁺.
- ROMK recycles K⁺ into the lumen and creates a lumen-positive voltage that drives Ca²⁺ and Mg²⁺ through the paracellular path.
- It is the 'diluting segment': fluid leaves at ≈ 100 mOsm/kg, more dilute than plasma.
- Loop diuretics block NKCC2: Na⁺, K⁺, Ca²⁺ and Mg²⁺ are lost and metabolic alkalosis follows; Bartter syndrome looks the same.

## 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)

Illustrative schematic drawn by Durgical (a long-loop juxtamedullary nephron); proportions and percentages are approximate and not for clinical decisions.

### The nephron: segments, transporters and diuretics

**Na⁺ reabsorbed** almost none **Water 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)

Illustrative schematic drawn by Durgical (a long-loop juxtamedullary nephron); proportions and percentages are approximate and not for clinical decisions.

## 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.

## Memory aid

'Down drinks, up salts': the descending limb gives up water, the ascending limb gives up salt.

## 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.

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## See it in 3D

The structures of Durgical's 3D anatomy where it happens.

- [Kidneys](https://durgical.com/en/anatomy/kidney/)

## Related topics

- [The countercurrent mechanism, urea recycling and urine concentration](https://durgical.com/en/physiology/the-countercurrent-mechanism-urea-recycling-and-urine-concentration/)
- [Where and how diuretics act](https://durgical.com/en/physiology/where-and-how-diuretics-act/)
- [Distal tubule and collecting duct](https://durgical.com/en/physiology/distal-tubule-and-collecting-duct/)
- [Renal blood flow, autoregulation and tubuloglomerular feedback](https://durgical.com/en/physiology/renal-blood-flow-autoregulation-and-tubuloglomerular-feedback/)
- [Renal handling of calcium, phosphate and magnesium](https://durgical.com/en/physiology/renal-handling-of-calcium-phosphate-and-magnesium/)
- [Urine dilution, free water and osmotic diuresis](https://durgical.com/en/physiology/urine-dilution-free-water-and-osmotic-diuresis/)

## Related conditions

- [Hypokalaemia](https://durgical.com/en/conditions/hypokalaemia/)
- [Metabolic alkalosis](https://durgical.com/en/conditions/metabolic-alkalosis/)
- [Hypercalcaemia](https://durgical.com/en/conditions/hypercalcaemia/)

## In Biochemistry

- [Na⁺/K⁺-ATPase (sodium pump)](https://durgical.com/en/biochemistry/enzymes/na-k-atpase/)
- [Magnesium](https://durgical.com/en/biochemistry/topics/magnesium/)
- [Calcium and phosphate](https://durgical.com/en/biochemistry/topics/calcium-and-phosphate/)

[← All of physiology](https://durgical.com/en/physiology/)

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](https://openstax.org/books/anatomy-and-physiology-2e/pages/25-6-tubular-reabsorption) (OpenStax (Rice University), 2022); [Low blood potassium: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/000479.htm) (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.

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