Loop of Henle

Thin Descending Limb

The thin descending limb is the first segment of the Loop of Henle and follows the proximal convoluted tubule. It is characterised by high water permeability, allowing passive water reabsorption from the filtrate into the medullary interstitium.

Water reabsorption occurs via abundant aquaporin-1 (AQP1) channels and leaky tight junctions – allowing water to move passively down an osmotic gradient into the medullary interstitium. Small amounts of urea, sodium and other ions are also reabsorbed. These cells have few mitochondria and minimal Na⁺/K⁺ ATPase activity, reflecting the predominantly passive nature of transport in this segment.

As the tubule descends into the increasingly hyperosmotic medulla, water leaves the lumen until osmotic equilibrium is reached. Water reabsorption is driven by the medullary osmotic gradient generated by counter-current multiplication in the ascending limb.

Thin Ascending Limb

The thin ascending limb is the segment of the Loop of Henle that follows the thin descending limb as the tubule begins to ascend back towards the renal cortex. Unlike the descending limb it is impermeable to water due to the absence of aquaporin channels.

The primary function of the thin ascending limb is the passive reabsorption of sodium (Na⁺) and chloride (Cl^–) from the tubular fluid into the medullary interstitium. The filtrate entering this segment is highly concentrated following water reabsoprtion in the descending limb. Therefore, ions diffuse out of the tubule down their concentration gradients.

Since there are no aquaporin channels, water cannot follow the solute that is removed from the tubular lumen. Consequently, the tubular fluid becomes progressively less concentrated (diluted) as it ascends.

Thick Ascending Limb (TAL)

The thick ascending limb is located distal to the thin ascending limb and continues ascending from the medulla towards the renal cortex. It contains metabolically active cuboidal cells rich in mitochondria.

Its primary function is the secondary active reabsorption of Na⁺, K⁺ and Cl^– ions from the tubular fluid. This segment plays a major role in generating the medullary osmotic gradient and diluting the tubular fluid.

It is impermeable to water, meaning solute removal directly lowers tubular osmolality. A large solute load enters this segment and approximately 75% of these (including 25% of filtered sodium) are reabsorbed, reducing tubular osmolality to up to ~50 mOsm/kg.

The key transporter is the Na⁺/K⁺/2Cl⁻ cotransporter (NKCC2) on the apical membrane, which moves one Na⁺ ion, one K⁺ ion and two Cl^– ions from the tubular lumen into the epithelial cell.

This transport is driven by Na⁺/K⁺ ATPase on the basolateral membrane, which actively pumps 3 Na⁺ ions out of the cell and 2 K⁺ ions into the cell. This maintains a low intracellular Na⁺ concentration, and since the exchange is not electroneutral, it also creates an electrochemical gradient required for sodium entry from the tubular lumen.

Potassium ions are recycled back into the tubular lumen by renal outer medullary potassium (ROMK) channels on the apical membrane. This maintains sufficient K⁺ to allow NKCC2 to function despite low luminal K⁺ concentration and generates a positive luminal charge which drives the paracellular reabsorption of Ca²⁺, Mg²⁺, Na⁺ and K⁺.

Chloride ions are transported into the tissue fluid via basolateral CIC-Kb channels.

The overall effects of this process are:

• Removal of Na⁺ whilst retaining water in the tubules – this leads to a hypotonic filtrate arriving at the DCT.
• Pumping Na⁺ into the interstitial space – this contributes to a hyperosmotic environment in the kidney medulla

This segment is highly energy-dependent and has one of the highest metabolic demands in the kidney, making it vulnerable to hypoxia and ischaemia.

Created in BioRender

Figure 2
Summary of ion transport in the thick ascending limb of the loop of Henle.

Counter-Current Multiplication

Counter-current multiplication is the mechanism by which the Loop of Henle generates the osmotic gradient within the renal medulla. This gradient enables the kidney to concentrate urine and conserve water.

The thick ascending limb is impermeable to water, allowing it to pump Na⁺ ions (without water) into the interstitium. This causes the interstitium to become concentrated with ions, increasing its osmolarity and creating a progressively increasing osmotic gradient in the medulla.

In contrast, the descending limb is permeable to water but not solutes. As a result, water is drawn out of the descending limb into the hyperosmotic interstitium and tubular fluid becomes concentrated before entering the ascending limb. This gradient allows the kidneys to reabsorb around 99% of filtered water before entering the ascending limb.

In the ascending limb, the selective reabsorption of filtrate without water produces a dilute filtrate to enter the distal convoluted tubule, despite having already reabsorbed the majority of water.

The opposing flow of filtrate (i.e. counter-current) through the two limbs and the water impermeable nature of the ascending limb are both necessary to allow the osmotic gradient to be multiplied along the loop of Henle.

OpenStax College, CC BY 3.0 <https://creativecommons.org/licenses/by/3.0>, via Wikimedia Commons

Figure 3
Diagram showing ion and water reabsorption within the Loop of Henle.

Counter-Current Exchange

The osmotic gradient generated by counter-current multiplication is maintained by the vasa recta, the specialised capillaries that run parallel to the loop of henle. As blood descends into the medulla, it gains solutes and loses water. As it ascends back towards the cortex, it loses solutes and gains water.

This process minimises the removal of solutes from the medulla while allowing reabsorbed water to enter circulation. As a result, the medullary osmotic gradient is preserved, enabling continued urine concentration.

By Human Bio Media (CC BY 4.0 [https://creativecommons.org/licenses/by/4.0/])

Figure 4
Diagram showing the vasa recta capillaries supplying the renal medulla