Ascending limb of loop of Henle

Function

Thin ascending limb

The thin ascending limb is impermeable to water; but is permeable to ions allowing for some sodium reabsorption. Na/K-ATPase is expressed at very low levels in this segment and thus this reabsorption is likely through passive diffusion. Salt moves out of the tubule and into the interstitium due to osmotic pressure created by the countercurrent system.

Thick ascending limb

Functionally, the parts of the ascending limb in the medulla and cortex are very similar.

The medullary ascending limb is largely impermeable to water. Sodium (Na⁺), potassium (K⁺) and chloride (Cl⁻) ions are reabsorbed by active transport. The predominant mechanism of active transport in this segment is through the Na⁺/K⁺/Cl⁻ co-transporter NKCC2 as well as the sodium/hydrogen exchanger NHE3. In total this segment accounts for approximately 25–30% of total Na⁺ reabsorption along the nephron. This is of clinical importance since commonly used "loop diuretics" act by inhibiting the NKCC2. This active transport enables the kidney to establish an osmotic gradient that is essential to the kidneys ability to concentrate the urine past isotonicity.

K⁺ is passively transported along its concentration gradient through a K⁺ leak channel in the apical aspect of the cells, back into the lumen of the ascending limb. This K⁺ "leak" generates a positive electrochemical potential difference in the lumen. This drives more paracellular reabsorption of Na⁺, as well as other cations such as magnesium (Mg²⁺) and importantly calcium Ca²⁺ due to charge repulsion.

This is also the part of the tubule that generates Tamm–Horsfall protein. The function of this protein is not well understood, but is responsible for creating urinary casts.

Clinical significance

The thick ascending limb symporter: Na-K-Cl cotransporter.