22nd June 2023

Loop of Henle

The loop of Henle consists of the thin descending limb, the thin ascending limb, and the thick ascending limb. Despite the description, the diameter of the tubule is in fact consistent throughout the loop of Henle; the ‘thin’ limbs refer to the thin squamous epithelial cells in these segments, which lack a brush border and have low metabolic activity, whereas the thick ascending limb has cuboidal epithelium with higher metabolic activity.

The thin descending limb has a high permeability to water due to the presence of aquaporin-1 channels and lower permeability to most solutes, including sodium ions and urea.

The thin ascending limb does not contain aquaporin channels and is, therefore, impermeable to water. Passive diffusion of sodium and chloride ions can continue to occur here due to the concentration gradient between the tubular fluid and interstitium.

The thick ascending limb (TAL) is also impermeable to water. Sodium, potassium, and chloride ions are actively reabsorbed in the TAL; Na⁺-K⁺-ATPase transporters on the basolateral membrane (as also seen in the PCT) pump three sodium ions out of the cell into the interstitium, in exchange for two potassium ions. This creates a low intracellular sodium concentration and an electrochemical gradient between the lumen and the epithelial cells, allowing the movement of sodium ions out of the lumen and into the epithelial cells via Na⁺/K⁺/2Cl⁻ co-transporters (NKCC2) and Na⁺/H⁺ antiporters on the luminal membrane. The NKCC2 to-transporter is the target site of loop diuretics such as furosemide.

There is also paracellular reabsorption of magnesium, calcium, sodium, and potassium ions in the TAL down an electrical gradient due to the slight positive charge in the lumen compared to the interstitium.

Ion transport in the thick ascending limb.

Image Source: Wikimedia Commons (2007). Renal Diuretics, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/wiki/File:Renal_Diuretics.gif (Accessed on: 13 February 2023).

Counter-current multiplication

As the TAL is impermeable to water, but reabsorbs solutes, the interstitium surrounding the loop of Henle has a high osmolarity. This high concentration of ions outside of the lumen drives the movement of water from the thin descending limb lumen into the interstitium by osmosis. This is known as counter-current multiplication.