Ion transport along the nephron is essential for the reabsorption of sodium and water, maintenance of plasma volume and blood pressure and production of urine. The Loop of Henle contributes to the absorption of approximately 25% of filtered sodium and can be targeted by diuretic therapy.
The Loop of Henle has a hairpin configuration with a thin descending limb and both a thin and thick ascending limb. The thin descending and ascending segments have thin epithelial membranes with no brush borders and minimal metabolic activity.
In this article we will describe the ion transport and water movement that occurs within the loop of henle, and we will consider the clinical relevance of this.
Thick Ascending Limb
The primary site of sodium reabsorption in the Loop of Henle is the thick ascending limb (TAL). The TAL is impermeable to water. Sodium (Na+ ) reabsorption is active- the driver is the Na+/K+ ATPase on the basolateral membrane which actively pumps three Na+ ions out the cell into the interstitium and two potassium(K+) ions into the cell. By creating a low intracellular concentration of sodium, the inside of the cell becomes negatively charged, creating an electrochemical gradient.
Sodium then moves into the cell (from the tubular lumen) down the electrical and chemical gradient, through the NKCC2 transporter on the apical membrane This transporter moves one Na+ ion, one K+ ion and two Cl– ions across the apical membrane. .
Potassium ions are transported back into the tubule by ROMK channels on the apical membrane to prevent toxic build up within the cell. Chloride ions are transported into the tissue fluid via CIC-KB channels.
The overall effects of this process are:
- Removal of Na+ whilst retaining water in the tubules – this leads to a hypotonic solution arriving at the DCT.
- Pumping Na+ into the interstitial space contributes to a hyperosmotic environment in the kidney medulla (see below)
There is also significant paracellular reabsorption of magnesium, calcium, sodium and potassium.
Thin Ascending Limb
Sodium reabsorption in the thin ascending limb is passive. It occurs paracellularly due to the difference in osmolarity between the tubule and the interstitium.
As the thick ascending limb is impermeable to water, the interstitium becomes concentrated with ions, increasing the osmolarity. This drives water reabsorption from the descending limb as water moves from areas of low osmolarity to areas of high osmolarity. This system is known as counter-current multiplication.
For further explanation of counter-current multiplication, please see this helpful video: https://www.youtube.com/watch?v=Vqce2dtg45U
Thin Descending Limb
The descending limb is highly permeable to water, with reabsorption occurring passively via AQP1 channels. Very low amounts of urea, Na+ and other ions are also reabsorbed. . As mentioned above, water reabsorption is driven by the counter-current multiplier system set up by the active reabsorption of sodium in the TAL.
Bartter syndrome is a group of autosomal recessive conditions caused by genetic mutations in the genes that code for the NKCC2 transporter, apical potassium channel or basolateral chloride ion channel. The consequences are biochemically similar to administration of loop diuretics (see below). It results in hyponatraemia, hypokalaemia and metabolic alkalosis
Loop diuretics such as furosemide inhibit the NKCC2 transporter in the thick ascending limb. Loss of sodium reabsorption reduces the hypertonicity of the renal medulla, which impairs water reabsorption in the DCT and CD. This leads to increased excretion of sodium in the urine and significant diuresis, reducing plasma volume. By increasing sodium delivery to the DCT, there is increased potassium excretion. This is the mechanism behind the hypokalaemia frequently observed with loop diuretics.