[box type=”download”] Primary functions of the thin and thick limbs Importance of the counter-current multiplier Effect of loop diuretics upon thick limb symporters [/box]
Fluid entering the descending limb of the loop of Henle is isotonic with plasma (∼290mosmol/kg H2O).
The thin descending limb is permeable to water but impermeable to urea, whereas the ascending limb is impermeable to water but permeable to urea; it is also very highly permeable to Na+ and Cl−.
The thick ascending limb actively reabsorbs Na+ and Cl− from the tubular fluid via apical Na+K+2Cl− cotransporters;
Na+ is primarily transported across the basolateral membrane by Na+ pumps (some by Na+HCO3 − cotransport), and Cl− by diffusion.
K+ leaks back into the lumen via apical K+ channels (ROMK, renal outer medullary potassium channel), creating a positive charge that drives the reabsorption of cations (Na+, K+, Ca2+, Mg2+) through paracellular pathways.
As the thick ascending limb is impermeable to water, the reabsorption of ions reduces the tubular fluid osmolality (to ∼90 mosmol/kg H2O) and increases the interstitial fluid osmolality, creating an osmotic difference of ∼200 mosmol/kg H2O.
The increased interstitial osmolality causes water to diffuse out of the descending limb, and some Na+ and Cl− to diffuse in, concentrating the tubular fluid.
As this concentrated fluid descends, it travels in the opposite direction to fluid returning from the still higher osmolality regions of the deep medulla.
This counter-current arrangement creates an osmotic gradient, causing Na+ and Cl− to diffuse out of the ascending limb (diluting the ascending fluid), and water to diffuse out of the descending limb (further concentrating the descending fluid).
This effect is potentiated by the fact that the ascending limb is impermeable to water, but highly permeable to Na+ and Cl−, and also by the recycling of urea between the collecting ducts and ascending limb, which makes an important contribution to urine concentration.
At the tip of the loop of Henle, the interstitial fluid can reach an osmolality of ∼1400 mosmol/kg H2O, due in equal parts to NaCl and urea.
The blood supply to the medulla is prevented from dissipating the osmotic gradient between the cortex and medulla by the counter-current exchanger arrangement of the vasa recta capillaries.
The vasa recta also removes water reabsorbed from the loop of Henle and medullary collecting ducts. It should be noted that O2 and CO2 are also conserved, so that, in the deep medulla, PO2 is low and PCO2 is high.