Countercurrent multiplication

Describe the mechanism by which the kidney concentrates urine, explaining the counter current mechanisms

1. In the thick ascending limb of the loop of Henle, reabsorption of sodium (via secondary active transport) occurs along its electrochemical gradient established by a basolateral Na-K pump. 2. Reabsorption of sodium occurs via a NKCC2 symporter protein, which utilises the energy released by the movement of sodium along its electrochemical gradient to move K+ and 2Cl- ions into the tubular cell. 3. Diffusion of these ions into the medullary interstitium establishes an osmotic gradient which drives the movement of water into the interstitium from the thin descending limb of the loop of Henle

4. Na and Cl are continually reabsorbed from the tubular fluid in the thick ascending limb with movement of fluid along the tubule 5. Consequently, the medullary interstitium becomes increasingly concentrated resulting in an osmotic gradient that ranges from 300 mOsm/L in the outer medulla to 1200 mOsm/L in the deep medulla 6. The descending limb is very permeable to water but impermeable to solutes except urea. As a result of the osmotic gradient established by reabsorption of ions in the TAL, water moves out of the tubular fluid via osmosis 7. This causes the osmolarity of the tubular fluid to increase 8. Osmolarity increase progressively as it moves along the tubule culminating at as high as 1200 mOsm/L at the hairpin bend of the loop in juxtamedullary nephrons. 9. As the thick ascending limb is impermeable to water but is involved in the reabsorption of ions from the tubular fluid, its osmolarity progressively decreases as it flows through the descending limb and becomes more dilute 10. Permeability of the late distal tubule and collecting ducts to water is regulated by ADH secreted from the posterior pituitary

11. ADH increases the permeability of principal cells to water which moves out of the collecting duct via osmosis and into the interstitial fluid of the inner medulla 12. Water is then reabsorbed into the bloodstream via the vasa recta 13. Urea within the late collecting duct then becomes increasingly concentrated and diffuses into the medullary interstitium 14. The thick ascending limb, distal tubule and CCD are impermeable to urea and so it remains within the tubular lumen

15. The thin limbs of the loop of Henle are however permeable to urea 16. As urea accumulates in the interstitium, some diffusion into the thin descending and ascending limbs occurs causing the osmolarity of the tubular fluid to increase further 17. As fluid flows along the collecting ducts water reabsorption continues via osmosis so long as ADH remains present 18. Water reabsorption further increases the concentration of urea in the tubular fluid such that more urea diffuses into the interstitium of the inner medulla 19. This is referred to as urea recycling 20. In this way, reabsorption of water from the tubular fluid of the collecting ducts promotes the accumulation of urea in the interstitial fluid of the medulla which in turn promotes further water reabsorption from the thin descending limb 21. The solutes within the tubular lumen thusly become highly concentrated and only a small volume of urine is produced

Countercurrent exchange The process whereby solutes and water are passively exchanged between blood of the vasa recta and medullary interstitium as a result of countercurrent flow 1. Vasa recta consist of descending and ascending limbs parallel to one another and the loop of Henle 2. Blood entering the vasa recta has an osmolarity of around 300 mOsm/L 3. As blood flows along the descending limb into the renal medulla which becomes increasingly hypertonic in relation to plasma, NaCl and urea diffuse from the interstitium into the blood and water moves from the blood into the interstitial fluid 4. After the osmolarity of the blood increases and flows into the ascending part of the vasa recta where the medullary interstitium becomes progressively less concentrated, NaCl and urea diffuse from the blood back into the interstitial fluid and water diffuses from the intersitital fluid back into the vasa recta 5. Osmolarity of the blood leaving the vasa recta is slightly higher than that entering 6. Thus vasa recta provide oxygen and nutrients to the renal medulla without diminishing the osmotic gradient