First, we will follow filtrate processing through the loop of Henle, to see how the loop functions as a countercurrent multiplier to establish the osmotic gradient. The countercurrent multiplier functions because of two factors:
- The descending limb of the loop of Henle is relatively impermeable to solute and freely permeable to water. Water passes osmotically out the filtrate all along this limb because the osmolality of the medullary interstitial fluid increases all along the descending limb. The filtrate osmolality reaches its highest point (1200 mOsm) at that bend of the loop.
- The ascending limb is permeable to solutes, but not to water. As the filtrate rounds the bend into the ascending limb, the tubule permeability changes, becoming impermeable to water and selectively permeable to salt. The Na+ and Cl- concentration in the filtrate entering the ascending limb is very high (and interstitial fluid concentrations of these two ions are lower). Na+ and Cl- reabsorption in the ascending limb is both passive (mostly in the thin segment) and active (via Na+K+2Cl- cotransporter in the thick segment). As Na+ and Cl- are extruded from the filtrate into the medullary interstitial fluid, they contribute to the high osmolality there. Because it losses salt but not water, the filtrate in the ascending limb becomes increasingly dilute. Finally, at 100 mOsm at the distal convoluted tube, it is hypoosmotic , or hypotonic, to blood plasma and cortical interstitial fluids.
There is a constant diffence in filtrate concentrations (200 mOsm) between the two limbs of the loop of Henle, and between the ascending limb and the interstitial fluid. This difference reflects the power of the ascending limb’s NaCl pumps, which are just powerful enough to create a 200 mOsm difference between the inside and outside of the ascending limb. A 200 mOsm gradient by itself would not be enough to allow excretion of very concentrated urine. The beauty of this system lies in the fact that, because of countercurrent flow, the loop of Henle is able to “multiply” these small changes in solute concentrations into a gradient change along the vertical length of the loop (both inside and outside) that is closer to 900 mOsm (1200 mOsm – 300 mOsm).
Although the two limbs of Henle are not in direct contact with each other, they are close enough to influence each other’s exchanges with the interstitial fluid they share. Water diffusing out of the descending limb leaves behind an increasingly “salty” filtrate that the ascending limb then uses to raise the osmolality of the medullary interstitial fluid, Furthermore, the more NaCl the ascending limb extrudes, the more water diffuses out of the descending limb and the saltier the filtrate in the descending limb becomes. This establishes a positive feedback cycle that produces the high osmolality of the fluids in the descending limb and interstitial fluid.