The ascending limb pumps out salt, the descending limb loses water, and the gradient multiplies
Mnemonic
“The loop makes the gradient, the vasa recta preserve it, and urea sharpens it”:
- The thick ascending limb actively pumps out sodium but is impermeable to water, making the interstitium salty and the filtrate dilute
- The thin descending limb is permeable to water only, so the filtrate entering the loop concentrates
- Repeated along the length of the loop, this multiplies a small transverse gradient into a large longitudinal one, reaching 1200 mosmol/kg at the papilla
- The vasa recta run alongside as a countercurrent exchanger, removing water without washing out the gradient
“Ascending loses salt, descending loses water” is the whole mechanism in six words.
Urea recycling in the inner medulla contributes up to half the gradient, which is why a low protein diet impairs concentrating ability.
Loop diuretics abolish the gradient by blocking the Na-K-2Cl transporter, which is why they are so powerful and why they prevent the kidney from concentrating urine at all.
Expansion
Two limbs with opposite permeabilities:
- Thick ascending limb: actively pumps sodium, potassium and chloride out via the NKCC2 transporter, but is impermeable to water. This dilutes the tubular fluid and loads the interstitium with salt
- Descending limb: permeable to water but not solute, so water leaves and tubular fluid becomes concentrated
The single effect is a gradient of only about 200 mOsm between tubule and interstitium at any one level. Because flow is countercurrent, this small effect is multiplied along the length of the loop, producing a corticomedullary gradient from 300 mOsm in the cortex to about 1200 mOsm at the papilla.
Urea recycling contributes roughly half of the papillary osmolality, entering the interstitium from the inner medullary collecting duct under the influence of antidiuretic hormone.
Long loops of juxtamedullary nephrons are essential; species with the longest loops produce the most concentrated urine. Loop diuretics block NKCC2, abolish the gradient and prevent both concentration and dilution.