Urea

Both a wasteful product and a useful factor in controlling water balance

Small (MW=60d)

Highly polar
--> Does not permeate lipid membrane

Step 1

Urea is freely filtered

NB:

• 100% of filtered amount
• About same concentration as plasma

Step 2

In proximal tubules, half is reabsorbed

Urea concentration increases as water is reabsorbed

--> Passive diffusion out of lumen
* Via paracellular route

NB:

• 50% of filtered amount present in lumen
• About 1.2 times the plasma concentration

Step 3

In loop of Henle (thin regions), about the same amount reabsorbed is secreted

Medullary interstitial urea concentration is high
* Increases from outer to inner medulla
* Peak concentration depends on hydration status and ADH level

Paracellular route not available because tight junctions in loop of Henle are not permeable

--> Facilitated diffusion into lumen
* Via urea uniporters
* In the thin regions only

From the thick ascending limb to medullary collecting ducts
--> Luminal membrane urea permeability is ZERO

NB:

• 100-110% of filtered amount present in lumen
• About 5.5 times the plasma concentration

Step 4

In medullary collecting duct, about half is reabsorbed again

As more water is reabsorbed, luminal urea concentration rises even more
* Can "easily reach 50 times greater than" plasma level

--> Diffusion out of lumen into medulla interstitium (via urea uniporter in inner medulla [AV6:p93])
* Urea uniporters can be constitutive, or stimulated by ADH

--> Provides the source of urea that diffuse into the lumen at the loop of Henle

NB:

• 50% of filtered amount present in lumen, and excreted in urine
• About 25 times the plasma concentration