Renal – Counter-current

Master answer

Medullary concentrating gradient

• physiological process which sets up a concentration gradient from cortex through to medulla
• allows formation of concentrated urine
• Mechanisms:
  • Counter current Multiplier: creates concentrated medullary interstitium
  • Counter current Exchange (vasa recta): maintains intersisital osmotic gradient
  • Recycling of urea: contributes to high osmolarity of medullary interstitium
• Normal cortico-medullary gradient 300-1400mOsmol.

Counter-current Mechanism in Kidney

Counter Current Multiplier:

Set-up

1. Descending limb LoH Permeable to water only 
2. Ascending limb LoH Permeable to NaCl only
   • Thin passive NaCl reabs
   • Thick NaCl via active NKCCT cotransport and paracellular 

Generation

1. Enters LoH osmolarity throughout = 300mOsm
2. Max effort of NKCCT = 100mOsm/kg
   • Tubular OSM = 200/kg
   • Interstitial Osm = 400/kg
3. Descending limb diffuses water down gradient
   • Descend limb OSM now 400
4. Process repeats (flow, pump salt, equilibrate water)

Counter Current Exchange:

• Hairpin loop arrangement of the vasa recta in the juxta-medullary nephrons.
• Provides blood flow to medullary tissue without impact of the cortico-medullary gradient.
• Relies on slow flow of blood.
• Mechanism
  • On descent, water is lost from capillaries and NaCl is absorbed into capillaries increasing osmolarity
  • On ascent water is reabsorbed and solute is lost

Role of Urea in Medullary Concentration Gradient

• 900mmol/day filtered
• 350-550mmol/day reabsorbed.
• Comprises 50% of osmolality (300-650 mOsm/kg)
• Freely filtered at the glomerulus
  • Secreted by thin limbs of LoH down concentration gradient from medullary interstitium to tubular fluid.

• As water and Na are reabsorbed, tubular [Urea] increases
• [Urea] = >500mmol/L at collecting ducts
• Equilibrates with interstium due to slow flow rates.
• ↑ADH
  • urea transporters UT1 and UT3 insertion → ↑ CD permeability to urea
  • → ↑ medullary gradient (further 10% reabsorption if required)

Gladwin / JC 2020

Answer by Gladwin, JC