H1v: The role of urea in the body

  • Urea = the end product of protein catabolism. Normal urea plasma levels:
    • 7 – 20mg/dL
    • 3 – 9mmol/L
  • 90% of nitrogen from protein catabolism enters the UREA CYCLE

Urea Cycle → occurs in liver + kidneys

2NH4+ + CO2 ⮂ UREA + 2H+ + H2O

  1. Formation of CARBAMOYL PHOSPHATE from Ammonia + HCO3
  2. Condensation of carbamoyl phosphate with ORNITHINE → CITRULLINE
  3. Citrulline condenses with ASPARTATE → ARGINOSUCCINATE
  4. Arginosuccinate is hydrolysed to form FUMARATE + ARGININE
  5. ARGININE is cleaved → UREA + ORNITHINE
  • ORNITHINE re-enters mitochondria & is combined with new CARBAMOYL PHOSPHATE to form CITRULLINE
Urea
Urea Cycle

Enterohepatic Circulation

  • Urea diffuses into blood → intestine
  • Bacterial URASE cleaves urea to liberate NH3 + CO2
  • Some NH3 → faeces
  • Some NH3 → reabsorbed back into blood → KA ENTEROHEPATIC CIRCULATION
Enterohepatic Circulation

Renal Handling of Urea

  • Urea has 2 roles in the kidney
    1. Excrete product of nitrogenous waste
    2. Concentrate urine

Filtration → all urea passes to ULTRAFILTRATE

Reabsorption

  • All urea movement is passive
  • 50% in PCT
  • As ultrafiltrate passes long PCT, H2O is reabsorbed, ↑[urea] in lumen → favouring diffusion from tubule lumen → ISF → peritubular capillaries
  • Then completely impermeable to UREA in LoH, DCT & cortical collecting duct
  • In CORTICAL collecting duct under influence of ADH –. Further 10% urea reabsorbed via facilitated diffusion (urea transporters which are ADH dependent)

NB: Urea reabsorption is completely dependent on H2O reabsorption

Urinary Concentration

  • Urea is responsible for 50% of medullary ISF hyperosmolarity
  • Because there is no urea reabsorption after PCT → medullary CD
  • There is a v. high [urea] medullary CD & when urea transporters are inserted under influence of ADH, there’s a huge [ ] grad to drive it into Medullary ISF
  • There it promotes even more H2O reabsorption to create a concentrated urine
Urea Recycling