Question 8(p.2)

College Answer

This question invited candidates to describe the Urea Cycle in the liver. Urea is a 
waste product derived from deamination of amino acids and the detoxification of 
NH3. Many candidates did not outline the major steps in the biochemical process.
The kidneys excrete up to 60% of the filtered urea load. The counter-current 
exchange mechanism in the renal medulla traps urea in the interstitium and 
generates a concentration gradient, essential for reabsorption of water. The 
handling of urea by the Loop of Henle and collecting duct, as well as the effect of 
ADH, should have been discussed.
Many candidates did not include sufficient detail in their answers.
Syllabus: D1 2c,g. I2a.
References: Textbook of Medical Physiology, Guyton p 795, 319.

Discussion

Renal urea handling:

• ​​​Urea is a small polar molecule which is not protein-bound
• It is freely filtered in the glomerulus
• 50% is then reabsorbed in the proximal tubule
  • This is a passive process (solute drag)
  • More water is reabsorbed than urea
  • As the result, urea is concentrated by about 50%
• In the thin descending limb, urea is concentrated signficantly
  • Some urea is added to the fluid by UT-A2 transport proteins
  • As water is removed in the loop of Henle, urea is concentrated by 30-40 times 
  • In the thick ascending limb, some urea may diffuse back out into the medullary interstitium
  • In the inner medulla, urea is recycled by countercurrent exchange and a high urea concentration is maintained to facilitate osmotic recovery of water from the tubular fluid
• The distal nephron is largely urea-impermeable
  • The recovery of water via aquaporins in the collecting duct further concentrates the urea in the lumen
  • Terminal collecting duct urea concentration can be up to 100 times greater than plasma
  • Here, urea permeability is increased, allowing urea diffusion into the inner medulla
  • Reuptake of urea from the terminal collecting duct is a part of urea recycling and helps maintain high urea concentration in the renal medulla

Klein, Janet D., Mitsi A. Blount, and Jeff M. Sands. "Urea transport in the kidney." Comprehensive Physiology 1.2 (2011): 699-729

Weiner, I. David, William E. Mitch, and Jeff M. Sands. "Urea and ammonia metabolism and the control of renal nitrogen excretion." Clinical Journal of the American Society of Nephrology 10.8 (2015): 1444-1458.

Bankir, Lise, and Baoxue Yang. "New insights into urea and glucose handling by the kidney, and the urine concentrating mechanism." Kidney international 81.12 (2012): 1179-1198.

Bankir, Lise, et al. "Direct and indirect cost of urea excretion." Kidney international 49.6 (1996): 1598-1607.