Question 4

College Answer

Higher scoring candidates described the counter-current multiplier mechanism, the counter-current exchanger and the contribution of urea cycling to the medullary osmotic gradient. Detailing the mechanisms as to how they may be established, maintained and or regulated. Descriptions of the multiplier (LOH) alone did not constitute a passing score. Values for osmolality at the cortex & medulla and within the different parts of the LOH was required. A description of the counter-current exchanger system where inflow runs parallel to, counter to and in close proximity to the outflow was expected. This could have been achieved by describing the anatomical layout of the loop of Henle and the vasa recta.

Discussion

• The "single effect":
  • The thick ascending limb of the loop of Henle extracts solutes from the tubule fluid 
  • This transfers the solutes to the renal medulla
  • The renal medulla then becomes hyperosmolar (1200 mOsm/kg)
  • This facilitates the removal of water from the thin descending limb of the loop of Henle
  • Thus, fluid in the thin descending limb also becomes hyperosmolar
• Countercurrent multiplication of the single effect
  • The movement of hyperosmolar fluid up into the thick ascending limb continuously delivers more solute
  • Thus, more solute is transferred to the medullary interstitium
  • The hyperosmolarity of the interstitium then extracts more water from the descending tubule fluid, maintaining its hyperosmolarity
  • The concentration gradient maintained in this way reduces the energy cost of extracting solutes from the thick ascending limb.
• Countercurent exchange in the vasa recta
  • The vasa recta are permeable to water and solutes
  • Solutes diffuse into the descending vasa recta, and then back out again as the blood returns via the ascending vasa recta
    • These vessels also have slower flow because of increased crossection, increasing the efficiency of solute exchange
  • This mechanism prevents the washout of concentrated inner medullary solutes
  • More water returns via the ascending vasa recta, removing reclaimed water from the renal medulla
• Role of intrarenal urea recycling:
  • Proximal cortical collecting duct is permeable to water but not to urea.
  • Water can move out of the cortical collecting duct, but urea cannot, which causes the concentration of urea in the duct
  • Distal collecting duct is permeable to urea
  • Thus, the concentrated urea can move into the renal interstitum
  • From there, it can be absorbed into the ascending limb fluid, and recycled
  • Vasopressin increases the permeability of the collecting duct to urea.
• ​​​​​​​The osmolalities at different points in the tubule are:
  • ​​​​​​​Renal interstitial osmolality values:
    • Cortex osmolality: 300 mOsm/kg
    • Outer medulla: 800 mOsm/kg
    • Inner medulla:  1200 mOsm/kg
  • Loop of Henle osmolality values:
    • Proximal tubule, straight part: 300 mOsm/kg
    • Descending limb: 800 mOsm/kg
    • Hairpin turn: 1200 mOsm/kg
    • Ascending thin limb: 800 mOsm/kg
    • Ascending thick limb: 100 mOsm/kg, at the end

Pallone, Thomas L., et al. "Countercurrent exchange in the renal medulla." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 284.5 (2003): R1153-R1175.

Sands, Jeff M., and Juha P. Kokko. "Current concepts of the countercurrent multiplication system." Kidney International Supplement 57 (1996).

Sands, Jeff M., and Harold E. Layton. "The physiology of urinary concentration: an update." Seminars in nephrology. Vol. 29. No. 3. WB Saunders, 2009.