Question 7

College Answer

Answering this question well required the demonstration of understanding of the concept of achieving maximum urinary concentrating ability. Answers required a description of the usual concentrating processes and the changes that would occur in circumstances where maximally concentrated urine would be made. A key concept was the creation of a medullary concentration gradient to allow water reabsorption independent of solute reabsorption. This required an explanation of the contribution of the loop of Henle, the vasa recta, and urea cycling in the creation and maintenance of this gradient, along with the impact of ADH. More detailed explanation of each contribution was required as overarching statements were not sufficient to attract all marks for each section. Answers that focused solely on the counter-current exchange and multiplier process were insufficient on their own to achieve a passing mark. The examiners commented that a significant proportion of candidates excluded the role of urea in their answers.

Discussion

This requires the candidate to explain the countercurrent mechanism, the role of urea, and the effects of vasopressin, all in 10 minutes.

• Countercurent exchange in the vasa recta maintains a high urea concentration in the renal medulla
  • 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
  • In this way, the inner medulla achieves an osmolality of 1200 mOsm/kg
• Vasopressin increases water reabsorption along the medullary concentration gradient
  • Vasopressin increases the luminal expression of aquaporin channels
  • Water is reabsorbed through aquaporin channels (driven mainly by  the osmotic gradient of the hypertonic medullary interstitium)
  • With maximal vasopressin stimulus, maximally concentrated urine can be produced (~1200 mOsm/kg)
• 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.

Schafer, James A. "Renal water reabsorption: a physiologic retrospective in a molecular era." Kidney International 66 (2004): S20-S27.

McDonald, Keith M., et al. "Hormonal control of renal water excretion." Kidney international 10.1 (1976): 38-45.

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.