Question 8

College Answer

This question covers a core physiology topic. The detail required is well described in the recommended reference texts. Generally, this question was poorly answered. From an answer template perspective, a "describe question" in this context involves both the stating the relevant potassium handling mechanism and then giving a description of how it occurs and how this system is regulated. Many answers that scored poorly simply listed sites of potassium handling but excluded the details surrounding the specific receptors and channels involved as well as the processes that exist to perpetuate and regulate these biological processes. Simple identification as to whether the potassium was being secreted or reabsorbed as well as the location as to where this may occur within the nephron, were often not specifically detailed or used interchangeably. Such answers scored poorly.

Discussion

• Potassium is freely filtered in the glomerulus
• 50-60% of potassium is reabsorbed in the proximal tubule:
  • Several mechanisms are involved, but the most important is solute drag
  • Potassium is carried across the epithelium by moving together with the reabsorbed water
  • This is not under any specific regulatory control
• In the thin limbs of the loop of Henle, potassium undergoes countercurrent exchange
  • Potassium is added to the tubular fluid in the thin descending limb
  • It then diffuses out again in the ascending limb
  • The net effect of this is a conservation of potassium in the inner medulla
• 30% of filtered potassium is reabsorbed in the thick ascending limb
  • This is due to the NKCC2 co-transporter, the drug target of frusemide
• Potassium is secreted into the tubular lumen in the distal convoluted tubule and the collecting duct
  • This happens because of ENac activity, which reclaims sodium from the tubular fluid
  • As the result of this, potassium leaks out of the tubule cells to maintain electroneutrality
  • With increased sodium delivery to the distal nephron, sodium reabsorption increases and potassium loss increases.
  • As the result of this potassium secretion, urinary potassium increases to 15-40 mmol/L
  • Apical ROMK channels are responsible for most of the potassium secretion in the distal nephron
• The regulatory influences that play a role in the distal nephron are:
  • Aldosterone (increases the activity of ENaC channels
  • Vasopressin (increases the availability of ROMK channels)
  • High potassium intake: leads to the increased expression of ROMK channels
  • High distal sodium delivery: compensatory increase in potassium secretion to maintain electroneutrality.
  • Acid-base disturbances: metabolic acidosis causes distal potassium secretion to decrease, probably because of the extreme sensitivity of sodium and potassium channels to intracellular pH. 

Palmer, Biff F., and Deborah J. Clegg. "Physiology and pathophysiology of potassium homeostasis: core curriculum 2019." American Journal of Kidney Diseases 74.5 (2019): 682-695.

Wright, Fred S. "Sites and mechanisms of potassium transport along the renal tubule." Kidney international 11.6 (1977): 415-432.

Ludlow, M. "Renal handling of potassium." ANNA journal 20.1 (1993): 52-58.

Malnic, Gerhard, et al. "Regulation of K+ excretion." Seldin and Giebisch's The Kidney. Academic Press, 2013. 1659-1715.

De Rouffignac, C., and F. Morel. "Micropuncture study of water, electrolytes, and urea movements along the loops of Henle in Psammomys." The Journal of clinical investigation 48.3 (1969): 474-486.

Burg, Maurice B. "Thick ascending limb of Henle's loop." Kidney international 22.5 (1982): 454-464.

Ellison, D. H., H. Velazquez, and F. S. Wright. "Mechanisms of sodium, potassium and chloride transport by the renal distal tubule." Mineral and electrolyte metabolism 13.6 (1987): 422-432.

Subramanya, Arohan R., and David H. Ellison. "Distal convoluted tubule." Clinical Journal of the American Society of Nephrology 9.12 (2014): 2147-2163.

Nichols, C. G., K. Ho, and S. Hebert. "Mg (2+)‐dependent inward rectification of ROMK1 potassium channels expressed in Xenopus oocytes." The Journal of Physiology 476.3 (1994): 399-409.

Huang, Chou-Long, and Elizabeth Kuo. "Mechanism of hypokalemia in magnesium deficiency." Journal of the American Society of Nephrology 18.10 (2007): 2649-2652.

Young, DAVID B. "Quantitative analysis of aldosterone's role in potassium regulation." American Journal of Physiology-Renal Physiology 255.5 (1988): F811-F822.

Siani, Alfonso, et al. "Comparison of variability of urinary sodium, potassium, and calcium in free-living men." Hypertension 13.1 (1989): 38-42.