Question 5

College Answer

This question related to the renal handling of potassium, the physiology of potassium in the rest of the body was not relevant. Ultimately net potassium flux is a function of filtration, reabsorption, secretion and excretion. Good candidates divided the nephron into relevant sections and described how potassium was handled in each section. They correctly described the percentage reabsorption along each section, as well as the relevant active and passive pathways for reabsorption and/or secretion, including the cells and channels/pumps involved. The physiological factors regulating each of these mechanisms were then described in correct detail.

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. 

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