Question 14

College Answer

The best answers demonstrated an appreciation of the multiple roles of potassium in normal physiology and described the integrated regulation of potassium concentration/distribution as opposed to many answers that seemed to focus purely on the renal handling of a filtered potassium load.

Discussion

• Physiological role of potassium
  • Maintenance of intracellular fluid tonicity / regulation of cell volume
  • Maintenenance of resting membrane potential
  • Responsible for the excitability of excitable tissues, action potentials etc
  • Structural function (incorporated into bone, ribosomes, DNA and RNA)
  • Intracellular and extracellular messenger function (mediator of nociception, inflammation, vasodilation)
• Distribution of potassium
  • Total body potassium is 40-55 mmol/kg
  • 90% is in the intracellular fluid.
  • 2% extracellular fluid
  • 8% non-exchangeable pool (bone)
• Regulation of potassium
  • Intake is not regulated (passive paracellular gut absorption)
  • Renal elimination is 95% of the total daily potassium excretion.
  • Transcellular flux maintains homeostasis of the ECF potassium concentration
• Elimination is influenced by:
  • Oral potassium intake 
    • Produces immediate kaliuresis; intestinal K⁺sensor is implicated
  • Aldosterone
    • Increases renal elimination by increasing the activity of ENaC channels in the nephron
    • Increases GI elimination in colon (5% of total)
  • 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
• Transcellular flux is influenced by:
  • Insulin  by the insertion of extra Na⁺/K⁺ ATPase pumps into the membrane, thus increased cellular potassium uptake
  • Catecholamines increase the activity Na⁺/K⁺ ATPase pumps
  • Aldosterone increases the activity of Na⁺/K⁺ ATPase pumps in skeletal muscle 
  • Nonspecific cation channels eg. acetylcholine-gated sodium channels in the neuromuscular junction are capable of leaking potassium out of the cell
  • Acid-base changes effectively produce H⁺/K⁺ exchange across the membrane, i.e. metabolic acidosis produces a movement of potassium into the ECF
  • Hyperosomolarity of the ECF dehydrates cells and moves potassium into the ECF by solute drag
  • Hypothermia produces an intracellular shift of potassium

Rastegar, Asghar. "Serum potassium." Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition (1990).

Palmer, Biff F. "Regulation of potassium homeostasis." Clinical Journal of the American Society of Nephrology 10.6 (2015): 1050-1060.

Gumz, Michelle L., Lawrence Rabinowitz, and Charles S. Wingo. "An integrated view of potassium homeostasis." New England Journal of Medicine 373.1 (2015): 60-72.

Greenlee, Megan, et al. "Narrative review: evolving concepts in potassium homeostasis and hypokalemia." Annals of internal medicine 150.9 (2009): 619-625.