Question 14

Describe the physiological role, distribution and regulation of potassium ions (K+ ).

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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.


  • 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, ribosomesDNA 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.