Question 12

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

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College Answer

Potassium is the second most common cation in the body and the main intracellular cation. 
It is widely distributed and has many important roles. Maintenance of potassium balance 
depends mainly on secretion by the kidneys in the distal and collecting tubules. Candidates 
were expected to mention the influence of aldosterone, and other hormones such as 
glucocorticoids, catecholamines and vasopressin have as well as factors such as 
acidosis/alkalosis. Candidates who had a systematic and structured approach performed 


  • 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.

Stone, Michael S., Lisa Martyn, and Connie M. Weaver. "Potassium intake, bioavailability, hypertension, and glucose control." Nutrients 8.7 (2016): 444.