Question 8(p.2)

College Answer

Most candidates did not appreciate that serum potassium is a function of two variables:

1. Total body potassium
2. Distribution between the extracellular and intracellular fluid compartments.

Approximately 98% of total body potassium is intracellular due to the action ofNa+/K+ATPase. Potassium is important in the electrophysiology of excitable cells and changes in serum potassium can affect their function. Hence the importance of keeping the serum potassium within a narrow normal range. Again most candidates did not provide the overview that serum potassium levels reflect a balance between intake, output and transcellular distribution. Normal dietary intake is highly variable. Transcellular distribution by the mechanisms of insulin and glucagon, catecholamine's and P2 activity and acid base changes all work to rapidly restore changes in serum potassium levels back towards the normal range. Many candidates did not provide any details on the long term renal regulation of serum potassium involving distal tubule potassium secretion and aldosterone and also the effect of distal tubular flow and sodium excretion.

The effects of hyperkalaemia were better described than the first part of the question. Most candidates concentrated on the cardiac effects where most marks were awarded. The effects of an increased potassium on the cardiac action potential earned extra marks. The correlation between actual serum potassium level and ECG  changes is variable and depends on many factors including how acute or chronic the hyperkalaemia is.
Treatment of hyperkalaemia was mentioned by a few candidates but attracted no extra marks.

Discussion

So, from the examiner comments, it seems like when they were asking for the "determinants of serum potassium" they actually meant "distribution and regulation of potassium". 

• 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)
• 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
• Consequences of hyperkalemia:
  • ​​​​​​ECG changes of hyperkalemia seems to be where the marks were:
    • Tall peaked T waves with a narrow base
    • Shortened QT interval
    • ST-segment depression
    • P wave widening/flattening, PR prolongation
    • Sinus bradycardia, high-grade AV block
    • Conduction blocks (bundle branch block, fascicular blocks)
    • QRS widening with bizarre QRS morphology
    • Cardiac arrest
  • Other consequences of hyperkalemia:
    • Paraesthesia
    • Weakness and flaccid paralysis (diaphragm is usually spared)
    • Loss of reflexes
    • Normal anion gap metabolic acidosis (due to decreased renal ammoniagenesis)

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.