Regulation of ECF Potassium

Question 1

Normal ECF potassium

Answer 1

• 3.5 - 5.0 mM
• < 3.5 mM = hypokalemia
• > 5.0 mM = hyperkalemia

Question 2

Potassium reabsorption & secretion @ kidney

Answer 2

• filtration = 30 g K⁺, but excretion = 0 - 45 g K⁺
• @ proximal segments: 80% of filtered load is reabsorped via passive, peracellular pathway
• @ LOH: transcellular reabsorption
  
  • Na/K/2Cl co-transporter @ apical then through channels @ basolateral (10-15% of filtered load)
• @ collecting duct: K⁺ reabsorbed by principal cells
• ~ all of filter K⁺ reabsorbed; regulated K⁺ secretion @ fine tuning segments = potassium excretion/balance

Question 3

Cellular mechanism of potassium secretion

Answer 3

• occurs @ principal cells @ fine tuning segments

1. basolateral entry of K⁺ (via Na/K ATPase)
2. apical secretion of K⁺ into tubular lumen via ion channels (passive)

Question 4

Regulation of potassium secretion: mass-action effect

Answer 4

• change in [ECF K⁺] ==> change in secretion via law of mass action
• K⁺ = rate-limiting step in ATPase pump cycle ==> [K⁺] determines rate of pump into cells
• [K⁺] w/in cells determines electrochemical gradient
• works best for large changes in [K⁺]

Question 5

Regulation of potassium secretion: hormonal regulation

Answer 5

• [K⁺] changes stimulate adrenal zona glomerulosa ==> increase aldosterone

1. aldosterone ==> increased # of Na/K/ATPase pumps
   
   1. increased rate of K⁺ entry
2. aldosterone ==> increased # of apical sodium channels
   
   1. increased outward K⁺ movement in exchange for inward flow of Na⁺
3. aldosterone ==> increased # of apical potassium channels

Question 6

Regulation of potassium secretion: tubular flow

Answer 6

• slow tubular flow ==> build up of K⁺ w/in lumen
  
  • lumenal [K⁺] increases = electrochemical gradient decreases = secretion decreases
• fast tubular flow ==> secreted K⁺ is “washed away” before gradient falls
  
  • maintains steep gradient for apical K⁺ flow
• e.g. Loop diuretics =
  
  • 1. inhibit reabsorption of 15% of K⁺
  • 2. increased water w/in tubule @ fine-tuning segments ==> increased flow ==> enhanced K⁺ secretion

Question 7

Regulation of potassium secretion: hormonal vs. tubular flow

Answer 7

• e.g. primary hyperaldosteronism:
  
  • aldosterone ==> increased potassium secretion + increased sodium reabsorption (+ water = decreased tubular flow)
  • ultimately: potassium secretion increases bc elevated ECF volume/MAP maintains tubular flow
• e.g. cardiac insufficiency ==> RAS ==> secondary hyperaldosteronism
  
  • ultimately: potassium secretion decreases bc decreased MAP = decreased GFR ==> decreased tubular flow

Question 8

Regulation of potassium secretion: pH

Answer 8

• alkalosis increaseds potassium secretion ==> hypokalemia
• high pH ==> K⁺ into cells (including tubular cells) = more K⁺ crosses apical membrane
• K⁺ ion channels inhibited by increased [H⁺]
  
  • w/alkalosis + low [H⁺] ==> inhibition is released ==> faster K⁺ flow into lumen
• acidosis
  
  • mild/moderate ==> inhibition of K⁺ channels ==> decreased K⁺ secretion
  • severe ==> decreases Na reabsorp = increased water and tubular flow ==> increased K⁺ secretion
  • overall slightly unpredictable