Potassium and Calcium Regulation - Muster

Question 1

What are the key regulators of immediate/short term extracellular potassium?

Answer 1

Main Factors:

1. Insulin
2. Catecholamines

Other Factors:

1. Plasma K⁺
2. Exercise (high intensity)
3. Cell breakdown
4. Chronic diseases

Question 2

How does insulin effect the regulation of potassium?

Answer 2

• Increases the activity of Na⁺/K⁺ ATPase
• Promotes bulk skeletal and muscle uptake of K⁺
• Eat => increased insulin => increase in accompanying K⁺ serum levels

Question 3

How do catecholamines effect the regulation of potassium?

Answer 3

• β-2 receptors stimulate the Na⁺/K⁺ ATPase
  
  • induces cellular uptake
• Likely a permissive action at baseline
  
  • no evidence that a K⁺ load stimulates Epi or NE

Question 4

How does plasma concentration effect regulation of potassium?

Answer 4

• Cellular uptake increased (perhaps passively) when serum K⁺ rises

Question 5

How does exercise effect the regulation of potassium?

Answer 5

• Muscle cells release K⁺ during exercise
  
  • release is related to the degree of exercise

Question 6

How does pH effect the regulation of potassium?

Answer 6

• Increase in systemic H⁺ => metabolic acidosis
  
  • gets buffered by the cells
    
    • If H⁺ goes into cell => K⁺ comes out to balance charge
      
      • result in serum rise is variable
    • up to 60%

Question 7

What cell facilitates renal excretion of potassium?

Answer 7

Principal Cell

(Collecting Duct)

Question 8

What specific channels facilitate renal excretion of potassium??

Answer 8

• Basolateral side of Principal Cell:
  
  • Na⁺/K⁺ ATPase
  • K⁺ channel (recycling)
• Luminal side of Principal Cell:
  
  • ROMK
  • Big K⁺ Channel (BK)

***Movement of K⁺ from the cell into the lumen is passive, being driven by a concentration gradient favorable to movement into the urinary space.

Question 9

What is the major physiologic regulator of potassium excretion? How does it act on the channels?

Answer 9

• Aldosterone
  
  • Increases the activity of the Na⁺/K⁺ pump
  • Increases the presence of the ROMK channel
  • Occurs in normal serum conditions or mildly elevated K⁺

Question 10

What are the locations of potassium reabsorption? Relative contribution of each tubular segment?

Answer 10

• Proximal tubule: 55-65%
  
  • via tight junctions (paracellular)
• Loop of Henle/Thick ascending limb: ~25%
• Collecting Duct—Intercalated Cell: ~10%

Question 11

What specific channels facilitate reabsorption of potassium in the intercalated cells of the collecting duct?

Answer 11

• Luminal side:
  
  • K⁺/H⁺ ATPase
    
    • pumps K⁺ against gradient into cell
    • lots of H⁺ must be processed to reabsorb K⁺
  • H⁺ ATPase
    
    • pumps H⁺ out of cell
  • Chloride channel (Cl^- leaves cell)
• Basolateral side:
  
  • Na⁺/K⁺ ATPase
  • HCO₃^-/Cl^- antiporter
    
    • reabsorb bicarb, excrete chloride

Question 12

What are the locations of calcium reabsorption? Relative contribution of each tubular segment?

Answer 12

• Proximal tubule: 65% (paracellular)
• Loope of Henle: 20% (paracellular)
• Distal Tubule: 10% (transcellular)

Question 13

What are the cellular mechanisms of calcium reabsorption?

Answer 13

• Distal Convoluted tubule:
  
  • Luminal side:
    
    • Ca²⁺ Channel (into cell)
      
      • Ca²⁺ binds Calbindin
  • Basolateral side:
    
    • PTH (parathyroid hormone)
    • Ca²⁺ ATPase
    • Ca²⁺/Na⁺ Antiporter
      
      • energy from Na⁺ with gradient powers exit of Ca²⁺

Question 14

What are the effects of PTH on bone?

Answer 14

• Stimulate an immediate release of stored skeletal calcium (and phosphorus) that is in equilibrium with extracellular fluid
• Stimulates bone reabsorption
  
  • appears to preserve trabecular bone at the expense of cortical bone with chronically stimulated PTH

Question 15

What are the effects of PTH on the kidneys?

Answer 15

• Increased Ca²⁺ reabsorption
• Increased production of activated Vitamin D
  
  • which increases gut reabsorption of Ca²⁺
• Decreases renal phosphorus absorption
  
  • actually increases excretion of PO₄^-

Question 16

What are the effects of PTH on the intestines?

Answer 16

• Increased active Vitamin D:
  
  • stimulates increased absorption of Ca²⁺ in the gut

Question 17

What does PTH respond to in order to regulate calcium?

Answer 17

• Responds to free calcium, not total body calcium
  
  • 40% of all Ca²⁺ is bound to albumin
  • 10% is bound to other stuff (phosphate, citrate)
  • 50% is available as ionized calcium (free calcium)
    
    • Plasma [Ca²⁺] is what is controlled

Question 18

What are the differences between the ROMK and BK channels?

Answer 18

• ROMK:
  
  • Renal Outer Medullary K⁺ Channel
  • usually in intracellular vesicles, unless stimulated by Aldosterone to incorporate into the plasma membrane and get rid of K⁺
  • Inhibited luminally by Angiotensin II
  • Inhibited intracellularly by Mg²⁺
• BK:
  
  • Big K⁺ Channel
  • Always present in plasma membrane
  • Usually closed (low K⁺ diet)
  • HIGH K⁺ states => a second BK will open

Question 19

What clinical situations are the ROMK & BK channels present or absent?

Answer 19

• Low potassium diets:
  
  • Limited/decreased presence of ROMK
  • No activity of BK channel
    
    • channel closed, but always present
• High potassium diets:
  
  • ROMK activated by Aldosterone
  • BK channel activated, maybe two open