Endo: Control of Mineral Metab

Question 1

Why are calcium and phosphate so tightly regulated?

Answer 1

Calcium-phosphate crystals easily precipitate out of solution (not very soluble) -> problems if there is excess

Question 2

Sx of hypercalcemia? (1)

Sx of hypocalcemia? (2)

Answer 2

• Hypercalcemia: lethargic
• Hypocalcemia: hyperactive muscles, seizures

Question 3

Why does hypocalcemia cause increased excitability when Ca is needed for muscle contraction?

Answer 3

• Less positive charge (less Ca) extracellularly makes the cell relatively more positive
• The effective resting potential is increased

Question 4

Describe 3 locations of calcium regulation

Answer 4

• Absorption/Secretion by gut
• Filtration by kidney
• Exchange with bone

Question 5

Describe the fast Calcium exchange in bones.

Answer 5

• Calcium level in canalicular fluid is maintained to be lower than plasma calcium level
  
  • Calcium naturally moves into canaliculi
  • Osteocytes pump Ca back out into plasma

*Fast calcium exchange does NOT include phosphate

Question 6

Describe the slow Calcium exchange in bone

Answer 6

Osteoclasts break down bone matrix, releasing both calcium and phosphate

Question 7

Name 2 other factors that stimulate PTH secretion besides Ca.

Answer 7

PTH is stimulated by

• High serum phosphate
• Mildly low serum magnesium (supressed if very low serum magnesium)

Question 8

Where is PTH produced?

What does it primarily respond to?

Answer 8

• PTH is made by chief cells of parathyroid
• PTH is made in response to low plasma calcium

Question 9

What type of hormone is PTH?

(peptide, steroid, catecholamine)

Answer 9

PTH is a peptide hormone (stored in vesicles)

Question 10

How does low extracellular calcium trigger PTH release? (4)

Answer 10

• Calcium sensor on chief cells is a GPCR (Gq)
  
  • When calcium is bound to GPCR, it’s inactive
  • When serum calcium decreases and the GPCR is unbound, GPCR (Gq) is activated
• Gq activation -> PLC -> IP3, DAG -> increased intracellular Ca release -> exocytosis of PTH veiscles

Question 11

PTH functions (5)

Answer 11

• Increases Ca concentration
  
  • Increases Ca reabsorption in distal convoluted tubule
  • Increases calcitriol production in kidneys (which increases gut absorption of Ca)
  • Causes osteocytes to pump more Ca out of canaliculi
• ​Decreases phosphate concentration
  
  • Decreases phos reabsorption in proximal convoluted tubule
• Increases bone resorption

Question 12

How does PTH increase Calcium absorption in the gut?

Answer 12

• PTH upregulates the kidney and liver enzymes that hydroxylate Vitamin D
• More calcitriol -> increased gut absorption of Ca

Question 13

Describe Vitamin D metabolism

Answer 13

• We obtain cholecalciferol from…
  
  • diet (ergocalciferol)
  • sunlight conversion of 7-dehydrocholesterol
• Cholecalciferol is hydroxylated in the liver to make calcidiol
  
  • Storage form
• Calcidiol is hydroxylated in kidneys to make calcitriol
  
  • Active form

Question 14

How is calcium absorbed by the enterocyte?

How does Vitamin D affect this?

Answer 14

• Trp V5 channel on apical side of enterocyte brings Ca into cell
• Within enterocyte, Calcium binds to calbindin (a transient calcium buffer)
• Calcium then released from basolateral side into bloodstream

Vitamin D increases both Trp V5 and calbindin

Question 15

What is the effect of PTH on serum Ca, serum phos, and urine phos?

Answer 15

PTH causes

• Increased serum Ca
• Decreased serum phos
• Increased urine phos

Question 16

What is the effect of PTH on RANK-L?

Answer 16

• PTH causes increased RANK-L secretion by osteocytes
• Binds RANK on osteoclasts to activate them