Function of Calcium and Vitamin D

Question 1

Effects of Hypercalcemia?

Answer 1

Nervous system depression, sluggish reflexes Increases QT interval in heart (i.e. arrythmia) Lack of appetite and constipation

Question 2

Effects of Hypocalcemia?

Answer 2

Nervous system excitement; tetany can occur (counter muscles are trying to contract) Carpopedal spasm in hands Lead to seizures Tetany at 6 mg/dl, death at 4 mg/dl

Question 3

Where is most of the Ca in the body?

Answer 3

99% in bones, 1% in cells, 0.1 % in extracellular fluid

Question 4

3 forms of plasma calcium

Answer 4

1. over 40% bound to albumin (protein)
2. < 10% in salts with citrate and phosphate
3. 50% ionized in free solution

all of these are in equilibrium

Question 5

Protein bound Ca acts as a reservoir to protect against?

Answer 5

• Ca precipitation and ectopic calcification
  
  • too much Ca in the wrong place starts to crystallize
• Ca2+ and PO43- exist in plasma at or near there solubility point
  
  • can’t afford to have free Ca, need to be bound to albumin

Question 6

True/False: Albumin bound to Ca2+ can’t be lost in kidney and can’t cross capillaries

Answer 6

True! Anything bound to albumin can’t be filtered out through kidneys or cross capillaries only free Ca can do this! Albumin levels affect Ca levels!!

Question 7

pH affects plasma Ca2+ levels: Acidosis _ free Ca2+ Alkalosis_ free Ca 2+

Answer 7

Acidosis increases free Ca 2+ (displaced from albumin by H+) Alkalosis decreases free Ca2+ (more binding to albumin)

Question 8

How does hyperventilation change free Ca2+ levels?

Answer 8

Hyperventilation —> acute respiratory alkalosis—> decrease free Ca2+ levels numbness and tingling associated with hyperventilation

Question 9

How does kidneys and bone contribute to calcium balance in the body?

Answer 9

Most Ca2+ filtered in kidney is reabsorbed (99%) small amount of bone calcium is reabsorbed, put into circulation similar amount of calcium is deposited so no net change overall (in equilibrium)

Question 10

How does 3 functions in the body control/affect processes where Ca2+ enters or leaves plasma?

Answer 10

Stomach/diet: increase or decrease absorption Kidney: may change excretion from kidney May change deposition in bone (increase or decrease free Ca)

Question 11

What are 2 regulators of Ca2+ metabolism?

Answer 11

PTH, Vitamin D

Question 12

• How is PTH synthesized?
• What is the biologically active portion?
• Synthesis and Storage levels?
  
  • what regulated this?

Answer 12

• Preprohormone (precursor to peptide hormone);
  
  • 1-34 is biologically active portion
• Is Constitutively synthesized
  
  • (Ca levels regulate degradation)
• Don’t make large excess

Question 13

What are the effects of PTH in bone and kidney and gut?

Answer 13

• Bone:
  
  • Increases bone resorption of Ca 2+
    
    • increase both Ca2+ and phosphate release from bone
• Kindey:
  
  • Increase renal phosphate clearance (prevent formation of calcium phosphate precipitates)
  • Increase renal reabsorption of Ca 2+
• Gut:
  
  • Increase intestinal reabsorption of Ca2+ (via Vitamin D)

Question 14

What else is released with Ca2+ from bone?

Answer 14

Phosphate

Question 15

How does PTH prevent hypocalcemia due to dietary insufficiency?

Answer 15

Release of Ca 2+ from bone (largest supply)

Question 16

Where in the body does PTH bind to receptors? What type of receptors are these?

Answer 16

Binds to receptor linked two G-proteins in the kidney and bone (osteoblasts)

Question 17

Low plasma levels of Ca2+ stimulate PTH secretion via?

Answer 17

• G-protein-Ca2+ receptor on the parathyroid membrane senses low Ca2+
• The G-proteins acts on adenyl cyclase
  
  • increases cAMP production which increases the release of PTH

Question 18

What is the clearance of PTH in the kidneys?

Answer 18

Very fast! this is because you want to keep the Ca2+ levels in a narrow range (don’t want PTH hanging around) ** Cut out parathyroid glands and PTH is gone in an hour!

Question 19

• Vitamin D (calciferol) is not really a vitamin but a?
• Made of?

Answer 19

• sterol hormone made in skin
• Vitamin D (calciferol) is:
  
  • D2 (ergocalciferol- diet) +
  • D3 (cholecalciferol-skin)

Question 20

• What is required in first step of Vitamin D (calciferol) synthesis?
• Where do the two hydroxylations occur?

Answer 20

• Requires sunlight in order to convert 7-Dehydrocholesterol to Vitamin D3
  
  • 1st hydroxylation in liver
  • 2nd hydroxylation in kidney

Question 21

What does adding the second hydroxyl to Vitamin D do?

Answer 21

1,2 (OH)2 D3 is 100 times more active

Question 22

• What is the key to vitamin D synthesis?
• What regulates it?

Answer 22

• 1 alpha-hydroxylase
  
  • PTH (stimulates)
  • 1,2 (OH)2D3 (inhibited by its own product)
  • Gucocorticoids (inhibits)

Question 23

What type of receptors do Vitamin D3 act on?

Answer 23

• Typical steroid hormone (intracellular receptor)
  
  • Hormone receptor complex (HRC) binds to DNA
  • Modulates transcription by recruiting RNA Pol II

Question 24

Where is the primary target of Vitamin D in GI?

Answer 24

• Intestines
  
  • (brush borders with calbindin a Ca2+ binding protein)
• Vitamin D in gut increases Ca2+ absorption by:
  
  • inducing transcription of calbindin

Question 25

What is primary target cell of vitamin D in bone?

Answer 25

• Osteoblast
• Build strong bones by stimulating transcription:
  
  • producing osteocalcin, collagen type 1, and alkaline phosphotases

Question 26

What does Vitamin D indirectly stimulate in the bone?

Answer 26

Osteoclasts Increases release of Ca2+ and PO4 3- *unlike direct stimulation of PTH

Question 27

What is the action of Vitamin D in the kidney?

Answer 27

Increases Ca2+ reabsorption

Question 28

Diseases of Vitamin D deficiency in children and adults?

Answer 28

Rickets (children); bones are weak and trying to grow Osteomalacia (adults)

Question 29

Alopecia totalis is lack of Vitamin D where?

Answer 29

In hair follicles- lack of maturation due to lack of vitamin D receptors