Calcium Homeostasis and the Parathyroid Gland

Question 1

How often in human skeleton replaced?

Answer 1

10-15 years, it is therefore very dynamic

Question 2

What is the function of calcium in bone?

Answer 2

• protects vital organs
• supports muscles
• reservoir of calcium

Question 3

What is the function soluble calcium?

Answer 3

• excitable tissues
• muscles/nerves
• cell adhesion

Question 4

What is the percentage of the body’s calcium is in the bones?

Answer 4

> 99%

Question 5

What are the 3 functions of the skeleton?

Answer 5

mechanical - support and muscle attachment
protective - vital organs and marrow
metabolic - calcium and phosphate

Question 6

What organs and chemicals are involved in calcium homeostatsis?

Answer 6

bones can increase and decrease Ca, GI tract can only increase Ca, kidneys can increase and decrease Ca
Vit D, PTH, FGF23

Question 7

What percentage of soluble calcium is free?

Answer 7

50% is free

50% is bound to albumin

Question 8

What stimulates PTH to be secreted?

Answer 8

Low calcium or high potassium

Question 9

What is the effect of PTH?

How does it bring about this effect?

Answer 9

Increase calcium reabsorption in renal distal tubule
Increases intensity calcium absoprtion (via activation of VitD)
Increases calcium release from bone by stimulating osteoclasts
Decreases phosphate reabsorption

Question 10

How does PTH affect the kidneys?

Answer 10

Increases distal tubular reabsorption of calcium (and inhibits PO4 reabsorption)
PTH stimulates the activation of VitD to 1,25(OH)2D3

Question 11

How does PTH affect bone?

Answer 11

Increases bone resorption by binding to GPCR’s on osteoclasts and stimulating their activity

Question 12

Describe the negative feedback of PTH?

Answer 12

PTH transcription inhibited by 1,25D3

PTH translation inhibited by increased serum calcium

Question 13

Describe the role of calcitonin?

Answer 13

Produced by parafollicular cells (c-cells) in hypercalcaemia
Direct affect of osteoclasts, decreases bone resorption
Plays small role, not essential to life

Question 14

Describe what happens during hypocalcaemia or hyperphosphataemia

Answer 14

Increased PTH secretion:

• decreases urinary calcium
• increases urinary phosphate
• increases osteoclast activity
• increases activation of VitD to 1,25D3 in kidneys –> increased absorption of calcium of GI tract

Question 15

Describe what happens during hypercalcaemia

Answer 15

PTH secretion decreased, calcitonin released

• Decreases bone resorption
• Decreases urinary phosphate
• Increases urinary calcium
• Decreases 1,25D3 production which decreases calcium and phosphate absorption in the GI tract

Question 16

What is the precursor of VitD in skin?
What is the inactive form of VitD?
What is the active form of VitD?
What is the VDR?

Answer 16

7-dehydrocholesterol
25-hydroxyvitamin D
1,25-dihydroxyvitamin E
active vitD binds to VDR intracellularly, similar to other steroid hormone receptors

Question 17

What is FGF23?
Where is it produced?
When is it released?
What effect does it have?

Answer 17

Fibroblast Growth Factor 23
Produced by osteocytes and osteoblasts
Released in response to high serum PO4
It increases renal excretion of PO4 and surpasses renal activation of VitD (reduces GI absorption of PO4)

Question 18

Describe VitD metabolism?

Answer 18

cholesterol in skin converted to VitD3 by UV light
VitD3 obtained in diet
Travels to liver –> 25(OH)D3. hydroxylated
Travels to kidneys –> active 1,25(OH)2D3
Active VitD increases Ca and PO4 absorption from GI tract

Question 19

What happens in hyperphosphataemia?

Answer 19

PTH secretion and secretion of FGF23 from bone

FGF23 increases renal excretion of PO4, decrease activation of VitD in kidneys

Question 20

What is bone made of?

Answer 20

collagen fibres with favourable orientation
other protein essential to bone function
contains several types of cells

Question 21

What are the 3 cell types within bone?

Answer 21

osteocytes - embedded in calcified bone, long processes which contact other 2 cells
osteoblasts - bone forming cells (origin: mesenchymal stem cells)
osteoclasts - bone resorbing cells (origin: bone marrow lineage)

Question 22

Where does the bone remodelling cycle take place?

Answer 22

In trabecular bone

Question 23

Name 4 types of metabolic bone disease

Answer 23

hyperparathyroidism
rickets/osteomalacia
renal osteodystrophy
osteoporosis

Question 24

3 types of hyperparathyroidism

Answer 24

primary - PTG adenoma, increases serum calcium, decreases serum phosphate, loss of negative feedback from calcium
secondary - renal disease, increased phosphate, decreased activation of VitD
tertiary - long standing 2nd leads to irreversible PTG hyperplasia.

Question 25

What are the clinical features of primary HPT?

Answer 25

``` lethargy, confusion thirst, renal stones constipation fractures depression hypertension ```

Question 26

What is the cause of rickets/osteomalacia? What are its effects? What is the treatment?

Answer 26

Deficiency of active Vit D, dietary/sunlight Lack of mineralisation of collagen, failure to absorb sufficient calcium from GI Vitamin D replacement

Question 27

What is renal osteodystrophy?

Answer 27

Renal failure that leads to low serum calcium and high serum phosphate, decreases VitD activation Increased PTH secretion Increased fracture risk

Question 28

What is osteoporosis? Effect of oestrogen deficiency? What is the treatment?

Answer 28

Loss of bone mass/density = both mineral and osteoid Oestrogen deficiency increases bone remodelling and degree of bone resorption Hormone replacement or bisphosphonates (poison osteoclasts.