The Skeleton And Metabolism

Question 1

What are the 6 hormones that have skeletal effects?

Answer 1

→ Estrogens
→ Androgens

→ Cortisol
→ PTH
→ Vitamin D
→ Calcitonin

Question 2

What is a hormone secreted from the skeleton?

Answer 2

→ FGF-23

Question 3

How is the calcium distributed in the body?

Answer 3

→ most is intracellular
→ the remaining 0.1% is in the plasma

→ half of the 0.1% is free calcium ions
→ the other half is protein bound

Question 4

What is the only way to increase Ca2+?

Answer 4

→ Increase calcium absorption through the gut

Question 5

What does bone turnover contribute to?

Answer 5

→ Homeostasis of serum calcium
→ phosphate

→ and PTH, vit D, calcitonin, FGF-23

Question 6

What is PTH synthesized from?

Answer 6

→ Parathyroid chief cells

Question 7

What is PTH secreted as?

Answer 7

→ 84 AA polypeptide

Question 8

Where is free Calcium sensed?

Answer 8

→ by GPCR on chief cells

Question 9

What are the endocrine hormones involved in the regulation of bone?

Answer 9

→PTH
→TH
→GH
→IGF
→Oestrogen

Question 10

How is TH involved in bone regulation?

Answer 10

→controls rate at which chondrocytes differentiate into growth plate
→In adults, excess results in activity of osteoclasts

Question 11

How is GH involved in bone regulation?

Answer 11

→regulates osteoclasts differentiation

Question 12

How is IGF involved in bone regulation?

Answer 12

chondrocyte differentiation and linear growth, also osteoblast differentiation

Question 13

Describe calcitriol synthesis

Answer 13

→ 7dehydrocholesterol is in the skin
→ UV light turns it into cholecalcitriol (CCF)

→ 25 hydroxylase adds an OH group in the liver
→ it becomes 25 hydroxyCCG
→ 1a hydroxylase stimulated by PTH in the kidney adds another OH group
→ 1,25 dihydroxyCCF is formed or calcitriol

Question 14

Where is the regulation site for calcitriol?

Answer 14

→ control of 1a hydroxylase in the kidney

Question 15

What is calcitriol increased by?

Answer 15

→ PTH - upregulates 1a hydroxylase

→ Low phosphate

Question 16

What is the function of calcitriol?

Answer 16

→ Increase absorption of Ca and Pi from the GI tract

→ inhibits PTH

Question 17

What are the 4 actions of PTH?

Answer 17

→ Promotes release of Ca from bone
→ Increases Ca reabsorption

→ increases renal Pi excretion
→ upregulates 1a hydroxylase activity

Question 18

Describe how PTH works

Answer 18

→ hypocalcaemia stimulates PTH
→ PTH binds to osteoblasts and stimulates RANK ligand

→ RANK ligand binds to RANK receptors on osteoclasts
→ Bone breaks down and Ca2+ and phosphate are released into the blood
→

Question 19

What are the effects of PTH release on the kidney?

Answer 19

→increased reabsorption of Ca
→increased 1,25-dihydroxy vit D formation
→reduced phosphate reabsorption

Question 20

What are the effects of PTH on the gut?

Answer 20

increased calcium absorption via D3

Question 21

What do high Ca and D3 do?

Answer 21

D3 inhibit PTH production

Question 22

What is phosphate important for?

Answer 22

→for nerve function

Question 23

What does high serum phosphate do?

Answer 23

→stimulates FGF23 synthesis in osteocytes

→ to decrease phosphate by increase phosphate excretion in the kidney.

Question 24

What is FG23?

Answer 24

→Fibroblast Growth Factor-23

→

Question 25

What are the effects of FG23 on the kidneys and parathyroid?

Answer 25

→Decreases phosphate reabsorption in kidneys →Inhibits PTH production Decrease release of phosphate via bone resorption →Inhibits active vitamin D3 production Decrease phosphate absorption in gut

Question 26

What is Rickets?

Answer 26

→Defective mineralisation of normally synthesized bone matrix →Osteoid are laid down normally but can’t be mineralised into mature bone and remains organic portion of bone

Question 27

What are the two types of Rickets?

Answer 27

→Deficiency of vitamin D3 (causing hypocalcemia) | →Deficiency of Phosphate

Question 28

What is oncogenic oesteomalacia?

Answer 28

→ mesenchymal tumours producing excess FGF23 | Causing excess phosphate excretion

Question 29

What are the outcomes of oesteomalacia?

Answer 29

→bonepain/tenderness fracture →proximal weakness- upper legs and arms are weak →bone deformity

Question 30

What are x-ray presentations of oesteomalacia?

Answer 30

→Bowing of long bones →Widening of growth plates →Looser’s Zones

Question 31

What is looser's zone?

Answer 31

→fracture through one side of bone at 90 degrees to the cortical bone → band of bone material of decreased density

Question 32

What are the effects of excess PTH?

Answer 32

→Hypercalcemia | →Hypophosphatemia

Question 33

What are primary causes of hyperparathyroidism?

Answer 33

→parathyroid adenoma (85-90%) | →chief cell hyperplasia

Question 34

What are the secondary causes of hyperparathyroidism?

Answer 34

→chronic renal deficiency | →vit D deficiency

Question 35

What is Osteitis fibrosa cystica?

Answer 35

→results from hyperparathyroidism | →bone pain

Question 36

Mnemonic for hyperparathyroidism?

Answer 36

Stones (Kidney stones) Bones (Pain from osteitis fibrosa cystica and excess bone resorption) Abdominal Moans (acute pancreatitis) Psychic Groans (psychosis & depression)

Question 37

What are the clinical features of hypercalcaemia?

Answer 37

→ Depression, fatigue, anorexia, nausea vomiting → Abdominal pain → Renal calcification → Bone pain

Question 38

How is primary hyperparathyroidism resolved?

Answer 38

→ removal of the affected gland