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

What is the daily calcium intake?

Answer 3

→ 1000-1200

Question 4

How is the calcium distributed in the body?

Answer 4

→ 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 5

What is the only way to increase Ca2+?

Answer 5

→ Increase calcium absorption through the gut

Question 6

What does bone turnover contribute to?

Answer 6

→ Homeostasis of serum calcium
→ phosphate
→ and PTH, vit D, calcitonin, FGF-23

Question 7

What is PTH synthesized from?

Answer 7

→ Parathyroid chief cells

Question 8

Where are the parathyroid glands located?

Answer 8

→ behind the thyroid

Question 9

What is PTH secreted as?

Answer 9

→ 84 AA polypeptide

Question 10

What is the role of PTH?

Answer 10

→ Defend against hypocalcaemia

Question 11

What is the concentration of plasma Ca2+?

Answer 11

→ 2.2-2.6 mM

Question 12

Where is free Calcium sensed?

Answer 12

→ by GPCR on chief cells

Question 13

What is the stimulus for PTH release?

Answer 13

→ Low calcium

Question 14

Where is calcitriol synthesized and in response to what?

Answer 14

→ in the skin

→ in response to UV

Question 15

What is calcitriol?

Answer 15

→ Vitamin D

Question 16

Describe calcitriol synthesis

Answer 16

→ 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 17

Where is the regulation site for calcitriol?

Answer 17

→ control of 1a hydroxylase in the kidney

Question 18

What is calcitriol increased by?

Answer 18

→ PTH - upregulates 1a hydroxylase

→ Low phosphate

Question 19

What is the function of calcitriol?

Answer 19

→ Increase absorption of Ca and Pi from the GI tract

→ inhibits PTH

Question 20

What are the 4 actions of PTH?

Answer 20

→ Promotes release of Ca from bone
→ Increases Ca reabsorption
→ increases renal Pi excretion
→ upregulates 1a hydroxylase activity

Question 21

Describe how PTH works

Answer 21

→ 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 22

Where are PTH receptors found?

Answer 22

→ osteoblasts

Question 23

How does PTH promote bone remodelling?

Answer 23

→ Activates osteoclasts via RANKL

→ promotes bone remodelling

Question 24

What does intermittent low dosage of PTH lead to?

Answer 24

→ favoring formation over reabsorption

Question 25

What does a persistent high concentration of PTH lead to?

Answer 25

→ excess resorption over formation

Question 26

Where is calcitonin secreted from?

Answer 26

→ C cells of the thyroid

Question 27

What stimulates calcitonin secretion?

Answer 27

→ high Ca2+

Question 28

What is the effect of calcitonin?

Answer 28

→ to lower Ca2+ by inhibiting osteoclasts

Question 29

What does calcitonin do in the kidney?

Answer 29

→ Decreases calcium and phosphate reabsorption

Question 30

What does calcitonin do in the bone?

Answer 30

→ Decreases bone resorption by inhibiting osteoclast activity

Question 31

What is used to treat Paget's?

Answer 31

→ Synthetic calcitonin

Question 32

What is the lacunar-canalicular system for?

Answer 32

→ Communication between osteocytes | → communication from osteocytes to surface cells and systemic circulation

Question 33

What is hypophosphatemic rickets?

Answer 33

→ Rare phosphate wasting conditions leading to bone mineralization defects

Question 34

What is the role of FGF-23?

Answer 34

→ to decrease phosphate

Question 35

What is FGF-23 expressed and secreted by?

Answer 35

→ osteocytes

Question 36

What is FGF-23 stimulated by?

Answer 36

→ Calcitriol and Pi

Question 37

What does FGF-23 do?

Answer 37

→ inhibits calcitriol synthesis | → Increases renal Pi excretion (by reducing Na-Pi reabsorption from the proximal tubule)

Question 38

What are the clinical features of hypercalcaemia?

Answer 38

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

Question 39

What are causes of hypercalcaemia in ambulatory patients?

Answer 39

→ Primary hyperparathyroidism

Question 40

What are causes of hypercalcaemia in hospitalised patients?

Answer 40

→ Malignancy

Question 41

What is primary hyperparathyroidism due to?

Answer 41

→ Benign adenoma in one or more PT glands

Question 42

How is primary hyperparathyroidism resolved?

Answer 42

→ removal of the affected gland

Question 43

What is hypercalcaemia of malignancy?

Answer 43

→ Tumor can secrete PTH related peptide | → Binds and activates PTH receptor