Lec 47- Calcium homeostasis

Question 1

Calcium balance

Answer 1

• We absorb Ca from intestines (Jejunum, ileum)- this is around 350mg
• From here it will enter the ECF (extracellular fluid) with a conc of 900mg
• From here it can enter many different compartments 1) ICF (intracellular fluid)
• inside the cells there are around 11,000mg and around 5000mg will passes between ECF
  2) Bone- We have exchangeable Ca which is around 4000mg which is regularly being interchanged (300mg) with ECF

+We also have stable bone (1,000,000 mg) this cannot be exchanged

3) Kidney- throughout the course of the day through filtration and reaborbastion (10,000) only 170mg will be lost in urine

NB we lose 190mg through GI so when we add this to 170mg we lose through kidneys we get 350mg which is as much as we absorb so we are said to be in Ca balance

Question 2

Hormonal regulation of Ca balance

Answer 2

• Parathyroid hormone; increases plasma Ca, decreases bone mass, Ca removal
• Calcitonin: decreases plasma Ca, increases bone mass, Ca excretion (mainly in juveniles) -Vit D3 increase Ca absorption

Question 3

Regulation of secretion of PTH and calcitonin

Answer 3

• C cells of thyroid glands secrete calcitonin and they respond to elevate [Ca] in blood
• This then lowers Ca blood levels
• The parathyroid glands then detect a Ca decrease in blood
• The chief cells of the parathyroid gland secretes PTH and Ca travels from intestine to blood; bone to blood and kidney to blood

NB- this is all negative feedback loops

Question 4

Vit D

Answer 4

• 2 sources of Vit D
  1) Endogenous precursors (require sunlight)
  2) Diet (fortified milk, fish, oil, egg yolks) –> vit D3 -Vit D3 —> -Liver –> -25-hydroxycholecalciferol (25(OH)D3) –> -Kidneys (stimulated by PTH) –> -1,25-dihydroxycholecalciferol (Calcitrol) –> -Bone and intestine (stimulated by PTH)–> -Plasma Ca (Inhibit PTH)

Question 5

Bone growth

Answer 5

• 2 area- compact bone (no growth) and epiphysis (growing section) this section is at the neck and the bone
• The epiphysis and diaphysis (Compact bone) it held together between the epiphyseal plate (layer of cartlidge)
• Chondrocytes lay down the cartilage
• Osteoblasts lay bone down on top of the cartilage and promote Calcification causing Calcium phosphate to be deposited on cartilage to turn it into bone

Question 6

Bone removal

Answer 6

• There is always a balance in the bones (even in adults)
• Osetoclasts secrete enzymes and acidify Ca crystals in bone causing them to dissolve
• The Ca and PO4 can be reabsorbed

Question 7

Bone formation and reabsorption balance

Answer 7

• Osteoclast (OC) precursor needs to differentiate to become a mature OC and this is promoted by Calcitriol, PTH< and cytokines (IL-6)
• Osteoblasts (OB) actually cause maturation of the OC this is because bone formations and reabsorbtion must occur in balance
• Once mature the OC then attacks the bone dissolving Ca and PO4 -Imbeded in bone are many cytokines including IGF (Insulin like growth factor) and TGF-b (Transforming growth factor Beta) are released
• Once released they stimulate the osteoblasts to lay new osteoid (new bone)
• OB are formed from precursor cells these are stimulated into mature cells when recombinant PTH (exogenous) as well as cytokines (BMP-2 and hormones)
• On the surface of OB there is RANK-ligand which interacts with RANK protein on OC precursors, when these binds, this stimulate OC to differentiate
• RANKL can be masked by osteoprotegerin which acts as a decoy receptor

Question 8

Inhibitors of OCs and OBs

Answer 8

• Estrogens and raloxifene inhibit OCs
• Glucocorticoids promote OCs and inhibit OBs

Question 9

Calcium and bone diseases

Answer 9

• Osteoporosis- postmenopausal oestrogen deficiency, excess glucocorticoids or thyroxine decrease osteoprotegerin (Binds RANKL)
• Rickets-Vit D deficiency
• Pagets disease- bone reabsorption
• Hypocalcaemia- Hypoparathyroidism or Vit D deficiency
• Hypercalcaemia- hyperparathyroidism
• Hyperphosphataemia- renal disease

Question 10

Drugs for bone metabolism

Answer 10

• Bisphosphonates- etidronate and alendronate (NICE). Bind to hydroxyapatite crystals
• Vit D-Ergocalciferol and Calcitriol
• Calcium salt-gluconate, lactate and hydroxyapatite
• Calcitonin
• Oestrogens (raloxifene) Used for postmenopausal osteoporosis with bisphosphonates
• Denosumab; binds and inhibits RANKL
• Teriparatide, synthetic PTH analogue
• Strontium ranelate; stim OBs, osteoprotegerin