11. Calcium regulation

Question 1

how much Ca is there in body and how is it stored

Answer 1

1kg, mainly stored as hydroxyapatite crystals in bone

1g present in extracellular fluid

Question 2

what are the 3 forms of Ca found in plasma

Answer 2

1. free ionised form - biologically active
2. complexed with albumin
3. complexed with low molecular weight organic anions

Question 3

which 3 organs are critical in Ca homeostasis

Answer 3

1. skeleton: calcium deposition = calcium resorption
2. GI tract: absorbs dietary calcium and secretes calcium for excretion
3. kidney: calcium excretion in kidneys = net absorption in GI tract

Question 4

why is Ca and phosphate homeostasis linked

Answer 4

1. both principal components of hydroxyapatite crystals

2. regulated by same hormones - PTH and calcitriol

Question 5

which 2 hormones act to increase serum Ca conc.

Answer 5

1. parathyroid hormone (PTH)

2. calcitriol (active form of vitD)

Question 6

how does PTH increase serum Ca

Answer 6

1. acts on BONE: activates osteoclasts to increase bone resorption and Ca release
2. acts on KIDNEY:
   - increase calcium reabsorption
   - increases 1a-hydroxylation of inactive vitD to calcitriol

Question 7

how does PTH prevent kidney stone formation

Answer 7

increases Ca reabsorption but decreases Pi reabsorption

Question 8

what is the effect of PTH on osteoblasts and osteoclasts

Answer 8

1. stimulates osteoblast synthesis and secretion of cytokines… stimulates differentiation and activity of osteoclasts and protects them from apoptosis… produce acid to dissolve hydroxyapatite
2. decreases osteoblast activity… exposes bony surfaces to osteoclasts

Question 9

how does calcitriol act to increase Ca serum conc.

Answer 9

1. acts on BONE: increases resorption
2. acts on KIDNEY: increases Ca reabsorption
3. acts on GI TRACT: increases intestinal absorption of dietary Ca via transcellular uptake

Question 10

which hormone is released from thyroid parafollicular/C cells and why

Answer 10

CALCITONIN - little effect but thought to counteract effects of PTH in pregnancy

Question 11

which cells produce PTH

Answer 11

parathyroid glands (2 at back of each thyroid lobe)

Question 12

which 2 cell types are found in parathyroid glands

Answer 12

1. CHIEF cells: produce PTH

2. OXYPHIL cells (more cytoplasm): role?

Question 13

how do chief cells sense serum Ca levels

Answer 13

Ca binds to GPCRs on cell surface

Question 14

what type of hormone is PTH

Answer 14

polypeptide hormone (synthesised as preprohormone and cleaved in liver)

Question 15

describe the synthesis of calcitriol

Answer 15

1. inactive vitD3 obtained from dairy or action of sunlight on 7-dehydrocholesterol in skin…
2. hydroxylation to 25-hydroxyvitamin D in liver…
3. transported to kidney via transcalciferin…
4. hydroxylation to calcitriol by 1a-hydroxylase in PCT

Question 16

how is 1a-hydroxylase regulated

Answer 16

• stimulated by PTH

- inhibited by high serum Ca

Question 17

why is PTH involve in short term Ca regulation and calcitriol in long term regulation

Answer 17

PTH has shorter 1/2 life (4 min) as no serum binding hormone, whilst calcitriol has longer 1/2 life (0.25 days)