hormonal regulation of calcium and phosphate balance

Question 1

what physiological processes is calcium essential for?

Answer 1

excitation-contraction coupling
stimulus-secretion coupling
blood coagulation
structural component in bone

Question 2

what is phosphate essential for?

Answer 2

it is an obligate component of cellular structures and chemicals eg. phospholipids, DNA, ATP

Question 3

what are hormones that regulate calcium and phosphate levels

Answer 3

• parathyroid hormone
• 1,25-dihydroxyvitamin D
• calcitonin

Question 4

what is parathyroid hormone?

Answer 4

a peptide hormone which is secreted by cheif cells of the parathyroid gland in response to low plasma calcium levels

Question 5

how does calcium levels causes secretion of PTH

Answer 5

1. calcium binds to the CasR (Ca2+- sensing receptor)
2. this leads to activation of a signalling pathway and generation of arachidonic acid
3. AA inhibits secretion of PTH
   Reduced Ca2+ levels switches of this signalling pathway and allows PTH secretion

Question 6

what is PTHR1?

Answer 6

parathyroid hormone receptor 1 - GPCR

Question 7

what are the two main targets of PTH?

Answer 7

bone and kidney cells

Question 8

what is the effects of PTH on calcium and phosphate in bone?

Answer 8

stimulates resorption by stimulating osteoclast activity

Question 9

what is the effects of PTH on calcium and phosphate in the kidney?

Answer 9

enhances reabsorption of Ca2+ but decreases reabsorption of phosphate (more excreted)

Question 10

how is absorption of calcium and phosphate increased?

Answer 10

indirectly by increased synthesis of 1,25-dihydroxyvitamin D

Question 11

what is the bone matrix containing several different cell types called?

Answer 11

osteoid

Question 12

what is the organic matrix mineralised by?

Answer 12

hydroxyapatite (calcium phosphate hydroxide salt)

Question 13

what mediates bone formation and how?

Answer 13

osteoblasts - they secrete collagen and other proteins such as osteocalcin and osteopontin

Question 14

what is it called when calcium and phosphate become associated with bone matrix?

Answer 14

mineralisation

Question 15

what can osteoblasts become upon being embedded in bone matrix?

Answer 15

osteoclasts

Question 16

what mediates bone resorption?

Answer 16

osteoclasts

Question 17

what do osteoclasts do?

Answer 17

• attach tightly to surface of bone
• secrete proteases and H+
• H+ ions dissolve the hydroxyapatite crystals and expose the organic matrix allowing degradation of collagen by proteases
• this results in release of calcium and phosphate from bone

Question 18

how does PTH act on osteoclasts?

Answer 18

don’t act directly cause thru lack a PTH receptor protein
- PTH binds to osteoblasts which leads to osteoclastogenesis from precursor cells

Question 19

how does PTH achieve osteoclastogenesis?

Answer 19

enhances the expression of RANK ligand and inhibits the expression of osteoprotegerin, a “decoy” receptor for RANKL

Question 20

what is RANK?

Answer 20

Receptor activator of nuclear factor-kappa B

Question 21

what are osteoblasts and osteoclasts in terms of RANK

Answer 21

osteoblasts - rank ligand which has affinity for rank
osteoclast - has a rank receptor

Question 22

what happens when PTH binds to osteoblasts?

Answer 22

increase in RANKL
Decrease in osteoprotegerin

Question 23

what does interaction of osteoblasts with osteoclasts precursor cells activate?

Answer 23

signalling pathways that promote differentiation of the precursor cells into mature osteoclasts which mediates bone resorption

Question 24

what is bone resorption?

Answer 24

when the body breaks down existing bone tissue to release minerals including calcium and phosphate into the bloodstream

Question 25

how does PTH affect reabsorption of calcium in the kidney?

Answer 25

Calcium reabsorption increased due to PTH stimulation of calcium transporter expression and activity

Question 26

how does PTH affect the reabsorption of phosphate in the kidneys?

Answer 26

phosphate reabsorption decreases due to PTH stimulated internalisation and lysosomal degradation of a phosphate transporter

Question 27

why is enhanced excretion of phosphate important for?

Answer 27

prevent plasma levels of this ion rising as a result of increased resorption from bone and increased absorption from intestine

Question 28

what does PTH increase the synthesis of?

Answer 28

1,25- dihydroxyvitamin D (by regulating expression of hydroxy vitamin D 1-alpha-hydroxylase) which increases calcium and phosphate absorption from the intestines

Question 29

what is the biologically active form of vitamin D?

Answer 29

1,25-dihydroxyvitamin D (calcitriol)

Question 30

what is the main effect of 1,25-dihydroxyvitamin D?

Answer 30

on intestines (increases calcium and phosphate absorption) also increases calcium reabsorption in kidneys

Question 31

what is the mechanism of 1,25-dihydroxyvitamin D on regulation of calcium absorption?

Answer 31

1. enter cells 2. activates receptor in nucleus 3. increased transcription of calcium transporter proteins - leads to increased absorption of calcium

Question 32

what food is vitamin D found in?

Answer 32

oily fish red meat liver egg yolks fortified food

Question 33

how much vitamin D do we need?

Answer 33

- babies upto one year - 8.5 to 10 micrograms a day - children from age of 1 year and adults need 10 micrograms a day

Question 34

what supplement should breast fed babies to age one be given

Answer 34

8.5-10micrograms vitamin D

Question 35

when should formula fed babies be given a vitamin D supplement?

Answer 35

until having less than 500 ml of formula per day (formula is fortified with vitamin D)

Question 36

when should you consider taking a vitamin D supplement?

Answer 36

october-march

Question 37

who is at risk of vitamin D deficiency?

Answer 37

- those who arent often outdoors - those who wear clothes that covers most the skin when outside - those with dark skin - woman pregnant or breastfeeding

Question 38

what happens if you take too much vitamin D

Answer 38

can cause hypercalcaemia which can weaken bone and damage the kidneys and heart

Question 39

what is calcitonin secreted by?

Answer 39

C-cells (parafollicular cells) of the thyroid gland in response to an elevation of plasma calcium levels

Question 40

where are the two main sites of action of Calcitonin?

Answer 40

osteoclasts in bone and kidney cells

Question 41

what does calcitonin inhibit?

Answer 41

- activity and differentiation of osteoclasts - inhibits resorption and promotes deposition

Question 42

does calcitonin have an effect on the balance of calcium and phosphate?

Answer 42

plays little role in the normal regulation

Question 43

what may calcitonin play a role in?

Answer 43

protecting skeletal integrity when there is high calcium depend such as during pregnancy or breastfeeding