LECTURE 19 - parathyroid gland and calcium regulation Flashcards
1
Q
What are the general functions of the skeleton?
A
Mechanical - support and muscle attachments
Protective - for vital organs and marrow
Metabolic - ion homeostasis (calcium and phosphate especially)
2
Q
What is soluble calcium needed for?
A
- excitable tissue
- muscle/nerves
- cell adhesion
3
Q
Why does calcium homeostasis occur?
A
- to keep serum calcium levels at 2.1-2.6mM
4
Q
How is calcium homeostasis maintained?
A
- calcium can be obtained from GI tract (from diet)
- kidney can help redistribute calcium
- as a last resort there is calcium available from the skeleton
5
Q
What are the parathyroid glands?
A
- there are 4 glands near the thyroid
- they regulate calcium homeostasis and phosphate levels
- secrete parathyroid hormone (PTH) in response to low calcium or high phosphate
6
Q
What does parathyroid hormone (PTH) do?
A
- increases calcium reabsorption in renal distal tubule
- increases intensity calcium absorption (via activation of vitamin D)
- increases calcium release from bone (stimulates osteoclast activity
- decreases phosphate reabsorption
7
Q
What happens when calcium levels are too low?
A
- calcium sensing receptors detect low calcium levels
- increase PTH secretion
- first act on kidney to recover calcium from urine, decreased urinary calcium, increased urinary phosphate
- increased 1,25D3 production (active form of vitamin D), tried to increase calcium and phosphate from intestine
- last resort is to promote release of calcium from bone into bloodstream
8
Q
What is parathyroid hormone?
A
- 84 amino acid peptide but biological activity in first 34 amino acids (PTH 1-34), half-life = 8 mins
- cleaved to smaller peptides
- assayed by two site assay (to avoid detecting fragments)
- normal adult reference range = 1.6 - 6.9 pmol/L
- binds to G protein coupled receptors mainly in kidney and osteoblasts
9
Q
How does negative feedback affect PTH?
A
- PTH transcription (mRNA production) is inhibited by 1,25D3
- PTH translation (mRNA to protein synthesis) is inhibited by increased serum calcium
10
Q
What is Vitamin D?
A
- precursor form (inactive) = 25-hydroxyvitamin D
- Vitamin D2 = found in plants
- Vitamin D3 = found in animals
- active form = 1,25-dihydroxyvitamin D (hormone that binds to VDR receptor)
11
Q
What is calcitonin?
A
- produced by thyroid c-cells (parafollicular)
- released in hypercalcaemia, inhibits bone resorption
- not essential to life
- two calcitonin genes product from a single gene and primary RNA transcript
12
Q
How does calcitonin work?
A
- hypercalcaemia causes calcitonin production
- shut downs calcium release from bone
- PTH levels also drop (thus active Vitamin D also drops)
13
Q
What is Fibroblast Growth Factor 23 (FGF23)?
A
- produced by bone cells
(osteocytes and maybe osteoblasts) - released in response to high serum PO4 (phosphate)
- increases renal excretion of PO4 and suppress renal synthesis of activate vitamin D
- main inducer of FGF23 appears to be 1,25D3
14
Q
What is the basic structure of bones?
A
- 2 epiphysis (growth plates) at each end separated by diaphysis (made of cortical bone)
- growth plates are the bits that grow, made of cancellous (trabecular) bone (aka spongy bone)
15
Q
What is bone made of?
A
- specialised connective tissue
- extracellular matrix which us able to calcify
- collagen fibres with preferential orientation (approx 90% of protein content)
- non-collagenous proteins essential to bone function e.g. osteocalcin, osteonectin, osteopontin, used as markers for bone turnover
- calcification occurs with formation of hydroxyapatite crystals - mixture of calcium and phosphate
- contains several types of cells
