parathyroid function Flashcards
what concentration must serum calcium be kept at? and how can we regulate it?
- between 2.1-2.6 mM
- GIT (Vitamin D stimulates increased uptake from diet)
- Kidney produces PTH, Vit D and FGF23
- Bone PTH/Vit D has action here
describe the parathyroid gland
- 4 of them
- found on the thyroid gland of the neck
- secrete PTH in response to hypcalceamia or high phosphate levels
- regulates both Ca and Po4 levels
actions of PTH include ?
- increase Ca absorption in the renal DCT
- Increased intestinal Ca absorption (indirectly via activation of vit D)
- increased bone resorption ( stimulated osteoclast activity)–> only if serum levels have not recovered so is seen as a last resort
- decreased po4 reabsorption
describe the structure of PTH
- is an 84 AA peptide hormone
- biological activity is in the first 34 AA
- cleaved to smaller active peptides
underline the actions of PTH in the kidneys
- increases distal tubular reabsorption of calcium (inhibiting Po4 reabsorption)
- stimulates production of the active form of vit D (1,25 (OH)2D)
how are PTH levels regulated via negative feed back?
- PTH transcription (mRNA production) is inhibited by 1,25 D3)
- PTH translation is inhibited by high serum Ca levels
explain the steps of vit D synthesis
- skin (7-dehydrocholesterol) —> vitD3 –> Liver ( 25-OHD3)—> kidney ( 1,25OH2D3)-> active form
steroid hormone that binds to an intracellular nuclear receptor
what is the normal reference range for vit D?
- 7.5 nmol/L (assayed for 25 (OH)D3)
- active form rarely measured
what is the normal adult range for PTH levels?
- 1.6–> 6.9 pmol/L
what does calcitonin do?
- produced by the parafollicular cells of the thyroid gland
- released in response to hypercalcaemia
- inhibits bone resorption via osteoclasts
- not essential for life
- essentially reverses all the actions of PTH on the periphery
what is FGF23?
produced by cells of the bone (osteocytes and osteoblasts)
- response to high serum Po4
- increases renal excretion of po4 and suppresses renal synthesis of active (1,25 OH2D3)
- ITS main inducer is 1,25D3
- levels become elevated during stages of kidney disease and dialysis
- dominant effects on kidney reverses high po4 levels
what do osteocytes do?
Osteocytes - embedded In calcified bone matrix with long processes which contact other osteocytes and osteoblasts
what do osteoblasts do?
bone forming cells which produce matrix constituents and aid calcification
Originate from mesenchymal stem cells (bone marrow stem cells or connective tissue mesenchymal cells).
what are osteoclast cells?
bone resorbing cells usually found in contact with calcified bone surface – in lacunae
Multinucleated - originate from bone marrow lineage
Produce acid (to resorb mineral) and enzymes (to resorb matrix) - to release Ca
briefly outline the bone resorption cycle
1) resting surface
2) resorption pit formed by osteoclast cells via release of acid and digestive enzymes to resorb the EC matrix
3) release of Ca
4) reversal phase –> formation of a cement line via osteoblast cells
5) bone reformation (production of osteoid composed of collagen T1)
6) osteoid mineralization is completed via the action of Ca –> formation of hydroxyapatite crystals
what is primary HPT?
- metabolic bone disease –> increased bone resorption
- caused by adenomas of the PTH glands (benign)
- loss of feedback control
- hypercalcaemia
what is secondary HPT?
- increased serum po4 (hyperphospataemia)
- decreased activation of VitD3
- reduced serum Ca
- increased serum po4 stimulates FGF23 of which increases inhibition of vitD3 production
- seen in renal osteodystrophy/ CKD-MBD
- elevated secretion of PTH in response to hyperP (kidney disease) , hypoCa (kidney disease) and decreased active vitD3 (increased FGF23 activity)
what is rickets ?
- affects growing skeletons
- lack of mineralization of collagen content (osteoid)
- failure to absorb sufficient Ca from GIT due to dietary deficiency of vitD3 (lack of sunlight too)
- rarely inherited ( mutations to VDR, 1-alpha OHlase)
during rickets
- there is weak osteoid growth at growth plates
- with growth plate expansion to compensate leading to swollen joints
during osteomalacia
- affects adult skeleton
- there is bone pain and pseudo fractures
treatment of rickets via?
vitamin D replacement therapy
how can CKD-MBD be treated?
- by po4 binders
- vitD analogues
what is spinal osteoporosis?
- loss of collagen and mineral component of bone
- as with increasing age, the digging pit and cement phase becomes less efficient ( less filling in)
- compression fractures within the spinal vertebrae
what is osteoporosis ?
- both mineral and osteoid decreased
- increased fracture risk
osteoporosis of ageing is?
- affects males and females
- gradual decline in bone density from early adult peak
postmenopausal osteoporosis is?
- rapid decline in female bone density following decline in oestrogen levels at the menopause
- oestrogen increases bone remodelling rate and degree of bone resorption
