Calcium metabolism Flashcards
1
Q
describe the calcium stores in the human body.
A
- adult = 1000g in which 99% in bone as hydroxyapatite crystals.
- there is dynamic movement in and out of bones as calcium phosphate. upto 33-600mg exchange between bones and ECF.
- serum calcium 2.2-2.6 mM as ionised, protein bound or complexed (Pi, citrate) calcium. (protein bound not biologically active until needed.)
2
Q
name some functions of calcium.
A
- maintain bones, teeth.
- regulates heart rhythm.
- assists blood clotting (F IV), important in cell signalling, nerve transmission.
- helps maintain proper nerve and muscle function.
- when blood samples taken placed in EDTA (calcium chelator) so blood won’t clot as calcium important in IV cascade.
- to prevent hypercalcaemia blood in transfusions have citrate which chelates calcium. need to monitor calcium levels closely.
3
Q
what are the 3 hormones involved in regulating calcium and phosphate?
A
- Parathyroid hormone (PTH).
- Calcitrol AKA 1,25 (OH) 2D.
- Calcitonin (C cells in thyroid).
4
Q
describe the parathyroid gland.
A
- attached to thyroid gland, usually 4 capsulated structures.
- contains chief cells and oxyphil cells that are thought to be old chief cells. also contains adipose tissue.
5
Q
how is PTH synthesised?
A
- straight chain pp hormone cleaved from 115AA pro-pre-hormone to 84AA.
- 4 min half life (cleaved in liver) which means responds quickly to slight changes.
- continually synthesised with little store, chief cells degrade it as well as synthesise.
*calcium binding to chief, activated GaQ to release more calcium to inhibit PTH secretion and synthesis.
LOOK OVER SLIDES.
6
Q
how is PTH synthesis regulated?
A
- at both transcriptional and post-transcriptional level.
- low serum calcium up-regulates gene transcription, and prolongs survival of mRNA.
- high serum calcium down regulates gene transcription.
- cleavage of PTH in chief cells accelerated by high serum calcium.
7
Q
what are the target organs of PTH for physiological effects.
A
- bone : increase resorption, release store from hydroxyapatite crystals within collagen.
(hydroxyapatite mineralises collagen matrix made by osteoblasts, osteoclasts dissolve these crystals.) - intestine : activate vitamin D increasing GI uptake of calcium. usually 30% of dietary intake taken up in gut this is increased.
- kidney : decrease loss to urine. also signals kidney to increase phosphate excretion to prevent crystals forming as serum calcium increases.
8
Q
describe action of PTH on bone.
A
- 1-2 hours PTH stimulates osteolysis inducing osteoblastic cells to synthesise and secrete cytokines thats stimulate osteoclast activity.
- PTH decreases osteoblast activity, reabsorption of mineralised bone and release of Pi and Ca2+ into ECF.
9
Q
what does calcitrol do?
A
- source and activation of vitamin D.
- vitamin D3 precursor (provided by UVB light onto skin, supplements) –> 25 (OH)D pre-hormone substrate made in liver –> 1,25 (OH)D or calcitrol made in kidney.
- vitamin D3 is not a hormone but acts as one, absorbed in gut.
- increases rate of calcium reabsorption in bone, gut and kidney.
10
Q
what is the significance of calcitonin?
A
- secreted by the C-cells of the thyroid gland.
- opposes action of PTH by decreasing serum calcium.
- inhibits osteoclast activity, decrease resorption at kidney.
11
Q
what are the complications of calcium imbalance?
A
- chronic hypercalcaemia : stones, moans, groans, bones.
- hypocalcaemia : more dangerous!
- hyper-excitability of NMJ : lower calcium means increased Na+ entry to neurones so depolarisation and increased AP. pins and needles, tetany, paralysis.
12
Q
name some symptoms of hypercalcaemia.
A
> 3.0 mmol/L
- polyuria –> dehydration which makes it worse and lead to lethargy weakness, confusion, coma, renal failure.
- rehydration mainstay treatment.
13
Q
what causes hypercalcaemia?
A
- malignancy osteolytic bone metastases ( common sites vertebrae, pelvis, ribs, proximal femur)
- multiple myeloma, breast, lung, renal and thyroid cancer.
- prostate cancers cause bone metastases but osteoblastic.
14
Q
what is hyperparathyroidism?
A
- primary : adenoma secreting more PTH causing serum calcium rise and serum phosphate fall. stones, moans, groans, bones!
- secondary : hyperplastic parathyroid with vitamin D deficiency, so low calcium absorption, so high PTH. also in chronic kidney failure due to 35 hydroxylation failure of vitamin D.
15
Q
how does calcium levels affect neuronal activity?
A
- calcium raises threshold for nerve membrane depolarisation so AP development.
- hyper : suppression of neuronal activity with lethargy and confusion.
- hypo : excitable nerves so tingling, tetany, epilepsy.
