Flashcards in 21. Parathyroid Gland - Calcium and Phosphate Regulation Deck (30):
Where is the majority of calcium stored?q
In the skeleton.
Give three examples of how the correct calcium levels affect a bodily function.
Eases insomnia, regulates passage of nutrients in and out of the cell walls, assists in normal blood clotting, preserves nerve and muscle function, lowers blood pressure, normal kidney function, reduces blood cholesterol levels etc.
Roughly how much calcium does an adult human contain?
In what form is calcium stored in the bone?
Hydroxyapatite crystals in the skeleton.
What are the two main roles of the skeleton?
Structural support and major reserve of calcium.
Roughly how much calcium is exchanged between bone and ECF every day?
What is the daily intake of calcium from a UK diet and what happens to that calcium?
175mg go to urinary loss and 825mg go to GI loss.
What are three regulators of calcium levels?
Parathyroid hormone - stimulates bone resorption and release of calcium into circulation, stimulates calcium reabsorption in kidney and excretion of phosphate, stimulate hydroxylation to make active vitamin D.
Dietary vitamin D - increase intestinal absorption of dietary calcium and renal reabsorption of calcium and increases bone resorption.
Calcitonin - counteracts the effects of PTH.
Where are the parathyroid glands found?
On the thyroid gland.
What are the three cells types in parathyroid glands?
Chief cells - secrete PTH
Oxiphil cells - function unknown.
What is the effect of PTH on the following?
a. Small intestine
a. Stimulates Ca2+ absorption indirectly
b. Stimulates synthesis of active vitamin D, stimulates calcium reabsorption and increases phosphate excretion.
c. Increases bone resorption and increases Ca2+ pumping to ECF.
How is PTH synthesised?
Pro-pre-hormone (115aa long) is cleaved to pre-hormone (90aa long) then cleaved to hormone (84aa long).
How is PTH synthesis regulated?
At transcriptional and post transcriptional levels. Low serum calcium up-regulates gene transcription (high serum down-regulates this), it also prolongs survival of mRNA.
How are high Ca2+ levels dealt with?
Ca2+ binds to Gq/i and Gi coupled receptors. PLC inhibiting adenylate cyclase leading to reduced cAMP and reduced PTH release. Reduced PTH release is from increased degradation, not decreased production.
In what way is bone dynamic?
It has osteoblasts that produce collagen matrix which is mineralised by hydroxyapatite and build up the bone, and also osteoclasts that produce acid micro-environment hydroxyapatite dissolves.
What affect does PTH have on the bone?
It stimulates osteolysis. The osteoblastic cells synthesise and secrete cytokines on the cell surface. The cytokines stimulate differentiation and activity in osteoclasts and protect them from apoptosis. So PTH decreases osteoblast activity and exposes bony surface ti osteoclasts. This means Pi and Ca2+ are released into ECF.
What affect does PTH have on the kidneys?
It affects the tubular cells. It increases Ca2+ reabsorption in ascending limb and DCT, reducing Ca2+ excretion. Pi is removed from circulation by inhibition of Kidney reabsorption. This prevents calcium stone formation.
What affect does PTH have on the gut?
It stimulates conversion of vitamin D into its active form which increases Ca2+ intake from the gut.
What are the two forms of vitamin D?
D3 (cholecalciferol) made in skin and from dairy, requires sun light.
D2 (ergocalciferol) from east and fungi added to margarines as a supplement.
How is vitamin D activated?
In the liver, 25-hydroxyvitamin D. In the kidneys, it produces 1,25(OH2)/ calcitriol.
What are the actions of calcitriol on the gut?
Active uptake and extrusion of Ca2+ ions.
Endocytosis and exocytosis of Ca2+-CaBP complex.
What effect does calcitriol have on the kidney?
Decreases urinary loss of calcium by stimulation reabsorption.
Where is calcitonin secreted from?
The parafollicular cells/ Cc ells of the thyroid gland.
What are the clinical features of hypocalcaemia?
Hyper-excitablilty of NMJ, leading to pins and needles, tetany/ muscle spasms, paralysis, convulsions and death is consistently low.
What are the clinical feasters of hypercalcaemia?
Renal calculi, kidney damage, constipation, dehydration, tiredness, depression and death eventually.
What is the normal response to hypercalcaemia?
Decreased PTH secretion. In the kidney, there is decreased calcitriol release and decreased Ca2+ reabsorption, which means less Ca2+ is take from the gut. In the bone, there is decreased breakdown of the bone and increased bone building. These lower plasms Ca2+ levels.
How is hypercalcaemia treated?
In primary hyperparathyroidism - removal of the benign tumour in one of the parathyroid glands.
How can a tumour lead to hypercalcaemia?
They may release PTHrp (PTH related peptides) that have the same function as PTH so increase Ca2+ plasma levels.
How is serum phosphate maintained?
There is a degree of co-regulation, as vitamin D stimulates uptake of both Ca2+ and Pi in the gut. The actions of vitamin D and PTH on the bone cause an increase in both Ca2+ and Pi. But in the kidney, PTH causes excretion of Pi so kidney stone formation is less likely.