Metabolism - Calcium Flashcards
How is calcium balance maintained in the bone?
Calcium + Pi —> hydroxyapatite crystals (found in collagen fibrils)
In deposition, osteoblasts produce collagen matrix which is mineralised = hydroxyapatite
In reabsorption, osteoclasts produce an acidic micro environment that dissolves hydroxyapatite to give calcium and Pi.
How is calcium balance maintained in the intestine?
It is taken up against a concentration gradient by carriers on the luminal membrane, using ATP.
The guts secretions are also rich in calcium, so it is secreted into the lumen down a concentration gradient.
How is calcium balance maintained in the kidney?
99% of ionised calcium is reabsorbed after filtration (bound calcium doesn’t fit through filter in first place).
What are the 3 hormones involved in calcium regulation and their function?
1) . PTH - raises calcium levels.
2) . Calcitriol - raises calcium levels.
3) . Calcitonin - thought to lower calcium levels.
Where is PTH secreted from?
The chief cells of the parathyroid gland.
How is PTH synthesised and how is this regulated?
It is synthesised as prePTH then cleaved to 84 a/a long.
It is regulated at transcriptional and post transcriptional levels.
Low serum Ca2+ = up regulates transcription and promotes mRNA survival
High serum Ca2+ = down regulates transcription and stimulates chief cells to degrade PTH via cleavage.
How is secretion of Ca2+ controlled?
Chief cells have a G protein calcium receptor on surface.
Increased Ca2+ binds and stimulates PLC inhibiting adenylate cyclase
=less cAMP
=less PTH release
What should serum calcium levels be?
2.2-2.5mM/L
How does PTH act on kidneys?
Affects tubular cells of the kidney
1) . Increases Ca2+ resorption in distal convoluted tube.
2) . Removes Pi from circulation = no calcium stone formation due to Pi and Ca2+ crystallising in blood.
How does PTH act on bone?
1) . Stimulates osteoblasts to release cytokines which cause osteoclasts to be stimulated, and protect osteoclasts from apoptosis.
2) . It decreases osteoblasts activity.
= resorption of mineralised bone, releasing Ca2+ and Pi into extra cellular fluid.
How is calcitriol formed?
2 forms of VitD are hydroxylated first in the liver, then the kidney to give 25hydroxyVitD.
How is calcitriol transported?
It is bound to CBP protein in the blood and can be stored.
How is calcitriol regulated?
Only the final conversion in the kidney is regulated by PTH.
What are the actions of calcitriol in the gut?
Increases absorption of Ca2+
What are the actions of calcitriol on the bone?
VitaminD stimulates osteoclasts activity and differentiation, therefore more bone erosion occurs. At the same time it inhibits osteoblasts, so more bone is broken down = release of Ca2+
What is hypocalcaemia and its symptoms?
Low serum Ca2+ levels.
1) . Hyper excitability of the neuromuscular junction - lowers axon threshold but still has the same resting potential = easier to trigger.
2) . Pins and needles
3) . Tetany/Paralysis
4) . Convulsions
5) . Death
6) . Rickets in children
What can cause hypocalcaemia?
A PTH deficiency due to removal of parathyroid glands or due to a failure to maintain Ca2+ levels.
What is hypercalcaemia and its symptoms?
High calcium levels.
1) . Renal calculi (kidney stones) = kidney damage
2) . Constipation
3) . Dehydration
4) . Tiredness/depression
What is the treatments for hypercalcaemia?
Fluids to tackle dehydration.
Treating the root of the cause of the hyperparathyroidism e.g. Removal of a benign tumour secreting PTH.
How does PTH act on intestines?
Stimulates the conversion of VitD to its active form = uptake of Ca2+ increases in the gut.
Where is calcitonin secreted from?
The parafollicular cells of the thyroid gland.
How is Pi regulated?
Co regulation:
- Vit D stimulates uptake of Ca2+ and Pi in gut
- PTH and VitD cause bone to release Ca2+ and Pi
BUT
- In the kidney, PTH causes uptake of Ca2+ whilst excreting Pi.
What is calcitonin thought to have a role in?
Lowering C2+ levels.
Maintaining the maternal skeleton during pregnancy.
What are the actions of calcitriol on the kidney?
It stimulates the reabsorption of Ca2+ = less urinary loss.
