Flashcards in Calcium Deck (41)
What are the three types of protein?
Peptide, steroid and amine
In what forms may calcium be found in the blood plasma?
50% is bound to protein such as albumin (but can be globulin), 40% is ionised and 10% is in a complex with phosphate or citrate
Where is most of the body calcium found?
What happens to ionised calcium levels in response to acidosis?
Albumin will bind to more H+ ions in order to buffer the decrease in pH and therefore there are less sites available for calcium to bind, and therefore the calcium is released as a non-bound ionic form (Ca2+)
What happens to ionised calcium levels in response to alkalosis?
Albumin will bind to less H+ ions in order to buffer the increased pH by allowing the circulation of more H+ and therefore there are more sites available on the albumin molecule for the binding of calcium, and therefore less is circulating in the ionised form
Where does most renal calcium reabsorption occur?
In the proximal tubule via paracellular routes
Describe the role of the proximal tubule in the reabsorption of calcium
This is where most of the calcium is reabsorbed, and this is by paracellular routes (between the cells) that is driven by the voltage gradient and is independent of PTH
Describe the role of the Loop of Henle in the reabsorption of calcium
About 20% of calcium reabsorption occurs here by paracellular and transcellular transport that is voltage-dependent
Describe the role of the distal tubule in the reabsorption of calcium
About 10% of calcium reabsorption occurs here via transcellular routes and this is PTH-dependent as it upregulates the TRPV calcium channels (apical surface), calcium ATPase and 3Na+/Ca2+ exchanger (basolateral membrane)
What happens when the calcium sensing receptor (CaSR) in the thick Loop of Henle is activated?
It causes the down regulation of the Na+/K+/2Cl- receptor on the apical surface
What drugs would inhibit the reabsorption of calcium in the Loop of Henle?
How does PTH affect the function of the proximal convoluted tubule?
Down-regulates sodium-phosphate transporters which reduces phosphate reabsorption, and increases gluconeogenesis in the PCT
How is PTH involved in the metabolism of vitamin D?
Allows conversion of calcidiol to calcitriol
How does PTH affect reabsorption of water, sodium and bicarbonate?
It inhibits their reabsorption via effects on the Na/H+ exchanger and the Na+/K+ ATPase
Describe how PTH is produced
There is translation to form pre-proPTH which migrates to the RER and is cleaved to form proPTH . The proPTH is then transported to the golgi apparatus where it is cleaved to form PTH and enters vesicles which are then stores or leave by exocytosis
What is the action of PTH on the kidney?
in the kidney PTH leads to decreased calcium excretion and increased phosphate excretion (to compensate for the increased phosphate levels derived from osteoclastic function).
Therefore there is more calcium reabsorbed and less phosphate reabsorbed
What is the action of PTH on bone?
To increase calcium and phosphate reabsorption
What is the action of PTH on the intestines?
Increased absorption of calcium and phosphate in the gut, mainly by indirect action of activating vitamin D
Where is the calcium sensing receptor found?
Everywhere, but most importantly the parathyroid gland and the kidney
What happens when calcium binds to the calcium sensing receptor?
Causes reduced PTH secretion, increased breakdown of stored PTH and suppressed transcription of the PTH gene
What is bone itself primarily made up of?
Collagen and hydroxyapatite
What causes mineralisation of bone?
Calcium, phosphate and alkaline phosphatase (ALP)
What is the mechanism of action of PTH on bone?
increases RANKL, decreased OPG, increases IGF1 and IL-1 which work to increase osteoclast activity (increased bone resorption)
What is the mechanism of action of calcitriol on bone?
Increases RANKL levels, decreased OPG (osteoprotegerin) and increases gut calcium absorption. Therefore increases serum calcium levels
What is the mechanism of action of glucocorticoid/cortisol on bone?
this reduces osteoblast numbers (reduced bone deposition) and mineral production as well as increasing RANKL
What is the mechanism of action of oestrogen on bone?
oestrogen contributes to epiphyseal closure, reduced cytokine sensitivity and inhibits bone remodelling
What molecule forms cholecalciferol on exposure to UVB light in the skin?
7-dehydrocholesterol is cleaved on exposure to UVB light and produces cholecalciferol
Which enzyme regulates the conversion of calcidiol to calcitriol in the kidneys?
What molecules promote conversion of calcidiol to calcitriol in the kidneys?
1-alpha hydroxylase is promoted/activated by increased PTH, decreased calcium or decreased phosphate levels