Regulation of Calcium and Phosphate Flashcards
Where is most of our calcium located?
Skeleton and teeth- extracellular ionised calcium is a biologically active component
2 sources of Vitamin D?
Diet and skin synthesis from sunshine- slight structural differences, D2 and 3
3 steps of Vitamin D metabolism?
- UVB light catalyses 7-dehydrocholesterol to pre-vitamin D3 and then vitamin D3. Transported to liver.
- 25-hydroxylase converts Vitamin D3 to 25(OH) cholecalciferol. Transported to kidneys
- 1-alpha-hydroxylase acts to produce 1,25(OH)2 cholecalciferol (calcitriol)
What substrate is used an as indicator of body Vitamin D status?
25(OH) cholecaliciferol
How is calcitriol regulated?
It regulates itself by decreasing transcription of 1-alpha hydroxylase
How does calcitriol increase calcium and phosphate?
Increases calcium absorption from bones
Increases Ca2+ from kidney
Increases Ca2+ from gut
Increases phosphate absorption from gut
Calcitriol action in the bones?
Low serum calcium- activates osteoclasts to increase Ca2+ absorption from bones
Normal serum calcium- activates osteoblasts to increase bone formation
PTH secreted by?
Chief cells in parathyroid glands as a large precursor molecule and then cleaved
Chief cells receptors?
G-coupled protein receptors
High extracellular Ca2+ binds to receptors which inhibits PTH secretion
PTH effects?
Ca2+ absorption from skeleton
Ca2+ reabsorption and phosphate excretion in kidneys- stimulates 1-alpha-hydroxylase activity
Ca2+ and phosphate absorption from gut
How is PTH regulated?
Negative feedback from increased serum calcium and 1,25(OH)2D3 synthesis
Calcitonin secreted by and 2 effects?
Parafollicular thyroid cells
Decreases osteoclast activity
Increases Ca2+ in kidney
Fibroblast Growth Factor 23?
FGF23 reduces phosphate levels by:
inhibiting Na+/PO43- co-transporter in proximal tube cells of kidney
Inhibits calcitriol to reduce phosphate reabsorption from gut
Hypocalcaemia causes?
Low PTH levels- hypoparathyroidism, surgery, auto-immune disorder, magnesium deficiency
Vitamin D deficiency- inadequate sun exposure, malabsorption or dietary insufficiency, liver disease, renal disease
Hypocalcaemia symptoms?
Paraesthesia
Convulsions
Arrhythmias
Tetany- contract but can’t relax muscles