Calcium Homeostasis Flashcards
What happens to ingested calcium? How is calcium transported?
Some used in calcium hydroxyapatite crystals in bone (stored)
Excreted in faeces and urine (most resorbed in kidneys)
Can be free or bound to citrate or plasma proteins in the ECF
What are some of the functions of calcium?
- builds/maintains bones & teeth
- regulates heart rhythm
- eases insomnia
- regulates passage of nutrients in/out of cells + intracellular pathways
- normal blood clotting
- nerve & muscle function (NMJs)
- lowers BP & blood cholesterol
- normal kidney function
- activity of some enzymes/hormone receptor binding
What hormones affect calcium control?
Parathyroid hormone (short term increase in calcium) PARATHYROID GLAND
Vitamin D derivative 1,25-(OH)2D3 (long term increase in calcium)
ACTIVATED BY PTH
Calcitonin (decreases calcium in animals, not much of a role in humans) THYROID GLAND
What is the structure of PTH? How is its synthesis regulated?
Straight chain polypeptide hormone
Synthesis regulated transcriptionally and post-transcriptionally (low calcium up-regulates gene expression and prolongs survival of mRNA)
Continually synthesised (chief cells synthesise and degrade PTH, released PTH degraded in liver)
Negative feedback: hypercalcaemia: binds to GPCR on chief cells, inhibits adenylate cyclase, reduces c.AMP production, and inhibits PTH release
What are the actions of PTH which raise calcium?
- induces osteoblast cells to secrete cytokines onto cell surface, stimulating differentiation and activity of osteoclasts —-> increased bone remodelling —> release of Ca2+ & Pi into ECF
- increased free calcium resorption in tubular cells of the distal convoluted tubule —> decreases excreted calcium (but Pi is excreted - prevents formation of kidney stones)
- activates vitamin D by stimulating C1-hydroxylase (liver) to form calcitrol (kidney)
What does calcitonin do?
Inhibits osteoclasts
What are the symptoms of hypocalcaemia?
Hyper-excitability of NMJ (calcium inhibits sodium channels —> low calcium means lowered depolarisation threshold?)
- pins & needles
- tetany
- paralysis
- convulsions
Normal [Ca2+] is maintained at expense of bone —> rickets
What are the symptoms of hypercalcaemia?
Stones, Moans, Groans
- renal calculi (kidney stones) due to excess Pi (forming calcium phosphate crystals)
- kidney damage
- constipation
- dehydration
- tiredness
- depression
What are some of the causes of hypocalcaemia?
Hypoparathyroidism
Malabsorption of vitamin D
What are some causes of hypercalcaemia?
Hyperparathyroidism
PTH-related peptide (PTHrp) (by BLTKP tumours)
Bony metastases promoting osteolysis
What is the key difference between PTH and PTHrp?
PTHrp does not activate vitamin D
How is vitamin D transported in the blood (fat-soluble hormone)?
Bound to transcalciferin.
