Calcium Flashcards
What percentage of calcium in our bodies is stored intracellularly in the sarcoplasmic reticulum?
0.9%
What is the concentration of free calcium in our systemic circulation?
1.2mM
Calcium taken in through our diet can go down one of 2 paths. Explain them.
- excreted
- absorbed
Explain the role of osteoblasts
Bone building cells.
Add osteocytes into the bone matrix as well as secreting a precursor for osteoclasts to repeat the cycle
Osteoclasts promote…
Bone resorption
Bone resorption results in a transfer of calcium from the ….. to the …..
Bone to the blood
Explain why trabecular bone has a greater surface area
Because it is more metabolically active
Osteons are the structural unit of…
Trabecular bone
What stimulates the release of parathyroid hormone (PTH)?
Low calcium levels (dropped before 1.2mM)
Where does PTH act within the body? 2 direct and 1 indirect
Bones and kidneys (direct)
GIT (indirect)
What action does PTH have on the kidneys?
Increases tubular reabsorption, therefore decreasing how much calcium is being excreted
Define bone resorption
Process where osteocytes break down bone tissue, releasing minerals and calcium into systemic circulation
What effect does PTH have on bones?
Increases bone resorption
What effect does PTH have on the GIT?
Stimulates the activation of vitamin D
Vitamin D 2 and 3 are both prohormones. What is the first stage of their metabolism
Gets converted into active form with UV exposure
Calcifediol is the form of vitamin D produced after which stage of metabolism?
Produced by the liver
Calcifediol is converted into —? by the kidneys
Calcitriol
What is the name of the biologically active form of vitamin D?
Calcitriol
Name 3 ways in which vitamin D increases the plasma concentration of calcium.
1 - stimulates the bone to mobilise Calcium and PO4
2 - Promotes calcium reabsorption in the kidneys.
Also stimulates production of the calcium binding protein, which helps calcium cross the gut wall
Which hormone has the opposite effect of PTH?
Calcitonin
Where is calcitonin produced?
Thyroid gland
List some of the actions of calcitonin
- decreases ca plasma concentration
- inhibits bone resorption
- decreases kidney reabsorption
Overall, protects against hypercalcaemia
Define hyperparathyroidism
Hypersecretion of PTH, leads to hypercalcemia
Causes of hyperparathyroidism?
Adenoma (cancer in thyroid)
Chronic renal failure
Hyperparathyroidism causes osteoporosis. True or false
True = caused by increased calcium metabolism
Does hyperparathyroidism increase or decrease nerve and muscle excitability? What are the symptoms of this?
Decrease
Fatigue, weakness, depression, etc
Implication of hypoparathyroidism?
Body cannot respond to low calcium levels due to decreased PTH secretion
Why can hypoparathyroidism occur in pregnancy?
Increase demand for calcium during pregnancy and lactation
Lack of vitamin D intake causes what condition?
Curved bones.
Rickets (children)
Osteomalacia (adults)
Rickets is also known as…
Osteomalacia
How can an increase in blood pH change your calcium levels?
More negatively charged ions are present, which then ‘mop up’ free calcium
Hypocalcaemia causes increased neuromuscular excitability. How can this cause death?
Low calcium causes the ion channel to be open for longer, which causes increased excitability. This can cause paralysis of the respiratory muscles, causing death by asphyxiation
Which form of vitamin D can be given to those in renal failure?
Calcitriol
Which form of vitamin D is formed in the liver but still requires metabolism by the kidneys?
Calcifediol
Biphosphonates are used to treat….
Osteoporosis
Compare first and second generation biphosphonates
First generation = induces apoptosis of osteoclasts
Second = reduces recruitment of osteoclasts
Why is biphosphonate treatment only every 6 - 12 months?
Biphosphonates get incorporated into the bone matrix as it is being built. Therefore, they only have their action once the osteoclasts come and try to break down the bone
Explain the action of SERM drugs
Oestrogen agonists that act on the bone. Main role is to stimulate osteoblasts and inhibit osteoclasts
Explain why women are more susceptible than men to osteoporosis?
Oestrogen acts as a protective mechanism against osteoporosis. Once menopause hits and oestrogen levels drop, women are more susceptible.
Which class of drugs are contraindicated in osteoporosis?
Synthetic glucocorticoids
Describe the action of glucocorticoids on bones.
Increase osteoclasts activity and decrease osteoblasts
When RANK-L binds to RANK, what happens?
Osteoclast activity is increased, which increases bone resorption. Osteoclasts are then acting more than osteoblasts, resulting in a loss of bone mass
True or false. The conversion of cholecalciferol into calcifediol is regulated by hormones.
False. The conversion that occurs in the liver is not regulated
Which form of vitamin D is formed when acted on by UV?
cholecalciferol
How does renal failure cause hyperparathyroidism
Renal failure means calcifediol is not being converted into the active calcitriol, meaning there is hypersecretion of PTH to try increase calcium levels
How does hypocalcaemia cause death?
Causes asphxiation due to increased excitability of nerve and muscle fibres. This is because calcium normally binds to a receptor on the sodium channel and modulates the receptor. But in low calcium state, calcium is removed from this pump meaning the channel opens more easily and more depolarisation occurs.
Why are women more susceptible to osteoporosis than men?
- lower starting bone mineral density
- loss of estrogen after menopause (men constantly produce testosterone which gets converted to estrogen anyway)
What can low vitamin D intake cause?
Rickets / osteomalacia
Which vitamin (D2 or D3) requires UV light activation?
Both
Calcitriol can be given in renal failure, true or false?
True
Is raloxifene steroidal? Can it cause breast cancer?
No it is not steroidal. Just an estrogen agonist. Not an agonist on breast or endometrial tissue, so cannot cause breast or uterine cancer
Define alkalosis and its effect on calcium
A change in blood pH means more negatively charged ions are available to mop up the calcium ions, meaning plasma calcium levels go down
Explain use of teriparatide
Recombinant PTH. Moa= increases number and activation of osteoblasts and therefore increases bone formation.
Why is teriparatide use limited?
Limited to 18months life time. Due to risk of osteosarcoma development
Teriparatide is contraindicated in hyperparathyroidism. Why?
Because it is recombinant PTH
What can excessive vitamin D cause?
Hypercalcaemia
How can hypercalcaemia cause kidney stones
Saturation causes the precipitation of calcium salts in the kidney
