Endocrine Control of Calcium and Bones Flashcards
State 4 important functions of calcium in the body
- nerve muscle excitability
- fusion of and secretion from storage vessels
- muscle contraction
- intracellular second messenger
- structural - skeleton/bone remodelling
Where is the majority of the calcium stored in the body? And what is it called?
99% found in bones and teeth - hydroxyapatite
What is the total concentration of Ca in ECF? How much is biologically active?
~2.5mM, and approximately half is ‘free’
Is calcium well absorbed by the body? Why/why not?
No, as it it highly charged
Name the three types of cells involved in the formation and resorption of bone
Osteoblasts
Osteocytes
Osteoclasts
Which type of bone cell monitors the bone matrix and has an essential role in exchanging the Ca between ECF and bone?
Osteocytes
What is the function of osteoblasts?
synthesise and secrete collagen and promote the deposition of CaPO4 crystals
What is the function of osteoclasts?
promote bone resorption
What is the purpose of the cortical and spongy bone?
Cortical = hard bone, mineralised for strength, 80%
Spongy =. trabecular bine, metabolically more active, big surface area, 20%
Is the dissolution of bone a fast or slow process?
Slow
How can calcium be quickly exchanged from bone into plasma?
Membrane bound Ca pump (hormonal control)
Explain a primary signal for bone resorption.
Expression of RANKL on osteoblasts and its interaction with RANK on osteoclast progenitors
What is RANK? Which cell is it present on?
receptor activator of nuclear factor kappa B (osteoclast progenitor cells)
What is RANKL? And which cell is it present on?
RANK ligand (osteoblasts)
Name the three hormones which regulate Ca metabolism and bone
Parathyroid hormone
Vitamin D3
Calcitonin
Which hormone is secreted by the chief cells of the parathyroid gland? And what is its overall action?
Parathyroid hormone
increase Ca2+ and decrease PO4 in plasma
What are the actions of the parathyroid hormone in the short term and long term?
Short term: stimulate Ca pump in osteocytes
Long term: stimulate osteoclasts and inhibit osteoblasts
Explain the role of the kidney with regards to PTH
Decrease Ca loss by increasing tubular reabsorption of Ca2+ and decreasing tubular reabsorption of PO4
What is the role of the GIT with regards to PTH?
Stimulates activation of Vitamin D3
Which hormone involved in Ca metabolism is known as a pro-hormone?
Vitamin D
Vitamin D can come from plants and animals, what are the respective terms for each?
Pro Vitamin D3 - 7-dehydro cholesterol
Pro Vitamin D2 - ergosterol
What role does the sun have to play in the activation of Vitamin D?
The UV rays transform the vitamin d in skin (which is originally from diet) into its active form.
Is the processing of Vitamin D in the liver regulated? What is the metabolite formed?
Not regulated
Calcifediol
Is processing of Vitamin D is the kidneys regulated? What is the metabolic formed?
Highly regulated
Calcitriol
What are the three main biological actions of Calcitriol in the blood?
Cell differentiation
Activation of osteoblasts
Calcium and phosphate homeostasis
What is the overall MOA of Vitamin D3?
increase the amount of Ca in plasma
Which hormone os produced in the thyroid gland in the c cells?
Calcitonin
What is the overall MOA of calcitonin?
decrease Ca2+ in the plasma and increase PO4 in plasma (i.e., inhibits bone resorption
Hyperparathyroidism is a disease of Ca metabolism. It involves which hormone and what is the direct consequence?
PTH hyper secretion which results in hypercalceamia
What is the primary cause of hyperparathyroidism?
adenoma (cancer of parathyroid gland)
What are the two secondary causes of hyperparathyroidism?
chronic renal failure
Nutritional
What controls PTH release?
Plasma Ca2+ levels
What are some of the effects of hyperparathyroidism?
Osteoporosis
Increased Ca2+ excretion (issues with kidney)
Decreased excitability of nerves and muscles - this seems unusual bc calcium is involved in excitation
What is the main cause of hypoparathyroidism? And what can it lead to?
primary destruction of the parathyroid/thyroid gland (immune mediated or post-surgical), hypocalcaemia
List three other causes of hypocalcaemia
pregnancy, lack of vitamin D, change in blood pH
Hypocalcaemia is a serious condition - in what way can it cause death?
Increased neuromuscular excitability, death due to asphyxiation
What is the MOA of the drug Calcitriol?
Increases Ca uptake from diet –> mobilises Ca from bones
List three bisphosphonates that are used in the treatment of osteoporosis.
Risedronate, Alendronate, Zoledronate
What is the MOA of the bisphosphonates?
Inhibit the activity of osteoclasts (effects can last months to years)
Which SERM is used in osteoporosis? What is it MOA? Who are you more likely to treat with this drug?
Raloxefine, stimulate osteoblast activity, inhibit osteoclast activity. Women
Why are women susceptible to osteoporosis?
Menopause = decrease in estrogen whereas the testosterone in men is converted to oestrogen in the bone
What is the MOA of Denosumab?
inhibits RANKL, therefore decreases bone resorption
