Endo 11 - calcium metabolism Flashcards
State some roles of calcium in the body.
Control of neuromuscular excitability (hypocalcaemia leads to hyperexcitability because Ca2+ normally blocks the Na+ channels) Muscle Contraction Strength in bone Blood clotting Intracellular second messenger
Where is calcium mainly stored?
Bone - 99% is stored as hydroxyapatite crystals in bone - complex hydrated salt
How is calcium present in the blood? What is the main component?
Unbound ionised calcium - 50% = biologically active - 1.25mM
Bound to plasma proteins - 45%
Tiny bit as soluble salts
Total blood conc = 2.5mM
What is the usual daily intake of calcium?
1000 mg/day but 850mg excreted by GI, some goes to blood - target organs = kidneys to regulate ion concentration than most is rejected in urine and bones - taken up from blood but calcium is also broken down and re released
What two hormones raise plasma calcium concentration?
Parathyroid Hormone (by parathyroid glands) Calcitriol (1,25-dihydroxycholecalciferol) = vit D3
What hormones decreases plasma calcium concentration?
Calcitonin (by parafollicular cells in the thyroid)
Where is parathyroid hormone produced?
Parathyroid Glands (four of them) - produced in the follicular cells
Where is calcitonin produced?
Parafollicular cells in the thyroid gland
Where are located calcium-sensing receptors?
on parathyroid glands - used for calcium homeostasis. release PTH in the absence of calcium
What is PTH’s mechanism of action?
PTH is a polypeptide
Binds to transmembrane Gprotein coupled receptor
Activation of AC but also probably PLC as secondary messenger system
What three organs does PTH have an effect on?
Kidneys
Bones
Small intestines
Describe the effects of PTH on bone.
Stimulates osteoclasts
Inhibits osteoblasts
So increase bone resorption
Describe the effects of parathyroid hormone on the kidneys.
Increases calcium reabsorption
Increases phosphate excretion
Stimulates 1aplha hydroxylase activity (which will increase vit D3 synthesis)
How does PTH increase calcium release from bone?
PTH has a direct effect in inhibiting osteoblasts. PTH makes the osteoblasts produce osteoclast activating factors (such as RANKL) that bind to receptors on osteoclasts and stimulates the break down of bone matrix to release calcium.
What can stimulate PTH release?
Low plasma calcium concentration
Catecholamines (by binding to beta receptors)
Describe the negative feedback loops on PTH.
Increased plasma calcium concentration has a negative feedback effect on PTH
Calcitriol also has a negative feedback effect
Describe the negative feedback loops on PTH.
Increased plasma calcium concentration has a negative feedback effect on PTH
Calcitriol also has a negative feedback effect
What are the three main PTH effects?
- increase Ca2+ absorption (gut)
- Increase ca2+ reabsorption (kidneys)
- increase Ca2+ mobilization (bones)
How is PTH regulatded?
PTH Regulation
Decreased plasma Ca2+
Leads to increased PTH production in parathyroid glands
o This leads to increased Ca2+
The increased Ca2+ then exhibits NEGATIVE FEEDBACK on the parathyroid glands
Increased PTH leads to:
o Synthesis of 1,25 (OH)2D3
o Synthesis exerts +ve influence increasing plasma Ca2+, but a NEGATIVE influence on the parathyroid glands to reduce PTH production, which then has a secondary effect reducing Ca2+
Catecholamines have a positive effect on the parathyroid glands via beta receptors
What is the precursor of calcitriol?
Cholecalciferol (vitamin D3)
Comes from the diet and the conversion by UV light from 7-dehydrocholesterol
Describe the effects of calcitriol.
Small Intestines:
Increased Ca2+ Absorption
Increased Phosphate Absorption
Bones:
Increased Osteoblast Activity x
Kidneys:
Increased Ca2+ Reabsorption
Increased Phosphate Reabsorption x
How is calcitrol formed from cholecalciferol (vit D3)?
Vit D3 –> 25(OH) D3 –> 1,25(OH)2 D3 =calcitrol Last step converted by 1alpha hydroxylase (synthesis stimulated by PTH)
What is calcitonin’s mechanism of action?
Polypeptide
Binds to transmembrane G protein linked receptor
Activation of AC or PLC
Describe the effects of calcitonin.
Exact opposite as PTH and calcitriol
Results in a reduction of the calcium concentrations in the blood.
- increases Ca2+ excretion in kidneys
- inhibition of osteoclast activity
