12 - Endocrine control of calcium metabolism Flashcards
What are the roles of calcium in the body?
Neuromuscular excitability Muscle contraction Bone strength Intracellular second messenger Intracellular co-enzyme Hormone/neurotransmitter stimulus-secretion coupling Blood coagulation (factor IV)
How is calcium found in the body?
As calcium salts.
99% in the bones as complex calcium salts.
Some is present in the blood as Ca2+ (ionised calcium)
Some is bound to protein and others are soluble salts.
Only the free unbound Ca2+ is bioactive.
What percentage of calcium stored in the blood is bioactive?
50% is unbound and bioactive
45% is bound to plasma proteins
5% is diffusible salts
Where does calcium enter the body and where in the body is it needed and excreted from?
Enters in gastro-intestinal tract. Goes into blood. Blood takes it to bones and kidneys. Some lost through kidneys in urine Most lost in GI tract in faeces.
What increases [Ca2+]?
Parathyroid hormone (PTH)
1,25 (OH2) Vitamin D3 (Calcitriol)
What decreases [Ca2+]?
Calcitonin
Where is parathyroid hormone (PTH) secreted from?
Parathyroid glands
Where is calcitonin secreted from?
Parafollicular cells (outside a thyroid follicle, outside the follicular cells)
How are calcium levels sensed?
What happens if calcium is detected?
G-protein coupled cell surface receptors.
When calcium is sensed, the receptors recognise this and suppress PTH release.
What is an antagonist and what happens if this binds to the calcium receptor?
It stops calcium from binding to the receptor.
This makes the body think there is less calcium so more PTH is released.
Where may calcium receptors be found?
Parathyroid gland
GI tract
Kidney
What is the precursor to parathyroid hormone?
How long is the final PTH?
Pre-proPTH.
Final PTH is 84 amino acids long.
How does PTH interact with receptors?
PTH binds to transmembrane G-protein linked receptors.
This activates adenyl cyclase & PLC (phospholipase C) as a second messenger.
What are the actions of PTH on the kidneys?
- Increases Ca2+ reabsorption
- Increases (PO4)3- excretion. (Phosphate)
- Stimulates 1a hydroxyls enzyme which is used to make 1,25 (OH)2 Vitamin D3.
What is 1,25 (OH)2 V3 used for?
It stimulates the small intestine to:
- Absorb more Ca2+
- Absorb more (PO4)3- (phosphate)
What are the actions of PTH on the bones?
- Stimulates osteoclasts
- Inhibits osteoblasts
= More bone broken down
= Increased bone reabsorption
What is the overall action of PTH?
INCREASES blood Ca2+
Via -
Increasing Ca2+ reabsorption in the kidneys
Increasing Ca2+ adsorption in the small intestine
Increasing Ca2+ mobilisation in the bones.
How does PTH work in bones?
PTH binds to PTH receptor on osteoblasts.
This stimulates osteoclast activating factors (OAFs), e.g. RANKL
They cause osteoclasts to reabsorb bone and extracting calcium from it.
How is PTH regulated? (Think feedback loops)
Decreased plasma [Ca2+] causes PTH release.
PTH causes an increase in [Ca2+].
Negative feedback on parathyroid gland so less PTH released.
ALSO:
PTH increases synthesis of Vit D3. This also has -ve feedback on pituitary.
Catecholamines stimulate parathyroids to make more PTH.
Explain how dihydroxy-cholecalciferol is synthesised.
1,25 (OH)2 D3
Cholecalciferol (Vitamin D3) is made from:
- Diet
- 7-dehydrocholesterol in skin with UV light
In the LIVER:
Cholecalciferol is made into 25-hydroxy-cholecalciferol (25 (OH) D3)
PTH stimulates 1a hydroxylase enzyme…
In the KIDNEYS:
25(OH)D3 is made into 1,25 Di-hydroxy-cholecalciferol
(1,25 (OH)2 D3) = main bioactive form.
What is 1,25 Di-hydroxy-cholecalciferol also called?
Calcitriol
What are the actions of 1,25 (OH)2 D3 in the bones, kidneys and small intestine?
SMALL INTESTINE:
Increased Ca2+ and phosphate absorption
KIDNEYS:
Increased Ca2+ and phosphate reabsorption
BONE:
Takes in Ca2+ and stimulates osteoblasts
What does Fibroblast Growth Factor 23 do?
Regulates phosphate metabolism. Protects you from having high phosphate levels.
High phosphate and high Vit D3 triggers FGF23 to decrease phosphate level.
How does FGF23 and PTH affect phosphate reabsorption in the kidneys?
FGF23 and PTH inhibit the sodium phosphate transporter.
This means that LESS sodium and phosphate are reabsorbed into the blood, so more in excreted in the urine.
Calcitriol (Vit D3) stimulates FGF23.
