Calcium regulation

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Why is calcium regulation essential for normal physiological function?
Essential mineral component of the skeleton and teeth, acts as an intracellular second messenger, muscle contraction, blood coagulation, enzyme activity, neuronal excitability, hormone secretion etc
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Where is most of the calcium stored?
In bone as inorganic, mineralised matrix as hydroxyapatite
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Where is the rest of the calcium stored?
Intracellular in endoplasmic reticulum or as extracellular fluid
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What form is the calcium stored in cytosol as?
Ionised Ca2+ and complexed Ca2+ (Diffusible and acidic) as well as protein bound (non diffusible and alkaline)
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Why is there a 10,000 fold Ca2+ concentration gradient between ECF and cytoplasm?
It permits Ca2+ to function as signalling ion to activate intracellular processes and a Ca2+ influx into the cytoplasm is controlled by Ca2+ channels
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What can an influx of Ca2+ cause in a cell?
It regulates cellular function by interaction with intracellular Ca2+ binding proteins and Ca2+ sensitive protein kinases. It stimulates biological responses such as neurotransmitter release, contraction and secretion
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Is uncontrolled Ca2+ good?
No
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Which 3 tissues are most important in terms of calcium?
The kidneys (reabsorbs 98% of filtered calcium), Gut (absorption from diet) and Bone (remodelling)
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Where do the bone resources for remodelling come from?
Readily mobilisable calcium ion found in the salt of the extracellular fluid and from hydroxyapatite crystals (what's laid down in bone minerals)
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Where is calcium gained?
Only from the diet
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Where is calcium lost?
Urine, faeces and lactation
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When is calcium exchanged?
During bone remodelling
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Which 3 hormones control calcium regulation processes?
Parathyroid hormone, calcitonin and 1,25 dihydroxycholecalciferol (active vitamin D)
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How does parathyroid hormone regulate calcium?
When blood Ca2+ falls below normal Ca2+ levels PTH is released from the parathyroid gland which stimulates Ca2+ release from bones and stimulates Ca2+ uptake in kidneys which causes active vitamin D to increase Ca2+ uptake in intestines
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Which cells in the parathyroid gland secrete parathyroid hormone?
Secretory granules of cheif cells
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How does the chief cell secrete the granules containing PTH?
High Ca2+ binds to receptors on cells which leads to inhibition of PTH secretion. Low Ca2+ means that Ca2+ isn't bound to cell receptors so there is no inhibition of PTH secretion
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What biological effects of PTH are there?
Elevate blood concentrations of Ca2+, increase kidney tubular reabsorption of Ca2+, increase Ca2+ release from osteoblasts (rapid) and accelerate vitamin D formation in tubule epithelial cells
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How does parathyroid hormone affect bone?
There's fast exchange of Ca2+ from bone fluid labile pool found in the canaliculi making use of the membrane bound Ca2+ pump. Slow exchange occurs in mineralised bone where bone undergoes dissolution through osteoclast activity and Ca2+ diffuses out
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How does PTH cause the fast exchange?
PTH binds to a receptor on the osteoblast layer causing cAMP to stimulate Ca2+ channel to open allowing an influx of Ca2+ which then leaves the cell through a Na+Ca2+ exchanger
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How does PTH cause slow exchange?
PTH activate osteoblasts that activate the RANK ligand that sppeds up the maturation of osteoclast releasing Ca2+ from the stable pool and increasing bone reabsorption
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How does Calcitonin affect Ca2+ levels in the blood?
When Ca2+ rises too much the thyroid gland releases calcitonin which stimulates Ca2+ deposition in bones and reduces Ca2+ uptake in kidneys
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Which cells in the thyroid gland secrete calcitonin?
C cells (different from chief cells)
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What can calcitonin be used for?
Prevent hypercalcaemia after postprandial absorption of Ca2+ and protect against excessive loss of Ca2+ from the maternal skeleton during pregnancy
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Where is active vitamin D produced?
in the proximal convoluted tubule cells of the kidney. It is steroidal. It is produced from cholesterol or from the diet
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What is the biological function of active vitamin D?
Increase Ca2+ absorption from the intestine which protects bone
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How does active vitamin D help with absorption of Ca2+ from the gut?
Active vitamin D binds to a receptor on the promoter region on the DNA in intestinal epithelial cells and cause protein synthesis of Ca2+ channels, calbindin, pumps and exchangers to increase Ca2+ uptake in the cell
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How does a decrease in the amount of active vitamin D cause rickets?
A decrease in vitamin D, decreases calcium uptake in the gut, which increases PTH which increases Ca2+ reabsorbed from bone which leads to cartilage not properly mineralised, weak and malformed bones
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What effect does primary hyperparathyroidism cause?
Increase in PTH which causes an increased uptake in kidneys and increased Ca2+ reabsorbed from the bone which causes a decrease in bone density making fractures easier
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What effect does secondary hyperthyroidism cause?
Chronic renal failure leads to decrease in calcitrol production and decreased Ca2+ absorption in the gut as well as decrease Ca2+ retention in kidneys that cause hypocalcaemia which increases PTH which leads to bone deformation
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What can cause hyperparathyroidism?
Low Ca2+ diet, excessive phosphorus with normal/low Ca2+ or inadequate amounts of vitamin D3
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Card 2

Front

Where is most of the calcium stored?

Back

In bone as inorganic, mineralised matrix as hydroxyapatite

Card 3

Front

Where is the rest of the calcium stored?

Back

Preview of the front of card 3

Card 4

Front

What form is the calcium stored in cytosol as?

Back

Preview of the front of card 4

Card 5

Front

Why is there a 10,000 fold Ca2+ concentration gradient between ECF and cytoplasm?

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Preview of the front of card 5
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