:73: Calcium Metabolism Flashcards
What is the physiological normal [CA]?
10mg/100mL
10mg%
How can Ca2+ be found in the blood?
51% ionized
46% bound to serum protein ex: albumine
3% complex w other ions
What is the role of Ca?
1) muscle contraction
2) Release of hormone
3) important component of skeleton
4) Propagation of nerve impulse
5) Activation of Calmodulin which is a ubiquitous enzyme and activates other enzymes
6) Blood clotting
What organs regulate the serum levels of Ca?
1) Bone (can increase Ca by osteoclasts which break bones)
2) Intestine: By increasing absorption of Ca
3) Kidney: By increasing reabsorption of Ca in distal tubules and decreasing the reabsorption of PO43- in distal and proximal tubules
What are the Hormones that increase the levels of Ca in the blood?
1) Parathyroid Hormone Secreted by Parathyroid Gland
2) Vit D in its active form
How is PTH secreted?
WHen Ca2+ levels decrease in the proximity of parathyroid Gland,
Increase transcription and translation of PTH
1) Pre-proPTH 110aa
2)ProPTH 90 aa
3) PTH 84 aa secreted into blood
How is PTH affected when Ca leveles rise?
Decresed
Where does PTH act directly?
1) Bone
2) Kidneys
Where does PTH act indirectly?
Intestine through Vit D
How does PTH act on bone
1) PTH binds to extracellular receptor on osteoblast
2) RANK Ligand secreted by osteoblast (osteoclast differentiating factor)
3) RANKL + Pre-Osteoclas –> Osteoclas
4) resorption of bone and increase of serum Ca2+
How can we treat osteoporosis?
Antibody against RANKL
- -> Osteoclast cannot mature
- ->stop resorption of bone
How does PTH act on kidneys?
Binds to receptor ion distal and proximal tubule
1) increases reabsorption of Ca in distal tubules
2) decreasing the reabsorption of PO43- in distal and proximal tubules
3) Activates 1 Hydroxylase which activates Vit D
4) Increase of cAMP in urine
How does PTH indirectly increases reabsorption of Ca in intestine?
Promotes activation of Vit D in the kidney
Vit D binds to receptor on kidneys which increase Ca BP and TRPV6 (Ca Channel) Transcritpion
–> More Ca absorbed in intestines
What is PTH gene related
This can cayse hypercalacemia of the tumors od kidney and lungs
PTHRP looks like PTH
–> Acts on its receptors
–> Increases levels in the serum even if we do not need it
How can we treat Hypercalacemia of the tumor?
We can give»_space;»»» Calcitonine (hyper physiological levels) which then decrease level of Ca by decrease resorption of bone and decreases the absorption if Ca in the intestine since calmodulin is at» levels
Where is Calcitonin made?
C cells of the thyroid hormone
32 aa
In response to high [ca]
What is the effect on Ca levels of hyperthyroidism?
Increase Calcitonine
Decrease Ca 2+
Problems w osteroporosis
What happens in hypothyroidism?
Decrease Calcitonin
Levels of Ca remain high
Calcification!
Where is the main action of calcitonin?
Bone
- -> Shrinking osteoclast
- -> less resorption
- -> less ca in the serum
What happens at hyperphsiological [calcitonin]
decrease of ca reabsorption by the kidneys but that rarely happens spontaneously
usually happens when we treat hypercalacemia of the tumor by giving a high dose of calcitonin
Where does calcitonin have no effect at all?
Intestine
What does calcitonin do to stomach?
inhibits gastrin secretion
-> does not affect ca metabolism just another fun fact that it does
How is vit D made?
From 7-dehydroxycholesterol in the skin
+ UV activation
–> Vit D3
Can also be in the diet (supplements, fish, dairy)
How is vit D activated
1st) In skin w UV -> VitD3 (cholecalciferol)
2nd) in liver –> 25 (OH) D3
3rd) In kidney –> 1,25 (OH2)D3
E- 1 hydroxylase activated by PTH
