Physiology-Calcium Regulation Flashcards
What factors go into calcium regulation?
Intestinal absorption/secretion, skeletal resorption/deposition, urinary excretion all contribute to regulation of BLOOD calcium levels.
Hormones involved in control of plasma calcium levels
PTH, Vit D and Calcitonin
Where is most of the majority of calcium found in the body?
The blood. It is much higher than intracellular levels and it is crystalized (99%) in bone so it doesn’t fall into the equilibrium equation.
What does calcium bind to when it acts as a second messenger?
Calmodulin changes conformation when it is bound to calcium and wraps around the binding site on the target protein.
How much Ca is ready to mobilize from bone at any point during hypocalcemia?
4-6g
How is vitamin D initially activated?
7-Dehydrocholesterol is split by UV light to vitamin D3 (cholecalciferol)
Vitamin D pathway
Travels from skin to liver, hydroxylated at 25 position and carried to kidney where it is activated by hydroxylation at the 1 position. 1,25(OH)2D3 increases Ca and PO4 uptake at the gut. It joins PTH at the bone in bone resorption.
What does PTH do in the kidney?
Increases Ca reabsorption, turns on the vitamin D hydroxylase and increases excretion of PO4
What things can turn on 1 hydroxylase in the kidney that activates vitamin D?
PTH, hypophosphatemia, testosterone and estrogen.
What things inactivate 1-hydroxylase and turn on the 24-hydroxylase in the kidney?
Hypercalcemia and hyperphosphatemia
Why does osteoporosis have a correlation with menopause?
Loss of follicles -> loss of estrogen -> decreased activation of vitamin D3 -> decrease gut absorption of Ca -> Bone loss to support serum Ca -> Osteoporosis. Other conditions are low Ca or high PO4 diet, low PTH and renal failure.
What effects does estrogen have on bone homeostasis?
Turns on vitamin D3 1-hydroxylase and allows for Ca uptake. Turns on osteoblasts, down regulates RANKL and upregulates OPG to decrease bone resorption.
How does calcitonin affect osteoclasts?
The same way as estrogen and opposite of PTH: down regulates RANKL and up regulates OPG in osteoblasts.
Hypophosphatemic vitamin D resistant rickets (VDRR)
The patient has low blood levels of phosphate, which should normally turn on 1-hydroxylase. However, there is a genetic defect on the phosphate transporter on the basal side of the cell. Phosphate builds up inside the renal cell that is producing 1-hydroxylase and high local levels turn it off.
Vitamin D dependent rickets treatment
Mutation in the 1-hydroxylase gene prevents activation of vitamin D. Treated with oral bioactive vitamin D 1,25(OH)2D. If it is type II then the target organ is resistant and nothing can be done and it is fatal.
Treatment for osteoporosis that inhibits osteoclasts
Bisphosphonates
Treatment for osteoporosis that sequesters RANK-L
Denosumab
