Zachow - Calcium And Phosphate Homeostasis Flashcards
What is responsible for increased mineralization? Increased resorption? Both?
Mineralization - estradiol, anabolic androgens, GH/IGF1, Insulin, calcitonin, load bearing exercise
Resorption - glucocorticoids
Both - PTH, calcitriol, thyroid hormone
Under what circumstances will Vitamin D cause reabsorption?
Too much vitamin D.
At which part of the bone do we have the most remodeling?
Trabecular
How is it that osteoblasts impact the proliferation of osteoclasts?
1) Osteoblasts make what is called “RANKL”, which is responsible for upregulating the creation of osteoclasts.
2) On the contrary, osteoblasts also secrete something called “osteoprotegerin” which inhibits RANKL and hence the production of osteoclasts.
How does estrogen (E2/estradiol) impact bone remodeling?
Estrogen causes an increase in bone density in both men and women in a few ways:
1) inhibiting RANKL, which will stall osteoclasts production
2) stimulating the release of osteoprotegerin from osteoblasts
3) stimulating production of osteoblasts
4) apoptosis of osteoclasts
How does the osteoclast aid in setting up a favorable environment for Cathespin K?
It creates Portons, which then through a H+ATPase will get into the lacuna of bone. This is necessary because Cathespin K only works in highly acidic environments.
How does bone help in the case of an Acidemia?
Osteoclasts have a HCO3-/Cl- transporter so that if the blood become acidotic, HCO3 can be released from the cell in order to combat it.
What is it called when you have too much bone resorption? Too much mineralization?
Resorption - osteoporosis if severe enough, otherwise it is osteopenia.
Mineralization - metastatic calcification
WHat role does PTH have in the case of hypocalcemia?
Hypocalcemia will cause an increase in PTH. PTH will them stimulate:
1) increasing calcium resorption in the kidney
2) increasing bone resorption
3) Stimulating CYP27B1, which is the rate limiting step in forming Vitamin D, which will cause dietary calcium reabsorption from the GI
4) It will also cause PO4 secretion the kidney because remember we are only low in calcium, not PO4, so if we are going to resorb bone, we got to get rid of the excess calcium.
WHat affects do PTH and calcitonin have in both the proximal nephron and distal nephron?
Proximal:
PTH - calcitonin synthesis, blocks PO4 resorption
Calcitonin - stimulates PO4 resorption
- calcium reabsorption is passive
Distal:
PTH - stimulates calcium resorption
Calcitonin - stimulates calcium reabsorption
How is Calcium sensed in the kidney (proximal tubule)?
It is sensed by a receptor called CaSR (calcium sensing receptor). When calcium levels are high in the filtrate (indicating high Ca in the plasma), CaSR shuts off the activity of CYP27B1, which is the rate limiting enzyme in the production of Vitamin D, which usually reabsorbs Ca+.
In what situation might PTH mineralized bone? Resorb bone?
How do they exert these Affects?
Mineralization - small dose intermittently - osteoblast differentiation, mitosis, inhibits osteoblast apoptosis
Resorption - large continuous dose - stimulation of RANKL, osteoprotegerin inhibition.
In the case of hypercalemia how will CaSR lower calcium levels?
1) CaSR will upregulate the Vitamin D Receptor to upregulate Vitamin D, which also inhibits PTH secretion.
2) CaSR will inhibit PHT
3) CaSR will inhibit Parathyroid chief cell proliferation.
- essentially it will make sure that no PTH is made.
In the case of hypocalcemia how will CaSR increase the plasma Ca concentration?
1) It will inhibit the Vitaming D receptor
2) upregulation of Parthyroid chief cells
3) increased secretion of PTH
What molecule regulates plasma PO4? How?
FGF23. An elevated serum PO4 will stimulate FGF23 activity. Caltriol will do this as well.
1) FGF23 inhibits PTH secretion
2) FGF23 will block the expression of CYP27B1, so calcitriol isn’t made.
3) FGF23 has direct affects on the kidney in that it can prevent reabsorption of PO4.
4) Upregulates 24 hydroxylase, so as to chew up Vitamin D in the proximal tubule
