Calcium Homeostasis Flashcards
What is cystalline form, phosphate and calcium is found in complexed form in bones
Hydroxyapatite
What cells causes bone resorption
Osteoclasts
What is the bone sensing cell that maintains balance between osteoblastic and osteoclastic activites
Osteocytes
What is the bone forming cells
Osteoblasts
When the load is high what factors does the osteocytes recruit to increase BMD
Osteonectin, nitric oxide and dentin matrix protein
When the load is low, what does the osteocytes recruit to decrease bone mineral density
Sclerostin , DKK-1, RANKL
What is Ecac1/TrpV5
They are calcium channels in the kidney that open up and cause calcium reabsorption in the kidneys
What are the four ways PTH increase serum calcium levels
- Increase calcium reabsorption from collecting tubules in the kidneys through ECAC 1 and TRPV 5. 2. Increase osteoclastic activity and numbers/increase calcium resorption. 3. Increase phosphate loss in the urine. 4. Increase production of vitamin D3 in the kidney
Through what receptor does the body sense low serum calcium level
Through the GPCR calcium level sensor. When calcium is bound to the receptor, it will secrete PLC that will inhibit PTH. But when calcium is not bound, it will not inhibit PTH. The sensor acts like a negative feedback loop
What is the active form of vitamin D3
1,25 dihydroxyl Vitamin D3
What does cholecalcifeoral look like
In the presences of 1 alpha hydroxylase and PTH, what form of vitamin D do we have
We have the active form, which is 1,25 dihydroxylvitamin D3
Under the enzyme 24-hydroxylase and no PTH, what do we have
24,25 dihydroxy vitamin D3
Apart from high calcium level having a negative feedback through GPCR on PTH, what other substances can inhibit PTH secretion
High levels of 1,25 dihydroxy vitamin D3, high levels of calcium and high levels of FGF 23
What does calbidin-D9k do
It binds to calcium and prevents it from beinf sequestered into intracellular organelles. It also presents the calcium to the calcium ATPase which pumps it out of the cell into the blood
What are the factors vitamin D3 upregultes
Calbidin-D9k, Trp v6, calcium ATPase, and NPt2B
Why is the regulation of PTH secretion dysregulated in people with kidney disease
Because they can not make 1,25 dijydroxy vitamin D3 an important inhibitor of PTH
What does calcitonin do
Decreases osteoclastic activity, blocks renal reabsorption of phosphate and calcium
How does calcitonin reduce calcium serum level
Inhibit osteoclastic bone resorption, taking away the ability to bring calcium out of the bone into the serum It also increases calcium and phosphate loss in the urine
Explain the pathophysiology of pagets disease
It is caused by uncontrolled osteoclastic and osteoblastic activity It is caused by a slow acting virus
What are the symptoms of pagets disease
Hearing loss secondary to hypercalcemia Bone deformities Bone pain
What are the risk factors of osteoprosis
Age. Physical inactivity Low calcium intake in early years Long term glucocorticoid use
What is cholecaiferol, who can get it as a drug
An unhydroxylated form of 1,25 dihydroxy vitamin D3. A person with a functioning kidney and liver
What is the mechanism of action of active form of vitamin D3
Increased calcium and phosphate absorption from the gut Increased calcium and phosphate reabsorption in the renal tubules
What is the mechansim of action of bisphosphonates
Inhibits bone resorption and increase bone building capacity through this means. 1. Serves as phosphate analog that can replenish hydroxyapatite in bone minerals increasinf osteoblastic activity. 2. Induce apoptosis of osteoclasts reducing their numbers. 3. Block farnesyl pp an important intermidate in the synthesis of osteoclasts
What are the two bisphosphonates used only for cancer and pagets disease
Pamidronate and etidronate
What are the second line treatment to treat osteoprosis
Estrogens and SERMS Calcitonin
What is teriparatide(forteo) and abaloparatide(tymos)
They are parathyroid hormone analogs that are used for severe osteoprosis
What important ligand bind to their receptors for osteoclasts to be made
Rank L binding to Rank induce the synthesis of osteoclasts
What does continuous release/high dose of PTH do
Increase RANK L, decrease OPG. Increase bone resorption and serum calcium level
What are the pros for teriparatide treatment for osteoprosis
Builds bone mass at higher rate than bisphosphonates
What is the con for teriparatide
You have to inject daily. Not recommended for more than 2 years cos of the black box warning of causing bone cancer
What is the mechanism of action for denosumab
It binds to rank L and prevents it from binding to rank on osteoclast precursors preventing the making and differentiation of osteoclasts
What is the mechanism of action for Romosozumab
It inhibits sclerostin which is released by osteoclasts when there is no load or estrogen present. Sclerostin inhibits osteoblasts but increases osteoclasts
What is the ADR for romosozumab
MACE( major adverse cardiovascular events). People with myocardial infraction or stroke within one year should not take it
How does cincalet work
It is a positive allosteric modulator that increases the calcium sensing ability of the calcium sensing receptors in people with Chronic kidney disease to decrease PTH secretion
What does etelcalcetide do
It is a peptide that works the same way as cincalet. It is a PAM that inhibits PTH secretion by increasing the responsiveness of the calcium sensing receptor in people with CKD
What are zemplar and hectorol
Viramin D analogs that inhibits secretion of PTH with less effects on calcium resorption in the gut compared to vitamin D3
What are the two phosphate binders drugs we have
Lanthanum carbonate(fosrenol). Sevelamer(renagel)
What is the MOA for phosphate binders
They stay in the gut and bind up phosphate preventing it from getting absorbed in the intestine leading to decreased serum phosphate level
What are the three functions of fibroblast growth factor
Inhibit vitamin D synthesis. Inhibits PTH secretion. Stimulates phosphates excretion
