Physiology Flashcards
What inhibitor prevents hydroxyapatite precipitation in tissues outside of bone tissue? Why is this needed?
Pyrophosphte
Ca and Phosphorus is in large enough conc in ECF to form crystals, so inhib is needed to prevent that in non-boney tissue
What medication class is used to treat brittle bones? What diseases does this treat?
Biophosphonates (after Ca and Vit D therapy fails)
Osteopenia, osteoporosis, Paget’s, and metastatic bone disease
What is the percentage of inorganic and organic components of bone?
66% inorganic, 33% organic
28% of organic is collagen
What does organic component of bone prevent? Inorganic?
Organic prevents bone shattering
Inorganic resists compression (aka they dont bend under you)
How many nuclei do osteoclasts have? What do they release to break down bone?
~50 nuclei
-acids and proteolytic enzymes
What is acid secretion by osteoclasts mediated by?
V-type H pump and the CIC-7 Cl- channel
What provides hydrogens for the V-type proton pump?
Intracellular carbonic anhydrase
What removes byproducts of carbonic hydrases from osteoclast osteolysis?
Cl-HCO3 exchangers
What enzyme is expressed in osteoclasts and macrophages that is a good indicator of osteoclast identification?
Tartrate-resistant acid phosphatase (TRAP)
-absence of TRAP= deficient osteoclast activity
What method of osteogenesis do flat bones use? Most other bones?
Intramembranous
Endochondral
What are the regulators of intramembranous osteogenesis? What kinds of regulators are these? What expresses these?
Cbfa1 and Runx2 (transcription factors) and Zinc Finger Transcription Factor
-expressed by mesenchymal cells
What is appositional growth in bones?
Growth that increases diameter of existing bones (like after a fracture)
NOT IN NEW BONES
What is the main purpose of bone remodeling?
Repair microscopic damage to bone (for strength)
To maintain calcium homeostasis
What are the key players in osteoclast signaling?
Calcitonin, adenylyl cyclase (AC), protein kinase A (PKA), IL-6, and osteoprotegerin (OPG)
What role does IL-6 play in osteoclast signaling?
Positive regulator in osteoclast differentation; induces expression of receptoir activator of NF-kB (RANKL) on osteoclast surface
What role does osteoprotegerin play in osteoclast signaling?
Secreted by oblasts and o-genic stromal stem cells; binds to RANKL and prevents its interaction w/ RANK
What causes the formation of RANKL? What else happens with this?
- PTH binding to receptors on osteoblasts
- macrophage colony stimulating factor (M-CSF) released
What does RANKL do after its formation?
Binds to RANK
How does RANKL and PTH interact? What is the result?
PTH binds to RANKL, preventing RANKL interaction on preosteoclasts to prevent differentation into o-clasts
What does M-CSF bind to? What is the result?
RANKL binds to M-CSF, then this complex binds to receptors on preoscteoclasts and promotes diff into mature o-clasts
What enzyme cascade is stimulated by monocyte colony stimulating factor when it binds to preo-clasts?
Tyrosine kinase (leads to generation of o-clasts)
What does the WNT/beta-catenin pathway induce?
OPG production
-WNT prod by osteoprogenitor cells, binds to LRP5 and 6 on osteoblasts, triggers beta-catenin and production of OPG (incr bone, decreased o-clast)
What parathyroid cells secrete PTH? What secretes calcitonin?
Chief cells
Thyroid
What are dangerous fluctuation percentages of calcium? Normal?
30-35%
10%
What Ca2+ concentration stimulates PTH release?
Less than 10 mg/dL
How quickly does a PTH response occur when Ca2+ levels are low?
Seconds
What are the ways calcium increases in intestines, bones, and kidneys by PTH?
Bones: Osteoclasts stimulated
Intestines: Calcitriol enhanced, incr absorption of Ca2+
Kidneys: Calcitrol released, Ca2+ reabsorbed
What is PTH’s effect on phosphate homeostasis?
-decreases reabsorption in kidneys (decr serum phosphate)_
What releases FGF23 (fibroblast growth factor)? What does this do?
- olsteocytes
- reduces serum Pi levels (in response to high [Pi])
What does estrogen deficiency lead to in bone? What relationship does testosterone have with bone?
- low estrogen = lower bone density
- testosterone acts indirectly to increase bone density
What are the factors influencing calcium homeostasis and bone homeo?
Age, Hormones, Vit C D K, protein intake, calcium intake, bone remodeling in response to stress (o-clast and o-blast activity)
