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Block 2- MSK > Physiology > Flashcards

Physiology Flashcards

1
Q

What inhibitor prevents hydroxyapatite precipitation in tissues outside of bone tissue? Why is this needed?

A

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

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2
Q

What medication class is used to treat brittle bones? What diseases does this treat?

A

Biophosphonates (after Ca and Vit D therapy fails)

Osteopenia, osteoporosis, Paget’s, and metastatic bone disease

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3
Q

What is the percentage of inorganic and organic components of bone?

A

66% inorganic, 33% organic

28% of organic is collagen

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4
Q

What does organic component of bone prevent? Inorganic?

A

Organic prevents bone shattering

Inorganic resists compression (aka they dont bend under you)

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5
Q

How many nuclei do osteoclasts have? What do they release to break down bone?

A

~50 nuclei

-acids and proteolytic enzymes

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6
Q

What is acid secretion by osteoclasts mediated by?

A

V-type H pump and the CIC-7 Cl- channel

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7
Q

What provides hydrogens for the V-type proton pump?

A

Intracellular carbonic anhydrase

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8
Q

What removes byproducts of carbonic hydrases from osteoclast osteolysis?

A

Cl-HCO3 exchangers

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9
Q

What enzyme is expressed in osteoclasts and macrophages that is a good indicator of osteoclast identification?

A

Tartrate-resistant acid phosphatase (TRAP)

-absence of TRAP= deficient osteoclast activity

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10
Q

What method of osteogenesis do flat bones use? Most other bones?

A

Intramembranous

Endochondral

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11
Q

What are the regulators of intramembranous osteogenesis? What kinds of regulators are these? What expresses these?

A

Cbfa1 and Runx2 (transcription factors) and Zinc Finger Transcription Factor

-expressed by mesenchymal cells

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12
Q

What is appositional growth in bones?

A

Growth that increases diameter of existing bones (like after a fracture)

NOT IN NEW BONES

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13
Q

What is the main purpose of bone remodeling?

A

Repair microscopic damage to bone (for strength)

To maintain calcium homeostasis

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14
Q

What are the key players in osteoclast signaling?

A

Calcitonin, adenylyl cyclase (AC), protein kinase A (PKA), IL-6, and osteoprotegerin (OPG)

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15
Q

What role does IL-6 play in osteoclast signaling?

A

Positive regulator in osteoclast differentation; induces expression of receptoir activator of NF-kB (RANKL) on osteoclast surface

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16
Q

What role does osteoprotegerin play in osteoclast signaling?

A

Secreted by oblasts and o-genic stromal stem cells; binds to RANKL and prevents its interaction w/ RANK

17
Q

What causes the formation of RANKL? What else happens with this?

A
  • PTH binding to receptors on osteoblasts

- macrophage colony stimulating factor (M-CSF) released

18
Q

What does RANKL do after its formation?

A

Binds to RANK

19
Q

How does RANKL and PTH interact? What is the result?

A

PTH binds to RANKL, preventing RANKL interaction on preosteoclasts to prevent differentation into o-clasts

20
Q

What does M-CSF bind to? What is the result?

A

RANKL binds to M-CSF, then this complex binds to receptors on preoscteoclasts and promotes diff into mature o-clasts

21
Q

What enzyme cascade is stimulated by monocyte colony stimulating factor when it binds to preo-clasts?

A

Tyrosine kinase (leads to generation of o-clasts)

22
Q

What does the WNT/beta-catenin pathway induce?

A

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)

23
Q

What parathyroid cells secrete PTH? What secretes calcitonin?

A

Chief cells

Thyroid

24
Q

What are dangerous fluctuation percentages of calcium? Normal?

A

30-35%

10%

25
Q

What Ca2+ concentration stimulates PTH release?

A

Less than 10 mg/dL

26
Q

How quickly does a PTH response occur when Ca2+ levels are low?

A

Seconds

27
Q

What are the ways calcium increases in intestines, bones, and kidneys by PTH?

A

Bones: Osteoclasts stimulated

Intestines: Calcitriol enhanced, incr absorption of Ca2+

Kidneys: Calcitrol released, Ca2+ reabsorbed

28
Q

What is PTH’s effect on phosphate homeostasis?

A

-decreases reabsorption in kidneys (decr serum phosphate)_

29
Q

What releases FGF23 (fibroblast growth factor)? What does this do?

A
  • olsteocytes

- reduces serum Pi levels (in response to high [Pi])

30
Q

What does estrogen deficiency lead to in bone? What relationship does testosterone have with bone?

A
  • low estrogen = lower bone density

- testosterone acts indirectly to increase bone density

31
Q

What are the factors influencing calcium homeostasis and bone homeo?

A

Age, Hormones, Vit C D K, protein intake, calcium intake, bone remodeling in response to stress (o-clast and o-blast activity)

Block 2- MSK (4 decks)

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