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Musculoskeleton > Physiology Of Bone And CT > Flashcards

Physiology Of Bone And CT Flashcards

1
Q

Key elements of bones

A

Large amounts of ECM w/ proteins and hydroxyapatite crystals.

Also contain Progenitor cells, osteocytes, blasts and clasts which continue to remodel bone as needed.

  • matrix is key provider of strength and stability
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2
Q

Connective tissue cells

A

Fibroblast, immigrant and resident chondrocytes, macrophages, mast cells and plasma cells.

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3
Q

Pyrophosphate

A

Inhibits spontaneous hydroxyapatite formation since the concentration of calcium and phosphate ions naturally well exceed the required amount to cause spontaneous formation.

Found in all normal tissues and plasma, except for bone.

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4
Q

% of nutrients bone contains

A

99% of entire body calcium and phosphate

80% of entire body carbonate

50% of entire body magnesium

35% of entire body sodium

33%/67% ratio of organic:inorganic compounds in bone composition.

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5
Q

Bisphosphonates

A

Used to combat loss of bone.

Contains high phosphate concentration which promotes hydroxyapatite formation and also encourages osteocytes apoptosis.

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6
Q

Organic 33% of bone consists of what?

A

28% collagen

5% proteins (non collagen)

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7
Q

67% of inorganic bone composition consists of what?

A

Primarily hydroxyapatite

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8
Q

What vitamin deficiency causes collagen formation deficiencies?

A

Vitamin C

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9
Q

Removing organic vs inorganic matrix of bones.

A

Remove organic = brittle bones (shatter easily)

Remove inorganic = twisty bones (cant resist compression)

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10
Q

Summary of 4 types of bone cells

A

Progenitor osteocytes: stem cells who differentiate into osteoblasts

Osteoblasts: immature bone cell that secretes osteoid.

Osteoclast: multinucleated cell differentiated from osteoblasts that dissolve hydroxyapatite via acidic molecules

Osteocyte: mature bone cell that maintains bone matrix

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11
Q

RUNX2 gene defects

A

Defective Gene that inhibits preosteoblast proliferation and differentiation ultimately reducing the total amount of osteoblasts.

  • causes lack ossification in teeth and bones, especially the collarbones

(Cleidocranial dysplasia)

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12
Q

Osx (Sp7)gene deficiency

A

Inhibits osteoblasts and osteocytes maturation and differentiation from preosteoblasts

Secrete poor osteoid that makes mineralization difficult and collagen synthesis poor.

Deficiencies lead to osteogenesis imperfecta (brittle bone disease)

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13
Q

Integrins

A

Integrins: bind vitronectins on bone surfaces to seal osteoclasts to bone

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14
Q

Vitronectins

A

Surface proteins that bind to integrins on bone to stabilize osteoclast for bone reabsorption.

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15
Q

Acid proteases and protons

A

Secreted in the vesicular zone right above the ruffled border of the osteoclast. Are released into the bone and cause break down of hydroxyapatite into Ca2+ and PO4

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16
Q

V-type proton pump and ClC7 channels

A

Channels and pumps that are located at the ruffled border that help initiate exocytosis of H+ ions and proteases.

Use ATP so is a form of active transport against the proton gradient

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17
Q

Carbonic anhydrase

A

Supplies the H+ ions in the osteoclast.

Gets protons from water and generates bicarbonate from OH + CO2. Bicarbonate is excreted via Cl-HCO3 pumps

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18
Q

CL-HCO3 exchangers

A

Antiport that pumps chloride in and bicarbonate out. Helps get chloride into the cell to secrete with protons into the howship lacuna

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19
Q

Clathrin

A

Mediates formation of secretory vesicles in vesicular zone.

Helps bind the vesicles to the correct area.

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20
Q

Tartrate-resistant Acid phosphatase (TRAP)

A

Metalloenzyme expressed in osteoclasts and macrophages

Staining of this enzyme is often done to determine osteoclast activity.

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21
Q

Factors that must be expressed for Mesenchymal cells to differentiate into osteoblasts

A

Cbfa1/Runx2 and Osx

22
Q

Primary (woven)bone

A

First bone formed at any site and contains random fiber orientations.

-ultimately replaced by lamellar bone with parallel fibers.

23
Q

Purposes of bone remodeling

A

Establish optimum bone strength

Repair damaged bone

Maintain calcium homeostasis

24
Q

RANKL

A

receptor activator of KB-nf ligand

Expressed by osteoblasts and helps control osteoclast activity and formation.

25
Q

RANK

A

Receptors themselves for RANKL

Located on osteoclast precursors and mature osteoclasts

26
Q

OPG

A

Osteoprotegerin

Binds to and inhibits RANKL

Expressed by osteoblasts and other body tissues

Prevents bone loss

27
Q

RANKL/RANK/OPG pathway

A

Osteoblasts release RANKL wither by itself or in conjunction with OPG

By itself: will bind to RANK receptors on osteoclasts and/or osteoclasts precursors.

Initiate differentiation to mature osteoclasts. And activates bone reabsorption.

Together w/ OPG: OPG binds to RANKL and inhibits it from binding to RANK.

28
Q

Estrogen (estradiol) vs menopause

A

Hormone that can limit release of RANKL. High estrogen increases OPG production as well and both increase bone production

Menopause (low estrogen) increases RANKL production and causes bone reabsorption.

29
Q

RANKL/RANK uses other than bone remodeling

A
  • High RANKL levels have been indicative of increased progesterone release and also the regulation of BRCA1 mutation for breast cancer.
  • lactation in mammary glands occurs via RANKL/RANK pathway
  • Dendritic cell production and maturation occurs in part due to RANK/RANKL pathway.
30
Q

Denosumab

A

Antibody that acts similar to OPG and inhibits RANKL binding to RANK receptors.

used in treatment of osteoporosis.

31
Q

Calcitonin vs PTH

A

Calcitonin: Tends to decrease plasma calcium and antagonize PTH

PTH: tends into increase plasma calcium and antagonize calcitonin.
- PTYH also lowers OPG levels.

32
Q

Protein Kinase A

A

Inhibits bone resorption in osteoclasts in high levels.

Is formed via cAMP and adenylyl Cyclase via calcitonin binding

33
Q

IL-6

A

Believed to play a role in up regulating RANKL production leading to overall increases in bone resorption

34
Q

M-CSF (macrophage colony stimulating factor)

A

Released with RANKL and binds to preosteoclasts stimulating a tyrosine kinase pathway for differentiation

Initiates differentiation from preosteoclasts -> mature osteoclasts.

35
Q

WNT/(b)-catenin pathway

A

WNT is produced by osteoprogenitor cells and binds to LRP5 and 6 receptors on osteoblasts.

This causes osteoblasts to release (b)-catenin which stimulates production of OPG

Ultimately reduces osteoclast activity.

36
Q

Sclerostin

A

Produced by osteocytes and inhibits the WNT/(b)-catenin pathway.

Decreases OPG secretion and increases osteoclast activity.

37
Q

BMPs

A

Bind to transmembrane serine and threonine receptors and induce heterotropic bone formation

  • ectopic cartilage formation followed by Endochondral bone. (Often proceeds major trauma)
  • increase osteoblast activity.
38
Q

PTH (84)

A

Secreted by parathyroid and is metabolized into active PTH (34) and inactive PTH (84)

39
Q

Actions of activated PTH throughout body

A

Blood:
- increase and decrease serum calcium and phosphate respectively.

Kidney:

  • cAMP, active Vitamin D and kidney absorption of urine Ca are increased.
  • Urine phosphate absorption is decreased

Bone
- osteoclast and osteoblast activity are increased.

40
Q

Chief cells

A

Primary cells of Parathyroid that secrete PTH

41
Q

Oxyphil cells

A

Unknown function but are thought to be modified or deprecated chief cells.

42
Q

Synthesis and secretion of calcitonin occur in what cells of the thyroid?

A

Parafollecular cells (C cells)

calcitonin is also a 32 amino acid peptide that is always released in active form

43
Q

Normal Ca2+ blood concentration

A

10mg/dl

<10mg = increased PTH secretion, decreased PTH

> 10mg = increased calcitonin secretion, decreased PTH

44
Q

Calcitriol

A

Hormone in intestines and kidneys that stimulate calcium reabsorption in digestive renal tract.

45
Q

Regulators of phosphate homeostasis

A

PTH (parathyroid cheif cells)

Active 1,25 vitamin D: (renal cells)

FGF23 (released by osteocytes

All reduce phosphate reabsorption / increase urination excretion of phosphate

46
Q

Vitamin D specific causes of rickets and osteomalacia

A

Deficiency in Vitamin D causes poor absorption of calcium in intestines and kidneys.

Leads to increased PTH secretion which ultimately increases osteoclast activity

Also leads to inhibition of phosphate ion reabsorption = cant make hydroxyapatite.

  • leads to defective hardening of bones (Soft bones and abnormal long bones)

Rickets = kids ; osteomalacia = adults

47
Q

Testosterone

A

Increase bone deposition/ growth

48
Q

Compression vs tensions vs pressure on bones

A

Compression = stimulates bone deposition/growth

Tension =. Stimulates bone deposition/growth

Pressure = sitmulates bone resorption/ breakdown

49
Q

Special CT subcategories

A

Adipose, cartilage, bone and bone marrow

50
Q

Embryonic Connective Tissue

A

Mesenchyme

51
Q

LRP5 & 6 receptors

A

Receptors on osteoblasts that receive signals from

BMP, Sclerostin, WNT.

Sclerostin = decreases (b)-catenin secretion and INHIBITS osteoblasts

WNT & BMP increases (b)-cateinin secretion and PROMOTES osteoblasts

52
Q

Albumin

A

Binds calcium and fatty acids found in plasma

Low ionized calcium binds best to albumin

Musculoskeleton (36 decks)

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