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Path Quiz 2 > wound healing and tissue repair II - lecture notes - julia > Flashcards

wound healing and tissue repair II - lecture notes - julia Flashcards

1
Q

what is a wound?

A

any type of disruption in the integrity of an organ or tissue

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2
Q

what is a scab?

A
  • coagulum that forms over a surface defect
  • initial attempt to seal
  • will have coagulation proteins, serum proteins, etc.
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3
Q

what is granulation tissue? (where in the body is it found, what does it consist of?)

A
  • early phase of the formation of a scar anywhere in the body except the brain
  • composed of very early capillaries, activated fibroblasts, new, watery ECM, lots of leukocytes
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4
Q

what is a scar?

A
  • mature collagen that has become relatively hypovascular
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5
Q

what is a keloid?

A

situation on the skin where a wound has healed but the formation of collagen never stopped - keeps piling up

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6
Q

what is cicatrix?

A

scar

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7
Q

what processes does repair by connective tissue (scaring) involve? (list)

A
  1. angiogenesis
  2. migration and proliferation of fibroblasts
  3. deposition of ECM
  4. maturation of fibrous tissue (remodeling)
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8
Q

what coagulation factor activities are involved in wound healing?

A
  • hageman factor fragments
  • bradykinin
  • complement activation
  • fibrin clot
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9
Q

what is the effect of hageman factor fragments?

A

vasopermeability

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10
Q

what is the effect of bradykinin?

A
  • vasodilation
  • vasopermeability
  • pain
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11
Q

what is the effect of complement activation?

A
  • leukocyte recruitment
  • vasopermeability
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12
Q

what is the effect of fibrin clots?

A
  • hemostatic plug
  • reseroir of growth factors
  • provisional matrix for cell migration
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13
Q

what are the roles of platelets in wound repair? (list)

A
  1. adhesion
  2. aggregation
  3. mediator release
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14
Q

what is the effect of adhesion of platelets?

A

plug small leaks in blood vessels

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15
Q

what is the effect of aggregation of platelets?

A
  • plug large leaks in blood vessels
  • induce coagulation
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16
Q

what is the effect of mediator release by platelets?

A
  • vasoconstriction
  • stimulate additional platelet aggregation
  • growth factor release
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17
Q

what growth factors are active in wound healing?

A
  • FGF (fibroblast growth factor)
  • PDGF (platelet-derived growth factor)
  • TGF-B (transforming growth factor)
  • VGEF (vascualar endothelial growth factor)
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18
Q

what is the effect of FGF?

A
  • fibroblast and epidermal cell proliferation
  • angiogenesis
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19
Q

what is the effect of PDGF?

A
  • fibroblast chemotaxis, proliferation and contraction
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20
Q

what is the effect of TGF-B?

A
  • fibroblast chemotaxis
  • ECM deposition
  • protease inhibitor secretion
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21
Q

what is the effect of VGEF?

A
  • vascular permeability
  • angiogenesis
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22
Q

what is the role of macrophages in wound repair?

A
  • recruitment and maturation
  • phagocytosis and killing of microorganisms
  • pahgocytosis of tissue debris
  • growth factor release
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23
Q

what is the effect of recruitment and maturation of macrophages in wound healing?

A

transition from ciruclating monocyte to tissue macrophage

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24
Q

what is the effect of macrophage phagocytosis and killing of microorganisms in wound repair?

A

wound decontamination

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25
Q

what is the effect of macrophage phagocytosis of tissue debris in wound repair?

A

wound debridement

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26
Q

what is the effect of macrophage growth factor release in wound repair?

A

autocrine and paracrine stimulation

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27
Q

what GFs cause monocyte chemotaxis?

A
  • PDGF
  • FGF
  • TGF-B
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28
Q

what GFs cause fibroblast migration?

A
  • PDGF
  • EGF
  • FGF
  • TFG-B
  • TNF
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29
Q

what GFs cause fibroblast proliferation?

A
  • PDGF
  • EGF
  • FGF
  • TNF
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30
Q

what GFs cause angiogenesis?

A
  • VEGF, Ang, FGF
31
Q

what GFs cause collagen synthesis?

A
  • TGF-B
  • PDGF
  • TNF
32
Q

what GFs cause collagenase secretion? what inhibits?

A
  • PDGF
  • FGF
  • EGF
  • TNF

TNF-beta inhibits

33
Q

what cells are most important at the begining of wound repair? what cells take over?

A
  • for the first few days, leukocytes
  • after that, fibroblasts take over
34
Q

what are the activities of fibroblasts in wound healing? (list)

A
  1. growth factor production
  2. proliferation and migration
  3. protease release
  4. ECM production
  5. dynamic linkage between actin bundles and ECM
  6. program cell death
35
Q

what is the effect of GF production by fibroblasts in wound repair?

A

autocrine and paracrine stimulation

36
Q

what is the effect of fibroblast proliferation and migration in wound repair?

A

granulation tissue formation

37
Q

what is the effect of protease release by fibroblasts in wound repair?

A

provisional matrix lysis and ECM remodeling

38
Q

what is the effect of ECM production by fibroblasts in wound repair?

A

connective tissue formation

39
Q

what is the effect of dynamic linkage between actin bundles and the ECM by fibroblasts in wound repair?

A

tissue contraction

40
Q

what is the effect of fibroblasts on cell death programing in wound repair?

A

transition from cell-rich granulation tissue to cell-poor scar

41
Q

what are the roles of epithelial cells in wound repair? (list)

A
  1. growth factor production
  2. migration and proliferation
  3. protease release
  4. ECM production
  5. termial differentiation
42
Q

what is the effect of GF production by epithelial cells in wound repair?

A

autocrine and paracrine stimulation

43
Q

what is the effect of migration and proliferation by epithelial cells in wound repair?

A

reepithelialization

44
Q

what is the effect of protease release by epithelial cells in wound repair?

A

dissection under clot and nonviable tissue - allows scabs to fall off

45
Q

what is the effect of ECM production by epithelial cells in wound repair?

A

provisional matrix and basement membrane formation

46
Q

what is the effect of terminal differentiation by epithelial cells in wound repair?

A

barrier function reestabilshed

47
Q

what are the roles of endothelial cells in tissue repair?

A
  1. thrombomodulin and syndecan surface expression
  2. prostacyclin release
  3. plasminogen activator release
  4. surface expression of cell adhesion molecules
  5. metalloproteinase release
  6. GF production
  7. migration and proliferation
  8. ECM production
  9. tube formation
48
Q

what is the effect of thrombomodulin and syndecan surface expression by endothelial cells in tissue repair?

A

limits coagulation

(part of mechanism to prevent thrombosis)

49
Q

what is the effect of prostacyclin release by endothelial cells in tissue repair?

A

limits platelet thrombi

(part of mechanisms ot prevent thrombosis in new vessels)

50
Q

what is the effect of prostacyclin release by endothelial cells in tissue repair?

A

clot lysis

part of mechanism to prevent thrombosis formation in new vessels

51
Q

what is the effect of the surface expression of cell adhesion molecules by endothelial cells in tissue repair?

A

leukocyte diapedesis

52
Q

what is the effect of metalloproteinase release by endothelial cells in tissue repair?

A

basement membrane degradation - digests material directly in front of leading endothelial cells - allows new blood vessels to grow into the area

53
Q

how do endothelial cells help to prevent fomration of thrombosis in new vessels?

A
  1. thrombomodulin adn syndecan surface expression
  2. prostacyclin release
  3. plasminogen activator release
54
Q

what is the effect of growth factor production by endothelial cells in tissue repair?

A

autocrine and paracrine stimulation

55
Q

what is the effect of migration and proliferation of endothelial cells in tissue repair?

A

angiogenesis

56
Q

what is the basic mechanism for scar tissue creation, response to dead tissue, wound healing, and resolution of inflammatory sites?

A
  1. neutrophils and macrophages remove debris
  2. fibroblasts make collagen
  3. new vessels form
  4. extracellular matrix matures and is remodelled
57
Q

what is the difference between the healing by first intention and healing by second intention?

A

1st: goal is to reduce the amount of scar tissue to the minimum possible - occurs when the wound is small and edges can be rejoined
2nd: when one end of wound can’t be opposed to other end - such as in burn or when a large area of tissue is lost that can’t be pulled together by sutures - get large amount of granulation tissue forming, big scar, simplified or sometimes defective endothelial coverage

58
Q

what does granulation tissue look like?

A
  • earliest form of scar
  • loose watery material in background - ECM (fibrin, fibronectin, collagen)
  • lots of inflammatory cells
  • many tiny, thin-walled blood vessels
  • big blue “angry looking” cells = highly activated fibroblasts
59
Q

what do fibroblasts look like?

A

very basophilic and huge

60
Q

how will granulation tissue and mature scar appear different using a trichrome stain?

A
  • mature collagen stains dark blue/purple
  • granulation tissue will barely have any purple
  • scar = mostly purple
61
Q

what would a skin wound in the process of scar formation look like?

A
  • reepithelialized
  • area of granulation tissue that’s maturing
  • will become a focus of scar
  • month - two months old
62
Q

what will a dermal scar look like when fully mature (histologically)?

A
  • no inflammation
  • virtually no blood vessels
  • everything linear - organized collagen
  • can take months to years
63
Q

what does heart tissue look like 24 hours after myocardial infarction?

A
  • necrotic myocytes
  • vast influx of neutrophils - these are breaking down themselves and degenerating
64
Q

what does heart tissue look like 3-4 days after an MI?

A
  • neutrophils virtually all gone
  • predominant cell type = macrophages
  • some fibroblasts too but they’re not in full swing of producing collagen yet
  • have a few capillaries
65
Q

what does heart look like 7 days after an MI?

A
  • still have inflammatory cells and macrophages
  • now a lot more background ECM
  • prominent fibroblasts - very enlarged
  • lots of little capillaries
66
Q

what does heart tissue look like 4-8 weeks after an MI?

A
  • inflammatory cells virtually all gone
  • ECM no longer as watery - beginning to organize, can see cords of collagen
  • blood vessels far more defined
67
Q

what are the systemic factors affecting the success of tissue repair?

A
  1. nutrition
  2. metabolic status
  3. circulation
  4. hormones
  5. genetic makeup
  6. medical treatment
68
Q

what are the local factors affecting the success of tissue repair?

A
  1. infection
  2. foriegn bodies
  3. mechanical factors
  4. size, location, and type of wound
69
Q

what are the potential complications/pathological outcomes of tissue damage? (list)

A
  1. scar formation and loss of function
  2. keloid formation
  3. desmoid (aggresive fibromatosis)
  4. ulceration
  5. wound dehiscence (separation)
  6. scar contraction
70
Q

what is desmoid?

A

when fibroblasts don’t stop prolilferating and making collagen - can fill retroperitoneum up with collagen

71
Q

what is wound dehiscence?

A

wound is put together and looks like it’s going to heal and then all of a sudden it just opens up on its own

72
Q

what does keloid look like histologically?

A
  • very dense collagen
  • lots of fibroblasts - don’t stop making collagen
  • huge ropey collagen

Path Quiz 2 (13 decks)

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