Tissue Repair Flashcards

1
Q

Regeneration of injured cells and tissues involves cell proliferation, which is driven by what and dependent on what?

A

driven by growth factors

dependent on the integrity of the ECM

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2
Q

Which cell types proliferate during repair? (3)

A

remnants of injured tissue - attempt to restore normal tissue structure

vascular endothelial - create new vessels for repair

fibroblasts - source of fibrous tissue that forms scar to fill defects that cannot be corrected via regeneration

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3
Q

repair proliferation is driven by growth factors - production of these growth factors and the tissue response determines?

A

the adequacy of the repair

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4
Q

intrinsic proliferative capacity of tissues influences ability to repair (3 groups of tissue)

A

labile (continuously dividing)

stable

permanent

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5
Q

labile tissue?

A

continuous turnover from stem cells and proliferation of mature cells (e.g. bone marrow, surface epithelium such as skin, oral cavity, GI, ducts, epithelium, etc.)

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6
Q

Stable tissues?

A

quiescent with minimal replicative activity, although capable of proliferating in response to injury or loss of tissue mass (e.g. parchyma of most solid organs such as liver, kidney, pancreas; also endothelial cells, fibroblasts, smooth muscle cells); with exception of liver stable tissues have limited capcity to regenerate after injury

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7
Q

Permanent tissues?

A

terminally differentiated and non-proliferative. Most neurons and cardiac muscle cells. Limited stem cell replication and differentiation, but insufficient for regeneration. Thus, repair dominated by scar formation

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8
Q

Proliferative capacity of tissues - labile / stable / permanent - what do most mature tissues contain?

A

with exception of permanent tissues, most mature tissues contain variable proportions of three cell types

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9
Q

regenerative capacity in most dividing tissues?

A

in most dividing tissues, mature cells are terminally differentiated and short lived

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10
Q

what happens when mature cell dies, tissue =

A

replaced by differentiation of cells generated from stem cells

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11
Q

what two properties characterize stem cells?

A

self renewal

asymmetric replication

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12
Q

two types of stem cells?

A

embryonic

adult

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13
Q

embryonic stem cells -

A

most undifferentiated, present in inner mass of blastocyst can form all three germ layers

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14
Q

adult stem cell -

A

aka tissue stem cells, less undifferentiated than ES cells found among differentiated cells within an organ or tissue. More limited self-renewal capacity, and more restricted lineage potential, Important in tissue homeostasis

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15
Q

what are growth factors?

A

proteins that stimulate the survival and proliferation of particular cells, and may also promote migration, differentiation, and other cellular responses

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16
Q

where do growth factors come from?

A

may be produced by macrophages and lymphocytes recruited to site of injury (or activated on-site) or by parenchymal / stromal cells

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17
Q

growth factors signaling types (3)

A

autocrine
paracrine
endocrine

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18
Q

ECM definition

A

complex of several proteins that assembles into a network that surrounds cells and constitutes a significant proportion of any tissue; regulates proliferation, movement and differentiation of cells, provides substrate for cell adhesion and migration, and serves as reservoir for growth factors

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19
Q

Components of extracellular matrix (3)

A
  1. fibrous structural proteins (collagens, elastins - tensile strength and recoil)
  2. water-hydrated gels (proteoglycans and hyaluronan - resilience and lubrication)
  3. adhesion glycoproteins - connect the matrix elements to one another and to cells
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20
Q

Two basic forms of ECM

A

Interstitial

Basement membrane

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21
Q

Interstitial matrix

  • present where
  • synthesized by
  • components?
A
  • present in spaces between cells in CT
  • synthesized by mesenchymal cells
  • major components: fibrillar and non-fibrillar collagens, fibronectin, elastin, proteoglycans, hyaluronate
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22
Q

Basement membrane

  • present where
  • synthesized by
  • components?
A
  • present beneath epithelial, endothelial, and smooth muscle cells
  • synthesized by overlying epithelium and underlying mesenchyme
  • major components: amorphous non-fibrillar type IV collagen and laminin
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23
Q

ECM main functions (4)

A
  • mechanical support
  • control of cell proliferation
  • scaffolding for tissue renewal
  • establishment of tissue microenvironments
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24
Q

ECM and role in tissue regeneration?

A

an intact ECM is required for tissue regeneration, and if the ECM is damage, repair can be accompished by scar formation only

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25
Q

regeneration in tissue repair

- labile tissues - what happens?

A

injured cells rapidly replaced by proliferation of residual cells and differentiation of tissue stem cells (provided underlying BM is intact)

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26
Q

regeneration in tissue repair

- stable tissues - what happens?

A

regeneration can occur, but (with exception of liver) usually more limited process

27
Q

Role of regeneration in tissue repair - the liver?

A

the liver is unique in its robust regenerative capacity

as much as 40-60% of the liver can be removed in living-donor transplantation

liver also can regenerate after other insults (hepatitis etc.) if enough of tissue framework intact

28
Q

what is tissue repair?

A

healing - restoration of tissue architecture and function (if possible) after injury

29
Q

scar formation results when

A

repair cannot be accomplished by regeneration alone

  • -> tissue injury is severe or chronic and results in damage to parenchymal cells and epithelia as well as the CT
  • -> non dividing cells are injured
30
Q

how does scar formation occur?

A

via replacement of non-regenerated cells with CT leading to formation of scar, or by combination of regeneration of some cells and scar formation

31
Q

steps in scar formation (3)

A
  1. angiogensis - formation of new blood vessels
  2. migration and proliferation of fibroblasts and deposition of CT (granulation tissue)
  3. maturation and reorganization of the fibrous tissue to produce a stable scar
32
Q

Angiogensis is mediated by?

A

Growth factor VEGF

33
Q

Deposition of CT (2)

A
  1. migration and proliferation of fibroblasts into the site of injury
  2. deposition of ECM proteins produced by these cells
34
Q

what / who orchestrates deposition of CT

A

Orchestrated by locally produced cytokines and GFs - including

  • TGF - b
  • PDGF
  • FGF - 2
35
Q

what are the sources of GFs and cytokines mediating CT deposition

A

inflammatory cells - particularly activated (M2) macrophages

36
Q

which GF is most important cytokine in synthesis and deposition of CT proteins (scar formation)

A

TGF-b

37
Q

Remodeling of CT - what influences outcome of repair?/

A

balance between synthesis and degradation of ECM proteins

38
Q

What accomplishes the degradation of ECM?

A

MMPs

39
Q

What produces MMPs?

A

variety of cell types (fibroblasts, macrophages, neutrophils, etc.) and include interstitial collagenases, gelatinases, stromelysins

40
Q

Systemic factors influencing tissue repair? (3)

A

nutrition
metabolic
vascular

41
Q

how does nutrition influence tissue repair?

A

protein deficiency
vitamin c deficiency

both can impair collagen synthesis

42
Q

how do metabolic factors influence tissue repair?

A

delay repair
e.g. diabetes
glucocorticoids can inhibit TGF-beta production and diminish fibrosis (some cases may be useful)?

43
Q

how do vascular factors influence tissue repair?

A

ischemia, venous drainage

  • thrombosis
  • ateriosclerosis and atherosclerosis / diabetic changes
  • venous drainage impairment: vericose veins
44
Q

Local factors influencing tissue repair

A major consideration regarding whether repair will take place effectively is whether or not (2)

A
  1. the inciting insult has been terminated or persists

2. the new insult in introduced (e.g. infection)

45
Q

infection influence on tissue repair?

A

infection prolongs inflammation and increases local tissue injury

46
Q

what 5 factors influence tissue repair locally?

A
infection
persistence of insult
trauma - early movement prior to completion of repair
foreign material 
size / location
47
Q

aberrations of cell growth and ECM production (2) influencing tissue repair locally?

A
hypertrophic scar (Regresses)
keloid (does not regress)
48
Q

does a hypertrophic scar regress?

A

yes

49
Q

does a keloid regress?

A

no

50
Q

what is a contracture

A

scar - any process that crosses joint space

51
Q

what is a keloid

A

a scar that does not regress

    • could be absence of MMP or
  • excessive collagen deposition
52
Q

Tissue repair

4 phases following injury

A
  1. vascular reaction
  2. acute inflammatory
  3. chronic inflammatory
  4. repair phase
53
Q

Vascular reaction is tissue repair (2)

A
  1. vessel dilation / congestion

2. vessel permeabilit increased

54
Q

Acute + chronic inflammatory phase in tissue repair (2)

A

inflammatory cell reaction to injury

  1. native / sentinel cells
  2. recruited from blood stream
55
Q

repair phase in tissue repair (3)

A
  1. fibroblast –> collagen/elastin
  2. endothelial cells –> blood vessels
  3. epithelial or mesenchymal cells –> re-epitheliazation –> regeneration (if possible)
56
Q

scar formation following injury (4 phases)

A
  1. early cell necrosis (hrs)
  2. acute phase (PMNs)
  3. Chronic phase
  4. Scar
57
Q

in Acute phase scar formation we see

A

PMNs

58
Q

in chronic phase scar formation we see

A
  • lymphs, macs
  • fibroblasts
  • endothelial cells
59
Q

in chronic phase scar maturation, we see?

A
  • scant mononuclear cells
60
Q

healing by first intention

A

epithelial regeneration is the principal mechanism of repair

  • superficial clean wounds - no contracture
61
Q

healing by second intention?

A

more complex repair involving combination of regeneration and scarring - get contracture

62
Q

healing by second intention is accomplished via?

A

myofibroblasts that contract tissue together

63
Q

4 differences between secondary healing and primary

A
  1. larger clot / scab rich in fibrin and fibronectin
  2. inflammation more intense
  3. larger volume granulation tissue
  4. wound contraction (myofibroblasts)
64
Q

wound strength of sutured wound

A

70 % normal skin

three months out 70-80%