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Principles of Science > Wound Healing > Flashcards

Wound Healing Flashcards

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Biology 101 flashcards
1
Q

How does foetal repair differ to adult?

A

foetal repair == regeneration, scarless healing

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2
Q

Outline the stages of mesengenesis

A
  • Mesenchymal stem celles
  • Commitment
  • Lineage progression (becoming an osteoblast, tenoblast, pre-vSMC, pre-fribroblast etc.
  • Differentiation and maturation (becoming an osteocyte, tenocyte, vSMC, fibroblast etc.)
  • Tissue formation (bone, tendon, vessel, skin etc.)
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3
Q

What regulates the migration, proliferation and differentiation of cells; synthesis and degradation of ECM protein?

A

soluble factors

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4
Q

How are the ECM and cells linked?

A

Dynamic relationship - collagen and elastin affected by ECM, ECM in turn affected by resident cells

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5
Q

Which cells organise new tissue?

A
  • resident mesenchymal derived stromal cells

- deposit and cross link matrix

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6
Q

Outline 6 stages of wound healing

A
  1. coagulation and initial acute inflammatory response
  2. parenchymal regeneration (resident functional/not stromal)
  3. re-epithelialisation and cell migration
  4. proliferation of parenchyma and stromal cells
  5. Synthesis of ECM proteins
  6. Remodelling
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7
Q

What are the 3 “classic” stages of wound healing? How long roughly do these persist for?

A
  1. inflammation ~48hours (hypoxic, fibrin clot, abundant bacteria, platelets then neutrophils)
  2. New tissue formation [granulation and re-epitheliasation, angiogenesis] ~2-10days (surface scab, most inflame cells moved away, new blood vessels predominate, epithelial cells migrate under scab)
  3. remodelling/maturation ~1year+ (disorganised collagen laid down by fibroblasts, wound contracted near surface but deep bit still wide, re-epithelialized wound raised.
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8
Q

Which other tissue fixes itself in a similar way to skin?

A

Bone - woven bone forms at Fx site as bone laid down quickly rather than neatly

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9
Q

Which cells predominate in the coagulation phase?

A

platelets

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10
Q

Which cells predominate in the inflammatory phase?

A

neutrophils (also platelets and macrophages)

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11
Q

Which cells predominate in the new tissue formation (proliferation) phase?

A

macrophages and fibroblasts (also lymphocytes, epithelial and endothelial cells)

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12
Q

Which cells predominate in the matrix remodelling phase?

A

fibroblasts and lymphocytes

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13
Q

What events happen initially after injury to epithelium and underlying dermis?

A
  • death of epithelial and dermal cells
  • damage of collagenous fibres in tissue
  • small vessel rupture -> vasodilation and permeability
  • release of blood into wound and surrounding tissue
  • coagulation
  • platelet deposition and aggregation
  • de-granulation releasing PDGF, TGFb, fibronectin
  • formation of fibrin clot
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14
Q

What happens during the inflammatory phase?

A
  • attraction and activation of infiltrating cells (leucocyte influx)
  • neutrophils phagocytose matrix and release free radicals
  • monocyte/macrophages debride wound and encourage matrix turnover, provide stimulatory signals
  • lymphocytes recruited later, important in early remodelling
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15
Q

outline 5 main roles of macrophages in wound healing

A
  • removal of wound debris (phagocytosis and matrix degredation using collagenases, elastase)
  • cell recruitment and activation via cyto and chemokines, growth factors
  • phagocytosis (antimicrobial function ROS)
  • angiogenesis using VEGF
    -matrix synthesis regulation via
    > growth factors (PDGF, TGFb)
    > cytokines (TNFa, IL1, IFNg)
    > degradive enzymes
  • eicosanoids (PGs)
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16
Q

What occours during the first half of the migration/proliferation stage?

A
  • single keratinocyte layer migrates under fibrin clot, from wound edges
  • during/after migration, differentiation and stratification of neo-dermis occours
17
Q

outline 5 main roles of keratinocytes in skin healing?

A
  • migration/proliferation via integrins and adhesion molecules
  • ECM production inc basement membrane
  • growth factor/cytokine production via VEGF, TNFa, PDGF
  • angiogenesis via chemoattractants and VEGF
  • release of proteases to dissolve non-viable teissue and penetrate fibrin barrier
18
Q

What occours during the second half of migration/proliferatioin stage?

A
  • re-epithliasation and angiogenesis
  • fibrin clot - platelets and inflammatory cells secrete factors to promote re-epithelialisation
  • endothelial cell migration into wound
  • angiogenesis begins as endothelial cell buds, move along ) graidents and VEGF
  • macrophages andkeratinocytes (epithelial cells) provide angiogenic stimuli
19
Q

What cells, factors etc. does vascular development require?

A

Arterial and venous endothelial cells producing VEGF

Pericytes and smooth mm. cells producing PDGF to coordinate development

20
Q

How else may angiogenesis occour?

A
  • sprouting of new capillaries from parent vessels
  • initiated by GFs (bGF, VEGF) from nearby cells or inflame/hypoxia
  • endothelial cells produce proteases (MMP) to digest surrounding BL
  • cells migrate towards GFs, proliferate and divide
  • cells form tubes, leaky at first hence granulation tissue is usually oedematous, become less leaky as tubes acquire surrounding cells
21
Q

What occours in the 3rd stage of migration/proliferation?

A
  • fibroplasia
  • fibronblasts migrate into wound, synthesis and deposit ECM (collagen and proteoglycans)
  • fibroblasts turn into myofibroblasts and express contractile proteins (-> itching)
22
Q

What is the role of fibroblasts in connective tissue formationand remodelling?

A 
> ECM production (bond intracellular actin and ECM)
- acts as scaffold for tensile strength 
> GF and cytokine production 
- EGF, FGF, CTGF, PDGF, Activin
> Protease release
- ECM remodelling, degrading non viable tissue and ECM 
> migration/proliferation
- recruited from nearby tissues
23
Q

When is granulation tissue established?

A

3-5d post injury

24
Q

What does granulation tissue look like? What is it composed of?

A
  • pink, soft, granular tissue below scab

- fibroblasts, thin walled capillaries and loose ECM

25
Q

What is granulation tissue refered to in horses?

A
  • proud flesh

- exuberant granulation tissue but part of normal healing process

26
Q

Outline the scarring process

A
  • Balance between ECM synthesis and degradation
  • inflammation primary driver
  • collagen accumulation relies on rate of collagen synth v degradation
  • collagenases and natural ihibitors from almost all cell types involved
27
Q

What is fibrosis?

A

prolonged scarring -> permenant scar

Principles of Science (27 decks)

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