Wound healing Flashcards

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1
Q

What are the stages of wound healing?

A

Acute inflammation
Parenchymal regeneration (resident funcitonal, not stroma)
Re-epithelialisation and cell migration
Proliferation of parenchyma and stromal cells
ECM protein synthesis
Remodelling (restores function and strength)

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2
Q

What are the 3 classic stages of wound healing?

A

Inflammation (–>48 hours after injury)
New tissue formation (2-10 days)
Remodelling/maturation (1 year +)

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3
Q

What is present in the inflammatory phase?

A
hypoxia +fibrin clot
bacteria
neutrophils 
platelets
macrophages
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4
Q

What is present during the new tissue formation stage?

A

surface scab
few inflammatory cells now
new BVs predminate
epithelial migration under scab

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5
Q

What is present in the remodelling/maturation phase?

A

disorganised collagen from fibroblasts
wund contraction near suface
re-epithelialised wound raised
healed region: no appendages

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6
Q

What are the 2 main things that occur during new tissue formation?

A

GT formation

Re-epithelialisation

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7
Q

Outline what happens in inflammation

A

Bleeding
coagulation
platelet activation
complement activation

granulocytes and phagocytes

macrophages and cytokines

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8
Q

What are the processes in new tissue formation?

A

fibroplasia
angiogenesis
re-epithelialisation
ECM synthesis

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9
Q

What happens in ECM remodelling?

A

increased tensile strength
decreased cellularity
decreased vascularity

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10
Q

Which cells are present during migration/proliferation stages?

A
macrophages
lymphocytes
fibroblasts
epithelial cells
endothelial cells
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11
Q

What is the main cell involved during remodelling?

A

fibroblasts

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12
Q

Outline the order of cell recruitment

A

Platelets –> neutrophils –> macrophages –> fibroblasts –> lymphocytes

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13
Q

What happens leading up to coagulation?

A
death of some epithelial and ermal cells
damage to collagenous fibres in tissue 
small vessel rupture
release of blood into wound and surrounding tissue
voagulation
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14
Q

What happens in coagulation?

A

platelet deposition and aggregation
platelet degranulation
release PDGF, TGFb, fibronectin
Formation of a fibrin clot

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15
Q

When are lympocytes present?

A
late inflammation (recruited later)
important in early remodelling phase
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16
Q

What role do macrophages have in wound healing?

A
removal of wound debris
cell recruitment and activation
phagocytosis
angiogenesis
matrix synthesis regulation
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17
Q

What happens in the initial stage of skin re-epithelialisatin?

A

Single keratinocyte layer migrates under fibrin clot, from wound edges across wound to re-surface the wound are. During and after migration, differentiation and stratificaion of neo-dermis occurs

18
Q

What do keratinocytes do in wound healing?

A
migration/proliferation
ECM production
growth factor/cytokine production
angiogenesis
protease release
19
Q

What are some important factors during the migration/proliferation phase?

A

fribrin
growth factors and cytokines
proteases/MMPs

20
Q

Outline angiogenesis

A

begin as endothelial cells buds
move toward wound space (along gradients - O2 and VEGF)
macrophages and keratinocytes (epithelial cells) provide the angiogenic stimuli

21
Q

Which are the 2 most important factors for vascular development?

A

VEGF and PDGF

22
Q

What are pericytes?

A

contractile cells that wrap around the endothelial cells of capillaries and venules

23
Q

T/F: granulation tissue is usually oedematous.

A

True

24
Q

Why are fibroblasts important during migration/proliferation?

A

migrate into wound and replicate
dominant cell type at wound edge
major cell type in remodelling
synthesise and deposit ECM

25
Q

Do fibroblasts differentiate?

A

Yes –> myofibroblasts and express contractile proteins –> these cells effect wound closure

26
Q

Why are fibroblasts important in CT formation and remodelling? 5

A
ECM production
GF and cytokine production
Angiogenesis
Protease release
Migration/proliferation
27
Q

When is GT established?
What does it look like?
What does it contain?

A

within 3-5 days post-injury.

APPEARANCE: Pink, soft granular tissue first appears beneath scab.
CONTAINS fibroblasts, thin walled capillaries and loose ECM.

28
Q

Is proud flesh a normal part of wound healing in the horse?

A

Yes

29
Q

Outline the phases of remodelling.

A

Changes in matrix composition over time:

ECM–> collagen –> scar –> fibrosis

30
Q

What is the primary ‘driver’ of scarring?

A

Inflammation

31
Q

What is prolonged scarring?

A

= fibrosis = permanent ‘scar’

32
Q

What does scar formation and net collagen accumulation rely on?

A

rate of collagen synthesis vs. rate of degradation

33
Q

What does EGF do?

A

mitogenic for epithelial cells and fibroblasts

34
Q

Where is PDGF released from? 4

What does PDGF do?

A

RELEASED FROM: platelets, macrophages, endothelial and vSM cells

Induces migration/proliferation of fibroblasts, vDMC and monocytes

35
Q

What does bFGF do?

A

induces fibroblast growth and angiogenesis

36
Q

Where is TGFb secreted from?

What does it do?

A

SECRETED FROM: endothelium, lymphocytes, macrophages

ACTION: promotes fibroblast migration/proliferation adn ECM synthesis

37
Q

What does VEGF do? 1

A

promotes angiogenesis

38
Q

Where do IL-1/TNFa come from?

Action? 1

A

Macrophage-derived

Induces fibroblast proliferation

39
Q

What sort of wounds may heal by acute fibrosis?

A

Burns and hypertrophic scars
radiation-induced fibrosis
cardiac scarring following myocardial infarction
surgical procedures

40
Q

When might you see chronic fibrosis?

A

major organ fibrosis (liver, kidney, cardiac, lung)
fibroproliferative diseases (SSc, ahterosclerosis, keloids)
Crohn’s and IBD

41
Q

How is wound healing regulate? 7

A
  • Coagulation component - fibrin, thrombin
  • Endogenous tissue factors
  • Growth factors - VEGF, EGF, PDGF, CTGF, TGFb
  • Interactions with ECM - collagens, fibronections, HS-PG
  • cell to cell contacts and gap junctions
  • mechanical stimulation
  • oxidative stress