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Flashcards in Wound healing Deck (41):
1

What are the stages of wound healing?

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)

2

What are the 3 classic stages of wound healing?

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

3

What is present in the inflammatory phase?

hypoxia +fibrin clot
bacteria
neutrophils
platelets
macrophages

4

What is present during the new tissue formation stage?

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

5

What is present in the remodelling/maturation phase?

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

6

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

GT formation
Re-epithelialisation

7

Outline what happens in inflammation

Bleeding
coagulation
platelet activation
complement activation

granulocytes and phagocytes

macrophages and cytokines

8

What are the processes in new tissue formation?

fibroplasia
angiogenesis
re-epithelialisation
ECM synthesis

9

What happens in ECM remodelling?

increased tensile strength
decreased cellularity
decreased vascularity

10

Which cells are present during migration/proliferation stages?

macrophages
lymphocytes
fibroblasts
epithelial cells
endothelial cells

11

What is the main cell involved during remodelling?

fibroblasts

12

Outline the order of cell recruitment

Platelets --> neutrophils --> macrophages --> fibroblasts --> lymphocytes

13

What happens leading up to coagulation?

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

14

What happens in coagulation?

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

15

When are lympocytes present?

late inflammation (recruited later)
important in early remodelling phase

16

What role do macrophages have in wound healing?

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

17

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

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

What do keratinocytes do in wound healing?

migration/proliferation
ECM production
growth factor/cytokine production
angiogenesis
protease release

19

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

fribrin
growth factors and cytokines
proteases/MMPs

20

Outline angiogenesis

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

21

Which are the 2 most important factors for vascular development?

VEGF and PDGF

22

What are pericytes?

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

23

T/F: granulation tissue is usually oedematous.

True

24

Why are fibroblasts important during migration/proliferation?

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

25

Do fibroblasts differentiate?

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

26

Why are fibroblasts important in CT formation and remodelling? 5

ECM production
GF and cytokine production
Angiogenesis
Protease release
Migration/proliferation

27

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

within 3-5 days post-injury.

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

28

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

Yes

29

Outline the phases of remodelling.

Changes in matrix composition over time:
ECM--> collagen --> scar --> fibrosis

30

What is the primary 'driver' of scarring?

Inflammation

31

What is prolonged scarring?

= fibrosis = permanent 'scar'

32

What does scar formation and net collagen accumulation rely on?

rate of collagen synthesis vs. rate of degradation

33

What does EGF do?

mitogenic for epithelial cells and fibroblasts

34

Where is PDGF released from? 4
What does PDGF do?

RELEASED FROM: platelets, macrophages, endothelial and vSM cells

Induces migration/proliferation of fibroblasts, vDMC and monocytes

35

What does bFGF do?

induces fibroblast growth and angiogenesis

36

Where is TGFb secreted from?
What does it do?

SECRETED FROM: endothelium, lymphocytes, macrophages
ACTION: promotes fibroblast migration/proliferation adn ECM synthesis

37

What does VEGF do? 1

promotes angiogenesis

38

Where do IL-1/TNFa come from?
Action? 1

Macrophage-derived
Induces fibroblast proliferation

39

What sort of wounds may heal by acute fibrosis?

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

40

When might you see chronic fibrosis?

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

41

How is wound healing regulate? 7

- 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

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