Wound healing

Question 1

What are the stages of wound healing?

Answer 1

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)

Question 2

What are the 3 classic stages of wound healing?

Answer 2

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

Question 3

What is present in the inflammatory phase?

Answer 3

hypoxia +fibrin clot
bacteria
neutrophils 
platelets
macrophages

Question 4

What is present during the new tissue formation stage?

Answer 4

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

Question 5

What is present in the remodelling/maturation phase?

Answer 5

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

Question 6

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

Answer 6

GT formation

Re-epithelialisation

Question 7

Outline what happens in inflammation

Answer 7

Bleeding
coagulation
platelet activation
complement activation

granulocytes and phagocytes

macrophages and cytokines

Question 8

What are the processes in new tissue formation?

Answer 8

fibroplasia
angiogenesis
re-epithelialisation
ECM synthesis

Question 9

What happens in ECM remodelling?

Answer 9

increased tensile strength
decreased cellularity
decreased vascularity

Question 10

Which cells are present during migration/proliferation stages?

Answer 10

macrophages
lymphocytes
fibroblasts
epithelial cells
endothelial cells

Question 11

What is the main cell involved during remodelling?

Answer 11

fibroblasts

Question 12

Outline the order of cell recruitment

Answer 12

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

Question 13

What happens leading up to coagulation?

Answer 13

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

Question 14

What happens in coagulation?

Answer 14

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

Question 15

When are lympocytes present?

Answer 15

late inflammation (recruited later)
important in early remodelling phase

Question 16

What role do macrophages have in wound healing?

Answer 16

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

Question 17

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

Answer 17

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

Question 18

What do keratinocytes do in wound healing?

Answer 18

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

Question 19

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

Answer 19

fribrin
growth factors and cytokines
proteases/MMPs

Question 20

Outline angiogenesis

Answer 20

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

Question 21

Which are the 2 most important factors for vascular development?

Answer 21

VEGF and PDGF

Question 22

What are pericytes?

Answer 22

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

Question 23

T/F: granulation tissue is usually oedematous.

Answer 23

True

Question 24

Why are fibroblasts important during migration/proliferation?

Answer 24

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

Question 25

Do fibroblasts differentiate?

Answer 25

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

Question 26

Why are fibroblasts important in CT formation and remodelling? 5

Answer 26

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

Question 27

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

Answer 27

within 3-5 days post-injury. APPEARANCE: Pink, soft granular tissue first appears beneath scab. CONTAINS fibroblasts, thin walled capillaries and loose ECM.

Question 28

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

Answer 28

Yes

Question 29

Outline the phases of remodelling.

Answer 29

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

Question 30

What is the primary 'driver' of scarring?

Answer 30

Inflammation

Question 31

What is prolonged scarring?

Answer 31

= fibrosis = permanent 'scar'

Question 32

What does scar formation and net collagen accumulation rely on?

Answer 32

rate of collagen synthesis vs. rate of degradation

Question 33

What does EGF do?

Answer 33

mitogenic for epithelial cells and fibroblasts

Question 34

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

Answer 34

RELEASED FROM: platelets, macrophages, endothelial and vSM cells Induces migration/proliferation of fibroblasts, vDMC and monocytes

Question 35

What does bFGF do?

Answer 35

induces fibroblast growth and angiogenesis

Question 36

Where is TGFb secreted from? | What does it do?

Answer 36

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

Question 37

What does VEGF do? 1

Answer 37

promotes angiogenesis

Question 38

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

Answer 38

Macrophage-derived | Induces fibroblast proliferation

Question 39

What sort of wounds may heal by acute fibrosis?

Answer 39

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

Question 40

When might you see chronic fibrosis?

Answer 40

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

Question 41

How is wound healing regulate? 7

Answer 41

- 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