Wound healing Flashcards
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)
What are the 3 classic stages of wound healing?
Inflammation (–>48 hours after injury)
New tissue formation (2-10 days)
Remodelling/maturation (1 year +)
What is present in the inflammatory phase?
hypoxia +fibrin clot bacteria neutrophils platelets macrophages
What is present during the new tissue formation stage?
surface scab
few inflammatory cells now
new BVs predminate
epithelial migration under scab
What is present in the remodelling/maturation phase?
disorganised collagen from fibroblasts
wund contraction near suface
re-epithelialised wound raised
healed region: no appendages
What are the 2 main things that occur during new tissue formation?
GT formation
Re-epithelialisation
Outline what happens in inflammation
Bleeding
coagulation
platelet activation
complement activation
granulocytes and phagocytes
macrophages and cytokines
What are the processes in new tissue formation?
fibroplasia
angiogenesis
re-epithelialisation
ECM synthesis
What happens in ECM remodelling?
increased tensile strength
decreased cellularity
decreased vascularity
Which cells are present during migration/proliferation stages?
macrophages lymphocytes fibroblasts epithelial cells endothelial cells
What is the main cell involved during remodelling?
fibroblasts
Outline the order of cell recruitment
Platelets –> neutrophils –> macrophages –> fibroblasts –> lymphocytes
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
What happens in coagulation?
platelet deposition and aggregation
platelet degranulation
release PDGF, TGFb, fibronectin
Formation of a fibrin clot
When are lympocytes present?
late inflammation (recruited later) important in early remodelling phase
What role do macrophages have in wound healing?
removal of wound debris cell recruitment and activation phagocytosis angiogenesis matrix synthesis regulation
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
What do keratinocytes do in wound healing?
migration/proliferation ECM production growth factor/cytokine production angiogenesis protease release
What are some important factors during the migration/proliferation phase?
fribrin
growth factors and cytokines
proteases/MMPs
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
Which are the 2 most important factors for vascular development?
VEGF and PDGF
What are pericytes?
contractile cells that wrap around the endothelial cells of capillaries and venules
T/F: granulation tissue is usually oedematous.
True
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
Do fibroblasts differentiate?
Yes –> myofibroblasts and express contractile proteins –> these cells effect wound closure
Why are fibroblasts important in CT formation and remodelling? 5
ECM production GF and cytokine production Angiogenesis Protease release Migration/proliferation
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.
Is proud flesh a normal part of wound healing in the horse?
Yes
Outline the phases of remodelling.
Changes in matrix composition over time:
ECM–> collagen –> scar –> fibrosis
What is the primary ‘driver’ of scarring?
Inflammation
What is prolonged scarring?
= fibrosis = permanent ‘scar’
What does scar formation and net collagen accumulation rely on?
rate of collagen synthesis vs. rate of degradation
What does EGF do?
mitogenic for epithelial cells and fibroblasts
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
What does bFGF do?
induces fibroblast growth and angiogenesis
Where is TGFb secreted from?
What does it do?
SECRETED FROM: endothelium, lymphocytes, macrophages
ACTION: promotes fibroblast migration/proliferation adn ECM synthesis
What does VEGF do? 1
promotes angiogenesis
Where do IL-1/TNFa come from?
Action? 1
Macrophage-derived
Induces fibroblast proliferation
What sort of wounds may heal by acute fibrosis?
Burns and hypertrophic scars
radiation-induced fibrosis
cardiac scarring following myocardial infarction
surgical procedures
When might you see chronic fibrosis?
major organ fibrosis (liver, kidney, cardiac, lung)
fibroproliferative diseases (SSc, ahterosclerosis, keloids)
Crohn’s and IBD
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
