Wound Healing Flashcards
What is angiogenesis?
Angiogenesis is the formation of new blood vessels. This process involves the migration, growth, and differentiation of endothelial cells, which line the inside wall of blood vessels.
What are the four stages of acute wound healing?
1) Haemostasis
2) Inflammation
3) Proliferation
4) Remodelling
What are the cell types involved in wound healing?
Platelets Neutrophils Fibroblasts Monocyte Endothelial cells
How long after a graze would haemostasis occur?
Seconds to hours
How long after a graze would inflammation occur?
Hours to Days
How long after a graze would proliferation occur?
Days to Weeks
How long after a graze would remodelling occur?
Weeks to Months
What processes occur directly after a vessel ruptures?
Platelet aggregation, Vasoconstriction, Activation of the Coagulation Cascade
When platelet degranulation occurs what mediators are released?
PDGF (Platelet Derived Growth Factor) IGF-1 (Insulin Like Growth Factor) PAF (Platelet Aggravating Factor) TGFB-1 (Transforming Growth Factor Beta-1) Fibronectin Serotonin
What is the role of Platelet Derived Growth Factor (PDGF) in coagulation?
Stimulates cell proliferation, recruits fibroblasts and promotes angiogenesis/epithelialisation
What is the role of Insulin Like Growth Factor (IGF) in coagulation?
Potentiates platelet activity
What is the role of Platelet Aggravating Factor (PAF) in coagulation?
Potentiates platelet activity
What is the role of Transforming Growth Factor Beta-1 (TGFB-1) in coagulation?
Regulation of development, proliferation, angiogenesis, inflammation and extracellular matrix production
What is the role of Fibronectin in coagulation?
Binds extracellular matrix components such as collagen, fibrin and heparin sulphate proteoglycans.
It also attracts neutorphils
What is the role of serotonin in coagulation?
It induces constriction of injured blood vessels and enhances platelet aggregation to minimise blood loss
What are the three major steps in haemostasis?
1) Platelets adhere to site of vascular injury
2) Platelet aggregation and activation
3) Haemostatic plug formation
Name five repair complications
Wound dehiscence (deficient healing) Keloid (excessive scar formation) Adhesions Infection Chronic Pain
What animal can be used to remove dead skin cells?
Maggots - they remove dead skin from the wound site, which can impede the wound healing process.
The maggots not only dissolve the dead skin with their digestive enzymes to debride the wound by also disinfect as they work.
What are the cells/chemical involved in the inflammation stage of wound healing?
- Cytokines (released by damaged cells)
- Neutrophils
- Macrophages
Describe the role of cytokines in the inflammatory phase of wound healing
Cytokines (released by damaged cells) cause vasodilation and attraction/activation of infiltrating cells (immune cells, part of innate response)
Describe the role of neutrophils in the inflammatory phase of wound healing
Phagocytose bacteria and debris (proteases)
- Not essential unless wound contaminated
Describe the role of macrophages in the inflammatory phase of wound healing
Debridement/matrix turnover
Major source of stimulatory signals
Important for wound healing
Blood Clot + Dead macrophage = Scab (acts as barrier)
Define fibroplasia
The process of forming fibrous tissue (as in wound healing)
Define Epithelialisation
The formation of epithelium over a denuded surface
What are the four major steps of proliferation/migration?
1) Angiogenesis
2) Fibroplasia
3) Epithelialisation
4) Contraction
Why is angiogenesis required during proliferation?
Oxygen is critical for fibroblasts to produce collagen in order to establish granulation tissue, therefore the formation of new blood vessels is required.
What cells provide angiogenic stimuli?
Macrophages and keratinocytes (via VEGF and fibronectin etc.)
How are new blood vessels formed during the angiogenesis stage of proliferation?
Macrophages and keratinocytes provide angiogenic stimuli (VEGF, fibronectin etc.)
Start as endothelial buds from existing vessels
Sprout towards wound following oxygen gradient
Immature vessels differentiate into capillaries, arterioles and venules.
What are the role of fibroblasts during fibroplasia?
Fibroblasts migrate into the wound site and replicate (activated by macrophages/ mast cells)
They synthesise and deposits collagen and proteoglycans.
- Acts as scaffolding to hold epidermal cells together (granulation tissue)
What is the dominant cell type at the wound edge during the proliferation phase?
Fibroblasts
What cells cause fibroblasts to migrate to the wound site and replicate?
Macrophages / mast cells
During fibroplasia, what does matrix deposition depend on?
Oxygen and substrate availability
Growth factors
Describe the epithelialisation stage of the proliferation phase
Epidermal covering (basal keratinocytes) reconstituted from wound margin and hair follicle remnants.
Keratinocytes migrate across wound
Neodermis differentiates and stratifies
Favoured by moist environment
New epidermal layer weak as dermal layer below not yet regenerated
Describe the contraction stage of the proliferation phase
Fibroblasts differentaite to myofibroblasts (similar to smooth muscle cells) that produce contractile proteins, pulling edges of wound together
During the contraction stage of proliferation what cell doe fibroblasts differentiate into?
Myofibroblasts
What do myofibroblasts produce during the contraction stage of proliferation?
Contractile proteins
What is the role of contractile proteins in the contraction stage of proliferation?
Contractile proteins pull the edges of the wound together
Describe the steps in the remodelling phase of wound healing
Formation of new granulation tissue stops
Changes collage composition over time:
- Type III collagen exchanged for type I (made by myofibroblasts)
- Collagen fibres oriented in better alignment
New blood vessels formed no longer required - removed by apoptosis
Fibrous scar formed by collagen cross linking, increase in fibre size
How strong is the mature scar (formed in remodelling) in comparison to the original tissue?
Mature scar has about 80% of the strength of the original tissue
How are new blood vessels that were formed during proliferation removed during remodelling?
Removed by apoptosis
During the remodelling phase of wound healing how does the collagen composition change over time?
Type III collagen is exchanged for type I (made by myofibroblasts)
Collagen fibres orientated in better alignment
What local factors impair wound healing?
Oxygenation
Infection
Foreign body
Venous sufficiency
What systemic factors impair wound healing?
Age and gender
Sex hormones
Stress
Ischemia
Diseases: diabetes, keloids, fibrosis, hereditary healing disorders, jaundice, uremia
Obesity
Medications: glucocorticoid steroids, non-steroidal anti-inflammatory drugs, chemotherapy
Alcoholism and smoking
Immunocompromised conditions: cancer, radiation therapy, AIDS
Nutrition
