Wound Healing

Question 1

What is angiogenesis?

Answer 1

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.

Question 2

What are the four stages of acute wound healing?

Answer 2

1) Haemostasis
2) Inflammation
3) Proliferation
4) Remodelling

Question 3

What are the cell types involved in wound healing?

Answer 3

Platelets 
Neutrophils 
Fibroblasts
Monocyte
Endothelial cells

Question 4

How long after a graze would haemostasis occur?

Answer 4

Seconds to hours

Question 5

How long after a graze would inflammation occur?

Answer 5

Hours to Days

Question 6

How long after a graze would proliferation occur?

Answer 6

Days to Weeks

Question 7

How long after a graze would remodelling occur?

Answer 7

Weeks to Months

Question 8

What processes occur directly after a vessel ruptures?

Answer 8

Platelet aggregation, Vasoconstriction, Activation of the Coagulation Cascade

Question 9

When platelet degranulation occurs what mediators are released?

Answer 9

PDGF (Platelet Derived Growth Factor)
IGF-1 (Insulin Like Growth Factor)
PAF (Platelet Aggravating Factor)
TGFB-1 (Transforming Growth Factor Beta-1)
Fibronectin
Serotonin

Question 10

What is the role of Platelet Derived Growth Factor (PDGF) in coagulation?

Answer 10

Stimulates cell proliferation, recruits fibroblasts and promotes angiogenesis/epithelialisation

Question 11

What is the role of Insulin Like Growth Factor (IGF) in coagulation?

Answer 11

Potentiates platelet activity

Question 12

What is the role of Platelet Aggravating Factor (PAF) in coagulation?

Answer 12

Potentiates platelet activity

Question 13

What is the role of Transforming Growth Factor Beta-1 (TGFB-1) in coagulation?

Answer 13

Regulation of development, proliferation, angiogenesis, inflammation and extracellular matrix production

Question 14

What is the role of Fibronectin in coagulation?

Answer 14

Binds extracellular matrix components such as collagen, fibrin and heparin sulphate proteoglycans.
It also attracts neutorphils

Question 15

What is the role of serotonin in coagulation?

Answer 15

It induces constriction of injured blood vessels and enhances platelet aggregation to minimise blood loss

Question 16

What are the three major steps in haemostasis?

Answer 16

1) Platelets adhere to site of vascular injury
2) Platelet aggregation and activation
3) Haemostatic plug formation

Question 17

Name five repair complications

Answer 17

Wound dehiscence (deficient healing)
Keloid (excessive scar formation)
Adhesions
Infection 
Chronic Pain

Question 18

What animal can be used to remove dead skin cells?

Answer 18

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.

Question 19

What are the cells/chemical involved in the inflammation stage of wound healing?

Answer 19

• Cytokines (released by damaged cells)
• Neutrophils
• Macrophages

Question 20

Describe the role of cytokines in the inflammatory phase of wound healing

Answer 20

Cytokines (released by damaged cells) cause vasodilation and attraction/activation of infiltrating cells (immune cells, part of innate response)

Question 21

Describe the role of neutrophils in the inflammatory phase of wound healing

Answer 21

Phagocytose bacteria and debris (proteases)

- Not essential unless wound contaminated

Question 22

Describe the role of macrophages in the inflammatory phase of wound healing

Answer 22

Debridement/matrix turnover
Major source of stimulatory signals
Important for wound healing

Blood Clot + Dead macrophage = Scab (acts as barrier)

Question 23

Define fibroplasia

Answer 23

The process of forming fibrous tissue (as in wound healing)

Question 24

Define Epithelialisation

Answer 24

The formation of epithelium over a denuded surface

Question 25

What are the four major steps of proliferation/migration?

Answer 25

1) Angiogenesis 2) Fibroplasia 3) Epithelialisation 4) Contraction

Question 26

Why is angiogenesis required during proliferation?

Answer 26

Oxygen is critical for fibroblasts to produce collagen in order to establish granulation tissue, therefore the formation of new blood vessels is required.

Question 27

What cells provide angiogenic stimuli?

Answer 27

Macrophages and keratinocytes (via VEGF and fibronectin etc.)

Question 28

How are new blood vessels formed during the angiogenesis stage of proliferation?

Answer 28

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.

Question 29

What are the role of fibroblasts during fibroplasia?

Answer 29

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)

Question 30

What is the dominant cell type at the wound edge during the proliferation phase?

Answer 30

Fibroblasts

Question 31

What cells cause fibroblasts to migrate to the wound site and replicate?

Answer 31

Macrophages / mast cells

Question 32

During fibroplasia, what does matrix deposition depend on?

Answer 32

Oxygen and substrate availability | Growth factors

Question 33

Describe the epithelialisation stage of the proliferation phase

Answer 33

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

Question 34

Describe the contraction stage of the proliferation phase

Answer 34

Fibroblasts differentaite to myofibroblasts (similar to smooth muscle cells) that produce contractile proteins, pulling edges of wound together

Question 35

During the contraction stage of proliferation what cell doe fibroblasts differentiate into?

Answer 35

Myofibroblasts

Question 36

What do myofibroblasts produce during the contraction stage of proliferation?

Answer 36

Contractile proteins

Question 37

What is the role of contractile proteins in the contraction stage of proliferation?

Answer 37

Contractile proteins pull the edges of the wound together

Question 38

Describe the steps in the remodelling phase of wound healing

Answer 38

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

Question 39

How strong is the mature scar (formed in remodelling) in comparison to the original tissue?

Answer 39

Mature scar has about 80% of the strength of the original tissue

Question 40

How are new blood vessels that were formed during proliferation removed during remodelling?

Answer 40

Removed by apoptosis

Question 41

During the remodelling phase of wound healing how does the collagen composition change over time?

Answer 41

Type III collagen is exchanged for type I (made by myofibroblasts) Collagen fibres orientated in better alignment

Question 42

What local factors impair wound healing?

Answer 42

Oxygenation Infection Foreign body Venous sufficiency

Question 43

What systemic factors impair wound healing?

Answer 43

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