Wound Healing Flashcards

1
Q

What is angiogenesis?

A

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.

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2
Q

What are the four stages of acute wound healing?

A

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

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3
Q

What are the cell types involved in wound healing?

A
Platelets 
Neutrophils 
Fibroblasts
Monocyte
Endothelial cells
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4
Q

How long after a graze would haemostasis occur?

A

Seconds to hours

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5
Q

How long after a graze would inflammation occur?

A

Hours to Days

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6
Q

How long after a graze would proliferation occur?

A

Days to Weeks

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7
Q

How long after a graze would remodelling occur?

A

Weeks to Months

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8
Q

What processes occur directly after a vessel ruptures?

A

Platelet aggregation, Vasoconstriction, Activation of the Coagulation Cascade

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9
Q

When platelet degranulation occurs what mediators are released?

A
PDGF (Platelet Derived Growth Factor)
IGF-1 (Insulin Like Growth Factor)
PAF (Platelet Aggravating Factor)
TGFB-1 (Transforming Growth Factor Beta-1)
Fibronectin
Serotonin
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10
Q

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

A

Stimulates cell proliferation, recruits fibroblasts and promotes angiogenesis/epithelialisation

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11
Q

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

A

Potentiates platelet activity

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12
Q

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

A

Potentiates platelet activity

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13
Q

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

A

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

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14
Q

What is the role of Fibronectin in coagulation?

A

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

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15
Q

What is the role of serotonin in coagulation?

A

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

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16
Q

What are the three major steps in haemostasis?

A

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

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17
Q

Name five repair complications

A
Wound dehiscence (deficient healing)
Keloid (excessive scar formation)
Adhesions
Infection 
Chronic Pain
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18
Q

What animal can be used to remove dead skin cells?

A

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.

19
Q

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

A
  • Cytokines (released by damaged cells)
  • Neutrophils
  • Macrophages
20
Q

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

A

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

21
Q

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

A

Phagocytose bacteria and debris (proteases)

- Not essential unless wound contaminated

22
Q

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

A

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

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

23
Q

Define fibroplasia

A

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

24
Q

Define Epithelialisation

A

The formation of epithelium over a denuded surface

25
Q

What are the four major steps of proliferation/migration?

A

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

26
Q

Why is angiogenesis required during proliferation?

A

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

27
Q

What cells provide angiogenic stimuli?

A

Macrophages and keratinocytes (via VEGF and fibronectin etc.)

28
Q

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

A

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.

29
Q

What are the role of fibroblasts during fibroplasia?

A

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)

30
Q

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

A

Fibroblasts

31
Q

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

A

Macrophages / mast cells

32
Q

During fibroplasia, what does matrix deposition depend on?

A

Oxygen and substrate availability

Growth factors

33
Q

Describe the epithelialisation stage of the proliferation phase

A

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

34
Q

Describe the contraction stage of the proliferation phase

A

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

35
Q

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

A

Myofibroblasts

36
Q

What do myofibroblasts produce during the contraction stage of proliferation?

A

Contractile proteins

37
Q

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

A

Contractile proteins pull the edges of the wound together

38
Q

Describe the steps in the remodelling phase of wound healing

A

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

39
Q

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

A

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

40
Q

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

A

Removed by apoptosis

41
Q

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

A

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

42
Q

What local factors impair wound healing?

A

Oxygenation

Infection

Foreign body

Venous sufficiency

43
Q

What systemic factors impair wound healing?

A

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