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Surgical biology and methods > Wound healing > Flashcards

Wound healing Flashcards

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1
Q

What are the phases of wound healing?

A
  1. Inflammatory phase
    a. Hemostasis
    b. Early inflammation
    c. Late inflammation
  2. Proliferative phase
    a. Angiogenesis
    b. Fibroblast migration
    c. Collagen synthesis
    d. Contraction
    e. Epithelialization
  3. Maturation phase
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2
Q

What is the partial pressure of oxygen required in the wound bed for effective killing of bacteria by neutrophils?

A

40 mm Hg

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3
Q

Describe the physiologic processes involved in the hemostasis inflammatory phase?

A
  1. Transient vasoconstriction
  2. Platelet activation and degranulation.
  3. Initiation of coagulation cascade
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4
Q

What proteins are released with platelet degranulation?

A

PDGF, TGF-beta, IGF-1, epidermal growth factor, fibronectin, fibrinogen, vWF. Function to activate and attract neutrophils and later macrophages to wound bed.

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5
Q

Describe the physiologic processes involved in the early inflammatory phase?

A
  1. Vasodilation and increased endothelial cell permeability
  2. Neutrophil margination, adherence and chemoattraction
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6
Q

What are the functions of neutrophils within the wound bed?

A

Killing of bacterial through release of reactive oxygen species, breakdown of extracellular matrix, phagocytosis, and release of cytokines.

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7
Q

What is superoxide?

A

The by-product of the reaction of NADPH oxidase with oxygen. This is formed after neutrophil phagocytosis of bacteria and enhanced bacterial killing capacity.

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8
Q

Describe the physiologic processes involved in the late inflammatory phase?

A
  1. Phenotypic change of monocytes in wound bed to macrophages
  2. Macrophage release of MMPs to degrade provisional extracellular matrix.
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9
Q

What cytokines and growth factors will macrophages produce during the late inflammatory phase?

A

Il-1, IL-6, IL-8, TNF-alpha, fibroblast growth factor, epidermal growth factor, TGF-beta, PDGF.

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10
Q

How long does the late inflammatory phase last?

A

3-5 days following injury

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11
Q

How long does the proliferative phase generally last?

A

4-12 days following injury

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12
Q

Describe the process of wound angiogenesis?

A
  1. Activated endothelial cells degrade basal membrane and migrate into extracellular scaffold
  2. Proliferate and form new tube under influence of vascular endothelial growth factor (predominantly produced by keratinocytes at the wound edge following cell disruption and hypoxia)
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13
Q

Is the capillary endothelial response to vascular endothelial growth factor oxygen dependent?

A

Yes - the response relies of the partial pressure of oxygen in the wound bed.

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14
Q

What causes fibroblast migration in the healing wound?

A
  1. Differentiation of fibroblasts from surrounding quiescent mesenchymal cells occurs 3-5 days post-wounding due to PDGF, TGF-beta, and epidermal growth factor
  2. Under the influence of FGF-2 begin to synthesize components of extracellular matrix (type III and I procollagen), hyaluronic acid, proteoglycans, glycosaminoglycans, elastin, fibronectin
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15
Q

What is the percentage of type I and type III collagen in the unwounded dermis?

A

80% type I, 20% type III

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16
Q

What type of collagen predominates initially during wound healing?

A

Type III

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17
Q

What is granulation tissue?

A

The bright red macroscopic appearance of newly vascularized extracellular matrix

18
Q

What role does TGF-beta play on extracellular matrix production?

A

Peaks at 7-14 days post-injury. Increases synthesis of type I collagen, decreased production of MMPs, and increases production of MMP inhibitors

19
Q

What causes anchored fibroblasts along the wound edges to undergo transformation into myofibroblasts?

A

TGF-beta

20
Q

How do myofibroblasts organize themselves along lines of tension?

A

Linearly

21
Q

How does epithelialization occur at the wound edges?

A
  1. Epidermal growth factor, TGF-alpha, FGF-2 cause proliferation of epithelial cells followed by detachment of keratinocytes from their basal layer.
  2. Keratinocytes secrete MMPs to breakdown the extracellular matrix in the path of cell migration.
  3. Cells advance over the wound bed.
22
Q

What causes cessation of epithelization?

A

Contact inhibition

23
Q

What happens to collagen during the maturation phase of wound healing?

A

Collagen bundles aligned with stress cross-link and increase in diameter. Bundles not aligned with stress are resorbed.

24
Q

How much of a final scar is composed of type III collagen?

A

10%

25
Q

What is the final strength of a scar compared to unwounded tissue?

A

Approximately 70-80%

26
Q

What happens in instances of persistent mechanical load across a wound?

A

Persistence of fibroblasts and myofibroblasts and consequent contracture

27
Q

How long does the maturation phase last?

A

Collagen production occurs rapidly up to 6-weeks, but final strengthening and scar formation can take 12-18 months

28
Q

What is the collagen composition of gastrointestinal submucosa?

A

Type I (68%), type III (20%), type V (12%)

29
Q

What is the effect of sepsis on GI anastomosis collagen deposition and breakdown?

A

Sepsis increases collagenase activity and leads to increased loss and decreased production of collagen at sites of anastomosis

30
Q

What causes the ‘lag phase’ in GI anastomosis wound healing?

A

Collagenase activity within the wound in the first 1-2 days results in net loss of strength of the anastomotic closure.

31
Q

Compare the differences in healing of the GI tract and skin.

A
32
Q

At what partial pressure of oxygen does mature collagen formation fail in the GI?

A

40 mmHg. Below 10 mmHg impairment of critical components of wound healing occurs resulting in anastomotic failure.

33
Q

What is the primary collagen in fascia?

A

Type 1

34
Q

How fast does bladder mucosa re-epithelialize following injury?

A

2-4 days

35
Q

What growth factors are involved in urinary bladder wound healing?

A

Epidermal growth factor, keratinocyte growth factor, TGF-alpha

36
Q

How do growth factor levels respond to wounding throughout the bladder?

A

GF levels increase by 8 (KGF) and 4.5 (TGF-alpha) times normal immediately adjacent to the wound, and by 6 and 3.5 times in unwounded areas

37
Q

How long does the urinary bladder take to regain unwounded strength?

A

Collagen synthesis peaks at 5-days post-injury. 100% of bladder strength occurs within 21 days. Collagen synthesis does not return to normal until 70-days post-injury.

38
Q

What are some described differences in wound healing between dogs and cats?

A
  1. Decreased breaking strength of linear cutaneous wounds at 7-days in cats.
  2. Earlier granulation tissue formation in 2cm squared wounds in dogs (4.5 days) compared to cats (6.3 days).
  3. Faster contraction and epithelialization in dogs (44% re-epithelialization of wounds at 14 days compared in dogs, compared to 13% in cats).
  4. Slower complete granulation tissue formation (19 days) in cats compared to dogs (7.5 days).
39
Q

Has superior healing been shown in intact female or male dogs?

A

Intact females

40
Q

What are local factors that cause impaired wound healing?

A
  1. Wound perfusion
  2. Tissue viability
  3. Wound fluid accumulation
  4. Wound infection
  5. Mechanical factors
  6. Envenomation
41
Q

What are the systemic factors that can impair wound healing?

A
  1. Conditions that impair immune function
  2. Cancer
  3. Age

Surgical biology and methods (11 decks)

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