VIVA: Pathology - Tissue response to injury

Question 1

What is the sequence of events for tissue healing by scar formation?

Answer 1

5/7 to pass:
1. Blood clot:
- Stop bleeding
- Creates scaffold for healing
2. Granulation tissue:
- Angiogenesis
- Migration and proliferation of fibroblasts
3. Cell proliferation and collagen deposition:
- ECM deposition
4. Scar formation:
- Blanching
- Increased collagen (initially type 3 then replaced by type 1)
5. Wound contraction by myofibroblasts
6. Connective tissue remodelling:
- ECM synthesis and degradation
7. Recovery of tensile strength

Question 2

How do skin wounds recover tensile strength?

Answer 2

Increase in collagen synthesis* (type 1) and reduction in collagen degradation* over the first 2/12 of healing
Then structural modification* of collagen with cross-linking and increased fibre size

Question 3

What is the approximate time frame for recovery of tensile strength in skin wounds?

Answer 3

Skin wounds have 10% of tensile strength at 1/52
Continues to improve over next 3/52
Plateaus at 3/12 when tensile strength is 70-80% (may never recover to 100%)

Question 4

Describe the phases of cutaneous wound healing

Answer 4

Inflammation, proliferation and maturation (2/3 required to pass):
- Phases overlap, and separation is arbitrary
- Inflammation: initial injury results in platelet adhesion and aggregation with formation of clot on wound surface
- Proliferation: formation of granulation tissue, with proliferation and migration of connective tissue cells, and re-epithelialisation of the wound surface
- Maturation: ECM deposition, tissue remodelling and wound contraction

Question 5

What factors influence cutaneous wound healing?

Answer 5

Local factors*:
- Infection (single most important cause of delay in healing)
- Mechanical factors (e.g. early motion of wounds)
- Foreign bodies
- Size, location and type of wound

Systemic factors*:
- Nutrition (especially protein and vitamin C deficiency)
- Metabolic status (e.g. diabetes mellitus)
- Circulatory status (inadequate blood supply or drainage, e.g. in arteriosclerosis or varicose veins)
- Hormones (e.g. glucocorticoids reduce inflammation and inhibit collagen synthesis)

*2 of each to pass

Question 6

What is wound contraction?

Answer 6

Wound contraction generally occurs in large surface wounds *, and is an important feature in healing by secondary intent. The contraction helps to close the wound * by decreasing the gap between its dermal edges and reducing the wound surface area *. Initial steps of wound contraction involve formation of a network of myofibroblasts * at the edge of the wound.

*needed to pass

Question 7

Describe the timeline of healing of an incised skin wound

Answer 7

1. Formation of blood clot (immediate)*
2. Neutrophil migration at wound margins (within 24hrs)*
3. Formation of granulation tissue (fibroblasts and vascular endothelial tissue); blood vessels are leaky and proteins and fluid pass into the extravascular space leading to oedema (24-72hrs)*
4. Cell proliferation and collagen deposition, with neutrophils replaced by macrophages (48-96hrs)
5. Scar formation (second week):
   - Leucocytic infiltrate, oedema and increased vascularity disappear
   - Increased accumulation of collagen
6. Wound contraction with formation of myofibroblasts at wound edges
7. Connective tissue remodelling
8. Recovery of tensile strength (10% at 1 week to a peak of 70-80% at 3 months)

*needed to pass + 2 others

Question 8

What is angiogenesis?

Answer 8

The process of blood vessel formation in the adult*

Takes place by two methods:
- Branching and extension of existing vessels
- Recruitment of endothelial progenitor cells (EPCs)

*needed to pass + one other

Question 9

Give examples of angiogenesis

Answer 9

2 to pass:
- Wound healing
- Chronic inflammation
- Proliferating endometrium
- Tumours

Question 10

What steps are involved in angiogenesis from pre-existing vessels?

Answer 10

3 needed to pass:
1. Vasodilation
2. Proteolytic degradation of basement membrane
3. Endothelial cells migrate to angiogenic stimuli
4. Maturation
5. Capillary formation
6. Recruitment of peri-endothelial cells for support structure formation
7. Inhibitors such as endostatin are released by proteinases (this is a small fragment of collagen that inhibits endothelial proliferation and also angiogenesis)