Lecture 20 How the Body Recovers from Injury

Question 1

What is meant by restituo ad integrum?

Answer 1

Complete restoration of tissue to its normal state

Question 2

How are macrophages involved in bodily recovery?

Answer 2

1) Monocytes go to specialised capillary areas called sinusoids
2) The macrophages act as a filter to remove abnormal molecules and cells
3) The macrophages clear offending stimuli, dead tissue and produce growth factors for the proliferation of various cells in the healing process

Question 3

Describe some cells involved in bodily recovery

Answer 3

• Chemotaxis - migration towards damaged tissues
• Hypertrophy - histiocytes become larger and accumulate more cell organelles and enzymes
• Pseudopodia - Active movement
• Pinocytosis - Ingest fluid from their surroundings
• Phagocytosis - Ingest larger particles, molecules or cells

Activated macrophages/histiocytes develop receptors for abnormal molecules or abnormal cells (foreign or own)

Question 4

What is the difference between regeneration and repair?

Answer 4

• Regeneration can result in restuio ad integrum (complete restoration)
• Repair does not result in restituio ad integrum and rather results in scarring

Question 5

What determines the mechanism of healing and which tissues repair by which mechanism.

Answer 5

• The type of tissue and the extent of injury, regeneration depends on limited damage and preserved integrity of the extracellular matrix, otherwise repair takes place
• Labile and Stable tissues heal by regeneration and repair
• Permanent tissues heal by repair only

Question 6

How is regeneration controlled?

Answer 6

• Interactions involving macrophages and the stromal scafolding / extracellular matrix
• Cell proliferation is dependent on production of growth factors and transcription factors (mainly by macrophages) which induce signalling pathways to unlock cell cycle controls
• Result: Proliferation of local adjacent cells and stem cells

Question 7

What is involved in repair and what happens?

Answer 7

The response is by fibroblasts which patch the damage with fibrosis thus forming a fibrotic scar

Question 8

Describe the basic sequence of repair of skin

Answer 8

1) Haemostasis and Blood Clotting
2) Inflammation
3) Formation of granulation tissue (angiogenesis and fibroblast formation)
4) Formation of connective tissue scar
5) Remodelling of Scar
6) Final Scar

Question 9

What is angiogenesis?

Answer 9

1) Vasodilatation (acute inflammatory response, histamine, NO)
2) Degradation of the BM of adjacent local blood vessels - sprout

3) Migration of endothelial cells and
recruitment of endothelial precursor cells from the bone marrow

4) Proliferation of endothelial cells
5) Maturation of endothelial cells into tubes
6) Development of blood vessel walls

Controlled by endothelial growth factor (VEGF-A)

Question 10

Describe how granulation tissue is formed

Answer 10

• Angiogenesis + proliferation of fibroblasts (via TGF-beta)
• Resulting in granulation tissue formation composed of new blood vessels, fibroblasts and remaining inflammatory cells (usually neutrophils)
• New vessels are leaky contributing to oedema/swelling/tumour

Question 11

What is a disadvantage of granulation tissue

Answer 11

Granulation tissue is weak and is 80% strength of normal skin

Question 12

What are the key features of scar formation?

Answer 12

• Growth factors from macrophages induce migration and proliferation of Pbroblasts into the granulation tissue
• Mainly controlled by fibroblast growth factors (FGFs)
• Fibroblasts produce ECM proteins (e.g. collagen, elastin)
• Mainly controlled by transforming growth factor beta (TGF-beta)

Question 13

Describe the key steps in scar remodelling

Answer 13

• Interactions of collagen deposition and degradation by matrix metalloproteinases (MMPs)
• Collagen changes to type I collagen
• The blood vessels disappear
• Contraction of the scar tissue

The final scar consists of collagen and remaining fibroblasts

Question 14

What clinical terminology is used to describe scar tissue?

Answer 14

Primary Intention - No/little loss of tissue, this includes lacerations and simple bone fractures

Secondary Intention - Significant loss of tissue and formation of abscess

Tertiary Intention - Very deep/infected, wound is kept open in order to heal from the bottom upwards

Question 15

What are some clinical complications of wound healing?

Answer 15

• Deficient scar formation leading to dehiscence or ulceration
• Excessive scar formation (eg keloid)
• Abdominal Adhesions (eg Crohn’s Disease)
• Contractures (often in burns)