Session 4 ILOs - Regeneration and repair

Question 1

Describe the differences between labile, stable and permanent tissues and be able to give examples of each

Answer 1

Labile tissue:

• Continuous replication of cells
• In the cell cycle
  e. g. epithelium

Stable tissue:

• Normally has a low level of cell replication
• Left cell cycle but can reenter (G0)
  e. g. liver

Permanent tissue:

• Cells do not replicate
• Left the cell cycle
  e. g. neurones

Question 2

Discuss the role of stem cells and know what is meant by unipotent, multipotent and totipotent

Answer 2

Stem cells can differentiate into other cell types and renew, to replace dead or damaged cells

Unipotent:

• Can differentiate into one cell type
  e. g. epithelial stem cells

Multipotent:

• Can differentiate into several cell types
  e. g. haemopoetic stem cells

Totipotent:

• Can differentiate into all cell types
  e. g. embryonic stem cells

Question 3

Describe basically how cells communicate and their involvement with cell signalling e.g. autocrine, paracrine and endocrine signalling, growth factors and adhesion molecules and the concept of contact inhibition

Answer 3

Cells communicate with each other to stimulate or inhibit cell proliferation

1. Direct cell to cell contact
2. Local mediators e.g. growth factors (paracrine)
   - Growth factors are polypeptides that work on the cell surface
   - Cause the cell to enter the cell cycle and proliferate, important ones include: epidermal growth factor, vascular endothelial growth factor and tumour necrosis factors
3. Hormones (endocrine)
4. Contact inhibition
   - Isolated cells replicate until they encounter other cells
   - Cadherins (cell surface receptors) bind between cells to inhibit further proliferation
   = defective in cancer (hallmark)

Question 4

Explain and discuss the processes involved with regeneration, resolution and fibrous repair/organisation and how these affect different tissues

Answer 4

Scar formation:

1. Haemostasis
   - Blood clot forms within minutes
2. Inflammation
   - Acute then chronic
   - Digestion of the blood clot in minutes - days
3. Proliferation of:
   - Capillaries
   - Fibroblasts
   - Myofibroblasts
   - Extracellular matrix
   = granulation tissue is produced in days - weeks (fills the gap as a physical barrier)
4. Remodelling
   - Maturation of the scar
   - Reduced cell population
   - Increased collagen and the myofibroblasts contract
   = mature scar in weeks - years

Question 5

Explain and distinguish between primary and secondary intention

Answer 5

Primary intention:
- Incised wound 
- Apposed edges (sutured)
- Minimal clot and granulation tissue
- Epidermis regenerates and the dermis undergoes fibrous repair
= small scar

Secondary intention:
- Significant wound
- Unapposed edges (not brought together)
- Abundant clot, inflammation and granulation tissue
- Epidermis regenerates from edges and the dermis undergoes significant fibrous repair
- Considerable wound contraction required (myofibroblasts)
= large scar

Question 6

Describe the local and systemic factors influencing the efficacy of healing and repair

Answer 6

Local factors:

• Size and location of wound
• Blood supply
• Local infection
• Presence of foreign bodies

Systemic factors:

• Age
• Anaemia/hypoxia/hypovolemia
• Obseity
• Diabetes
• Drugs
• Vitamin deficiencies e.g. vit C deficiency
• Malnutrition

Question 7

Recognise and describe the complications of fibrous repair e.g. insufficient fibrosis, etc.

Answer 7

Insufficient fibrosis:

• Wound dehiscence (opening of previous wounds)
  e. g. can occur in obesity, the elderly, malnutrition and steroid use

Excessive fibrosis:
- Keloid scar (scar formation into surrounding tissue) or hypertrophic scar (scar formation within original wound boundary)

Adhesions:
- Result in fibrous bands that can cause obstruction of tubes

Loss of function:

• Replacement of specialised tissue by fibrous tissue
  e. g. in cardiac tissue

Disruption of architecture:
- Especially occurs in the liver (cirrhosis)

Excessive contraction:

• If it occurs in tubes, it can cause constriction and narrowing e.g. the oesophagus
• Can occur at joints e.g. from burns, resulting in fixed flexion deformities = contractures (reduced joint mobility)