5) Healing and repair

Question 1

Define fibrous repair?

Answer 1

Replacement of functional tissue by scar tissue

Question 2

Describe the key components of fibrous repair? (3)

Answer 2

1) Cell migration
2) Angiogenesis
3) Extracellular matrix

Question 3

Cells involved in fibrous tissue cell migration? (2 types)

Answer 3

1) Inflammatory cells: Requires chemical mediators (lymphocytes, macrophages) and phagocytes to remove debris (neutrophils, macrophages)
2) Endothelial cells for angiogenesis and myofibroblasts for wound contraction and secrete ECM proteins w.g collagen

Question 4

Describe the process of angiogenesis?

Why is angiogenesis important?

Answer 4

1) Endothelial proliferation and proteolysis of BM
2) Migration of more endothelial cells via chemotaxis
3) Increased endothelial proliferation (stimulated by VEGF)
4) Endothelial maturation and tubular remodelling
5) Recruitment of periendothelial cells

Blood supply required for wound healing - to deliver O2 and metabolites and provides access for cell migration

Question 5

Describe the functions of ECM (5)?

Answer 5

1) Supports and anchors cells
2) Separates tissue compartments
3) Sequesters growth factors - released when needed
4) Allows communication between cells
5) Facilitates cell migration

Question 6

What are the contents of the ECM (4)?

Answer 6

1) Glycoproteins - Organise cells, support cell migration e.g Fibronectin
2) Proteoglycans - Cell support, matrix organisation, regulate available growth factors
3) Elastin - Tissue elasticity
4) Collagen - Extracellular framework (defects: Scurvy)

Question 7

Describe the mechanism of fibrous repair?

Answer 7

1) Inflammatory cells infiltrate -> blood clot forms -> neutrophils digest clot from the outside and macrophages/ lymphocytes migrate into the clot
2) Clot replaced by granulation tissue: angiogenesis (blood vessels and lymphatics sprout), myofibroblasts migrate and secrete collagen
3) Maturation -> cells decrease, collagen increases and remodels via myofibroblasts contraction
4) Vessels differentiate and are reduced
5) Left with fibrous scar

Question 8

How to control fibrous repair? (3)

Answer 8

1) Inflammatory cells recruited by chemotaxis
2) Angiogenesis controlled by growth factors e.g VEGF, bFGF
3) Macrophages release cytokines e.g TNF alpha, IL1 used for fibroblast proliferation

Question 9

Define regeneration?

Answer 9

Replacement of dead/damaged cells by functional, differentiated cells. Differentiated cells derived from stem cells

Question 10

3 classes of stem cells?

Answer 10

1) Unipotent - can only produce one type of differentiated cell e.g epithelia
2) Multipotent - can produce several types of differentiated cells e.g haemopoeitic
3) Totipotent - can produce all types of differentiated cells e.g embryonic stem cell

Question 11

Describe the 3 types of regeneration capacities?

Answer 11

1) Labile - rapid proliferation, normal state is active cell division e.g epithelia, haemopoietic cells
2) Stable - speed of regeneration is variable, normal state is resting at G0 e.g hepatocytes, osteoblasts, fibroblasts
3) Permanent - unable to regenerate, normal state is permanent G0 e.g myocytes, neurones

Question 12

How to control regeneration? (2)

Answer 12

1) Growth factors

2) Contact between BM and adjacent cells

Question 13

Describe how growth factors work?

Answer 13

1) Promote proliferation of stem cells
2) Promote expression of genes in cell cycle
3) Extracellular signals transducer into the cell

Can be proteins (EGF), hormones (oestrogen) or cytokines

Question 14

Describe how contact between the BM and adjacent cells affect regeneration? (2)

Answer 14

1) Signalling through adhesion molecules
2) Contact inhibition - Loss of contact promotes proliferation, when in contact anti-proliferative signals are sent between cells

Question 15

Explain healing via primary intention?

Answer 15

• Incised wound with apposed edges e.g surgical wound
• Minimal blood clot and granulation tissue
• Epidermis regenerates and dermis undergoes fibrous repair
• Minimal contracture and scarring with good strength
• Granulation tissue -> Scar tissue -> Maturation 2yrs
• Risk of trapping infection -> abscess

Question 16

Explain healing via secondary intention?

Answer 16

• Unapposed wound edges with large blood clot -> dries to eschar e.g ulcer, infarct, abscess
• Necrotic tissue removed by neutrophils - inflammation around the wound
• More granulation tissue, angiogenesis and contractors
• Epithelial regeneration upwards and from sides to form thin layer of tissue
• Scar tissue forms with chronic inflammation

Question 17

Differences between primary and secondary intention healing? (3)

Answer 17

Secondary is

1) Longer
2) Produces large scar (not necessarily weaker)
3) Increased contracture to reduce volume of wound

Question 18

Define contracture?

How to prevent contractors? (4)

Answer 18

Shortened and inflexible muscle

Prevention = Exercise, splints in extended position, physiotherapy, skin graft

Question 19

Local factors affecting wound healing? (6)

Answer 19

1) Type, size, location of wound
2) Radiation damage
3) Infection
4) Apposition
5) Blood supply
6) Foreign material

Question 20

General factors affecting wound healing? (5)

Answer 20

1) Age - older takes longer
2) Drugs - e.g steroids, immunosuppressants, hormones
3) Dietary deficiencies - e.g Vit C, essential AA’s
4) General state of health - e.g diabetes, obesity
5) General state of CVS

Question 21

3 complication of repair with their corresponding risk factors?

Answer 21

1) Insufficient fibrosis - hernia, ulceration wound reopens. Risk factors: obesity, elderly, malnutrition, steroids
2) Excessive fibrosis - cosmetic scarring, keloid, cirrhosis. Risk factors: alcoholics
3) Extreme contracture - obstruct tubes (strictures) and limited joint movement. Risk factor: burn

Question 22

Describe healing processes in bone, cardiac muscle, CNS, cartilage, smooth muscle cells, skeletal muscle?

Answer 22

1) Bone - haematoma -> pro callus -> hard callus -> remodelling
2) Cardiac - Fibrosis only
4) CNS - no regeneration, Glial cells proliferate -> Gliosis
5) Cartilage - limited, harder for adults to regenerate as cartilage becomes more avascular with age
6) Smooth muscle cells - regenerate by mitosis
7) Skeletal muscle - limited, use satellite cells combining with original cells for hypertrophy or satellite cells divide for hyperplasia

Question 23

Describe healing processes in Liver?

Answer 23

Liver - acute = regenerate + chronic = cirrhosis
Hepatocytes are stable cells and re-enter cell cycle, however architecture doesn’t regenerate (nodules form when there’s an imbalance between hepatocyte regeneration and architecture regeneration)

Question 24

Describe healing processes in peripheral nerves?

Answer 24

Regenerate 2mm/day
- Wallerian degeneration: nerve severed, distal segment degenerates (not attached to cell body), myelin sheath empty, if close relation between 2 parts of myelin sheath -> growth factors release by sheath -> axon sprouting -> axon connects to proximal segment to re-establish innervation

Question 25

Appendix function and location?

Describe acute appendicitis symptoms, visible differences, treatment and consequences if not treated?

Answer 25

• No function, found off sedum of large intestine
• Symptoms: right quadrant pain, fever sweating, pallor, nausea, tachycardia
• Differences: plump due to oedema, red, inflamed, pus exudate
• Treatment: Appendectomy, antibiotics, fluid
• If untreated: rupture leading to peritonitis and shock -> death