Regeneration And Repair

Question 0

What are stem cells?

Answer 0

• Limitless proliferation
• Daughter cells either remain as stem cells to maintain stem cell pool or differentiate
• Internal repair system to replace lost/damaged cells in tissues

Question 1

What is regeneration?

Answer 1

• Replacement of dead or damaged cells by functional, differentiated cells (derived from stem cells)

Question 2

What are labile cells?

Answer 2

• Rapid proliferation
• State is active cell division G1-M-G1
• E.g epithelial/haematopoietic cells

Question 3

What are stable cells?

Answer 3

• Variable regeneration speed

- E.g hepatocytes/osteoblasts

Question 4

What are permanent cells?

Answer 4

• Unable to divide

- Unable to regenerate

Question 5

What are the factors controlling regeneration?

Answer 5

• Growth factors

- Contact between basement membrane and adjacent cells

Question 6

How do growth factors control regeneration?

Answer 6

• Promote proliferation in stem cell population
• Extracellular signals transduced into the cell
• Promotes expression of genes controlling cell cycle
• Hormones: oestrogen/testosterone/GH
• Autocrine/paracrine/endocrine signals from many cell types

Question 7

How does contact between basement membranes and adjacent cells control regeneration?

Answer 7

• Signalling through adhesion molecules
• Inhibits proliferation in intact tissue
• Contact inhibition
• Loss of contact promotes proliferation
• Mech is deranged in cancer

Question 8

What is fibrous repair?

Answer 8

• Replacement of functional tissue by scar tissue

Question 9

What are the 3 main parts of fibrous repair?

Answer 9

• Cell migration
• Blood vessels - angiogenesis
• ECM production and remodelling
• These initiate fibrous repair by combining to form granulation tissue

Question 10

What are the main cell types in fibrous repair

Answer 10

• Inflammatory cells: phagocytosis of debris - neutrophil/macrophages
  chemical mediators - lymphocytes and ^
• Endothelial cells: angiogenesis
• Fibro/myofibroblasts: ECM proteins e.g collagen
  wound contraction

Question 11

What is angiogenesis?

Answer 11

• Blood supply development is vital to wound healing
• Provides access to the wound for inflammatory cells and fibroblasts
• O2 and nutrient delivery
• Endothelial proliferation induced by pro-angiogenesis GF e.g VEGF
• Pre existing blood vessel sprout new vessels
• Mech exploited by malignant cells

Question 12

Outline the process of angiogenesis.

Answer 12

• Endothelial proteolysis of basement membrane
• Migration of endothelial cell via chemotaxis
• Endothelial proliferation
• Endothelial maturation and tubular remodelling
• Recruitment of peri-endothelial cells

Question 13

What is the role of the extra cellular matrix in fibrous repair

Answer 13

• Supports and anchors cells
• Separates tissue compartments e.g basement membrane
• Sequesters GF
• Allows communication between cells
• Facilitates cell migration

Question 14

What is the role of collagen in fibrous repair?

Answer 14

• Provides extracellular framework
• Composed of triple helices of various polypeptide alpha chains
• Remodelled by specific collagenates

Question 15

How are fibrillar collagens I-III synthesised?

Answer 15

• Polypeptide alpha chains are syn. in ER
• Enzymatic modifications (Vit C dependent hydroxylation)
• Alpha chains align and cross-link forming the procollagen triple helix
• Soluble procollagen in secreted

Question 16

What diseases are due to defects in collagen synthesis?

Answer 16

• Vit C deficiency (scurvy)
• Ehlers-Danlos syndrome (defective conversion of procollagen to tropocollagen)
• Osteogenesis imperfecta
• Alport syndrome

Question 17

What is present in the ECM and what does it do?

Answer 17

• Matrix glycoproteins: organise and orientate cells, support cell migration
• Proteoglycans: matrix organisation, cell support, regulate GH availability
• Elastin: tissue elasticity

Question 18

What are the 3 steps of the fibrous repair mechanism?

Answer 18

• Inflammatory cell infiltrate
• Clot replaced by granulation tissue
• Maturation

Question 19

What happens in inflammatory cell infiltration?

Answer 19

• Blood clot forms
• Acute inflammation around the edges
• Chronic inflammation: macrophages and lymphocytes migrate into clot

Question 20

What is meant by ‘clot replaced by granulation tissue’?

Answer 20

• Angiogenesis: capillaries and lymphatics sprout and infiltrate
• Myofibroblasts migrate and differentiate
• ECM produced by (myo)fibroblasts

Question 21

What is maturation?

Answer 21

• Cell population falls
• Collagen levels increase, matures and remodels
• Myofibroblasts contract reducing volume of defect
• Vessels differentiate and are reduced
• Result: fibrous scar

Question 22

How are the inflammatory cells recruited for repair?

Answer 22

• Chamotaxis

Question 23

What is healing by primary intention?

Answer 23

• Incised wound
• Apposed edges (fall back on each other)
• Minimal clot and granulation tissue
• Epidermis regeneration
• Dermis undergoes repair

Question 24

How can primary wounds be aided in healing?

Answer 24

- Sutures for ~10 days | - Then at about 10% of normal strength

Question 25

In a clean sutured wound how long will maturation take?

Answer 25

- ~2 years

Question 26

When may a secondary wound occur?

Answer 26

- Infarct - Ulcer - Abscess/large wound

Question 27

What is healing by secondary intention?

Answer 27

- Unapposed edges - Clot forms -> scab (ESCHAR) - Epidermis regeneration from base up - Repair process produces MORE granulation tissue

Question 28

If there is a bone fracture. What is the first step of bone fracture repair and why is this organised?

Answer 28

- Haematoma | - Framework for macrophages, endothelial cells, fibroblasts and osteoblasts

Question 29

Outline the full process of bone fracture repair.

Answer 29

- Necrotic tissue removed - Capillaries develop - Specialised maturation of cells -> callus - Bone laid down in irregular woven pattern and islands of cartilage - External callus provides splint-like support - Woven bone gradually replaced by more organised lamellar bone - Lamellar bone gradually remodelled to direction of mechanical stress

Question 30

What are the local factors influencing wound healing?

Answer 30

- Type/size/location of wound - Apposition/lack of movement - Blood supply - Infection - Foreign material

Question 31

What are the general factors influencing wound healing?

Answer 31

- Age - Drugs hormones - Dietary deficiencies - Health state - CV status

Question 32

What are the possible complications of repair and why?

Answer 32

- Insufficient fibrosis: wound dehiscence (falling apart): hernia/ulceration/obesity/malnutrition/steroids/elderly - Excessive fibrosis: cosmetic scarring: keloid/cirrhosis - Excessive contraction: obstruction of tubes and channels (strictures)