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ESA 2 Mech Of Disease > Regeneration And Repair > Flashcards

Regeneration And Repair Flashcards

0
Q

What are stem cells?

A
  • 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
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1
Q

What is regeneration?

A
  • Replacement of dead or damaged cells by functional, differentiated cells (derived from stem cells)
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2
Q

What are labile cells?

A
  • Rapid proliferation
  • State is active cell division G1-M-G1
  • E.g epithelial/haematopoietic cells
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3
Q

What are stable cells?

A
  • Variable regeneration speed

- E.g hepatocytes/osteoblasts

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4
Q

What are permanent cells?

A
  • Unable to divide

- Unable to regenerate

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5
Q

What are the factors controlling regeneration?

A
  • Growth factors

- Contact between basement membrane and adjacent cells

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6
Q

How do growth factors control regeneration?

A
  • 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
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7
Q

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

A
  • Signalling through adhesion molecules
  • Inhibits proliferation in intact tissue
  • Contact inhibition
  • Loss of contact promotes proliferation
  • Mech is deranged in cancer
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8
Q

What is fibrous repair?

A
  • Replacement of functional tissue by scar tissue
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9
Q

What are the 3 main parts of fibrous repair?

A
  • Cell migration
  • Blood vessels - angiogenesis
  • ECM production and remodelling
  • These initiate fibrous repair by combining to form granulation tissue
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10
Q

What are the main cell types in fibrous repair

A
  • Inflammatory cells: phagocytosis of debris - neutrophil/macrophages
    chemical mediators - lymphocytes and ^
  • Endothelial cells: angiogenesis
  • Fibro/myofibroblasts: ECM proteins e.g collagen
    wound contraction
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11
Q

What is angiogenesis?

A
  • 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
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12
Q

Outline the process of angiogenesis.

A
  • Endothelial proteolysis of basement membrane
  • Migration of endothelial cell via chemotaxis
  • Endothelial proliferation
  • Endothelial maturation and tubular remodelling
  • Recruitment of peri-endothelial cells
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13
Q

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

A
  • Supports and anchors cells
  • Separates tissue compartments e.g basement membrane
  • Sequesters GF
  • Allows communication between cells
  • Facilitates cell migration
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14
Q

What is the role of collagen in fibrous repair?

A
  • Provides extracellular framework
  • Composed of triple helices of various polypeptide alpha chains
  • Remodelled by specific collagenates
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15
Q

How are fibrillar collagens I-III synthesised?

A
  • 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
16
Q

What diseases are due to defects in collagen synthesis?

A
  • Vit C deficiency (scurvy)
  • Ehlers-Danlos syndrome (defective conversion of procollagen to tropocollagen)
  • Osteogenesis imperfecta
  • Alport syndrome
17
Q

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

A
  • Matrix glycoproteins: organise and orientate cells, support cell migration
  • Proteoglycans: matrix organisation, cell support, regulate GH availability
  • Elastin: tissue elasticity
18
Q

What are the 3 steps of the fibrous repair mechanism?

A
  • Inflammatory cell infiltrate
  • Clot replaced by granulation tissue
  • Maturation
19
Q

What happens in inflammatory cell infiltration?

A
  • Blood clot forms
  • Acute inflammation around the edges
  • Chronic inflammation: macrophages and lymphocytes migrate into clot
20
Q

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

A
  • Angiogenesis: capillaries and lymphatics sprout and infiltrate
  • Myofibroblasts migrate and differentiate
  • ECM produced by (myo)fibroblasts
21
Q

What is maturation?

A
  • Cell population falls
  • Collagen levels increase, matures and remodels
  • Myofibroblasts contract reducing volume of defect
  • Vessels differentiate and are reduced
  • Result: fibrous scar
22
Q

How are the inflammatory cells recruited for repair?

A
  • Chamotaxis
23
Q

What is healing by primary intention?

A
  • Incised wound
  • Apposed edges (fall back on each other)
  • Minimal clot and granulation tissue
  • Epidermis regeneration
  • Dermis undergoes repair
24
Q

How can primary wounds be aided in healing?

A
  • Sutures for ~10 days

- Then at about 10% of normal strength

25
Q

In a clean sutured wound how long will maturation take?

A
  • ~2 years
26
Q

When may a secondary wound occur?

A
  • Infarct
  • Ulcer
  • Abscess/large wound
27
Q

What is healing by secondary intention?

A
  • Unapposed edges
  • Clot forms -> scab (ESCHAR)
  • Epidermis regeneration from base up
  • Repair process produces MORE granulation tissue
28
Q

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

A
  • Haematoma

- Framework for macrophages, endothelial cells, fibroblasts and osteoblasts

29
Q

Outline the full process of bone fracture repair.

A
  • 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
30
Q

What are the local factors influencing wound healing?

A
  • Type/size/location of wound
  • Apposition/lack of movement
  • Blood supply
  • Infection
  • Foreign material
31
Q

What are the general factors influencing wound healing?

A
  • Age
  • Drugs hormones
  • Dietary deficiencies
  • Health state
  • CV status
32
Q

What are the possible complications of repair and why?

A
  • 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)

ESA 2 Mech Of Disease (11 decks)

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