Session 4 - healing and repair Flashcards

1
Q

Where are the differentiated cells of regeneration derived from?

A

-Stem cells

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2
Q

What is asymmetric division?

A

-The division undergone by stem cells; One daughter cell remains as a stem cell and the other differentiates into a specialist cell type

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3
Q

Define unipotent

A

-Cells only produce one type of differentiated cell, eg epithelia

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4
Q

Define multipotent

A

-Can produce several types of differentiated cell, eg haematopoietic

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5
Q

Define totipotent

A

-Can produce any type of cell eg embryonic stem cell

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6
Q

What is a labile cell population?

A

-A cell population which undergoes rapid active proliferation eg epithelia

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7
Q

What is a stabile cell population?

A
  • A population of cells which are in a resting state, yet have the ability to exit G0 and enter the cell cycle
  • Eg renal tubule epithelium/hepatocytes
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8
Q

What is a permanent cell population?

A

-The cels are unable to divide and thus unable to regenerate

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9
Q

What are the two main factors which control regeneration?

A
  • Growth factors

- Contact between basement membrane and adjacent cells

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10
Q

How do growth factors control regeneration?

A

-Promote proliferation in the stem cell population via extracellular signals which are transduced into the cell and control the expression of genes which control cell cycle

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11
Q

What type of molecules are growth factors?

A
  • Hormones (eg oestrogen,testosterone, GH)

- Proteins (EGF, PDGF, FGF)

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12
Q

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

A
  • Contact inhibition -> signalling through adhesion molecules inhibits proliferation in intact tissues
  • Loss of contact promotes proliferation
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13
Q

What are E-cadherins?

A
  • Calcium-dependant adhesion transmembrane proteins which dimerise with E-cadherins of other cells and link the actin cytoskeletons together
  • Play a role in contact inhibition through regulatory proteins
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14
Q

What is fibrous repair?

A

-Replacement of functional tissue by scar tissue

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15
Q

When does fibrosis repair and scarring occur?

A
  • When there is cell injury to permanent populations

- When the collagen framework is destroyed in labile and stable cell population

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16
Q

What are the three key components of fibrous repair?

A
  • Cell migration
  • Angiogenesis
  • Extracellular matrix production and remodelling
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17
Q

What tissue forms before fibrous repair?

A

-Granulation tissue

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18
Q

What cell types migrate during fibrous repair?

A
  • Inflammatory cells (neutrophils/macrophages/lymphocytes)
  • Endothelial cells
  • Fibroblasts/myofibroblasts
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19
Q

What role do inflammatory cells play in fibrous repair?

A
  • Responsible for phagocytosis of deris

- Release chemical mediators to influence repair

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20
Q

Why do endothelial cells migrate to the site of injury in fibrous repair?

A

-For angiogenesis

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21
Q

Why are fibroblasts/myofibroblasts involved in fibrous repair?

A
  • Extracellular matrix production

- Wound contraction

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22
Q

What is angiogenesis?

A

-The development of a new blood supply

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23
Q

Why is angiogenesis critical in wound healing?

A
  • Delivery of oxygen and nutrients

- Provides access for inflammatory cells and fibroblasts

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24
Q

What are proangiogenic growth factors?

A

-GF which induce endothelial proliferation eg VEGF

25
Q

Describe angiogenesis

A

1) Endothelial proteolysis of BM in exsisting BVs
2) Migration of endothelial cells via chemotaxis
3) Endothelial proliferation
4) Endothelial maturation + tubular remodelling -link to venous system
5) Recruitment of periendothelial cells for support

26
Q

What is the function of the ECM produced in fibrous repair?

A
  • Supports and anchors cells
  • Sequesters growth factors
  • Allows communication between cells
  • Facilitates cell migration
27
Q

What is ECM composed of?

NB. Revise MGD session 8

A
  • Collagen/Elastin
  • GAGs
  • Proteoglycans
28
Q

Describe collagen sysnthesis

A

1)Preprocollagen synthesised in ribosome
2)Translocated to ER and signal sequence cleaved producing procollagen
3)Hydroxylation of selected proline/lysine residues
4)N-linked Glycosylation
5)Alignment of procollagen subunits and DSB formation at C terminal initiates folding of helices into procollagen helix ->C and N terminal peptides not incorporated in helix
7)Translocation to the golgi
8)O linked glycosylation
9)Packaged into vesicle
10)secreted via constitutive pathway
11)Procollagen peptidases cleave C and N terminal peptides producing tropocollagen units
12)Lysine residues converted to aldehyde derivative allowing crosslinks between subunits
130 Tropocollagen units assemble into collagen fibrils stabilised by H bonds and cross-links and bundles of fibrils form collagen fibres

29
Q

Define regeneration

A

-The replacement of dead/damaged cells by functionally differentiated stem cells

30
Q

How is scurvy a defect of collagen?

A
  • Inadequate vit C-dependant hydroxylation of proline residues by prolyl hydroxylase
  • Reduction in H bonds between polypeptide chains of Collagen
  • Collagen fibres lack strength and resistance to degredation
31
Q

What is Ehlers-Danlos Syndrome caused by?

A
  • Defective converison off procollagen to tropocollagen by lysyl oxidase (aldehyde derivatives not formed and not crosslinked)
  • Weak collagen
32
Q

What is osteogenesis imperfecta?

A

-Brittle bone disease caused by T1 collagen mutation

33
Q

Describe the mechanism of fibrous repair

A

1) Exudate clots, neutrophils infiltrate (Acute inflammation) Macrophages and lymphocytes infiltrate (Chronic inflammation)
2) Area becomes more cellular with fibroblasts and endothelial cells migrating too and angiogenesis begins -> granulation tissue replaces the clot
3) Myo/fibroblasts differentiate and produce ECM and contract
4) Vascular network and inflammatory cells reduce
5) Maturation of fibrous scar as ECM increases and collagen matures, contracts and remodels

34
Q

How is fibrous repair controlled?

A
  • Inflammatory cells recruited by chemotaxis
  • Angiogenesis occurs in response to growth factors
  • ECM production by fibroblasts controlled by cytokines
35
Q

When does healing by ‘primary intention’ occur?

A

-Incised wounds with apposed edges

36
Q

Describe the characteristics of a skin wound healing by primary intention

A
  • Minimal clot and granulation tissue

- Epidermis regenerates and dermis undergoes fibrous repair with minimal contraction and scarring

37
Q

When does healing be secondary intention occur?

A

-When there is an infact, ulcer, abscess or any large wound with unopposed edges

38
Q

Describe the characteristics of a skin wound healing by secondary intention

A
  • Large clot which dries to form a scab
  • Epidermis regenerates from the base up with a high amount of granulation tissue
  • Produces more contraction and scarring as wound needs to reduce in volume
39
Q

What are the 4 stages of healing of bone fractures?

NB revise TOB session 6

A

1) Haematoma formation
2) Soft callus formation
3) Bony callus formation
4) Remodelling

40
Q

What local factors influence wound healing?

A
  • Size, type and location of wound
  • Apposition
  • Blood suply
  • Infection and foreign material
41
Q

What general factors influence wound healing?

A
  • Age
  • Drugs and hormones
  • Dietary deficiencies and general state of health
42
Q

What happens if there is insufficient fibrosis within a wound?

A

-The wound has insufficient strength and can lead to herniation, ulceration and wound dehiscence (splitting open)

43
Q

What are risk factors of insufficient fibrosis occuring?

A
  • Obesity
  • Elderly
  • Steroids
44
Q

What are the consequences of excessive fibrosis?

A
  • Induced chronic inflammation
  • Keloid formaiton
  • Cirrhosis
  • Impaired functions of organs
45
Q

What are some possible consequences of excessive contraction?

A
  • Obstruction of tubes or channels by strictures

- Contractures

46
Q

What is alport syndrome?

A

-X-linked disease where type IV collagen is abnormal resulting in dysfunction of basement membrane

47
Q

What is the function of EGF?

A

-mitogenic for epithelia cells, hepatocytes and fibroblasts

48
Q

What is the function of VEGF?

A

-Potent inducer of blood vessel development and angiogenesis

49
Q

What is the function of PDGF?

A

-Causes migration and proliferation og fibroblasts, smooth muscle and monocytes

50
Q

What is the function of TNF?

A

-Induces fibroblast migration, fibroblast proliferation and collagenase secreion

51
Q

Does cardiac muscle have regeneration capacity?

A
  • Limited, if any

- MI is followed by scar formation which can comprimise cardiac function

52
Q

Describe the liver’s ability to regenerate

A
  • Almost all hepatocytes are replicate during regeneration, replacing any damaged/dead tissue.
  • Followed by the replication of non-parenchymal cells
53
Q

Can peripheral nerves regenerate?

A

-Yes, the severed nerve undergoes wallarian degeneration and then the proximal stump grows back to the tissue, guided by the now vacant distant schwann cells at approximately 1-3mm/day

54
Q

Can cartilage regenerate?

A

-Limited regeneration as there is a poor blood supply, lymphatic drainage and innervation

55
Q

Can the CNS regenerate?

A
  • No, neural tissue is a permanent cell population

- Dead/damaged tissue is replaced by the proliferation of glial cells

56
Q

What is a neuroma?

A

-Overproliferation of nervous tissue, arranged in a disordered and unorganised manner due to loss of scaffold and rapid regeneration

57
Q

What local factors may cause a delay in healing of a fracture?

A
  • Anatomical location
  • Size of break
  • Blood supply
  • Infection or foreign material
  • surrounding soft tissue injury
58
Q

Which people are at risk of developing a keloid?

A

-Afro-carribeans

59
Q

How does a keloid differ from a hypertrophic scar?

A
  • In a keloid , fibrous proliferation goes beyond the boundaries of the wound to healthy tissue
  • Hypertrohpic scars are contained