Healing and Repair Flashcards

1
Q

By what 2 ways can healing occur?

A

By regeneration
- Replacement with functional, differentiated cells

By repair
- Production of a fibrous scar

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2
Q

What dictates whether healing is carried out using regeneration or repair?

A

Depends on the severity and location of damage

  • Some tissues have better regenerative capacity than others
  • Eradication of insult important
  • Environmental factors also contribute
  • Genetic background (defects in healing capacity
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3
Q

What are the characteristics of labile cells?

A
  • Normal state is active cell division

- Usually rapid regeneration e.g. oral keratinocytes

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4
Q

What are the characteristics of stable cells?

A

Conditional renewal cells

  • Not normally dividing at significant rate
  • Speed of regeneration variable
  • If forced to can undergo rapid proliferation in response to injury e.g. oral fibroblasts, hepatocytes etc
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5
Q

What are the characteristics of permanent cells?

A
  • Unable to divide

- Unable to regenerate (injury to these can be catastrophic) e.g. nerve cells

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6
Q

What are the 5 stages in the action of wound healing?

A
  1. Haemostasis
  2. Inflammation
  3. Proliferation
  4. Remodelling
  5. Maturation
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7
Q

In the process of wound healing what is ‘haemostasis’?

A
  • Contraction of the capillaries to reduce bleeding
  • Red blood cells and platelets released from damaged blood vessels flow into the wound, aggregate and produce a plug or clot in the wound
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8
Q

In the process of wound healing what is ‘inflammation’?

A
  • Dilation of the capillaries - increased permeability allows serum and white blood cells to migrate into the wound area
  • Here, the white blood cells differentiate into different cells including neutrophils, and macrophages. These are attracted to the damaged cells and bacteria by chemical substances, they become phagocytic and engulf dead tissue and bacteria
  • Once all the dead tissue is eliminated the inflammation gradually subsides
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9
Q

In the process of wound healing what is ‘proliferation’?

A
  • The wound if filled with granulation tissue, which consists of newly formed capillaries and connective tissue
  • The formation of new capillaries - angiogenesis - ensures that nutrients are supplied for granulation tissue formation and is essential for wound healing
    Fibroblasts are the predominant cells in the proliferation phase, they migrate into the wound site from surrounding tissue and start to multiply
  • In the last part of this phase the wound is made smaller by wound contraction - this is brought about by specialised fibroblasts with contractile peptides called myofibroblasts
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10
Q

In the process of wound healing what is ‘remodelling’?

A
  • When the granulation tissue filling the wound is almost at level with the surrounding skin, re-epithelialisation starts
  • The epithelial cells change shape to facilitate locomotion and crawl across the wound bed to cover it. Migration stops as soon as cells regain contact
    The cells change back to their normal appearance and reattach themselves to the basement membrane - the wound is closed
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11
Q

In the process of wound healing what is ‘maturation’?

A
  • The transition from granulation tissue to scar tissue involves reorganisation and maturation of collagen fibres to maximise tensile strength
  • During re-modelling the fibred are orientated along the lines of tension and cross linked to form a strong wound
  • Remodelling can take up to 2 years after wounding
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12
Q

What are primary intentions in relation to wounds?

A

Neat cutis like a surgical incision - minimal evidence of scarring

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13
Q

What are secondary intentions in relation to wounds?

A

More severe than primary - dirty/ragged

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14
Q

What is the proliferation phase of granulation tissue?

A
  • Organisation of tissues is their replacement by granulation tissue
  • Laying down of granulation tissue (pink tissue underneath scab) - fundamentally important in the healing process
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15
Q

What is the first stage of the proliferation phase?

A
  • Vascular granulation tissue
  • Mix of proliferating capillaries fibroblasts and immune cells
  • New capillaries are relatively ‘leaky’ allowing cells and fluid into tissue
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16
Q

What is the second stage of the proliferation phase?

A
  • Over time capillaries regress and immune cells return to blood
  • Mature fibroblasts lay down collagen (building blocks of scar tissue)
17
Q

What is angiogenesis?

A

The formation of new capillaries

- Growth of blood vessels from the existing vasculature

18
Q

What are the 2 mechanisms of angiogenesis?

A
  • Sprouting

- Intussusceptive (splitting angiogenesis)

19
Q

Which growth factor is angiogenesis controlled by?

A

Vascular Endothelial Growth Factor (VEGF)

20
Q

What are the 2 groups of growth factor?

A
  • Cytokines

- Hormones

21
Q

What do growth factors do and what is the process of this?

A
  • Promote or inhibit cell growth and differentiation
  • Bind to receptors on cell surfaces
  • Balance between activating and inhibitory signals in health
  • Alteration is the balance - dysregulated cellular proliferation and survival of abnormal cells - link to potential cancers
22
Q

What processes do growth factors control?

A
  • Have restricted or multiple target cells
  • Promote cell survival
  • Locomotion
  • Contractility
  • Differentiation
  • Angiogenesis
23
Q

What is the inflammation phase of fracture healing?

A
  • Soon after the fracture occurs, a hematoma forms at the injury site. Macrophages and inflammatory leukocytes move into the damaged area to scavenge debris and begin producing the pro-inflammatory agents that initiate healing
24
Q

What is the soft callus phase of fracture healing?

A

Inflammation triggers cell division and the growth of new blood vessels. Among the new cells, chondrocytes secrete collagen and proteoglycans, creating fibrocartilage that forms the soft callus (granulation tissue)

25
Q

What is the hard callus phase of fracture healing?

A

Through endochondral ossification and direct bone formation, woven bone replaces the soft callus to create a hard callus around the broken fragments of bone

26
Q

What is the remodelling phase of fracture healing?

A

Over time, mechanically strong, highly organised cortical bone replaces the weaker, disorganised woven bone. Because it is continually remodelled, bone is the only tissue to heal without a scar

27
Q

What is the term ‘fibrosis’ used to describe?

A

The EXTENSIVE deposition of collagen and the formation of excess fibrous connective tissue - uncontrolled, fibroblasts are overactivated

28
Q

When does fibrosis occur?

A

When there is substantial or repeated damage or is the healing process is dysregulated
- In essence similar to process by which scar tissue is generated but the process has ‘gone wrong’

29
Q

Explain the process of fibrosis?

A
  • Process initiated by immune cells (M2 macrophages) releasing growth factors such as transforming growth factor beta (TGF-beta) - activating fibroblasts
  • This drives proliferation and activation of fibroblasts which deposit ECM into the surrounding connective tissue where we don’t want it
  • Chronic inflammation can drive fibrosis