7 - Regeneration and Repair Flashcards

1
Q

What are the three processes involved in wound repair?

A

- Haemostasis: open vessels

- Inflammation: as tissue injury

- Regeneration (resolution/restitution) and repair

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2
Q

What is regeneration and when does it occur?

A
  • Growth of cells and tissues to replace lost structures.
  • Healed by primary intention, when there is a superficial abrasion. When there is an intact connective tissue scaffold, no harmful agent persisting
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3
Q

How are cells induced to regenerate?

A
  • Growth factors in microenvironment
  • Cell-to-cell communication
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4
Q

Where are the stem cells in:

  • Epidermis
  • Intestinal mucosa
  • Liver
A
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5
Q

What is asymmetrical replication?

A

How stem cells replicate

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6
Q

What are some examples of unipotent and multipotent stem cells?

A
  • Uni: Epithelia
  • Multi: Haemopoietic stem cells
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7
Q

Can all tissue proliferate?

A
  • No only labile and stable tissues

- Labile (e.g surface epithelia): short lived cells constantly dividing

- Stable/Quiescent (e.g liver, kidneys, pancreas) : low level of replication but cells can undergo rapid division in response to stimuli. Mature and stem cells replicate

- Permanent (e.g cardiomyocytes): left cell cycle and can’t divide

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8
Q

What happens if there is an injurty where the connective tissue scaffold is not in tact?

A
  • Fibrous repair/ Organisation
  • Healing by secondary intention leaving a scar
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9
Q

What is the time scale of a scar formation?

A
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10
Q

Outline the process of the fibrous repair.

A
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11
Q

What is granulation tissue and what is it’s function?

A
  • Contains developing capillaries, fibroblasts, myofibroblast, chronic inflammatory cells
  • Fills the gap, capillaries supply oxygen and nutrients, contracts and closes the hole
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12
Q

What is the function of fibroblasts in the granulation tissue?

A
  • Produce the extracellular matrix, collagen
  • Contract the wound
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13
Q

How is a scar matured?

A
  • Remodelled due to collagen being remodelled slowly by collagenases
  • Vaculature matures and shrinks so scar goes from being pink to white
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14
Q

Why do people with scurvy have an issue with bleeding?

A
  • Fragile capillaries
  • Old scars break down and open up as fresh wounds as collagen remodelling is resulting in weak collagen being incorporated to the scar
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15
Q

What is Alport syndrome?

A

- X-linked recessive

- Type IV Collagen abnormality

  • Dysfunction in basement membrane in glomerular, cochlea or ear and lens of eye
  • Present with haematuria as children that can progress to chronic renal failure. Often deafness and eye disorders
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16
Q

What factors control regeneration and repair?

A
  • Cell to cell communication either directly or via local mediators/hormones
    e. g growth factors
17
Q

How do growth factors affect wound healing?

A
  • Coded for by proto-oncogenes
  • Bind to specific receptors that stimulate transcription of genes that cause the cell to enter into the cell cycle
  • Causes cell proliferation for repair

(also involved in differentiation, angiogenesis, inhibiting division etc)

18
Q

What are some examples of growth factors?

A

1. Epidermal GF: binds to EGFR. produced by macrophafes, keratinocytes, inflammatory cells. Used for epithelia, hepatocytes and fibroblasts

2. Vascular endothelial GF: vasculogenesis and angiogenesis in tumours

3. Platelet-derived GF: stored in platelet alpha granules and released on platelet activation. also produced by smooth muscle, tumours etc. cause migration and proliferation of fibroblasts, smooth muscle, monocytes

4. Tumour Necrosis Factor: induce fibroblast migration/proliferation and collagenase secretion

19
Q

What is the importance of cell to cell contact in wound healing?

A
  • Contact inhibition: cells replicate until they touch each other and then stop
  • Integrins bind cells to x-cellular matrix and cadherins to other cells
  • This mechanism is lost in malignancy, e.g breast cancer have no E-cadherins
20
Q

What is the process of healing by primary intention?

A
  • Occurs in incisional, closed, non-infected, clean wounds with opposed edges
  • Disruption of basement membrane but only a few epithelial cells have died so small scar
21
Q

What is the process of healing by secondary intention?

A

- Excisional wounds or wounds with tissue loss and separated edges or infection

  • Open wound filled by abundant granulation tissue which grows in from wound margins. More intense inflammatory reaction and contraction to bring wound together as more necrotic tissue
  • Shape of scar depends on original wound. Healing delayed in infection and new epidermis thinner
22
Q

What are the two different types of skin grafts?

A
  • Full thickness and split thickness
23
Q

What is the process of healing after bone fracture?

A
24
Q

What factors influence wound healing?

A

Local: Type/Size/Location of wound, mechanical stress, blood supply, local infection, denervation, foreign bodies, haematoma, necrotic tissue, protection, surgical techniques

General: Age, anaemia, obesity, diabetes, malignancy, genetic disorders (EDS), drugs like steroids, vitamin deficiency, malnutrition

25
Q

What are some complications with fibrous repair?

A

- Fibrous adhesions: can block tubes

- Loss of function due to replacement of cells by non-functioning collage: e.g myocytes

- Disruption of tissue relationships in an organ: cirrhosis

  • Overproduction of fibrous tissue: keloid, common in afrocarribbeans

- Excessive scar contraction: impair blood supply, disfigured scars, tubes and joints

26
Q

How do each of the following tissues regenerate?

  • Cardiac muscle
  • Liver
  • Peripheral Nerve
  • Cartilage
  • CNS
A
  1. Limited, leads to scar formation and loss of function
  2. If architecture not severely damage hepatocytes followed by non-parenchymal ells replicate. Regenerative nodules of hepatocytes with intervening fibrosis leads to cirrhosis
  3. Axons degenerate and they sprout and elongate from proximal stumps using Schwann cells 1-3mm/day
  4. Not well as no blood, lymph or nerves
  5. Permanent tissue, when damaged replaced by glial cells, gliosis.
27
Q

What is the difference between a keloid scar and a hypertrophic scar?

A
  • Keloid scars grow onto normal skin outside the range of the wound
  • Hypertrophic remain in the boundaries of the wound
28
Q

What is the most common complication of wound healing?

A
  • Insufficient fibrosis: wound dehiscence, ulceration
  • Elderly, obesity, malnutrition, steroids, EDS
29
Q

What is traumatic neuroma and some of the symptoms?

A

When proximal and distal nerve fibres are not close together so the proximal fibres grow in tangles of connective tissue, forming lumps under the skin.

  • Painful palpable nodule
  • Parasthesia
  • Fatigue
30
Q

What is Walerian degeneration?

A

When a nerve fibre is crushed or cut the fibres distal to the cut is degenerated

31
Q

What is proud flesh and how can it be treated?

A
  • Hypergranulation leading to too much connective tissue and vessels in an open wound
  • Trim away, silver nitrate dressing, cortisone cream