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ESA2 > MoD 4 (Healing & Repair) > Flashcards

MoD 4 (Healing & Repair) Flashcards

1
Q

Define regeneration:

A

The growth of cells and tissues to replace lost structures. This requires an intact tissue scaffold (cannot occur if extensive damage).

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2
Q

Define ‘labile’ tissue:

A

Tissue with continuously dividing cells

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3
Q

Define ‘stable’ tissue:

A

Tissue with quiescent cells

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4
Q

What is a quiescent cell?

A

A cell that has reversibly left the cell cycle (G0), as it is not dividing or preparing to divide.

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5
Q

Where can labile cells be found?

A

Surface epithelia:
- Lining mucosa of secretory ducts of glands
- Epithelia of GI, uterus and urinary tract
Haemopoetic tissue (red bone marrow)

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6
Q

Where can stable cells be found?

A 
Mesenchymal cells (ie fibroblasts, smooth muscle cells)
Parenchymal (functional) cells of Liver, Kidney and Pancreas
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7
Q

Define ‘permanent’ tissue:

A

Tissue containing non-dividing, terminally differentiated cells

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8
Q

Where can permanent cells be found?

A
  • Neurones
  • Skeletal muscle cells
  • Cardiac muscle cells
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9
Q

What type of cell undergoes asymmetric replication?

A

Stem cells

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10
Q

What is meant by asymmetric replication?

A

When a stem cell replicates producing 1 stem cell and 1 stable/permanent cell.

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11
Q

Define fibrous repair:

A

The replacement of functional tissue with scar tissue

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12
Q

Fibrous repair occurs in response to what 3 triggers?

A

1 - Chronic inflammation
2 - Damage to collagen framework of a tissue
3 - Necrosis of specialised cells which cannot be replaced

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13
Q

What cell types are required for fibrous repair?

A 
Fibroblasts/Myofibroblasts
Endothelial cells
Inflammatory cells
 - Neutrophils
 - Macrophages
 - Lymphocytes
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14
Q

What is the role of endothelial cells in fibrous repair?

A

Angiogenesis

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15
Q

What is the role of fibroblasts in fibrous repair?

A

Synthesis of extracellular matrix proteins

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16
Q

What is the roles of macrophages/neutrophils in fibrous repair?

A

Phagocytosis of debris

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17
Q

Which growth factor stimulates angiogenesis?

A

VEGF

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18
Q

Describe the key steps in angiogenesis:

A
  • VEGF binds to endothelial cell = ACTIVATES
  • Activated endothelial cell causes vasodilation and proteolysis of basement membrane
  • Endothelial cells proliferate and migrate, then mature and undergo remodelling
  • Periendothelial cells are recruited
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19
Q

What is Scurvy caused by?

A

Vitamin C deficiency

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20
Q

What is Scurvy?

A

Weak collagen formation due to vitamin C deficiency, causing bleeding gums and prolonged healing.

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21
Q

What are the symptoms of Scurvy?

A 
Bleeding/swollen gums
Prolonged healing
Fatigue
Myalgia
Shortness of breath
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22
Q

Why does a vitamin C deficiency cause weak collagen (Scurvy)?

A

Vitamin C is required for Prolyl hydroxylase and Lysyl hydroxylase, which hydroxylate amino acid residues during collagen synthesis, allowing many cross-linkages to occur, increasing the strength of Collagen

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23
Q

What is Ehlers-Danlos syndrome?

A

Inherited disease which causes the defective conversion of Procollagen to Tropocollagen (Collagen types I-III have reduced tensile strength), this causing hypermobility of joints and hyperextensible fragile skin

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24
Q

What are the symptoms of Ehlers-Danlos syndrome?

A
  • Hypermobility of joints
  • Hperextensible fragile skin
  • Poor wound healing
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25
Q

What is Alport syndrome?

A

Inherited disease affecting type IV collagen primarily in kidneys, cochlea and lens of eye.
Causes kidney failure, cataracts, progressive hearing loss, oedema

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26
Q

What is the name of the inherited condition which causes progressive fibrous repair of type IV collagen in the body?

A

Alport syndrome

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27
Q

Define growth factor:

A

Polypeptide coded for by proto-oncogenes, which act on specific cell surface receptors, stimulating gene transcription

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28
Q

In what types of cells does Epidermal Growth Factor cause mitosis?

A
  • Epithelial cells
  • Hepatocytes
  • Fibroblasts
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29
Q

What type of cells produce Epidermal Growth Factor?

A
  • Keratinocytes

- Inflammatory cells (ie macrophages)

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30
Q

What does VEGF stand for?

A

Vascular Endothelial Growth Factor

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31
Q

What does VEGF cause?

A
  • Angiogenesis
  • Vasculogenesis
  • Chronic inflammation
  • Wound healing
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32
Q

Define vasculogenesis:

A

Process of new blood vessel formation during embryonic development of the CVS

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33
Q

What does PDGF stand for?

A

Platelet Derived Growth Factor

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34
Q

Which cells can produce/release PDGF?

A
  • Platelets
  • Macrophages
  • Smooth muscle cells
  • Endothelial cells
  • Tumour cells
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35
Q

What is the role of PDGF?

A

Causes migration and proliferation of fibroblasts, smooth muscle cells and monocytes

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36
Q

What does G-CSF stand for?

A

Granulocyte-Colony Stimulating Factor

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37
Q

What is the role of G-CSF?

A

Stimulates bone marrow to produce granulocytes (ie neutrophils)

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38
Q

What does TNF stand for?

A

Tumour Necrosis Factor

39
Q

What is the role of TNF?

A

Induces fibroblast migration and proliferation, and collagenase secretion

40
Q

What is the role of Cadherins?

A

Bind cell to each other

41
Q

What is the role of Integrins?

A

Bind cells to the extracellular matrix

42
Q

Describe the wound appearance if it is healing by primary intention:

A
  • Opposed edges
  • Clean cut (via scalpel)
  • May be sutured
43
Q

What are the 6 stages of wound healing?

A

1) Haemostasis
2) Inflammation
3) Cell migration
4) Regeneration
5) Scarring
6) Scar maturation

44
Q

What is the 1st stage of wound healing, and what does it involve?

A

Haemostasis

Arteries contract, clotted blood fills space and dehydrates, forming a scab

45
Q

What is the function of a scab in wound healing?

A

Prevents infection

Seals wound from outside environment

46
Q

What is the 2nd stage of wound healing and what does it involve?

A

Inflammation

Neutrophils gather at the margins of the wound

47
Q

What is the 3rd stage of wound healing and what does it involve?

A

Cell migration
Macrophages appear (phagocytose dead neutrophils and secrete cytokines for endothelial cells and fibroblasts)
Endothelial cells begin angiogenesis
Basal epidermal cells deposit basement membrane

48
Q

What are the functions of Macrophages in wound healing?

A
  • Phagocytose dead neutrophils and necrotic tissue

- Secrete cytokines for fibroblasts and endothelial cells

49
Q

What is the function of endothelial cells in wound healing?

A

Angiogenesis

50
Q

What is the role of basal epidermal cells in wound healing?

A

Deposit basement membrane

51
Q

What is the 4th stage of wound healing and what does it involve?

A 
Regeneration
Formation of granulation tissue
Proliferation of epithelial cells
Scab falls off
Activated fibroblasts secrete collagen
52
Q

In which stage of wound healing does granulation tissue form?

A

Regeneration stage ~ 3 days after trauma

53
Q

What is the 5th stage of wound healing, and what does it involve?

A 
Scarring
Fibroblasts proliferate and form scar
Epidermis keratinises (no sweat glands/hair follicles)
WBCs and Oedema disappears
Vascular channels regress
54
Q

What is the 6th stage of wound healing and what does it involve?

A

Scar maturation
Type III collagen is gradually replaced by type I collagen
May contract via myofibroblasts

55
Q

In which direction does wound healing take place if healing by primary intention?

A

From the surface downwards

56
Q

In which direction does healing take place if healing by secondary intention?

A

From the bottom up, towards the surface

57
Q

What is the risk involved with healing by primary intention?

A

Infection may be trapped below sutures, may cause abscess formation

58
Q

Describe the wound appearance if it is healing by secondary intention:

A
  • Unopposed edges

- Large amount of tissue lost (due to infarct/abscess/ulcer/infection)

59
Q

Apart from the appearance of the wound, what is the difference between healing by primary and secondary intention?

A

Healing by secondary involves:

  • More clot formation
  • More necrotic debris produced
  • Increased inflammatory reaction
  • More granulation tissue formed
  • May require contraction
60
Q

Which cell type mediates contraction of a wound?

A

Myofibroflast

61
Q

List some local factors which may influence the efficacy of wound healing:

A
  • Infection
  • Location of wound
  • Mechanical stress applied
  • Blood supply
  • Denervation
  • Protection used
  • Size of haematoma formed
  • Amount of necrotic tissue
  • Size of wound
  • Surgical techniques
62
Q

List some systemic factors which may influence the efficacy of wound healing:

A
  • Age
  • General health
  • Obesity
  • Drugs
  • O2 delivery (anaemia/hypovolaemia/hypoxia)
  • Genetic disorders
  • Dietary deficiencies
63
Q

How do steroids affect wound healing and repair?

A

Delay, as inhibit collagen synthesis

64
Q

How do antibiotics affect wound healing and repair?

A

Speed up, as prevent infection occurring

65
Q

What are the main complications of fibrous repair?

A
  • Insufficient fibrosis
  • Excessive fibrosis
  • Excessive contraction
66
Q

What factors can increase the risk of insufficient fibrosis during wound healing and repair?

A
  • Increasing age
  • Dietary insufficiencies
  • Obesity
  • Steroids
67
Q

What is a keloid?

A

Overgrowth of fibrous tissue due to an overproduction of collagen, which exceeds the border of the scar (expands outside the border of the original damage)

68
Q

Which ethnicity is most at risk of keloid formation?

A

Afro-Caribbean

69
Q

Which complication of fibrous repair may lead to strictures or contractures?

A

Excessive contraction

70
Q

Which complication of fibrous repair may lead to keloid formation?

A

Excessive fibrosis (collagen synthesis)

71
Q

Can cardiac muscle regenerate?

72
Q

What is the outcome of repair in cardiac muscle?

A

Scar formation

73
Q

Can the liver regenerate?

74
Q

What type of cell is activated by hepatocyte damage?

A

Hepatic stellate cell

75
Q

What is the role of a hepatic stellate cell in liver repair?

A
  • Activates macrophages
  • Secretes pro-inflammatories/cytokines to recruit T cells and Neutrophils
  • Transdifferentiates into myofibroblasts
76
Q

What cell type can a hepatic stellate cell transdifferentiate into?

A

Myofibroblast

77
Q

What is the role of myofibroblasts in liver repair?

A
  • Proliferation

- Deposit Collagen type I

78
Q

What type of collagen is deposited in liver repair?

A

Collagen type I

79
Q

If the cause of injury to the liver is removed, what happens in the liver? (If cirrhosis has not occurred)

A
  • Myofibroblasts transdifferentiate back into hepatic stellate cells
  • Collagen is broken down and removed
  • Hepatocyte regeneration
80
Q

Can a peripheral nerve regenerate?

81
Q

What is the speed of axon growth during repair?

A

~ 1-3 mm/day

82
Q

Can cartilage regenerate?

83
Q

Why can’t cartilage repair itself following damage?

A

Cartilage is avascular, and lacks lymph drainage and innervation

84
Q

What may the body replace hyaline cartilage with if damaged?

A

Fibrocartilage

85
Q

Can the CNS regenerate?

86
Q 
Which of the following can regenerate?
Cardiac muscle cells
Liver cells
Peripheral nerves
CNS
A

Liver cells

Peripheral nerves

87
Q

Which cell type inhibits axon repair and/or remyelination in the CNS?

A

Oligodendrocytes

88
Q

What is the automatic response of the CNS to injury?

A

Gliosis formation (scar) to prevent spread of damage

89
Q

What forms in the CNS due to injury, to prevent spread of damage?

90
Q

What is the most common cause of oesophageal strictures?

A

Acid reflux

91
Q

Name some symptoms of an oesophageal stricture:

A
  • Trouble/pain when swallowing
  • Unintentional weight loss
  • Regurgitation of food
92
Q

What causes Marfan syndrome?

A

Inherited defective fibrillin-1 gene

93
Q

Name some complications associated with Marfan syndrome:

A
  • Aortic dissection
  • Valve malformation
  • Early Cataracts/Glaucoma
  • Lens dislocation
  • Retina tear
  • Abnormal spinal curvatures

ESA2 (27 decks)

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