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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
What is Alport syndrome?
Inherited disease affecting type IV collagen primarily in kidneys, cochlea and lens of eye. Causes kidney failure, cataracts, progressive hearing loss, oedema
26
What is the name of the inherited condition which causes progressive fibrous repair of type IV collagen in the body?
Alport syndrome
27
Define growth factor:
Polypeptide coded for by proto-oncogenes, which act on specific cell surface receptors, stimulating gene transcription
28
In what types of cells does Epidermal Growth Factor cause mitosis?
- Epithelial cells - Hepatocytes - Fibroblasts
29
What type of cells produce Epidermal Growth Factor?
- Keratinocytes | - Inflammatory cells (ie macrophages)
30
What does VEGF stand for?
Vascular Endothelial Growth Factor
31
What does VEGF cause?
- Angiogenesis - Vasculogenesis - Chronic inflammation - Wound healing
32
Define vasculogenesis:
Process of new blood vessel formation during embryonic development of the CVS
33
What does PDGF stand for?
Platelet Derived Growth Factor
34
Which cells can produce/release PDGF?
- Platelets - Macrophages - Smooth muscle cells - Endothelial cells - Tumour cells
35
What is the role of PDGF?
Causes migration and proliferation of fibroblasts, smooth muscle cells and monocytes
36
What does G-CSF stand for?
Granulocyte-Colony Stimulating Factor
37
What is the role of G-CSF?
Stimulates bone marrow to produce granulocytes (ie neutrophils)
38
What does TNF stand for?
Tumour Necrosis Factor
39
What is the role of TNF?
Induces fibroblast migration and proliferation, and collagenase secretion
40
What is the role of Cadherins?
Bind cell to each other
41
What is the role of Integrins?
Bind cells to the extracellular matrix
42
Describe the wound appearance if it is healing by primary intention:
- Opposed edges - Clean cut (via scalpel) - May be sutured
43
What are the 6 stages of wound healing?
1) Haemostasis 2) Inflammation 3) Cell migration 4) Regeneration 5) Scarring 6) Scar maturation
44
What is the 1st stage of wound healing, and what does it involve?
Haemostasis | Arteries contract, clotted blood fills space and dehydrates, forming a scab
45
What is the function of a scab in wound healing?
Prevents infection | Seals wound from outside environment
46
What is the 2nd stage of wound healing and what does it involve?
Inflammation | Neutrophils gather at the margins of the wound
47
What is the 3rd stage of wound healing and what does it involve?
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
What are the functions of Macrophages in wound healing?
- Phagocytose dead neutrophils and necrotic tissue | - Secrete cytokines for fibroblasts and endothelial cells
49
What is the function of endothelial cells in wound healing?
Angiogenesis
50
What is the role of basal epidermal cells in wound healing?
Deposit basement membrane
51
What is the 4th stage of wound healing and what does it involve?
``` Regeneration Formation of granulation tissue Proliferation of epithelial cells Scab falls off Activated fibroblasts secrete collagen ```
52
In which stage of wound healing does granulation tissue form?
Regeneration stage ~ 3 days after trauma
53
What is the 5th stage of wound healing, and what does it involve?
``` Scarring Fibroblasts proliferate and form scar Epidermis keratinises (no sweat glands/hair follicles) WBCs and Oedema disappears Vascular channels regress ```
54
What is the 6th stage of wound healing and what does it involve?
Scar maturation Type III collagen is gradually replaced by type I collagen May contract via myofibroblasts
55
In which direction does wound healing take place if healing by primary intention?
From the surface downwards
56
In which direction does healing take place if healing by secondary intention?
From the bottom up, towards the surface
57
What is the risk involved with healing by primary intention?
Infection may be trapped below sutures, may cause abscess formation
58
Describe the wound appearance if it is healing by secondary intention:
- Unopposed edges | - Large amount of tissue lost (due to infarct/abscess/ulcer/infection)
59
Apart from the appearance of the wound, what is the difference between healing by primary and secondary intention?
Healing by secondary involves: - More clot formation - More necrotic debris produced - Increased inflammatory reaction - More granulation tissue formed - May require contraction
60
Which cell type mediates contraction of a wound?
Myofibroflast
61
List some local factors which may influence the efficacy of wound healing:
- 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
List some systemic factors which may influence the efficacy of wound healing:
- Age - General health - Obesity - Drugs - O2 delivery (anaemia/hypovolaemia/hypoxia) - Genetic disorders - Dietary deficiencies
63
How do steroids affect wound healing and repair?
Delay, as inhibit collagen synthesis
64
How do antibiotics affect wound healing and repair?
Speed up, as prevent infection occurring
65
What are the main complications of fibrous repair?
- Insufficient fibrosis - Excessive fibrosis - Excessive contraction
66
What factors can increase the risk of insufficient fibrosis during wound healing and repair?
- Increasing age - Dietary insufficiencies - Obesity - Steroids
67
What is a keloid?
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
Which ethnicity is most at risk of keloid formation?
Afro-Caribbean
69
Which complication of fibrous repair may lead to strictures or contractures?
Excessive contraction
70
Which complication of fibrous repair may lead to keloid formation?
Excessive fibrosis (collagen synthesis)
71
Can cardiac muscle regenerate?
No
72
What is the outcome of repair in cardiac muscle?
Scar formation
73
Can the liver regenerate?
Yes
74
What type of cell is activated by hepatocyte damage?
Hepatic stellate cell
75
What is the role of a hepatic stellate cell in liver repair?
- Activates macrophages - Secretes pro-inflammatories/cytokines to recruit T cells and Neutrophils - Transdifferentiates into myofibroblasts
76
What cell type can a hepatic stellate cell transdifferentiate into?
Myofibroblast
77
What is the role of myofibroblasts in liver repair?
- Proliferation | - Deposit Collagen type I
78
What type of collagen is deposited in liver repair?
Collagen type I
79
If the cause of injury to the liver is removed, what happens in the liver? (If cirrhosis has not occurred)
- Myofibroblasts transdifferentiate back into hepatic stellate cells - Collagen is broken down and removed - Hepatocyte regeneration
80
Can a peripheral nerve regenerate?
Yes
81
What is the speed of axon growth during repair?
~ 1-3 mm/day
82
Can cartilage regenerate?
No
83
Why can't cartilage repair itself following damage?
Cartilage is avascular, and lacks lymph drainage and innervation
84
What may the body replace hyaline cartilage with if damaged?
Fibrocartilage
85
Can the CNS regenerate?
Yes
86
``` Which of the following can regenerate? Cardiac muscle cells Liver cells Peripheral nerves CNS ```
Liver cells | Peripheral nerves
87
Which cell type inhibits axon repair and/or remyelination in the CNS?
Oligodendrocytes
88
What is the automatic response of the CNS to injury?
Gliosis formation (scar) to prevent spread of damage
89
What forms in the CNS due to injury, to prevent spread of damage?
Gliosis
90
What is the most common cause of oesophageal strictures?
Acid reflux
91
Name some symptoms of an oesophageal stricture:
- Trouble/pain when swallowing - Unintentional weight loss - Regurgitation of food
92
What causes Marfan syndrome?
Inherited defective fibrillin-1 gene
93
Name some complications associated with Marfan syndrome:
- Aortic dissection - Valve malformation - Early Cataracts/Glaucoma - Lens dislocation - Retina tear - Abnormal spinal curvatures

ESA2 (27 decks)

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