MoD 4 (Healing & Repair) Flashcards Preview

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Flashcards in MoD 4 (Healing & Repair) Deck (93):
1

Define regeneration:

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

2

Define 'labile' tissue:

Tissue with continuously dividing cells

3

Define 'stable' tissue:

Tissue with quiescent cells

4

What is a quiescent cell?

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

5

Where can labile cells be found?

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

6

Where can stable cells be found?

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

7

Define 'permanent' tissue:

Tissue containing non-dividing, terminally differentiated cells

8

Where can permanent cells be found?

- Neurones
- Skeletal muscle cells
- Cardiac muscle cells

9

What type of cell undergoes asymmetric replication?

Stem cells

10

What is meant by asymmetric replication?

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

11

Define fibrous repair:

The replacement of functional tissue with scar tissue

12

Fibrous repair occurs in response to what 3 triggers?

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

13

What cell types are required for fibrous repair?

Fibroblasts/Myofibroblasts
Endothelial cells
Inflammatory cells
- Neutrophils
- Macrophages
- Lymphocytes

14

What is the role of endothelial cells in fibrous repair?

Angiogenesis

15

What is the role of fibroblasts in fibrous repair?

Synthesis of extracellular matrix proteins

16

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

Phagocytosis of debris

17

Which growth factor stimulates angiogenesis?

VEGF

18

Describe the key steps in angiogenesis:

- 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

19

What is Scurvy caused by?

Vitamin C deficiency

20

What is Scurvy?

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

21

What are the symptoms of Scurvy?

Bleeding/swollen gums
Prolonged healing
Fatigue
Myalgia
Shortness of breath

22

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

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

23

What is Ehlers-Danlos syndrome?

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

24

What are the symptoms of Ehlers-Danlos syndrome?

- Hypermobility of joints
- Hperextensible fragile skin
- Poor wound healing

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