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M1 General Pathology > Wound Healing and Repair > Flashcards

Wound Healing and Repair Flashcards

1
Q

What is healing?

A

A repair process consisting of 2 parallel ongoing processes:
(i) regeneration and (ii) organisation/fibrous tissue (scar) formation

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2
Q

What is regeneration?

A

The growth of cells/tissues to replace lost structures and restore normal architecture.

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3
Q

What is organisation?

A

Conversion of an inflammatory exudate into a fibrous scar

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4
Q

What is fibrosis?

A

The accumulation of excessive amounts of fibrous tissue (complication of healing)

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5
Q

What is resolution?

A

The complete disappearance of inflammatory exudate

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6
Q

Why is there loss of function in healing?

A

Fibrous tissue repair producing non-native, non-functional fibrous tissue

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7
Q

Does healing occur after inflammation?

A

no, they are concurrent

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8
Q

What is the different between regeneration and repair?

A

Endpoint (original tissue restoration vs fibrous scar)

Loss of function

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9
Q

What are the 5 steps of healing?

A

1) Hemostasis + inflammation
2) Granulation tissue + angiogenesis
3) ECM deposition
4) Re-epithelialisation
5) Scar formation and remodelling

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10
Q

Why are macrophages important in wound healing?

A

1) Clear site of cell debris (neutrophils and exudate)

2) Secrete cytokines and growth factor → ECM synthesis

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11
Q

What is a prominent effect of macrophage deficiency?

A

Delayed wound healing

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12
Q

What are the components of the ECM?

A

1) Collagen
2) Proteoglycan
3) Hyaluronic acid
4) Elastin
5) Fibronectin
6) Laminin

Cell adhesion molecules
1) Cadherins
2) Integrins
3) Selectins
4) Ig Superfamily

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13
Q

What are the prerequisites to tissue regeneration?

A

1) must contain pluripotent cells
2) underlying ECM scaffold must be intact as good support

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14
Q

What are the 3 classification of cells with regards to their ability to regenerate?

A

1) Labile (always in cell cycle)
2) Stable (usually in G0 but can be stimulated to enter cell cycle)
3) Permanent (always in G0/cannot divide)

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15
Q

Why do myocardial infarctions often result in hyperplasia?

A

cardiomyocytes are permanent so those which survive under go hypertrophy to compensate

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16
Q

What structure does granulation tissue grow from?

A

Basement membrane

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17
Q

What are the 1st 3 steps of repair?

A

1) Proliferation of cells
2) Angiogenesis
3) ECM deposition

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18
Q

What are the 3 classes of cells involved in granulation tissue formation?

A

1) Inflammatory/immune cells
2) Vascular connective tissue cells (endothelial, RBCs → angiogenesis)
3) Fibroblasts → ECM deposition

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19
Q

Where do myofibroblasts come from?

A

1) resident/circulating fibroblast
2) mesenchymal transformation (from regenerating immature epithelial/endothelial cells)

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20
Q

What are the 3 functions of myofibroblasts?

A

1) Secrete ECM (collagen)
2) Wound contraction (exp. smooth muscle actin and myosin)
3) Undergo apoptosis after healing

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21
Q

What are the cytokines that promote myofibroblast migration?

A

TNF, PDGF, TGF-ß, FGF

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22
Q

What are the cytokines that promote myofibroblast proliferation?

A

PDGF, EGF, TGF-ß, IL-1, TNF

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23
Q

How long after injury does angiogenesis occur?

A

48-72hrs

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24
Q

Describe the mechanism of angiogenesis

A

1) Endothelial cells divide to form sprouts

2) Sprouts develop a lumen (by fusion of intracytoplasmic vacuoles containing RBCs) → formation of capillaries

3) Capillaries join to form arborising vascular network

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25
Q

What happens to blood vessels formed from angiogenesis as a wound heals?

A

They undergo involution/resorption.

26
Q

Does wound contraction occur before or after granulation tissue formation?

A

After

27
Q

Does collagen remodelling begin before or after wound contraction?

A

neither, they are concurrent

28
Q

What nutrient is required in collagen synthesis and maturation?

A

Vitamin C

29
Q

When does collagen synthesis occur?

A

Begins 1 day post-injury, significant accumulation after day 4

30
Q

What is the process of collagen synthesis and maturation?

A

1) Collagen III provisional matrix
2) Replacement with collagen I
3) Rearrangement along new lines of stress

31
Q

How does the collagen in a site of repair change during scar formation?

A
  • initially type III
  • replace w type I
32
Q

How does synthesised collagen develop tensile strength?

A

Development of cross-linkages

33
Q

What is the relationship between collagen synthesis, tensile strength and mature collagen?

A

Mature collagen and tensile strength share a positive correlation, while collagen synthesis decreases.

34
Q

What are 5 local factors affecting wound healing?

A

1) Type, size, location
2) Local vascular supply
3) Secondary infection
4) Movement
5) Others (eg. radiation)

35
Q

What are 5 systemic factors affecting wound healing?

A

1) Age
2) Circulation status
3) Nutrition
4) Metabolic status (eg. DM)
5) Endocrinopathies (eg. hypothyroidism, Cushing’s syndrome)

36
Q

What are 3 complications of wound healing?

A

1) Defective scar formation (eg. wound dehiscence, incisional hernias)
2) Excessive scar tissue formation (eg. hypertrophic scar and keloid formation)
3) Excessive contraction (eg. contracture formation)

37
Q

What are the 2 types of healing in response to skin injuries?

A

1) healing by primary intention
2) healing by secondary intention

38
Q

What differentiates healing by primary intention from healing by secondary intention?

A

Healing by primary intention
- closely apposed edges
- minimal hematoma

Healing by secondary intention
- large gaping wounds w non-apposed edges
-&raquo_space;inflammation and angiogenesis (granulation tissue formation)
-&raquo_space;tissue fibrosis and wound contraction (↑time to cover)

39
Q

What are the 4 fates of a cutaneous abscess?

A

1) Scarring
2) Sinus
3) Fistula
4) Cyst

40
Q

What is the common result for chronic peptic ulcers?

A

Fibrous scarring with a loss of contractility

41
Q

What are 5 possible complications in the healing of chronic peptic ulcers?

A

1) ↓contractility
2) ↑chance of fistula
3) ↑chance of rupture
4) bleeding
5) peritonitis

42
Q

What is the common result of myocardial infarctions?

A

Fibrous repair and hypertrophy

43
Q

What are 3 possible complications of healing after a myocardial infarct?

A

1) Aneurysm (thromboemboli → peripheral ischaemia/stroke)
2) Rupture → pericardial effusion
3) Arrythmia (if nodes/bundle of His/purkinje fibers are affected)

44
Q

How can a lung heal post-infection/pneumonia?

A

1) Basement membrane intact
- Type 2 pneumocytes re-epithelialise and differentiate into type 1 pneumocytes
- complete resolution w minimal scarring

2) Basement membrane damaged
- intra-alveolar/interstitial organisation
- fibrous scarring

45
Q

In healing by primary intention does re-epithelialisation occur before or after angiogenesis?

A

Before

46
Q

Where are the stem cells in the liver?

A

At the sinusoids near the bile ducts

47
Q

What degree of regenerative capacity are hepatocytes?

A

Stable

48
Q

When can Liver damage be healing with complete resolution?

A

In acute injury if connective tissue stroma, vasculature, and bile ducts survive

49
Q

When does Liver damage lead to cirrhosis?

A

In chronic/persistent liver injury

50
Q

What are some potential complications to liver damage?

A

1) portal hypertension → bleeding
2) Hypoalbuminemia → edema → Heart failure, susceptibility to infection, immunosuppression

51
Q

How does Glomerular injury normally heal?

A

by fibrosis

52
Q

How does damage to the cortical tubule usually heal?

A

can regenerate rapidly if not prolonged and tubular membrane is undisrupted

53
Q

How does damage to the medullary tubule usually heal?

A

By fibrosis (usually associated with damage to the interstitium and blood vessels

54
Q

How do mature neurons usually heal?

A

They don’t regenerate ALTHOUGH axons can regenerate if cell body is undamaged (under the right conditions)

55
Q

How does damage in Gliosis usually heal?

A

via proliferation of glial cells → with fibrous scarring

56
Q

Can spinal cord injuries regenerate?

A

Axonal regeneration possible <2 weeks after injury

57
Q

Outline how fracture healing occurs?

A

1) initially bridged by hematoma
2) bridged by granulation tissue and collagenous fibrous tissue
3) osteoblasts proliferation from endo and periosteum → deposit new immature woven bone → callus
4) osteoclasts remodel bone with formation of mature lamellar bone

58
Q

Why is a fracture unstable a few days into healing?

A

The callus (immature woven bone) has no strength and tears easily.

59
Q

How is stronger bone formed after a fracture?

A

The callus is remodelled by osteoclasts while mature lamellar bone with good tensile strength is formed.

60
Q

What are some possible complications of fracture healing?

A

1) non-union
2) fibrous union → pseudoarthrosis (false joint) → unstable
3) malunion (w angulation) → mildly unstable
4) osteomyelitis (infection) esp in open fracture

61
Q

What chemicals are critical in fracture healing?

A

HIF-1α → VEGF → PIGF

M1 General Pathology (4 decks)

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