Wound Healing and Repair Flashcards by Wei Shynn Tan

What is healing?

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

How well did you know this?

Not at all

Perfectly

What is regeneration?

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

How well did you know this?

Not at all

Perfectly

What is organisation?

Conversion of an inflammatory exudate into a fibrous scar

How well did you know this?

Not at all

Perfectly

What is fibrosis?

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

How well did you know this?

Not at all

Perfectly

What is resolution?

The complete disappearance of inflammatory exudate

How well did you know this?

Not at all

Perfectly

Why is there loss of function in healing?

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

How well did you know this?

Not at all

Perfectly

Does healing occur after inflammation?

no, they are concurrent

How well did you know this?

Not at all

Perfectly

What is the different between regeneration and repair?

Endpoint (original tissue restoration vs fibrous scar)

Loss of function

How well did you know this?

Not at all

Perfectly

What are the 5 steps of healing?

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

How well did you know this?

Not at all

Perfectly

Why are macrophages important in wound healing?

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

2) Secrete cytokines and growth factor → ECM synthesis

How well did you know this?

Not at all

Perfectly

What is a prominent effect of macrophage deficiency?

Delayed wound healing

How well did you know this?

Not at all

Perfectly

What are the components of the ECM?

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

How well did you know this?

Not at all

Perfectly

What are the prerequisites to tissue regeneration?

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

How well did you know this?

Not at all

Perfectly

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

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)

How well did you know this?

Not at all

Perfectly

Why do myocardial infarctions often result in hyperplasia?

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

How well did you know this?

Not at all

Perfectly

What structure does granulation tissue grow from?

Basement membrane

How well did you know this?

Not at all

Perfectly

What are the 1st 3 steps of repair?

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

How well did you know this?

Not at all

Perfectly

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

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

How well did you know this?

Not at all

Perfectly

Where do myofibroblasts come from?

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

How well did you know this?

Not at all

Perfectly

What are the 3 functions of myofibroblasts?

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

How well did you know this?

Not at all

Perfectly

What are the cytokines that promote myofibroblast migration?

TNF, PDGF, TGF-ß, FGF

How well did you know this?

Not at all

Perfectly

What are the cytokines that promote myofibroblast proliferation?

PDGF, EGF, TGF-ß, IL-1, TNF

How well did you know this?

Not at all

Perfectly

How long after injury does angiogenesis occur?

48-72hrs

How well did you know this?

Not at all

Perfectly

Describe the mechanism of angiogenesis

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

How well did you know this?

Not at all

Perfectly

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

They undergo involution/resorption.

Does wound contraction occur before or after granulation tissue formation?

After

Does collagen remodelling begin before or after wound contraction?

neither, they are concurrent

What nutrient is required in collagen synthesis and maturation?

Vitamin C

When does collagen synthesis occur?

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

What is the process of collagen synthesis and maturation?

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

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

- initially type III - replace w type I

How does synthesised collagen develop tensile strength?

Development of cross-linkages

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

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

What are 5 local factors affecting wound healing?

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

What are 5 systemic factors affecting wound healing?

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

What are 3 complications of wound healing?

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)

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

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

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

Healing by primary intention - closely apposed edges - minimal hematoma Healing by secondary intention - large gaping wounds w non-apposed edges - >>inflammation and angiogenesis (granulation tissue formation) - >>tissue fibrosis and wound contraction (↑time to cover)

What are the 4 fates of a cutaneous abscess?

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

What is the common result for chronic peptic ulcers?

Fibrous scarring with a loss of contractility

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

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

What is the common result of myocardial infarctions?

Fibrous repair and hypertrophy

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

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

How can a lung heal post-infection/pneumonia?

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

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

Before

Where are the stem cells in the liver?

At the sinusoids near the bile ducts

What degree of regenerative capacity are hepatocytes?

Stable

When can Liver damage be healing with complete resolution?

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

When does Liver damage lead to cirrhosis?

In chronic/persistent liver injury

What are some potential complications to liver damage?

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

How does Glomerular injury normally heal?

by fibrosis

How does damage to the cortical tubule usually heal?

can regenerate rapidly if not prolonged and tubular membrane is undisrupted

How does damage to the medullary tubule usually heal?

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

How do mature neurons usually heal?

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

How does damage in Gliosis usually heal?

via proliferation of glial cells → with fibrous scarring

Can spinal cord injuries regenerate?

Axonal regeneration possible <2 weeks after injury

Outline how fracture healing occurs?

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

Why is a fracture unstable a few days into healing?

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

How is stronger bone formed after a fracture?

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

What are some possible complications of fracture healing?

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

What chemicals are critical in fracture healing?

HIF-1α → VEGF → PIGF