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Mechanisms of Disease > Lecture 4.1: Healing, Regeneration & Repair > Flashcards

Lecture 4.1: Healing, Regeneration & Repair Flashcards

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1
Q

What processes are involved in wound healing?

A

1) Haemostasis
2) Inflammation
3) Regeneration (resolution, restitution) and/or repair (organisation)

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2
Q

What is Regeneration?

A

• Restitution with no, or minimal, evidence that there was a previous injury
• Healing by primary intention

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3
Q

Abrasions vs Ulcers

A

• Abrasions are from superficial scrapes
• Ulcers are from deeper “gouges,” from invasion/infection of a more superficial
injury by bacteria or another pathogen

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4
Q

What are Stem Cells?

A

• Prolonged proliferative activity
• Show asymmetric replication
• ‘Internal repair system’ to replace lost or damaged cells in tissues

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5
Q

Where are Stem Cells in the Epidermis?

A

Basal layer adjacent to the basement membrane

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6
Q

Where are Stem Cells in the Liver?

A

Between hepatocytes and bile ducts

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7
Q

Where are Stem Cells in the Intestinal Mucosa?

A

Bottom of Crypts of Lieberkuhn

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8
Q

Types of Stem Cells: Unipotent

A

• Most adult stem cells
• Only produce one type of differentiated cell (e.g.
epithelia)

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9
Q

Types of Stem Cells: Multipotent

A

• Produce several types of differentiated cell (e.g.
haematopoietic stem cells)

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10
Q

Types of Stem Cells: Totipotent

A

• Embryonic stem cells
• Can produce any type of cell and therefore any
tissues of the body

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11
Q

What types of tissues can regenerate?

A

Labile Tissues

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12
Q

What is Fibrous Repair (Organisation)?

A

• Healing with formation of fibrous connective
tissue = scar
• Specialised tissue is lost
• Healing by secondary intention

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13
Q

When does Fibrous Repair occur?

A

• Significant tissue loss
• If permanent or complex tissue is injured

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14
Q

What types of tissue that cannot regenerate?

A

Permanent/Stable Tissues

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15
Q

How does a scar form? Chronological order?

A

• Seconds - Minutes: Haemostasis
• Minutes - Hours: Acute Inflammation
• 1-2 Days: Chronic Inflammation
• 3 Days: Granulation Tissue Forms
• 7-10 Days: Early Scar
• Weeks – 2 Years: Scar Maturation

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16
Q

What is Granulation Tissue composed of?

A

• Developing Capillaries
• Fibroblasts and Myofibroblasts
• Chronic Inflammatory Cells

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17
Q

Functions of Granulation Tissue

A

• Fills the gap
• Capillaries supply oxygen, nutrients and cells
• Contracts and closes the hole

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18
Q

What is the Process of Fibrous Repair?

A

1) Blood Clots
2) Neutrophils infiltrate and digest clot
3) Macrophages and Lymphocytes are recruited
4) Blood vessels spout myo/fibroblasts that make
glycoproteins
5) Vascular network, collagen synthesised,
macrophages reduced
6) Maturity, cells much reduced, collagen
matures, contraction + remodelling

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19
Q

What is the most common types of Collagen?

A

Type I

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20
Q

What type of collagen makes up basement membranes?

A

Type IV

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21
Q

How long does Synthesis of Fibrillar Collagens take?

Study These Flashcards
A

• Whole process takes 1-2 hours

22
Q

How are Fibrillar Collagens made?

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A

• Polypeptide alpha chains synthesised in ER of
fibroblasts & myofibroblasts
• Enzymatic modification steps including vitamin
C dependent hydroxylation
• Alpha chains align and cross-link to form
procollagen triple helix
• Soluble procollagen is secreted
• Procollagen cleaved to give tropocollagen
• Tropocollagen polymerises to form microfibrils
and then fibrils
• Bundles of fibrils form fibres
• Cross-linking between molecules produces
tensile strength
• Slow remodelling by specific collagenases

23
Q

Defective Collagen Diseases: Scurvy

Study These Flashcards
A

• It is acquired
• Inadequate vitamin C dependent hydroxylation of procollagen alpha chains
• Leads to reduced cross-linking and defective helix formation
• Leading to gum ulceration and haemorrhage

24
Q

Defective Collagen Diseases: Ehlers-Danlos Syndrome

Study These Flashcards
A

• Defective conversion of procollagen to tropocollagen
• Collagen fibres lack adequate tensile strength
• Wound healing poor
• Skin is hyperextensible, thin, fragile and susceptible to injury

25
Defective Collagen Diseases: Osteogenesis Imperfecta
• Brittle Bone Disease • Too little bone tissue and therefore extreme skeletal fragility
26
Defective Collagen Diseases: Alport Syndrome
• Usually X-linked disease, therefore patients usually male • Type IV collagen abnormal • Dysfunction of glomerular basement membrane, cochlea of ear & lens of eye • Presents with haematuria in children/adolescents progressing to renal failure • Also neural deafness and eye disorders
27
Types of Cell Signalling: Autocrine
Cell signal released from the cell binds to the same cell, i.e., 'self'
28
Types of Cell Signalling: Paracrine
A cell produces a signal to induce changes in nearby cells
29
Types of Cell Signalling: Endocrine
The signalling molecules (hormones) are secreted by specialised endocrine cells and carried through the circulation to act on target cells at distant body sites
30
What are Growth Factors?
• Polypeptides that act on cell surface receptors • Bind to specific receptors, stimulate transcription of genes (tyrosine kinase) • These regulate entry of cell into cell cycle and the cell’s passage through it
31
What other effects can growth factors have? (7)
• Inhibition of division • Locomotion • Contractility • Differentiation • Viability • Activation • Angiogenesis
32
Types of Growth Factors (4)
• Epidermal growth factor • Vascular endothelial growth factor • Platelet derived growth factor • Tumour necrosis factor
33
What are Growth Factors produced by?
• Platelets • Macrophages • Endothelial cells
34
What binds cells together?
Cadherins
35
What binds the extracellular matrix of cells together?
Integrins
36
What is Contact Inhibition?
• Inhibits proliferation in intact tissue • Promotes proliferation in damaged tissues • Altered in malignant cells
37
What is Healing by Primary Intention?
• When doctors close a wound • Using staples, stitches, glues, or other forms of wound-closing processes • Minimal clot and granulation tissue
38
What occurs in Healing by Primary Intention?
• Epidermis regenerates • Dermis undergoes fibrous repair • Sutures out at about 10 days - approximately 10% normal strength • Minimal contraction & scarring, good strength
39
What is Healing by Secondary Intention?
• A wound will be left open (rather than being stitched together) • Left to heal by itself, filling in and closing up naturally • Open wound filled by abundant granulation tissue • This grows in from wound margins
40
What occurs in healing by Secondary Intention?
• Considerable wound contraction must take place to close wound • Initially occurs as scab contracts when it dries and shrinks • After 1 week myofibroblasts appear and contract • Contracts as if margins are drawn into the centre • Substantial scar formation, new epidermis often thinner than usual
41
How does bone heal?
• Haematoma: fills gap and surrounds injury • Granulation tissue forms: cytokines activate osteoprogenitor cells • Soft callus: fibrous tissue and cartilage within which woven bone forms • Hard callus: weaker and less organised than lamellar bone • Lamellar bone: replaces woven bone, remodelled, outline re-established
42
How does bone heal?
• Haematoma: fills gap and surrounds injury • Granulation tissue forms: cytokines activate osteoprogenitor cells • Soft callus: fibrous tissue and cartilage within which woven bone forms • Hard callus: weaker and less organised than lamellar bone • Lamellar bone: replaces woven bone, remodelled, outline re-established
43
What local factors can influence wound healing? (5)
1) Type, size, location of wound 2) Mechanical stress 3) Blood supply 4) Local infection 5) Foreign bodies
44
What general factors can influence wound healing? (8)
1) Age 2) Anaemia, hypoxia and hypovolaemia 3) Obesity 4) Diabetes 5) Genetic disorders 6) Drugs 7) Vitamin deficiency 8) Malnutrition
45
Complications of Fibrous Repair: Insufficient Fibrosis
• Wound dehiscence, hernia, ulceration • For example obesity, elderly, malnutrition, steroids
46
Complications of Fibrous Repair: Formation of Adhesions
• Compromising organ function or blocking tubes • E.g. intestinal obstruction following abdominal surgery
47
Complications of Fibrous Repair: Loss of Function
• Due to replacement of specialised functional parenchymal cells by scar tissue • E.g. healed myocardial infarction with non- contracting area of myocardium
48
Complications of Fibrous Repair: Disruption of complex tissue relationships within an organ
• Distortion of architecture interfering with normal function • E.g. liver cirrhosis
49
Complications of Fibrous Repair: Overproduction of Fibrous Scar Tissue
• Keloid Scar
50
Complications of Fibrous Repair: Excessive Scar Contraction
• Can cause obstruction of tubes • Disfiguring scars following burns or joint contractures (Fixed Flexures)

Mechanisms of Disease (11 decks)

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