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

Lecture 4.1: Healing, Regeneration & Repair Flashcards

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?

A

• Whole process takes 1-2 hours

22
Q

How are Fibrillar Collagens made?

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

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

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
Q

Defective Collagen Diseases: Osteogenesis Imperfecta

A

• Brittle Bone Disease
• Too little bone tissue and therefore extreme skeletal fragility

26
Q

Defective Collagen Diseases: Alport Syndrome

A

• 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
Q

Types of Cell Signalling: Autocrine

A

Cell signal released from the cell binds to the same cell, i.e., ‘self’

28
Q

Types of Cell Signalling: Paracrine

A

A cell produces a signal to induce changes in nearby cells

29
Q

Types of Cell Signalling: Endocrine

A

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
Q

What are Growth Factors?

A

• 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
Q

What other effects can growth factors have? (7)

A

• Inhibition of division
• Locomotion
• Contractility
• Differentiation
• Viability
• Activation
• Angiogenesis

32
Q

Types of Growth Factors (4)

A

• Epidermal growth factor
• Vascular endothelial growth factor
• Platelet derived growth factor
• Tumour necrosis factor

33
Q

What are Growth Factors produced by?

A

• Platelets
• Macrophages
• Endothelial cells

34
Q

What binds cells together?

A

Cadherins

35
Q

What binds the extracellular matrix of cells together?

A

Integrins

36
Q

What is Contact Inhibition?

A

• Inhibits proliferation in intact tissue
• Promotes proliferation in damaged tissues
• Altered in malignant cells

37
Q

What is Healing by Primary Intention?

A

• When doctors close a wound
• Using staples, stitches, glues, or other forms of
wound-closing processes
• Minimal clot and granulation tissue

38
Q

What occurs in Healing by Primary Intention?

A

• Epidermis regenerates
• Dermis undergoes fibrous repair
• Sutures out at about 10 days - approximately
10% normal strength
• Minimal contraction & scarring, good strength

39
Q

What is Healing by Secondary Intention?

A

• 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
Q

What occurs in healing by Secondary Intention?

A

• 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
Q

How does bone heal?

A

• 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
Q

How does bone heal?

A

• 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
Q

What local factors can influence wound healing? (5)

A

1) Type, size, location of wound
2) Mechanical stress
3) Blood supply
4) Local infection
5) Foreign bodies

44
Q

What general factors can influence wound healing? (8)

A

1) Age
2) Anaemia, hypoxia and hypovolaemia
3) Obesity
4) Diabetes
5) Genetic disorders
6) Drugs
7) Vitamin deficiency
8) Malnutrition

45
Q

Complications of Fibrous Repair: Insufficient Fibrosis

A

• Wound dehiscence, hernia, ulceration
• For example obesity, elderly, malnutrition, steroids

46
Q

Complications of Fibrous Repair: Formation of Adhesions

A

• Compromising organ function or blocking tubes
• E.g. intestinal obstruction following abdominal
surgery

47
Q

Complications of Fibrous Repair: Loss of Function

A

• Due to replacement of specialised functional
parenchymal cells by scar tissue
• E.g. healed myocardial infarction with non-
contracting area of myocardium

48
Q

Complications of Fibrous Repair: Disruption of complex tissue relationships within an organ

A

• Distortion of architecture interfering with normal
function
• E.g. liver cirrhosis

49
Q

Complications of Fibrous Repair: Overproduction of Fibrous Scar Tissue

A

• Keloid Scar

50
Q

Complications of Fibrous Repair: Excessive Scar Contraction

A

• Can cause obstruction of tubes
• Disfiguring scars following burns or joint contractures (Fixed Flexures)

Mechanisms of Disease (11 decks)

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