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ESA 2 SK > MOD 5 Healing and Repair > Flashcards

MOD 5 Healing and Repair Flashcards

1
Q

What is fibrous repair?

A

The replacement of functional tissue by scar tissue

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2
Q

What is regeneration?

A

The replacement of dead or damaged cells by functional, differentiated cells

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3
Q

What are differentiated cells derived from?

A

stem cells

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4
Q

What happens to daughter cells of proliferated stem cells?

A

Either remain as a stem cell to maintain stem cell pool or differentiates to a specialised cell type

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5
Q

What are the functions of stem cells?

A

In early life differentiate into many different cell types
Internal repair system to replace lost or damaged cells in tissues
Therapeutic utility in degenerative disease

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6
Q

What does unipotent mean?

A

Can only produce one type of differentiated cell e.g. epithelia

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7
Q

What does multipotent mean?

A

Can produce several types of differentiated cell e.g. haematopoietic

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8
Q

What does totipotent mean?

A

Can produce any type of cell e.g. embryonic stem cells

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9
Q

What are labile cells?

A

Continuously cycling cells whose normal state is active cell division
Usually rapid proliferation
e.g epithelial or haematopoietic cells

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10
Q

What are stable cells?

A

Cells who go into a resting state G0 after mitosis
They have varying speeds of regeneration
e.g. hepatocytes, osteoblasts, fibroblasts

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11
Q

What are permanent cells?

A

Cells that are unable to divide and regenerate

e.g neurones, cardiac mycocytes

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12
Q

What factors control regeneration?

A

Growth factors

Contact between basement membranes and adjacent cells

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13
Q

What do growth factors do?

A

Promote proliferation in stem cell population
Extracellular signals transduced into cell
Promote expression of genes controlling the cell cycle

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14
Q

What are examples of growth factors?

A

Proteins e.g. EGF, PDGF, FGF
Hormones e.g. oestrogen, testosterone, growth hormone
Autocrine, paracrine and endocrine signals from many cell types e.g inflammatory, mesenchymal
Some cytokines

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15
Q

How does contact between adjacent cells and basement membranes affect growth?

A 
Signalling through adhesion molecules
Inhibits  proliferation in intact tissue
'Contact inhibition'
Loss of contact promotes proliferation
These mechanisms deranged in cancer
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16
Q

What are the key components of fibrous repair?

A

Cell migration
Blood vessels- angiogenesis
Extracellular matrix production and remodelling

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17
Q

What inititates fibrous repair?

A

The formation of granulation tissue

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18
Q

What kind of cells migrate to the area?

A

Inflammatory cells
-Phagocytosis of debri: neutrophils, macrophages
Chemical mediators: lymphocytes, macrophages
Endothelial cells: angiogenesis
Fibroblasts/ Myofibroblasts: ECM proteins e.g. collagen, wound contraction

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19
Q

What is angiogenesis?

A

The development of a blood supply to the wound

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20
Q

Why is a blood supply needed for wound healing to occur?

A

Provides acces for inflammatory cells and fibroblasts

Delivery of oxygen and other nutrients

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21
Q

What is endothelial proliferation induced by?

A

proangiogenic growth factors like VEGF

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22
Q

What are the steps in angiogenesis?

A
  1. Endothelial proteolysis of basement membrane
  2. Migration of endothelial cells via chemotaxis
  3. Endothelial proliferation
  4. Endothelial maturation and tubular remodelling
  5. Recruitment of periendothelial cells
23
Q

What is the function of the extracellular matrix?

A 
Supports and anchors cells
Separates tissue compartments e.g basement membrane
Sequesters growth factors 
Allows communication between cells
Facilitates cell migration
24
Q

What type of collagen is in the basement membrane?

25
Give an overview of collagen synthesis
Polypeptide alpha chains made in ER Enzymatic modification steps including vitamin C dependent hydroxylation Alpha chains align and cross link to form procollagen triple helix Soluble procollagen secreted Procollagen cleaved to give tropocollagen Tropocollagen poymerises to form fibrils Bundles of fibrils form fibres which undergo slow remodelling by specific collagenases
26
Give some defects of collagen synthesis
Scurvy Ehlers-Danlos Syndrome Osteogenesis imperfecta Alport syndrome
27
What do matrix glycoproteins do?
Organise and orientate cells, support cell migration | Fibronectin, laminin, tenascin
28
What do proteoglycans do?
Matrix organisation, cell support, regulate growth factor availability e.g Heparan sulphate proteoglycan
29
What does elastin do?
Provide tissue elasticity
30
What is the rabbit ear chamber model?
An experiment done where plastic chamber surgically inserted into ear of lop eared rabbit Thin tissue bed develops between the layers of the chamber enabling in vivo microscopic visualisation of healing and repair
31
What are the first steps after a wound has occurred?
Blood clot forms Acute inflammation occurs around the edges: neutrophils infiltrate and digest clot Chronic inflammation: macrophages and lymphocytes migrate into clot
32
What us the blood clot replaced by?
Granulation tissue
33
What are the next steps after macrophage and lymphocyte infiltration?
Angiogenesis- capillaried and lymphatics sprout and infiltrate Myo/fibroblasts migrate and differentiate The myo/fibroblasts synthesis collagen and an extracellular matrix is produced Macrophage numbers reduce
34
What happens in maturation of a wound?
``` Comparatively long lasting Cell population falls Collagen increases, matures and remodels Myofibroblasts contract reducing wound volume Vessels differentiate and are reduced Left with fibrous scar ```
35
How are inflammatory cells recruited?
chemotaxis
36
How is angiogenesis controlled?
Platelets, ECM and others produce angiogenic cytokines in response to hypoxia e.g VEGF and bFGF
37
How is fibrosis controlled?
Macrophages produce various pro-fibrotic cytokines e.g IL1, TNF alpha Fibroblast proliferation and ECM production
38
What type of wound heals by primary intention?
An incised wound with apposed edges
39
What is the process of healing by primary intention?
Minimal clot and granulation tissue Epidermis regenerates Dermis undegoes fibrous repair Sutured- sutures removed after approx 10 days (10% original strength) Transition from granulation tissue to scar tissue Maturation of scar taking up to 2 years Minimal contraction and scarring, good strength
40
What is there a risk of in healing by primary intention?
Trapping infection-abscess
41
What type of wounds heal by secondary intention?
Infarct, ulcer, abscess or any large wound
42
What is the process of healing by secondary intention?
``` Unapposed edges Large clot dries to form scab/eschar Epidermis regenerates from base up Much more granulation tissue produced More contraction to reduce volume of defect Larger scar produced ```
43
What are the differences between primary intention healing and secondary intention healing?
More granulation tissue in secondary Eschar produced in secondary Unapposed edges, more contraction and larger scar produced in secondary Secondary takes longer
44
Give an overview of fracture repair?
HAEMATOMA forms from ruptured vessels within marrow cavity and periosteum SOFT CALLUS forms as haematoma organises and there is an ingress of macrophages, endothelial cells, fibroblasts and osteoblasts HARD CALLUS forms as bone is laid down in an irregular woven pattern sometimes with islands of cartilage REMODELLING occurs as woven bone gradually replaced by lamellar bone which is remodelled to shape in the direction of mechanical stress
45
What happens when cardiac muscle is injured?
Fibrosis occurs
46
What happens when there is liver injury?
Acute damage->regeneration Chronic damage->cirrhosis Liver hepatocytes have some regenerative capacity but the architecture cannot regenerate. The imbalance that occurs between these leads to nodules and cirrhosis
47
What occurs in Wallerian degeneration?
Nerve axons have been cut and there is corresponding atrophy in the muscle and degeneration of distal axons Proximal nerve terminals send sprouts towards the schwann cell tubes Some of the sprouts make it into the tubes and reinnervate the muscle which has undergone neurogenic rearrangement
48
Where does Wallerian degeneration occur?
Peripheral nervous system
49
What happens when there is damage to the CNS
The CNS has no regenerative capacity | Gliosis occurs where astrocytes enlarge and proliferate to form a glial scar which blocks axonal growth
50
Does skeletal muscle regenerate?
The muscle cells can't proliferate but some regeneration can occur due to differentiation of satellite cells
51
What local factors can affect wound healing?
``` Type size and location Apposition and lack of movement Blood supply Infection Foreign material Radiation damage ```
52
What general factors affect wound healing?
``` Age Drugs and hormones Dietary deficiencies General health General CVS health ```
53
What are some complications of wound healing?
Insufficient fibrosis- hernia, wound dehiscence, ulceration. Found in elderly, obese, malnutrition etc, Excessive fibrosis- keloid, excessive scarring, lung fibrosis, cirrhosis Excessive contraction- occluding channels(strictures), limiting movement (contractures)

ESA 2 SK (35 decks)

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