MOD 5 Healing and Repair Flashcards Preview

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Flashcards in MOD 5 Healing and Repair Deck (53):

What is fibrous repair?

The replacement of functional tissue by scar tissue


What is regeneration?

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


What are differentiated cells derived from?

stem cells


What happens to daughter cells of proliferated stem cells?

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


What are the functions of stem cells?

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


What does unipotent mean?

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


What does multipotent mean?

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


What does totipotent mean?

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


What are labile cells?

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


What are stable cells?

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


What are permanent cells?

Cells that are unable to divide and regenerate
e.g neurones, cardiac mycocytes


What factors control regeneration?

Growth factors
Contact between basement membranes and adjacent cells


What do growth factors do?

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


What are examples of growth factors?

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


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

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


What are the key components of fibrous repair?

Cell migration
Blood vessels- angiogenesis
Extracellular matrix production and remodelling


What inititates fibrous repair?

The formation of granulation tissue


What kind of cells migrate to the area?

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


What is angiogenesis?

The development of a blood supply to the wound


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

Provides acces for inflammatory cells and fibroblasts
Delivery of oxygen and other nutrients


What is endothelial proliferation induced by?

proangiogenic growth factors like VEGF


What are the steps in angiogenesis?

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


What is the function of the extracellular matrix?

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


What type of collagen is in the basement membrane?



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


Give some defects of collagen synthesis

Ehlers-Danlos Syndrome
Osteogenesis imperfecta
Alport syndrome


What do matrix glycoproteins do?

Organise and orientate cells, support cell migration
Fibronectin, laminin, tenascin


What do proteoglycans do?

Matrix organisation, cell support, regulate growth factor availability
e.g Heparan sulphate proteoglycan


What does elastin do?

Provide tissue elasticity


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


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


What us the blood clot replaced by?

Granulation tissue


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


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


How are inflammatory cells recruited?



How is angiogenesis controlled?

Platelets, ECM and others produce angiogenic cytokines in response to hypoxia e.g VEGF and bFGF


How is fibrosis controlled?

Macrophages produce various pro-fibrotic cytokines e.g IL1, TNF alpha
Fibroblast proliferation and ECM production


What type of wound heals by primary intention?

An incised wound with apposed edges


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


What is there a risk of in healing by primary intention?

Trapping infection-abscess


What type of wounds heal by secondary intention?

Infarct, ulcer, abscess or any large wound


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


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


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


What happens when cardiac muscle is injured?

Fibrosis occurs


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


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


Where does Wallerian degeneration occur?

Peripheral nervous system


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


Does skeletal muscle regenerate?

The muscle cells can't proliferate but some regeneration can occur due to differentiation of satellite cells


What local factors can affect wound healing?

Type size and location
Apposition and lack of movement
Blood supply
Foreign material
Radiation damage


What general factors affect wound healing?

Drugs and hormones
Dietary deficiencies
General health
General CVS health


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)