Healing And Repair Flashcards
3 components of fibrous repair?
Cell migration, angiogenesis, extracellular matrix
Define resolution
Subsidence of a pathological state
What cells are involved in fibrous repair?
Inflammatory cells such as neutrophils and macrophages
Chemical mediators such as lymphocytes and macrophages
Endothelial cells for angiogenesis
Fibroblasts and myoblasts for production of extracellular proteins like collagen and for wound contraction
What is fibrous repair?
Replacement of functional tissue by scar tissue
Why is angiogenesis important?
Provides access to the wound for cells
Delivers oxygen and nutrients
What induces endothelial proliferation (therefore angiogenesis)
Proangiogenic growth factors such as VEGF
Why is the extracellular matrix important in fibrous repair?
Supports and anchors cells Separates tissue compartments Sequesters growth factors Allows communication between cells Facilitates cell migration
Describe synthesis of collagen
Polypeptide α chains synthesised in the ER
Cleavage of signal peptide
Hydroxylation of proline/lysine residues
Addition of N-linked oligosaccharides
Disulphide bond formation
Procollagen triple helix formed by cross linking of α chains
O-linked glycosylation
Golgi then soluble procollagen secreted
Removal of terminal peptidases to produce tropocollagen
Lateral aggregation to form fibrils which bundle into fibres
Slow remodelling by specific collagenases
Describe fibrous repair
Inflammatory cells infiltrate Blood clot forms Acute inflammation around the edges Macrophages and lymphocytes migrate into the clot - chronic inflammation Clot is replaced by granulation tissue Angiogenesis Myo/fibroblasts migrate and differentiate They produce extracellular matrix Maturation occurs
What happens in maturation?
Cell population falls Collagen increases, matures and remodels Myofibrils contract to reduce volume of defect Vessels differentiate and are reduced Left with a fibrous scar
What is granulation tissue made out of?
Capillary loops and myofibroblasts
What causes fibrosis?
Macrophages releasing pro-fibrotic cytokines causing fibroblast proliferation
Define regeneration
Replacement of dead/damaged cells by functional, differentiated cells.
In regeneration, where are the regenerated cells derived from?
Stem cells
What does unipotent mean? (In relation to stem cells)
Only produce one type of differentiated cell eg epithelia
What does multi potent mean?
Can produce several types of cells eg haemopoietic
What does totipotent mean?
Can produce any type of cell eg embryonic stem cells
What are labile cells? Example
They are in state of rapid division and constantly in the cell cycle
Epithelial cells
What are stable cells? Example?
Normally in resting G0 stage but can exit this if damage occurs
Hepatocytes, osteoblasts, fibroblasts
What are permanent cells? Example?
Constantly in G0 so cannot regenerate
Neurones
What are factors controlling regeneration?
Growth factors
Contact of the cell between basement membrane and adjacent cells
How do growth factors control regeneration?
Promote proliferation in the stem cell population
Promote expression of genes controlling the cell cycle
How does contact with basement membrane/adjacent cells control regeneration?
Signalling through adhesion molecules inhibits proliferation in intact tissue
Contact inhibition
Loss of contact promotes proliferation
List some LOCAL factors that influence efficacy of healing and repair
Type, size and location of the wound Apposition and lack of movement Blood supply - arterial or venous Infection Foreign material Radiation damage
List some systemic factors that influence efficacy of healing and repair
Age Drugs (steroids) and hormones General dietary deficiencies such as protien, zinc, vit C and amino acids Chronic diseases Cardiovascular status
What happens of there is chronic damage to the liver?
Cirrhosis
Outcome if there is damage to cardiac muscle?
Fibrosis
Outcome if there is damage to bone?
Callus formation
Outcome of there is damage to peripheral nerves? (Go over in text book)
Wallerian degeneration
Proximal degeneration, distal proliferation
Outcome of damage to CNS?
No regenerative capacity
Glial cells can proliferate - gliosis
Outcome of there is damage to smooth muscle?
Replaced by scar tissue
Vascular smooth muscle has some limited regeneration
Outcome if there is damage to skeletal muscle?
Satellite cells can carry out limited regeneration
Describe process of angiogenesis
Proteolysis of basement membrane by endothelial cells
Chemotaxis of endothelial cells
Endothelial proliferation
Endothelial maturation and tubular remodelling
Recruitment of periendothelial cells
