L2- Repair, regeneration and fibrosis Flashcards
What is regeneration?
Restoration of original tissue matrix and architecture
What is repair?
- Needs a wound, inflammatory process or necrosis
- Fibrosis (scarring) follows healing
- Requires a connective tissue scaffold
- Fibrosis occurs in proportion to the damage of the ECM
What are the three groups of body tissues?
- Labile tissues- continuously proliferating and can easily regenerate after injury, contain a pool of stem cells e.g skin
- Stable tissues- limited ability to proliferate and regenerate, normally in G0 but proliferate if injured and residual tissue is intact
- Permanent tissues- terminally differentiated, can’t proliferate
What is the extracellular matrix made up of?
- Basement membrane (basal lamina)- type IV collagen, laminin, proteoglycan
- Connective tissue (interstitial matrix or stroma)- fibrillar collagen, elastins, proteoglycans
What are superficial wounds?
Involve epidermis only and there is no bleeding or breach of basement membrane
What are partial thickness wounds?
Epidermis and basement membrane is breached
What are full thickness wounds?
Epidermis, basement membrane and dermis breached
Extends injury into subcutaneous fat, muscles, bones etc
What are early responses to tissue injury?
Within hours
• Vasoconstriction by mediators to constrict blood vessels and reduce blood supply to injured area (less blood loss)
• Coagulation forms fibrin mesh to stabilise the wound area and prevent blood loss
• Platelet activation- release of mediators causing vasodilation
What are early-mid term responses?
2-24/48 hours
• Neutrophil arrival, called to wound by presence of fibrinogen and fibrin
What are mid-term responses?
After 24 hours/2 days
• Macrophage arrival- phagocytose bacteria and exogenous debris
• Secrete collagenases to remove damaged ECM
• Release NO to kill bacteria
• Stimulate angiogenesis
What are late phase responses?
- Angiogenesis
- Formation of granulation tissue
- Re-epithelialisation
- Restoration of extra-cellular matrix
What is the mechanism of angiogenesis?
- NO dilates pre-existing vessels
- VEGF induces increased permeability
- Metalloproteinases degrade basement membrane components
- Plasminogen activator disrupts endothelial cell-cell contact
- Endothelial cells proliferate and migrate towards an angiogenic stimulus
- Endothelial cell maturation occurs
- Peri-endothelial cells are recruited
What is granulation tissue?
- Specialised vascular tissue found transiently during inflammation with a pebbled and glistening appearance
- Directs angiogenesis
- Degradation of provisional matrix
- Activates fibroblasts to lay down new stroma
What happens in the proliferative phase?
- Fibroblast migration and regeneration
- Day 2-21 post injury
- Collagen synthesised by fibroblasts adds tensile strength
- Capillaries grow across wound increasing blood supply
What happens in the maturation phase?
- Begins day 21 post injury and can last 1-2 years
- Fibroblasts continue to synthesise colllagen
- Increasing tension and TGF-b specific matrix proteins promote myofibroblast differentiation
- Wound is remodelled and contracted
