Healing Flashcards
What are the responses to injury?
- Regeneration= renewal/ compensatory growth to replace damaged tissues
- Repair= fibrous scar production (fibrosis) to patch damaged tissues
What types of cells are involved in regeneration?
Labile
Stable
Permanent
What are labile cells?
Dividing in homeostasis, rapid regeneration (skin, GI tract) high turnover rate due to constant exposure to damage
What are stable cells?
Non-proliferative in homeostasis, capable of regenerating after injury (ischaemic/ toxic) (liver/ kidney)
How does the liver regenerate?
Proliferation of remaining cells and progenitor cells
Rapid restitution after 70% PHx rodent model, significant human capacity after injury/ surgery
What are permanent cells?
Unable to regenerate (neurons, cardiac myocytes), cannot be replaced
How is regeneration controlled?
-Soluble growth factors
-Physical stimuli
Cell number tightly controlled (balanced growth and loss)- unbalance= neoplasia
What are soluble growth factors and how do they work?
- Autocrine (act on cell surface receptor on won cell), paracrine (immediate local cells), endocrine (bloodstream travel)
- Bind to receptors, trigger intracellular cascade to change behaviours (EGF, TGF-alpha)
What is physical stimuli and how does it work?
- Cell-cell and cell-matrix interactions (receiving signals from scaffolding)
- Cell-matrix interactions mediated by integrins, triggering similar cascades
- Phosphorylation cascade
What is the process of healing by scarring (stages)?
- Bleeding
- Clot formation
- Acute to chronic inflammation (matrix and blood vessels changes, granulation, epithelial proliferation and dermis= stable/permanent)
- Fibroblast infiltration neomatrix (blood vessels mature)
- Angiogenesis- fibrillar collagen
- Scar maturation
What is granulation tissue?
Forms rapidly (1 day), grainy/shiny wound base, early new vessels, acute inflammation= neutrophils and neomatrix
What is angiogenesis?
- Blood vessel formation in adulthood= mature, sprout off to form new branches
- Wound healing; physiological (endometrium), pathological (neoplasia)
- VGEF loosens endothelial cells so room to move around, restrictive matrix removed (degraded by specialist enzymes). migrate towards damage by chemotaxis, organise into new vessel and lumen, recruit pericytes to make extracellular matrix, stabilised and matures
What does scar formation involve?
- Fibroblast migration and proliferation
- Extracellular matrix deposition
- Tissue remodelling
Describe fibroblast migration and proliferation
-Resident mesenchymal cells non polar so no direction- mobile and responsive
-Source of connective tissue
-TGF- beta produces fibroblast migration and proliferation, ECM increased production an reduced degradation, PDGF produces proliferation
Produce TIMPs to stop breakdown
Describe ECM deposition
- Produced by fibroblasts
- Collagens- fibrillar type 1/3, basement membrane type 4, finer collagen epithelia sit on
- Elastin, proteoglycans and glycoproteins
- Net fibrillar collagen accumulation- increased production, decreased degradation
