Wound healing and repair Flashcards
What does healing depend on?
- Retention of tissue scaffold
- Cells ability to regenerate
- Hypoxia, blood supply
What is the role of macrophages in healing?
- secretion of cytokines and GFs
- Causes angiogenesis, multiplication of endothelial cells and division of stromal cells
- Recruits immune cells
What is the role of endothelial cells in healing?
- ECs damaged → facilitation of platelet adherence to exposed ECM
- Platelets activated → more platelets
- Ecs→ trigger fibrin polymerisation - entraps RBCs
What is the role of mast cells in wound healing?
Proteolytic enzyme release - can help in remodelling ECM
What is the role of fibroblasts in wound healing?
- produce collagen and ECM proteins
- Cytokine and MMPs produced regulate composition of the extracellular environment
- Proliferate with tissue injury/hypoxia
- Transform to myofibroblasts
What are the 4 stages of wound healing?
- Haemostasis
- Inflammation
- Proliferation
- Remodelling
What occurs in haemostasis?
- Begins immediately
- Initial vasoconstriction
- Platelets adhere to the damaged endothelium which plugs the wound
- Fibrin mesh formed
- Blood vessels subsequently dilate which begins the inflammatory phase
What occurs in the inflammatory phase?
- Removal of debris & bacteria
- Neutrophils reach their peak population at the site and decrease after 3 days
- Macrophages increase after debris removal
What occurs in the proliferative phase of inflammation?
- Initiates filling & covering of the wound site
- The defect begins to be formed by immature connective tissue
- Granulation tissue forms over the defect
- On the body surface, re-epithelialisation occurs as epithelial cells migrate from the wound bed & margins to cover the surface
What factors induce angiogenesis
- Hypoxia
- Cytokines
- Growth factors
- All induce VEGF which stimulates angiogenesis
What are the stages of angiogenesis?
- Degradation of ECM
- Leads to migration of endothelial cells via chemostaxis
- Multiplication of endothelial cells
- Lumen formation
What occurs in granulation formation?
- VEGF increases permeability → exudation of plasma proteins (fibrinogen)
- GFs (TGF-ß) and cytokines recruit and stimulate fibroblasts → deposits collagen
- Granulation tissue replaced by fibroblasts, collagen and other ECM components
What stimulates and inhbuts MMPs?
- stimulated by some GFs and cytokines that stimuate collagen production, phagocytosis & physical stress
- inhbited by Steroids, TGF-Beta and tissue inhibitors (TIMPS)
What occurs in the remodelling phase?
- Collagen fibres progressively reorganise, remodel & mature
- Wound bed progressively increases in tensile strength & flexibility
- Fibroblasts mature into myofibroblasts
- The wound margin contracts
What are primary union of tissues?
When the wound edges are in close contact and can be closed by stitches or staples
What are secondary union of tissues?
- Greater tissue defect - edges wont meet
- Longer repair and heal time
- More likely to have scar tissue
- More likely to become infected
What complications of wound healing can occur?
- Deficient repair
- Excessive formation of repair products
- Contractures & adhesions
What factors favour fibrosis (scarring)?
- Prolonged/repetitive tissue damage
- Large area of damage
- Tissue cells not able to renew
- Inadequate blood supply/hypoxia
- Wound contamination
- General state of health and nutrition
- Movement/instability
How does the development of fibrosis occur in chronic inflammation?
- Persistent stimulus of chronic inflammation activates macrophages & lymphocytes which produce growth factors & cytokines which cause remodel ECM
- Prolonged synthesis of collagen & increased fibroblast formation (also increases collagen synthesis)
- Deposition of collagen is enhanced by a decrease in activity of MMPs because MMPs act to degrade collagen
