Wound healing / Flashcards
What is a wound, causes and consequences?
Any disruption to the integrity of skin, mucosal surfaces or organ tissue
Causes: accidental or intentional (surgery) aetiology, part of a disease process
Consequences: coordinated sequence of cellular and non-cellular processes to restore tissue - haemostasis, inflammation, proliferation, remodelling/maturation
What are acute wounds and causes?
Acute wounds occur suddenly
Acute wounds affecting soft tissue, usually pass through healing phases quickly
Usually caused by trauma
What will abnormal wound healing lead to?
Increased patient morbidity and mortality
Poor cosmetic outcome
Health economic outcomes
Psychological sequelae for the patients
What are the different types of wound closure in soft tissue?
Closure by primary intention:
Deliberate closure of a small wound, edges are aligned
Closure by secondary intention:
extensive tissue loss, no deliberate closure. Repair prolonged, much granulation tissue
Tertiary intention healing:
Intentional delay of wound healing due to decontamination, risk of infection. Closure performed after interventions
What are the events leading up to haemostasis?
Vascular injury
Damaged arterioles rapidly constrict by smooth muscle contraction - triggered by SNS and vasoconstrictors released locally (thromboxane A2 and endothelin)
Vessels up to 5mm can close just by contraction if transverse wound
Reduced BF leads to tissue hypoxia and acidosis which promotes production of vasoactive metabolites e.g. NO, adenosine
>vasodilation and relaxation of the arterial vessels
Coagulation is then needed
What occurs in the early stages of inflammation?
Mast cells release histamine
Increases vasodilation and increases vascular permeability
Entry of inflammatory cells into the wound
Complement is activated
Neutrophils infiltrate wound and carry out phagocytosis, degranulation and NETosis over first 48 hours
What occurs in late stage inflammation with macrophages?
Macrophages are pro-inflammatory in the first days - M1 phenotype
Become anti-inflammatory/more pro-resolution later - M2 phenotype
Macrophages release collagenases (MMPs 1, 8 & 13) - break down collagen and allow remodelling
Macrophages release PDGF which recruits fibroblasts and FGF stimulates them to migrate and proliferate
Release TGF-B - stimulates fibroblasts to secrete collagen
Release VEGF stimulates endothelial cells to proliferate >granulation tissue
What occurs in late stage inflammation with other cells than macrophages?
Lymphocytes appear in wound ~72hrs and regulate healing, Persist until healed
Dendritic epidermal T cells secret keratinocyte GF (stimulate keratinocyte prolif) and IGF-1 (differentiation)
Products of arachidonic acid metabolism have anti-inflam properties which dampen immune response and allow next phase
What processes occur during proliferation phase?
Angiogenesis
Formation of granulation tissue
Fibroblast migration
Collagen deposition
Epithelialisation
Wound contraction
What stimulates and drives angiogenesis?
Triggered from formation of haemostatic plug; platelets release VEGF (and TGF-B, PDGF and FGF)
Hypoxia drives it. VSGF secreted by macrophages, fibroblasts and others
Stimulate endothelial cell proliferation and migration to form tubes
MMPs are important for remodelling of the ECM
What happens during fibroblast proliferation and migration stage of proliferative stage in wound healing?
- Wound rich in fibroblasts that proliferate and migrate in response to growth factors
- TGF-B stimulates fibroblasts to lay down ECM proteins (collagen, fibronectins, proteoglycans)
- Fibroblasts release MMPs - collagenases MMPs 1, 8, 13
- Collagens synthesised by fibroblasts provide strength to tissues
- Fibroblasts then change to myofibroblast phenotype and connect to surrounding cells and ECM proteins
- Scar formation
What happens in the re-epithelialisation stage of proliferation?
Cytokines and growth factors at the wound site stimulate basal epithelial cells at wound edge to migrate across the wound bed by EMT
Basal epithelial cells adhere to deposited ECM
Epithelial cells proliferate, differentiate and stratify to repopulate epithelial cell levels
If the wound area is large contraction of the wound is required
What occurs during wound contraction in proliferation contraction?
Mediated mainly by myofibroblasts
Cell bodies are pulled closer together decreasing the area of tissue needing to heal
Remodelling phase of wound healing
Balance between synthesis and degradation of collagen and other proteins which become increasingly well organised
Wounds never achieve the same level of tissue strength
> Normal epithelium and maturation of scar tissue
As scar matures, level of vascularity decreases and scar changes from pink to grey with time
Influenced by wound size, shape and location
What are chronic wounds?
Soft tissue wounds that have not healed within 12 weeks after insult
