Basic Sciences Flashcards
Tell me about wound healing?
Wound healing is a global response to injury with activation of complex series of systemic processes.
Divided into 3 overlapping phases (Howes, Sooy and Harvey 1929)
Each phase has key role and involves specific key cell types/growth factors
- Inflammatory phase (0-3 days)
- Haemostasis
- Platelets release PDGF and TGFb
- Trigger inflammatory cascade
- Proinflammatory cells e.g IL-1, TNFa cause chemotaxis of neutrophils and monocytes/macrophages
- Attracts fibroblasts - Proliferative phase (3 days - 3 weeks)
- Fibroblast proliferation and production of type III collagen
- Granulation tissue
- VEGF stimulates angiogenesis
- Re-epithelialisation - Remodelling phase (3 weeks - 12 months)
- Collagen organisation and cross linking - Type III to Type I collagen
- Increased wound strength
- Wound contraction
Phase 1 - Inflammatory phase
2 key components:
- HAEMOSTASIS
Within first 5-10mins
Damaged cells release THROMBOXANE + PROSTAGLANDINS
Cause transient VASOCONSTRICTION which allows platelet aggregation
PLATELETS bind to exposed collagen - release PDGF and TGFb
Trigger intrinsic pathway of clotting cascade
Extrinsic pathway triggered by release of tissue factor direct from damaged cells.
Final common pathway of CLOTTING CASCADE is conversion of factor X to Xa
Causes conversion of prothrombin to thrombin
Fibrinogen to fibrin and ultimately development of stable fibrin clot - THROMBUS - INFLAMMATORY CASCADE
Within first 2-3 days
PDGF + TGFb also trigger COMPLEMENT CASCADE and attract other PROINFLAMMATORY CELLS
Cause cell migration and proliferation of:
NEUTROPHIlS - arrive within hours and phagocytose debris/bacteria
MONOCYTES - arrive within 2-3 days and transform into macrophages which attract fibroblasts/trigger production of collagen
LYMPHOCYTES - arrive within 5-7 days and ? help bring on subsequent proliferative phase
Phase 2 - Proliferative phase
- From 3/7 to 3/52
- Macrophages continue to attract FIBROBLASTS - peak D7
- Mediate fibroblast production of TYPE III COLLAGEN
- Also stimulate endothelial cells to produce new vessels under influence of VEGF i.e. ANGIOGENESIS
- Net effect production of GRANULATION TISSUE
- At same time keratinocytes adjacent to the wound actively start to migrate into the wound to commence RE- EPITHELALISATION
- Re-epithelialisation comprises:
1. Mobilisation
2. Migration
3. Mitosis
4. Cellular differentiation
Phase 3 - Remodelling
- From 3/52 onwards
- Can last beyond 12 months
- Programmed end of angiogenesis and regression of granulation tissue results in production of SCAR
- Macrophages, fibroblasts and endothelial cells mediate COLLAGEN REMODELLING and replacement of TYPE III to TYPE I
- REORGANISATION of collagen along tension lines and increased CROSS-LINKING gives added strength to the wound
- MYOFIBROBLASTS interact with collagen matrix to cause WOUND CONTRACTION
Scar will increase strength over time
- 20% at 3/52
- 50% at 3/12
- 80% final strength
Describe the process of re-epithelialisation?
Re-establishing epithelial continuity consists of 4 phases:
- MOBILISATION
- Epithelial cells at the wound edges elongate, flatten and form pseudopodia
- Detach from neighbouring cells - MIGRATION
- This reduced contact inhibition allows cell migration
- As cells migrate other epithelial cells at wound edge proliferate to replace them
- Cells continue to migrate until they meet those from opposite wound edge
- Contact inhibition is then resumed and migration ceases - MITOSIS
- Morphological changes are reversed to allow epithelial cells to re-anchor themselves
- Epithelial cells then start to proliferate and form new epithelial layer covering the wound surface - CELLULAR DIFFERENTIATION
- The normal structure of stratified squamous epithelium is restored
What are the factors affecting wound healing?
The complexity of wound healing makes it vulnerable to interruption at many levels and there are a number of factors which may affect wound healing
These can be broadly divided into:
- PATIENT factors - including CONGENITAL v ACQUIRED factors
- WOUND factors
Patient factors incl:
CONGENITAL
- Pseudoxanthoma elasticum
- Ehlers Danlos
- Cutis laxa
- Progeria
- Werners syndrome
- Epidermolysis bullosa
ACQUIRED
- Age
- Nutritional deficiencies
e. g Vitamins A,C,E
e. g Zinc, Copper, Selenium - Comorbid conditions e.g diabetes, immunosuppression, hypothyroid
- Psychological problems e.g Dermatitis artefacta
- Drugs e.g steroids, NSAIDS, anti TNFa
- Smoking
Wound factors incl:
- Vascularity/ischaemia
- Infection
- Radiation
- Oedema
- Trauma
- Denervation
Tell me more about the factors affecting wound healing?
Patient factors incl:
CONGENITAL
- Pseudoxanthoma elasticum
- Ehlers Danlos - defective collagen metabolism - total failure of mechanical properties of skin
- Cutis laxa - defective elastin - skin is thick and abnormally lax
- Progeria
- Werners syndrome
- Epidermolysis bullosa
- Osteogenesis imperfecta - defective gene for Type I collagen
ACQUIRED
- Age - thought to be related to abnormal initiation of healing due to insuffient levels of growth factors
- Nutritional deficiencies
e. g Vitamins A,C,E
e. g Zinc, Copper, Selenium - Comorbid conditions
e. g diabetes -
e. g immunosuppression
e. g hypothyroid - decreased collagen production and wound tensile strength - Psychological problems e.g Dermatitis artefacta
- Drugs
e. g steroids
e. g NSAIDS
e. g anti TNFa - Smoking
Wound factors incl:
- Vascularity/ischaemia - hypoxia has negative effect on wound neutrophil activity, fibroblast activity and endothelial cell proliferation
- Infection - prolongs the inflammatory phase and interferes with epithelialization, collagen deposition and wound contraction
- Radiation
- Oedema - compromises perfusion with resultant ischaemia/hypoxia effects
- Trauma
- Denervation
What is the effect of radiation on tissue?
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Tell me about foetal wound healing?
Tissue healing in the first 24-26 weeks of foetal life occurs via regeneration characterised by absence of scarring
Different physiological mechanism
- reduced platelet aggregation
- reduced inflammation
- wound matrix lacks collagen and contains predominantly hyaluronic acid
- reduced angiogenesis
- faster epithelialisation
- collagen deposition during remodelling is more rapid and more organised - type III only
- less myofibroblast activity and wound contraction
What is a scar?
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What is the physiological basis behind wound contracture?
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What is abnormal wound healing?
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What is the main difference between a hypertrophic and keloid scar?
A HYPERTROPHIC scar is an elevated scar which does NOT extend outside the margin of the original wound
A KELOID scar is an elevated scar which DOES extend outside the margin of the original wound
Tell me about hypertrophic scars?
A hypertrophic scar is an elevated scar that remains confined to the limits of the original wound
Classified as LINEAR v WIDESPREAD
Usually occurs within 6-8/52
May increase rapidly for 3-6/12 then reach plateau. May then regress
Typically form at locations under tension
Microscopy shows well organised type III collagen with lots of myofibroblasts.
How do you manage a pt with a hypertrophic scar?
My algorithm for management of a hypertrophic scar is based on paper by Mustoe et al (PRS 2002) - consensus recommendations on scar Mx
Can be broadly divided into:
- PREVENTION
- TREATMENT
PREVENTION
It is much more efficient to prevent hypertrophic scars than to treat them
Aim to reduce the risk of a problem scar evolving:
- excellent surgical technique
- efforts to prevent post surgical infection
- micropore tape until wound re-epithelialised ~2/52
- in low risk pts continue tape for 6/52 then basic massage/moisturise
- in high risk pts change to silicone minimum 12hrs/day
TREATMENT
Most successful treatment of a hypertrophic scar is whilst scar is stil immature
May be NON-SURGICAL v SURGICAL +/- adjuncts
If clear reason for poor initial scar e.g wound infection - revise scar
Otherwise I would first try non surgical measures:
- Silicone gel sheets as above
- If resistant or more severe then use corticosteroid injections ev 4-6 weeks for up to 6 sessions
Triamcinolone 10mg/ml or 40mg/ml
- Consider adjunctive pressure clip/garments if appropriate e.g wide area
- If refractory consider intralesional excision + adjunctive steroid injection
Only evidence for role with silicone sheets and steroid injections rest is consensus.
Other modalities available but no evidence e.g laser, 5-FU
