symposium on wound healing Flashcards
Why is wound healing important?
Essential Trauma, injury, surgery Most commonly skin £180M to £2B per year to NHS Research ongoing Cosmetic Industry
What is healing?
Follows tissue damage
Attempts to restore integrity to an injured tissue
Over overlaps the inflammatory process
What does resolution mean?
Return to normal
What does regeneration mean?
Lost tissue replaced by same type to restore tissue
What does repair mean?
Tissue lost is replaced by fibrous scar
What determines whether tissue will be regenerate or repair?
- Cell type involved-
~labile- continual cell division eg. Liver
~stable- infreq cell division but can increase eg. Muscle
~permanent- no cell division possible eg. Nerve - Tissue architecture-
~simple
~complex - Amount of tissue lost-
~small
~large- esp if basement membrane/ECM lost
What does the repair process involve?
The formation of a fibrous scar via granulation tissue
~endothelial cells and fibroblasts at edges
~these migrate into area forming loose c. tissue- granulation tissue
~increase in blood vessels and collagen
~vascularity decreases and scar formed
What is granulation tissue?
Named due to appearance in skin Cells in repair process- ~macrophages (phagocytosis and secretion) ~fibroblasts (collagen and other tissue support) ~endothelial cells (nutrition) Chronic inflammation is concurrent Often covered with fibrin slough Not to be confused w granuloma
What does granulation tissue look like histologically?
Fibroblasts- spindle shaped
Macrophages- larger, pale stained
Endothelial cells- blood vessels
How does the appearance of granulation tissue change?
3 layers- like a trifle
Top layer- fibrin slough and acute inflammatory cells (neutrophils)
Middle layer- granulation tissue, mainly macrophages and endothelial cells- blood vessels
Bottom layer- more mature granulation tissue, more fibroblasts
What does normal skin look like?
3 layers
Top layer- epidermis- keratinocytes
Middle layer- dermis- fibroblast and supporting layer
Bottom layer- hypodermis- fatty subcutaneous layer
However on top of all this- dead cells
What are the phases of wound healing?
Haemostasis
Inflammation
Proliferation
Remodelling
What is haemostasis?
Vessel rupture- bleeding
Coagulation cascade activated
Vasoconstriction- 5-10mins due to serotonin, adrenaline etc
Blood components (esp platelets) come into contact w exposed ECM to form thrombus (fibrin and fibrinogen glue wound together)
Cytokines and growth factors released from platelets (PDGF and TGF- beta) which act as chemo-attractants
Vasodilation
What is PDGF?
Platelet derived growth factors
What is TGF-beta?
Transforming growth factor- beta
What is inflammation?
Neutrophils- recruited from circulation (by PDGF etc), remove bacteria and foreign material by phagocytosis and enzymes, short lived (2 days)
Macrophages- recruited as monocytes or already resident, phagocytose remaining debris
Both further secrete cytokines and growth factors (cascade)
What is proliferation?
Granulation tissue forms
Fibroblasts proliferate, migrate and become myofibroblasts which synthesise matrix proteins (eg. Type III collagen)
Then proliferation and migration of cells over wound bed
Keratinocytes- re-epithelialisation and angiogenesis (new blood vessel formation)
What is remodelling?
2 weeks onwards
Provisional matrix remodelled
Reduction in cell and capillary density so less red
Proteases (collagenases) required
Wound contraction
Type III collagen (quickly made) replaced by stronger bundles of Type I
Strength relies on cross-linked Type I aided by Vit C (activates myofibroblasts to produce)
7-10 days- wound=10% strength
2-3 months- wound=70-80%
Why is wound healing considered dynamic?
The phases overlap
What is primary intention?
Wound edged are apposed (brought together) and held in place by mechanical means eg. Suture
What is the secondary intention?
Wound left open, edges come together naturally by means of granulation and contraction
When should you use primary/secondary intention?
Primary- wound clean, straight line, little loss of tissue, wound edges well approximated, rapid, minimal scarring
Secondary- considerable tissue loss, natural healing, longer, more scarring
How does bone healing work?
Fracture ~tissue formation- calus (like granulation tissue) ~cells grow into this ~becomes mature and solidifies ~inflam, proliferation, remodelling Primary intention
How does socket healing work?
Same principles to bone healing w/o calus
Secondary intention unless underlying haematalogical issues
4 days- residual clot
8 days- granulation tissue
52 days- bony infill
Osteoclast resorption to take away excess
What are local factors influencing wound healing?
Type, size and location of wound Movement within wound Infection Presence of foreign/necrotic material Irradiation Poor blood supply
What are systemic factors influencing wound healing?
Age
Nutrition (Vit C, Zinc)
Systemic disease- circulatory, diabetes etc
Drugs, esp steroids
How is the healing process controlled?
Epithelial cells-
Growth (PGDF, KGF, EGF etc)
Migration (contact inhibition)
Fibroblasts-
Activation to myof. (TGF-beta)
Proliferation (PGDF, FGF etc)
Migration (fibronectin, chemo-attractants)
Cell-ECM interactions (integrins)
Angiogenesis (macrophages secrete proangiogenic factor esp low in O2)
Neutrophils and macrophages (chemotaxis)
What is dysregulated healing?
Similar to cancer
Keratinocyte proliferation and migration Fibroblast activation Angiogenesis Proteases upregulated Integrin expression altered
However, this is reversible whereas cancer is irreversible
What is a scar?
Macroscopic disturbance of the normal structure and function of skin architecture resulting from the end product of a healed wound
What is a burn?
Tissue melts
Only repair process
What is a hypertrophic scar?
High risk in darker skin
Tissue sticks out of wound
What is a contracture?
Muscle/tendon shortening
Muscle not replaced
Tissue filled w fibroblasts so when healed, wound contracts
Very deep wound
What is a keloid scar?
Gross growth of tissue
Thick bundles of collagen w high levels of Type III
Abnormal cross-linkage and high turnover
Altered cytokine levels
What is a neuroma?
Eg. Wisdom tooth removal
Nerve bruised/traumatised
Scar tissue forms around nerve
Affects nerve transmission and induction
Potential tingling
Removing scar tissue may return to normal
What is a chronic wound?
Stuck in inflam phase Increased proteases (destroy ECM) Reduced growth factors (PDGF, FGF, EGF) Underlying disease (eg. Venous insufficiency, diabetes) Infection Necrosis
How do oral wounds compare to skin wounds?
Oral- heal faster, less inflam
Due to saliva (skin wounds heal faster where moist) (contains peptides and proteins [EGF, VEGF, FGF])
Earlier influx of neutrophils/macrophages
Fibroblasts are heterogenous- produce more KGF, increased ability to contract and more foetal like (younger phenotype- longer telomeres due to more telomerase [protects chromosomes from degradation when cell divides])
Increased keratinocyte proliferation and migration so faster re-epithelialisation
More proteinases to contribute to remodelling
What are aids to wound healing?
Basic wound care
Assisted wound care- dressings, hyperbaric oxygen, alternative therapies (Maggots and leeches)
What are alternative therapies?
Maggots- eat dead tissue which is stopping wound from healing
Leeches- encourages circulation, their saliva contains nitric oxide, when they suck blood, they inject the saliva
