Transcript of Frederick N. Eko, MD Senior Fellow Division of Plastic Surgery Tulane University School of Medicine.
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- Frederick N. Eko, MD Senior Fellow Division of Plastic Surgery
Tulane University School of Medicine
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- History of Wound Healing 1700 BC Papyrus: Lint/animal
grease/honey 100 BC Egypt: Wound closure preserved soul 1000 AD Gun
Powder 1500 AD Hot Oil 20 th Century Scientific Method
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- Wounds Customize Shotgun approach not acceptable No two
patients OR wounds are identical 58y DM, Neuropathy: unaware of R
foot gangrene
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- Wounds
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- Reconstructive Ladder Simple to Complex Formal Debridement,
Elevation/ABIs Appropriate IV ABX, Wound Vac, Skin Graft
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- Review of Wound Healing Three basic types of healing Primary
Delayed Primary Secondary
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- Primary Wound surfaces opposed Healing without complications
Minimal new tissue Results optimal
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- Delayed Primary Left open initially Edges approximated 4-6 days
later
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- Secondary Surfaces not approximated Defect filled by
granulation Covered with epithelium Less functional More sensitive
to thermal and mechanical injury
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- Secondary Wound Healing
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- Three Phases of Wound Healing Inflammatory Phase Proliferative
Phase Remodeling Phase
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- Three Phases of Wound Healing Inflammatory Phase Proliferative
Phase Begins when wound is covered by epithelium Production of
collagen is hallmark 7 days to 6 weeks Remodeling Phase (Maturation
Phase)
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- Inflammatory Phase Hemostasis and Inflammation Days 4 - 6
Exposed collagen activates clotting cascade and inflammatory phase
Fibrin clot = scaffolding and concentrate cytokines and growth
factors
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- Inflammatory: Granulocytes First 48 hours (Neutrophils)
Attracted by inflammatory mediators Oxygen-derived free radicals
Non-specific
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- Inflammatory: Macrophages Monocytes attracted to area by
complement Activated by: fibrin foreign body material exposure to
hypoxic and acidotic environment Reached maximum after 24 hours
Remain for weeks
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- Inflammatory: Macrophages Activated Macrophage: Essential for
progression onto Proliferative Phase Mediate: Angiogenesis: FGF,
PDGF, TGF- & and TNF- Fibroplasia: ILs, EGF and TNF Synthesize
NO Secrete collagenases
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- Inflammatory Phase
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- Three Phases of Wound Healing Inflammatory Phase Proliferative
Phase Remodeling Phase
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- Proliferative Phase Epithelization, Angiogenesis and
Provisional Matrix Formation Begins when wound is covered by
epithelium Day 4 through 14 Production of collagen is hallmark 7
days to 6 weeks
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- Epithelialization Basal epithelial cells at the wound margin
flatten (mobilize) and migrate into the open wound Basal cells at
margin multiply (mitosis) in horizontal direction ) Basal cells
behind margin undergo vertical growth (differentiation )
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- Proliferative: Fibroblast Work horse of wound repair Produce
Granulation Tissue: Main signals are PDGF and EGF Collagen type III
Glycosaminoglycans Fibronectin Elastin fibers Tissue fibroblasts
become myofibroblasts induced by TGF-1
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- Wound Contraction Actual contraction with pulling of edges
toward center making wounds smaller Myofibroblast: contractile
properties Surrounding skin stretched, thinned Original dermal
thickness maintained No hair follicles, sweat glands
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- Epithelialization/Contraction
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- Epithelialization
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- Collagen Homeostasis After Wounding (Optimal Healing) Days 3 -
7 Collagen production begins Days 7 42 Synthesis with a net GAIN of
collagen Initial increase in tensile strength due to increased
amount of collagen Days 42+ Remodeling with No net collagen
gain
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- Collagen Normal Skin collagen ratio 4 : 1 Type I/III
Hypertrophic Scar collagen ratio 2 : 1 Type I/III
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- Proliferative Phase
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- Three Phases of Wound Healing Inflammatory Phase Proliferative
Phase Remodeling Phase
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- Maturation Phase Random to organized fibrils Day 8 through
years Type III replaced by type I Wound may increase in strength
for up to 2 years after injury Collagen organization Cross linking
of collagen
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- Maturation Phase
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- Impaired Wound Healing
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- Wound Healing To treat the wound, you have to treat the patient
Optimize the patient Circulatory Pulmonary Nutrition Associated
diseases or conditions
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- Oxygen Fibroblasts are oxygen-sensitive PO2 < 40 mmHg
collagen synthesis cannot take place Decreased PO2: most common
cause of wound infection Healing is Energy Dependent Proliferative
Phase has greatly increased metabolism and protein synthesis
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- Hypoxia: Endothelium responds with vasodilation Capillary leak
Fibrin deposition TNF-a induction and apoptosis
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- Edema Increased tissue pressure Compromise perfusion Cell death
and tissue ulceration
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- Infection Decreased tissue PO2 and prolongs the inflammatory
phase Impaired angiogenesis and epithelialization Increased
collagenase activity
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- Nutrition Low protein levels prolong inflammatory phase
Impaired fibroplasia Of the essential amino Methionine is critical
Hydration A well hydrated wound will epithelialize faster than a
dry one Occlusive wound dressings hasten epithelial repair and
control the proliferation of granulation tissue
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- Temperature Wound healing is accelerated at environmental
temperatures of 30C Tensile strength decreases by 20% in a cold
(12C) wound environment Denervation Denervation has no effect on
either wound contraction or epithelialization
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- Diabetes Mellitus Larger arteries, rather than the arterioles,
are typically affected Sorbitol accumulation Increased dermal
vascular permeability and pericapillary albumin deposition Impaired
oxygen and nutrient delivery Stiffened red blood cells and
increased blood viscosity affinity of glycosylated hemoglobin for
oxygen contributing to low O2 delivery impaired phagocytosis and
bacterial killing neuropathy
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- Radiation Therapy Acute radiation injury stasis and occlusion
of small vessels fibrosis and necrosis of capillaries decrease in
wound tensile strength direct, permanent, adverse effect on
fibroblast may be progressive fibroblast defects are the central
problem in the healing of chronic radiation injury
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- Medications Steroids Stabilize lysosomes and arrest of
inflammation response Inhibit both macrophages and neutrophils
Interferes with fibrogenesis, angiogenesis, and wound contraction
Also direct effect on Fibroblasts Minimal endoplasmic reticulum
vitamin A oral ingestion of 25,000 IU per day pre op and 3d post op
(not to pregnant women) Restores inflammatory response and promotes
epithelializaton Does not reverse detrimental effects on
contraction and infection
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- Nutritional Supplements Vitamin C ( Ascorbic Acid) Essential
cofactor in synthesis of collagen Excessive concentrations of
ascorbic acid do not promote supranormal healing Vitamin E
Therapeutic efficacy and indications remain to be defined Large
doses of vitamin E inhibit healing Increase the breaking strength
of wounds exposed to preoperative irradiation
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- Nutritional Supplements Glutamine Enhance actions of
lymphocytes, macrophages and neutrophils Glycine Inhibitory effect
on leukocytes, might reduce inflammation related tissue injury Zinc
common constituent of dozens of enzymes Influences B and T cell
activity epithelial and fibroblastic proliferation is impaired in
patients with low serum zinc levels
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- Factors in Wound Healing Smoking 1ppd = 3x freq of flap
necrosis 2ppd = 6x freq of flap necrosis Nicotine acts via the
sympathetic system Vasoconstriction and limit distal perfusion 1
cigarette = vasoconstriction > 90 min Decrease proliferation of
erythrocytes, macrophages and fibroblasts Smoke contains high
levels of carbon monoxide shifts the oxygen-hemoglobin curve to the
left decreased tissue oxygen delivery
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- Syndromes Associated with Abnormal Wound Healing Cutis Laxa
Think defective elastin fibers Congenital AD, recessive or X-linked
recessive Acquired Drug, neoplasms or inflammatory skin conditions
Ehlers-Danlos Syndrome Think defective collagen metabolism AD and
recessive patters 10 phenotypes
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- Syndromes Associated with Abnormal Wound Healing Ehlers-Danlos
Syndrome Connective tissue abnormalities due to defects: Inherent
strength Elasticity Integrity Healing properties
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- Syndromes Associated with Abnormal Wound Healing Ehlers-Danlos
Syndrome Four major clinical features Skin hyper-extensibility
Joint hyper-mobility Tissue fragility Poor wound healing
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- Electrostimulation Electrical current applied to wounds
Increases migration of cells 109% increase in collagen 40% increase
in tensile strength 1 to 50 mA direct or pulsed based on wound
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- Hyperbaric Oxygen Developed 1662 by Henshaw: Domicillium
Atmospheric pressure at sea level = 1 ATA = 1.5ml O2/dL Normal SubQ
O2 tension is 30-50 mmHg. SubQ O2 tension < 30 mmHg = chronic
wound
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- Excessive Healing Hypertrophic Scars Keloids
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- Hypertropic Scar
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- Keloids Extends beyond original bounds Raised and firm Rarely
occur distal to wrist or knee Predilection for sternum, mandible
and deltoid Rate of collagen synthesis increased Water content
higher Increased glycosaminoglycans
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- Keloid Treatment Triamcinolone (steroid) injections 3-4 weeks
Cross linking modulated Injections continued until no excess
abnormal collagen Excise Prevention during healing pressure and
injection
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- Keloid
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- Keloid Scar
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- Acknowledgements Edward R. Newsome, MD
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- Thank You