Wound Healing and the Problem Wound

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Wound Healing and the Problem Wound

• R. Edward Newsome, MD
• Program Director and Chief
• Division of Plastic Surgery
• Tulane University School of Medicine

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History of Wound Healing

• 1700 BC Papyrus Wound Healing
• 100 BC Egypt Wound Healing Methods
• 1000 AD Gun Powder
• 1500 AD Hot Oil
• 20th 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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Wounds

• 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 optional

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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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Secondary Wound Healing
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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
• 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-ab and TNF-a
• Fibroplasia ILs, EGF and TNF
• Synthesize NO
• Secrete collagenases

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Inflammatory Phase
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Inflammatory Phase
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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-b1

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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 week
• Collagen production begins
• Days 7 42
• Synthesis with a net GAIN of collagen
• Initial increase in tensile strength due to
  increase 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 lt 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 prolonged 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)
• is an essential cofactor in the 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 gt 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 lt 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 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
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Keloid Scar
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Keloid Scar
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• Questions

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• The proliferative phase of wound healing occurs
  how long after the injury?
• 1 day
• 2 days
• 7 days
• 14 days

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• Which type of collagen is most important in wound
  healing?
• Type III
• Type V
• Type VII
• Type XI

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• The tensile strength of a wound reaches normal
  (pre-injury) levels
• 10 days after injury
• 3 months after injury
• 1 year after injury
• never

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• Which of the following is commonly seen in
  Ehlers-Danlos syndrome?
• Small bowel obstructions
• Spontaneous thrombosis
• Direct hernia in children
• Abnormal scarring of the hands with contractures.

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• Steroids impair wound healing by
• Decreasing angiogenesis and macrophage
  migration
• Decreasing platelet plug integrity
• Increasing release of lysosomal enzymes
• Increasing fibrinolysis

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• Supplementation of which of the following
  micronutrients improves wound healing in patients
  without micronutrient deficiency?
• Vitamin C
• Vitamin A
• Selenium
• Zinc

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• Signs of malignant transformation in a chronic
  wound include
• Persistent granulation tissue with bleeding
• Overturned wound edges
• Non-healing after 2 weeks of therapy
• Distal edema

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• The treatment of choices for keloids is
• Excision alone
• Excision with adjuvant therapy (e.g. radiation)
• Pressure treatment
• Intralesional injection of steroids

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• The major cause of impaired wound healing is
• Anemia
• Diabetes mellitus
• Local tissue infection
• Malnutrition

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• Bradykinin, serotonin, and histamine in wounds
  are released from
• Lymphocytes
• Mast cells
• Polymorphonuclear leukocytes
• Platelets

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• Platelets in the wound form a hemostatic clot and
  release clotting factors to produce
• Fibrin
• Fibrinogen
• Thrombin
• Thromboplastin

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• In a healing wound, metalloproteinases are
  responsible for
• Establishing collagen cross-link
• Glycosylation of collagen molecules
• Incorporation of hydroxyproline into the collagen
  chain
• Initiating collagen degradation

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• Severe cases of hidradenitis suppurativa in the
  groin area are best managed by excision of the
  involved area and?
• Closure by secondary intension
• Delayed primary closure
• Primary closure
• Split thickness skin grafting

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• All of the following statements about keloids are
  true except?
• Keloids do not regress spontaneously
• Keloids extend beyond the boundaries of the
  original wound
• Keloids or hypertrophic scars are best managed by
  excision and careful reapproximation of the wound
• Keloid tissue contains an abnormally large amount
  of collagen.

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• Thank You