Frederick N. Eko, MD Senior Fellow Division of Plastic Surgery Department of Surgery Tulane...
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Wound Healing and the Problem Wound Frederick N. Eko, MD Senior Fellow Division of Plastic Surgery Department of Surgery Tulane University School of Medicine
Frederick N. Eko, MD Senior Fellow Division of Plastic Surgery Department of Surgery Tulane University School of Medicine
Frederick N. Eko, MD Senior Fellow Division of Plastic Surgery
Department of Surgery Tulane University School of Medicine
Slide 2
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
Slide 3
Wounds Customize Shotgun approach not acceptable No two
patients OR wounds are identical 58y DM, Neuropathy: unaware of R
foot gangrene
Slide 4
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Wounds
Slide 6
Reconstructive Ladder Simple to Complex Formal Debridement,
Elevation/ABIs Appropriate IV ABX, Wound Vac, Skin Graft
Slide 7
Review of Wound Healing Three basic types of healing Primary
Delayed Primary Secondary
Slide 8
Primary Wound surfaces opposed Healing without complications
Minimal new tissue Results optimal
Slide 9
Delayed Primary Left open initially Edges approximated 4-6 days
later
Slide 10
Secondary Surfaces not approximated Defect filled by
granulation Covered with epithelium Less functional More sensitive
to thermal and mechanical injury
Slide 11
Secondary Wound Healing
Slide 12
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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)
Slide 17
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
Slide 18
Inflammatory: Granulocytes First 48 hours (Neutrophils)
Attracted by inflammatory mediators Oxygen-derived free radicals
Non-specific
Slide 19
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
Slide 20
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
Slide 21
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Inflammatory Phase
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Three Phases of Wound Healing Inflammatory Phase Proliferative
Phase Remodeling Phase
Slide 27
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
Slide 28
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 )
Slide 29
Slide 30
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
Slide 31
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
Slide 32
Epithelialization/Contraction
Slide 33
Epithelialization
Slide 34
Slide 35
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
Slide 36
Collagen Normal Skin collagen ratio 4 : 1 Type I/III
Hypertrophic Scar collagen ratio 2 : 1 Type I/III
Slide 37
Proliferative Phase
Slide 38
Three Phases of Wound Healing Inflammatory Phase Proliferative
Phase Remodeling Phase
Slide 39
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
Slide 40
Maturation Phase
Slide 41
Impaired Wound Healing
Slide 42
Wound Healing To treat the wound, you have to treat the patient
Optimize the patient Circulatory Pulmonary Nutrition Associated
diseases or conditions
Slide 43
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
Slide 44
Hypoxia: Endothelium responds with vasodilation Capillary leak
Fibrin deposition TNF-a induction and apoptosis
Slide 45
Edema Increased tissue pressure Compromise perfusion Cell death
and tissue ulceration
Slide 46
Infection Decreased tissue PO2 and prolongs the inflammatory
phase Impaired angiogenesis and epithelialization Increased
collagenase activity
Slide 47
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
Slide 48
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
Slide 49
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
Slide 50
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
Slide 51
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
Slide 52
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
Slide 53
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
Slide 54
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
Slide 55
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
Slide 58
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
Slide 61
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
Slide 62
Excessive Healing Hypertrophic Scars Keloids
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Hypertropic Scar
Slide 64
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
Slide 65
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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Marjolins Ulcer Jean-Nicolas Marjolin (1828) Aggressive
ulcerating SCC Occurs in setting of chronic inflammation Burn
wounds Venous stasis ulcers Previous radiation therapy
Characterized by Slow growth Painless Persistent granulation
Slide 71
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Questions
Slide 73
The proliferative phase of wound healing occurs how long after
the injury? A. 1 day B. 2 days C. 7 days D. 14 days
Slide 74
The proliferative phase of wound healing occurs how long after
the injury? A. 1 day B. 2 days C. 7 days D. 14 days
Slide 75
Which type of collagen is most important in wound healing? A.
Type III B. Type V C. Type VII D. Type XI
Slide 76
Which type of collagen is most important in wound healing? A.
Type III B. Type V C. Type VII D. Type XI
Slide 77
The tensile strength of a wound reaches normal (pre-injury)
levels: A. 10 days after injury B. 3 months after injury C. 1 year
after injury D. never
Slide 78
The tensile strength of a wound reaches normal (pre-injury)
levels: A. 10 days after injury B. 3 months after injury C. 1 year
after injury D. never
Slide 79
Which of the following is commonly seen in Ehlers- Danlos
syndrome? A. Small bowel obstructions B. Spontaneous thrombosis C.
Direct hernia in children D. Abnormal scarring of the hands with
contractures.
Slide 80
Which of the following is commonly seen in Ehlers- Danlos
syndrome? A. Small bowel obstructions B. Spontaneous thrombosis C.
Direct hernia in children D. Abnormal scarring of the hands with
contractures.
Slide 81
Steroids impair wound healing by: A. Decreasing angiogenesis
and macrophage migration B. Decreasing platelet plug integrity C.
Increasing release of lysosomal enzymes D. Increasing
fibrinolysis
Slide 82
Steroids impair wound healing by: A. Decreasing angiogenesis
and macrophage migration B. Decreasing platelet plug integrity C.
Increasing release of lysosomal enzymes D. Increasing
fibrinolysis
Slide 83
Supplementation of which of the following micronutrients
improves wound healing in patients without micronutrient
deficiency? A. Vitamin C B. Vitamin A C. Selenium D. Zinc
Slide 84
Supplementation of which of the following micronutrients
improves wound healing in patients without micronutrient
deficiency? A. Vitamin C B. Vitamin A C. Selenium D. Zinc
Slide 85
Signs of malignant transformation in a chronic wound include:
A. Persistent granulation tissue with bleeding B. Overturned wound
edges C. Non-healing after 2 weeks of therapy D. Distal edema
Slide 86
Signs of malignant transformation in a chronic wound include:
A. Persistent granulation tissue with bleeding B. Overturned wound
edges C. Non-healing after 2 weeks of therapy D. Distal edema
Slide 87
The treatment of choice for keloids is: A. Excision alone B.
Excision with adjuvant therapy (e.g. radiation) C. Pressure
treatment D. Intralesional injection of steroids
Slide 88
The treatment of choice for keloids is: A. Excision alone B.
Excision with adjuvant therapy (e.g. radiation) C. Pressure
treatment D. Intralesional injection of steroids
Slide 89
The major cause of impaired wound healing is: A. Anemia B.
Diabetes mellitus C. Local tissue infection D. Malnutrition
Slide 90
The major cause of impaired wound healing is: A. Anemia B.
Diabetes mellitus C. Local tissue infection D. Malnutrition
Slide 91
Bradykinin, serotonin, and histamine in wounds are released
from: A. Lymphocytes B. Mast cells C. Polymorphonuclear leukocytes
D. Platelets
Slide 92
Bradykinin, serotonin, and histamine in wounds are released
from: A. Lymphocytes B. Mast cells C. Polymorphonuclear leukocytes
D. Platelets
Slide 93
Platelets in the wound form a hemostatic clot and release
clotting factors to produce: A. Fibrin B. Fibrinogen C. Thrombin D.
Thromboplastin
Slide 94
Platelets in the wound form a hemostatic clot and release
clotting factors to produce: A. Fibrin B. Fibrinogen C. Thrombin D.
Thromboplastin
Slide 95
In a healing wound, metalloproteinases are responsible for: A.
Establishing collagen cross-link B. Glycosylation of collagen
molecules C. Incorporation of hydroxyproline into the collagen
chain D. Initiating collagen degradation
Slide 96
In a healing wound, metalloproteinases are responsible for: A.
Establishing collagen cross-link B. Glycosylation of collagen
molecules C. Incorporation of hydroxyproline into the collagen
chain D. Initiating collagen degradation
Slide 97
Severe cases of hidradenitis suppurativa in the groin area are
best managed by excision of the involved area and? A. Closure by
secondary intension B. Delayed primary closure C. Primary closure
D. Split thickness skin grafting
Slide 98
Severe cases of hidradenitis suppurativa in the groin area are
best managed by excision of the involved area and? A. Closure by
secondary intension B. Delayed primary closure C. Primary closure
D. Split thickness skin grafting
Slide 99
All of the following statements about keloids are true except?
A. Keloids do not regress spontaneously B. Keloids extend beyond
the boundaries of the original wound C. Keloids or hypertrophic
scars are best managed by excision and careful reapproximation of
the wound D. Keloid tissue contains an abnormally large amount of
collagen.
Slide 100
All of the following statements about keloids are true except?
A. Keloids do not regress spontaneously B. Keloids extend beyond
the boundaries of the original wound C. Keloids or hypertrophic
scars are best managed by excision and careful reapproximation of
the wound D. Keloid tissue contains an abnormally large amount of
collagen.
Slide 101
The following photograph most accurately demonstrates: A.
Hypertropic Scar B. Auricular Lymphedema C. Keloid Scar D.
Cauliflower ear
Slide 102
The following photograph most accurately demonstrates: A.
Hypertropic Scar B. Auricular Lymphedema C. Keloid Scar D.
Cauliflower ear
Slide 103
The Proliferative Phase of wound healing is classically
described as beginning: A. Immediately after injury B. When the
wound is covered with epithelium C. When the collagen content has
reached equilibrium D. When the macrophage enters the wound
Slide 104
The Proliferate Phase of wound healing is classically described
as beginning: A. Immediately after injury B. When the wound is
covered with epithelium C. When the collagen content has reached
equilibrium D. When the macrophage enters the wound
Slide 105
Under ideal circumstances the tensile strength of the wounded
area reaches what % of strength compared to normal skin? A. 10-20%
B. 20-40% C. 60-70% D. 70-90%
Slide 106
Under ideal circumstances the tensile strength of the wounded
area reaches what % of strength compared to normal skin? A. 10-20%
B. 20-40% C. 60-70% D. 70-90%
Slide 107
Which of the following does NOT affect wound healing A.
Infection B. Hydration C. Nutrition D. Denervation
Slide 108
Which of the following does NOT affect wound healing A.
Infection B. Hydration C. Nutrition D. Denervation