Wound Healing and the Problem Wound

Abigail E. Chaffin, M.D.Assistant Professor of Plastic Surgery

Division of Plastic SurgeryTulane University School of Medicine

History of Wound Healing1700 BC Papyrus: Wound Healing100 BC Egypt: Wound Healing

Methods1000 AD Gun Powder1500 AD Hot Oil20th Century Scientific Method

WoundsCustomize

Shotgun approach not acceptable

No two patients OR wounds are identical

58y DM, Neuropathy: unaware of R foot gangrene

Wounds

Wounds

Reconstructive LadderSimple to

ComplexFormal Debridement, Elevation/ABI’sAppropriate IV ABX, Wound Vac, Skin Graft

Review of Wound HealingThree basic types of healing

PrimaryDelayed PrimarySecondary

PrimaryWound surfaces opposedHealing without complicationsMinimal new tissueResults optional

Delayed Primary

Left open initiallyEdges approximated 4-6 days later

SecondarySurfaces not approximatedDefect filled by granulationCovered with epitheliumLess functionalMore sensitive to thermal and mechanical

injury

Three Phases of Wound Three Phases of Wound HealingHealing

Inflammatory Phase Proliferative Phase Remodeling Phase

Three Phases of Wound HealingInflammatory PhaseProliferative Phase

Begins when wound is covered by epithelium

Production of collagen is hallmark7 days to 6 weeks

Remodeling Phase (Maturation Phase)

Inflammatory PhaseHemostasis and InflammationDays 4 - 6 Exposed collagen activates clotting

cascade and inflammatory phaseFibrin clot = scaffolding and

concentrate cytokines and growth factors

Inflammatory: Granulocytes

First 48 hoursAttracted by inflammatory mediators Oxygen-derived free radicals Non-specific

Inflammatory: MacrophagesMonocytes

attracted to area by complementActivated by:

fibrinforeign body material exposure to hypoxic and acidotic

environmentReached maximum after 24 hours Remain for weeks

Inflammatory: Macrophages Activated Macrophage:

Essential for progression onto Proliferative Phase

Mediate:Angiogenesis: FGF, PDGF, TGF-a&b

and TNF-aFibroplasia: IL’s, EGF and TNF

Synthesize NO Secrete collagenases

Three Phases of Wound HealingInflammatory PhaseProliferative PhaseRemodeling Phase

Proliferative PhaseEpithelization, Angiogenesis and

Provisional Matrix FormationBegins when wound is covered by

epitheliumDay 4 through 14Production of collagen is hallmark7 days to 6 weeks

EpithelializationEpithelialization 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))

Proliferative: FibroblastWork horse of wound repairProduce Granulation Tissue:

Main signals are PDGF and EGFCollagen type IIIGlycosaminoglycansFibronectin Elastin fibers

Tissue fibroblasts become myofibroblasts induced by TGF-b1

Wound ContractionActual contraction with pulling of edges

toward center making wounds smallerMyofibroblast: contractile propertiesSurrounding skin stretched, thinnedOriginal dermal thickness maintainedNo hair follicles, sweat glands

Epithelialization/ContractionEpithelialization/Contraction

EpithelializationEpithelialization

Collagen HomeostasisAfter Wounding (Optimal Healing)

Days 3 - 7 weekCollagen production begins

Days 7 – 42Synthesis with a net GAIN of collagenInitial increase in tensile strength due

to increase amount of collagenDays 42+

Remodeling with No net collagen gain

CollagenNormal Skin

collagen ratio 4 : 1 Type I/III

Hypertrophic Scarcollagen ratio 2 : 1 Type I/III

Three Phases of Wound HealingInflammatory PhaseProliferative PhaseRemodeling Phase

Maturation PhaseRandom to organized

fibrils Day 8 through yearsType III replaced by type IWound may increase in

strength for up to 2 years after injuryCollagen organizationCross linking of

collagen

Impaired Wound Healing

Wound HealingTo treat the wound, you have to treat

the patientOptimize the patient

CirculatoryPulmonaryNutritionAssociated diseases or conditions

Oxygen

Fibroblasts are oxygen-sensitivePO2 < 40 mmHg collagen synthesis

cannot take place Decreased PO2: most common cause of

wound infectionHealing is Energy DependentProliferative Phase has greatly

increased metabolism and protein synthesis

Hypoxia:

Endothelium responds with vasodilation

Capillary leakFibrin depositionTNF-a induction and apoptosis

Edema

Increased tissue pressureCompromise perfusionCell death and tissue ulceration

Infection

Decreased tissue PO2 and prolongs the inflammatory phase

Impaired angiogenesis and epithelialization

Increased collagenase activity

NutritionLow protein levels prolonged inflammatory phase impaired fibroplasiaOf the essential amino

Methionine is critical

Hydration A well hydrated wound will epithelialize faster

than a dry oneOcclusive wound dressings hasten epithelial

repair and control the proliferation of granulation tissue

TemperatureWound healing is accelerated at

environmental temperatures of 30°CTensile strength decreases by 20% in

a cold (12°C) wound environment

DenervationDenervation has no effect on either

wound contraction or epithelialization

Diabetes MellitusLarger arteries, rather than the arterioles,

are typically affected Sorbitol accumulationIncreased dermal vascular permeability

and pericapillary albumin depositionImpaired 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 killingneuropathy

Radiation TherapyAcute radiation injury

stasis and occlusion of small vesselsfibrosis and necrosis of capillariesdecrease in wound tensile strengthdirect, permanent, adverse effect on

fibroblast may be progressivefibroblast defects are the central problem

in the healing of chronic radiation injury

MedicationsSteroids

Stabilize lysosomes and arrest of inflammation response

inhibit both macrophages and neutrophilsinterferes with fibrogenesis, angiogenesis,

and wound contractionAlso direct effect on Fibroblasts

Minimal endoplasmic reticulumvitamin 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

Nutritional Supplements

Vitamin C ( Ascorbic Acid) is an essential cofactor in the

synthesis of collagenexcessive concentrations of ascorbic

acid do not promote supranormal healing

Vitamin Etherapeutic efficacy and indications

remain to be definedlarge doses of vitamin E inhibit

healingincrease the breaking strength of

wounds exposed to preoperative irradiation

Nutritional SupplementsGlutamine

Enhance actions of lymphocytes, macrophages and neutrophils

GlycineInhibitory effect on leukocytes, might reduce

inflammation related tissue injuryZinc

common constituent of dozens of enzymesInfluences B and T cell activityepithelial and fibroblastic proliferation is

impaired in patients with low serum zinc levels

Factors in Wound HealingSmoking

1ppd = 3x freq of flap necrosis2ppd = 6x freq of flap necrosisNicotine acts via the sympathetic system

vasoconstriction and limit distal perfusion1 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

Syndromes Associated with Abnormal Wound HealingCutis Laxa

Think defective elastin fibersCongenital

AD, recessive or X-linked recessiveAcquired

Drug, neoplasms or inflammatory skin conditions

Ehlers-Danlos SyndromeThink defective collagen metabolismAD and recessive patters10 phenotypes

Syndromes Associated with Abnormal Wound HealingEhlers-Danlos Syndrome

Connective tissue abnormalities due to defects:Inherent strengthElasticityIntegrityHealing properties

Syndromes Associated with Abnormal Wound HealingEhlers-Danlos Syndrome

Four major clinical featuresSkin hyper-extensibilityJoint hyper-mobilityTissue fragilityPoor wound healing

Electrostimulation

Electrical current applied to woundsIncreases migration of cells109% increase in collagen40% increase in tensile strength1 to 50 mA direct or pulsed based on

wound

Hyperbaric Oxygen

Developed 1662 by Henshaw: DomicilliumAtmospheric pressure at sea level = 1

ATA = 1.5ml O2/dLNormal SubQ O2 tension is 30-50 mmHg.SubQ O2 tension < 30 mmHg = chronic

wound

Excessive Healing

Hypertrophic ScarsKeloids

KeloidsExtends beyond original boundsRaised and firmRarely occur distal to wrist or kneePredilection for sternum, mandible and

deltoidRate of collagen synthesis increased Water content higherIncreased glycosaminoglycans

Keloid TreatmentTriamcinolone injections3-4 weeksCross linking modulatedInjections continued until no excess

abnormal collagenExcisePrevention during healing – pressure and

injection

Keloid

Keloid

Questions

The proliferative phase of wound healing occurs how long after the injury?

A. 1 dayB. 2 daysC. 7 daysD. 14 days

Which type of collagen is most important in wound healing?

A. Type IIIB. Type VC. Type VIID. Type XI

The tensile strength of a wound reaches normal (pre-injury) levels:

A. 10 days after injuryB. 3 months after injuryC. 1 year after injuryD. never

Which of the following is commonly seen in Ehlers-Danlos syndrome?

A. Small bowel obstructionsB. Spontaneous thrombosisC. Direct hernia in childrenD. Abnormal scarring of the hands with

contractures.

Steroids impair wound healing by:

A. Decreasing angiogenesis and macrophage migration

B. Decreasing platelet plug integrityC. Increasing release of lysosomal enzymesD. Increasing fibrinolysis

Supplementation of which of the following micronutrients improves wound healing in patients without micronutrient deficiency?

A. Vitamin CB. Vitamin AC. SeleniumD. Zinc

Signs of malignant transformation in a chronic wound include:

A. Persistent granulation tissue with bleedingB. Overturned wound edgesC. Non-healing after 2 weeks of therapyD. Distal edema

The treatment of choices for keloids is:

A. Excision aloneB. Excision with adjuvant therapy (e.g. radiation)C. Pressure treatmentD. Intralesional injection of steroids

The major cause of impaired wound healing is:

A. AnemiaB. Diabetes mellitusC. Local tissue infectionD. Malnutrition

Bradykinin, serotonin, and histamine in wounds are released from:

A. LymphocytesB. Mast cellsC. Polymorphonuclear leukocytesD. Platelets

Platelets in the wound form a hemostatic clot and release clotting factors to produce:

A. FibrinB. FibrinogenC. ThrombinD. Thromboplastin

In a healing wound, metalloproteinases are responsible for:

A. Establishing collagen cross-linkB. Glycosylation of collagen moleculesC. Incorporation of hydroxyproline into the

collagen chainD. Initiating collagen degradation

Severe cases of hidradenitis suppurativa in the groin area are best managed by excision of the involved area and?

A. Closure by secondary intensionB. Delayed primary closureC. Primary closureD. Split thickness skin grafting

All of the following statements about keloids are true except?

A. Keloids do not regress spontaneouslyB. Keloids extend beyond the boundaries of the

original woundC. 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.

Thank You