Wound HealingWound Healing

Junior Basic ScienceJunior Basic Science

1/25/20111/25/2011

3 Phases of Wound Healing3 Phases of Wound Healing

• 1. Inflammation- day 1-101. Inflammation- day 1-10

• 2. Proliferation-5 days-3 weeks2. Proliferation-5 days-3 weeks

• 3. Remodeling-3 weeks-1 year3. Remodeling-3 weeks-1 year

Inflammation Phase: InjuryInflammation Phase: Injury

• Bleeding and vasoconstriction(5-Bleeding and vasoconstriction(5-10min), followed by vasodilation10min), followed by vasodilation

• Plt plug formation and clottingPlt plug formation and clotting• Fibrin binds the plt plug and forms the Fibrin binds the plt plug and forms the

provisional matrix provisional matrix (platelets+fibrin+fibronectin)(platelets+fibrin+fibronectin)

• Platelet degranulation Platelet degranulation (alpha and dense (alpha and dense granules)granules)

-> PDGF and TGF-B-> PDGF and TGF-B• Chemotaxis for inflammationChemotaxis for inflammation

InflammationInflammation

• PMNs-almost immediately, clear PMNs-almost immediately, clear debrisdebris

• Macrophages-Day 2-3 (essential)Macrophages-Day 2-3 (essential)– Fibroblast proliferation, endothelial cell proliferation Fibroblast proliferation, endothelial cell proliferation

(angiogenesis), and extracellular matrix production, and (angiogenesis), and extracellular matrix production, and they recruit and activate additional macrophages.they recruit and activate additional macrophages.

• LymphocytesLymphocytes

Proliferation Phase (5-21 Proliferation Phase (5-21 days)days)• Fibroblasts-enter provisional matrix and initiate Fibroblasts-enter provisional matrix and initiate

collagen synthesiscollagen synthesis– Prominent cell type during this phaseProminent cell type during this phase

• Macrophages->angiogenesis and Macrophages->angiogenesis and neovascularizationneovascularization

• Collagen and proteoglycans or ground substance Collagen and proteoglycans or ground substance replaces the provisional fibronectin–fibrin matrixreplaces the provisional fibronectin–fibrin matrix

Remodeling Phase (3wks-1 Remodeling Phase (3wks-1 year)year)

• Max collagen accumulation at 2-3 weeks. Max collagen accumulation at 2-3 weeks. Only remodeling/crosslinking after 3 Only remodeling/crosslinking after 3 weeks.weeks.

• Type III collagen predominates early (days Type III collagen predominates early (days 1-3), but is replaced by type I 1-3), but is replaced by type I

• 6 weeks-80% of final strength and 60% of 6 weeks-80% of final strength and 60% of original strengthoriginal strength

• 8 weeks-max tensile strength (70-80%)8 weeks-max tensile strength (70-80%)

CollagenCollagen

• Need alpha-ketoglutarate, vit C, O2, and Need alpha-ketoglutarate, vit C, O2, and iron for hydroxylation of proline, and iron for hydroxylation of proline, and crosslinking of proline residuescrosslinking of proline residues

• Proline is every 3Proline is every 3rdrd amino acid. Lysine is amino acid. Lysine is abundant from hydroxylysine crosslinkingabundant from hydroxylysine crosslinking

• Type I, most common and most abundant Type I, most common and most abundant in healed woundin healed wound

• D-penicillamine inhibits collagen D-penicillamine inhibits collagen crosslinkingcrosslinking

Surgical Wound HealingSurgical Wound Healing

• Primary Intention-Tensile strength is Primary Intention-Tensile strength is important in healing closed incisionsimportant in healing closed incisions– Depends on collagen deposition and cross-Depends on collagen deposition and cross-

linkinglinking

• Secondary Intention-Epithelial integrity is Secondary Intention-Epithelial integrity is important in healing open woundsimportant in healing open wounds– Dependent on granulation tissue (capillaries, Dependent on granulation tissue (capillaries,

fibroblasts and collagen)fibroblasts and collagen)– Migration from wound edges, sweat glands and Migration from wound edges, sweat glands and

hair follicleshair follicles

Essential for wound healingEssential for wound healing

• Moist environment- Moist environment- optimizes epithelial optimizes epithelial migrationmigration

• Oxygen delivery- Oxygen delivery- EssentialEssential

• Avoid edema- Avoid edema- edema causes decreased O2 edema causes decreased O2 in woundsin wounds

• Remove necrotic tissue- Remove necrotic tissue- leads to infectionleads to infection

Factors affecting wound Factors affecting wound healinghealing• Nutrition-Albumin <3Nutrition-Albumin <3• InfectionInfection• Foreign bodyForeign body• DrugsDrugs• DiabetesDiabetes• IschemiaIschemia• AgingAging• RadiationRadiation• NeuropathyNeuropathy

ScarsScars

• Contain proteoglycans, hyaluronic acid, Contain proteoglycans, hyaluronic acid, and water.and water.

• Keloids-Keloids- AD, dark skinned. Collagen goes AD, dark skinned. Collagen goes beyond original scarbeyond original scar

• Hypertrophic scarHypertrophic scar- Collagen stays within - Collagen stays within scarscar

• Treatment: Steroids, silicone, pressure Treatment: Steroids, silicone, pressure garments, XRT.garments, XRT.

• Infants heal with little/no scarring-Infants heal with little/no scarring-multifactorial, decreased inflammatory multifactorial, decreased inflammatory response, increase hyaluronic acid?response, increase hyaluronic acid?

Chronic WoundsChronic Wounds

• Pressure Sores-Pressure Sores- pressure over bony area, pressure over bony area, occurs when tissue pressure exceeds the occurs when tissue pressure exceeds the capillary filling pressure of 25 mm Hgcapillary filling pressure of 25 mm Hg– Tx: Pressure off loading, debridement, Tx: Pressure off loading, debridement,

myocutaneous flap myocutaneous flap • Leg ulcers-Leg ulcers- 90% due to venous insuff. 90% due to venous insuff.

– Tx: Unna boot, elastic wrapTx: Unna boot, elastic wrap• Diabetic foot ulcers-Diabetic foot ulcers- 2 2ndnd MTP joint MTP joint

(Charcot’s joint). Neuropathy leads to (Charcot’s joint). Neuropathy leads to increased pressure-> Ischemiaincreased pressure-> Ischemia– Tx: Depends on extent of ulcerTx: Depends on extent of ulcer

QuestionQuestion

• The most prominent cell type in the The most prominent cell type in the 11stst 24 hours of a wound is : 24 hours of a wound is :– PMN’sPMN’s– MacrophagesMacrophages– LymphocytesLymphocytes– FibroblastsFibroblasts

AnswerAnswer

• PMN’sPMN’s– Most abundant in 1Most abundant in 1stst 24 hrs, help clear 24 hrs, help clear

debridebri

QuestionQuestion

• The most prominent cell type day 2-The most prominent cell type day 2-4?4?– PMN’sPMN’s– MacrophagesMacrophages– LymphocytesLymphocytes– PlateletsPlatelets

AnswerAnswer

• MacrophagesMacrophages– Fibroblast proliferation, endothelial cell Fibroblast proliferation, endothelial cell

proliferation (angiogenesis), and extracellular proliferation (angiogenesis), and extracellular matrix production, and they recruit and matrix production, and they recruit and activate additional macrophages.activate additional macrophages.

QuestionQuestion

• What is the most prominent cell type What is the most prominent cell type at 1 week?at 1 week?– PMN’sPMN’s– MacrophagesMacrophages– LymphocytesLymphocytes– FibroblastsFibroblasts

AnswerAnswer

• FibroblastsFibroblasts

-Enter provisional matrix and -Enter provisional matrix and initiate collagen synthesis. Days 5-initiate collagen synthesis. Days 5-21.21.

QuestionQuestion

• The most predominant type of The most predominant type of collagen in the body?collagen in the body?– II– IIII– IIIIII– IVIV

AnswerAnswer

Type I most common, seen in skin, bone, Type I most common, seen in skin, bone, tendons, and healed woundstendons, and healed wounds

– I I – II CartilageII Cartilage– IIIIII– IV Basement membraneIV Basement membrane

QuestionQuestion

• Most abundant collagen in healing Most abundant collagen in healing wound during 1wound during 1stst 24hrs? 24hrs?– II– IIII– IIIIII– IVIV

AnswerAnswer

• Type III- Most abundant the first Type III- Most abundant the first 48hrs, and is then replaced by type I.48hrs, and is then replaced by type I.

QuestionQuestion

• What is the most important cell What is the most important cell involved in wound healing?involved in wound healing?– PMN’sPMN’s– MacrophagesMacrophages– LymphocytesLymphocytes– FibroblastsFibroblasts

AnswerAnswer

• MacrophagesMacrophages– Essential, synthesizes cytokines and Essential, synthesizes cytokines and

growth factors necessary for wound growth factors necessary for wound healing.healing.

QuestionQuestion

• Maximal tensile strength of a wound Maximal tensile strength of a wound occurs at:occurs at:– 3 weeks3 weeks– 6 weeks6 weeks– 8 weeks8 weeks– 3 months3 months

AnswerAnswer

• 8 weeks- Has 80-90% of original 8 weeks- Has 80-90% of original strengthstrength

QuestionQuestion

• What vitamin can you give to What vitamin can you give to prevent the negative affects on prevent the negative affects on wound healing?wound healing?– AA– DD– OO– KK

AnswerAnswer

• Vitamin AVitamin A– 25,000 UI daily25,000 UI daily

QuestionQuestion

• Peripheral nerves regenerate at:Peripheral nerves regenerate at:– 0.01mm/year0.01mm/year– 0.1mm/day0.1mm/day– 1mm/day1mm/day– 5mm/day5mm/day

AnswerAnswer

• 1mm per day1mm per day

QuestionQuestion

• The most important factor in the The most important factor in the healing wounds by secondary healing wounds by secondary intention is:intention is:– Tensile strengthTensile strength– Epithelial integrityEpithelial integrity– Platelet activating factorPlatelet activating factor– cocainecocaine

AnswerAnswer

• Epithelial integrity- epithelial cells Epithelial integrity- epithelial cells migrate from hair follicles, wound migrate from hair follicles, wound edges and sweat glands.edges and sweat glands.

QuestionQuestion

• The most important factor in the The most important factor in the healing wound by primary intention healing wound by primary intention is:is:– Double cheeseburger from McDonaldsDouble cheeseburger from McDonalds– Tensile strengthTensile strength– Epithelial integrityEpithelial integrity– Platelet activating factorPlatelet activating factor

AnswerAnswer

• Tensile strength, not double Tensile strength, not double cheeseburgercheeseburger– This is created by collagen cross linkingThis is created by collagen cross linking

QuestionQuestion

• The dressing change regimen that The dressing change regimen that will produce maximal debridement is:will produce maximal debridement is:– Wet-to-dry dressing changes with saline. Wet-to-dry dressing changes with saline. – Dressing changes with Xeroflo. Dressing changes with Xeroflo. – Dressing changes with silver Dressing changes with silver

sulfadiazine. sulfadiazine. – Dressing changes with an occlusive Dressing changes with an occlusive

dressing. dressing.

AnswerAnswer

• Maximal debridement is Maximal debridement is accomplished when the dressing is accomplished when the dressing is changed utilizing wet-to-dry changed utilizing wet-to-dry dressings. Enzymatic agents, such as dressings. Enzymatic agents, such as collagenase, may augment the collagenase, may augment the debriding effect of wet to dry debriding effect of wet to dry dressing changes. dressing changes.

QuestionQuestion

• Hypoxia in a wound stimulates:Hypoxia in a wound stimulates:– collagen synthesis collagen synthesis – contraction contraction – ovulation ovulation – angiogenesis angiogenesis – epithelialization epithelialization

AnswerAnswer

• AngiogenesisAngiogenesis

QuestionQuestion

• Cofactors necessary for successful Cofactors necessary for successful hydroxylation of proline include all hydroxylation of proline include all the following except:the following except:– Vitamin C. Vitamin C. – Magnesium. Magnesium. – Ferrous ion. Ferrous ion. – α-Ketoglutarate. α-Ketoglutarate. – Oxygen. Oxygen.

AnswerAnswer

• MagnesiumMagnesium

QuestionQuestion

• Local factors which invite wound Local factors which invite wound infection include all of the following infection include all of the following except:except:– Foreign material. Foreign material. – Radiation injury. Radiation injury. – Poor circulation. Poor circulation. – Disruption of fascia. Disruption of fascia. – Hematoma. Hematoma.

AnswerAnswer

• Disruption of fasciaDisruption of fascia– Depth of injury into the fascia has not Depth of injury into the fascia has not

been identified as a wound been identified as a wound characteristic that predisposes to characteristic that predisposes to infection infection

QuestionQuestion

• Significant collagen synthesis first Significant collagen synthesis first begins in a wound at:begins in a wound at:– 2 to 4 weeks. 2 to 4 weeks. – 7 to 10 days. 7 to 10 days. – 0 to 12 hours. 0 to 12 hours. – 12 to 24 hours. 12 to 24 hours. – 3 to 5 days. 3 to 5 days.

AnswerAnswer

• Significant collagen synthesis begins Significant collagen synthesis begins in a wound at 3 to 5 days. in a wound at 3 to 5 days.