Subject: SURGERY Topic: Healing and Wound care Lecturer: Dr.

Marquina Date of Lecture: June 22, 2011 Transcriptionist: Mopster Pages: 11

Types of wounds Wounding: disruption of tissue integrity y Insect bite:

Laceration: y Burn

Scalp avulsion: y Foreign body reaction: from silicone injection. Picture that follows shows revisional surgery.

Electrical burn: probably will sustain digital amputation

SY 2011-2012

General Objectives At the end of the lecture, the students should be able to discuss the basic concepts of wound healing, as well as, the fundamental principles of wound management. Specific Objectives y At the end of the lecture, the students should be able to: o To discuss the body s response to injury and the sequence of events that follow during the course of normal wound healing, o To define the effects of local and systemic factors on wound healing o To describe the steps in the proper evaluation, care, and treatment of the different types of wounds Course Outline I. Historical background II. Biology of normal wound healing A. Phases of wound healing 1. Inflammatory phase 2. Proliferative phase 3. Maturation and remodeling phase B. Epithelialization C. Wound Contraction D. Fetal wound healing III. Factors affecting wound healing IV. Excessive healing/abnormal scars V. Wound care and management A. Classification of wound B. Types of wound closure C. Local wound care D. Dressings Historical Background y Ancient times o 2000 BC Sumerians  Incantations: probably in the belief that the wounds were caused by evil spirits or the gods.

Application of poultice like materials 1650 BC: Egyptian papyrus documents  Infected vs. non infected wounds  Used concoctions containing  Honey (antibacterial properties  Lint (absorbent properties)  Grease (barrier) for treating wounds 2nd-3rd century AD  Greeks  Acute vs. chronic wounds  Practiced gentle tissue handling, foreign body removal, suturing skin edges, and protecting the wound with clean materials  Galen, a doctor to Roman gladiators  Emphasized the importance of a moist wound environment to ensure adequate healing Present  Mid 1500: Ambroise Pare (French army doctor)  Rediscovered the value of gentle methods of wound care  Wounds healed rapidly when milder measures were used.  1728 - 1793: John Hunter  Injury alone has in all cases a tendency to produce the deposition and the means to produce a cure  1818-1865: Ignaz Philipp Semmelweiss (Hungarian obstetrician)  Introduced washing of hands with soap and hypochlorite to decrease puerperal infection. During those times, the students, sometimes coming from anatomy dissections assisted with deliveries, which probably led to many infections.  1822-1895: Louis Pasteur.  Concept of germs entering the wound from the environment.  Used phenol to disinfect instruments and OR which resulted in a markedly reduced mortality rate  1876: Robert Johnson.  Antiseptic dressing (cotton gauze impregnated with iodoform)  1929: Howe, et al  3 classic phases of wound healing  1962: Winter.  Proved scientifically that epithelialization rate increased

by 50% in a moist wound environment Recent advances in research have not changed our knowledge of the events of wound healing but rather have added new information on the methods by which wound healing responses are controlled: y Inflammatory cytokines y Growth factors y Bioengineered tissues: for wound coverage Biology of Normal Wound Healing Phases of Wound Healing 1. Inflammatory (hemostasis and inflammation) 2. Proliferative (Fibroblastic phase) 3. Maturation and Remodeling There is overlap of the stages Time Sequence of Classical Wound Healing y Note the overlap of the different stages

Platelet activation results in: y Release of wound active substances o Platelet derived growth factor (PDGF) o Transforming growth factor (TGF ) o Platelet activating factor o Fibronectin o Serotonin o Promote migration and adhesion of neutrophils, monocytes, fibroblasts, and endothelial cells into the wound Activation of coagulation cascade y Culminates in the formation of fibrin clot which serves as scaffolding for the migration of PMNs, monocytes, and fibroblasts into the wound

Inflammatory Phase (Hemostasis and Inflammation) y Inflammation o Vascular and cellular response o Serves to clean the wound of devitalized tissue and foreign material y Stimulus to inflammation o Physical injury o Antigen antibody reaction o Infection y After the injury, initial changes are vascular . o Within 5-10 minutes, vasoconstriction occurs to slow blood flow o Followed by active vasodilation and increased permeability o Platelets, erythrocytes, leukocytes line the vessel walls and serum gains entry into the wound Wounding disrupts tissue integrity Division of blood vessels Direct exposure of extracellular matrix (collagen) to platelets Platelet aggregation and degranulation Activation of coagulation cascade

Cellular infiltration follows a characteristic pattern: y Note: platelets come first, last to arrive are the fibroblasts and capillaries.

Peak at 1 week post injury o Produce lymphokines o Found to both inhibit and stimulate fibroblast recruitment and proliferation Peterson, et al, have shown that: o Depletion of T lymphocytes within 1 week after wounding results in impaired collagen synthesis and deposition, and decreased breaking strength of the wound

Polymorphonuclear cells (PMNs) y Neutrophils o 1st infiltrating cells o Peak at 24-48 hours post wounding o Phagocytosis of bacteria and tissue debris (main task is to clean wound) o Releases collagenases  Matrix and ground substance degradation o Do not appear to play a role in collagen deposition or acquisition of mechanical wound strength  Simpson and Ross induced neutropenia in guinea pigs, and noted that in the absence of gross infection, wound repair proceeded identically to that of normal animals Macrophages y From monocytes y Peak at 48-96 hours post wounding y Wound debridemnt via phagocytosis y Contribute to microbial stasis by oxygen radial and nitric oxide synthesis y Release cytokines and growth factors that regulate fibroblast proliferation, matrix synthesis, and angiogenesis y Activated by: o IL-1 o TNF o TGF o VEGF (Vascular Endothelial Growth Factor) o Insulin like Growth Factor o Epithelial Growth Factor o Lactate Leibovich and Ross y Complete disappearance of macrophage from the wound by administration of system hydrocortisone and subcutaneous antimacrophage serum y Documented impairment of phagocytosis, qualitative as well as quantitative decrease in fibrinogenesis T-Lymphocytes

Proliferative Phase y Begins around 4th day and lasts 2-4 weeks post injury y Fibroblasts (matrix synthesis) and endothelial cells (angiogenesis): most important cells at this stage. y Culminates in the re-establishment of tissue continuity y Fibroblasts o Activated by cytokines and GFs released by macrophages o Move along a framework of fibrin fibers established during the initial hemostasis o Responsible for matrix synthesis (glycosaminoglycans and fibrillar collagen) y Endothelial cells o Participate in angiognenesis o Migrate and replicate form new capillary tubules under influence of TNF, TGF, VEGF y Matrix synthesis o GAGS  Ground substance that plays a role in the subsequent aggregation of collagen fibers  An amorphous gel made up of a repeating disaccharide units attached to a protein core  Chondroitin 4 sulfate  Dermatan sulfate  Heparan sulfate  Hyaluronic acid o Collagen  Most abundant protein in the human body  18 types; 5 types are found in human body  Type I (skin, tendon, and bone) is 90% of all collagen  Normal skin contains Type I and III collagen in ratio of 4:1  Type and distribution of collagen (see below):

Collagen synthesis o Occurs intracellularly and extracellularly o Glycine Proline - Lysine o Protocollagen is translated from mRNA o Hydroxylation  Proline Hydroxyproline  Lysine Hydroxylysine o Prolyl hydroxylase requires oxygen and iron as cofactors , ketoglutarate as cosubstrate, ascorbic acid (vitamin C) as an electron donor o Protocollagen is also glycosylated and assumes an -helical configuration o 3 -helical chains form a right handed superhelical structure called procollagen o Excreted extracellularly, procollagen undergo polymer and cross - linking forming collagen filaments o Protocollagen Procollagen Collagen filaments Collagen fibrils Collagen fibers

Tensile Strength y Tensile strength of the wound o Measurement of its load capacity per unit area o Constant y Breaking strength of the wound o The force required to break it regardless of its dimension o Dependent of the thickness of tissues o Collagen fibers are largely responsible for tensile strength of wounds o All wounds gain strength at approximately the same rate during first 14-21 days o In the skin, peak tensile strength is achieved at approximately 60 days after injury o Tensile strength of a wound reaches only about 80% of the original unwounded skin Maturation and Remodeling Phase y Begins approximately 3 weeks post injury y Collagen synthesis and degradation are accelerated no net increase in the wound collagen content

y y y

Reorganization of previously synthesized collagen o More stable and permanent cross links are established o Gain in tensile strength Normal Type I: Type III collagen ratio of 4:1 is achieved Remodeling continues for 6 12 months post - injury Initially indurated, raised and pruritic scar becomes a mature scar o Large number of new capillaries growing into wound regress and disappear o Water content of tissue return to normal o Avascular and acellular scar

y y

The area of the wound is decreased by this action (healing by secondary intention) In contrast to contracture which is: o Undesirable effect of wound healing o Shortening of the scar that may result in deformities o May be due to contraction, fibrosis, or other tissue damage Myofibroblasts o Cells postulated to be responsible for wound contraction (still controversial) o Cytoskeletal structure ( smooth muscle actin) o Well formed intercellular attachments such as desmosomes and macula adherens

Epithelialization y Proliferation and migration of epithelial cells adjacent to the wound y Begins within 1 day of injury y Seen as thickening of the epidermis at the wound edge y Reepithelialization is complete in less than 48 hours in the case of approximated incised wound y In split thickness graft donor or superficial partial thickness burns, healing consists primarily of re epithelialization with minimal or no fibroplasias and granulation tissue formation y Process: o Mobilization  Epithelial cells immediately adjacent to wound enlarge, flatten and detach from neighboring cells and the basement membrane o Migration  Loss of contact inhibition, so cell moves away from its original neighboring cells.  Cells flow away from the adjoin cells until they meet cells from the opposite side of the wound o Mitosis  Fixed basal cells divide to replace the migrating cells while the migrating cells, in turn, also divide and multiply o Cellular differentiation  Upon reepithelialization, the orderly progression from the basal mitotic cells through layers of differentiated keratinocytes to stratum corneum is again established Wound Contraction y Part of the repair process that closes a gap in soft tissue

Fetal Wound Healing y Lack of scar formation y More of a regenerative process with minimal or no scar formation y Transition wound o Occurs at the beginning of the 3rd trimester o Scarless healing but there is a loss of ability to generate appendages Difference between adult and fetal wound healing y Wound environment o Fetus is bathed in sterile and temperature stable fluid environment o However scarless healing can occur outside the amniotic fluid environment y Inflammation o Reduced fetal inflammation due to the immaturity of the immune system o Less PMNs and macrophages y Growth Factors o Absence of TGF  Studies have shown that neutralizing TGF using antibiotics reduce scar formation in adult wounds o Wound matrix  Fetal fibroblasts produce more collagen  Excessive and sustained hyaluronic acid production in the fetus which may aid in the orderly organization of collagen Factors Affecting Wound Healing y Oxygen o Fibroblasts are oxygen sensitive o Collagen synthesis occurs at PO2 is >40mm Hg o Fibroblast and collagen production can be stimulated by maintaining the wound in a state of hyperoxia y Hematocrit o Mild to moderate normovolemic anemia does not adversely affect

collagen synthesis, unless the hematocrit falls below 15% Infection o Threshold >105 microorganisms/gm of tissue or lower for hemolytic streptococcus o Decrease leukocyte chemotaxis and migration, phagocytosis, and intercellular killing o Impairs angiongenesis and epithelialization o Promotes collagenolytic activity resulting in decreased wound strength and contraction Radiation therapy o Stasis and occlusion of small vessels o Direct adverse effect of ionizing radiation on fibroblast proliferation o Decreased in wound tensile strength and total collagen deposition o Recommendation is thorough debridement and coverage with a well vascularized flap Chemotherapy o Generally decrease fibroblast proliferation and wound contraction Smoking o Nicotine: produce vasoconstriction and limit capillary blood flow necessary for distal perfusion o Carbon monoxide: Forms carboxyhemoglobin; shifts oxygen hemoglobin curve to left Age o Tensile strength and closure rates decrease with age o The phases of healing are protracted as one gets older Nutrition o Protein energy malnutrition impairs fibroplasias and diminish collagen deposition o Malnutrition correlates with high rates of wound complication o Nutritional intervention (parenteral or enteral), can reverse the effect of malnutrition or postoperative starvation on healing Steroids o Inhibit wound macrophages o Interferes with fibrogenesis, angiogenesis, and wound contraction Vitamin A o Stimulates collagen deposition and reepithelialization o Contributes to increased breaking strength of wounds o Vitamin A deficiency retards wound repair o Vitamin A restores monocytic inflammation that has been replaced by anti inflammatory steroids

Daily oral dose of 25,000 IU Topical application of 200,000 IU every 8 hours Vitamin C o Essesntial cofactor in synthesis of collagen o Scurvy or Vitamin C deficiciency  Failure of collagen synthesis and cross linking  Formation of defective capillaries leading to local hemorrhages  Muscle weakness, joint and muscle aches, rashes on legs, and bleeding gums o Excessive concentrations do not promote supranormal healing Zinc o Constituent of several enzymes essential for normal wound healing o Low serum levels impair epithelial and fibroblastic proliferation o Studies have shown that zinc enhances wound healing only when there is a pre existing zinc deficiency state Diabetes mellitus o Results in reduced inflammation, angiogenesis, and collagen synthesis o Large and small vessel diseases contributes to local hypoxemia o Careful preoperative correction of blood sugar levels improves outcome of wounds in pts. o Insulin restores collagen synthesis and granulation tissue formation to normal levels

 

Excessive Wound Healing/Abnormal Scars y Widespread scars y Hypertrophic scars y Keloids A preferred scar is one that has matured rapidly without contracture or increase in width, and without forming more collagen than necessary for its strength. Wide spread scar y Typically flat, wide, and often depressed y Consequence of continued tension in the dermis (covered by epidermis instead) and mobility of the wound

Hypertrophic scar y Elevated above skin surface but limited to the initial boundaries of the injury y Tend to regress spontaneously y Responsive to treatment

Keloids y Extend beyond the border of the original wound y Lack regression y Commonly in presternal, deltoids, back, and earlobes y Resistant to treatment, often worse after surgery y Familiar predilection y Young age and dark skin color

Wound Care and Management Classification y Acute wounds o Lacerations, tissue avulsions, surgical wound o Heal in a predictable manner and time table o Result in a well healed wound with few or no complications y Chronic wounds o Wounds that have not healed in 3 months o Risk factors include repeated trauma, poor tissue perfusion, excessive inflammation  Ischemic arterial ulcers  Due to lack of blood supply  Symptoms of peripheral vascular disease like rest pain, intermittent claudication, and color changes  On examination, diminished or absent pulses and poor formation of granulation tissue  Management is revascularization of tissue and wound care  Venous stasis ulcers  Due to venous stasis and hydrostatic back pressure  Distention of dermal caps result in leaking of fibrinogen and the formation of perivascular fibrin cuffs that impede oxygen delivery to tissue  Lipodermatosclerosis

 Treatment modalities y Intralesional corticosteroind injection y Silicone sheet/gel: shown to have some positive effect on scar remodeling y Irradiation and pressure y Surgery (high recurrence rate)

 Management is compression and wound care Diabetic wounds  Neuropathy, foot deformity, and ischemia  Unrecognized injury from ill fitting shoes, foreign body, and trauma  Severe micro- and macrovascular impairment  Mangement includes adequate control of blood glucose,

control of infection by debridement and antibiotic

y  Decubitus/Pressure Ulcer  When soft tissue is compressed between bony prominence and external surface  Excessive pressure causes capillary collapse and impedes the delivery of nutrients to tissues  Risk factors include immobility, chronic conditions, altered mental status  Pressure ulcer at the trochanteric area

Delayed primary closure: in contaminated wounds, wound edges are approximated after a delay of several days Secondary Intention or Secondary Closure o Due to bacterial contamination and tissue loss, the wound is left open to heal by granulation tissue formation and contraction Tertiary Closure o Wound is closed by bringing tissues from elsewhere in the form of graft or flap See below: scar formation for the different types of closure. o

Stages of Pressure Ulcer Formation I. Non blanching erythema of intact skin II. Partial thickness kin loss III. Full thickness skin loss but not thru fascia IV. Full thickness skin loss with involvement of muscle and bone Marjolin s Ulcers: y Malignant transformation of long standing chronic ulcer y Squamous or basal carcinomas

Types of Wound Closure y Primary intention or primary closure o Wound edges are immediately approximated using sutures, staples, or tape

Local Wound Care y Obtain a history of events surrounding injury y Examine the wound to assess its depth and configuration, extent of non-viable tissues as well as the presence of FB and contaminants y Irrigation and debridement of the edges of the wound under local anesthesia o High pressure (70 PSI) irrigation with normal saline o Gentle handling of tissues o Marginally viable flap of skin and tissues should be resected or revascularized before wound repair o Use of povidone iodine, hydrogen peroxide impair wound healing y Antibiotic administration o Must appropriate for organism o Must be given at proper time, in proper dose, via proper route  Eg, elective surgery, contaminated, traumatic wounds y Tetanus prophylaxis y Planning the type and timing of wound repair 9

o Dressing y Mimics the barrier role of epithelium y Primary dressing vs. secondary dressing o Primary dressing  Placed directly on the wound  Absorption of secretions, prevent dessication, infection and adhesion of secondary dressings o Secondary dressing  Placed over the primary dressing  Provide compression and occlusion and form a barrier y Absorbent dressing o Cotton, wool, and sponge o Should absorb without getting soaked through, as this would permit entrance of bacteria from the outside y Non adherent dressings o Impregnated with paraffin, petroleum jelly, water soluble jelly o Used as primary dressing y Medicated dressings o Used as a drug delivery system o May contain benzoyl peroxide, zinc oxide, neomycin, bacitracin, and chlorhexidine o Shown to increase epithelializaton by 28% Skin Replacements y Conventional skin grafts o Split or partial thickness skin grafts  Epidermis and part of dermis  Donor site heals by epithelialization  Lower rate of primary contraction (contraction after harvesting) but higher rate of secondary contraction (contracture)  Contraction: centripetal movement of the whole thickness of surrounding skin reducing scar  Contracture: the physical constriction or limitation of function as the result of Contraction (scars across joints, mouth, eyelid)

Full thickness skin grafts  Entire epidermis and dermis  Higher rate of contraction (contraction after harvesting) but lower rate of secondary contraction (contracture  Best coverage of lesion on the face and over jts.  Donor site should be closed primarily, but size is limited

Sources of Grafts y Autograft: from same individual y Isograft: from a twin y Allograft/homograft: from the same species. Eg, from non identical donor or cadaver y Xenograft/heterograft: from another species. Eg, porcine Skin substitutes y Provide coverage for extensive wounds with limited availability of autografts y Product of tissue engineering; novel materials are combined with living cells y Disadvantages include limited survival, high cost, and the need for multiple applications y Types: o Cultured epithelial autografts  Keratinocytes harvested from a biopsy of patient s skin are cultured with fibroblasts and growth factors, and grown into sheets. o Cultured allogenic keratinocyte graft  From cadavers and unrelated donors o Cultured bilayer skin equivalent  Acellular (collagen or synthetic materials) elements that act as scaffolding for cell growth and migration and cellular elements to reestablish lost tissue.  Eg, Biobrane

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Important points 1. Regardless of the cause of injury, the body responds in a predictable sequence of events 2. An understanding of the biology of normal wound healing guides the physician in the care of wounds. 3. Several local and systemic factors affect wound healing; controlling these factors will ensure that the normal processes of wound healing shall proceed efficiently 4. In the care of wounds, the physician must remember the basic surgical principles: gentle handling of tissues, maintenance of aseptic technique, ensuring tissue viability, and avoidance of tension.

End of transcription In all these things we have complete victory through him who loved us. Romans 8:37-39

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