Lecture 12: Healing of Skin Wounds and Fibrosis PDF

Lecture 12 Healing of skin wounds and Fibrosis Dr Mohammad Shahid Iqbal M.D Assistant Professor of Pathology 1  Examples of Tissue Repair and Fibrosis Two clinically significant types of Repair 1. The healing of skin wounds (cutaneous wound healing) 2. Fibrosis in injured parenchym...

Lecture 12 Healing of skin wounds and Fibrosis Dr Mohammad Shahid Iqbal M.D Assistant Professor of Pathology 1  Examples of Tissue Repair and Fibrosis Two clinically significant types of Repair 1. The healing of skin wounds (cutaneous wound healing) 2. Fibrosis in injured parenchymal organs  Cutaneous wound healing Healing of Skin Wounds (Cutaneous wound healing)  Cutaneous wound healing is a process that involves both epithelial regeneration and the formation of connective tissue scar  Depending on the nature and size of the wound, the healing of skin wounds is said to occur either by first (primary) intention or second intention  Healing by first intention  Healing of a clean, uninfected surgical incision approximated by surgical sutures  Incision causes only focal disruption of epithelial basement membrane continuity and death of relatively few epithelial and connective tissue cells  Epithelial regeneration is the principal mechanism of repair  A small scar is formed with minimal wound contraction  The narrow incisional space first fills with fibrin-clotted blood  Rapidly invaded by granulation tissue and covered by new epithelium. Healing by first intention  Healing by first intention Within 24 hours  Neutrophils are seen at the incision margin, migrating toward the fibrin clot  Basal cells show increased mitosis  Epithelial cells from both edges migrate and proliferate along the dermis  Deposition of basement membrane components  The cells meet in the midline beneath the surface scab; yields a thin but continuous epithelial layer.  Healing by first intention By day 3  Neutrophils largely replaced by macrophages  Granulation tissue progressively invades the incision space  Collagen fibers are evident at the incision margins;  Epithelial cell proliferation continues  Yields thickened epidermal covering layer  Healing by first intention By day 5  Neovascularization peak and Granulation tissue abundance  Bridging by collagen fibrils  Epidermis recovers its normal thickness  Mature epidermal architecture with surface keratinization  Healing by first intention During the second week  Continued collagen accumulation and fibroblast proliferation  Diminished leukocyte infiltrate, edema, and vascularity  Blanching: Accomplished by increasing collagen deposition within the incisional scar and the regression of vascular channels  Healing by first intention By the end of the first month  Scar consists of a cellular connective tissue, largely devoid of inflammatory cells  Covered by an essentially normal epidermis  Dermal appendages destroyed in the line of the incision are permanently lost  The tensile strength of the wound increases with time  Healing by Second Intention  A complex repair process involving combination of regeneration and scaring  Occurs when cell or tissue loss is more extensive  Such as in large wounds, at sites of abscess formation, ulceration, and ischemic necrosis (infarction) in parenchymal organs  The inflammatory reaction is more intense  Development of abundant granulation tissue, with accumulation of ECM and formation of a large scar  Followed by wound contraction mediated by the action of myofibroblasts Healing by Second intention  Healing by Second Intention  Secondary healing differs from primary healing in several respects  A larger clot or scab rich in fibrin and fibronectin forms at the surface of the wound.  Inflammation is more intense because large tissue defects have a greater volume of necrotic debris, exudate, and fibrin that must be removed.  Consequently, large defects have a greater potential for secondary, inflammation-mediated, injury.  Healing by Second Intention  Secondary healing involves wound contraction  Within 6 weeks large skin defects may be reduced to 5% to 10% of their original size, largely by contraction  Contraction occurs due to the presence of myofibroblasts Scar tissue Dermal Scar  Wound Strength  Carefully sutured wounds have approximately 70% of the strength of normal skin  Wound strength is approximately 10% of that of unwounded skin at 1 WEEK  Increases rapidly over the next 4 weeks  Wound strength reaches approximately 70% to 80% of normal by 3 months  Usually does not improve substantially beyond that point  Complications in tissue repair  Deficient scar formation  Excessive formation of the repair components  Formation of contractures  Complications in tissue repair  Seen in numerous clinical situations Examples  Venous leg ulcers  Arterial ulcers  Pressure sores  Diabetic ulcers  VENOUS LEG ARTERIAL LEG ULCER ULCER DIABETIC ULCER PRESSURE SORE GRANULATION TISSUE DIABETIC ULCER  Excessive scarring  Excessive formation of the components of the repair process can give rise to hypertrophic scars and keloids Hypertrophic scar:  Accumulation of excessive amounts of collagen results in a raised scar  Tend to grow rapidly and contain abundant myofibroblasts  Tend to regress over several months  Generally develop after thermal or traumatic injury that involves the deep layers of the dermis Keloid:  A scar which grows beyond the boundaries of the original wound and do not regress HYPERTROPHIC KELOID SCAR  Fibrosis in parenchymal organs Fibrosis:  Excessive deposition of collagen and other ECM components in tissues.  Terms Scar and Fibrosis may be used interchangeably  ‘Fibrosis most often refers to the ‘abnormal deposition of collagen that occurs in internal organs in chronic diseases’  Fibrosis is a pathologic process induced by persistent injurious stimuli such as chronic infections and immunologic reactions  Typically associated with loss of tissue  May be responsible for substantial organ dysfunction and even organ failure  Fibrosis in parenchymal organs  Major cytokine involved in fibrosis : TGF-β  Cell death by necrosis or apoptosis and the production of ROS seem to be important triggers  Myofibroblasts are the main source of collagen in lungs and kidney  Stellate cells are the major collagen producers in liver  References: Kumar V. et al, 2021. Robbins & Cotran Pathologic basis of disease, 10th ed. Chapter 3, P 71-125 HarshMohan Text book of pathology Thank You