Phases of Wound Healing

Chapter 6 This chapter outlines the concepts of innate immunity, inflammation, and wound healing. Innate immunity refers to the body's initial defense mechanisms against invasion and injury. Inflammation is the body's response to injury and infection, aimed at protecting and healing the body. Wound healing involves several phases, including hemostasis, inflammation, tissue formation, and remodeling. Bullet points Phases of Wound Healing  Hemostasis (coagulation)  Inflammation  Proliferation with new tissue formation  Remodeling and maturation Phase III: Proliferation and New Tissue Formation  The proliferative phase begins 3 to 4 days after the injury and continues for as long as 2-3 weeks  The wound is sealed and the fibrin clot is replaced by normal tissue or scar tissue during this phase  Macrophages invade the wound and serve several functions essential to the healing process  These functions include clearing debris, releasing growth factors, recruiting fibroblasts, and promoting collagen synthesis and angiogenesis  Debridement, the cleanup of the lesion and dissolution of fibrin clots (or scabs), occurs during this phase  Remaining debris is drained away by blood and lymphatic vessels  Granulation tissue grows into the wound from surrounding healthy connective tissue, characterized by invasive cells, new lymphatic vessels, and new capillaries  Capillaries and lymphatic vessels extend into the debriefed areas, providing nutrients and removing waste  Epithelial cells migrate and seal the wound, facilitating epithelialization  Fibroblasts secrete collagen and other connective tissue proteins, depositing them in débrided areas  Collagen molecules form fibrils and fibers, taking several months to complete the process  In granulation tissue, some fibroblasts transition into myofibroblasts responsible for wound contraction  Wound contraction occurs as myofibroblasts establish connections between neighboring cells and exert tension on them  Wound contraction is necessary for the closure of all wounds Phase I Remodeling and Maturation of Tissues  Tissue remodeling and maturation process begins several weeks after injury and is completed within 2 years  During this phase, there is tissue regeneration, wound contraction, and recovery of normal tissue structure  Fibroblasts are the major cells involved in tissue remodeling, depositing collagen into an organized matrix  Scar tissue is remodeled and capillaries disappear, resulting in an avascular scar  Within 2-3 weeks, scar tissue gains about two-thirds of its eventual maximal strength Dysfunctional Wound Healing  Dysfunctional wound healing and impaired epithelialization can occur during any phase of the healing process  Causes of dysfunctional wound healing include ischemia, excessive bleeding, excessive fibrin deposition, underlying disorders, wound infection, inadequate nutrition, use of certain drugs, and tobacco smoking  Ischemic tissue is susceptible to cellular death and infection, prolonging inflammation and delaying healing  Excessive bleeding delays healing and provides a medium for bacterial growth  Excessive fibrin deposition can lead to fibrous adhesions that impair organ function Effects of Obesity and Diabetes on Wound Healing  Obesity delays wound healing by impairing leukocyte function, increasing infection risk, decreasing growth factor production, and increasing proinflammatory cytokines  In individuals with diabetes, wounds tend to be ischemic due to small-vessel diseases and impaired blood flow  Hyperglycemia in diabetes affects wound healing by increasing glycosylated hemoglobin levels, suppressing macrophage function, and impairing tissue oxygenation Effects of insulin resistance on wound healing in diabetes:  Insulin resistance in persons with diabetes leads to deficient glucose within leukocytes, impairing their function in wound healing Causes and effects of wound infection:  Wound infection occurs when pathogens infiltrate injured or compromised tissues  Pathogens damage cells, stimulate release of inflammatory mediators, consume nutrients, and delay wound healing Importance of optimal nutrition in wound healing:  Optimal nutrition is important for all phases of healing due to increased metabolic needs of affected tissues  Hyperglycemia in diabetes impairs wound healing  Hypoproteinemia impairs fibroblast proliferation and collagen synthesis  Deficiency in vitamins A and C leads to poorly formed connective tissue and impaired healing  Other cofactors for collagen synthesis include iron, zinc, manganese, and copper Medications and toxic agents that delay wound healing:  Medications: antineoplastic agents, NSAIDs, and steroids  Antineoplastic agents slow cell division and inhibit angiogenesis  NSAIDs suppress acute inflammation and inhibit prostaglandin production  Steroids prevent macrophages from migrating to the injury site and inhibit collagenase and plasminogen activator release  Tobacco smoke toxins delay healing by compromising tissue blood flow and predisposing to ischemia and infection Abnormal collagen synthesis: hypertrophic scar and keloid:  Hypertrophic scar: raised scar within original wound boundaries, tends to regress over time  Keloid scar: raised scar that extends beyond original wound boundaries, tends to recur after surgical removal  Familial tendency to keloid formation, higher incidence in darker-skinned individuals, especially African Americans Complications of wound closure: dehiscence and contracture:  Dehiscence: wound pulling apart at suture line; often occurs 5 to 12 days after suturing  Approximately half of dehiscence cases are associated with wound infection  Excessive strain or suture rupture can also cause dehiscence  Adipose tissue is difficult to suture, increasing risk of dehiscence in obese individuals  Wound contraction may result in anatomic deformity or contracture of scar tissue, especially common in burns and can lead to joint function loss Regeneration and Repair of Tissue  Regeneration: Replacement of damaged tissue with the same type of cells  Repair: Formation of scar tissue to restore structural integrity Healing by Primary Intention  Healing with minimal tissue loss, such as surgical incisions  Wound edges are close together and can be easily repaired Role of Fibroblasts in Wound Healing  Fibroblasts produce collagen, a protein that strengthens wound tissue  They contribute to the formation of granulation tissue Dysfunctional Wound Healing  Peptic ulcer, esophageal strictures, and abdominal adhesions can cause contracture  Contracture can occur in cirrhosis of the liver