Chapter 9: Inflammation, Tissue Repair, and Wound Healing

The acute inflammatory response occurs in two interconnected stages: a vascular stage characterized by increased blood flow, vessel permeability, and fluid exudation into tissue spaces, followed by a cellular stage in which neutrophils and macrophages migrate to the injury site and perform phagocytosis under the direction of chemical mediators such as cytokines and complement proteins. When inflammation persists beyond the acute phase, chronic inflammation develops, sometimes manifesting as granulomatous inflammation—a localized defensive mechanism in which epithelioid macrophages and foreign body giant cells attempt to wall off foreign or indigestible materials. Systemic inflammatory manifestations include activation of the acute-phase response with alterations in circulating acute-phase proteins, changes in leukocyte counts, and lymph node enlargement. Following tissue injury, the body initiates repair through regeneration, in which specialized cells replace damaged tissue of the same type—a process limited to labile tissues like epithelium and stable tissues like liver but absent in permanent cells such as neurons and cardiomyocytes. When regeneration is insufficient, fibrous tissue repair occurs, producing scar tissue through extensive extracellular matrix deposition. Wound healing progresses through three sequential but overlapping phases: the inflammatory phase involving hemostasis, clot formation, and debris clearance; the proliferative phase characterized by fibroblast-mediated collagen synthesis, angiogenesis, and epithelial resurfacing; and the maturation phase in which the extracellular matrix undergoes remodeling and mechanical strengthening. Primary intention healing describes surgical wounds with clean, approximated edges, while secondary intention describes larger wounds healing by epithelialization from margins. Multiple factors impair the healing process, including hypoxia, nutritional deficiency, microbial infection, and age-related physiological decline.