Inflammation and Repair

Inflammation brings circulating host defenses into vascularized tissues affected by infection or injury, allowing elimination of harmful agents and initiation of repair. →

Inflammation produces recognizable external signs and proceeds through a sequence of defensive and reparative steps. Under some circumstances, the reaction itself causes disease. →

Inflammation begins with recognition of microbes or damaged cells by tissue cells. It contributes to tissue injury in several diseases, while inadequate inflammation increases susceptibility to infection. →

Inflammation may be triggered by infection, tissue necrosis, foreign bodies, or immune reactions. After elimination of the offending agents, repair replaces injured tissue. →

Inflammation begins when cellular receptors and circulating proteins recognize microbes or necrotic cells. →

Acute inflammation delivers plasma proteins and leukocytes to sites of infection or tissue injury through coordinated vascular and cellular responses. →

Increased microvascular permeability follows vasodilation and allows protein-rich fluid to enter extravascular tissues. →

Acute inflammation increases lymphatic drainage and recruits circulating leukocytes through a sequence of endothelial interactions and tissue migration. →

Selectins mediate early leukocyte attachment to endothelium. The accompanying fluid-formation material contrasts transudates with inflammatory exudates. →

Inflammation increases vascular permeability and recruits leukocytes through a sequence of interactions with the endothelium. →

Leukocyte adhesion molecules bind specific endothelial ligands. Weak selectin interactions slow leukocytes so that they can recognize additional adhesion molecules. →

Leukocytes stop rolling and attach firmly to endothelium at sites of inflammation through coordinated activation of leukocyte integrins and endothelial integrin ligands. →

After adhering to endothelium, leukocytes cross the vessel wall and follow chemical gradients toward injury. The predominant recruited cell changes with time. →

Early neutrophil predominance commonly gives way to longer-lasting macrophage infiltration, but the inflammatory stimulus can alter this pattern. →

Recruited neutrophils and monocytes are activated by microbial products, necrotic cells, and local cytokines to destroy microbes and clear dead tissue. →

Neutrophils and macrophages share phagocytosis, migration into tissues, and chemotaxis, but differ in origin, longevity, and responses to activation. →

Activated phagocytes generate destructive oxygen- and nitrogen-derived molecules that damage microbial cellular constituents. →

Phagocytosis brings microbes into intracellular compartments where granule enzymes and reactive oxygen and nitrogen species destroy them. →

Activated leukocytes destroy microbes but can also injure normal tissues through extracellular release of antimicrobial substances. →

Besides neutrophils and macrophages, several immune cell types contribute to inflammatory defense and allergic reactions. →

Chemical mediators initiate and regulate inflammation. They may originate from local cells or from circulating precursors activated at the inflammatory site. →

Vasoactive amines are preformed mediators that influence vascular responses during inflammation. →

Arachidonic acid supplies lipid mediators that participate in vascular and cellular reactions of acute inflammation. →

Arachidonic acid metabolites regulate vascular reactions, platelet aggregation, and leukocyte recruitment; some also suppress inflammation. →

Inflammatory mediators have overlapping vascular and leukocyte effects. Drugs targeting eicosanoid synthesis can reduce inflammatory symptoms. →

Inflammatory responses can be reduced by suppressing mediator production or blocking mediator receptors. Cytokines coordinate immune and inflammatory reactions. →

Tumor necrosis factor (TNF) and interleukin-1 (IL-1) promote leukocyte adhesion to endothelium and migration through vessels during inflammation. →

Tumor necrosis factor (TNF) and interleukin-1 (IL-1) support leukocyte recruitment and activation, produce systemic inflammatory responses, and provide therapeutic targets in chronic inflammation. →

Cytokines coordinate systemic inflammatory responses, leukocyte recruitment, and macrophage activation. Their roles overlap between acute and chronic inflammation. →

Chemokines direct leukocyte movement during inflammation and maintain the normal anatomical distribution of cells within tissues. →

The complement system comprises soluble proteins and membrane receptors involved mainly in antimicrobial defense and pathological inflammatory reactions. →

Following C3 cleavage, complement activation produces mediators of inflammation, opsonins for phagocytosis, and a membrane attack complex that lyses cells. →

Complement regulators protect normal host tissues by limiting active complement fragments and removing deposited fragments. Failure of this protection can cause tissue injury. →

Complement supports host defense, but its activation on host tissues or inadequate regulation can contribute to disease. →

Several additional mediator systems influence vascular responses, platelet activation, pain, and inflammatory signaling, although some of their roles remain uncertain. →

Acute inflammatory reactions share vascular and cellular changes, while their specific morphologic patterns can help identify the underlying cause. →

Acute inflammation can produce fibrin-rich exudates or pus. The composition and subsequent fate of these exudates determine their morphologic appearance and consequences. →

Inflammatory lesions differ in their exudates, distribution of tissue necrosis, cellular composition, and subsequent repair. →

Acute inflammation typically ends in resolution, connective tissue replacement, or progression to chronic inflammation. The outcome depends partly on the injury, affected tissue, and host response. →

Chronic inflammation can arise from persistent infection, inappropriate immune responses, or prolonged exposure to harmful substances. →

Chronic inflammation combines inflammatory cell infiltration, tissue destruction, and attempts at repair. →

Macrophages are professional phagocytes with roles in host defense, inflammation, and repair. Their circulating counterparts are monocytes. →

Macrophages follow two major activation pathways, classical and alternative, according to the activating signals they receive. →

Activated macrophages help eliminate injurious agents and initiate repair, while also causing much of the tissue injury in chronic inflammation. →

Lymphocytes amplify chronic inflammation, while macrophages differ in their developmental origins and activation-dependent functions. →

CD4 T-cell subsets produce distinct cytokines that shape inflammation. Reciprocal interactions between lymphocytes and macrophages sustain chronic inflammatory reactions. →

Chronic inflammatory reactions may contain organized lymphoid structures, eosinophils, and persistent neutrophilic infiltrates. →

Granulomatous inflammation is a form of chronic inflammation characterized by collections of activated macrophages, often accompanied by T lymphocytes and sometimes central necrosis. →

Granulomas narrow the possible causes of inflammation, while cytokines can produce systemic reactions even when inflammation is localized. →

Systemic inflammatory responses include fever and changes in circulating leukocytes. The target passage also describes granulomatous findings in tuberculosis and leprosy. →

Granulomatous diseases differ in their causes, inflammatory cell composition, and patterns of necrosis. →

Systemic inflammation alters blood cell counts, induces hepatic plasma protein synthesis, and produces metabolic and constitutional effects. →

Severe systemic inflammation can cause widespread abnormalities, while repair restores tissue architecture and function through regeneration and scar formation. →

A tissue's ability to repair injury depends partly on the proliferative capacity of its cells and the preservation of its supporting framework. →

Regeneration combines proliferation of surviving cells with the production of mature cells from stem cells. →

Regeneration depends on the tissue involved, its capacity for cell proliferation, and preservation of the supporting tissue structure. →

Growth factors support repair through effects on fibroblasts, keratinocytes, blood vessels, and extracellular matrix. Liver regeneration also depends on preservation of tissue structure. →

The liver regenerates through residual hepatocyte proliferation or stem cell repopulation, with the dominant mechanism determined by the injury. →

Skin wounds progress through hemostasis, inflammation, and cell proliferation before remodeling produces a fibrous scar. →

Later wound repair reorganizes deposited connective tissue, while new vessel formation supports healing and has wider roles in ischemia and tumor growth. →

Repair involves new vessel formation, fibroblast recruitment, and deposition of extracellular matrix (ECM), followed by maturation into a scar. →

The extracellular matrix (ECM) regulates cell behavior and supplies the structural scaffold needed for regeneration. Persistent injury can instead lead to replacement of normal tissue by connective tissue. →

Extracellular matrix (ECM) components provide tensile strength, recoil, resistance to compression, and attachment sites that support wound repair. →

Cells interact with the extracellular matrix (ECM) through integrins. During wound repair, fibroblasts and myofibroblasts migrate, contract the wound, and synthesize connective tissue proteins. →

Scar maturation reflects the balance between extracellular matrix (ECM) synthesis and degradation. Remodeling strengthens the wound while reducing scar size. →

Granulation tissue develops at an injury site and progresses toward a collagen-rich scar. Infection, metabolic disease, nutritional deficiency, and glucocorticoids can interfere with repair. →

Local mechanical factors, inadequate perfusion, and foreign material can impair tissue repair. Chronic ulcers illustrate several distinct mechanisms of healing failure. →

Abnormal repair may produce wound rupture, excessive scar tissue, or exaggerated wound contraction. →

Fibrosis in chronic disease shares mechanisms with cutaneous scar formation. Inflammation coordinates recognition and removal of injury, followed by regulation and repair. →

Inflammation changes vascular flow and permeability and recruits circulating leukocytes into affected tissues through a sequence of endothelial interactions. →

Leukocytes eliminate microbes and debris using mechanisms that can also injure normal tissue. Inflammatory mediators coordinate these responses, which produce recognizable morphologic patterns. →

Persistent inflammatory stimuli produce chronic cellular responses and scarring. Inflammation also has systemic effects, while tissue regeneration depends on the proliferative capacity of surviving cells. →

Repair by scarring replaces injured tissue with connective tissue when regeneration cannot occur. The passage also describes factors affecting wound healing and the significance of C-reactive protein in inflammation. →

The erythrocyte sedimentation rate (ESR) increases when red cells aggregate and sediment more rapidly. This passage explains how inflammatory proteins promote aggregation and lists conditions associated with elevated ESR. →