Lecture IV

• Chronic inflammation is characterized by prolonged duration (weeks or months) in which inflammation, tissue injury, and attempts at repair coexist in varying combinations
• Etiology of chronic inflammation includes:

  • Autoimmune diseases
  • Chronic exposure to toxic pathogens and foreign material (e.g., silica)
  • Nondegradable pathogens (e.g., foreign material)
  • Persistent infections (e.g., tuberculosis, syphilis, certain viral and fungal infections) leading to type IV hypersensitivity reaction
• Cells involved in chronic inflammation:

  • Mononuclear cells
  • Monocytes
  • Macrophages
  • Lymphocytes
  • Plasma cells
  • Fibroblasts
  • T lymphocytes
• Morphologic features of chronic inflammation:

  • Infiltration with mononuclear cells, including macrophages, lymphocytes, and plasma cells
  • Tissue destruction induced by the persistent offending agent or by the inflammatory cells
  • Attempts at healing by connective tissue replacement of damaged tissue, accomplished by angiogenesis (proliferation of small blood vessels) and fibrosis
• Granulomatous inflammation is a distinct type of chronic inflammation characterized by the formation of granulomas in affected tissues
• Etiology of granulomatous inflammation includes:

  • Infections (most common cause)
  • Fungal infections (e.g., histoplasmosis)
  • Bacterial infections (e.g., mycobacteria such as leprosy and tuberculosis)
  • Immune-mediated diseases like sarcoidosis and Crohn disease
  • Foreign body exposure such as berylliosis and talcosis
• Granuloma formation involves macrophages activating Th1 cells, stimulating the formation of epithelioid cells and multinucleated giant cells by releasing IFN-γ
• Systemic effects of inflammation include:

  • Cytokine-induced systemic reactions known as the acute-phase response
  • Fever induced by pyrogens stimulating the release of IL-1 and TNF
  • Elevated levels of acute-phase proteins like C-reactive protein, fibrinogen, and serum amyloid A protein
  • Leukocytosis with accelerated release of granulocytes from the bone marrow
  • Increased pulse and blood pressure, decreased sweating, rigors, chills, anorexia, somnolence, and malaise
• Tissue repair occurs by two processes:

  • Regeneration, which restores normal cells
  • Scarring, the deposition of connective tissue
• Cell and tissue regeneration is determined by the intrinsic proliferative capacity of tissues and the presence of tissue stem cells
• Repair by connective tissue deposition involves steps like inflammation, cell proliferation, formation of granulation tissue, and deposition of collagen
• Angiogenesis is the process of new blood vessel development from existing vessels, involving steps like vasodilation, separation of pericytes, migration and proliferation of endothelial cells, and remodeling into capillary tubes
• Healing of skin wounds can occur by first or second intention, depending on the nature and size of the wound