Chronic Inflammation Lecture Notes

Overview of Inflammation

• Inflammation is a non-specific protective mechanism.
• Aimed at eliminating foreign invaders and damaged tissues.
• Two types: Acute Inflammation and Chronic Inflammation.
  • Chronic inflammation is prolonged and involves ongoing tissue destruction and repair by fibrosis.

Characteristics of Chronic Inflammation

• Tissue Destruction: Ongoing destruction with fibrosis.
• Repair Attempts: May occur with or without cell regeneration.
• Can develop after acute inflammation or insidiously.
• Associated with significant morbidity due to tissue destruction.

Causes of Chronic Inflammation

1. Persistent Infections
   • Organisms difficult to eradicate, e.g., Mycobacterium tuberculosis, Mycobacterium leprae.
   • Evoke a type 4 hypersensitivity reaction.
2. Persistent Indigestible Materials
   • Endogenous: Necrotic bone, adipose tissue, calcium, uric acid deposits.
   • Exogenous: Silica, asbestos fibers, suture material.
3. Immune-Mediated Reactions
   • Autoimmune (e.g., rheumatoid arthritis, systemic lupus erythematosus).
   • Organ transplant rejections.
   • Unregulated immune responses (e.g., inflammatory bowel disease).
   • Hypersensitivity reactions (e.g., asthma, hypersensitivity pneumonitis).
4. Following Acute Inflammation
   • Persistent abscesses that do not drain.
   • Repeated acute inflammation episodes (e.g., chronic pancreatitis, chronic cholecystitis).

Morphological Features

Macroscopic Features

• Ulcer formation on epithelial surfaces.
• Cavitatory lesions in parenchymal tissue (e.g., pulmonary tuberculosis).
• Chronic abscesses with fibrous capsule.
• Sinus and fistula formation (e.g., Crohn's disease).

Microscopic Features

• Mononuclear cell infiltration: Predominantly macrophages and lymphocytes.
• Tissue necrosis and regeneration with fibrosis.
• Granulomatous inflammation with multi-nucleated giant cells in some cases.

Role of Macrophages

• Recruitment from blood to site (mediated by TGF-beta and PDGF).
• Proliferation at the site of inflammation.
• Immobilization (mediated by migration inhibition factor).
• Activation by interferon gamma and exotoxins.
• Functions: Secretion of destructive agents, increased phagocytic activity, secretion of growth-promoting agents.

Clinical Manifestations

• Ulceration, sinus, and fistula formation.
• Cavitatory lesions and loss of function.
• Wall thickening and stricture formation due to fibrosis.
• Organ distortion and fibrous adhesions (e.g., in intestines, meninges, pericardium).
• Systemic manifestations: Splenomegaly, hepatomegaly, lymphadenopathy, anemia of chronic disease, high ESR, low-grade fever, loss of appetite and weight.

These notes should provide a comprehensive overview of chronic inflammation, capturing essential points about its causes, characteristics, macrophage role, and associated clinical manifestations.