26. Chronic inflammation - classification, etiology, pathogenesis.

Chronic inflammation - classification, etiology, and pathogenesis.

Chronic inflammation is a prolonged inflammatory response that occurs when acute inflammation fails to eliminate the injurious agent, or when the stimulus persists.

Duration: Weeks to years.

Main cells involved: Mononuclear cells (macrophages, lymphocytes, plasma cells), fibroblasts.

Classification of Chronic Inflammation

1. 1 Primary chronic inflammation

Starts as chronic without a preceding acute phase.

Examples:

• Tuberculosis.
• Autoimmune diseases (e.g., rheumatoid arthritis).
• Viral infections (e.g., hepatitis B).

1. 2 Secondary chronic inflammation

Follows unresolved or repeated acute inflammation.

Examples:

• Chronic osteomyelitis.
• Chronic non- healing ulcers.

1. 3 Specific (granulomatous) chronic inflammation

Characterized by granuloma formation — organized collection of macrophages.

Examples:

• TB (caseating granuloma).
• Sarcoidosis (non- caseating granuloma).
• Foreign body granulomas (around sutures).

Etiology (Causes)

1. 1 Persistent infections

Difficult-to-eradicate microbes (e.g., Mycobacterium tuberculosis, certain fungi).

1. 2 Prolonged exposure to toxic agents

Exogenous: silica particles (silicosis).

Endogenous: cholesterol crystals in atherosclerosis.

1. 3 Autoimmune diseases

Self- antigens persistently stimulate immune response.

Examples: Systemic lupus erythematosus (SLE), rheumatoid arthritis.

Pathogenesis of Chronic Inflammation

1. 1 Persistent antigenic stimulation

Continuous presence of microbes, foreign bodies, or self- antigens.

Sustained cytokine and chemokine production → ongoing leukocyte recruitment.

1. 2 Cellular components

Macrophages

Central role; derived from monocytes.

Activated by IFN-γ (from T cells) and microbial products.

Functions:

• Phagocytosis.
• Secretion of cytokines (TNF-α, IL-1), growth factors → fibroblast activation, angiogenesis.
• Presentation of antigens to T cells → perpetuates inflammation.

Lymphocytes

CD4+ T cells (Th1, Th2, Th17) help orchestrate responses.

B cells and plasma cells produce antibodies (especially in autoimmune conditions).

Other cells

Eosinophils: prominent in parasitic infections and allergic reactions.

Mast cells: release mediators that can sustain chronic inflammation.

1. 3 Tissue destruction and repair

Ongoing tissue damage due to ROS, proteases.

Simultaneous healing:

• Angiogenesis (new vessel formation).
• Fibrosis (fibroblast activation, collagen deposition).

1. 4 Granuloma formation (in specific chronic inflammation)

Aggregates of epithelioid macrophages surrounded by lymphocytes.

May contain multinucleated giant cells.

Aim: isolate difficult-to-remove agents.

Outcomes of Chronic Inflammation

Progressive tissue destruction → loss of function.

Fibrosis and scar formation.

Possible development of metaplasia or neoplasia in persistent cases.