Chronic inflammation is a long-lasting inflammatory process where inflammation and tissue destruction occur simultaneously. Unlike acute inflammation, which is sudden and short, chronic inflammation develops slowly and persists for weeks, months or years.
Causes of Chronic Inflammation
Chronic inflammation may arise in three major ways:
1. Chronic Inflammation Following Acute Inflammation
If the initial acute response fails to eliminate the irritant—for example when bacteria survive or tissue destruction is extensive—the inflammation becomes chronic. Examples: osteomyelitis, pneumonia ending in lung abscess.
2. Recurrent Attacks of Acute Inflammation
Repeated acute episodes eventually lead to chronicity. Examples: recurrent UTI → chronic pyelonephritis, repeated gallbladder infection → chronic cholecystitis.
3. Chronic Inflammation Starting De Novo
Some agents cause chronic inflammation from the beginning, especially organisms with low pathogenicity. Example: Mycobacterium tuberculosis.
General Features of Chronic Inflammation
1. Mononuclear Cell Infiltration
Chronic inflammation is dominated by mononuclear cells:
- Macrophages (most important)
- Lymphocytes
- Plasma cells
- Eosinophils
- Mast cells
Macrophages arrive from blood monocytes and accumulate due to:
- Continuous chemotaxis
- Local proliferation
- Longer survival at the site
Activated macrophages release proteases, reactive oxygen species, nitric oxide, and cytokines (IL-1, IL-8, TNF-α) causing tissue damage and promoting fibrosis.
2. Tissue Destruction or Necrosis
This is a central feature. Enzymes and toxic mediators released by macrophages damage the surrounding tissue.
3. Proliferative Changes
Tissue destruction stimulates:
- Formation of new blood vessels (neovascularisation)
- Fibroblast proliferation
- Development of inflammatory granulation tissue
- Healing by fibrosis and collagen deposition
Systemic Effects of Chronic Inflammation
- Fever: Usually mild; associated with weight loss and weakness.
- Anaemia: Common due to chronic disease.
- Leucocytosis: Increased WBC count, often with relative lymphocytosis.
- Raised ESR: A consistent sign in chronic inflammation.
- Amyloidosis: Long-standing suppurative inflammation may lead to secondary AA amyloidosis.
Types of Chronic Inflammation
Chronic inflammation is conventionally divided into:
1. Chronic Non-Specific Inflammation
Occurs when the irritant causes a general inflammatory response without a special tissue pattern. Examples: chronic osteomyelitis, chronic ulcers.
A variant is chronic suppurative inflammation, where pus formation and polymorph infiltration are prominent. Example: actinomycosis.
2. Chronic Granulomatous Inflammation
This type shows the formation of granulomas, which are organised collections of modified macrophages (epithelioid cells) surrounded by lymphocytes.
Examples: tuberculosis, leprosy, syphilis, sarcoidosis, actinomycosis.
Granulomatous Inflammation
What is a Granuloma?
A granuloma is a small, well-defined lesion (~1 mm) made up of:
- Central macrophages transformed into epithelioid cells
- Multinucleated giant cells (sometimes)
- Peripheral lymphocytes
- Fibroblasts or collagen in older granulomas
Pathogenesis of Granuloma
Granuloma formation is a type IV hypersensitivity reaction and a defence mechanism against indigestible material (e.g., Mycobacterium, talc particles, suture material).
The steps are:
1. Engulfment by Macrophages
Macrophages try to phagocytose the antigen but fail because the material is poorly degradable. They then transform into epithelioid cells.
2. Activation of CD4+ T Cells
Macrophages present the antigen to CD4+ T lymphocytes. Activated T cells release lymphokines (IL-1, IL-2, interferon-γ, TNF-α).
3. Cytokine-Mediated Granuloma Formation
Cytokines regulate granuloma development:
- IL-1, IL-2: Stimulate more T-cell proliferation
- Interferon-γ: Activates macrophages
- TNF-α: Stimulates fibroblasts, endothelial cells → promotes fibrosis
- Growth factors: Support fibroblast proliferation and collagen formation
The final granuloma consists of epithelioid cells, occasional giant cells and a lymphocyte ring, ultimately healing by fibrosis.
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