Pathomechanism and types of chronic inflammation, organic example

1. Definition & characteristics

Chronic inflammation is inflammation of prolonged duration (weeks to months) in which active inflammation, tissue injury, and attempts at repair coexist. Acute inflammation becomes chronic when the offending agent is not removed. Compared with acute inflammation it shows:

• No edema, no vascular changes, fewer neutrophils — it is essentially non-exudative.
• Infiltration by mononuclear cells (macrophages, lymphocytes, plasma cells).
• Tissue destruction by inflammatory cells, plus repair (angiogenesis + fibrosis).

2. Causes

• Persistent infections — slow-growing microbes (M. tuberculosis, T. pallidum, many viruses) → lymphocyte/macrophage-dominated reactions.
• Hypersensitivity / immune-mediated — autoimmune disease (rheumatoid arthritis, IBD) and allergic disease (bronchial asthma); the agent cannot be cleared, so disease persists.
• Prolonged toxic exposure — exogenous (silica → silicosis) or endogenous (cholesterol crystals → atherosclerosis).
• Mild chronic inflammation — contributes to Alzheimer’s, atherosclerosis, metabolic syndrome, T2DM, and tumor promotion.

3. Cells and mediators

• Macrophages — dominant cells; from blood monocytes that migrate and transform. Resident forms = Kupffer (liver), histiocytes (lymph node), microglia (CNS), alveolar (lung) → mononuclear phagocyte system. Activation:

  • Classical (M1) — endotoxin, IFN-γ → ROS, NO, lysosomal enzymes → microbicidal + pro-inflammatory.
  • Alternative (M2) — IL-4, IL-13 → growth factors → angiogenesis, fibroblast activation, collagen → repair + anti-inflammatory.

  Fusion of macrophages → multinucleated giant cells.

• Lymphocytes — B cells → plasma cells (antibodies); T cells → cytokines (IFN-γ) that sustain inflammation.

• Eosinophils — IgE/parasite reactions; granules contain major basic protein.

• Mast cells — IgE-mediated histamine release.

4. Granulomatous inflammation

A special form of chronic inflammation: aggregates of activated (epithelioid) macrophages with a lymphocyte collar = granuloma.

• Composition: central necrosis, epithelioid cells (compulsory), giant cells (fused epithelioid cells, often Langhans-type), lymphocytes, fibroblasts.
• Formation: persistent T-cell response (Th1) → IFN-γ → chronic macrophage activation; also immune-mediated disease (Crohn’s) and foreign-body reactions.
• Classification: by necrosis (necrotizing — TB, syphilis vs non-necrotizing — sarcoidosis, Crohn’s); by type (immune — infective/non-infective — vs foreign-body).

Disease	Cause	Key feature
Tuberculosis	M. tuberculosis	Caseating granuloma, Langhans giant cells, Ranke–Ghon complex; Ziehl–Neelsen +
Syphilis	T. pallidum	Gumma (tertiary); Hutchinson triad (congenital)
Sarcoidosis	Unknown	Non-caseating; asteroid & Schaumann bodies
Cat-scratch	Bartonella henselae	Stellate granuloma + neutrophils
Crohn’s	Immune vs gut flora/self	Non-caseating, patchy, near ileocecal junction
Rheumatic fever	Post-streptococcal	Aschoff body, Anitschkow cells

5. Fibrosis / scarring

Fibrosis = hardening/scarring from excess deposition of fibrous connective tissue (collagen + fibronectin), either as normal wound healing or as the pathological end-result of chronic inflammation. Key effector cells are myofibroblasts (from fibrocytes) → collagen production; progressive fibrosis causes organ malfunction.

• Organ examples:
  • Cardiac (LV hypertrophy + hypertension) — interstitial collagen accumulation → myocardial stiffness → ventricular dysfunction.
  • Liver cirrhosis (HCV, alcohol) — collagen distorts architecture → hepatocellular dysfunction + ↑ resistance → hepatic insufficiency and portal hypertension.
  • Chronic gastritis (H. pylori) — lymphoplasmacytic infiltrate, gland atrophy, intestinal metaplasia.

💡 High-yield: Chronic inflammation = mononuclear cells (macrophages, lymphocytes, plasma cells) + tissue destruction + repair (angiogenesis/fibrosis), non-exudative. M1 (IFN-γ, microbicidal) vs M2 (IL-4/IL-13, repair). Granuloma = epithelioid macrophages (compulsory) + giant cells; caseating = TB, non-caseating = sarcoidosis/Crohn’s. Fibrosis is driven by myofibroblasts → collagen → cirrhosis, cardiac stiffness.