Intro & Causes - The Slow Burn
- Inflammation of prolonged duration (weeks to months).
- Characterized by co-existing:
- Active inflammation
- Tissue destruction
- Repair attempts (angiogenesis, fibrosis)
- Onset:
- May follow unresolved acute inflammation.
- May begin insidiously (de novo).
- Principal Causes:
- Persistent infections (e.g., Mycobacterium tuberculosis, Treponema pallidum, fungi, viruses).
- Hypersensitivity diseases (e.g., autoimmune: RA, IBD; allergic: asthma).
- Prolonged exposure to toxic agents (exogenous: silica; endogenous: cholesterol).
⭐ Infiltration with mononuclear cells (macrophages, lymphocytes, plasma cells) is a hallmark of chronic inflammation.
Cellular Players - The Chronic Crew
Persistent inflammation is orchestrated by a specialized cellular cast (📌 MLP-EM: Macrophages, Lymphocytes, Plasma cells, Eosinophils, Mast cells). These cells interact, releasing mediators sustaining the response and influencing tissue injury/repair.
| Cell | Origin/Key Features | Key Functions in Chronic Inflammation |
|---|---|---|
| Macrophages | Monocytes; M1 (classical), M2 (alternative) | Phagocytosis, Ag presentation, cytokines (TNF, IL-1, IL-6), growth factors |
| Lymphocytes | T-cells (CD4+, CD8+), B-cells | Bidirectional macrophage activation (IFN-γ, IL-12); adaptive immunity |
| Plasma Cells | Differentiated B-lymphocytes | Produce antibodies against persistent antigens/autoantigens |
| Eosinophils | Granulocytes; recruited by eotaxin | Helminth defense; IgE-mediated allergic reactions (MBP release) |
| Mast Cells | Tissue-resident; surface IgE receptors | Release histamine, leukotrienes, proteases, cytokines; modulate inflammation |
⭐ Epithelioid cells in granulomas are activated macrophages with abundant pink cytoplasm, resembling epithelial cells, key for granulomatous inflammation.
Mediators & Mechanisms - Fueling the Fire
- Key Mediators:
- Cytokines: Pro-inflam: TNF, IL-1, IL-6; IFN-γ (T-cell driven macrophage activation); IL-10 (anti-inflam), TGF-β (fibrosis).
- Chemokines: Attract specific leukocytes (e.g., MCP-1).
- Growth Factors: PDGF, FGF, TGF-β stimulate angiogenesis & fibrosis.
- Mechanisms:
- Persistent stimuli (microbes, irritants).
- Macrophage-Lymphocyte interactions: Bidirectional activation.
- Concurrent tissue injury & attempted repair (fibrosis).
⭐ IFN-γ, produced by NK cells and T lymphocytes (Th1, CD8+), is the most potent endogenous macrophage-activating cytokine.
Granulomatous Inflammation - Walling Off Trouble
- Hallmark: Aggregates of activated macrophages (epithelioid cells), often with a collar of lymphocytes; may fuse to form multinucleated giant cells (e.g., Langhans, foreign body type).
- Purpose: To contain or "wall off" an offending agent that is difficult to eradicate.
| Type | Mechanism | Key Mediators | Examples |
|---|---|---|---|
| Immune | Persistent T-cell (Th1) response to antigen (Ag) | IFN-γ (activates Mφ) | Tuberculosis (caseating), Sarcoidosis (non-caseating), Leprosy, Fungal inf., Crohn's d. |
| Foreign Body | Inert material; direct Mφ activation | - | Sutures, talc, silica, asbestos, beryllium (can also be immune-mediated) |
Systemic Effects & Outcomes - The Body's Burden
- Fever: Persistent low-grade; IL-1, TNF mediated.
- Acute Phase Response:
- Liver: ↑CRP, SAA, Fibrinogen (IL-6 driven).
- Results in ↑ESR.
- Leukocytosis: ↑WBC count; pattern indicates etiology (e.g., neutrophilia, lymphocytosis).
- Anemia of Chronic Disease (ACD):
- IL-6 → ↑Hepcidin → ↓iron absorption & release.
- Cachexia: TNF-α (cachectin) causes muscle/fat loss.
- Secondary (AA) Amyloidosis: Chronic inflammation → ↑SAA → organ deposition.
⭐ ACD: Characterized by ↓ serum iron, ↓ TIBC, and normal/↑ ferritin.
High‑Yield Points - ⚡ Biggest Takeaways
- Chronic inflammation is characterized by prolonged duration and co-existing active inflammation, tissue injury, and healing attempts.
- Key cellular players are macrophages, lymphocytes (T and B cells), and plasma cells.
- Tissue destruction is often mediated by inflammatory cells and their products.
- Repair involves angiogenesis and fibrosis (scarring).
- Granulomatous inflammation (e.g., TB, sarcoidosis) features epithelioid macrophages and giant cells.
- Mediators include cytokines (e.g., TNF, IL-1, IFN-γ) and growth factors.
- Potential long-term sequelae include loss of function, fibrosis, and neoplastic transformation (e.g., chronic gastritis and cancer).
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