Inflammation: High-Yield Pathology
Inflammation is a protective, vascularized tissue response to injury or infection. It is broadly divided into acute (rapid onset, neutrophil-dominated) and chronic (prolonged, mononuclear cell-dominated) phases.
1. Cardinal Signs of Acute Inflammation
Driven by hemodynamic changes and chemical mediators:
| Sign | Mechanism | Key Mediator(s) |
|---|---|---|
| Rubor (Redness) & Calor (Heat) | Vasodilation, increased blood flow | Histamine, Prostaglandins ( ), Nitric Oxide |
| Tumor (Swelling) | Increased vascular permeability (exudate) | Histamine, Leukotrienes ( ) |
| Dolor (Pain) | Sensitization of nerve endings | Prostaglandins ($LatexPGE_2$), Bradykinin |
| Functio Laesa | Loss of function | Combined structural/chemical effects |
2. Leukocyte Extravasation Sequence
The recruitment of neutrophils to the site of injury follows a highly regulated multistep cascade:
- Margination and Rolling: Leukocytes line up along the endothelium. Loose, transient attachments are mediated by Selectins (E-selectin, P-selectin on endothelium; L-selectin on leukocytes) binding to Sialyl Lewis X.
- Firm Adhesion: Leukocytes attach firmly to the endothelial wall. Mediated by Integrins on leukocytes (LFA-1, Mac-1, VLA-4) binding to immunoglobulin superfamily ligands on endothelium (ICAM-1, VCAM-1).
- Transmigration (Diapedesis): Leukocytes squeeze through endothelial junctions, primarily mediated by PECAM-1 (CD31).
- Chemotaxis: Leukocytes migrate toward the injury gradient driven by chemoattractants: LTB4, IL-8, C5a, and bacterial products (formyl peptides).
3. Chronic & Granulomatous Inflammation
- Cellular Profile: Macrophages, lymphocytes, and plasma cells replace neutrophils. Driven by persistent infections, autoimmune diseases, or foreign material.
- Granuloma Formation: A specialized pattern of chronic inflammation designed to wall off an indigestible agent. Characterized by a collection of activated epithelioid macrophages surrounded by a collar of lymphocytes.
- Key Cytokine: IFN-gamma (secreted by Th1 cells) is the crucial signal that activates macrophages into epithelioid cells and promotes the formation of multinucleated giant cells (e.g., Langhans giant cells).