INFLAMMATION - Exam Answers (1.5 Page Format)

Q1. Acute Inflammation

Components of Acute Inflammation

1. Dilation of small vessels - increasing blood flow
2. Increased vascular permeability - allowing plasma proteins and leukocytes to exit circulation
3. Emigration and activation of leukocytes at the site of injury

Vascular Changes

• Vasodilation: Earliest manifestation. Mediators (especially histamine) cause dilation of postcapillary venules, increasing blood flow → redness and heat.
• Increased vascular permeability: Protein-rich fluid (exudate) leaks into tissues → edema and swelling. Contrasts with transudate (low protein, from hydrostatic/osmotic imbalance).
• Stasis: As fluid leaves, blood thickens and flow slows; leukocytes (mainly neutrophils) begin to accumulate along vessel walls (margination).

Cellular Events (Leukocyte Recruitment)

1. Margination and rolling - via selectins (L-, E-, P-selectin) binding sialyl-Lewis X ligands
2. Adhesion - via integrins (LFA-1, MAC-1) binding ICAM-1 on endothelium
3. Transmigration (diapedesis) - through endothelial junctions, CD31 (PECAM-1) mediates
4. Chemotaxis - directed migration toward chemoattractants: C5a, LTB4, IL-8, bacterial products

Phagocytosis

• Recognition and attachment (aided by opsonins: IgG, C3b)
• Engulfment into phagosome
• Killing via reactive oxygen species (respiratory burst), NO, lysosomal enzymes, and neutrophil extracellular traps (NETs)

Chemical Mediators of Acute Inflammation

Morphologic Patterns of Acute Inflammation

1. Serous inflammation - watery, protein-poor fluid (e.g., skin blister, pleural effusion)
2. Fibrinous inflammation - fibrin-rich exudate (e.g., fibrinous pericarditis - "bread and butter" appearance)
3. Purulent (suppurative) inflammation - pus-forming; neutrophil-rich (e.g., abscess)
4. Ulceration - necrosis with surface erosion (e.g., peptic ulcer)

Outcomes of Acute Inflammation

1. Complete resolution - elimination of agent, removal of debris by macrophages, return to normal (ideal outcome when tissue can regenerate)
2. Healing by scarring (fibrosis) - when tissue destruction is extensive or tissue cannot regenerate
3. Progression to chronic inflammation - when the agent persists or healing is impaired

Q2. Chronic Inflammation

Causes of Chronic Inflammation

1. Persistent infections by organisms difficult to eradicate - mycobacteria (TB, leprosy), certain fungi, parasites; often evoke delayed-type hypersensitivity
2. Hypersensitivity (immune-mediated) diseases - autoimmune diseases (rheumatoid arthritis, multiple sclerosis), inflammatory bowel disease, bronchial asthma; self-perpetuating T and B lymphocyte reactions
3. Prolonged exposure to toxic substances - silica (silicosis), excess cholesterol (atherosclerosis)

Morphologic Features

• Infiltration by mononuclear cells - macrophages, lymphocytes, and plasma cells (in contrast to neutrophils in acute)
• Tissue destruction induced by persistent offending agents or inflammatory cells
• Attempts at healing - angiogenesis (new blood vessel proliferation) and fibrosis (connective tissue replacement)

Cells Involved

• Phagocytose microbes and dead tissue
• Secrete cytokines (TNF, IL-1, chemokines) perpetuating inflammation
• Initiate tissue repair (M2/alternatively activated macrophages via IL-4, IL-13 → TGF-β, VEGF)
• Classically activated (M1) macrophages: induced by IFN-γ, produce NO and ROS → destroy microbes
• Alternatively activated (M2) macrophages: promote tissue repair and fibrosis

Q3. Granulomatous Inflammation

Pathogenesis

• The inciting agent (persistent microbe or foreign material) activates Th1 CD4+ cells
• Th1 cells produce IFN-γ → activates macrophages to become epithelioid cells
• Activated macrophages fuse to form multinucleated giant cells (Langhans giant cells: nuclei arranged in horseshoe pattern at periphery)
• In some parasitic infections (e.g., schistosomiasis), strong Th2 responses + eosinophils are involved

Types of Granulomas

• Reaction to inert, non-immunogenic foreign material (talc, suture, splinters)
• Too large for single macrophage to phagocytose
• No T cell-mediated immune response required
• Foreign material often visible in center (may appear refractile under polarized light)

• Caused by persistent agents that induce T cell-mediated immune responses
• Driven by Th1 cells secreting IFN-γ → macrophage activation

Morphology (H&E appearance)

• Epithelioid cells: Activated macrophages with abundant pink granular cytoplasm and indistinct cell borders; resemble epithelial cells
• Langhans giant cells: 40-50 μm; multinucleated (nuclei at periphery in horseshoe pattern); formed by fusion of activated macrophages
• Collar of lymphocytes surrounding the aggregate
• Rim of fibroblasts in older granulomas
• Caseous necrosis (central): amorphous, granular, eosinophilic, cheesy debris; seen especially in TB; represents hypoxia + free radical injury
• Healing accompanied by fibrosis

Examples of Diseases with Granulomatous Inflammation