24. Inflammation - pathogenesis (primary damage, vascular phase, cellular phase, secondary damage, resolution) and clinical manifestations.

Inflammation - pathogenesis (phase of primary damage, vascular phase, cellular phase, phase of secondary damage, resolution) and clinical manifestation

A complex, protective response of vascularized tissues to harmful stimuli (microbes, trauma, toxins) designed to eliminate the cause of injury and start repair.

Phases of Inflammatory Response

1. 1 Phase of Primary Damage

• Initial tissue injury by pathogens or physical/ chemical insults.
• Release of molecular signals: DAMPs (damage-associated molecular patterns) and PAMPs (pathogen- associated molecular patterns).
• Activation of sentinel cells (mast cells, macrophages, dendritic cells).

Key mediators involved:

• TNF- α, IL- 1 → further recruit and activate immune cells.

1. 2 Vascular Phase

Vasodilation:

• Mediated by histamine, nitric oxide → increased local blood flow → redness and heat.

Increased vascular permeability:

• Due to histamine, bradykinin, leukotrienes → plasma proteins and leukocytes exit → swelling.

Stasis and margination:

• Slowed blood flow allows leukocytes to move toward vessel walls.

1. 3 Cellular Phase

Leukocyte adhesion and migration:

• Rolling (selectins), firm adhesion (integrins), transmigration (PECAM- 1).

Chemotaxis:

• Directed migration toward chemokines (e.g., IL- 8, C5a).

Phagocytosis:

• Recognition via opsonins (IgG, C3b).
• Engulfment → formation of phagolysosome → intracellular killing (via reactive oxygen species and enzymes).

Main cells:

• Early: neutrophils (acute inflammation).
• Later: monocytes/ macrophages (chronic or late acute).

1. 4 Phase of Secondary Damage

Mechanism:

• Excessive or misdirected inflammatory mediator release (e.g., ROS, proteases) causes bystander tissue injury.
• Seen in abscess walls or adjacent tissues during intense acute inflammation.

Functional consequences:

• Local necrosis, impaired function of affected organ.

1. 5 Resolution (Outcomes Phase)

Complete resolution:

• Mediators cleared, tissues return to normal.

Repair by fibrosis:

• If damage is extensive or tissues cannot regenerate.

Chronic inflammation:

• Persistent stimuli → continuous immune activation (e.g., tuberculosis granuloma).