Acute Inflammation Pathogenesis

Acute Inflammation Pathogenesis

• Learning Objectives: Students will be able to evaluate leukocyte recruitment, understand the role of neutrophils and macrophages, classify acute inflammation types, and correlate subtypes with clinical conditions.

Leukocyte Recruitment

• Neutrophils and macrophages are recruited to sites of injury to eliminate pathogens and debris, initiating tissue repair.
• The type of leukocyte recruited depends on the initial stimulus and duration of the inflammatory response.
  • Bacterial infections primarily recruit neutrophils.
  • Viral infections recruit lymphocytes.
  • Allergic reactions increase eosinophils.
  • Necrosis initially induces neutrophilic recruitment, transitioning to monocytes after 24-48 hours.

Leukocyte Migration

• Leukocytes move from blood vessels to tissue interstitium through a multi-step process:
  • Margination, rolling, and adhesion to endothelium.
  • Transmigration across the endothelium.
  • Migration towards chemoattractants (chemotaxis).
  • Apoptosis (programmed cell death) occurs in neutrophils after 24-48 hours, whereas monocytes survive longer.

Leukocyte Adhesion & Interactions

• Leukocyte movement involves adhesion molecules on both leukocytes and endothelium.
• Key adhesion molecule pairs include selectins (initiating weak interactions) and integrins (mediating firm adhesion).
• Cytokines (e.g., TNF, IL-1) enhance adhesion molecule expression.

Leukocyte Transmigration

• Leukocytes migrate through the vessel wall by squeezing between endothelial cells at intercellular junctions.
• They cross the basement membrane and enter the extravascular tissue, without significant vessel wall injury.

Chemotaxis

• Chemotaxis is directional cell movement along a chemical gradient.
• Chemotactic agents (e.g., bacterial products, complement components, chemokines) attract leukocytes to the site of injury.
• Leukocyte movement is facilitated by actin polymerization and interaction with the extracellular matrix.

Phagocytosis

• Phagocytosis is the process of engulfing and destroying pathogens or cellular debris.
• Phagocytes recognize and attach to targets via phagocytic receptors.
• Internalization of the target forms a phagosome, which fuses with lysosomes to form phagolysosomes.
• Reactive oxygen species (ROS), reactive nitrogen species, and lysosomal enzymes degrade the target material within the phagolysosome.

Role of Neutrophils and Macrophages

• Neutrophils and macrophages are crucial in pathogen clearance and tissue damage repair.
• These cells contain granules with antimicrobial enzymes and proteins.

ROS & other Products

• Reactive oxidative species (ROS) are potent antimicrobial products.
• Activated leukocytes, particularly macrophages, produce cytokines regulating inflammatory reactions and growth factors promoting collagen synthesis.

Termination of Acute Inflammation

• Mediators have short half-lives and stop signals (anti-inflammatory cytokines, e.g., TGF-β, IL-10) regulate the inflammatory response.

Morphologic Hallmarks

• Vasodilation of small blood vessels.
• Fluid and leukocyte accumulation in extravascular tissue.

Serous Inflammation

• Fluid exudation in body cavities lining or surface epithelium.
• This fluid is mostly protein-poor, sterile with little leukocyte accumulation (not typically infected).
• Examples include skin blisters due to burns or infections.

Fibrinous Inflammation

• Procoagulant stimulus or increased vascular permeability causing higher-molecular-weight proteins like fibrinogen to leak out from the blood, forming fibrin deposits in the extracellular space.
• Examples include linings of body cavities, meninges, pericardium, and pleura.
• Fibrin may be removed by lysis or cleared by macrophages, ultimately leading to scarring.

Purulent(Suppurative) Inflammation

• Characterized by pus formation (neutrophils, liquefied necrotic debris, and edema fluid).
• Usually caused by bacterial infections with pyogenic (pus-forming) bacteria.
• Examples include abscesses and some ulcers.