Acute Inflammation: Mediators & Patterns

Acute Inflammation: Chemical Mediators & Morphological Patterns

• Acute inflammation has four major components: vascular changes, microvascular changes, cellular events, and mediators.
• Vascular changes include alterations in vascular caliber (vasodilation), increasing blood flow.
• Microvascular changes involve alterations in microvasculature permeability, leading to plasma protein and white blood cell (WBC) leakage.
• Cellular events encompass WBC emigration, accumulation, and activation at the injury site.
• Mediators are derived from plasma proteins and cells.

Inflammatory Mediators

• Inflammatory mediators are chemical substances triggering processes in inflammatory reactions.
• Mediators are categorized as cell-derived and plasma-derived.

Cell-Derived Mediators

• Preformed mediators stored in secretory granules (e.g., histamine, serotonin, lysosomal enzymes).
• Newly synthesized mediators (e.g., prostaglandins, leukotrienes, platelet-activating factors, activated oxygen species, nitric oxide, cytokines).
• Examples of sources for these mediators include mast cells, basophils, platelets, neutrophils, macrophages, leukocytes, and various cell types.

Plasma-Derived Mediators

• Circulate in an inactive form, requiring activation.
• Examples include components of the complement system (e.g., C3a, C5a), kinin system (bradykinin), and coagulation/fibrinolysis system.
• The complement system, bradykinin, and factor XII are interrelated protein systems involved in inflammatory reactions.

Principles of Mediators

• Initially bind to specific receptors and act.
• Stimulate the release of other mediators.
• Can act on one or a few target cell types.
• Are short-lived after activation.
• Can be potentially harmful.

Active Mediators

• Active mediators are produced in response to injurious stimuli, such as microbial products and substances released from necrotic cells.
• Proteins of the complement, kinin, and coagulation systems activated by microbes and damaged tissues.
• Inflammation is triggered only when and where needed.

Roles of Mediators

• Mediators affect blood vessels, inflammatory cells, and other body cells.

Effects of Mediators

• Vasodilation, vasoconstriction, altered vascular permeability, activation of inflammatory cells, chemotaxis, cytotoxicity, tissue degradation, pain, and fever.

(A) Cell-Derived Mediators

• Vasoactive amines (e.g., histamine).
• Arachidonic acid derivatives (e.g., prostaglandins, leukotrienes).
• Platelet-activating factor (PAF).
• Cytokines.
• Nitric oxide (NO).

1. Serous Inflammation

• Outpouring of thin fluid derived from plasma and mesothelial cells lining cavities (e.g., peritoneal, pleural, pericardial).
• Accumulation of fluid is called effusion.
• Skin blisters are an example.

2. Fibrinous Inflammation

• Characterized by fibrin deposition in extracellular spaces.
• Occurs during severe injuries with increased vascular permeability.
• Examples include exudates in the meninges, pericardium, and pleura.

3. Purulent Inflammation & Abscess

• Production of large amounts of pus (purulent exudate).
• Consists of neutrophils, liquefactive necrosis, and edema fluid.
• Caused by pyogenic bacteria (e.g., staphylococci).
• Abscesses are localized collections of purulent inflammatory exudate (pus).

4. Ulcer

• A local defect or excavation on an organ or tissue surface.
• Resulting from sloughing (shedding) of inflammatory necrotic tissue.
• Occurs when tissue necrosis and inflammation exist on or near a surface.
• Common sites include the mucosa of the mouth, stomach, intestines, genitourinary tract, and skin/subcutaneous tissues.