Inflammation Overview

Inflammation

• Complex biological response to injury or harmful stimuli involving vascularized tissues.
• Induced by chemical mediators produced by host cells in response to injurious stimuli.
• Termed by adding "-itis" to the affected organ or tissue.

Significance of Inflammation

• Can cause life-threatening hypersensitivity reactions.
• Can cause progressive organ damage from chronic inflammation and subsequent fibrosis.
• Examples: Rheumatoid arthritis and atherosclerosis

Components of Inflammation

• Plasma fluid proteins.
• Circulating leukocytes: neutrophils, monocytes, eosinophils, lymphocytes, basophils, and platelets.
• Blood vessels.
• Connective tissue cells: mast cells, fibroblasts, macrophages, and lymphocytes.
• Extracellular matrix: Structural proteins (collagen, elastin), adhesive glycoproteins (fibronectin, laminin), and proteoglycans.

Types of Inflammation

• Acute inflammation: Early onset (seconds-minutes), short duration (minutes-days), fluid exudation (edema), polymorphonuclear leukocyte emigration (neutrophils).
• Chronic inflammation: Later onset (days), longer duration (weeks-years), inducing blood vessel proliferation and scarring, involving lymphocytes and macrophages infiltration.

Cardinal Signs of Inflammation

• Redness (rubor).
• Swelling (tumor).
• Heat (calor).
• Pain (dolor).
• Loss of function (functio laesa).
• More prominent in acute inflammation than in chronic inflammation.

General Characteristics of Inflammation

• Vascular wall response: Increased blood flow and vascular permeability.
• Inflammatory cell response: Leukocytes, macrophages, etc.
• Mediated by inflammatory mediators: Circulating plasma proteins and factors locally produced by vessel wall or inflammatory cells.
• Termination: Occurs when causative agents are eliminated and secreted mediators are removed.

Acute Inflammation: Vascular Changes

• Increased blood flow: Initial transient vasoconstriction followed by vasodilation (cause of heat and redness).
• Increased vascular permeability (vascular leakage): Leads to protein-rich fluid (exudate) escaping into extravascular tissue.
• Mechanisms of vascular leakage:
  • Endothelial cell contraction (histamine, bradykinin, leukotrienes).
  • Direct endothelial injury (burns, infections).

Acute Inflammation: Cellular Changes

• Leukocyte recruitment: Margination and rolling, adhesion, transmigration (diapedesis).
• Leukocyte activation: Stimulated by microbes, products of necrotic cells, and mediators.

Phagocytosis: Leukocyte Activation Process

• Recognition and attachment: Receptors on leukocytes recognize microbes and host proteins (opsonins).
• Engulfment: Formation of a phagocytic vacuole.
• Killing and degradation: Oxygen-dependent mechanisms (reactive oxygen and nitrogen species, lysosomal enzymes).

Examples of Inflammation Types

• Serous inflammation: Fluid called effusion in pleural, pericardial, and peritoneal cavities.
• Fibrinous inflammation: Increased vascular permeability, fibrinogen deposited in the extracellular space (meninges, pericardium, pleura).
• Suppurative (purulent) inflammation: Formation of pus, neutrophil infiltration, necrotic cells, edema, caused by bacteria (acute appendicitis).
• Pseudomembranous inflammation: Severe injury, extensive epithelial necrosis and sloughing, formation of a pseudo-membrane (Diphtheria).

Abscess

• Localized collection of purulent inflammatory exudates in tissue or organ.
• Central mass of necrotic leukocytes and tissue debris surrounded by preserved neutrophils.
• Can be walled off and replaced by connective tissue.

Ulcer

• Local defect or excavation of the surface of an organ caused by shedding inflammatory necrotic tissue.
• Common in:
  • Inflammatory necrosis of mucosa-lined cavities (mouth, larynx, stomach).
  • Subcutaneous inflammation of lower extremities in older adults with vascular defects.

Effects of Acute Inflammation

• Beneficial:
  • Dilution of toxins by edema fluid.
  • Production of antibodies.
  • Fibrin network formation as a scaffold for inflammatory cells and limiting spread of infection.
• Harmful:
  • Swelling and edema (acute epiglottitis).
  • Increased tissue pressure leading to tissue necrosis.
  • Digestion of viable tissue.
  • Severe damage in allergic reactions.
  • Generalized increased vascular permeability - shock (anaphylactic shock).