Inflammation Overview and Significance

Inflammation is a complex biological response to injury or harmful stimuli, involving vascularized tissues.
Induced by chemical mediators released by host cells in response to injury.
Classified by adding "-itis" to the affected organ or tissue.

Can cause life-threatening hypersensitivity reactions.
Can lead to progressive organ damage through chronic inflammation and fibrosis, such as in rheumatoid arthritis and atherosclerosis.

Includes circulating cells and proteins, cells of blood vessels, and cells and proteins of the extracellular matrix.
Involves plasma fluid proteins, circulating leukocytes (neutrophils, monocytes, eosinophils, lymphocytes, basophils, platelets), blood vessels, and connective tissue cells (mast cells, fibroblasts, macrophages, lymphocytes).
Extracellular matrix includes structural proteins (collagen, elastin), adhesive glycoproteins (fibronectin, laminin), and proteoglycans.

Acute Inflammation:
- Early onset (seconds to minutes).
- Short duration (minutes to days).
- Fluid exudation (edema).
- Polymorphonuclear leukocyte (neutrophil) emigration.
Chronic Inflammation:
- Later onset (days).
- Longer duration (weeks to years).
- Induces blood vessel proliferation and scarring.
- Involves lymphocyte and macrophage infiltration.

Redness (Rubor): Increased blood flow due to vasodilation.
Swelling (Tumor): Increased vascular permeability leading to fluid accumulation.
Heat (Calor): Increased blood flow.
Pain (Dolor): Release of inflammatory mediators that stimulate nerve endings.
Loss of Function (Functio Laesa): Due to pain, swelling, and tissue damage.

Vascular Wall Response: Changes in blood vessel caliber and flow, increased vascular permeability.
Inflammatory Cell Response: Recruitment and activation of leukocytes.
Mediators: Circulating plasma proteins and factors produced locally by vessel walls or inflammatory cells.
Termination: Active anti-inflammatory mechanisms begin when the causative agent is eliminated and secreted mediators are removed.

Vascular Changes: Increased blood flow and vascular permeability to deliver cells and proteins to the site of injury.
- Initial transient vasoconstriction followed by vasodilation (causing redness and heat).
- Increased vascular permeability leads to exudate (protein-rich fluid) leakage into extravascular tissue (causing swelling).
Cellular Changes: Leukocyte recruitment and activation.
Leukocyte Recruitment:
- Margination: Leukocytes move to the periphery of the blood vessel.
- Rolling: Leukocytes attach transiently to the endothelium, rolling along the vessel wall.
- Adhesion: Firm attachment of leukocytes to the endothelium mediated by adhesion molecules.
- Transmigration: Leukocytes migrate through the endothelium and into the extravascular tissue.
Leukocyte Activation:
- Phagocytosis: Engulfment and destruction of foreign particles or cellular debris.
- Release of mediators: Chemical signals that contribute to the inflammatory response.
Phagocytosis: Involves attachment, engulfment, and killing/degradation.
- Enhanced by opsonization (coating with antibodies or complement).
- Killing mechanisms include reactive oxygen species (ROS), reactive nitrogen species (RNS), and lysosomal enzymes.

Resolution: Complete restoration of normal tissue structure and function.
- Occurs with limited injury, minimal tissue damage, and tissue capable of regeneration.
Progression to Chronic Inflammation: Continued tissue injury, persistent offending agent, or limited tissue regenerative capacity.
- May lead to restoration of function or scarring.
Suppuration (Pus Formation): Purulent exudate composed of neutrophils, bacteria, cellular debris, and edema fluid.
- Often caused by pyogenic bacteria (e.g., staphylococcus, streptococcus).
Abscess: Localized collection of pus surrounded by a layer of neutrophils and fibroblasts.
Scarring and Fibrosis: Replacement of injured tissue by fibrous connective tissue.
- Occurs with extensive tissue destruction or in tissues with limited regenerative capacity.

Serous Inflammation: Characterized by outpouring of thin fluid (plasma or mesothelial secretion).
- Examples: Pleural, pericardial, and peritoneal effusions.
Fibrinous Inflammation: Characterized by deposition of fibrin in the extracellular space due to increased vascular permeability.
- Occurs in lining of body cavities (e.g., meninges, pericardium, pleura).
Suppurative (Purulent) Inflammation: Characterized by large amounts of pus (neutrophils, necrotic cells, edema fluid).
- Caused by pyogenic bacteria (e.g., staphylococcus, streptococcus).
- Example: Acute appendicitis.
Pseudomembranous Inflammation: Inflammation of mucous membranes with extensive epithelial necrosis and sloughing.
- Forms a pseudo-membrane composed of fibrin, dead epithelium, neutrophils, red cells, and bacteria.
- Example: Diphtheria.

A local defect or excavation of an organ's surface caused by shedding of necrotic tissue.
Common in mucosal-lined cavities (mouth, larynx, stomach) and subcutaneous inflammation of lower extremities.

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