Inflammation Overview and Significance

A complex biological response of vascularized living tissues to local injury or harmful stimuli.
It is induced by chemical mediators produced by host cells in response to injurious stimuli.
Used to describe a range of disorders, named by adding “-itis” to the affected organ or tissue, e.g. pulpitis, gingivitis, hepatitis, appendicitis

Can cause life-threatening hypersensitivity reactions, e.g. anaphylactic shock.
Can cause progressive organ damage from chronic inflammation leading to fibrosis, e.g. rheumatoid arthritis and atherosclerosis.

Circulating cells and proteins: neutrophils, monocytes, eosinophils, lymphocytes, basophils, platelets, plasma fluid proteins.
Cells of blood vessels: endothelial cells.
Cells and proteins of the extracellular matrix: mast cells, fibroblasts, macrophages, lymphocytes, collagen, elastin, fibronectin, laminin, proteoglycans.

Acute inflammation:
- Early onset (seconds - minutes)
- Short duration (minutes - days)
- Fluid exudation (edema)
- Characterized by polymorphonuclear leukocyte emigration (neutrophils)
Chronic inflammation:
- Later onset (days)
- Longer duration (weeks - years)
- Characterized by increased blood vessel proliferation, scarring, lymphocytes, macrophage infiltration.

Two main components: vascular wall response and inflammatory cell response.
Mediated by inflammatory mediators: circulating plasma proteins and factors produced locally by vessel walls or inflammatory cells.
Termination: active anti-inflammatory mechanism starts when the causative agents are eliminated, and the secreted mediators are removed.

Increased blood flow (hyperemia): secondary to vasodilation & increased vascular permeability designed to transport blood cells and proteins.
Initial transient vasoconstriction: immediately after injury, followed by vasodilation.
Vasodilation: increases blood flow to the area of injury, causing heat (calor) and redness (rubor).
Increased Vascular Permeability: leading to the escape of protein-rich fluid (exudate) into the extravascular tissue.
- This reduces intravascular osmotic pressure and increases interstitial osmotic pressure, resulting in edema (swelling).
Mechanisms of vascular leakage:
- Endothelial cell contraction (endothelial gaps): caused by histamine, bradykinin, leukotrienes.
- Direct endothelial injury: burns or infections.
Edema: excessive interstitial fluid or body cavity fluid - can be exudate or transudate.
- Exudate: inflammatory extravascular fluid with high protein concentration and cellular debris - indicates increased vascular permeability.
- Transudate: fluid with low protein content, caused by increased hydrostatic pressure, e.g. reduced venous return - occurs in non-inflammatory conditions.

Leukocyte Recruitment and Activation: critical function to deliver leukocytes to the site of injury and activate them for host defense.
Leukocyte functions: ingest offensive agents, kill bacteria, and get rid of necrotic tissue and foreign substances.
Leukocyte migration sequence:
- Margination and rolling
- Adhesion
- Transmigration across the endothelium (diapedesis)
Leukocyte activation: stimulated by microbes, products of necrotic cells, and mediators.
Phagocytosis: engulfment and degradation of bacteria and cellular debris by neutrophils and macrophages.
- Steps: recognition and attachment, engulfment, phagocytic vacuole formation

Resolution: regaining normal tissue structure and function.
- Occurs when injury is limited or short-lived, minimal tissue damage, and tissue can replace injured cells.
Progression to chronic inflammation:
- Offending agent is not removed, continuous tissue injury, impaired tissue regeneration.
- May lead to restoration or scarring.
Suppuration (pus formation): purulent inflammatory exudate caused by pyogenic bacteria.
- Composition: living and dead neutrophils, bacteria, cellular debris, edema fluid.
- Abscess: focal collection of pus, with a central necrotic region surrounded by preserved neutrophils and dilated vessels.
Scarring and fibrosis: replacement of injured tissue by fibrous connective tissue.
- Occurs with large tissue destruction, e.g. abscess, or in tissues that do not regenerate.

Depends on the nature and intensity of injury, site and tissues affected, and responsiveness of the host.
Types:
- Serous inflammation: characterized by outpouring of thin fluid (plasma or mesothelial secretion) - called effusion, e.g. pleural, pericardial, and peritoneal cavities.
- Fibrinous inflammation: characterized by inflammation of body cavity lining, e.g. meninges, pericardium, pleura. More severe injury with increased vascular permeability, leading to fibrin deposition.
- Suppurative (purulent) inflammation: characterized by formation of pus (purulent exudate), involving infiltration of neutrophils, necrotic cells, and edema - caused by bacteria (e.g. staph, strep, pneumo), e.g. acute appendicitis.
- Pseudomembranous inflammation: characterized by severe injury and extensive epithelial necrosis and sloughing, creating shallow ulcers covered by fibrin, dead epithelium, neutrophils, red cells, and bacteria - forming a white-creamy pseudo-membrane, e.g. diphtheria.

Localized collection of purulent inflammatory exudate.
Consists of a central mass of necrotic leukocytes and tissue debris surrounded by preserved neutrophils.
May become walled off and replaced by connective tissue.

Local excavation of an organ surface caused by inflammatory necrotic tissue.
Most common in:
- Inflammatory necrosis of mucosa-lined cavities (mouth, larynx, stomach)
- Subcutaneous inflammation of lower extremities (elderly with vascular defects)

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