Introduction to Inflammation

Introduction to Inflammation

• Inflammation is a Latin word derived from the word "inflammare," meaning to burn.
• It's a localized response (reaction) of living, vascular tissues to endogenous and exogenous stimuli.
• The main purpose is to localize and eliminate the causative agent and to limit tissue injury.
• Inflammation is a protective response to injury, observed by Sir John Hunter in 1794.
• It's a physiological response, not a disease itself, often a result of violence or another disease.
• Inflammation is fundamentally designed to remove the initial cause of cell injury (like microbes or toxins) and the consequences (like necrotic cells).

Cardinal Signs of Inflammation

• Redness (rubor): Caused by dilation of small blood vessels in damaged tissues (e.g., cellulitis).
• Heat (calor): Results from increased blood flow (hyperemia) due to dilated blood vessels.
• Swelling (tumor): Accumulation of fluid in the extravascular space, caused by increased vascular permeability.
• Pain (dolor): Partly from tissue stretching and destruction due to inflammation, and pressure of pus in abscesses. Chemicals like bradykinins, prostaglandins, and serotonin also cause pain.
• Loss of function: Pain and swelling can inhibit function and immobilize tissues.

Causes of Inflammation

• Physical agents: Injuries from mechanical, temperature, or pressure changes, or radiation.
• Chemical agents: Drugs and toxins.
• Biological agents (infectious): Bacteria, viruses, fungi, and parasites.
• Immunologic disorders: Hypersensitivity reactions, autoimmunity, and immunodeficiency.
• Genetic/metabolic disorders: Gout and diabetes mellitus.

Nomenclature

• Inflammatory lesions are usually named using the suffix "-itis".
• For example, inflammation of the appendix is called appendicitis, and inflammation of the meninges is called meningitis.

Classification of Inflammation

• Inflammation is crudely classified based on duration and histological appearance.
• It is categorized into acute and chronic inflammation.

Acute Inflammation

• An immediate and early response to an injurious agent.
• Short-duration response (minutes to a few days).
• Characterized by fluid exudation (edema) and the emigration of neutrophils to the injured site.
• The five cardinal signs of acute inflammation are redness, heat, swelling, pain, and loss of function.

Cellular Response to Acute Inflammation

• Migration, rolling, pavementing, and adhesion of leukocytes
• Transmigration of leukocytes (escape from venules)
• Chemotaxis (leukocytes to the site of inflammation)
• Phagocytosis

Phagocytosis

• Phagocytosis is the engulfment and internalization of material (e.g., microorganisms, damaged cells, and debris) by specialized cells.
• Phagocytic cells include neutrophils, monocytes, and tissue macrophages.

Morphology of Acute Inflammation

• Exudates: Edema fluid with high protein concentration, often containing inflammatory cells.

Effects of Acute Inflammation

• Dilution of toxins: Exudates reduce and dilute chemical/bacterial toxins.
• Protective antibodies: Plasma proteins, including antibodies, are present at the injury site, leading to destruction of organisms by phagocytosis or complement-mediated cell lysis.
• Fibrin formation: Prevents bacterial spread and enhances leukocyte phagocytosis.
• Plasma mediator systems: Complement, coagulation, fibrinolytic, and kinin systems are provided to the injured area.
• Promotion of immunity: Micro-organisms and toxins are carried to the lymph nodes, stimulating an immune response and thus the generation of antibodies.

Chronic Inflammation

• A prolonged inflammatory process (weeks or months).
• Active inflammation, tissue destruction, and repair attempt simultaneously.
• There are two main subtypes: nonspecific chronic and specific (granulomatous) inflammation.
• Potential causes: Persistent infections (e.g., tuberculosis, leprosy), prolonged exposure to non-degradable/toxic substances (e.g., endogenous lipid components causing atherosclerosis, silica, asbestos), or autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus.

Cells Involved in Chronic Inflammation

• Monocytes and macrophages
• T-lymphocytes
• B-lymphocytes and plasma cells
• Mast cells and eosinophils (predominantly in response to parasitic infections & allergic reactions).

Classification of Chronic Inflammation

• Nonspecific chronic inflammation: Macrophage and lymphocyte accumulation at the injury site, often accompanied by fibrous tissue. (e.g., chronic cholecystitis).
• Specific (granulomatous) inflammation: Characterized by granuloma formation—a microscopic aggregate of epithelioid cells (activated macrophages with a modified epithelial appearance). Causes include bacteria (tuberculosis, leprosy, syphilis), fungi (histoplasmosis, cryptococcosis), helminths (schistosomiasis), protozoa (leishmaniasis, toxoplasmosis), chlamydia (lymphogranuloma venerum), and inorganic materials (berylliosis).

Outcomes of Acute Inflammation

• Complete resolution
• Healing by connective tissue replacement
• Progression to chronic inflammation
• Abscess formation

Systemic Effects of Inflammation

• Fever
• Endocrine and metabolic responses (e.g., liver secretes acute-phase proteins like C-reactive proteins and amyloid A)
• Autonomic responses (e.g., redirection of blood flow, increased pulse rate and blood pressure)
• Behavioral Responses (e.g., rigor, chills, anorexia, somnolence)
• Leukocytosis (increased white blood cells) or Leukopenia (decreased white blood cells)
• Weight loss

Causes of Chronic Inflammation (more detail)

• Persistent Infections: Certain microorganisms (e.g., tuberculosis, leprosy, fungi) cause chronic inflammation.
• Toxic substances: Prolonged exposure to non-degradable/partially toxic substances (e.g., endogenous lipids that lead to atherosclerosis, or exogenous substances like silica and asbestos)
• Autoimmunity: Rheumatoid arthritis, systemic lupus are chronic from the onset.