Introduction to Inflammation

Introduction to Inflammation

• Inflammation functions as the response of vascularized living tissue to injury
• The purpose of inflammation is to dilute toxins, destroy and isolate offending agents, and initiate tissue repair

Types of Inflammation

• Acute inflammation is an immediate response to injury, lasting minutes to 2 days
• Acute inflammation is characterized by exudation of fluid and plasma protein, edema, and emigration of leukocytes, predominantly neutrophils
• Chronic inflammation has a longer duration with the presence of lymphocytes and macrophages
• Chronic inflammation also involves the proliferation of blood vessels and connective tissue

Causes of Acute Inflammation

• Infections, including bacterial, viral, and parasitic infections, can cause acute inflammation
• Trauma can cause acute inflammation
• Physical and chemical agents like thermal injury, burns, frostbite, irradiation, and some environmental chemicals can cause acute inflammation
• Tissue necrosis from any cause can cause acute inflammation
• Foreign bodies such as splinters, dirt, and sutures can cause acute inflammation
• Immune or hypersensitivity reactions can cause acute inflammation

Cardinal Signs of Acute Inflammation

• Rubor indicates redness
• Tumor indicates swelling
• Calor indicates heat
• Dolor indicates pain
• Functio laesa indicates loss of function

Nomenclature of Inflammation

• Inflammation nomenclature involves using the tissue name and adding the suffix "-itis" to it
• Pancreatitis refers to inflammation of the pancreas
• Meningitis refers to inflammation of the meninges
• Pericarditis refers to inflammation of the pericardium
• Arthritis refers to inflammation of the joints

Acute Inflammation Processes

• Alteration of vascular caliber causes vasodilation and leads to increased blood flow
• Changes in microvasculature result in increased permeability for plasma proteins and cells
• Emigration of leukocytes from microcirculation occurs, with leukocyte activation eliminating the offending agent

Components of Inflammatory Responses

• Circulating cells and proteins, cells of blood vessels, and cells and proteins of the extracellular matrix are responsible for the acute and chronic inflammatory responses

Edema and Exudation in Acute Inflammation

• Vascular changes and fluid leakage during acute inflammation lead to edema through exudation

Exudate

• Exudate forms as a result of inflammation
• It contains high protein and cell debris
• Exudate has a specific gravity greater than 1.020

Transudate

• Transudate forms as a result of hydrostatic or osmotic imbalance
• It is an ultrafiltrate of plasma without increased vascular permeability
• Transudate has a low protein content and a specific gravity of less than 1.012

Pus

• Pus is an inflammatory exudate rich in neutrophils, debris of dead cells, and microbes

Major Changes in Acute Inflammation

• Vascular and cellular changes are the two major changes
• These cause three of the five classic local signs: heat, redness, and swelling
• Pain and loss of function are the other two cardinal features of acute inflammation caused by elaboration mediators

Vascular Changes in Detail

• Transient momentary vasoconstriction occurs for approximately 5 seconds
• This is followed by vasodilation resulting in increased blood flow and engorgement of blood vessels
• Vessel permeability increases, prompting movement of protein-rich fluid to the extravascular system
• Increased vessel permeability manifests as edema in the microcirculation, including small arterioles, capillaries, and venules

Cellular Changes in Detail

• Leukocytes routinely leave the vasculature through the following sequence of events: margination and rolling, adhesion and transmigration, and chemotaxis and activation
• Leukocytes may then participate in phagocytosis and degranulation or cause leukocyte-induced tissue injury

Chemotaxis

• Leukocytes follow a chemical gradient to the site of injury
• Soluble bacterial products, complement components (C5a), cytokines (e.g. IL-8), and LTB4 (AA metabolite) act as chemotactic agents

Phagocytosis and Degranulation Actions

• Leukocytes recognize and attach to the particle
• Engulfment occurs forming a phagocytic vacuole
• Killing involves degradation of ingested material

Chemical Mediators in Inflammation Types

• Plasma-derived chemical mediators come from the complement, kinins, and coagulation factors
• Many plasma-derived mediators are in a pro-form requiring activation through enzymatic cleavage
• Cell-derived chemical mediators include preformed and sequestered substances like mast cell histamine, and synthesized mediators like prostaglandin as needed

Cell-Derived Mediators

• Vasoactive amines, mainly histamine cause vasodilation and venular endothelial cell contraction
• It also leads to junctional widening and is released by mast cells, basophils, and platelets
• Leukotrienes and Lipoxins affect the lipoxygenase pathway
• Leukotrienes (LTB4) are chemotaxins and vasoconstrictors that cause increased vascular permeability and bronchospasm
• Lipoxins (LX) act mainly as inhibitors of inflammation, and serve as endogenous antagonists of LT
• Platelet-activating factor (PAF) is derived from cell membrane phospholipids, causing vasodilation and increased vascular permeability, as well as increasing leukocyte adhesion
• Cytokines are protein cell products that act as mediators of inflammation and immune responses
• IL-1 and TNF are especially important in inflammation
• Cytokines increase endothelial cell adhesion molecule expression, activation, and aggregation of PMNs
• Reactive oxygen species (ROS), including nitric oxide, are short-acting soluble free-radical gases with many functions
• ROS is produced by endothelial cells and macrophages, causing vascular smooth muscle relaxation and vasodilation
• ROS also kills microbes in activated macrophages

Plasma-Derived Mediators

• The complement system, clotting system, and kinin system are plasma-derived mediators