Acute Inflammation Flashcards
Overview of Inflammation
Definitions and General Features
The major participants in the inflammatory reaction in tissues are blood vessels and leukocytes
Inflammation is a response of vascularized tissues to infections and damaged tissues that brings cells and molecules of host defense from the circulation to the sites where they are needed, in order to eliminate the offending agents
Inflammatory reaction develops through a series of sequential steps
The offending agent, which is located in extravascular tissues, is recognized by host cells and molecules.
Leukocytes and plasma proteins are recruited from the circulation to the site where the offending agent is located.
The leukocytes and proteins are activated and work together to destroy and eliminate the offending substance.
The reaction is controlled and terminated.
The damaged tissue is repaired
Causes of Inflammation
Infections (bacterial, viral, fungal, parasitic) and microbial toxins are among the most common and medically important causes of inflammation.
Tissue necrosis elicits inflammation regardless of the cause of cell death, which may include ischemia (reduced blood flow, the cause of myocardial infarction), trauma, and physical and chemical injury (e.g., thermal injury, as in burns or frostbite; irradiation; exposure to some environmental chemicals).
Foreign bodies (splinters, dirt, sutures) may elicit inflammation by themselves or because they cause traumatic tissue injury or carry microbes.
Immune reactions (also called hypersensitivity) are reactions in which the normally protective immune system damages the individual’s own tissues.
Recognition of Microbes and Damaged Cells
Cellular receptors for microbes
Sensors of cell damage
Other cellular receptors involved in inflammation
Circulating proteins
Acute inflammation has three major components:
Dilation of small vessels leading to an increase in blood flow
Increased permeability of the microvasculature enabling plasma proteins and leukocytes to leave the circulation
Emigration of the leukocytes from the microcirculation, their accumulation in the focus of injury, and their activation to eliminate the offending agent
Reactions of Blood Vessels in Acute Inflammation
The vascular reactions of acute inflammation consist of changes in the flow of blood and the permeability of vessels, both designed to maximize the movement of plasma proteins and leukocytes out of the circulation and into the site of infection or injury
Changes in Vascular Flow and Caliber
Vasodilation is induced by the action of several mediators, notably histamine, on vascular smooth muscle
Vasodilation is quickly followed by increased permeability of the microvasculature, with the outpouring of protein-rich fluid into the extravascular tissues
The loss of fluid and increased vessel diameter lead to slower blood flow, concentration of red cells in small vessels, and increased viscosity of the blood.
As stasis develops, blood leukocytes, principally neutrophils, accumulate along the vascular endothelium.
Increased Vascular Permeability (Vascular Leakage)
Contraction of endothelial cells resulting in increased interendothelial spaces is the most common mechanism of vascular leakage.
Endothelial injury, resulting in endothelial cell necrosis and detachment.
Increased transport of fluids and proteins, called transcytosis, through the endothelial cell.
Responses of Lymphatic Vessels and Lymph Nodes
The lymphatics may become secondarily inflamed (lymphangitis), as may the draining lymph nodes (lymphadenitis).
Inflamed lymph nodes are often enlarged because of hyperplasia of the lymphoid follicles and increased numbers of lymphocytes and macrophages. This constellation of pathologic changes is termed reactive, or inflammatory, lymphadenitis.
For clinicians the presence of red streaks near a skin wound is a telltale sign of an infection in the wound. This streaking follows the course of the lymphatic channels and is diagnostic of lymphangitis; it may be accompanied by painful enlargement of the draining lymph nodes, indicating lymphadenitis
Cut with red streaks– what?
lymphangitis
lymphangitis can lead to
inflammatory lymphadenitis, signs of early sepsis. Get on it!
Leukocyte Recruitment to Sites of Inflammation
The changes in blood flow and vascular permeability are quickly followed by an influx of leukocytes into the tissue
Selectins- SLOW, or STOP the white cells.
Integrins- Cause attachment.
The journey of leukocytes from the vessel lumen to the tissue is a multistep process that is mediated and controlled by adhesion molecules and cytokines called chemokines
In the lumen: margination, rolling, and adhesion to endothelium.
Vascular endothelium in its normal, unactivated state does not bind circulating cells or impede their passage.
In inflammation, the endothelium is activated and can bind leukocytes as a prelude to their exit from the blood vessels.
Migration across the endothelium and vessel wall
Migration in the tissues toward a chemotactic stimulus
Leukocyte Adhesion to Endothelium
The attachment of leukocytes to endothelial cells is mediated by complementary adhesion molecules on the two cell types whose expression is enhanced by cytokines
The two major families of molecules involved in leukocyte adhesion and migration are the selectins and integrins
Leukocyte Migration through Endothelium
The next step in the process of leukocyte recruitment is migration of the leukocytes through the endothelium, called transmigration or diapedesis
Chemotaxis of Leukocytes
After exiting the circulation, leukocytes move in the tissues toward the site of injury by a process called chemotaxis
Phagocytosis and Clearance of the Offending Agent
Recognition of microbes or dead cells induces several responses in leukocytes that are collectively called leukocyte activation
Phagocytosis
Recognition and attachment of the particle to be ingested by the leukocyte
Engulfment, with subsequent formation of a phagocytic vacuole
Killing or degradation of the ingested material.
Intracellular Destruction of Microbes and Debris
Killing of microbes is accomplished by reactive oxygen species (ROS, also called reactive oxygen intermediates) and reactive nitrogen species, mainly derived from nitric oxide (NO), and these as well as lysosomal enzymes destroy phagocytosed debris
Neutrophil Extracellular Traps
Neutrophil extracellular traps (NETs) are extracellular fibrillar networks that provide a high concentration of antimicrobial substances at sites of infection and prevent the spread of the microbes by trapping them in the fibrils
Leukocyte-Mediated Tissue Injury
Leukocytes are important causes of injury to normal cells and tissues under several circumstances
As part of a normal defense reaction against infectious microbes, when adjacent tissues suffer collateral damage. In some infections that are difficult to eradicate, such as tuberculosis and certain viral diseases, the prolonged host response contributes more to the pathology than does the microbe itself.
When the inflammatory response is inappropriately directed against host tissues, as in certain autoimmune diseases.
When the host reacts excessively against usually harmless environmental substances, as in allergic diseases, including asthma