General Pathology Lecture 5 PDF

# General Pathology Lecture 5 ## Inflammation - The survival of all organisms requires that they eliminate foreign invaders through a complex host response called inflammation. - Inflammation is a protective response involving host cells, blood vessels, and proteins and other mediators that is inten...

# General Pathology Lecture 5 ## Inflammation - The survival of all organisms requires that they eliminate foreign invaders through a complex host response called inflammation. - Inflammation is a protective response involving host cells, blood vessels, and proteins and other mediators that is intended to eliminate the initial cause of cell injury, as well as the necrotic cells and tissues resulting from the original insult, and to initiate the process of repair. - Inflammation accomplishes its protective mission by first diluting, destroying, or otherwise neutralizing harmful agents (e.g., microbes, toxins). - The cells and molecules of host defense, including leukocytes and plasma proteins, normally circulate in the blood, and the goal of the inflammatory reaction is to bring them to the site of infection or tissue damage. In addition, resident cells of vascular walls and the cells and proteins of the extracellular matrix are also involved in inflammation and repair. ## Classification of Inflammation - Inflammation can be acute or chronic. Acute inflammation is rapid in onset and of short duration, lasting from a few minutes to as long as a few days, and is characterized by fluid and plasma protein exudation and a predominantly neutrophilic leukocyte accumulation. - Chronic inflammation may be more insidious, is of longer duration (days to years), and is typified by influx of lymphocytes and macrophages with associated vascular proliferation and fibrosis (scarring). ## Stimuli for Acute Inflammation - Infections (bacterial, viral, fungal, parasitic) are among the most common and medically important causes of inflammation. - Trauma (blunt and penetrating) and various physical and chemical agents (e.g., thermal injury, such as burns or frostbite; irradiation) injure host cells and elicit inflammatory reactions. - Tissue necrosis (from any cause), including ischemia (as in a myocardial infarct) and physical and chemical injury. - Foreign bodies (splinters, dirt, sutures). - Immune reactions (also called hypersensitivity reactions) against environmental substances or against "self" tissues. ## Recognition of Microbes, Necrotic Cells and Foreign Substances - It is established that phagocytes, dendritic cells (cells in connective tissue and organs that capture microbes and initiate responses to them), and many other cells, such as epithelial cells, express receptors that are designed to sense the presence of infectious pathogens and substances released from dead cells. - These receptors have been called “pattern recognition receptors” because they recognize structures that are common to many microbes or to dead cells. - Toll-like receptors and The inflammasome ## Vascular Changes - The main vascular reactions of acute inflammation are increased blood flow secondary to vasodilation and increased vascular permeability, both designed to bring blood cells and proteins to sites of infection or injury. - After transient vasoconstriction (lasting seconds), arteriolar vasodilation occurs, resulting in locally increased blood flow and engorgement of the down-stream capillary beds. This vascular expansion is the cause of the redness (erythema) and warmth characteristic of acute inflammation. ## Formation of Transudates and Exudates - **Normal:** Hydrostatic pressure is approximately 32 mm Hg at the arterial end of a capillary bed and 12 mm Hg at the venous end; the mean colloid osmotic pressure of tissues is approximately 25 mm Hg. - **Transudate:** Formed when fluid leaks out because of increased hydrostatic pressure or decreased osmotic pressure. - **Exudate:** Formed in inflammation because vascular permeability increases as a result of the increase in interendothelial spaces. ## Vascular Changes - The microvasculature becomes more permeable, and protein-rich fluid moves into the extravascular tissues. This in turn increases the osmotic pressure of the interstitial fluid, leading to more outflow of water from the blood into the tissues. The resulting protein rich fluid accumulation is called an exudate. Exudates must be distinguished from transudates, which are interstitial fluid accumulations caused by increased hydrostatic pressure usually a consequence of reduced venous return. Transudates typically contain low concentrations of protein and few or no blood cells. Fluid accumulation in extravascular spaces, whether from an exudate or a transudate, produces tissue edema. ## Cellular Events: Leukocyte Recruitment and Activation - In an inflammatory response leukocytes are delivered to the site of injury and activated. Leukocytes ingest offending agents, kill bacteria and other microbes, and eliminate necrotic tissue and foreign substances. - However, they may induce tissue damage and prolong inflammation, since the leukocyte products that destroy microbes can also injure normal host tissues. - Therefore, host defense mechanisms include checks and balances that ensure that leukocytes are recruited and activated only when and where they are needed. ## Leukocyte Recruitment - Leukocytes normally flow rapidly in the blood, and in inflammation, they have to be stopped and brought to the offending agent or the site of tissue damage, which are typically outside the vessels. The sequence of events in the recruitment of leukocytes from the vascular lumen to the extravascular space consists of: - Margination and rolling along the vessel wall - Firm adhesion to the endothelium - Transmigration between endothelial cells - Migration in interstitial tissues toward a chemotactic stimulus - Chemical mediators (chemoattractants and certain cytokines) affect these processes by modulating the surface expression and binding affinity of the adhesion molecules and by stimulating directional movement of the leukocytes. ## Mechanisms of Leukocyte Migration - Leukocytes first roll, then become activated and adhere to endothelium, then transmigrate across the endothelium, pierce the basement membrane, and migrate toward chemoattractants emanating from the source of injury. ## Leukocyte Activation - Once leukocytes have been recruited to the site of infection or tissue necrosis, they must be activated to perform their functions. Stimuli for activation include microbes, products of necrotic cells, and several mediators. - Leukocytes use various receptors to sense the presence of microbes, dead cells, and foreign substances. Engagement of these cellular receptors induces a number of responses in leukocytes that are part of their normal defensive functions and are grouped under the term leukocyte activation. ## Phagocytosis - Phagocytosis consists of three steps: - Recognition and attachment of the particle to the ingesting leukocyte. Leukocytes bind and ingest most microorganisms and dead cells by means of specific surface receptors.(host proteins, called opsonins) - Engulfment, with subsequent formation of a phagocytic vacuole. - Killing and degradation of the ingested material. This happens by the introduction of microbicidal substances within lysosomes to the engulfed microbe. ## Outcomes of Acute Inflammation - Acute inflammation generally has one of three outcomes: - **Resolution:** Regeneration and repair. When the injury is limited or short-lived, when there has been no or minimal tissue damage, and when the injured tissue is capable of regenerating. - **Chronic inflammation:** May follow acute inflammation if the offending agent is not removed. Depending on the capacity of the affected tissues to regrow, chronic inflammation may be followed by restoration of normal structure and function or may lead to scarring. - **Scarring:** Is a type of repair after substantial tissue destruction (as in abscess formation) or when inflammation occurs in tissues that do not regenerate, in which the injured tissue is filled in by connective tissue (fibrosis). ## Morphologic patterns of acute inflammation - **Serous inflammation:** Is characterized by the outpouring of a watery, relatively protein-poor fluid that, depending on the site of injury. (skin blister resulting from a burn). - **Fibrinous inflammation:** Severe injuries resulting in greater vascular permeability that allows large molecules (such as fibrinogen) to pass the endothelial barrier. Histologically, the accumulated extravascular fibrin. - **Suppurative (purulent) inflammation and abscess formation:** Manifested by the collection of large amounts of purulent exudate (pus) consisting of neutrophils, necrotic cells, and edema fluid. Abscesses are focal collections of pus that may be caused by seeding of pyogenic organisms into a tissue or by secondary infections of necrotic foci. Abscesses typically have a central, largely necrotic region rimmed by a layer of preserved neutrophils with a surrounding zone of fibroblast proliferation. - **An ulcer:** Is a local defect, or excavation, of the surface of an organ or tissue that is produced by necrosis of cells and sloughing (shedding) of necrotic and inflammatory tissue. ## Thank You - The image shows a glass bottle with the label "Thank You" on top, and some silver drops of mercury spilling out of the bottle.