Inflammation Lecture Notes PDF

Inflammation Prepared by Dr. Ava Taher Ismael Assistant professor- MD. PhD Path  Is the reaction of living tissue and it’s microcirculation to pathological insults i.e (defense mechanism & protective response to eliminate the injurious agents). The inflammatory nature of lesion usually denoted...

Inflammation Prepared by Dr. Ava Taher Ismael Assistant professor- MD. PhD Path  Is the reaction of living tissue and it’s microcirculation to pathological insults i.e (defense mechanism & protective response to eliminate the injurious agents). The inflammatory nature of lesion usually denoted by suffix-(itis): e.g. appendix- appendicitis Inflammation of the liver- hepatitis Some exception, inflammation of the lung- pneumonia  Cardinal sign of inflammation 1- Redness, due to dilation of small blood vessels within the area of injury. 2- Heat, due to increase blood flow 3- Swelling, due to edema caused by accumulation of fluid exudate in EVS (extra vascular spaces) 4- Pain, due to chemical mediator (prostoglandin, serotonin, bradykinin) 5- Loss of function, result from pain The first four signs are typically more prominent in acute inflammations than in chronic inflammation. What is the aim of inflammation? 1. Get rid of the injurious agents (microbes, toxins) as well as its consequences (necrotic cells & tissues) 2. limit tissue injury 3. Restore tissue to normality or close to normality What will happen without inflammation??? Infection would go uninhibited, Wounds would never heal, Injured organs remain permanently damaged. Inflammation and its associated repair may sometimes be potentially harmful. Anti-inflammatory drugs control the harmful effect of inflammation yet don’t interfere with its beneficial effects. What are the participants in inflammation??? 1. Plasma fluid proteins, 2. The blood vessels, 3. The circulating leukocytes neutrophils , monocytes , eosinophils, lymphocytes , basophils and platelets. 4. The connective tissue cells : macrophages , mast cell , fibroblasts and lymphocytes 5. The extra-cellular matrix which consists of structural proteins (collagen, elastin), adhesive glycoproteins (fibronectin, laminin), and proteoglycans.  What are the types of inflammation??? Inflammation is divided into acute or chronic. Acute inflammation is rapid in onset (seconds or minutes), of relatively short duration (minutes, hours, or at most a few days), characterized by the exudation of fluid and plasma proteins, & the emigration of leukocytes, predominantly neutrophils.  Chronic inflammation is of insidious onset, of longer duration. Tissue injury, inflammatory response and healing attempt proceed at the same time. is associated histologically with the presence of lymphocytes, macrophages, plasma cells, proliferation of blood vessels and fibroblasts.  ACUTE INFLAMMATION What are the stimuli of acute inflammation? 1. Infections: bacterial, viral, parasitic and microbial toxins 2. Physical and chemical agents (trauma, burns, irradiation, toxins, strong acids, etc.) 3. Tissue necrosis (of any from or cause) 4. Foreign bodies (splinters, dirt, sutures) 5. Immune reactions (hypersensitivity and autoimmune reactions)  What are the major components of acute inflammation? A. Vasodilation associated with increased blood flow (hyperemia) B. Increased vascular permeability associated with decreased blood flow and result in exudate formation and local edema C. Emigration and activation of leukocytes and phagocytosis  A. Vasodilatation and increased blood flow Vasodilatation of arterioles occurs first  increase in blood flow  opening of new capillary beds in the area  subsequent dilation of capillaries & venules. This process which allows more blood to flow into the area is known as “active hyperemia” (hyper- = increased; -emia = blood). These changes explain the clinically noted heat and redness. Normal blood vessele  Under normal circumstances, there is continual movement of fluid from the intravascular compartment to the extravascular space. Fluid that accumulates in the extravascular space is then cleared through lymphatics and returned to the circulation.  B. Increased Vascular Permeability and decreased blood flow Increased vascular permeability leads to the escape of exudates into the extravascular tissue. Escape of fluid from blood vessels into extra- vascular space  (Edema) Exudation is the escape of fluid, proteins, and blood cells from the vascular system into the interstitial tissue due to increased vascular permeability. An exudate is an extravascular fluid that has a high protein concentration and a specific gravity > 1.020 Transudate is a fluid with low protein content (most of which is albumin) and a specific gravity < 1.012. It is essentially an ultrafiltrate of blood plasma Edema refers to an excess of fluid in the interstitial tissues or body cavities; the accumulated fluid can be either an exudate or a transudate. Pus (purulent exudate) is an inflammatory exudate rich in leukocytes (mostly neutrophils), the debris of dead cells and, in many cases, microbes (pyogenic bacteria).  C. Emigration and activation of leukocytes and phagocytosis A critical function of inflammation is to : Deliver leukocytes to the site of injury Activate the leukocytes to defend the host. Leukocytes: ingest offending agents kill bacteria and other microbes. get rid of necrotic tissue and foreign substances. However, these cells may induce tissue damage and prolong inflammation.  The journey of leukocytes from the vessel lumen to the interstitial tissue is called Extravasation This can be divided into the following steps: 1. Binding of leukocytes to the endothelial cells. 2. Transmigration of leukocytes across the endothelium (diapedesis) 3. Migration of leukocytes within the interstitial tissues toward the focus of tissue injury.  Sequence of events in leukocytes emigration in inflammation 1. Margination 2. rolling 3. adhesion 4. transmigration (diapedesis) & movement toward the injurious agent (Chemotaxis)  Blood flow slows down in inflammation, more white cells assume a peripheral position along the endothelial surface. This process is called margination. Subsequently, leukocytes tumble and roll over slowly along the endothelium and eventually come to rest through firm adhesions with the endothelial cells. In time, the endothelium becomes virtually lined by white cells, an appearance called pavementing.  After firm adhesion, leukocytes insert pseudopods into the junctions between the endothelial cells, squeezing through these junctions, traverse the basement membrane and escape into the extravascular space. The migration of the leukocytes through the endothelium is called transmigration or diapedesis.  Piercing the basement membrane is achieved by secreting degrading enzymes such as collagenases & elastases. Leukocyte diapedesis, similar to increased vascular permeability, occurs predominantly in the venules. Neutrophils, monocytes, lymphocytes, eosinophils, and basophils, all use the same pathway to migrate from the blood into tissues. The type of emigrating leukocyte varies with the age of the inflammatory response and with the type of stimulus. In most forms of acute inflammation, Neutrophils predominate in the inflammatory infiltrate during the first 6 to 24 hours, and then are replaced by Monocytes in 24 to 48 hours. After entering tissues, neutrophils are short-lived; they undergo apoptosis (self destruction) and disappear after 24 to 48 hours, whereas monocytes (by now called macrophages: macro- = large and phage = eater) survive longer and thus outlive neutrophils and become more apparent.  In certain infections, for example, those produced by Pseudomonas organisms- neutrophils predominate over 2 - 4 days. In viral infections, lymphocytes may be the first cells to arrive. In some hypersensitivity reactions and parasitic infestations, eosinophils may be the main cell type. Chemotaxis is defined as locomotion oriented along a chemical gradient of chemoattractants. All granulocytes, monocytes and, to a lesser extent, lymphocytes respond to chemo- attractants (chemotactic stimuli) with varying rates of speed. Exogenous chemoattractants are exemplified by bacterial products. Endogenous chemoattractants include: Components of the complement system. What is Phagocytosis ??? Phagocytosis is one of the major functions of the accumulated neutrophils and macrophages at the inflammatory focus, being responsible for eliminating the injurious agents and necrotic debris. Phagocytosis involves three distinct but interrelated steps: 1. Recognition and attachment of the particle to be ingested by the leukocyte 2. Its engulfment, with subsequent formation of a phagocytic vacuole 3. Killing and degradation of the ingested material. Phagocytosis of a particle (e.g., a bacterium) involves (1) attachment and binding of the particle to receptors on the leukocyte surface, (2) engulfment and fusion of the phagocytic vacuole with (lysosomes), and (3) destruction of the ingested particle. iNOS, Inducible nitric oxide synthase; NO, nitric oxide; ROS, reactive oxygen species