PowerPoint Presentation

[Audio] The body's response to tissue damage and infections is inflammation. This is a complex process which involves the activation of blood vessels to bring in white blood cells and other molecules that tackle the source of the problem and help to prevent further harm..

[Audio] The immune system is an intricate and constantly active system of cells and proteins which protects us from diseases and infections. When the body is exposed to any foreign body such as bacteria virus or any foreign material the immune system responds by initiating an inflammatory response. This leads to specialized white blood cells attacking the stimulus and releasing various chemicals that cause the typical signs of inflammation heat pain swelling redness and loss of function. These symptoms can last for a short period in certain cases and on the other hand can result in long-term damage if the inflammation persists for a long time. Infections physical agents chemical agents immunological agents auto immune disorder and inert material all can trigger an inflammatory response..

It may be triggered by variety of stimuli.

[Audio] Inflammatory process is a complex and highly regulated reaction to an offending agent. Recognition of the offending agent initiates the process wherein leukocytes and proteins are recruited from the circulation and mobilize to the site of the offending agent where they are activated and work together to eliminate it. The reaction is then controlled and terminated and the damaged tissue is subsequently repaired. This typical inflammatory reaction is developed through a series of intricate and regulated steps..

[Audio] Characterized by the cardinal signs of heat redness swelling pain and loss of function inflammation is the result of a heightened immune response and the associated body's effort to heal itself. Heat is caused by an increased amount of blood flow to the area of inflammation whereas redness swelling and pain are the result of an increase in fluid. Lastly the disruption of the normal function of the affected organ or tissue is what manifests as the loss of function..

[Audio] We will discuss Acute Inflammation the initial rapid response to infections and tissue damage. It typically develops rapidly within minutes or hours and is of short duration lasting for several hours or a few days. The main characteristics of Acute Inflammation are the exudation of fluid and plasma proteins (edema) and the emigration of leukocytes predominantly neutrophils (also called polymorphonuclear leukocytes). Once the offenders are eliminated the reaction subsides and the residual injury is repaired. There are two types of inflammation: Acute and Chronic..

[Audio] Chronic inflammation is a protracted type of inflammation that follows from an initial response when the stimulus is not cleared. It happens when a person's immune system does not detect and eliminate an antigen in a reasonable period of time that results in a sustained 'state of alert' that is marked by high levels of inflammatory mediators like cytokines chemokines and growth factors. This type of inflammation can lead to a variety of health problems and is often associated with tissue damage. It is important to identify and address any potential causes of chronic inflammation as soon as possible in order to avoid long-term damage and health complications..

[Audio] Vascular events are an important part of the inflammatory process. Haemodynamic changes occur first where the blood flow is affected due to local changes in blood pressure. This in turn affects the amount of oxygen available to the affected area and produces signs and symptoms of inflammation. Altered vascular permeability is the next step of the process which involves a change in the blood vessel structure allowing plasma and other constituents of lymph to flow from the blood vessel into the affected tissue resulting in swelling and redness..

[Audio] Haemodynamic changes are essential in the inflammatory process. To comprehend them they should be divided into two distinct types transient vasoconstriction of arterioles and elevated capillary permeability. When faced with trauma arterioles rapidly and briefly contract however even in mild injury the blood flow normally returns to normal within 3 to 5 seconds..

[Audio] Inflammation is typically followed by vasodilation a widening of blood vessels beginning with the arterioles and usually resulting in a greater flow of blood to the capillaries. This increased blood flow is associated with an increased heat and redness known as erythema in the affected area. Inflammation can have many causes such as infections physical agents chemical agents immunological agents auto-immune disorders and inert materials..

[Audio] Progressive vasodilation during acute inflammation can cause an increase in local hydrostatic pressure forcing fluid into nearby tissue and resulting in swelling..

[Audio] Endothelial cells line the walls of our blood vessels and when they contract the interendothelial spaces between them widen. This increase in spaces between the cells is caused by chemicals such as histamine bradykinin and leukotrienes which act as mediators. This is known as the immediate transient response which typically occurs within 15 to 30 minutes..

[Audio] Endothelial injury associated with inflammation is divided into two types: endothelial cell necrosis and endothelial cell detachment. Endothelial cell necrosis happens when leukocytes attach to the endothelium and secrete enzymes that make the endothelial cells die. Activated leukocytes can also cause the detachment of endothelial cells leading to increased vascular permeability. This produces the typical symptoms of inflammation heat redness swelling pain and loss of function..

[Audio] During inflammation the diameter of the blood vessels enlarge and fluid is lost. This results in a slowdown of the blood flow velocity as well as a higher concentration of red cells and an increase in the viscosity of the blood in smaller vessels. This puts the body in an imbalanced state which facilitates a more effective response to injury and infection..

[Audio] Leucocytes play a vital role in the cellular events of inflammation which include exudation and phagocytosis. During exudation leucocytes are released from the circulatory system in response to chemical signals and migrate to the area of injury. Phagocytosis is the process whereby leucocytes engulf and destroy pathogens that have caused infection. Once a pathogen has been engulfed it is broken down and its components destroyed or recycled. Both exudation and phagocytosis are essential for a localized inflammatory response which ultimately resolves the infection..

[Audio] Leucocytes exudate during the process of inflammation. This process involves modifications in the elements of the blood such as rolling and adhesion of leucocytes emigration or transmigration chemotaxis and phagocytosis all of which allow leucocytes to escape the lumen of microvasculature of the interstitial tissue and take part in the inflammatory response. As a result leucocytes are able to begin the tissue healing process and play a critical role in controlling inflammation..

[Audio] White blood cells migrate at the endothelial cells and pavementing occurs when neutrophils move close to the wall of the vessel. This enables the white blood cells to fight off potential invaders playing a role in the inflammatory response..

[Audio] Rolling of leukocytes to their destination is facilitated by Selectins which are cell adhesion molecules. There are three primary kinds of Selectins namely P-selectin E-selectin and L-selectin. All of these have essential roles to play in regulation and activation of the inflammatory process. P-selectin is expressed on stimulated platelets and endothelial cells while E-selectin is expressed in response to inflammatory cytokines and L-selectin is present on leukocytes..

[Audio] Leucocytes and endothelial cells form transient bonds known as adhesion which is mediated by molecules from the integrins and immunoglobulin gene superfamily. Among these molecules are Integrins Beta 1 and Beta 2 as well as Intracellular Adhesion Molecules (ICAMs) and Vascular Cell Adhesion Molecules (VCAMs)..

[Audio] Leucocytes have the ability to move out of the bloodstream and penetrate the tissue during the inflammatory process called emigration or diapedesis. This is caused by gaps between endothelial cells opening up which lets the leucocytes migrate out of the capillaries and resulting in a hemorrhagic appearance to the inflammatory exudate..

[Audio] Leukocytes employ chemotaxis to migrate towards areas of infection or injury. Chemical signals enable the leukocytes to traverse multiple barriers before arriving in the interstitial tissue. This facilitates their movement in response to inflammation..

[Audio] Phagocytosis plays an essential role in the body's defense system. Opsonins are recognised and attached to identify microbes followed by the engulfment of these organisms into cytoplasmic pseudopods. The engulfed particles are then destroyed and broken down by hydrolytic enzymes. These processes blend together into a strong protective shield against harmful pathogens thus safeguarding our bodies and health..

[Audio] I am presenting on the intracellular and extracellular mechanisms involved in inflammation. Intracellularly this involves the creation of reactive oxygen species reactive nitric oxide and lysosomal granules. Extracellular mechanisms include the formation of a neutrophil trap an immunological chain and the activation of leucocytes. All of these processes work in conjunction to initiate an inflammatory response..

[Audio] Reactive oxygen species are released as an intracellular mechanism of inflammation which are formed by the main enzyme nadph-oxidase resulting in a supraoxide ion and hydrogen peroxide. Myeloperoxidease-dependent killing occurs through the formation of hypochlorous acid from hydrogen peroxide and water. Myeloperoxidease-independent killing is achieved through the Haber-Weiss reaction and the formation of hydroxyl radicals..

[Audio] Nitric oxide is involved in inflammation with its main enzyme being nitric oxide synthase a component of reactive oxygen species. This enzyme is responsible for producing lysosomal granules small vesicles necessary for cell function. In terms of inflammation these granules aid the body's response to infection and injury. Therefore nitric oxide is a key factor in the inflammatory process..

[Audio] Inflammation can be divided into acute and chronic. Acute inflammation is a relatively short-term process that is usually induced by infection trauma or other physical agents. It is caused by rapid changes in the body including the recruitment of neutrophils and the secretion of various mediators. Its effects can range from infarction to bacterial infections depending on the level of severity. Chronic inflammation on the other hand is a long-term process which results in the formation of scar tissue resulting in a loss of function. However if the cause is properly dealt with then the inflammation can be resolved. This resolution involves clearing bacteria inflammatory cells and other stimuli and repairing the injured cells restoring the body's functioning..

[Audio] Chronic inflammation can cause many diseases. It occurs when the immune system response stays activated after the injury has healed or tissue injury is not fully eliminated. To determine a normal or pathogenic process inflammatory markers are used to aid with disease diagnosis and decision-making for treatments. Macrophages and adipocytes are inflammatory cells that activate and produce inflammatory cytokines proteins enzymes. Some examples of these are IL-6 TNF C-reactive protein nadph oxidase and COX-2. Obesity is an example of one condition that is caused by chronic inflammation..

[Audio] Excess fat accumulation in adipose tissue can have serious consequences for obese individuals. Adipose tissue is not only responsible for storing fat but also serves as a type of endocrine organ secreting proteins such as cytokines T-N-F alpha IL-6 adiponectin leptin angiotensin and resistin that regulate inflammation insulin sensitivity and blood pressure. When too much fat is consumed it starts to accumulate in and enlarge the adipose tissue preventing the oxygen and blood supply from reaching the fat cells. Macrophages migrate into the adipose tissue to remove these dead cells and release inflammatory cytokines such as T-N-F alpha and IL-6 which then cause chronic inflammation throughout the body. This can lead to insulin resistance type 2 diabetes and atherosclerosis..

[Audio] Fat cells come in two varieties lean healthy fat and obese dysfunctional fat. Lean healthy fat cells are smaller and exhibit normal hormonal responses adipokine secretion mitochondrial function angiogenesis blood flow and extracellular matrix. On the other hand obese dysfunctional fat cells are larger and display impaired hormonal responses adipokine secretion inflammation and endoplasmic reticulum stress mitochondrial dysfunction reduced angiogenesis and capillary density reduced blood flow and impaired extracellular matrix remodeling..

[Audio] Adipocytes and macrophages can be involved in the inflammatory response of obesity. Adipocytes which usually store lipids and regulate metabolism can become producers of inflammatory cytokines and macrophages can accumulate lipid to become foam cells. This leads to an inflammatory response of adipose tissue which is a step in the development of insulin resistance. ER stress and increased R-O-S production can also contribute to insulin resistance showcasing the complex relationship between adipocytes macrophages and the inflammatory response in obesity..

[Audio] T NF-alpha is a pro-inflammatory cytokine that has been found to induce insulin resistance. By targeting the protein Insulin Receptor Substrate 1 (IRS-1) and phosphorylating it on serine residues instead of tyrosine TNF-alpha causes IRS-1 to dissociate from the insulin receptor and eventually be degraded. This results in the establishment of insulin resistance. TNF-alpha has been identified as a major risk factor for insulin resistance in numerous chronic diseases including obesity..

[Audio] Insulin sensitizers such as rosiglitazone and pioglitazone have been found to both inhibit inflammation and improve insulin sensitivity. Non-steroidal anti-inflammatory drugs like aspirin may also be effective in decreasing TNF-a and C-R-P levels and improving insulin sensitivity. As such anti-inflammatory agents have been proposed as a possible treatment for insulin resistance. In summary anti-inflammatory drugs may help to reduce inflammatory factors and restore insulin resistance..