Information AboutInflammation |
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Inflammation ( Latin , ''inflammatio'', to set on fire) is the complex biological response of Vascular tissues to harmful stimuli, such as Pathogen s, damaged cells, or irritants. It is a protective attempt by the organism to remove the injurious stimuli as well as initiate the healing process for the tissue. Inflammation is not a synonym for Infection . Even in cases where inflammation is caused by infection it is incorrect to use the terms as synonyms: infection is caused by an exogenous pathogen, while inflammation is the response of the organism to the pathogen. In the absence of inflammation, wounds and infections would never heal and progressive destruction of the tissue would compromise the survival of the organism. However, inflammation which runs unchecked can also lead to a host of diseases, such as Hay Fever , Atherosclerosis , and Rheumatoid Arthritis . It is for this reason that inflammation is normally tightly regulated by the body. Inflammation can be classified as either ''acute'' or ''chronic''. ''Acute inflammation'' is the initial response of the body to harmful stimuli and is achieved by the increased movement of Plasma and Leukocyte s from the blood into the injured tissues. A cascade of biochemical events propagates and matures the inflammatory response, involving the local Vascular System , the Immune System , and various cells within the injured tissue. Prolonged inflammation, known as ''chronic inflammation'', leads to a progressive shift in the type of cells which are present at the site of inflammation and is characterised by simultaneous destruction and healing of the tissue from the inflammatory process. CAUSES
TYPES Acute inflammation Acute inflammation is a short-term process which is characterised by the classic signs of inflammation - swelling, redness, pain, heat, and loss of function - due to the infiltration of the tissues by plasma and Leukocyte s. It occurs as long as the injurious stimulus is present and ceases once the stimulus has been removed, broken down, or walled off by scarring ( Fibrosis ). The first four characteristics have been known since ancient times and are attributed to Celsus . ''Loss of function'' was added to the definition of inflammation by Rudolf Virchow in the 19th century1. The process of acute inflammation is initiated by the blood vessels local to the injured tissue, which alter to allow the exudation of Plasma proteins and Leukocyte s into the surrounding tissue. The increased flow of fluid into the tissue causes the characteristic swelling associated with inflammation, and the increased blood flow to the area causes the reddened colour and increased heat. The blood vessels also alter to permit the extravasation of leukocytes through the Endothelium and Basement Membrane constituting the blood vessel. Once in the tissue, the cells migrate along a Chemotactic gradient to reach the site of injury, where they can attempt to remove the stimulus and repair the tissue. Meanwhile, several biochemical cascade systems, consisting of chemicals known as plasma-derived inflammatory mediators, act in parallel to propagate and mature the inflammatory response. These include the Complement System , Coagulation System and Fibrinolysis System . Finally, down-regulation of the inflammatory response concludes acute inflammation. Removal of the injurious stimuli halts the response of the inflammatory mechanisms, which require constant stimulation to propagate the process. Additionally, many inflammatory mediators have short half lives and are quickly degraded in the tissue, helping to quickly cease the inflammatory response once the stimulus has been removed . Chronic inflammation See Also: Chronic inflammation Chronic inflammation is a pathological condition characterised by concurrent active inflammation, tissue destruction, and attempts at repair. Chronic inflammation is not characterised by the classic signs of acute inflammation listed above. Instead, chronically inflammed tissue is characterised by the infiltration of mononuclear immune cells ( Monocyte s, Macrophage s, Lymphocyte s, and Plasma Cell s), tissue destruction, and attempts at healing, which include Angiogenesis and Fibrosis . Endogenous causes include persistent acute inflammation. Exogenous causes are varied and include bacterial infection, especially by '' Mycobacterium Tuberculosis '', prolonged exposure to chemical agents such as Silica , or Autoimmune Reaction s such as Rheumatoid Arthritis . In acute inflammation, removal of the stimulus halts the recruitment of monocytes (which become macrophages under appropriate activation) into the inflamed tissue, and existing macrophages exit the tissue via lymphatics. However in chronically inflamed tissue the stimulus is persistent, and therefore recruitment of monocytes is maintained, existing macrophages are tethered in place, and proliferation of macrophages is stimulated (especially in Atheromatous Plaque s). EXUDATIVE COMPONENT The ''exudative component'' involves the movement of plasma fluid, containing important Protein s such as Fibrin and Immunoglobulin s (antibodies), into inflamed tissue. This movement is achieved via the chemically-induced dilation and increased permeability of Blood Vessel s, which results in a net loss of Blood Plasma . The increased collection of fluid into the tissue causes it to swell ( Edema ). Vascular changes Acute inflammation is characterised by marked vascular changes, including Vasodilation , increased permeability, and the slowing of blood flow, which are induced by the actions of various inflammatory mediators. Vasodilation occurs first at the Arteriole level, progressing to the Capillary level, and brings about a net increase in the amount of blood present, causing the redness and heat of inflammation. Increased permeability of the vessels results in the movement of Plasma into the tissues, with resultant ''stasis'' due to the increase in the concentration of the cells within blood - a condition characterised by enlarged vessels packed with cells. Stasis allows leukocytes to marginate along the endothelium, a process critical to their recruitment into the tissues. Normal flowing blood prevents this, as the Shearing Force along the periphery of the vessels moves cells in the blood into the middle of the vessel. Plasma cascade systems
Plasma derived mediators
CELLULAR COMPONENT The ''cellular component'' involves Leukocyte s, which normally reside in blood and must move into the inflamed tissue via ''extravasation'' to aid in inflammation. Some act as Phagocyte s, ingesting Bacteria , viruses, and cellular debris. Others release enzymatic Granule s which damage pathogenic invaders. Leukocytes also release inflammatory mediators which develop and maintain the inflammatory response. Generally speaking, acute inflammation is mediated by Granulocyte s, while chronic inflammation is mediated by mononuclear cells such as Monocyte s and Lymphocyte s. Leukocyte extravasation See Also: Leukocyte extravasation Various Leukocyte s are critically involved in the initiation and maintenance of inflammation. These cells must be able to get to the site of injury from their usual location in the blood, therefore mechanisms exist to recruit and direct leukocytes to the appropriate place. The process of leukocyte movement from the blood to the tissues through the blood vessels is known as ''extravasation'', and can be divided up into a number of broad steps: # Leukocyte localisation and recruitment to the endothelium local to the site of inflammation – involving margination and adhesion to the endothelial cells: Recruitment of leukocytes is Receptor -mediated. The products of inflammation, such as Histamine , promote the immediate expression of P-selectin on endothelial cell surfaces. This receptor binds weakly to carbohydrate ligands on leukocyte surfaces and causes them to "roll" along the endothelial surface as bonds are made and broken. Cytokines from injured cells induce the expression of E-selectin on endothelial cells, which functions similarly to P-selectin. Cytokines also induce the expression of Integrin ligands on endothelial cells, which further slow leukocytes down. These weakly bound leukocytes are free to detach if not activated by chemokines produced in injured tissue. Activation increases the affinity of bound integrin receptors for ligands on the endothelial cell surface, firmly binding the leukocytes to the endothelium. # Migration across the endothelium, known as'' transmigration, ''via the process of diapedesis: Chemokine gradients stimulate the adhered leukocytes to move between endothelial cells and pass the basement membrane into the tissues. # '''Movement of leukocytes within the tissue via proteins via expressed integrins and CD44 to prevent their loss from the site. Chemoattractant s cause the leukocytes to move along a chemotactic gradient towards the source of inflammation. Cell derived mediators
MORPHOLOGIC PATTERNS '']] Specific patterns of acute and chronic inflammation are seen during particular situations that arise in the body, such as when inflammation occurs on an Epithelial surface, or Pyogenic bacteria are involved.
INFLAMMATORY DISORDERS Abnormalities associated with inflammation comprise a large, unrelated group of disorders which underly a variety of human diseases. The immune system is often involved with inflammatory disorders, demonstrated in both Allergic Reaction s and some Myopathies , with many Immune System Disorder s resulting in abnormal inflammation. Non-immune diseases with aetiological origins in inflammatory processes are thought to include cancer, Atherosclerosis , and Ischaemic Heart Disease . A large variety of proteins are involved in inflammation, and any one of them is open to a genetic mutation which impairs or otherwise dysregulates the normal function and expression of that protein. Examples of disorders associated with inflammation include: Allergies An allergic reaction, formally known as Type 1 Hypersensitivity , is the result of an inappropriate immune response triggering inflammation. A common example is Hay Fever , which is caused by a hypersensitive response by skin Mast Cell s to Allergen s. Pre-sensitised mast cells respond by Degranulating , releasing Vasoactive chemicals such as histamine. These chemicals propagate an excessive inflammatory response characterised by blood vessel dilation, production of pro-inflammatory molecules, cytokine release, and recruitment of leukocytes. Severe inflammatory response may mature into a systemic response known as Anaphylaxis . Other Hypersensitivity reactions (''type 2'' and ''type 3'') are mediated by antibody reactions and induce inflammation by attracting leukocytes which damage surrounding tissue. Myopathies Inflammatory myopathies are caused by the immune system inappropriately attacking components of muscle, leading to signs of muscle inflammation. They may occur in conjunction with other immune disorders, such as Systemic Sclerosis , and include Dermatomyositis , Polymyositis , and Inclusion Body Myositis . Leukocyte defects Due to the central role of leukocytes in the development and propagation of inflammation, defects in leukocyte function often result in a decreased capacity for inflammatory defence with subsequent vulnerability to infection . Dysfunctional leukocytes may be unable to correctly bind to blood vessels due to surface receptor mutations, digest bacteria ( Chediak-Higashi Syndrome ), or produce Microbicide s ( Chronic Granulomatous Disease ). Additionally, diseases affecting the Bone Marrow may result in abnormal or few leukocytes. Pharmacological Certain drugs or chemical compounds are known to affect inflammation. Vitamin A deficiency causes an increase in inflammatory responses2, and Anti-inflammatory drugs work specifically by inhibiting normal inflammatory components. TERMINATION The inflammatory response must be actively terminated when no longer needed to prevent unnecessary "bystander" damage to tissues. Failure to do so results in chronic inflammation, cellular destruction, and attempts to heal the inflamed tissue. One intrinsic mechanism employed to terminate inflammation is the short half-life of inflammatory mediators ''in vivo''. They have a limited time frame to affect their target before breaking down into non-functional components, therefore constant inflammatory stimulation is needed to propagate their effects. Active mechanisms which serve to terminate inflammation include :
SYSTEMIC EFFECTS An organism can escape the confines of the immediate tissue via the Circulatory System or Lymphatic System , where it may spread to other parts of the body. If an organism is not contained by the actions of acute inflammation it may gain access to the lymphatic system via nearby Lymph Vessel s. An infection of the lymph vessels is known as Lymphangitis , and infection of a lymph node is known as Lymphadenitis . A pathogen can gain access to the bloodstream through lymphatic drainage into the circularitory system. When inflammation overwhelms the host, Systemic Inflammatory Response Syndrome is diagnosed. When it is due to Infection , the term Sepsis is applied, with Bacteremia being applied specifically for bacterial sepsis and Viremia specifically to viral sepsis. Vasodilation and organ dysfunction are serious problems associated with widespread infection that may lead to Septic Shock and death. Acute-phase proteins Inflammation also induces high systemic levels of ''acute-phase proteins''. In acute inflammation, these proteins prove beneficial, however in chronic inflammation they can contribute to Amyloidosis These proteins include C-reactive Protein , Serum Amyloid A , Serum Amyloid P , Vasopressin , and Glucocorticoid s, which cause a range of systemic effects including :
Leukocyte numbers Inflammation often affects the numbers of leukocytes present in the body:
Systemic inflammation and obesity With the discovery of Interleukin s (IL), the concept of ''systemic inflammation'' developed. Although the processes involved are identical to tissue inflammation, systemic inflammation is not confined to a particular tissue but involves the Endothelium and other organ systems. High levels of several inflammation-related markers such as IL-6 , IL-8 , and TNF-α are associated with Obesity .34 During clinical studies, inflammatory-related molecule levels were reduced and increased levels of anti-inflammatory molecules were seen within four weeks after patients began a very low calorie diet.5 The association of systemic inflammation with Insulin Resistance and Atherosclerosis is the subject of intense research. OUTCOMES The outcome in a particular circumstance will be determined by the tissue in which the injury has occurred and the injurious agent that is causing it. There are three possible outcomes to inflammation: #Resolution The complete restoration of the inflamed tissue back to a normal status. Inflammatory measures such as vasodilation, chemical production, and leukocyte infiltration cease, and damaged Parenchyma l cells regenerate. In situations where limited or short lived inflammation has occurred this is usually the outcome. #Fibrosis Large amounts of tissue destruction, or damage in tissues unable to regenerate, can not be regenerated completely by the body. Fibrous Scarring occurs in these areas of damage, forming a scar composed primarily of Collagen . The scar will not contain any specialized structures, such as Parenchyma l cells, hence functional impairment may occur. #Chronic inflammation In acute inflammation, if the injurious agent persists then chronic inflammation will ensue. This process, marked by inflammation lasting many days, months or even years, may lead to the formation of a Chronic Wound . Chronic inflammation is characterised by the dominating presence of macrophages in the injured tissue. These cells are powerful defensive agents of the body, but the Toxin s they release (including Reactive Oxygen Species ) are injurious to the organism's own tissues as well as invading agents. Consequently, chronic inflammation is almost always accompanied by tissue destruction. EXAMPLES Inflammation is usually indicated by adding the suffix " -itis ", as shown below. However, some conditions such as Asthma and Pneumonia do not follow this convention. More examples are available at List Of Types Of Inflammation . |
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