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Definition: It is defined as the reaction of vascularized connective tissue to a sub lethal injury. It is fundamentally a protective response which occurs in a living mammalian tissue to get rid of the offensive injurious agent.

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Wright defines inflammation as the process by means of which cells and exudates accumulate in irritated tissues and tend to protect them from further injury. It is a progressive reaction in living tissues, and is always accompanied by or followed by the process of repair i.e.,. Regeneration or healing.
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The agents causing the injury, and thus leading to inflammation are : Physical agents. Chemical agents. Biological agents. Immunological agents.

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Physical agents: Exposure to extremes of temperature, trauma, radiation. Chemical agents : Exposure to acids and alkalis. Biological agents: Bacteria, Virus, Fungi, and Parasites. Immunological agents: Antigen-Anti body reactions, Mismatched blood transfusion, Anaphylaxis.

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The irritant apparently induces direct injury of cells, the resulting altered metabolism liberating materials that initiate the inflammatory process. Inflammation is the most common and fundamental pathologic reaction and, in general, is protective, tending to localize or dispose of the injurious and set the stage for repair.

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Inflammation is generally categorized as acute and chronic. Acute inflammation: On set is insidious, runs a short course, resolves completely with out leaving any scar tissue. Predominant cell is neutrophil, and cardinal event is exudates. E.g.. Pharyngitis.

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Chronic inflammation: Onset is gradual, runs a prolonged course, resolves slowly, and always leaves behind a scar tissue. Predominant cells are Lymphocytes/Macrophages. Cardinal event include Tissue necrosis with proliferation of blood vessels and fibrosis. E.g. Pulmonary tuberculosis.

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Calor Heat. Rubor Redness. Dolor Pain. Tumor Swelling. Functio leesa Transient loss of function.

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The three most important events in acute inflammation includes: 1. Hemodynamic changes. 2. Vascular changes or structural changes in the blood vessels. 3. Cellular changes.

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Immediately after the injury there is a transient vasoconstriction and this is followed by a massive vasodilatation resulting increased flow of blood to the inflamed area. This is called HYPEREMIA. This is the factor which produces heat and redness at the site of inflammation.

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The normal flow of blood inside the blood vessel is called Laminar flow or Axial flow. The formed elements flow in the center and plasma flows in the periphery. Due to the inflammatory process there will be a change in the permeability of the blood vessels.

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This results in the escape of plasma in to the interstitial space. Fluid moving from intravascular compartment to extra vascular compartment is called Transudate. Due to the inflammatory process there will be cellular injury resulting in loss of integrity of cell wall.

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The resulting damage causes the fluid from intracellular space move to extracellular space. The fluid moving from intracellular space to extra cellular space is called Exudates. The exudates are rich in protein, has a specific gravity more than 1.020 and rich in cellular debries.

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This can be distinguished from transudate which is an ultra filtrate of plasma, comes out of the vessel due to imbalances in the hydro static pressure. The specific gravity of transudate is less than 1.020, does not contain protein and is acellular.

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The increase in vascular permeability is due to the formation of endothelial gaps, contraction and retraction of endothelial cells, and endothelial injury. Slowing of circulation (Stasis): As the protein rich plasma escapes out of the vessels, there will be accumulation of red cells, white cells, and platelets within the vessel resulting in slowing down of circulation.

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They play a critical role in inflammation and delivers the appropriate leucocytes to the site of injury. This can be grouped into intravascular and extra vascular events. Intravascular events: It includes Margination, rolling and pavementing, and adhesion. Extra vascular events : It includes Trans migration, Diapedesis, chemo taxis and phagocytosis.

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Margination: During normal blood flow the leucocytes occupy the central column of flow rimmed by the red cells and platelets in the periphery. This is called the axial flow or laminar flow. During inflammation as a result of movement of plasma from intravascular space to extra vascular space and resulting stasis, the laminar flow is disturbed.

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This results in reorientation of formed elements of blood. The leucocytes from the central column move to the periphery. This movement of Leucocytes from the center to the periphery is called Margination. Rolling and Pavementing: The leucocytes on reaching the periphery roll on the endothelium and arrange themselves on the endothelium which appears like the stones placed on the pavement. The event is called pavementing.

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Adhesion: The leucocytes are tightly bound to the endothelial cells by a group of proteins called adhesion molecules. They act as cellular glue and bridges leucocytes and endothelium. Trans migration (Emigration) : Once the leucocytes adhere to the endothelium they slowly put forth long foot processes called pseudo pods which extend which extend to the endothelial cell junctions and insert themselves into the gaps.

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The leucocytes then slowly escape out of the blood vessel. This active movement of leucocytes from the intravascular compartment to the extra vascular compartment is called Emigration. This is followed by movement of Red blood cells through the gaps of endothelium passively. This passive movement of RBCs from intravascular space to extra vascular space is called Diapedesis.

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Chemo taxis : (Chemo- Chemical, TaxisMovement). It is defined as a locomotion oriented along a chemical gradient. It is a process in which leucocytes are attracted by certain chemicals to reach the site of injury. Chemo attractants: The chemicals that attract the leucocytes are called as chemo attractants.

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They include the following : a. Bacterial products rich in N Formyl Methionine. b. Complement fraction 5a. c. Leucotriene B4. d. Interleukin-8.

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Mechanism : The leucocytes has cell surface receptors for the chemo attractants and once receptor is occupied, it leads to sequence of events activating the contractile proteins of the leucocyte which makes the cell move and reach the site of injury. The contractile proteins include actin, myosin, filamin, gelsolin, calmodulin, and profilin.

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Phagocytosis: It is an important and critical cellular event in acute inflammation in which the offending pathogen is recognized and killed by the leucocytes. It comprises of three stages: 1. Stage of recognition and attachment. 2. Stage of engulfment. 3. Stage of killing and degradation.

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Sta ge of recognition and attachment: The leucocyte s will be able to recognize the offending pathogen only when they are coated with protein substance called opsonin. This process is called opsonisation. Stage of Engulfment: Once the receptor is occupied by opsonin, the contractile proteins of the cell gets activated and it put forth cytoplasmic extensions called pseudo pods which slowly engulf the organism .

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This is called Phagosome. By this process the organism gets internalized with in the cytoplasm of the leucocyte. With in the cytoplasm the phagosome is slowly moved close to the lysosome of the leucocyte and they both fuse to form phagolysosome. After the fusion the contents of the lysosome are released into the phagosome which activates the killing process.

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Stage of killing and degradation: All lysosomes moves towards the vacuole and release Acid Hydrolases. They are responsible for killing of organisms. Finally lyses takes place. Not all bacteria are killed by phagocytosis. Some continue to live and even multiply with in the phagocytes. This is true of the organisms of Histoplasmosis, Kalaazar, Leprosy and T.B.

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Killing is usually done by two processes called oxygen dependent mechanism and oxygen independent mechanism. The oxygen dependent mechanism is carried out by the generation of free oxygen radicals which undergo a chain reaction to kill the pathogen. The generation of free oxygen radicals occur due to the activation of NADPH oxidase which generates superoxide free radical.

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This superoxide free radical (O2-.) undergoes spontaneous dismutation and gets converted to hydrogen peroxide. The hydrogen peroxide in the presence of an enzyme Myeloperoxidase gets activated to another radical called hypochlorite which is potent microbicidal agent. Along with the microbial agent the WBC also dies. A pus is formed.

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A pus is a straw colored liquid which contains transudate, exudate, dead WBC ,dead microbes and RBC.

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General manifestations of inflammation include malise, fatigue, headache, and anorexia. Fever or pyrexia is common if inflammation is extensive. Fever results from the release of pyrogens or fever producing substances from the white blood cells or macrophages. If infection has caused the inflammation, fever can be severe.

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Fever is a protective mechanism initiated by the body and creates an inhospitable atmosphere for the pathogenic organism there by preventing their growth and development. Pyrogens circulate in the blood and cause the body temperature control system (Thermostat) in the hypothalamus to be reset at a higher level.

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Heat production mechanisms such as shivering are activated to increase cell metabolism. It is paradoxical because patient will be febrile but still shivers. By inducing shivering the core temperature of the body Rises. Involuntary cutaneous vasoconstriction (characterized by pale cool skin) reduces heat loss from the body.

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The body adapts a fetal position by curling (Thighs are flexed up to thigh and legs are flexed ninety degrees to thigh and shoulders are abducted towards chest). This position traps and conserves the heat. These mechanisms continue until the body temperature reaches the new higher setting.

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Diagnostic tests: Leucocytosis, an elevated Erythrocyte sedimentation rate, increased plasma proteins and cell enzymes in the serum are non specific changes; since they do not indicate the site or cause of inflammation. They provide helpful screening and monitoring information when a problem is suspected.

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In patients with leucocytosis there is often an increase in immature neutrophils. A differential count (The proportion of each type of WBC) may helpful in distinguishing acute from chronic infections, and allergic reactions. If it is an acute inflammation it is always the neutrophils level be high. If it is a chronic inflammation it is always lymphocyte level which goes up.

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Allergic reactions commonly produce eosinophilia. Examination of a peripheral blood smear may disclose significant number of abnormal cells which may provide a clue to identify the problem. The increase in leucocytes is usually accompanied by a Left shift in the ratio of immature to mature leucocytes.

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The other important systemic response for an infection/inflammation is a rise in Erythrocyte sedimentation rate. ESR is a prognostic index and remains elevated as long as the disease process is present in the body. Increased plasma proteins (Fibrinogen, Prothrombin, and alpha-antitrypsin) result from a response in the liver that increases protein synthesis.

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Cell enzymes and isoenzymes may be elevated in the blood in the presence of severe inflammation and necrosis. This sign may be helpful in locating the site of necrotic cells that have released the enzymes. Some of the enzymes are not tissue specific. For e.g., Asparate Amino Transferase (AST) formerly known as Serum glutamic oxaloacetic trans aminase (SGOT).

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This enzyme is elevated in liver disease and in the acute stage of Myocardial infarction. However, the iso-enzymes CK-MB is specific to Myocardial tissue and is elevated in Acute myocardial infarction. Similarly Troponine which is specific to myocardial tissue and is elevated in acute myocardial infarction. The enzyme alanine amino transferase is specific to liver and is elevated in liver diseases.

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If the cause of the inflammatory response is a brief exposure to a damaging agent , for instance, touching a hot object, the response often subsides in approximately 48 hours, vascular integrity is recovered, and excess fluid and protein are recovered by lymphatic capillaries and returned to general circulation. The manifestation of inflammation gradually decrease. Otherwise inflammation persists until the causative agent is removed.

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