Pathophysiology-Unit 2.pptx
- 1. UNIT-I I Mechanism of Infection & Inflammation BY DILEEP KUMAR (RN, MSN, Dip: CHN, DIT)
- 2. OBJECTIVES The objectives of this unit are to; Describe the stages of an infectious disease after the point at which the potential pathogen enters the body. List systemic manifestation of infectious diseases Discuss the purpose of inflammation Describe the physiological mechanism involved in the production of five cardinal signs of inflammation Differentiate the hemodynamic and cellular phases of inflammatory response Differentiate between chronic and acute inflammation
- 3. Infection is a host organism’s response to a pathogen, or disease-causing substance. Infectious Disease is an illness caused by harmful agents (pathogens) that get into body. most common causes are; viruses, bacteria, fungi and parasites. Infectious diseases usually spread from person to person through contaminated food or water through bug bites etc. Some infectious diseases are minor and some are very serious. INFECTIOUS DISEASE
- 4. An infection is an illness caused by a harmful microscopic organism that invades the body, called a pathogen, such as a bacteria, virus, parasite, or fungi. There are five stages of infection: Incubation Prodromal Illness Decline Convalescence STAGES OF AN INFECTIOUS DISEASE
- 5. The period between the first exposure to a pathogen and the first emergence of symptoms. During this stage, a person does not show any signs or symptoms of sickness. duration varies based on the type of pathogen. Incubation can last hours, days, months, or (rarely) years. Incubation Stage
- 6. period after incubation & before the characteristic symptoms of infection occur. People can also transmit infections during this stage. infectious agent continues replicating, which triggers the body’s immune response and mild, nonspecific symptoms. These symptoms can include: low-grade fever fatigue Prodromal Stage
- 7. This stage includes the time when a person shows apparent symptoms of an infectious disease. The symptoms of infection vary widely depending on the underlying cause. In general, people who have an active infection may experience: Fever Fatigue Headache Muscle Aches Swollen Lymph Nodes Illness or Clinical Stage
- 8. During this stage, the immune system mounts a successful defense against the pathogens, and the number of infectious particles decreases. Symptoms will gradually improve. However, a person can develop secondary infections during this stage if the primary infection has weakened their immune system. During this stage, the virus can still transmit to other people Decline Stage
- 9. The final stage of infection is known as convalescence. During this stage, symptoms resolve, and a person can return to their normal functions. Depending on the severity of the infection, some people may have permanent damage even after the infection resolves. Convalescence Stage
- 10. Infection typically occurs in five stages. The incubation stage occurs right after exposure and before symptoms develop. This stage can range from hours for some infections to days, weeks, or even years for other infections. The next stage is prodromal, which involves mild, nonspecific symptoms. During the illness stage, a person shows the characteristic symptoms of infection, such as a rash in chickenpox or vomiting due to food poisoning. The decline stage occurs when the number of infectious microbes declines and symptoms resolve. The final stage is convalescence. During this stage, symptoms disappear, and the body starts to recover. SUMMARY
- 11. refers to the collection of signs & symptoms expressed by the host during the disease course. also known as the clinical picture, or disease presentation, and can be characteristic of any given infectious agent. In terms of pathophysiology, symptoms are the outward expression of the struggle between invading organisms and the retaliatory inflammatory and immune responses of the host. Symptomatology
- 12. Manifestations of infection may be local (eg, cellulitis, abscess) or systemic (most often fever). may be specific & reflect site of infection (e.g., diarrhea, rash, convulsions, hemorrhage, & pneumonia) or non-specific & can be shared by a No. of diverse infectious diseases such as fever, myalgia, headache, and lethargy. Manifestations in a diseased host can be obvious, as in the case of chickenpox or measles. or covert such as an increased white blood cell count, may require laboratory testing to detect. Systemic Manifestation of Infectious Diseases
- 13. Severe, generalized infections may have life- threatening manifestations (eg, sepsis and septic shock). Manifestations may develop in multiple organ systems. Accurate recognition and documentation of symptomatology can aid in the diagnosis of an infectious disease Most manifestations resolve with successful treatment of the underlying infection. Continue
- 14. Inflammation is the body's mechanism for coping with agents that could damage it. A protective response to rid the body of the cause of cell injury and the resultant necrotic cells that cell injury produces. A set of complex changing responses to tissue injury primarily caused by toxic chemicals, some environmental agents, trauma, overuse, or infection. Inflammation is a “second-line” defense against infectious agents. INFLAMMATION
- 15. Inflammation involves a wide variety of physiologic and pathologic responses intended to: eliminate the initial cause of cell injury remove the necrotic cells & damaged tissue, generate new tissue. accomplishes by destroying, enzymatically digesting, walling off, or otherwise neutralizing the harmful agents such astoxins, foreign agents, or infectious organisms. Thus, inflammation is intimately interwoven with the repair processes that replace damaged tissue or fill in the residual defects with fibrous scar tissue. PURPOSE OF INFLAMMATION
- 16. The causes of inflammation are many and varied: Exogenous causes: Physical agents Mechanic agents: fractures, foreign corps, sand, etc. Thermal agents: burns, freezing Chemical agents: toxic gases, acids, bases Biological agents: bacteria, viruses, parasites Endogenous causes: Circulation disorders: thrombosis, infarction, hemorrhage Enzymes activation – e.g. acute pancreatitis Metabolic products – uric acid, urea ETIOLOGY
- 17. The five cardinal signs of inflammation 1. Rubor (Redness), 2. Tumor (Swelling), 3. Calor (Heat), 4. Dolor (Pain). 5. Functio Laesa (Loss of Function) FIVE CARDINAL SIGNS OF INFLAMMATION
- 18. RUBOR (REDNESS): caused by active hyperemia after momentary vasoconstriction due to stress reaction (catecholamines) related e.g to pain (injury) - dependent on vasoactive inflammatory mediators, in the developed (end stage) inflammation hypoperfusion of the inflamed area can appear due to micro- thrombotisation of vessels hyperemia increases delivery (supply) of cells (leukocytes) to the place of inflammation PHYSIOLOGICAL MECHANISM IN THE PRODUCTION OF FIVE CARDINAL SIGNS OF INFLAMMATION
- 19. TUMOR (SWELLING): develops because of increased hydrostatic pressure and increased permeability of vessels (caused by inflammatory mediators ); besides transudation into the interstitium, active exudative (secretion) processes also take place (peritoneal cavity, pericardium, pleural cavity) CALOR (HEAT): Increased temperature of the inflamed area due to hyperemia and increased metabolism
- 20. DOLOR (PAIN). – irritation of free neural endings by inflam. mediators - mainly prostaglandins, substance P, bradykinin compression of nerves by edema developing acidosis in the case of thrombotisation of vessels (in developed, chronic inflam. process) FUNCTIO LAESA (LOSS OF FUNCTION) caused by pain and edema - disabling mainly motion - prevents overload of the involved parts of the body
- 21. Vascular phase leads to an increase in blood flow and changes in the small blood vessels of the microcirculation. characterized by changes in the small blood vessels at the site of injury. begins with momentary vasoconstriction followed rapidly by vasodilation. Vasodilation involves the arterioles & venules with a resultant increase in capillary blood flow, causing heat and redness. (Two Cardinal signs) This is accompanied by an increase in vascular permeability with outpouring of protein-rich fluid (exudate) into the extravascular spaces.
- 22. The loss of proteins reduces the capillary osmotic pressure and increases the interstitial osmotic pressure. This, coupled with an increase in capillary pressure, causes a marked outflow of fluid and its accumulation in the tissue spaces, producing the swelling, pain, and impaired function (Other Cardinal signs) As fluid moves out of the vessels, stagnation of flow and clotting of blood occur. This aids in localizing the spread of infectious microorganisms. Continue
- 23. The cellular stage of acute inflammation is marked by changes in the endothelial cells lining the vasculature and movement of phagocytic leukocytes into the area of injury or infection. Focused on recruitment of leukocytes from blood release of chemical mediators from tissue cells (mast cells and macrophages) prepositioned in the tissues. The sequence of events in cellular phase includes; o Leukocyte Margination & adhesion to endothelium o Transmigration across the endothelium. o Chemotaxis CELLULAR PHASE
- 24. The cellular phase of acute inflammation involves delivery of leukocytes, mainly polymorphonuclear neutrophils (PMNs), to the site of injury so they can perform their normal functions of host defense through phagocytosis. The delivery and activation of leukocytes can be divided into the following steps: o endothelial activation, adhesion and margination, o transmigration o chemotaxis. LEUKOCYTE MARGINATION & ADHESION TO THE ENDOTHELIUM
- 25. The recruitment of leukocytes to the precapillary venules, where they exit the circulation, is facilitated by the slowing of blood flow and margination along the vessel surface Leukocyte adhesion and transmigration from the vascular space into the extravascular tissue is facilitated by complementary adhesion molecules (e.g., selectins, integrins) on the leukocyte and endothelial surfaces. After extravasation, leukocytes migrate in the tissues toward the site of injury by chemotaxis or locomotion oriented along a chemical gradient. Continue
- 26. Leukocyte Margination, Adhesion, & Transmigration
- 27. Once at the sight of injury, the products generated by tissue injury trigger a number of leukocyte responses, including phagocytosis and cell killing. Opsonization of microbes by complement factor C3b and antibody facilitates recognition by neutrophil C3b and the antibody Fc receptor. Receptor activation triggers intracellular signaling and actin assembly in the neutrophil, leading to formation of pseudopods that enclose the microbe within a phagosome. The phagosome then fuses with an intracellular lysosome to form a phagolysosome into which lysosomal enzymes Oxygen free radicals are released to kill and degrade the microbe. LEUKOCYTE ACTIVATION & PHAGOCYTOSIS
- 29. SELECTINS : E-selectin - (cytokine-activated Endothelial cells) P-selectin - (Preformed and stored in endothelial cells) L-selectin (expressed on surface of Lymphocytes and neutrophils) INTEGRINS: Activated during the process of loose and transient adhesions between the endothelial cells and leucocytes. IMMUNOGLOBULIN SUPER FAMILYADHESION MOLECULE: ICAM-1,2 ADHESION MOLECULES:
- 30. Acute inflammation is the early response of the organism to adverse stimuli. It is acquired by an increased transport of leukocytes (especially granulocytes) and plasma from the blood in the damaged tissues. In acute inflammation develops the so called “triple response of Lewis: (1) redness, (2) increased blood flow, and (3) edema. The inflammatory response is spread by series of biochemical events. The immune system, the local vascular system, and different cells in the damaged tissue are included in the process. ACUTE INFLAMMATION
- 31. The acute inflammation process is initiated by immune cells, which are already present in the involved tissue. These are: Dendritic cells, Kupffer cells, Histiocytes, Resistant macrophages, Mast cells. When infections, burns or injuries occur, the immune cells are subject to activation and release inflammatory mediators. Mediators cause clinical signs of inflammation. ACUTE INFLAMMATION
- 32. Vasodilatation and the resulting increased blood flow cause redness and increased temperature. Increased permeability of the blood vessels leads to exudation of fluid and plasma proteins into the tissue. This results in swelling. Some of the released mediators (e.g. bradykinin) raise the sensitivity to pain (hyperalgesia). The mediators also alter blood vessels to allow migration of leukocytes, primarily macrophages and neutrophils, out of the blood vessels (extravasation) into the tissue. White blood cells migrate along the chemotaxis gradient created by local cells to reach the site of injury. ACUTE INFLAMMATION
- 33. chemicals originate primarily from blood plasma, white blood cells (basophils, neutrophils, monocytes, and macrophages), platelets, mast cells, endothelial cells lining the blood vessels, and damaged tissue cells. Histamine, stored in granules of circulating basophils and mast cells triggers vasodilation and increases vascular permeability. Lysosomal compounds, and small proteins in the complement system, namely C3a and C5a. released from neutrophils, involved in increasing vascular permeability Cytokines secreted by cells involved in inflammation also have vasoactive and chemotactic properties. Chemical mediators of inflammation
- 34. The prostaglandins a group of fatty acids produced by many types of cells. increase the effects of other substances that promote vascular permeability. affect the aggregation of platelets, which is part of the clotting process. associated with pain and fever of inflammation. The plasma contains 04 interrelated systems of protein - generate various mediators of inflammation. 1. Activated complement proteins serve as chemotactic factors for neutrophils, increase vascular permeability, and stimulate the release of histamine from mast cells. also adhere to the surface of bacteria, making them easier targets for phagocytes. Continue
- 35. 2. kinin system, is activated by coagulation factor XII, produces substances that increase vascular permeability. The most important of the kinins is bradykinin, which is responsible for much of the pain and itching experienced with inflammation. 3. Coagulation system converts the plasma protein fibrinogen into fibrin, which is a major component of the fluid exudate. 4. Fibrinolytic system contributes to inflammation primarily through the formation of plasmin, which breaks down fibrin into products that affect vascular permeability. Continue
- 36. The chronic inflammation is an inflammatory reaction that lasts for months or years. Most often acute inflammation precedes the chronic, but this is not always the case. The chronic inflammation can be due to: Prolonged irritation of chemicals, Foreign particles – dust, surgical thread, etc., Infection by microorganisms that cannot be overcome for a long time by the body – tuberculosis, syphilis, brucellosis. CHRONIC INFLAMMATION
- 37. The following immune cells are involved in the chronic inflammation process: Macrophages, Neutrophils, Lymphocytes. Depending on the body’s response, the chronic inflammation is: Granulomatous inflammation, Non-granulomatous inflammation. The aim of the chronic inflammation is to limit and remove the agent, which cannot be removed by acute response (acute inflammation). Restriction and removal of the agent depend on the reactivity of the immune system. Chronic Inflammation
- 38. Acute inflammation is of relatively short duration, lasting from a few minutes to several days, and is characterized by the exudation of fluid and plasma components and emigration of leukocytes, predominantly neutrophils, into the extravascular tissues. Chronic inflammation is of a longer duration, lasting for days to years, and is associated with the presence of lymphocytes and macrophages, proliferation of blood vessels, fibrosis, and tissue necrosis. Chronic Versus acute inflammation
- 39. FEATURE ACUTE CHRONIC Onset Fast Minutes or hours Slow Days or months Cellular infiltrate Mainly neutrophils Also have macrophage Monocytes/ macrophages & lymphocytes/ plasma cells, fibroblasts, giant cells Tissue injury, fibrosis Usually mild and self-limiting Often severe and progressive Local & systemic signs prominent Less prominent; may be subtle DIFFERENCES BETWEEN ACUTE & CHRONIC INFLAMMATION
- 40. DIFFERENCES BETWEEN ACUTE & CHRONIC INFLAMMATION