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Practical 4 Inflammation.ppt

  2. Definition Inflammation is a complex reaction of vascularized connective tissue to any injury.
  3. CLASSIFICATION Acute inflammation Chronic inflammation
  4. Patterns of Inflammation Acute * Short duration (minutes-days) with exudation of fluid & plasma proteins, and emigration of neutrophils into tissue. Chronic * Longer duration (days-months) with tissue accumulation of lymphocytes, plasma cells, & macrophages plus variable proliferation of blood vessels, fibrosis and necrosis.
  5. Inflammation: essential definitions Exudation = Escape of fluid, proteins, and blood cells from vessels into tissues Exudate = Inflammatory fluid, high protein concentration and > 1.020 Transudate = Watery fluid, low protein concentration and sp. gr. < 1.012 Oedema = Excess fluid in tissues & excess fluid in serous cavities lined by mesothelium (pleural, pericardial, peritoneal) Pus = Inflammatory exudate rich in neutrophils and cell debris
  6. Cardinal Signs of Inflammation Redness : Hyperaemia. Warm : Hyperaemia. Pain : Nerve, Chemical mediators. Swelling : Exudation Loss of Function: Pain
  7. Function of inflammatory exudates 1-Dilute the invading microorganism and its toxins. 2-Bring antibodies through the plasma to the inflamed area for neutralization. 3-Bring leukocytes that engulf the invading microorganisms. 4-Bring fibrinogen through the plasma, which is converted, to fibrin mesh, helping in trapping the microorganism and localize the infection. 5- Initiate the process of repair
  8. Stimuli For Acute Inflammation Infections- * Bacterial, Viral, Parasitic, Microbial toxins Trauma- * Blunt and Penetrating Physical  Thermal injury.e.g.Burns,Frostbite,Irradiation Chemical agents- Tissue Necrosis Foreign Bodies(Splinters, Dirt, Sutures) Immune Reaction
  9. Pathogenesis Vascular events * Changes in Vascular Flow and Caliber * Increased Vascular Permeability Cellular events * Extravasation of Leukocytes • In lumen of blood vessel (3 phases): – Margination – Rolling – Adhesion • Transmigration of leukocytes • Migration into interstitium toward injury site by locomotion along a chemical gradient: Chemotaxis * Phagocytosis
  10. HAEMODYNAMIC CHANGES Vascular events Cellular events
  11. Vascular Events Alteration in vascular flow and caliber 1. Vasoconstriction (Transient) 2. Vasodilatation 3. Slowing 4. Stasis Increased vascular permeability
  12. Mechanisms vascular permeability Mechanism Gaps due to endothelial contraction New blood vessel formation Direct injury Leukocyte- dependent injury Increased transcytosis Mediators Histamine, bradykinin, substance P VEGF Toxins, burns, chemicals Enzymes , toxic oxygen species VEGF Five proposals, Fig. 3-4, Pathologic Basis of Disease, 6th ed, WB Saunders, 1999.
  13. Cellular Events Margination, Rolling, and Adhesion to endothelium Chemotaxis Leukocyte activation and phagocytosis
  14. Leukocyte emigration: overview Fig. 2-6, Pathologic Basis of Disease, 2006.
  15. TRANSUDATE AND EXUDATE TRANSUDATE  Filtrate of blood plasma without changes in endothelial permeability.  Non-inflammatory edema  <1gm/dl protein  pH <7.3  Few cells,mainly mesothelial  Eg:congestive cardiac failure EXUDATE  Edema of inflamed tissue associated with increased permeability  inflammatory edema  >3.5gm/dl protein  pH>7.3  Many cells,inflammatory as well as parenchymal  Eg:purulent exudate such as pus
  16. MORPHOLOGIC PATTERNS OF ACUTE INFLAMMATION Serous Fibrinous Suppurative or Purulent Ulcers
  17. SEROUS INFLAMMATION: Serous inflammation is marked by the outpouring of a thin fluid * e.g. the skin blister resulting from a burn or viral infection represents a large accumulation of serous fluid
  18. FIBRINOUS INFLAMMATION More severe injuries and More greater vascular permeability, Larger molecules such as * fibrinogen pass the vascular barrier, and fibrin is formed and deposited
  19. FIBRINOUS PERICARDITIS(GROSS)  Exudation of a protein- rich fluid into a cavity leads to a transudate. The fibrin in this fluid can form a fibrinous exudate on the surfaces. Here, the pericardial cavity has been opened to reveal a fibrinous pericarditis with strands of stringy pale fibrin between visceral and parietal pericardium.
  20. FIBRINOUS INFLAMMATION * A fibrinous exudate is characteristic of inflammation in the lining of body cavities, such as the meninges, pericardium and pleura
  21. FIBRINOUS INFLAMMATION Fibrinous exudates may be removed by fibrinolysis But when the fibrin is not removed, it may stimulate the in-growth of fibroblasts and blood vessels and thus lead to scarring (organization)
  22. SUPPURATIVE OR PURULENT INFLAMMATION Characterized by the production of large amounts of pus or purulent exudate consisting of neutrophils, necrotic cells, and edema fluid Certain bacteria (e.g., staphylococci) produce this localized suppuration and are therefore referred to as pyogenic (pus-producing) bacteria
  23. G 1
  24. Acute Appendicitis(Gross) Here is acute appendicitis with Yellow to tan exudate and Hyperemia, including The peri-appendiceal fat superiorly, rather than a smooth, glistening pale tan serosal surface.
  25. Acute Appendicitis(Micro) Here, the mucosa shows ulceration and undermining by an extensive neutrophilic exudate.
  26. PYOGENIC MENINGITIS(GROSS) A purulent exudate is seen beneath the meninges in the brain of this patient with acute meningitis from Streptococcus pneumoniae infection. The exudate obscures the sulci.
  27. G 55
  28. Pyogenic Meningitis(Micro)  Microscopically, a neutrophilic exudate is seen involving the meninges at the left, with prominent dilated vessels.  There is edema and focal inflammation in the cortex to the right.  This acute meningitis is typical for bacterial infection.
  29. G 7
  30. LOBAR PNEUMONIA(MICRO) At medium power magnification, numerous neutrophils fill the alveoli in this case of acute bronchopneumonia in a patient with a high fever. Pseudomonas aeruginosa was cultured from sputum. Note the dilated capillaries in the alveolar walls from vasodilation with the acute inflammatory process.
  31. SUPPURATIVE OR PURULENT INFLAMMATION Abscesses : * Localized collections of purulent inflammatory tissue caused by suppuration buried in a tissue, an organ, or a confined space
  32. Suppurative inflammation. A, A subcutaneous bacterial abscess with collections of pus. B, The abscess contains neutrophils, edema fluid, and cellular debris.
  33. Kidney Abscess(Gross) In the lower pole of this kidney is a 1 cm pale yellow abscess.
  34. G 2
  35. KIDNEY ABSCESS(MICRO) This is an ascending bacterial infection leading to kidney abscess. Numerous PMN's are seen filling renal tubules across the center and right of this picture.
  36. Lung Abscess(Gross)  Here is lung abscess, in the upper lobe of this left lung. An abscess is a complication of severe pneumonia, most  typically from virulent organisms such as S. aureus.
  37. Brain Abscess
  38. G 8 Liver abscess
  39. Localized liquefactive necrosis liver abscess Removal of the dead tissue leaves behind a scar
  40. Cellulitis  It is an acute diffuse suppurative inflammation caused by streptococci, which secrete hyaluronidase & streptokinase enzymes that dissolve the ground substances and facilitate the spread of infection. Sites: * Areolar tissue; orbit, pelvis, … * Lax subcutaneous tissue
  41. Ulcers An ulcer is a local defect of the surface of an organ or tissue that is produced by the sloughing (shedding) of inflammatory necrotic tissue
  42. Ulceration can occur only when tissue necrosis and resultant inflammation exist on or near a surface Epithelial Defect Fibrinopurulent exudates Granulation tissue Fibrosis Necrotic base
  43. Systemic effects of Inflammation Acute phase reaction/response * IL-1 and TNF * Fever * Malaise * Anorexia Bone marrow * Leukocytosis * IL-1 + TNF Lymphoid organs Liver IL-6, IL-1, TNF Acute phase proteins * C-reactive protein * Lipopolysaccharide binding protein * Serum amyloid A * a-2 macroglobulin * Haptoglobin * Ceruloplasmin * fibrinogen
  44. Systemic Effects of Inflammation Fever Fever is produced in response to Pyrogens What are pyrogens? * act by stimulating prostaglandin synthesis in the vascular and perivascular cells of the hypothalamus.  Bacterial products (called exogenous pyrogens), stimulate leukocytes to release cytokines such as IL-1 and TNF (called endogenous pyrogens) that increase the enzymes (cyclooxygenases) that convert AA into prostaglandins.
  45. Outcomes of acute inflammation Fig. 3-24, Pathologic Basis of Disease, 6th ed, WB Saunders, 1999.
  46. Chronic inflammation Chronic inflammation is inflammation of prolonged duration (weeks or months) in which inflammation, tissue injury, and attempts at repair coexist, in varying combinations. Types of chronic inflammation 1. Chronic non specific inflammation 2. Chronic specific inflammation: It includes granulomatous inflammation
  47. Causes of chronic inflammation Prolonged acute inflammation or repeated bout of acute inflammation may lead to the presence of more mononuclear cells and chronic inflammation.
  48. Causes of chronic inflammation Persistent infection by microorganisms that are difficult to eradicate such as mycobacteria, certain viruses, fungi and parasites. These often evoke delayed-type hypersensitivity reaction. Immune-mediated inflammatory diseases: Include autoimmune diseases & allergic diseases. May show mixture of acute and chronic inflammation. Prolonged exposure to potentially toxic agents, either exogenous (e.g. silicosis) or endogenous (e.g. atherosclerosis).
  49. CHRONIC INFLAMMATION Morphologically, characterized by: Infiltration by mononuclear cells i.e. macrophages, lymphocytes, and plasma cells. Tissue destruction.  Attempts at healing by connective tissue replacement of damaged tissue accompanied by angiogenesis and in particular, fibrosis.
  50. Chronic non specific inflammation  It is seen affecting any organ for a prolonged period of time.  It is characterized by diffuse infiltration with mononuclear inflammatory cells.  Examples: 1. Chronic nonspecific cervicitis 2. Chronic cholecystitis 3. Chronic osteomyelitis
  52. Chronic cholecystitis
  53. Chronic cholecystitis
  54. CHRONIC OSTEOMYELITIS(GROSS) Gross specimen of bone shows outer casing of necrosed,dead bone known as sequestrum. Inner new bone formation can be seen,known as involucrum.
  55. CHRONIC OSTEOMYELITIS There is fibrosis of the marrow space accompanied by chronic inflammatory cells. There can be bone destruction with remodeling.
  56. Granulomatous inflammation Granulomatous inflammation is the ditinctive pattern of chronic inflammation. It is caused by organisms which are difficult to eradicate and induce immune response known as delayed hypersensitivity. Immune reactions usually lead to development of granuloma, which is a cellular attempt to contain an offending agent.
  57. GRANULOMA Granuloma is a focus of chronic inflammation consisting of a microscopic aggregation of macrophages that are transformed into epithelium like cells- epithelioid cells surrounded by a collar of mononuclear leukocytes, principally lymphocytes and occasionally plasma cells. Frequently, epithelioid cells fuse to form giant cells, having many nuclei arranged either peripherally (Langhans-type) or haphazardly (Foreign body-type). Older granuloma develop an enclosing rim of fibroblasts and connective tissue.
  58. Defination Chronic Inflammation- Defined as a prolong process in which tissue destruction and inflammation occurs at the same time. Granuloma-Defined as a circumscribed ,tiny,lesion,about 1mm in diameter ,composed predominantly of collection of modified macrophages called epitheloid cells and rimmed at the periphery by lymphoid cells.
  59. Tuberculosis Mycobacterium tuberculosis Caseating granuloma (tubercle) Leprosy Mycobacterium leprae AFB in macrophages; noncaseating granuloma Syphillis Treponema pallidum Gumma(enclosing wall of histiocytes; plasma cells) Cat-scratch disease Gram neg bacillus Round or stellate granuloma Crohn disease Immune reaction against intestinal bacteria, self antigens Occasional noncaseating granuloma in the wall of intestine Sarcoidosis Unknown etiology Noncaseating granulomas with abundant activated macrophages Inorganic metals ,dusts,silicosis Foreign body Granuloma with foreign body type giant cells.
  60. GRANULOMATOUS INFLAMMATION (GROSS) Granulomatous disease can become quite extensive. Here are numerous confluent granulomas in a case of pulmonary tuberculosis.
  61. GRANULOMATOUS INFLAMMATION(MICRO,L.P.) The focal nature of granulomatous inflammation is demonstrated in this microscopic section of lung in which there are scattered granulomas in the parenchyma.
  63. G 4 Identify the condition Describe gross findings
  66. Actinomycosis Causative Agent is Bacterium Actinomycosis Israeli.. Gross-Painless mass at jaw cervicofacial, pulmonary, ileocecal region. The mas has discharging sinuses draining yellow sulfur granules with centrsl necrotic area.
  67. ACTINOMYCOSIS(MICRO) Actinomy cotic colony in dilated bronchus.
  68. Repair The injured tissue is replaced through regeneration of native parenchymal cells, by filling of the defect with fibrous tissue (scarring) or, most commonly, by a combination of these two processes. Granulation tissue It is formed during the process of repair. Grossly, pink & granular soft tissue formed at the surface of the wounds and is characterized by proliferation of blood vessels & fibroblasts and with some degree of inflammatory cells infiltrate .
  69. GRANULATION TISSUE(H.P.)  At high magnification, granulation tissue has capillaries, fibroblasts, and a variable amount of inflammatory cells (mostly mononuclear).
  70. GRANULATION TISSUE Healing of inflammation often involves in growth of capillaries and fibroblasts. This forms granulation tissue. Here, an acute myocardial infarction is seen healing.
  71. Pathological aspects of repair Repair will be abnormal in following conditions: 1. Deficient scar formation: Wound dehiscence (or rupture) and ulceration. 2. Excessive formation of the repair components: Hypertrophic scar and keloid. 3. Formation of contractures.
  72. Cont… Hypertrophic scar shows excess amount of collagen deposits. Keloid is overgrowth of scar tissue beyond the boundaries of original wound healing. It shows excessive hyalinisation.
  75. Definition • TB (Tuberculosis) is potentially fatal contagious disease that can affect almost any part of the body but is mainly an infection of the lung. • Tubercle-Round nodule/swelling • Osis-Condition
  76. Etiology • Mycobacterium Tuberculosis from the family Mycobacteiaceae. • First discovered by Robert KOCH in 1882. • So called as KOCH BACILLI. • Although classified as gram positive but its reaction is weak.
  77. TUBERCULOSIS Genus Mycobacterium waxy cell wall composed of mycolic acid Acid Fast
  78. METHODS FOR DEMONSTRATION Ziehl Neelson’s stain 20% Sulphuric acid Culture in LJ medium-6 weeks Sputum,bronchial washings,urine,fluid analysis-microscopic & culture PCR IgG antibodies
  79. TB flourishes wherever there there is poverty, crowding & chronic deblitating disease. DISEASES INCREASING RISK * Diabetes mellitus - Hodgkins lymphoma * malnutrition - immunosupression * chronic lung & renal disease
  80. Development of Monocytes/Macrophages
  81. < 3 weeks
  82. Lung, Ghon complex - In the radiograph and in the photograph, a calcified, well-circumscribed nodule in the left lung represents an old healed focus of primary tuberculosis; these are characteristically peripheral in location. In addition, other calcified nodules can be seen in the radiograph in the left hilar region -This is a former focus of infection by TB in draining lymph nodes. •CALCIFIED LYMPHNODE •SUBPLEURAL NODULE
  83. •Caseous necrosis •Zone of epitheloid cells Lung, left, caseous necrosis - Low power There is a large central area of caseous necrosis, which is seen as granular pink structureless material with complete destruction of the lung parenchyma. The caseous material is surrounded by a cellular zone that contains epithelioid cells and giant cells. These cells are seen at a higher magnification in the next image. At the periphery, some alveolar spaces can be seen.
  84. In this higher magnification of the lung lesion, caseous necrosis is seen as pink granular structureless material that has destroyed the lung alveoli. Epithelioid cells surrounding the caseous material are elongated cells with indistinct cell boundaries. Individual epithelioid cells are difficult to see in this lesion. A large multinucleated giant cell is clearly visible. The cells with dark round nuclei are lymphocytes.
  85. Testis, granulomatous inflammation - High power Granulomatous inflammation with caseous necrosis. •Caseous necrosis •Epitheloid histiocytes
  86. Lymph node, noncaseating granulomas - Low power. This image is of a lymph node from a patient with sarcoidosis and is provided here for comparison with the caseating granulomas of tuberculosis. Each of these clusters of pink cells is a granuloma composed of interlacing epithelioid cells and giant cells. Note the absence of caseous necrosis. While granulomas in sarcoidosis do not have caseous necrosis, it should be remembered that early lesions in tuberculosis may also have noncaseating granulomas. . •GRANULOMA •GIANT CELL
  87. - Lung, left, acid-fast stain - High power Reddish rods = acid-fast bacteria (Mycobacterium tuberculosis) seen within an area of caseous necrosis
  88. Lung, tuberculosis, secondary (reactivation) - The cavities in the upper lobes are the pathologic and radiographic findings in secondary, or reactivation, tuberculosis. The major bronchi have been opened to reveal mucosal hyperemia, which indicates congestion or inflammation of the bronchial mucosa. In addition, patchy consolidation is present in the upper lobe; this may represent either superimposed bronchopneumonia or progressive •CYSTIC CAVITIES •PATCHY CONSOLIDATION
  89. Spleen, miliary tuberculosis - Gross, cut surface This cut surface of the spleen shows multiple light tan areas of caseous necrosis, which look like multiple small abscesses grossly. Miliary tuberculosis may occur in patients after either primary or secondary (reactivation) tuberculosis
  90. PRIMARY TB Ghon focus-lung lesion Ghon complex-lung+LN Ranke complex-detected on X-ray
  91. SECONDARY TB Fibrocalcification Miliary TB Progressive pulmonary TB Endobronchial,endotracheal,laryngeal TB Systemic miliary TB Isolated organ TB Lymphadenitis,intestinal TB
  92. EXTRAPULMONARY TB Often due to reactivation or re-infection. REACTIVATION: Common Represents breakdown of immunity REINFECTION: Due to partial immunity. Load of bacteria to cause this must be relatively large.
  93. MODE OF SPREAD OF EXTRA PULMONARY TB Primary focus Bacteria invade pulmonary vein in vicinity Bacteria try to invade systemic circulation Impaired Phagocyte Function M E T A S T A S I S Kidney Adrenals Fallopian tubes Epididymis Bones & Joints Tendon Sheaths
  94. Tuberculous Lymphadenitis Commonest form of extra pulmonary TB. Cervical lymphadenopathy most common. Nodes are firm and often matted due to periadenitis. Common cause of pyrexia of unknown origin
  95. Stages Of Cervical Lymphadenitis  Enlargement  Matting  Cold Abscess Formation  Burst abscess in deep fascia (Collar Stud Abscess)  Sinus Formation. (1) (2) (3) (4) (5)
  96. CNS Tuberculosis  Organisms reach brain via blood.  Common in HIV patients 1) TB Meningitis 2) Tubercular Abscess (Tuberculoma)
  97. Tuberculoma
  98. Abdominal TB  It may be Primary or secondary.  Swallowing of sputum in patients with active tuberculosis causes sec. TB  Most common site - Terminal Ileum  Types Of Intestinal TB: 1. Ulcerative 2. Hyperplastic 3. TB Peritonitis 4. TB Lymphadenitis
  99. Tuberculous Ulcer
  100. TB Bones and Joints Occurs secondary to lypho-haematogenous dissemination from primary focus and later reactivation. Most commonly involves Spine (Pott’s Spine) Tuberculous arthritis and Ankylosis.
  101. Potts Spine
  102. Renal TB
  103. Lupus Vulgaris
  104. MILIARY TB Haematogenous spread Millet sized casseous necrosis 2-3mm foci Involvement of multiple organs Rapid spread and detioration occurs in a short period of time
  105. MAC COMPLEX Mycobacterium avium intracellulare complex More common in soil,water,dust and domestic animals More seen in AIDS with CD4 lymphocytes<60 cells/mm3 Abundant acid fast bacilli seen within macrophages involve LN,lung,liver,spleen Granulomas,lymphocytes, tissue destruction is rare
  106. CLINICAL FEATURES Malaise,fever,anorexia,weight loss Low grade ,intermittent with night sweats Haemoptysis and cough Pleuritic pain
  108. Modified Ridley & Jopling’s classification of leprosy TT – Tuberculoid polar BT – Borderline tuberculoid BB – Mid borderline BL – Borderlinne lepromatous LL – Lepromatous polar
  109. Lepromin Test Used for classifying leprosy on basis of immune response Early reaction: induration within 24 to 48 hrs Delayed granulomatous lesion: After 3 to 4 wks Pts with tuberculoid leprosy give positive lepromin test and lepromatous leprosy pts are negative
  110. Tuberculoid (TT): well defined infiltrated lesion
  111. Borderline tuberculoid (BT) : Note loss of hair and a satellite lesion.
  112. Borderline (BB)Large tuberculoid type and small lepromatous type lesions.
  113. Borderline(BB): Close up of a typical BB lesion with ‘inverted saucer’ appearance.
  114. Borderline (BB) in reaction : the lesions are oedematous and scaly
  115. Borderline lepromatous(BL):multiple illdefined and some ‘BB’ type lesions
  116. Trophic ulcer on anaesthetic foot.
  117. Neuritic leprosy: bilateral ulnar neerve palsy: no skin lesions
  118. Downloaded from: StudentConsult (on 19 March 2012 01:29 AM)
  119. 1048
  120. 1032
  121. 1035 Lepromatous leprosy
  122. 1048 Foamy macrophages/ lepra cells in lepromatous leprosy
  123. 1048
  124. 1025
  125. Acid fast stain shows organisms (arrows) in a perineural inflammatory infiltrate.
  126. Syphilis Primary syphilis (2 to 4 wks) : Chancre Secondary syphilis (2 to 3 months): Mucocutaneous lesions and painless lymphadenopathy Tertiary syphilis (2 to 3 yrs): Syphilitic gumma Diffuse lesions – cardiovascular and neurosyphilis
  127. Syphilitic aneurysm Ascending aorta Arch Location
  128. Syphilitic Aortitis - VDRL Gross  Tree bark appearance  Cor osteal narrowing  Aortic root dilatation  AV – commissural widening, shortening of cusps/ bowing/ thickening of cusps  Jet lesion of AI
  129. Syphilitic Aortitis Microscopy  Endarteritis/Periarteritis  Lymphoplasmacytic infiltrate  Neovascularisation of media  Periadventitial scarring  Secondary intimal thickening/ atherosclerosis
  130. Periarteritis
  131. Endarteritis
  132. Periadventitial scarring
  133. Syphilitic aortitis
  134. Syphilitic gumma of liver
  135. Thank You