ObjectivesThis lecture provides an understanding of   Cells involved, etiologies, cellularconstituents, general histologic...
Learning outcomesAt the end of the lecture ,student will be able toIdentify and distinguish the cells involved in chronic...
Tissue response to an injury
Definition of chronic inflammation  an inflammatory response of prolonged    duration (weeks – months - years)provoked by ...
DEFINITIONInflammation of prolonged duration( weeks or months) in which- active inflammation- tissue destruction and- atte...
Chronic Inflammation arrives in 3 ways:1.May follow acute inflammation  e.g pneumonia -> chronic lung abscess2. Repeated b...
Chronic inflammation arises in the    following settings: (CAUSES)Persistent infectionsImmune-mediated inflammatorydisea...
Persistent infections by microbesthat are difficult to eradicateEg: mycobacteria,Treponema pallidum (causative organismof ...
Immune-mediated inflammatory diseasesautoimmune diseases(under certain conditions, immune reactionsdevelop against the in...
Prolonged exposure to toxic substances(non-degradable)  – Exogenous (asbestos, silicon)  – Endogenous  (chronically elevat...
Cells of Chronic Inflammationmacrophageslymphocytesplasma cellseosinophilsneutrophils
Maturation of Mononuclear Phagocytes
Macrophage• Mononuclear Phagocyte System (MPS) Circulating blood monocytes →Tissue  macrophages                           ...
MacrophageDuring chronic inflammation macrophages serve to eliminate injurious agents and initiate repairhowever, they are...
Tissue macrophage                                                   Activated T cell or NK cellNon Immune activation:     ...
Macrophage:component of MPStransformed from monocytesprime cell of chr: inflammⁿActivated bylymphokinesbact: endotoxinActi...
In chronic inflammation   macrophage accumulation persists by          different mechanismsContinued recruitment of monoc...
Lymphocytes:Naive lymphocytes encounter antigen-presentingcells and become antigen-specific lymphocytesActivated T lymphocy...
Plasma cells:develop from activated B lymphocytesproduce antibody directed either against  persistent antigen in the infla...
Mast Cells:  - Widely distributed in connective tissues and   participate in both acute and persistent   inflammatory reac...
Cells of Chronic Inflammation Eosinophils:  - parasitic infections  - Mediated by IgE  - Eotaxin – a chemokine that has th...
Chronic inflammation is characterized byInfiltration with mononuclear cells   (including macrophages, lymphocytes, and pla...
Chronic inflammation in the lunghowing all three characteristic histologic features:1) collection of chronic inflammatory ...
Chronic ulcer such aschronic peptic ulcer of the stomach withbreach of the mucosa, a base lined bygranulation tissue and w...
Chronic abscess cavity for exampleosteomyelitis, empyema thoraccisThickening of the wall of a hollow viscus byfibrous tiss...
FibrosisThe most prominent feature of the chronicinflammatory reaction when most of thechronic inflammatory cell infiltrat...
Gallbladder showing chronic cholecystitisThe wall is greatly thickened by fibrous tissue
Chronic inflammation in the wall of a gallbladderthat has experienced previous episodes of acute cholecystitisAggregates o...
Chronic peptic ulcer of the stomachContinuing tissue destruction and repaircause replacement of the gastric wall muscle la...
CHRONIC GRANULOMATOUS         INFLAMMATIONA distinctive pattern of chronic inflammation characterized by focus of chronic ...
CHRONIC GRANULOMATOUS       INFLAMMATIONA distinctive pattern of chronic inflammation characterised by granulomas which ar...
MORPHOLOGYGranuloma:A granuloma is a focus of chronic inflammation consisting ofa microscopic aggregation of macrophages t...
Epitheloid cell:(Activated Macrophage)-pale pink granular cytoplasm-indistinct cell boundary-oval or elongated nucleus +/-...
Giant cells:- 40 to 50 µ in diam- abundant cytoplasmLanghans type - 20 or more nuclei in periphery ( horse shoe pattern)Fo...
Caseous necrosisGrossly - this has a granular, cheesy appearanceMicroscopically - appears as amorphous, structureless, gra...
central caseous necrosisEpitheloid Cells
Typical tuberculous granuloma showingan area of central necrosis surrounded bymultiple Langhans-type giant cells, epitheli...
Granuloma with caseous necrosis
Scattered granulomasThe lung of a patient with miliary tuberculosis1 to 2 mm granulomas are scattered around like millet s...
Types of granuloma:1. Foreign body granuloma2. Immune granuloma  (a) indigestible particles or organisms  (b) T cell media...
In tuberculosis, granuloma is referredto as tubercle,• Hard tubercle• Soft tubercle – characterized by presence of central...
Examples of Diseases withGranulomatous Inflammation Tuberculosis Leprosy Syphillis Cat – scrath disease Sarcoidosis ...
Examples of Chronic Granulomatous Inflammation:BacterialTB, leprosy, syphilis,ParasiticSchistosomiasisFungalCryptococcosis...
Common Causes of Epithelioid Cell Granulomas.Disease                                  CausesImmunologic response Tuberculo...
COMPARISON OF ACUTE AND       CHRONIC INFLAMMATIONFEATURE          ACUTE                  CHRONIC                 INFLAMMA...
COMPARISON OF ACUTE AND          CHRONIC INFLAMMATIONFEATURE       ACUTE INFLAMMATION     CHRONICINFLAMMATIONPrimary cells...
Differences between Acute and Chronic Inflammation                              Acute                                     ...
In acute inflammation the lymphatic channelsbecome dilated & drain away the oedema fluid of  the inflammatory exudateThis ...
Lecture 50  chronic inflammation.ppt 4.11.11
Lecture 50  chronic inflammation.ppt 4.11.11
Lecture 50  chronic inflammation.ppt 4.11.11
Lecture 50  chronic inflammation.ppt 4.11.11
Lecture 50  chronic inflammation.ppt 4.11.11
Lecture 50  chronic inflammation.ppt 4.11.11
Lecture 50  chronic inflammation.ppt 4.11.11
Lecture 50  chronic inflammation.ppt 4.11.11
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Lecture 50 chronic inflammation.ppt 4.11.11

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  • Lecture 50 chronic inflammation.ppt 4.11.11

    1. 1. ObjectivesThis lecture provides an understanding of Cells involved, etiologies, cellularconstituents, general histologic features, of chronic inflammation Granulomatous inflammation Role of lymphatics in the inflammation
    2. 2. Learning outcomesAt the end of the lecture ,student will be able toIdentify and distinguish the cells involved in chronicinflammationList various causes of chronic inflammationDescribe the morphological features of chronicinflammationDefine chronic granulomatous inflammationList examples of diseases with granulomatousinflammationDescribe the morphology of granulomatous inflammationDescribe the role of lymphatics in the inflammation
    3. 3. Tissue response to an injury
    4. 4. Definition of chronic inflammation an inflammatory response of prolonged duration (weeks – months - years)provoked by the persistence of the causative stimulus simultaneous presence of activeinflammation, tissue destruction and repair
    5. 5. DEFINITIONInflammation of prolonged duration( weeks or months) in which- active inflammation- tissue destruction and- attempts at healingproceed simultaneously
    6. 6. Chronic Inflammation arrives in 3 ways:1.May follow acute inflammation e.g pneumonia -> chronic lung abscess2. Repeated bouts of acute inflammⁿ e.g cholecystitis , pyelonephritis3. Begin insiduously as a low gradesmouldering reponse
    7. 7. Chronic inflammation arises in the following settings: (CAUSES)Persistent infectionsImmune-mediated inflammatorydiseasesProlonged exposure to non-degradablebut potentially toxic substances
    8. 8. Persistent infections by microbesthat are difficult to eradicateEg: mycobacteria,Treponema pallidum (causative organismof syphilis)certain viruses, fungi and parasites
    9. 9. Immune-mediated inflammatory diseasesautoimmune diseases(under certain conditions, immune reactionsdevelop against the individuals own tissues)Eg:rheumatoid arthritis, multiple sclerosisallergic diseases hypersensitivity reaction that are caused by excessive and inappropriate activation of the immune system)Eg:bronchial asthma
    10. 10. Prolonged exposure to toxic substances(non-degradable) – Exogenous (asbestos, silicon) – Endogenous (chronically elevated plasma lipid components which may contribute to atherosclerosis)
    11. 11. Cells of Chronic Inflammationmacrophageslymphocytesplasma cellseosinophilsneutrophils
    12. 12. Maturation of Mononuclear Phagocytes
    13. 13. Macrophage• Mononuclear Phagocyte System (MPS) Circulating blood monocytes →Tissue macrophages ↓ Kupffer cells (liver) Sinus Histiocytes (spleen) Microglia (CNS) Alveolar Macrophages (lung)
    14. 14. MacrophageDuring chronic inflammation macrophages serve to eliminate injurious agents and initiate repairhowever, they are as well responsible for much of the tissue injury that occurs
    15. 15. Tissue macrophage Activated T cell or NK cellNon Immune activation: IFN-gEndotoxins,fibronectin,chemical mediators Activated macrophage Fibrosis (Scaring) Growth factors involved in fibroblast proliferation (PDGF,TGFb,FGF)Tissue injury Angiogenesis factorsToxic oxygen metabolites (FGF,VEGF)Metallo-proteases Collagen depositionCoagulation factors (IL-13 and TGFb)AA metabolites and NO
    16. 16. Macrophage:component of MPStransformed from monocytesprime cell of chr: inflammⁿActivated bylymphokinesbact: endotoxinActivated macrophagessecrete:EnzymesO2 metabolites , cytokinesgrowth factorsNO , PAF,IFN αresultingt/s destructionneovascularisation fibrosis
    17. 17. In chronic inflammation macrophage accumulation persists by different mechanismsContinued recruitment of monocytes from the circulationLocal proliferationProlonged survival and immobilization
    18. 18. Lymphocytes:Naive lymphocytes encounter antigen-presentingcells and become antigen-specific lymphocytesActivated T lymphocytesRegulate macrophage activation and recruitmentby secreting specific mediators cytokines(lymphokines) (IFN-γ)Modulate anti-body production and cell-mediatedcytotoxicity and maintain immunologic memory
    19. 19. Plasma cells:develop from activated B lymphocytesproduce antibody directed either against persistent antigen in the inflammatory site or against altered tissue components
    20. 20. Mast Cells: - Widely distributed in connective tissues and participate in both acute and persistent inflammatory reactions - Binds the Fc portion of the IgE antibody
    21. 21. Cells of Chronic Inflammation Eosinophils: - parasitic infections - Mediated by IgE - Eotaxin – a chemokine that has the ability to prime eosinophils for chemotaxis - have granules that contain major basic protein, a highly cationic protein that is toxic to parasites but also causes lysis of mammalian epithelial cells
    22. 22. Chronic inflammation is characterized byInfiltration with mononuclear cells (including macrophages, lymphocytes, and plasma cells) indicates persistent reaction to injury Tissue destruction (largely induced by the products of the inflammatory cells) Repair (Healing)(involving new vessel proliferation (angiogenesis) and fibrosis) Attempt to replace lost tissue
    23. 23. Chronic inflammation in the lunghowing all three characteristic histologic features:1) collection of chronic inflammatory cells2) destruction of parenchymanormal alveoli are replaced by spaces lined by cuboidal epithelium3) replacement by connective tissue (fibrosis)
    24. 24. Chronic ulcer such aschronic peptic ulcer of the stomach withbreach of the mucosa, a base lined bygranulation tissue and with fibrous tissueextending through the muscle layers of thewall
    25. 25. Chronic abscess cavity for exampleosteomyelitis, empyema thoraccisThickening of the wall of a hollow viscus byfibrous tissue in the presence of a chronicinflammatory cell infiltrate, for exampleCrohns disease, chronic cholecystitis
    26. 26. FibrosisThe most prominent feature of the chronicinflammatory reaction when most of thechronic inflammatory cell infiltrate hassubsided. This is commonly seen inchronic cholecystitishour-glass contracture of the stomach, lead to acquiredpyloric stenosisthe strictures that characterise Crohns diseas
    27. 27. Gallbladder showing chronic cholecystitisThe wall is greatly thickened by fibrous tissue
    28. 28. Chronic inflammation in the wall of a gallbladderthat has experienced previous episodes of acute cholecystitisAggregates of lymphocytes and ingrowing fibroblasts
    29. 29. Chronic peptic ulcer of the stomachContinuing tissue destruction and repaircause replacement of the gastric wall muscle layers by fibrous tissueAs the fibrous tissue contractspermanent distortion of the gastric shape may result
    30. 30. CHRONIC GRANULOMATOUS INFLAMMATIONA distinctive pattern of chronic inflammation characterized by focus of chronic inflammation consisting of a microscopic aggregation of macrophages that are transformed into epithelium-like cells, surrounded by a collar of mononuclear leukocytes, principally lymphocytes and occasionally plasma cells fibroblasts
    31. 31. CHRONIC GRANULOMATOUS INFLAMMATIONA distinctive pattern of chronic inflammation characterised by granulomas which are small nodular collections in which the predominant cell is the activated macrophage with epithelial like (epitheloid) appearance with abundant pink cytoplasm
    32. 32. MORPHOLOGYGranuloma:A granuloma is a focus of chronic inflammation consisting ofa microscopic aggregation of macrophages that are transformed into epithelium-like cells (epitheloid cells) surrounded by a collar of mononuclear leukocytes, principally lymphocytes and occasionally plasma cells
    33. 33. Epitheloid cell:(Activated Macrophage)-pale pink granular cytoplasm-indistinct cell boundary-oval or elongated nucleus +/- folding of nuclear membrane-may fuse to form giant cells
    34. 34. Giant cells:- 40 to 50 µ in diam- abundant cytoplasmLanghans type - 20 or more nuclei in periphery ( horse shoe pattern)Foreign body type - nuclei scattered in cytoplasm
    35. 35. Caseous necrosisGrossly - this has a granular, cheesy appearanceMicroscopically - appears as amorphous, structureless, granular debris, with complete loss of cellular details
    36. 36. central caseous necrosisEpitheloid Cells
    37. 37. Typical tuberculous granuloma showingan area of central necrosis surrounded bymultiple Langhans-type giant cells, epithelioid cells, and lymphocytes. lymphocytes central necrosis Langhans-type giant cells
    38. 38. Granuloma with caseous necrosis
    39. 39. Scattered granulomasThe lung of a patient with miliary tuberculosis1 to 2 mm granulomas are scattered around like millet seeds(millet is a type of cereal grain)With poor immune responseextensive spread of infection with the production of a "miliary" pattern of granulomas
    40. 40. Types of granuloma:1. Foreign body granuloma2. Immune granuloma (a) indigestible particles or organisms (b) T cell mediated Immune Response3. Toxic granuloma – due to silicon, beryllium
    41. 41. In tuberculosis, granuloma is referredto as tubercle,• Hard tubercle• Soft tubercle – characterized by presence of central caseous necrosis; caseation necrosis is rare in other granulomatous disease
    42. 42. Examples of Diseases withGranulomatous Inflammation Tuberculosis Leprosy Syphillis Cat – scrath disease Sarcoidosis Crohn disease (inflammatory bowel disease)
    43. 43. Examples of Chronic Granulomatous Inflammation:BacterialTB, leprosy, syphilis,ParasiticSchistosomiasisFungalCryptococcosis,Histoplasmosis,Blastomycosis,UnknownSarcoidosis
    44. 44. Common Causes of Epithelioid Cell Granulomas.Disease CausesImmunologic response Tuberculosis Mycobacterium tuberculosis Leprosy (tuberculoid type) Mycobacterium leprae Histoplasmosis Histoplasma capsulatum Coccidioidomycosis Coccidioides immitis Q fever Coxiella burnetii (rickettsial organism) Brucellosis Brucella species Syphilis Treponema pallidum Sarcoidosis2 Unknown Crohns disease2 Unknown Berylliosis3 Beryllium (? +protein)Nonimmunologic response Foreign body (eg, in intravenous drug Talc, fibers (? +protein)
    45. 45. COMPARISON OF ACUTE AND CHRONIC INFLAMMATIONFEATURE ACUTE CHRONIC INFLAMMATION INFLAMMATIONOnset &duration Immediate & Delayed & Transient (few weeks,months, years days)Pathogenesis Microbial pathogens, Persistent acute inflammation, foreign bodies (e.g., silicone, trauma, burns glass), autoimmune disease, certain types of infection (e.g., tuberculosis, leprosy)
    46. 46. COMPARISON OF ACUTE AND CHRONIC INFLAMMATIONFEATURE ACUTE INFLAMMATION CHRONICINFLAMMATIONPrimary cells Neutrophils Monocytes/macrophages cells), B and T lymphocytes plasma cells, fibroblastsNecrosis Present Less prominentScar tissue Absent PresentOutcome Complete resolution, Scar tissue formation disability, amyloidosis progression to chronic inflammation abscess formation
    47. 47. Differences between Acute and Chronic Inflammation Acute ChronicDuration Short (days) Long (weeks to months)Onset Acute InsidiousSpecificity Nonspecific Specific (where immune response is activated)Inflammatory cells Neutrophils, macrophages Lymphocytes, plasma cells, macrophages, fibroblastsVascular changes Active vasodilation, increased permeability New vessel formation (granulation tissue)Fluid exudation and edema + –Cardinal clinical signs + –(redness, heat, swelling,pain)Tissue necrosis – (Usually) + (ongoing) + (Suppurative and necrotizing inflammation)Fibrosis (collagen – +deposition)Operative host responses Plasma factors: complement, immunoglobulins, properdin, Immune response, phagocytosis, repair etc; neutrophils, nonimmune phagocytosisSystemic manifestations Fever, often high Low–grade fever, weight loss, anemiaChanges in peripheral blood Neutrophil leukocytosis; lymphocytosis (in viral infections) Frequently none; variable leukocyte changes, increased plasma immunoglobulin
    48. 48. In acute inflammation the lymphatic channelsbecome dilated & drain away the oedema fluid of the inflammatory exudateThis drainage tends tolimit the extent of oedema in the tissuescarry large molecules and some particulate matter &antigens are carried to the regional lymph nodes for recognition by lymphocytes
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