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Chronic Granulomatous
    Inflammation


 Prepared by: Rana Ahsan Javed
          Roll No. 255
         3rd Year MBBS
Chronic Inflammation
► Definition:
    Inflammation of prolonged duration in which active inflammation,
     tissue injury and the healing proceed simultaneously
    Endogenous (Atherosclerosis)
► Causes:
► Persistent Infections
    Ex. Treponema palladium (causative organism of syphilis)
    Organism of low toxicity and evoke an immune reaction =
     delayed hypersensitivity
► Prolonged Exposure to toxic Agents,
    Exogenous (Silicosis)
► Autoimmunity
    Ex. Autoimmune diseases
Definition:
►   Granulomatous inflammation is a distinctive pattern of
    chronic inflammatory reaction

►   It is a protective response to chronic infection or foreign
    material, preventing dissemination and restricting
    inflammation.

►   Some autoimmune diseases such as rheumatoid arthritis
    and Crohns disease are also associated with granulomas.
Granuloma:
►   Epithelioid cells fuse to form giant cells containing 20 or
    more nuclei.

►   The nuclei arranged either peripherally (Langhans-type
    giant cell ) or

►   haphazardly (foreign body-type giant cell).

►   These giant cells can be found either at the periphery or
    the center of the granuloma.
Granulomatous inflammation
► Types of Granulomatous Inflammation
► 1. Immune granulomas
    Caused by insoluble particles that are capable of inducing a cell-
      mediated immune response
    Macrophages are transformed into Epitheloid cells and
      multinucleate giant cells
    Examples:
      ► Bacteria
         Tuberculosis *** (high incidence due to drug resistant stains)
         Leprosy
      ► Parasites
         Schistosomiasis (3 types)
      ► Fungi
         Histoplasmosis
         Blastomycosis
Histoplasmosis Granuloma
Granulomatous inflammation
2. Foreign Body Granulomas

  Don’t incite either an inflammatory or immune response.
  Epitheloid cells and giant cells are apposed to the surface and
      encompass the foreign body.
  The foreign body is usually found in the center of the granuloma.
     Examples:
          Metal/Dust
               Berylliosis
               Silicosis
          Foreign body
              Splinter
              Suture
► 3.   Sarcoidosis

   Bad systemic disease, probably autoimmune
    disease
   Etiologic agent is unknown
Sarcoidosis Granuloma.
Infectious causes:
► Bacteria
     Tuberculosis
     Leprosy
► Parasites
     Schistosomiasis
► Fungi
     Histoplasmosis
     Blastomycosis

►   Metal/Dust
      Berylliosis
      Silicosis
Foreign body aspiration




        Berrylliosis
►   Granuloma:
    bacilli are inhaled by droplets

►   Bacteria are phagocytosed by
    alveolar macrophages
►   After amassing substances that
    they cannot digest, macrophages
    lose their motility, accumulate at
    the site of injury and transform
    themselves into nodular
    collections; the Granuloma

►   A localized inflammatory response
     recruits more mononuclear cells

►   The granuloma consists of a
    kernel of infected macrophages
    surrounded by foamy
    macrophages and a ring of
    lymphocytes and a fibrous cuff
    (containment phase)

►   Containment usually fails when
    the immune status of the patient
    changes; the granuloma caseates,
► 2-10micrometer in length.
► Struntrually gram positive but also containslarge
  amount of lipids in the cell wall:making them
  acid fast.
► No toxins
► No spores
► Obligate Aerobic


► Elicit granulomatous inflammation.
TUBERCULOSIS

► Primary TB
► SecondaryTB
► Progressive pulmonary TB
► Miliary TB
►            PATHOGENESIS

► The course of tuberculosis depends on age and
  immune competence AND total burden of the
  organisms
► Tuberculous Infection : refers to growth of the
  organism in a person,whether there is
  symptomatic disease or not.
► Active Tuberculosis ; refers to infection
  manifested by tissue destruction-----symptomatic
  disease.
Multiplication of the organism inside the
alveolar macrophage

   processing& presentation of the antigen on
the surface

    A clone of sensitized T-cells proliferate,
produce gamma INT.

                      Activation of the
macrophages(augmenting their capacity to kill
Clinical and pathologic implications of
                  primary tuberculosis
1]      Development of resistance to the infection.
2]      The foci of scarring may harbor viable bacilli
   for life and act as a nidus for  reactivation.
3]      The disease may develop into       progressive
        primary tuberculosis in      immunocompro-
   mised patients such as AIDS patients,
   elderly, and malnourished children.
Tuberculin Test
► It is a classic example of delayed
  hypersensitivity.
► The tuberculin reaction, is produced by the
  intracutaneous injection of tuberculin, a
  protein-lipopolysaccharide component of the
  tubercle bacillus.
Gram stain              Most bacteria
Acid fast stain         Mycobacteria, nocardiae (modified)
Silver stains           Fungi, legionellae, pneymocytosis
Period acid-Schiff      Fungi, amebae
Mucicarmine             Cryptococci
Giemsa                  Campylobacteria, leishmaniae, malaria,
                parasites
Antibody probes         Viruses, rickettsiae
Culture                          All classes
DNA probes              Viruses, bacteria, protozoa

Polarizing
microscope            Foreign body
Chronic Granulomatous Inflammation Types and Causes

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Chronic Granulomatous Inflammation Types and Causes

  • 1. Chronic Granulomatous Inflammation Prepared by: Rana Ahsan Javed Roll No. 255 3rd Year MBBS
  • 2. Chronic Inflammation ► Definition:  Inflammation of prolonged duration in which active inflammation, tissue injury and the healing proceed simultaneously  Endogenous (Atherosclerosis) ► Causes: ► Persistent Infections  Ex. Treponema palladium (causative organism of syphilis)  Organism of low toxicity and evoke an immune reaction = delayed hypersensitivity ► Prolonged Exposure to toxic Agents,  Exogenous (Silicosis) ► Autoimmunity  Ex. Autoimmune diseases
  • 3. Definition: ► Granulomatous inflammation is a distinctive pattern of chronic inflammatory reaction ► It is a protective response to chronic infection or foreign material, preventing dissemination and restricting inflammation. ► Some autoimmune diseases such as rheumatoid arthritis and Crohns disease are also associated with granulomas.
  • 4. Granuloma: ► Epithelioid cells fuse to form giant cells containing 20 or more nuclei. ► The nuclei arranged either peripherally (Langhans-type giant cell ) or ► haphazardly (foreign body-type giant cell). ► These giant cells can be found either at the periphery or the center of the granuloma.
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  • 7. Granulomatous inflammation ► Types of Granulomatous Inflammation ► 1. Immune granulomas  Caused by insoluble particles that are capable of inducing a cell- mediated immune response  Macrophages are transformed into Epitheloid cells and multinucleate giant cells  Examples: ► Bacteria  Tuberculosis *** (high incidence due to drug resistant stains)  Leprosy ► Parasites  Schistosomiasis (3 types) ► Fungi  Histoplasmosis  Blastomycosis
  • 9. Granulomatous inflammation 2. Foreign Body Granulomas Don’t incite either an inflammatory or immune response. Epitheloid cells and giant cells are apposed to the surface and encompass the foreign body. The foreign body is usually found in the center of the granuloma. Examples: Metal/Dust Berylliosis Silicosis Foreign body Splinter Suture
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  • 11. ► 3. Sarcoidosis  Bad systemic disease, probably autoimmune disease  Etiologic agent is unknown
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  • 15. Infectious causes: ► Bacteria  Tuberculosis  Leprosy ► Parasites  Schistosomiasis ► Fungi  Histoplasmosis  Blastomycosis ► Metal/Dust  Berylliosis  Silicosis
  • 16. Foreign body aspiration Berrylliosis
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  • 18. Granuloma: bacilli are inhaled by droplets ► Bacteria are phagocytosed by alveolar macrophages ► After amassing substances that they cannot digest, macrophages lose their motility, accumulate at the site of injury and transform themselves into nodular collections; the Granuloma ► A localized inflammatory response recruits more mononuclear cells ► The granuloma consists of a kernel of infected macrophages surrounded by foamy macrophages and a ring of lymphocytes and a fibrous cuff (containment phase) ► Containment usually fails when the immune status of the patient changes; the granuloma caseates,
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  • 20. ► 2-10micrometer in length. ► Struntrually gram positive but also containslarge amount of lipids in the cell wall:making them acid fast. ► No toxins ► No spores ► Obligate Aerobic ► Elicit granulomatous inflammation.
  • 21. TUBERCULOSIS ► Primary TB ► SecondaryTB ► Progressive pulmonary TB ► Miliary TB
  • 22. PATHOGENESIS ► The course of tuberculosis depends on age and immune competence AND total burden of the organisms ► Tuberculous Infection : refers to growth of the organism in a person,whether there is symptomatic disease or not. ► Active Tuberculosis ; refers to infection manifested by tissue destruction-----symptomatic disease.
  • 23. Multiplication of the organism inside the alveolar macrophage processing& presentation of the antigen on the surface A clone of sensitized T-cells proliferate, produce gamma INT. Activation of the macrophages(augmenting their capacity to kill
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  • 26. Clinical and pathologic implications of primary tuberculosis 1] Development of resistance to the infection. 2] The foci of scarring may harbor viable bacilli for life and act as a nidus for reactivation. 3] The disease may develop into progressive primary tuberculosis in immunocompro- mised patients such as AIDS patients, elderly, and malnourished children.
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  • 28. Tuberculin Test ► It is a classic example of delayed hypersensitivity. ► The tuberculin reaction, is produced by the intracutaneous injection of tuberculin, a protein-lipopolysaccharide component of the tubercle bacillus.
  • 29. Gram stain Most bacteria Acid fast stain Mycobacteria, nocardiae (modified) Silver stains Fungi, legionellae, pneymocytosis Period acid-Schiff Fungi, amebae Mucicarmine Cryptococci Giemsa Campylobacteria, leishmaniae, malaria, parasites Antibody probes Viruses, rickettsiae Culture All classes DNA probes Viruses, bacteria, protozoa Polarizing microscope Foreign body