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Chronic inflammation

  1. Prolonged duration with inflammation, tissue repair and destruction
  2. Arise during 3 conditions:-                
    1. Persistent infection by micro organisms              ---------        endogenous
    2. Prolonged exposure to potentially toxic agents   ---------         exogenous
    3. Autoimmunity

Histologic Features

  1. Infiltration by mononuclear cells - macrophage, lymphocyte, plasma cell
  2. Tissue destruction
  3. Healing by connective tissue replacement
    1. Macrophage
      1. Dominant cell of chronic inflammation
      2. Part of mononuclear phagocyte system.
      3. Macrophages in different tissues - microglia (CNS), Kupffer cells (Liver), Alveolar macrophages (Lung), osteoclasts (Bone) Q
      4. Bone marrow stem cell → Blood monocyte → Tissue macrophage
    2. Mechanism of macrophage accumulation in tissues  
      1. Recruitment of monocytes from circulation - chemotactic stimuli - chemokines (MCP­1), C5a, PDGF, TGF alpha etc..
      2. Local proliferation in tissue.
      3. Immobilization at the site of inflammation.
    3. After accumulation, macrophages get activated. Activated macrophages release a variety of substances, which-
  4. Kill the injurious agent
  5. Cause tissue destruction - hall mark of chronic inflammation
  6. Initiate repair

  1. Chronic Granulomatous inflammation
    1. Distinctive type of chronic inflammation.
    2. Granuloma is a microscopic aggregation of macrophages that are transformed into epithelium like cells (Epithelioid cells) surrounded by a collar of mononuclear leucocytes principally lymphocytes. Old granulomas may have a enclosing rim of fibrosis.
    3. Granuloma also has giant cells - Langhans type with horse shoe shaped nuclear arrangement or foreign body type with haphazard nuclear arrangement
  2. 2 Types
    1. Foreign body granuloma
      1. Inert foreign bodies - sutures, fibers, talc   
      2. Foreign material in centre of granuloma.
    2. Immune granuloma
      1. Insoluble microbes that can induce cell mediated immune response
      2. IFN gamma important in transformation of activated macrophages into epithelioid cell.
    3. Common causes
      1. Tuberculosis            
      2. Syphilis                  
      3. LGV                                  
      4. Brucellosis             
      5. Berylliosis              
      6. Leprosy                 
      7. Cat Scratch disease          
      8. Sarcoidosis
      9. Some fungal infection

Table: Example of diseases with Granulomatous inflammations



Tissue Reaction





Mycobacterium tuberculosis

Noncaseating tubercle (granuloma prototype): a focus of epithelioid cells, rimmed by fibroblasts, lymphocytes, histiocytes, occasional giant cells

Caseating tubercle: central amorphous granular debris, loss of all cellular detail; acid-fast bacilli





Mycobacterium leprae

Acid-fast bacilli in macrophages; noncaseating granulomas





Treponema pallidum

Gumma: microscopic to grossly visible lesion, enclosing wall of histiocytes; plasma cell infiltrate; central cells are necrotic without loss of cellular outline




Cat-scratch disease

Gram-negative bacillus

Rounded or stellate granuloma containing central granular debris and recognizable neutrophils; giant cells uncommon





Unknown etiology

Noncaseating granulomas with abundant activated macrophages




Crohn disease (inflammatory bowel disease)

Immune reaction against intestinal bacterial, self-antigens

Occasional noncaseating granulomas in wall of intestine, with dense chronic inflammatory infiltrate

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