Response to Injury III: Chronic Inflammation

• How does chronic inflammation arise?

  It arises as:

  a progression from acute inflammation

  following repeated episodes of acute inflammation

  de novoif the causative agent only produces a mild acute response
• What happens in chronic inflammation?

  The process of tissue destruction takes place alongside that of healing and repair so it's integrated and the 2 processes should be considered together
• What are the features of chronic inflammation?

  It's very variable but some prevailing themes are:

  
  

  - Tissue destruction & ulceration

  
  

  - The inflammatory infiltrate is a mixture of macrophages, plasma cells, and lymphocytes; some polymorphs may be present

  
  

  - The relative contribution of each cell type varies depending on the inflammatory stimulus

  
  

  - Chronic inflammation is associated with the production of new fibrous tissue through granulation tissue formation (healing)
• What is a mechanism of chronic inflammation?

  Proliferation of macrophages and lymphocytes

  
• What are the causes of chronic inflammation?

  These signals converge on target cells, lymphocytes, macrophages, plasma cells, this will cause an inflammatory response

  
• What pharmacological agents can you use to interfere with production of inflammatory mediators?

  Aspirin

  NSAIDs

  Hydrocortisone

  Antihistamines

  Inhalers (various)

  Other steroids
• What patterns can you divide chronic inflammation into?

  Serous

  Fibrinous

  Suppurative (purulent)

  Granulomatous
• What is granulomatous inflammation?

  A form of chronic inflammation characterised by the formation of granulomas
• What is a granuloma?

  A collection of activated macrophages
• What do granulomas look like histologically?

  Abundant eosinophilic cytoplasm and look vaguely like epithelial cells so are termed 'epithelioid cells
• What can macrophages aggregate to form?

  Giant cells
• What may solitary granulomas form in response to?

  Persistent local inflammatory stimuli (e.g. foreign bodies)
• What are some examples of chronic granulomatous diseases?

  TB

  Leprosy

  Sarcoidosis

  Crohn's disease

  Oro-facial granulomatosis

  Chronic granulomatosis disease
• What is acid fast bacilli (AFB)?

  A general term used to describe bacteria stained using the 'Ziehl Neelsen' (ZN) technique

  
  

  In common usage, the term refers to M. tuberculosis
• What happens in TB?

  Mycobacteria are ingested into the macrophages which excite a T cell response

  
  

  As they are intracellular, they are protected from immunological attack & persist in the tissues.

  
• What is a caseating granuloma?

  It is a cheese-like necrosis ( tissue death), typically a feature of a granuloma of TB

  
  

  Features include:

  
  

  -dense mass of epithelioid cells

  -T lymphocytes

  -caseous necrosis centrally,

  -Langerhans type giant cells,

  - AFBs

  
• Why can TB be considered a (Type IV) hypersensitivity reaction?


  Because the intracellular mycobacteria drive ongoing inflammatory activity

  
  

  This is characterised by a cell mediated (T cell) response

  
  

  A sequel to this is tissue damage & repair

  
  

  Tissue damage is caused by the hosts own cells

  
• What is rheumatoid arthritis?

  A chronic, systemic inflammatory disorder that mainly affects joints

  
  

  These become deformed and painful with loss of function

  It may also have extra-articular features
• What makes rheumatoid arthritis a poly-arthritis?

  Typically when >5 joints are involved
• What cytokines are involved in the signalling pathway for inflammatory arthritis?

  TNF-a

  Interleukin-1

  Interleukin-6

  
• Describe the process of what happens in rheumatoid arthritis.

  The inflammatory process causes the damage

  
• Summarise chronic inflammation:

  - Can be both protective and destructive

  
  

  -Reflects a complex interrelationship between the response to damaging stimuli and hypersensitivity

  
  

  -Is associated with granulation tissue formation and fibrous repair - in some instances this is helpful but in others it leads to tissue damage and loss of function.