Response to Injury III: Flashcards
How does chronic inflammation arise?
It arises as:
a progression from acute inflammation
following repeated episodes of acute inflammation
de novo if 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:
Continued recruitment of lymphocytes an macrophages to the area
‘Activation’ of lymphocytes and macrophages
Proliferation locally at site of inflammation
Enhanced survival and immobilisation in the inflamed aea
What signals cause chronic inflammation?
-Tissue derived chemical mediators
-Inflammatory cell derived chemical mediators
-Plasma enzyme systems
-Extracellular matrix components
-Extraneous products
These signals converge on target cells, lymphocytes, macrophages, plasma cells, this will cause an inflammatory response.
give examples of Cellular mediators of inflammation:
Cellular mediators of inflammation: Histamine (biocative amines) Prostaglandins
Leukotrienes Cytokines/Lymphokines
Plasma derived mediators
Clotting factors
Complement cascade
Kallikrein-Kinin system
Fibrinolytic system
give examples of Plasma derived mediators
Clotting factors
Complement cascade
Kallikrein-Kinin system
Fibrinolytic system
give other examples of inflammatory mediators:
Bacterial products /extraneous factors
Reactive oxygen intermediates
What pharmacological agents can you use to interfere with production of inflammatory mediators?
Aspirin
NSAIDs
Hydrocortisone
Antihistamines
Inhalers (various)
Other steroids
What are the type of chronic inflammation?
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 - a chronic disease of unknown cause characterized by the enlargement of lymph nodes in many parts of the body and the widespread appearance of granulomas derived from the reticuloendothelial system.
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.
look at slide 10
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
look at slide 11
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.
IN TB AND OTHER CHRONIC INFLAMATORY CONDITIONS THERE IS A COMPLEX INTERPLAY BETWEEN HYPERSENSITIVITY AND TISSUE DAMAGE.
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
explain the Pathogenesis of Rheumatoid Arthritis check
-Bone and cartilage erosion
- increased synovial fluid
- pannus formation
What cytokines are involved in the signalling pathway for inflammatory arthritis? (check lecture recording)
TNF-a
Interleukin-1
Interleukin-6
Describe the process of what happens in rheumatoid arthritis.
The inflammatory process causes the damage.
- Unknown stimulus leads to chronic inflammation of the joints
- Fibrous repair occurs in response to tissue damage
- Fibrous tissue remodelling and contraction
- Characteristic deformation and ankylosis of the joints (commonly symmetrical involvement of the small joints of the hand)
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.