Chronic Inflammation 1 Flashcards
What are the 3 outcomes of acute inflammation?
1) Resolution
2) Repair
3) Chronic inflammation
(Chronic inflammatory - unable to eliminate the inflammatory mediator. Get some repair happening. Occasionally It can become very overwhelming and lead to tissue death.
Depends on nature and strength of inflammatory responses, we get different responses)
When does chronic inflammation arise?
- As a progression from acute inflammation
- Following repeated episode of acute inflammation
- De novo if the causative agent only produces a mild acute response
(In chronic inflammation, the process of tissue destruction takes place along side that of healing and repair.
The process of chronic inflammation is integrated with that of healing and repair and the processes should be considered together.)
What are features of chronic inflammation comparing it to acute inflammation?
- Very variable but have some prevailing themes
- Tissue destruction and ulceration (more than in acute inflame response)
- Inflammatory infiltrate is a mixture of macrophages, plasma cella and lymphocytes: some polymorphs may be present (acute inflammation have neutrophil domination)
- 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 process)
What is the mechanism of chronic inflammation?
Continuous recruitment of lymphocytes and macrophages to the area
Activation of lymphocytes and macrophages
Proliferation locally at site of inflammation
Enhanced survival and immobilisation in the inflamed area
What are the 5 groups of molecules that can cause chronic inflammation?
1) Tissue derived chemical mediators
2) Inflammatory cell derived chemical mediators
3) Plasma enzyme systems
4) Extracellular matrix components
5) Extraneous products
These signals converge on target cells, lymphocytes, plasma cells, macrophages, cells on lymph nodes and give the ingredients to drive chronic inflammatory response.
Give some examples of inflammatory mediators under these groups
Cellular mediators of inflammation:
- Histamine
- Prostaglandins
- Leukotrienes
- Cytokines/Lymphokines
Plasma derived mediators
- Clotting factors
- Complement cascade
- Kallikrein-kinin system
- Fibrinolytic system
Others
- Bacterial products
- Reactive oxygen intermediates
Give some drugs involved in inflammatory mediators
Aspirin and NSADIs- impact on prostaglandin leukotrienes production
Hydrocortisone - reduction in gene expression of genes involved in protein synthesis of enzymes important in chronic inflammatory pathways
Anti-histamines - work against histamine
Inhalers - suppresses acute inflammatory response and stabilises membrane so inflammatory process is less likely to take place.
What are the 4 types of chronic inflammation?
- Serous (watery)
- Fibrinous (lots of fibrous tissue if you get lots of blood clotting)
- Suppurative (purulent - production of pus)
- Granulomatous
What is granulomatous?
A granuloma is a collection of activated macrophages
They have a particular histological appearance with an abundant eosinophilic (pale staining) cytoplasm and are termed epithelia cells
Macrophages may aggregate to form ‘giant cells’ e.g. langerhans giant cells
Solitary (single) graunolomas may form in response to persistence local inflammatory stimuli (foreign bodies)
Several important diseases are characterised by granuloma formation - the chronic granulomatous diseases
Some have oral significance
Give details on TB as a chronic inflammatory disease
It is a chronic granulomatous disease caused by Mycobacterium tuberculosis.
Prehistoric bones show tuberculosis damage.
The process in TB:
- Initially get primary lesion typically affecting part of lung. May remain localised, may be eliminated or may spread to lymph node
- If spread to lymph node, you get a ghon complex. The immune system can deal with this which may lead to healing bu the immune system may wall off this infection and keep it under control but the disease is not eliminated
- After time, can become immune compromised or elderly and immune system cannot keep resin under control. The bacteria proliferates and they start to spread to distant sites in body
Chronic infection here that body keeps under control but it may spread over time if something changes in body.
What is the histopathology of TB?
Mycobacteria are ingested into the macrophages.
They excite a T cell response.
As they intra-cellular, they are protected from immunological attack and persist in the tissues.
The principal features of caseating granuloma include:
- dense mass of epithelioid cells
- T lymphocytes
- Caseous necrosis centrally
- Langerhans type giant cells
- Acid fact bacteria
(Get a mass of macrophages with a necrotic area in the centre called a caveating granuloma.
Get lymphocytes and epithelial cells around granuloma. The body will produce fibrous tissues to try and wall it off.)
How is TB an example of hypersensitity?
Intracellular mycobacteria within the macrophages drive ongoing inflammatory activity
This is characterised by the cell mediated T response
A sequel to this is tissue damage and repair
Tissue damage is caused by the host own cells (mediator production driven by bacteria so host cell produces inflammatory cells, fibrous tissue produced and this does the damage along with the T cell response)
TB can be considered as a type 4 hypersensitivity reaction
How is rheumatoid arthritis an example of chronic inflammation?
A chronic, systemic inflammatory disorder that mainly affects joints
These become deformed and painful with loss of function
Typically >5 joints are involved making it a poly-arthritis
It may also have extra-articular features
(Get inflammation of the synovium and inflammatory cells within joint space. Inflammatory process set up and can see the synovium expands to allow for joint space. Get chronic inflammatory process elating to fibrous repair tissue that can block the joint space.
Fibrous tissue can being to ossify which can lead to loss of function, distorting of the joints).
- 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
Is pulpitis a chronic inflammatory disease?
Yes
Summarise chronic inflamamtion
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 fibrough repair - in some instances, this is helpful but in others it leads to tissue damage and loss of function.
