Chronic inflammation pt 1 Flashcards
what events occur simultaneously in chronic inflammation - 3
- active inflammation, tissue destruction and attempts at repair
Causes of chronic inflammation
Persistant/ prolonged exposure to initial noxious stimuli
Foreign material
Delayed healing
Hypersensitivity
Lowered host resistance
Repeated bouts of acute inflammation
Classification of chronic inflammation
- non specific
- granulomatous
Morphological features of non specific chronic inflammation - 3
- exudation
- macrophage accumulation and proliferation
- repair
Exudation
- persistence of acute inflammatory changes with neutrophils, fibrin, fluid exudate and pus formation due to the persistence of injurious agent
- results in continued tissue destruction
Macrophage accumulation and proliferation
demolition phase
Repair
- angiogenesis - formation of new blood vessels
- proliferation of fibroblasts which lay down collagen
- inflitration by other mononuclear cells: lymphocytes and plasma cells
macrophages are scattered in connective tissue or in organs such as
- liver = kuppfer cells
- spleen/lymph nodes = sinus histiocytes
- lungs = alveolar macrophages
- CNS = microglia
Classical macrophage activation - 4
- activated by endotoxins engagement with TLRs and other sensors, specifically IFNy, foreign substances including crystals and particulate matter
- release ROS, NO and upregulate lysosomal enzymes which kill ingested organism and produce cytokines which stimulate inflammation
- important in host cell defense and inflammatory reactions
- can cause injury to normal tissues
Alternative macrophage activation - 4
- IL-4, IL-13
- they are not actively microbicidal and the cytokines can inhibit the classical activation
- key role in tissue repair
- promote angiogenesis, activate fibroblasts and stimulate collagen synthesis
Role of macrophages - 4
- ingest and eliminate microbes and dead tissue
- tissue repair and are involved in scar formation and fibrosis
- produce cytokines (IL-12) and eicosanoids
- present antigen to T lymphocytes and also respond to signals from T lymphocytes
what are eicosanoids
signaling molecules made from arachidonic acid (a fatty acid) and play a role in inflammation, immune response, and blood flow. Examples include prostaglandins, leukotrienes, and thromboxanes.
why is the feedback loop in macrophage-lymphocytes important
- promotes more antigen presentation and cytokine secretion
- this sustains chronic inflammation (bad)
what activate lymphocytes
microbes and environmental antigens
and when they are activated they can propagate inflammation
Activated B lymphocytes and plasma cells target
self antigens, foreign antigens and altered tissue components
Eosinophils - 2
- are abundant in rxns mediated by IgE and parasitic infections
- have granules that contain major basic proteins and a highly cationic protein that is highly toxic to parasites and can also cause lysis of mammalian epithelial cells
Mast cells
- have receptors that bind the fc portion of IgE
- this portion has antibodies which when bind to antigens they cause the mast cell to degranulate, releasing histamine and prostaglandins
Examples of chronic non specific inflammation - 4
- chronic osteomyelitis
- chronic pyelonephritis
- chronic bronchitis
- chronic cholecystitis
Chronic osteomyelitis pathology
- increased tissue tension due to exudate against the unyielding bone
- this compresses blood vessels causing ischemia and necrosis
- pus is form under the periosteum and it is discharged in the form of sinuses
- the dead bone is also known as sequestrum acts as a foreign body and this is where microbes and bacteria continue to grow
- the dead bone is broken down by osteoclasts and discharged as sinuses, however, not all of it can be discharged and this leads to the continued attempts to healing and formation of new bone
- new bones is formed, known as the involucrum which surround the dead bone
- however, chronic suppurative inflammation, and chronic osteomyelitis occurs
Who is mostly affected by chronic osteomyelitis
- long bone of young children and adults
- occurs at the end of the long bone
- follows acute inflammation in the bone
Implications of the dead bone acting as a foreign body
this trigger an immune response and the inflammatory process persists forming chronic abscess
where is the sequestrum
embedded in the pus/infected granulation tissue
Cloaca
the opening i the involucrum through which pus and sequestra make their way out
chronic bronchitis - 5
- chronic cough that leads to the production of sputum in at least 3 moths for at least 2 consecutive years
- caused by cigarette smoking which irritates the airways, damages the cells lining the airways and predisposes to infection
- leads to increase in number and size of mucus producing glands in the bronchial walls and increase in the size of goblet cells in the epithelium
- hyperaemia and oedema of the submucosa with lymphocytic infiltration… later results in scarring of the bronchial wall
what is lymphocytic infiltration
the accumulation of lymphocytes in response to chromic inflammation
what causes chronic pyelonephritis
repeated attacks to the kidney parenchyma
scarring during the healing phase of pyelonephritis
during healing, scarring ,may form on either one or both poles but this doesnt always occur (the scarring)
what happens in chronic cholecystitis
- the wall of the organ, gallbladder thickens due to repeated attacks of acute inflammation
what forms during cholecysetitis
calculi, which act as foreign bodies
5 systemic effects of chronic inflammation
- fever = manifests as night sweats
- weight loss and loss of appetite = increased catabolism due to actions of TNFa and IL-1
- leukocytosis = accumulation… more likely to involve the mononuclear than the polymorphs
- protein synthesis by the liver which results in increased CRP, ESR and fibrinogen
- amyloidosis = due to long standing chronic inflammation
examples of polymorphs
- neutrophils
- eosinophils
- basophils
