L6: Chronic Inflammation Flashcards
Define chronic inflammation?
Prolonged inflammation with associated repair
What are the features of chronic inflammation?
- Delayed onset
- Variable duration–> days–> years
- Variable response–> no cardinal signs
- Limits damage and initiates repair
- Debilitating symptoms
How does chronic inflammation arise?
1- Takes over from acute inflammation
–> acute inflammation unable to clear the pathgen
2- Arises at same time as acute inflammation
–> Repeated stimulus, persistant irritation
3- Arises without acute inflammation
–> De novo, autoimmune conditions
What does chronic inflammation look like?
Variable appearance depending on cells present
What are the different cells types of chronic inflammation?
Macrophages (histiocyte) Lymphocytes --> plasma cell Eosinophil Fibroblast/ myofibroblasts Giant cells - Foreign body giant cell - Langhans giant cell - Touton giantcell
What is the difference between a monocyte and a macrophage?
Monocyte- in circulation
Macrophage- in tissue
What is the appearance of a macrophage?
Large cells
Abundant, foamy cytoplasm –> phagolysosome
Slipper shaped nucleus–> indented
However, appearance can vary a lot– can look like cancer cells
What is the function of macrophages?
Phagocytosis
- Removal of pathogens/ necrosis/ debris
- Antigen presentation to the immune system
Inflammatory mediators
- Synthesis and release of many mediators
- Controls and regulates the inflammatory response
What do lymphocytes look like?
Smaller but still bigger than RBC
Large central spherical nucleus
Dark staining nucleus
Small rim of cytoplasm
What is the function of lymphocytes?
T cells
- -> Variety of types
- -> ‘Helper’ –> CD4+ –> assist other inflammatory cells
- -> ‘Cytotoxic’–> CD8+ –> destroy pathogens
B cells
- -> Mature into plasma cells
- -> Produce antibodies
- -> Neutralise and destroy pathogens
Note= Not possible to distinguish between them on H&E stain
What are plasma cells? What are the characteristic features?
Mature B cells
Eccentric nucleus
Chromatin clumps into sphere around periphery of nucleus –> Clock face nucleus
Perinuclear cytoplasmic apperance–> golgi apparatus
What is the function of plasma cells?
Fully differentiated B lymphocyte Produces antibodies (synthesis and secrete)
What are eosinophils?
Larger than RBC
2 lobed nucleus–> bilobed
Cytoplasm stains bright red
Contains granules
What is the function of eosinophils?
Granules –> Contains mediators (eosinophil cationic proteins and elastases)
Release a variety of mediators
Hypersensitivity reactions–> allergic reactions
Parasitic infections
What are fibroblast/myofibroblasts?
Important for regeneration and repair
Lay down collagen
What are giant cells?
Multinucleated cells
Produced–> fusion of multiple macrophages –> macrophages unable to destroy pathogen on its own–> frustrated phagocytosis
What are the different types of giant cells?
Foreign body giant cells–> Big cytoplasm, random nuclei
Langhans giant cells–> Nuclei line up around periphery–> horseshoe shaped–> seen in TB
Touton giantcell–> nuclei line up in concentric circle in middle–> seen in fat necrosis
How can cell type indicate a diagnosis?
Generally cells involved in chronic inflammation are non specific
Sometimes–> proportion of cell types can indicate a diagnosis
- Rheumatoid arthritis= mainly plasma cells
- Chronic gastritis= mainly lymphocytes
- Leishmaniasis (protozoal infections)= mainly macrophages
What are the effects of chronic inflammation?
1- Fibrosis–> repair–> deposition of collagen
2- Impaired function–> loss of function e.g. IBD, Rarely=↑ function–> thyrotoxicosis in Graves Disease
3- Atrophy–> reduction in size of an organ
4- Stimulation of the immune response–> antigen presentation, continuous by macrophages–> prolonged response
How does fibrosis occur in the gall bladder?
Repeated obstruction of bile duct –> gallstone
Result in acute inflammation
Gallstones move–> bouts of acute inflammation–> chronic inflammation
Fibrosis of gall bladder–> thickened and pale
Example of how chronic inflammation impairs function?
Idopathetic inflammatory bowel disease: Crohn's and Ulcerative colitis Inflammation --> Abdominal pain --> Altered bowel movement --> Weight loss --> Rectal bleeding --> Diarrhoea
What does idopathetic mean?
Unknown cause yet
Compare and contrast Crohn’s and Ulcerative Colitis?
Crohn’s
- -> Affect all GI tract
- -> Discontinuous –> one bit inflammed one bit not
- -> Affect full thickness of bowel wall–> transmural –> stictures/fistulae
- -> Sometimes get granulomata
- -> Less likely to get rectal bleeding
Ulcerative Colitis
- -> Large bowel effected only
- -> Continuous inflammation
- -> Affect superficial wall only–> mucosa + submucosa
- -> No granulomata
- -> More likely to have rectal bleeding (result of continuous inflammation)
Why do you get cirrhosis?
End stage liver damage to liver Caused by --> Alcohol --> Hepatitis --> Drugs and toxins --> Fatty liver disease Fibrosis and attempted regeneration
What is granulomatous inflammation?
Specific of chronic inflammation with granuloma
What is a granuloma?
Spherical collection of epithelioid histiocytes, surrounded by lymphocytes
Sometimes get giant cells in them
What are epithelioid histiocytes?
Macrophages that look like epithelial cells
What causes granulomatous inflammation?
Foreign body reaction
–> Foreign body giant cells–> (collection of macrophages)–> next step is to form a granuloma
Infections
- -> Mycobacterium (mycobacterium tuberculosis and leprae)
- -> Difficult to destroy because–> thick cell wall and mycolic acids (proteins on cell surface)
- -> Usually caseous necrosis in middle
Idiopathic–> currently no known cause
- ->Cronh’s disease–> Non-caseating granulomata in GI tract
- ->Sarcoidosis–> multiple well formed granulomata in the lymph nodes, lungs and skin (enlarged lymph nodes, shortness of breath and dry cough and skin lumps)
What is special about mycobacterium granuloma?
Middle of granulomatous is caseous necrosis
Caseous–> looks like cheese
Caseous necrosis, surrounded by epithelioid histiocytes and then lymphocytes
