Session 3 Flashcards by Klaudia Figa

What happens after acute inflammation? (3 things)

Complete resolution
Repair with connective tissue (FIBROSIS)
Progression to chronic inflammation (inflammation with repair)

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What is chronic inflammation?

Prolonged inflammation with associated repair

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What are the features of chronic inflammation?

Delayed onset
Variable duration
Limits damage and initiates repair
Variable appearances

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How does chronic inflammation arise?

Takes over from acute inflammation if acute is not enough to resolve it
Develops alongside acute inflammation
Arises ‘de novo’ without any preceding acute inflammation (autoimmune conditions)

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Why are there no cardinal features of chronic inflammation?

There are a variety of cell types involved, which result in variable appearances

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What are monocytes?

Cells that are in the circulation and then develop into macrophages when enter the tissue.

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What are the features of macrophages?*

Foamy, bubbly cytoplasm (phagolysosomes that allow phagocytosis)
Some have a ‘slipper shaped’ nucleus
Irregular in appearance and can sometimes look like cancer cells
Large cells

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What are the functions of macrophages?

Phagocytosis: removal of pathogens and presenting the antigen to stimulate adaptive immune response
Synthesis and release of inflammatory mediators that regulate the response

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What are the features of lymphocytes?*

Smaller (slightly bigger than RBC)
Large, central, spherical, dark staining nucleus
Very little thin rim of cytoplasm, sometimes can’t be seen

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What are the functions of T cells (lymphocytes)?

Helper: assists inflammatory cells (CD4)
Cytotoxic: destroys pathogens directly (CD8)

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What are the functions of B cells (lymphocytes)?

Maturing into plasma cells that produce immunoglobulins/antibodies

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How to distinguish between B cells and T cells?

Immunohistochemistry as they all look the same

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What are the features of plasma cells?*

Bigger
Have more cytoplasm
Nucleus is ecentric: pushed to one side
Clockface chromatin pattern (clumped into spheres)
Perinuclear clearing (lighter patch near nucleus - part of golgi)

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What are the features of eosinophils?*

Bilobed nucleus
Granular cytoplasm that stains bright red (due to chemical mediators, eg. histamine)
“tomato with sunglasses”

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What are the functions of eosinophils?

Releasing chemical mediators (eg. prostaglandin, histamine, NO)
Hypersensitivity reactions
Parasitic infections

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What are the functions of fibroblasts/myofibroblasts?

Repair

- Production and laying down collagen to reconstruct tissues

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What are giant cells?*

Multinucleate cells with one giant cytoplasm

- Formed by fusion of several macrophages

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Why do giant cells form?

‘Frustrated phagocytosis’ - clumping together to increase effectiveness of phagocytosis when resistant foreign bodies are present

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What are foreign body giant cells?*

Random assortment of nuclei

- Destroy foreign bodies

What are Langhans giant cells?*

Nuclei line up around periphery in crescent shape

- Important in TB

What are Touton giant cells?*

Nuclei line up in the middle and form a circle

- Can be seen in fat necrosis

What are the cells in rheumatoid arthritis?

Mainly plasma cells

What are the cells in chronic gastritis?

Mainly lymphocytes

What are the cells in leishmaniasis?

Mainly macrophages

What are effects of chronic inflammation?

1. Fibrosis: deposition of collagen (eg. cirrhosis) 2. Impaired function: (eg. IBD - can no longer absorb nutrients well) 3. (rare) Increased function: eg. thyrotoxicosis increases T3 + T4 production 4. Atrophy: reduction in organ size 5. Continued stimulation of immune response

When can fibrosis occur in the gallbladder?*

Chronic cholecystitis. - Repeated obstruction by gallstones - Chronic inflammation arises along acute inflammation - Fibrosis of wall (thick, pale)

When can impaired function occur in IBD?*

Crohn's disease and ulcerative colitis (not absorbing nutrients due to the inflammation) - Neutrophils destroy intestinal crypts - Pain, altered bowel motion

What are the features of Crohn's disease?

- Affects all GI tract, mouth to anus - 'Skip lesions', discontinuous inflammation - Transmural inflammation of bowel wall - Granulomata sometimes present - Rectal bleeding less likely

What are strictures and fistulae as complications of Crohn's disease?

- Strictures: narrowing of bowel | - Fistulae: abnormal connections between 2 epithelial cells.

What are the features of ulcerative colitis?

- Only affects large bowel - Continuous inflammation - Only affects superficial bowel wall (mucosa/submucosa) - No granulomata - Rectal bleeding more likely

What is an example of fibrosis and impaired function?* (look at histology)

Liver cirrhosis. - End stage liver damage - Fatty liver disease - Attempted regeneration

What is a granuloma?*

- Collection of epithelioid histiocytes (macrophages that look like epithelial cells) - Surrounding lymphocytes - Large, polygonal

What are causes of granulomatous infection?

Foreign body reaction. (Foreign body giant cell will form first, then foreign body granuloma) Infection (mycobacterium) eg. tubercolosis, leprosae Idiopathic (eg. sometimes occurring in Crohn's disease and sarcoidosis)

Why are mycobacteria so difficult to destroy?

They have thick cell walls and mycolic acids which resist phagocytosis.

What is the specific subtype of mycobacterium granuloma?*

- CASEOUS NECROSIS in the middle of the granuloma, looks like 'soft cheese' to the naked eye - Stains pink with H&E

What is the difference between a biopsy and a resection?

- Biopsy will only have small tissue fragments (little slides) - Resection is the analysis of the whole organ (lots of slides)

What are the features of benign neoplasia?

- Localised - No invasion - No metastases - Slow growth - Well differentiated - Compress tissue - Uniform cell size

What are the features of malignant neoplasia?

- Metastases (vascular/lymphatic) - Poor differentiation - Invasion of other tissues - Destruction of other tissues - Varying nuclei and cell shapes - Rapid growth

What are primary malignancies?

Neoplasia originating from the tissue it is found in.

What are secondary malignancies/metastases?

Spread from a primary tumour elsewhere.

How to determine whether the malignancy is primary or secondary?

Immunohistochemistry - test for the cytokeratins that are found on the cancer.

What is the H&E stain and what does it stain?

Haematoxylin & Eosin. H: stains nuclei purple, attracted to nucleic acid particles E: stains cytoplasm pink, has a neg. charge

What else does eosin stain?

Collagen.

What are examples of histology?

- Core biopsies | - Cancer resection specimens

What are examples of cytology?

- Fine needle aspirates (eg. breast/lung/lymph nodes) - Cervical smears - Sputum

What are advantages of histology?

- Therapeutic as well as diagnostic - Can differentiate invasive from in situ disease - Better for immunohistochemical testing

What are key points about cytology?

- Faster and cheaper - Can be used for cells in fluids - Noninvasive - Higher error rates - Used for confirming/excluding rather than diagnosing