5. Chronic Inflammation Flashcards
What is chronic inflammation?
Prolonged inflammation with associated repair
What are the features of chronic inflammation?
- Delayed onset
- Can cause debilitating symptoms
- Variable duration (d ays -> years)
- Variable appearances
- Limits damage and initiates repair
How does a chronic inflammation arise?
1) Takes over from acute inflammation
- If resolution not possible with acute inflammation
2) Develops alongside acute inflammation
- Severe/persistent irritation
3) Arises “de novo”
- Without preceding acute inflammation Eg autoimmune conditions Rheumatoid arthritis/Inflammatory Bowel Disease…
What does chronic inflammation look like?
- There are variable appearances due to the variety of cell types
- Variety of sites of inflammation
• under the microscope mononuclear cells (macrophages and lymphocytes) are now the predominant cell type rather than neutrophils and a new type of tissue called granulation tissue begins to form as healing simultaneously gets underway
What are the cells principally involved in chronic inflammation and why?
- Macrophages
- Lymphocytes (T cell, B cell, plasma cell)
- Eosinophils
- Fibroblasts/myofibroblasts
Can do things neutrophils can’t eg macrophages can replicate unlike neutrophils. Forms granular tissue
Where are macrophages and monocytes found?
Monocytes —> precursor for macrophages, exist in circulation
Macrophages (aka histiocytes) —> when monocytes enter tissue spaces
Where are monocytes made?
Bone marrow
Describe the appearance of macrophages
- Large Cells
- Abundant, foamy cytoplasm - Phagolysosomes
- “Slipper shaped” nucleus
What are phagolysosomes?
When a macrophage fuses with a lysosome. Ingested material is digested by the action of lysosomal enzymes inside of them.
What is the function of macrophages?
PHAGOCYTOSIS
- Removal of pathogen/necrosis/debris
- Antigen presentation to immune system
INFLAMMATORY MEDIATORS
- Synthesis and release of many mediators to Control and regulate inflammatory response:
• Stimulating angiogenesis (the formation of new blood vessels) which is important in wound healing
• Inducing fibrosis
• Inducing fever, acute phase reaction and cachexia.
Are macrophages as good as neutrophils are at phagocytosis?
not always as effectively as neutrophils, however they are better at destroying some difficult to kill bacteria such as Mycobacterium tuberculosis
What is the appearance of lymphocytes?
- Small Cells - Slightly larger than RBC
* Dark staining Spherical Nucleus - Very thin rim of cytoplasm
What are the two types of lymphocytes?
T cells
B cells
How are different T cells distinguished?
different proteins on surface:
• CD4+ - T helper cells
• CD8+ - T killer cells
What are the functions of lymphocytes?
• processing antigens
T cell:
• “Helper” - Assist other inflammatory cells - secrete cytokines
• “Cytotoxic” - Destroy Pathogens
B cell:
• mature into plasma cells that produce and secrete antibodies (immunoglobins)
• antibodies neutralise pathogens
Can T cell sand B cells be distinguished by appearance?
No
Describe the plasma cell appearance
- Eccentric nucleus
- “Clock-face” chromatin - chromatin in the nucleus that form spherical clumps, these line up on the edge of the nucleus
- Peri-nuclear clearing (Golgi) - paler area next to the nucleus
What is the function of plasma cells?
Fully differentiated B lymphocyte
Produces antibodies
Describe the appearance of eosinophils
- Bi-lobed Nucleus
- Granular Cytoplasm - granules contain chemical mediators such as histamine
- Stains red
What is the function of eosinophils?
• Release of a variety of mediators
• Present during :
- Hypersensitivity reactions
- Parasitic infections
What does the presence of lymphocytes suggest?
Lymphocytes are the predominant cells of the immune system. If they are present in tissues where they are usually absent, it indicates that some antigenic material is or has been there
What are fibroblasts?
cells that secrete fibrous proteins like elastin and collagen
What are fibroblasts, give their function and products
- Fibroblasts are cells that secrete fibrous proteins like elastin, collagen and glucosaminoglycans.
- They respond to stimuli and move to sites where they’re needed.
- They’re also able to differentiate into myofibroblast cells that are part muscle and part fibroblast, these cells are able to contract
What are giant cells?
- multi nucleate cells
- fusion of multiple macrophages to increase the effectiveness of phagocytosis e.g. if there’s a particularly resistant microbe - frustrated phagocytosis
What are the 3 types of giant cells?
- Langhans giant cells
- Foreign body giant cells
- Touton giant cells
What do foreign body giant cells look like and when are they seen?
- the nuclei are arranged randomly in the cell.
- They are often (but not exclusively) seen when a hard to digest foreign body is present.
- If the foreign body is small it is phagocytised by the giant cell and can be seen within it. If it is large the foreign body giant cell sticks to its surface,
What do Langhan giant cells look like and when are the often seen?
- the nuclei arranged around the periphery of the giant cell sometimes as a horseshoe shape
- they are often (but not exclusively) seen in tuberculosis
What do Touton giant cells look like and when do they normally form?
- the nuclei are arranged in a ring towards the centre of the cell.
- They form in lesions where there is a high lipid content such as fat necrosis and xanthomas.
- Such lesions will also contain cells called foam cells which are simply macrophages whose cytoplasm appears foamy as they have phagocytised a lot of lipid.
In chronic inflammation, what can the proportion of cell types indicate?
Proportion of cell types can indicate a diagnosis
In rheumatoid arthritic, which cells will be seen mainly?
Rheumatoid arthritis = mainly plasma cells
In chronic gastritis, which cells are mainly seen?
Chronic gastritis = mainly lymphocytes
In leishmaniasis, which cells can be seen mainly?
Leishmaniasis (protozoal infection) = mainly macrophages
What are the effects of chronic inflammation?
- FIBROSIS
- IMPAIRED FUNCTION
- ATROPHY
- STIMULATION OF IMMUNE RESPONSE
What is fibrosis
Fibrosis means an excess of fibrous tissue.
What causes fibrosis?
when fibroblasts are stimulated by cytokines to produce excess collagen
What is the initial advantage of fibrosis?
Production of collagen is initially helpful in chronic inflammation as it helps to wall off infected areas and the production of a fibrous scar to replace damaged tissue is essential in wound healing
How does fibrosis cause complications in chronic inflammation?
- Replace normal parenchymal tissue and impair the function of an organ, e.g., interstitial fibrosis of the lung.
- If the area of fibrosis contains enough myofibroblasts, it can slowly contract and cause further problems, e.g., contraction in a cirrhotic liver will impair the flow of portal blood resulting in ascites. All such sclerosing conditions are difficult to treat.
How does gall stones lead to fibrosis?
- Repeated obstruction of bile duct by gall stones
- Repeated bouts of acute inflammation -> chronic inflammation
- Fibrosis of gall bladder wall (thickened and pale)
What are examples of idiopathic inflammatory bowel diseases?
Crohns and ulcerative colitis
What are symptoms of inflammatory bowel disease?
Abdominal pain, altered bowel motion, weight loss due to reduced intake of nutrients with loss of function of bowel, rectal bleeding, diarrhoea
What is the difference between Crohn’s disease and ulcerative colitis?
Crohns:
• can affect all of GI tract from mouth to anus,
• discontinuous patches of inflammation “skip lesions”,
• inflammation affects full thickness of bowel wall (Transmural from inside to outside which can cause strictures - narrowing of tube, and fistulae - abnormal connections between two epithelial surfaces),
• can sometimes find granulomata,
• less likely to have rectal bleeding
UC: • affects large bowel only, • continuous inflammation, • inflammation affects superficial bowel wall only -mucosa and submucosa, • no granulomata, • more likely to have rectal bleeding
What is cirrhosis?
- end stage damage to liver
- caused by: alcohol, hepatitis, drugs and toxins, fatty liver disease
- fibrosis and attempted regeneration of liver - nodule of regenative hepatocytes separated by thick bands of fibrous tissue
What is granulomatous inflammation?
Chronic inflammation with presence of granuloma
What is a granuloma?
- A collection of epithelioid histiocytes (macrophages that look like epithelial cells) with surrounding lymphocytes
- May have a giant cell within the granuloma
What are causes of granulomatous inflammation?
- foreign body reaction: arises from giant cell trying to destroy a foreign body
- infections: specifically infections difficult to destroy e.g. mycobacterium (TB, leprae) so need army of macrophages
- idiopathic (don’t know why) e.g. Crohn’s disease, sarcoidosis
Why are mycobacterium difficult to destroy?
Mycolic acids - proteins on surface that resist phagocytosis
Thick cell wall - resist phagocytosis
What are the 2 different types of granulomas?
Caseating granuloma
Non-caseating granuloma
What does a mycobacterium granuloma look like?
- caseous necrosis in the centre - stains pink in centre with H and E stain
- Epithelioid Histiocytes, Lymphocytes also present
What does Crohn’s disease granulomatous inflammation look like?
Non-caseating granulomata in GI tract
What does sarcoidosis granulomatous inflammation look like?
- Non- caseating granulomata
- Multiple well formed granulomas form in lymph nodes, lungs and skins
- SOB, dry cough, skin lumps
What do granulomas do?
walls pathogen off whilst concentrating mononuclear cells within its centre with which it hopes todestroy the particle. Stops the pathogen spreading - when it is difficult to kill pathogen
Describe Foreign body granulomas
Foreign body granulomas:
– contain macrophages, foreign body giant cells, epithelioid cells and some fibroblasts (at the periphery) but very few, if any, lymphocytes,
– develop around material that is not antigenic, e.g., surgical thread.
Describe Hypersensitivity or immune type granulomas
– contain macrophages, giant cells (which may be of Langhans type), epithelioid cells (which are usually more prominent than in foreign body granulomas), some fibroblasts (at the periphery) and lymphocytes,
– can undergo central necrosis which is particularly seen in granulomas associated with tuberculosis,
– develop around insoluble but antigenic particles that cause cell-mediated immunity, e.g., the organisms that cause syphilis, tuberculosis, leprosy, cat scratch disease; fungi
– also seen in sarcoidosis, a disease with an unknown cause in which granulomas are seen in organs throughout the body, and other diseases where the aetiology is unknown such as Wegener’s granulomatosis and Crohn’s disease,
– can be harmful as they occupy parenchymal space within an organ.
What is synovitis?
inflammation of a synovial membrane.
