Chronic Inflammation Flashcards
What is chronic inflammation?
Chronic response to injury with associated fibrosis
Longer and more variable, less known about it than acute, overlap with host immunity
What are the two types of insults that result in chronic inflammation?
Chronic and acute
How does chronic inflammation arise?
- take over from acutes inflammation (if damage is too severe to be resolved within a few days)
- arise de novo: autoimmune conditions (rheumatoid arthritis), chronic infection (viral hep), ‘chronic low-level irritation’
- alongside acute acute inflammation (in severe persistent or repeated irritation)
What does chronic inflammation look like?
Defined by the cells present:
- macrophages
- lymphocytes ***
The mononuclear cells are the predominant cell type (macrophages and lymphocytes)
What are the cell types most commonly found in chronic inflammation?
Macrophages Lymphocytes Plasma cells Eosinophils Fibroblast/myofibroblasts
Discuss macrophages:
What from?
When important?
Functions? (7)
What from: derived from monocytes made in bone barrow (in the blood)-become macrophages (/histiocytes) in the tissue spaces
Importance: v important in acute and chronic inflammation
Functions: phagocytosis of debris and bacteria, Antigen presenting (initiation of immune response), stimulating angiogenesis, synthesis of cytokines, blood clotting factors and proteases, control other cells by cytokines release, inducing fibrosis
What do macrophages synthesis?
Cytokines, complement components, blood clotting factors and proteases
How do macrophages control other cells?
By their release of cytokines
Discuss lymphocytes:
Microscopic appearance?
Other names?
Functions? (4)
Microscopic appearance: small blue dots- large nucleus and little cytoplasm
Other names: chronic inflammatory cells
Functions: immunological-processing antigens, B lymphocytes differentiate to plasma cells and produce antibodies, T lymphocytes involved in control and some cytotoxic functions, killing cells (NK cells)
Where are B lymphocytes produced and what do they do?
Mature in bone marrow
Differentiate into plasma cells which produce antibodies
Where are T lymphocytes produced and what do they do?
Produced in bone marrow, mature in thymus
Varied in cellular functions (controlling immune reactions) and cytotoxic functions (killing cells)
What are plasma cells?
Why do they indicate chronic inflammation and what do they look like microscopically?
Differentiated antibody-producing B lymphocytes
They take a while to be produced so their presence suggests that the inflammation is long term
Open nucleus- clot phase-lots of chromatin around nucleus, cytoplasm is visible, large GA
Eosinophils:
When are they present?
What do they do?
What do they look like microscopically?
Present for v specific stimuli eg allergic reaction/parasite infestation/some tumours
Attach large parasites
Bi lope nucleus- (sun burnt face with shades on)
Why are fibroblast/myofibroblasts present in a chronic inflammatory response?
What to they do?
Because they’re recruited for by macrophages,
Fibroblasts produce C.T (collagen, elastin and glucosaminoglycans), differentiate into myofibroblasts- contractile cells
What is a giant cell?
Multinucleated cells made by fusion of macrophages happens because of frustrated phagocytosis
(If they cant deal with something alone, they fuse to make something bigger)
Seen in granulomatous inflammation
List some types of giant cells and what they fight (3)
Langhans->TB
Foreign body type-> foreign bodies
Touton-> fat necrosis
Describe the microscopic appearance of a langhans type giant cell, what do these cells fight?
Horse shoe nuclei around peripheral
TB (because TB is hard to get rid of)
What do foreign body type giant cells look like microscopically?
Not very organised, multiple irregular aggregates of nuclei (around outside?), blue-ish stuff in the middle=foreign body (exogenous/endogenous)
If the foreign body is small it is phagocytise by the giant cell and can be seen within it. If it is large the foreign body giant cell sticks to its surface
What does a Touton giant cell look like microscopically? And what it is involved in?
Nicely organised centre-multi nuclei, folded cytoplasm, accumulates a lot of fat (bubbles)
Involved in Fat Necrosis and xanthomas
Form in lesions where there is a high lipid content (such lesions will also contain cells called foam cells which are simply macrophages whose cytoplasm appears foamy as the have phagocytised a lot of lipid
Morphology of most chronic inflammatory
reactions is non-specific, BUT proportions of
each cell type may vary in different
conditions. Giant cell types are also helpful in diagnosis. What cell is most abundant in the following conditions:
Rheumatoid arthritis
Chronic gastritis
Leishmaniasis (a protozoan infection)
Rheumatoid arthritis-mainly plasma cells
Chronic gastritis- mainly lymphocytes
Leishmaniasis- mainly macrophages
What are the unwanted side effects of chronic inflammation? (4)
Give examples of all these effects
-Fibrosis (eg gall bladder-chronic cholecystitis, chronic peptic ulcer, cirrhosis)
-Impaired function (eg chronic inflammatory bowel disease- ulcerative colitis and Crohn’s disease)
(**rarely increased function eg mucus secretion thyrotoxicosis)
- Atrophy (eg gastric mucosa, adrenal glands)
- Stimulation of inappropriate immune response (eg macrophages-lymphocyte interactions, hay fever)
What is chronic cholecystitis?
the gallbladder is damaged (mucosa) by repeated attacks of acute inflammation, usually due to gallstones, and may become thick-walled, scarred (fibrosis occurs) and small. The gallstones may block the opening of the gallbladder into the cystic duct or block the cystic duct itself. If scarring is extensive, calcium may be deposited in the walls of the gallbladder, causing them to harden (called porcelain gallbladder).
People have recurrent upper left quadrant abdominal pain (less severe and long lasting pain as in acute) and nausea
What is inflammatory Bowel disease? Name two types
Idiopathic inflammatory disease affecting large and small bowel. Patients present with diarrhoea, rectal bleeding and other symptoms.
Ulcerative colitis and Crohn’s disease
What effect of chronic inflammation is seen in inflammatory bowel disease?
Impaired function
Describe the differences between ulcerative colitis and Crohn’s disease
UC-superficial (affected mucosa and not the deeper tissue), cause diarrhoea and bleeding
CD- transmutation (affects mucosa, submucosa, lamina propria and adventitia, causes strictures and fistulae
What is a stricture?
Also called a stenosis- abnormal narrowing in a blood vessel/tubular organ/structure
What is a fistulae?
Abnormal connection between two hollow spaces (ie blood vessels, intestines, hollow organs)
Abnormal anastomosis
Name a chronic condition in which both fibrosis and impaired function occurs. What are the common causes of this condition?
Cirrhosis
Alcohol, infection HBV, HCV, immunological, fatty liver disease, drugs and toxins
What is cirrhosis and when does it occur along the time line of chronic liver disease?
Cirrhosis is a condition in which the liver does not function properly due to long-term damage. This damage is characterized by the replacement of normal liver tissue by scar tissue
At the end stage of CLD
Sufferer may get: tired, weak, itchy, have swelling in the lower legs, develop yellow skin, bruise easily, have fluid build up in the abdomen, or develop spider-like blood vessels on the skin
Disorganisation of architecture, attempted regeneration.
What does cirrhosis look like microscopically?
Lots of blue lines- collagen/ connective tissue
Name a condition in which you get increased function and what is often the underlying cause
Thyrotoxicosis (hyperthyroidism)
Graves disease
(Other causes include multinodular goiter, toxic adenoma, inflammation of the thyroid, eating too much iodine, and too much synthetic thyroid hormone)
What is thyrotoxicosis ?
Thyrotoxicosis is the condition that occurs due to excessive thyroid hormone of any cause and therefore includes hyperthyroidism
Name a condition in which there is chronic inflammation causing atrophy?
Atrophic gastritis
What is atrophic gastritis?
chronic inflammation of the stomach mucosa, there is cell injury and death and the cells aren’t regenerated therefore replaced by scar tissue which impacts upon the function of the stomach
How do chronic inflammation and immune responses overlap?
Immune disease cause pathology by chronic inflammation
And
Chronic inflammation processes can stimulate immune responses
What is granulomatous inflammation?
Chronic inflammation with granulomas
What is a granuloma?
It is a collection of immune cells (such as macrophages and lymphocytes=histiocytes) Granulomas form when the immune system attempts to wall off substances it perceives as foreign but is unable to eliminate.
Foreign bodies=infectious organisms/exogenous/endogenous material not normally there
The presence of a foreign body elicits granulomas
Why do granulomas arise?
Persistent, low grade antigenic stimulation
Hypersensitivity (immunological reaction)
Body’s way of dealing with particles that are poorly soluble or difficult to eliminate
Eg thorns, splinters, TB, leprosy
What are the main causes of a granulomatous inflammation?
- mild irritant ‘foreign material’
- infection: mycobacteria eg TB/leprosy, other infections eg some fungi
- unknown causes: sarcoidosis, wegener’s granulomatosis, Crohn’s disease (common)
What is tuberculosis?
Caused by Mycobacteria (difficult and slow to culture)
Produces no toxins or lytic enzyme- very difficult to diagnose
Causes disease by persistence and induction of cell mediated immunity
What is a good indication of TB?
A granuloma in the lung-made of langhans’ type giant cells and caseous necrosis
When someone is immmunised against TB they’re given a BCG jab, what can these cause and what so they consist of?
BCG granulomas
Containing giant cells
Name 3 granulomatous diseases of unknown cause
Sarcoidosis-variable clinical manifestations, young adult women, non-caseating granulomas ‘sarcoid granulomas’ (different from TB), giant cells, involves lymph nodes, lungs…
Crohn’s disease- regional enteritis: patchy full-thickness inflammation through bowel (type of inflammatory bowel disease)
Wegener’s granulomatosis
How does chronic inflammation happen?
Severe acute inflammation
De novo chronic inflammation
Repeated attacks of acute inflammation
Which of the clinical signs of acute inflammation persist during chronic inflammation?
Swelling and pain
Tumor and dolor
What is main cell type in chronic inflammation?
Macrophages
What are the predominant cells of the immune system?
Lymphocytes
What is fibrosis?
Means excess of fibrosis tissue
Fibroblast stimulated by cytokines to produce excess collagen, initially helpful because it walls off the infected area but can impair function etc
Myofibroblasts also causes issues because they cause the contraction of fibrotic structures
What cell will you find in a granuloma?
Epithelia cells- modified macrophages to like epithelial cells (elongated), have eosinophilic cytoplasm and appear tightly packed together
What are the two main types of granuloma?
Foreign body granulomas and hypersensitivity/immune type granulomas
Describe 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/immune type granulomas
contain macrophages, giant cells (Langhans type), epithelioid cells (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.
