Chronic Inflammation Flashcards
What is the difference in the immune systems involved in acute and chronic inflammation?
Acute inflammation involves only innate immunity
Chronic inflammation involves innate and adaptive immunity
How long does acute inflammation last?
Hours to days
The response is very rapid and short-lived
How do the blood vessels change in acute inflammation?
Blood vessels dilate and increase in permeability
This allows an increased blood flow into the area
What is the name of the process where fluid leaks out of blood vessels in acute inflammation?
Fluid exudation
The fluid is rich in proteins e.g. Igs, fibrinogen
What are the main cells involved in an acute inflammatory response?
- neutrophils
- mast cells
- macrophages
What are the 4 terms (latin) used to characterise the symptoms of acute inflammation?
- rubor - redness
- calor - heat
- tumor - swelling
- dolor - pain
What are the stages involved in resolution of acute inflammation?
- phagocytosis of the insulting agent
- fibrinolysis
- phagocytosis of debris
What is involved in fibrinolysis?
fibrin leaks out of the blood vessels and forms fibrinogen
fibrinolysis is the breaking down of the fibrin
What is meant by organisation in repair after acute inflammation?
Replacement of damaged tissue by granulation tissue
What are the main cells that phagocytose cell debris after resolution of acute inflammation?
macrophages
When does repair occur after acute inflammation, opposed to resolution?
When there is too much damage to a tissue that it can’t be repaired
Some tissues are unable to regenerate and replace lost cells
What is the role of granulation tissue?
It allows new blood vessels to form
It contains fibroblast cells that deposit collagen to form the fibrous scar
How long does chronic inflammation last for?
Weeks, months, years
It has a slow onset and a longer duration
What are the 2 processes in chronic inflammation that involve granulation tissue?
- angiogenesis
2. fibrosis
What is angiogenesis?
Development of new blood vessels
What is fibrosis?
Laying down of collagen that will go on to form the fibrous scar
What cells are involved in chronic inflammation that are not involved in acute inflammation?
- lymphocytes
- plasma cells
(also more macrophages are involved)
What are the 3 main conditions that are secondary to chronic inflammation?
- amyloidosis
- cachexia
- anaemia of chronic disease
What is amyloidosis?
Proteins misfold and form aggregates that are deposited around the body
they can cause damage to the tissues that they are deposited in
What is cachexia?
When a patient appears emaciated and thin
What causes anaemia of chronic disease?
cytokines reduce the amount of erythropoietin produced
red blood cell production decreases
cytokines affect iron production around the body, producing mild anaemia
What are the main chemicals involved in cachexia, anaemia of chronic disease and amyloidosis?
cytokines produced in chronic inflammation
What is meant by concomitant tissue destruction and repair?
Both tissue destruction and repair are happening at the same time
What are the types of cells involved in chronic inflammation?
mononuclear cells - single round nucleus
Under what circumstances may acute inflammation lead to chronic inflammation?
- if acute inflammation is not resolved
2. if there are frequent recurrent episodes of acute inflammation
What are examples of conditions that can cause acute inflammation to progress to chronic inflammation?
- if helicobacter pylori causing acute gastritis is not treated
- from chronic cholecystitis -inflammation of the gall bladder
What are the other causes of acute inflammation?
- persistent infection by certain microorganisms
- prolonged exposure to potentially toxic agents
- autoimmunity
- unknown
Why do certain microorganisms cause chronic inflammation?
the macrophages find it difficult to remove all the bacteria
What is meant by endogenous and exogenous toxic agents?
endogenous factors come from within the body
exogenous factors are external stimuli
What is an example of an endogenous toxic agent that can cause chronic inflammation?
a splintered segment of bone that is difficult to break down
What is an example of an exogenous toxic agent that can cause chronic inflammation?
asbestos fibres
sutures
Why are autoimmune diseases an example of chronic inflammation?
The body is having an immune reaction to its own antigens which is persistent and ongoing
What are the 3 unknown factors that cause chronic inflammation?
- crohn’s disease
- ulcerative colitis
- sarcoidosis
What is chronic pyelonephritis?
chronic inflammation affecting the kidney
What life-threatening consequence can chronic ulcers in the stomach lead to?
Perforations
these are holes going through the lining of the stomach that are caused by inflammation destroying the overlying tissue
What causes liver cirrhosis?
prolonged exposure to toxic agents
e.g. alcohol, high lipid levels, hepatitis viruses
What happens in liver cirrhosis?
- underlying liver tissue is destroyed
- it tries to regenerate, leading to nodules
- deposition of collagen in the liver leads to a shrunken liver with poor function
What causes interstitial fibrosis?
asbestos bodies entering the alveoli in the lungs
What happens in interstitial fibrosis?
the alveolar walls thicken which interferes with gas exchange
What happens in lupus nephritis?
The kidney becomes shrunken and granular
The glomerulus is replaced by collagen and no longer functions
What causes cells to become involved in the inflammatory response?
cytokines cause cells and proteins in the blood vessels to emigrate out of the vessels and towards the sites of injury
Where do macrophages originate?
What are they called when they are in the blood and tissue?
originate in the bone marrow
in the blood, they are monocytes
when they enter tissue, they are macrophages
What are macrophages called in the CNS, liver, bone and lungs?
CNS - microglia
Liver - Kupffer cells
Bone - osteoclasts
Lung - alveolar macrophages
What causes the macrophages to become activated?
What signals do they produce?
they are activated in response to cytokines from t cells
they ingest agents by phagocytosis and then produce signals to the fibroblasts, b cells and t cells
What does a plasma cell look like?
What does it do?
it has a clock-faced nucleus with speckles
it is a form of b cell that produces antibodies
What do fibroblasts look like?
What do they do?
they are long, thin cells that produce collagen
they are responsible for forming scars
When will eosinophils and mast cells be involved in the chronic inflammatory response?
eosinophils and mast cells are activated by IgE
If there is a type of chronic inflammation involving IgE
What is involved in the cycle of chronic inflammation?
- macrophages follow chemokines to the injured area
- macrophage is activated in the tissue, produces cytokines and presents antigens to t cells
- t cells are activated and go on to activate b cells
- b cells become plasma cells and release antibodies
- inflammatory mediators from the t cells can activate more macrophages
How can macrophages cause tissue injury and damage?
they release reactive oxygen species and enzymes
What are the 2 roles of granulation tissue?
- angiogenesis is the formation of new blood vessels
2. fibroblasts are involved in collagen deposition
When looking at chronic inflammation under the microscope, what is significant about what is seen?
- angiogenesis means that there are many blood vessels visible
- inflammatory cells - especially lymphocytes
What is a granuloma?
a collection of activated epitheloid macrophages
What does epitheloid mean?
looks like epithelial cells
What does a granuloma look like under the microscope?
pink cytoplasm, indistinct cell membranes, oval nucleus
What are the epitheloid macrophages in a granuloma surrounded by?
mononuclear leucocytes (b cells and t cells) and occasionally some plasma cells
What are the 2 types of granulomatous inflammation?
- caseating
2. non-caseating
What is significant about the appearance of a caseating granuloma?
when cutting into the granuloma, any area looks like cream cheese
What is the difference between a caseating and non-caseating granuloma?
in a caseating granuloma, the cells in the centre are necrotic
in a non-caseating granuloma, the cells in the centre are not dead
What infection commonly causes a caseating granuloma?
tuberculosis
What other type of cells are often found in granulomatous inflammation?
multinucleate giant cells
What are multinucleate giant cells?
many macrophages merge together to form a giant cell
Why is it important to be able to identify a granuloma?
There are only a limited number of conditions that cause granulomatous inflammation
Identifying it informs further tests
What are the 6 categories that cause granulomatous inflammation?
- bacterial
- parasitic
- fungal
- inorganic metals or dust
- foreign bodies
- unknown
What are common bacterial infections that cause granulomatous inflammation?
- tuberculosis
- leprosy
- syphilis
- cat-scratch
What are common parasitic and fungal infections that cause granulomatous inflammation?
parasitic - schistosomiasis
fungal - histoplasma, cryptococcus
What are examples of inorganic metals/dust or foreign bodies that cause granulomatous inflammation?
inorganic metals - silicosis, beryliosis
foreign body - sutures, vascular grafts
What conditions cause unknown granulomatous inflammation?
sarcoidosis and ulcerative colitis
