Chronic Inflammation Flashcards
What is chronic inflammation?
A chronic response to injury with associated fibrosis
What is the timescale for chronic inflammation?
It is not rapid or immediate, and not short lived,
How does our knowledge of chronic inflammation differ from that of acute?
Less is known
Why is less known about chronic inflammation?
Because it’s so diverse
What does chronic inflammation overlap with?
Host immunity
How is the immune system different from chronic inflammation?
It’s very specific, and delivered by specific reactions with specific immunological reagents, whereas chronic inflammation is a generalised response to any injury
What is chronic inflammation usually associated with?
Some sort of the permanent tissue damage
What is the major difference between acute and chronic inflammation?
The long term outcomes are different
What are the long term outcomes of chronic inflammation?
No resolution, always leads to repair and scarring
Is function regained in chronic inflammation?
Sometimes
Can acute inflammation lead to chronic inflammation?
Yes, if the damage is not slight
When does chronic inflammation take over from acute?
If acute inflammatory processes don’t work immediately
If damage is too severe to be resolved within a few days
If infection arises
What is meant by chronic inflammation arising de novo?
When there is no acute phase- it goes straight to chronic
When may chronic infection arise de novo?
In some autoimmune conditions
In some chronic infections
Because of ‘chronic low level irritation’
Give an example of an autoimmune condition that can lead to chronic inflammation?
Rheumatoid arthritis
Why does chronic inflammation arise in some chronic infections?
Partly becomes of the bodies immunological response to them
What kind of inflammation does bacteria cause?
Acute
Give an example of an infection that causes chronic inflammation?
Vital hepatitis
What can chronic low level irritation be caused by?
A reaction to foreign material
How can a bone replacement cause chronic inflammation?
If there is a joint replacement, a lot of compounds are inserted during the operation which can cause chronic inflammation, e.g. cement and bone fragments
What may chronic inflammation develop alongside?
Acute inflammation
When may chronic inflammation arise alongside acute inflammation?
In severe persistent or repeated infection
Can repeated attacks of acute inflammation which get better result in chronic inflammation?
Yes
How is chronic inflammation characterised?
It’s microscopic appearance
How does the microscopic appearance of chronic inflammation differ from that of acute?
It is much more variable
What is the microscopic appearance of chronic inflammation characterised by?
What the cellular infiltrate is
What is the most important characteristic of the cellular infiltrate?
What type of cell is present
What cells are involved in chronic inflammation?
Macrophages Lymphocytes Plasma cells Eosionphils Fibroblasts/myofibroblasts
Are macrophages used in acute inflammation?
They may be important in resolving it
What are macrophages more specifically associated with?
Chronic inflammatory reactions
What do macrophages have lots of?
Granular cytoplasm
Why do macrophages have a lot of granular cytoplasm?
Because they have lots of organelles to do with their phagocytic process
What are macrophages derived from?
Blood monocyte
What is a monocyte?
What we call a macrophage when it’s circulating in the blood
When is a monocyte called a macrophage?
When it gets into tissues
In what manner do macrophages get activated?
In various levels
Why are the various levels of activation of the macrophage important?
Because it would be bad if the monocyte performed it’s function in the circulation
When do blood monocytes get activated?
In chronic inflammation
What are the functions of macrophages?
Phagocytosis and destruction of debris and bacteria
Processing and presentation of antigen to immune system
Synthesis of substances
Control of other cells by cytokine release
What do macrophages synthesise?
Cytokines
Complement components
Blood clotting factors
Proteases
What do cytokines do?
Communicate with other cells
What are lymphocytes sometimes called?
Chronic inflammatory cells
Why may it be inappropriate for lymphocytes to be called chronic inflammatory cells?
They are a normal component of many tissues
What parts of the body are populated with lymphocytes?
Lymph nodes, gut, airway and lots of other places
What are the functions of lymphocytes?
Complex
Mainly immunological
What do B lymphocytes do?
Differentiate to produce antibodies
What do T lymphocytes do?
Involved in control and some cytotoxic functions
Signal to other cells
What are plasma cells largely cells of?
Chronic inflammation reactions
Describe the structure of plasma cells?
Bilobed nucleus
Bright pink eosinophilic cytoplasm
What are plasma cells?
Differentiated antibody producing B lymphocytes
What do plasma cells do?
They are a factor synthesising and secreting lots of antibodies
What do plasma cells usually imply?
Considerable chronicity
Why do plasma cells usually imply considerable chronicity?
Because it takes about 7 days for a plasma cell to develop an antibody response, and a chronic inflammatory response gives that duration
What are eosionphils involved in?
Allergic reactions
Parasite infections
Some tumours
How are eosionphils involved in allergic reactions?
IGE related processes
What tumours are eosionphils involved in?
Certain lymphomas
What are fibroblasts/myofibroblasts?
Connective tissue cells
What do (myo)fibroblasts do?
Produce collagen responsible for fibrosis
What recruits (myo)fibroblasts?
Macropages
What are giant cells?
Multinucleate cells made by the fusion of macrophages
When are giant cells made?
In frustrated phagocytosis
What is frustrated phagocytosis?
A situation where macrophages alone can’t phagocytose the target
Give 3 types of giant cells
Langerhans
Foreign body type
Touton
What do Langerhans type giant cells look like?
Horseshoe of nuclei around the periphery
Have very pale, foamy cytoplasm
When do Langerhans type giant cells occur?
Usually in the context of TB
Why does TB form Langerhans type giant cells?
Myobacterium TB is very resistant to phagocytosis and destruction, so can survive in the organelle/cytoplasm of a macrophage. The macrophage forms a giant cell to try and deal with them
When do foreign body type giant cells occur?
When cells engulf foreign bodies of any sort, e.g. calcium, bone fragments
Where do touton giant cells usually occur?
In areas of fat necrosis, e.g. in adipocytes
Why does fat necrosis cause Touton giant cells?
When you get fat necrosis in areas of high fat content, a lot of fat needs to be phagocytosed- can’t cope
Is the morphology of chronic inflammations specific or non-specific?
Non-specificin most
Give 3 example of conditions where the proportions of each cell in chronic inflammation vary?
Rheumatoid arthritis
Chronic gastritis
Leishmaniasis
What cell types are present in chronic inflammation with rheumatoid arthritis?
Mainly plasma cells
What cell types are present in chronic inflammation with chronic gastritis?
Mainly lymphocytes
What cell types are present in chronic inflammation with Leishmaniasis?
Mainly macrophages
Why does Leishmaniasis produce chronic inflammation with mainly macrophages?
Protozoa parasites can survive in macrophages, so get lots of foamy macrophages reacting
How can the cell type present in chronic inflammation be helpful?
It can aid diagnosis
What are the effects of chronic inflammation?
Fibrosis Impaired function Rarely, increased function Atrophy Stimulation of the immune response
Where may fibrosis be a problem?
In the gall bladder
Chronic peptic ulcers
Cirrhosis
What is chronic cholecystitis?
A chronic inflammatory proces that leads to scarring of the gall bladder
Give an example of where chronic inflammation causes impaired function?
Chronic inflammatory bowel disease
Give two examples of where chronic inflammation can cause increased function
Mucus secretion
Thyrotoxicosis
Give an example of thyrotoxicosis?
Graves disease
What happens in Graves disease?
An antibody stimulates the TSH receptor, which leads to an excess of thyroxin
What is atrophy?
Loss of functional tissue mass
Give two examples of places that chronic inflammation can cause atrophy?
Gastric mucosa
Adrenal glands
How can chronic inflammation cause stimulation of the immune response?
Macrophage-lymphocyte interactions
Is the production of gall stones in the gall bladder a problem?
Not in itself
When is the production of gall stones a problem?
If they go into the cystic duct, they block bile flow.
Gall stones move about, and might eventually pass down the billary tree
What is the problem with a blockage of bile flow?
Bile is highly toxic, so its blockage causes tissue injury, leading to inflammation and ulceration in the gall bladder mucosa
What happens if gall stones pass down the billary tree?
They cause inflammatory damage to the billary epithelium
What is the net effect in patients with gall stones?
They get multiple, repeated episodes of acute inflammation, which over time develops into chronic inflammation
What is the problem once the gall bladder is chronically inflamed?
It won’t resolve, and therefore can’t get better
What does chronic inflammation in the gall bladder lead to?
Fibrosis of the gall bladder wall
What is an ulcer?
A full thickness defect in the mucosa, which can be caused by necrosis
What can gastric ulceration be caused by?
Acute gastritis or chronic gastritis
What causes acute gastritis?
Alcohol and drugs
What causes chronic inflammation?
Helicobacter pylori
When does ulceration occur?
Because of an imbalance of acid production and mucosal defence
How does gastric ulceration appear?
As a rounded, discreet area of mucosal necrosis
What happens if gastric ulcers don’t get better quickly?
Can get a lot of tissue damage and scarring
Is tissue damage and scarring in the stomach a problem?
Not in most of the stomach, however if the antrum or pyloris are scarred, can get gastic outlet obstruction
What is the problem with a gastric outlet obstruction?
It can affect the perilstaltic function of the stomach
What is inflammatory bowel disease?
The specific term for a family of idiopathic inflammatory diseases
What is meant by idiopathic?
Unknown cause
What does inflammatory bowel disease look like?
Get cobblestone mucosa
What gives the cobblestone mucosa appearance?
Islands of surviving mucosa, inbetween which are ulcers
How does inflammatory bowel disease usually present?
Most patients have relaxing and remitting course
Why do most patients have a relaxing and remitting course of inflammatory bowel disease?
Because they get attacks of acute inflammation which will convert asymptomatic chronic disease into something symptomatic
What are the symptoms of inflammatory bowel disease?
Bleeding and diarrhoea
Why does inflammatory bowel disease cause bleeding?
It ulcerates any mucosal surface, and so the protective mucosa underneath damaged
Why does inflammatory bowel disease cause diarrhoea?
The function of the colon is compromised by the degree of inflammation
What is the prognosis for inflammatory bowel disease?
It pretty much stays- it can get better or worse.
If treated, it can largely go away
What is the result of chronic inflammation to the bowel mucosa?
Chronic damage to the mucosa, leading to abnormal crypts and inflammation to the wall
What are the two types of inflammatory bowel disease?
Ulcerative colitis and Crohn’s disease
What is ulcerative colitis?
A superficial colonic disease, that leads to a lot of ulceration
What are the symptoms of ulcerative colitis?
Diarrhoea, bleeding
What is Crohn’s disease?
A transmural disease- inflammation through the full thickness of the bowel wall
What does Crohn’s disease lead to?
Strictures
Fistulae
What is a fistula?
An abnormal connection between two epithelium-lined organs
What is cirrhosis a consequence of?
Severe, chronic liver disease
What are the common causes of cirrhosis?
Alcohol Infection with HBV, HCV Immunological Fatty liver disease Drugs and toxins
How does a cirrotic liver usually appear?
Shrunken
Diffuse process with bands of fibrous tissue and nodules of regenerating liver
When does cirrhosis cause complications?
When the normal liver architecture is destroyed
What leads to cirrhosis?
Chronic inflammation with fibrosis, disorganisation of architecture and attempted regeneration
What happens in Graves disease?
Get antibodies produced by plasma cells in chronic inflammatory infiltrate that stimulate the TSH receptor that causes thyroid epithelial cells to produce thyroxin
How does an atrophic gastric mucosa appear?
Lots of lamina propria, lots of lymphocytes
Why are there lots of lymphocytes with an atrophic gastric mucosa?
Because the epithelium has been destroyed by lymphocytes
How does atrophic gastric mucosa cause problems?
Get loss of acid producing cells, giving achlorhydria
What problems can gastric mucosa atrophy cause?
Gastric cancer
What kind of disease is rheumatoid arthritis?
Autoimmune
What causes rheumatoid arthritis?
Localised and systemic immune response
What problem does the localised immune response cause in rheumatoid arthritis?
Localised chronic inflammation leads to joint destruction
What problem does the systemic immune response cause in rheumatoid arthritis?
Can affect other organs and amyloidosis
What is amyloidosis?
A chemical process where proteins that can be laid down as ß pleated sheets can cause tissue problems
How does chronic inflammation lead to amyloidosis?
It can lead to an increase in plasma proteins, and therefore cause amyloidosis
How does rheumatoid arthritis present?
Classically symmetrical disease of small joints of hands and feet, leading to ulnar deviation of the hands and marked swelling of the joints
How do chronic inflammation and immune responses overlap?
Immune diseases cause pathology by chronic inflammation
Chronic inflammatory processes can stimulate immune responses
What is granulomatous inflammation?
Chronic inflammation with granulomas
What is a granuloma?
A cohesive group of (usually) macrophages and other inflammatory cells
What do granulomas invariably have present?
Some other inflammatory cells, usually lymphocytes
Why do granulomas usually have lymphocytes present?
Because the role of T lymphocytes is in communicating with the macrophages with T helper cells, which is important in forming
What does a small granuloma consist of?
Epithelioid histiocytes on the inside
Lymphocytes on the outside
What are epithelioid histiocytes?
Modified, immobile macrophages
What do granulomas arise with?
Persistent, low-grade antigenic stimulation
Hypersensitivity
What are hypersensitivity reactions?
Pathological immunological reactions
What are the main causes of granulomatous inflammation?
Mildly irritant ‘foreign’ material
Infections
Granulomatous diseases of unknown cause
What infections can cause granulomatous inflammation?
Tuberculosis Leprosy Syphilis Chronic fungal infections Cat-scatch disease Xanthogranulomatous pyelonephritis and malakoplakia
What unknown causes can cause granulomatous inflammation?
Sarcoid
Wegener’s granulomatosis
Crohn’s disease
What is Wegener’s granulomatosis?
Granulomatous vasculitis, usually affecting the lung and kidneys
What can happen if a patient gets a bowel perforation?
Often see little granulomas of feacel material
What causes tuberculosis?
Mycobacteria, especially M. tuberculosis
What is the problem with M. TB?
It is difficult and slow to culture, so to be sure of a negative result, have to give 6 weeks growth time
What wall lipids do TB have?
Mycosides
What is the result of TBs wall lipids?
They can be taken up by phagocytosis and survive
How does TB cause disease?
By persistence (leading to chronic inflammation) and induction of cell-mediated immunity
Does TB produce toxins or lytic enzymes?
No
What does a TB granuloma have in the middle?
Caseous necrosis
What are the outcomes of TB?
Arrest, fibrosis and scarring
Erosion into bronchus
Tuberculous empyema
Erosion into blood stream
What is meant by arrest of TB?
The immune system controls it within granulomas
What can erosion of TB into the bronchus cause?
Bronchopneumonia
TB in GIT
How can TB get into the GIT?
If coughed up and swallowed
What is empyema?
Formation of pus in pleural
What happens is TB erodes into the blood stream?
It circulates in the blood and spreads to multiple organs
What is it called when there are many TB bugs?
Miliary tuberculosis
What is it called when there are few TB bugs?
Single organ TB
How does sarcoidosis manifest clinically?
Variably
Who does sarcoidosis occur in?
Young adult women
What does sarcoidosis produce?
Non-caseating granulomas and giant cells
What does sarcoidosis involve?
Usually upper air and digestive tract
Usually bilateral hylar lymph node
What does the severity of sarcoidosis depend on?
Location
What is Crohn’s disease?
Region enteritis- patchy full thickness inflammation throughout the bowl
