3 chronic inflammation Flashcards
Chronic inflammation is the host response to an ..1…. Trying to manage the …2… with some success ?
1 = insult
2 = insult
Chronic inflammation can …1… but also …2…
- last a long time (lifetime of patinet)
- resolve
Chronic inflammation can last a long time but also resolve but often with what ?
results that can be troublesome to the patient
List 4 possible troubles to a patient because of chronic inflammation
- fibrosis and malfunction of the organ
- deformity e.g. rheumatoid arthritis
- gradual organ destruction e.g tuberculosis
- pain
Host defences and response to chronic inflammation include ?
- natural barriers (skin , mucous membranes)
- innate immunity -> non-specific immune responses (phagocytic cells [neutrophils, macrophages], thier products)
- adaptive immunity -> specific immune responses (antibodies, lymphocytes)
How does acute insult lead to possible resolution or repair and scarring ?
- acute insult
- acute inflammation
- damage slight ? -> no -> chronic inflammation -> repair & scarring
- damage slight ? -> yes -> possible resolution
2 ways chronic inflammation arise?
- may ‘take over’ from acute inflammation
- may arise gradually without an obvious acute phase
How does chronic inflammation arise if it ‘takes over’ from acute inflammation ?
- insult / damage is too severe to be resolved within a few days
- or following persistent or recurrent acute episodes
How does chronic inflammation arise gradually without an obvious acute phase ?
- some chronic infections (e.g. hepatitis, B, C, Tuberculosis, leprosy)
- autoimmune conditions (e.g. RA)
- unknown aetiology / idiopathic
Clinical definition of ‘chronic’
> 6 weeks
Clinical features of chronic inflammation?
may be similar to acute inflammation :
* pain (dolor)
* loss of function
* rubor (redness)
* swelling (tumor)
* heat (calor)
On inspection what tissue is seen in chronic inflammation
granulation
what is chronic inflammation characterised by ?
microscopic appearances which are much more variable than acute inflammation
An important characteristic of chronic inflammation is ?
the predominant type of cell present
6 typical features of chronic inflammation in terms of microscopic appearances ?
[Question to CE are polymorphs neutrophils]
- macrophages
- lymphocytes
- plasma cells
- absence of polymorphs (cells with more than one morphology e.g. granulocytes , neutrophils !!)
- proliferation of fibroblasts with collagen production leading to fibrosis
- angiogenesis (formation of new blood vessels from pre-existing vessels)
Where are macrophages derived from ?
blood monocytes
Which inflammation type are macrophages important in ?
both acute and chronic
Functions of macrophages
- phagocytosis and destruction of debris & bacteria
- Processing and presentation of antigen to immune system (APCs)
- synthesis of cytokines e.g. interleukins, TNF
- control of other cells by releasing : EGF, FGF, PDGF
- induce fibrosis and angiogenesis needed for healing
What is EGF ?
epidermal growth factor
what is FGF ?
fibroblast growth factors
what is PDGF ?
platelet-derived growth factor
What are 3 growth factors that macrophages need to release to control other cells ?
- EGF = epidermal growth factor
- FGF = fibroblast growth factor
- PDGF = platelet-derived growth factor
Name 3 cells under the term ‘lymphocytes’
- B-cells
- T-cell
- NK cells
% of cicrulating leukocytes that lymphocytes constitute of ?
25 - 33 %
diameter of lymphocytes ?
~ 10 µm
Why are B- and T- lymphocytes unusual in terms of their genomic DNA?
it undergoes somatic rearrangements to create a vast repertoire of cell surface receptors
How many years can memory B-cells live for ?
many
How do lymphocytes appear in blood smears ?
spherical with thin strip of cytoplasm surrounding a regularly-shaped nucleus
How do B-lymphocytes create a repertoire of antibodies to be able to recognise a vareity of antigens ?
‘shuffle’ the DNA encoding their immunoglobulins
What will happen if a B-cell is presented to a foreign antigen that it ‘recognises’ ?
It will proliferate (under the control of T-helper cells) to form a population of plasma cells producing antibodies specific for that antigen
What a long-lived memory B-lymphocytes able to do ?
expand again following re-exposure to the antigen
Where do T-lymphocytes originate and mature in ?
originate -> bone marrow
mature -> thymus or in adults spleen
what happens to T-lymphocytes when they mature in the thymus or spleen ?
undergo rearrangement of their T-cell receptor genes
What do CD4+ (T helper) cell induce ?
proliferation and differentiation of T&B cells, and activate macrophages
What do T-cytotoxic (CD8+) cells induce ?
apoptosis in cell that present foreign antigens in the correct MHC context by punching holes in the plasma membrane and injecting perforins or granzyme
NK cells produce ..1…. and are an important component of ..2…
- a rapid response to viral infection
- innate immunity
what do NK cells recognise ?
“stressed” cells like tumour cells
What’s the mechanism of killing that NK cells have ?
similar to cytotoxic T cells but without the requirement for MHC presentation
Apart from macrophages, lymphocytes (B&T), NK cells what other cells are involved in the chronic inflammatory response ?
- plasma cells
- eosinophils are related to neutrophils
- fibroblasts / myofibroblasts
Plasma cells are differentiated ….1….. lymphocytes
usually implies considerable …2…
- antibody - producing B
- chronicity
Name some conditions in which trigger eosinophilia
- allergic reactions
- parasite infestations
- some forms of vasculitis
- some tumours
Fibroblasts / myofibroblasts are recruited by ..1…. and make …2…
- macrophages
- collagen and elastin
In the bladder wall where are massive eosinophilia found ?
around schistosome eggs
what are giant cells ?
multinucleate cells made by fusion of macrophages
3 types of recognised giant cells?
- langhans giant cell -> tuberculosis
- foreign body type -> adaptive/memory immunity NOT involved
- touton type -> pale cytoplasm = lipid phagocytosed
In touton giant cell what does the pale cytoplasm indicate ?
lipid phagocytosed
when does frustrated phagocytosis occur ?
when a cell (usually macrophage) attempts to engulf a larger particle but is unable to complete the process whcih can lead to the formation of giant cells
What pathology do T-cell mediated immunity usually involve ?
Langhans type giant cell
How is the nuclei in Langhans giant cell arranged ?
around the periphery of the giant cell
- How is the nuclei of foreign body type giant cell arranged ?
- often seen when what is present e.g. ?
- randomly in cell
- foreign body is present e.g. surgical suture
How is the nuclei of a touton giant cell arranged ?
In a ring structure towards the centre of the cell
Where are touton giant cells often found ? [alter later]
In lesions with a high lipid content such as fat necrosis and xanthomas
Toutan giant cells are often found in lesions with a high lipid content, additionally what do these lesions typically contain ? [alter later]
foam cells, which are macrophages laden with lipids
Of most chronic inflammatory reactions what is the morphology
non-specific
In most chronic inflammatory reactions although the morphology is non-specific, what about the proportions of each cell type ?
It may vary in different conditions
In rheumatoid arthritis, mainly what cell type can be observed?
plasma cells
In chronic gastritis, mainly what cell type can be observed ?
lymphocytes and plasma cells
In leishmaniasis (protozoal parasite), mainly what cell type can be observed?
macrophages
Drugs that would worsen chronic peptic ulcer ? [alter after lecture !]
- NSAID (non-steroidal anti-inflammatory drugs)
- genetic
- alcohol
- cigarettes
- steroids
2 potential complications that could arise from chronic peptic ulcer
- fibrosis - narrowing
- pyloric stenosis (can obstruct the passage of food from the stomach into the small intestine)
is chronic peptic ulcer common ?
it was common a few decades ago
Example of fibrosis and impaired function as an effect of chronic inflammation
hepatitis and cirrhosis
Explain hepetitis and cirrhosis as an effect of chronic inflammation from fibrosis and impaired function [alter question!]
Inflammation with destruction of …1…., fibrosis and ..2…. regeneration to ..3…
- hepatocytes
- hodular
- cirrhosis
5 common causes of cirrhosis
- Alcohol
- Fatty liver disease
- Infection with HBV, HCV (Hepatitis B and hepatitic C virus)
- Immunological- primary biliary cirrhosis
- Idiopathic, unknown
3 complications of liver cirrhosis
- portal hypertension
- liver failure
- hepatocellular carcinoma
In cirrhosis under the microscope what colour is fibrous tissue ?
blue
what is chronic cholecystitis ?
chronic swelling (inflammation) and irritation of the gallbladder that occurs over time
Granulation tissue :
* ..1.. reaction to injury
* influx of ..2.. cells - all types
* ..3… proliferation
* ..4… of agents
* …5… lay down …6…
* when scraped ‘..7…’
* nothing to do with ..8…
- universal body
- inflammatory
- blood vessel
- phagocytosis
- fibroblasts
- fibrous tissue
- granulates
- granuloma
what features reflects the chronic inflammatory process that characterizes conditions like inflammatory bowel disease?
- oedematous mucosa
- ulceration
- scar tissue
- What type of disease is inflammatory bowel disease ?
- affecting what ?
- idiopathic inflammatory disease
- large and small bowel
Inflammatory bowel disease presents with what ?
GI symptoms
* abdominal pain
* diarrhoea
* rectal bleeding
sometimes non-GI symptoms e.g. uveitis (inflammatory condition affecting middle layer of eye)
2 conditions that inflammatory bowel disease contains ?
- ulcerative colitis
- crohn’s disease
What part of the body does Crohn’s disease involve ?
may involve any part of GI tract
Features of crohn’s disease
- skip lesions
- granulomas
- transmural inflammation causing pain
- loose stools
- malabsorption
- fibrosis leading to obstruction / strictures
- full thickness inflammation leading to fistula formation
What are skip lesion in the context of crohn’s disease ?
patches of inflamed tissue that are separated by segments of healthy tissue
characteristic pattern of inflammation that distinguishes Crohn’s disease from other IBD’s like ulcerative colitis
What are granulomas, and how are they related to Crohn’s disease?
Granulomas are small collections of immune cells that form in response to chronic inflammation.
characteristic feature of Crohn’s disease and can be found in the affected tissue, helping to confirm the diagnosis
How does transmural inflammation contribute to the symptoms of Crohn’s disease?
involves inflammation that extends through the entire thickness of the intestinal wall
can cause abdominal pain , which result from disruption of normal intestinal function , symptoms can vary in severity and may come and go over time
How does Crohn’s disease affect the process of nutrient absorption in the GI tract?
impair the absorption of nutrients from food due to inflammation and damage to the intestinal lining.
leading to malabsorption of essential nutrients
What is full-thickness inflammation ?
Full-thickness inflammation involves inflammation that extends through all layers of the intestinal wall.
What part of the GI tract is primarily affected by ulcerative colitis (UC)?
primarily affects the large bowel , approx 90% cases involving the rectum
Are granulomas typically present in the affected tissue in ulcerative colitis (UC)?
no granulomas unlike Crohn’s disease
What is the potential complication of ulcerative colitis (UC) in terms of malignant changes?
an increased risk of developing colorectal cancer, particularly in cases of long-standing, extensive disease involving a significant portion of the colon and rectum.
What characterizes the pattern of inflammation in ulcerative colitis (UC)?
continuous mucosal inflammation along the lining of the colon and rectum. This inflammation is typically uniform and does not involve skip lesions.
Characteristic features of ulcerative colitis (UC) :
- affects large bowel (approx 90% rectum)
- continuous mucosal inflammation no skip lesions
- no granulomas like Crohn’s
- malignant change possible
What type of disease is thyrotoxicosis (grave’s disease) ?
autoimmune
Difference between crohn’s disease and ulcerative colitis IBD
Crohn’s Disease
* May involve any part of the GI tract
* Involves granuloma formation
Ulcerative colitis
* Usually involves the large bowel (90% - rectum)
* No granuloma formation
Symptoms of thyrotoxicosis (grave’s disease)
- exophthalmos (protruding eyes)
- thyrotoxic signs (palpitations, tremor)
- enlarged thyroid (multinodular toxic goitre)
Pathogenesis of thyrotoxicosis (grave’s disease)
- autoantibodies - long-acting thyroid stimulating antibodies - TSI (thyroid stimulating immunoglobulin)
- TSI antibody acts on TSH surface receptor on thyroid epithelium and it mimics TSH
- increased T4 and T3, reduced TSH
- hyperactive thyroid (hyperthyroidism)
an example where atrophy can be observed in a disease pathogenesis is one chronic condition of the gut known as ?
autoimmune gastritis
An example where inappropriate immune response can be observed in a disease pathogenesis is one chronic condition of the joints known as ?
rheumatoid arthritis
Name some examples of atopic diseases characterised by inappropriate immune responses to relatively innocuous everyday substances
1) Asthma
2) Hay-fever
3) Eczema
4) Food allergies
5) Anaphylaxis
How do immune diseases cause pathology ?
chronic inflammation
What does chronic inflammation overlap with ?
immune responses
Ratio of RA in female and males
female: male = 3:1
RA involves systemic immune response like what ?
- rheumatoid nodules
- splenomegaly
- amyloidosis
- pulmonary fibrosis
RA (rheumatoid arthritis):
* quite ..1…
* …2… disease
* ….3… affects joints
* localised …4…. inflammation leads to …5.. destruction - ..6… joints
- common
- systemic
- invariably
- chronic
- joint
- small
What is granulomatous inflammation ?
chronic inflammation with granulomas
What is a granuloma ?
what is nuclei shape ?
organised collection of epithelioid cells which are modified/activated macrophages, often have elongated banana-like nuclei
granulomas mar or may not contain / be what ?
- contain giant cells
- be necrotic
what do foreign body granulomas deal with ?
- particles which are poorly soluble (foreign bodies)
- organisms difficult to eliminate (mycobacterium tuberculosis or mycobacterium leprae) - but fail, so need to bring in…
examples of foriegn body granulomas that are organisms that are difficult to eliminate
- mycobacterium tuberculosis
- mycobacterium leprae
what is a immune granuloma ?
granuloma caused by a variety of agents that are capable of inducing cell-mediated response ; known as tubercles
3 Main causes of granulomatous inflammation
- mildly irritant ‘foreign’ material
- infectious
- unknown causes
example of mildly irritant ‘foreign’ material as a cause of granulomatous inflammation
suture material
examples of infections that are a cause of granulomatous inflammation
- mycobacteria: tuberculosis, leprosy
- other infections e.g. some fungi
name 3 unknown causes of granulomatous inflammation
- sarcoidosis
- granulomatosis with polyangiitis GPA (was Wegner’s granulomatosis)
- Crohn’s disease
What bacteria causes tuberculosis ?
mycobacterium tuberculosis
- what adaptations does mycobacterium tuberculosis have to evade immune response ?
- what stain ?
- thick waxy wall of lipids (mycolic acid) that protects against ROS
- Ziel-neelsen stain
How does M. tuberculosis cause disease ?
by persistence and induction of cell - mediated immunity
What is not produced by M. tuberculosis ?
toxins or lytic enzymes
Caseating granuloma ?
central necrosis ; characteristic of TB and fungal infections
what is ghon focus ?
formation of a granuloma, or walled off area of bacteria, which is considered the primary lung lesion in tuberculosis (primary subpleural lesion caused by TB bacilli)
what is latent TB ?
asymptomatic, noncontagious but infected by TB - results in positive tuberculin skin test / TB blood test must be treated regardless
TB can erode into the bronchus leading to ?
tuberculous bronchopenumonia
What can haematogenous spread of tubercle bacilli lead to?
infection spreading anywhere in the body -> lead to miliary tuberculosis
what is miliary TB ?
- may complicate primary or reactivation disease
- hematogenous dissemination
- diffuse bilateral 2- to 3-mm pulmonary nodules
Miliary TB generalised symptoms ?
- malaise
- fever
- loss of appetite
- cachexia = weakness/ wasting of body due to chronic illness
some examples of other granulomatous infections
- leprosy
- syphilis
- chronic fungal infections
- cat-scratch disease
what does tumour necrosis factor (TNF) cause ?
- migration of fibroblasts
- proliferation of fibroblasts
- secretion of collagenase
what does vascular endothelial growth factor (VEGF) cause ?
- development of blood vessels in chronic inflammation (angiogenesis)
- wound healing
- tumours
what does epidermal growth factor (EGF) cause ?
mitosis in fibroblasts, epithelial cells and hepatocytes
What does platelet derived growth factor (PDGF) cause?
migration and proliferation of fibroblasts, smooth muscle cells and monocytes which can differentiate into macrophages and myeloid lineage dendritic cells
sarcoidosis:
* …1… clinical manifestations
* commoner in ….2…
* involves …3… nodes, lungs, ….4… granulomas, ..5… cells
- variable
- young adult women
- lymph
- non-caseating
- giant
3 granulomatous diseases of unknown cause
- sarcoidosis
- crohn’s disease
- granulomatosis with polyangiitis (GPA)
