3 chronic inflammation Flashcards
(129 cards)
1
Q
Chronic inflammation is the host response to an ..1…. Trying to manage the …2… with some success ?
A
1 = insult
2 = insult
2
Q
Chronic inflammation can …1… but also …2…
A
- last a long time (lifetime of patinet)
- resolve
3
Q
Chronic inflammation can last a long time but also resolve but often with what ?
A
results that can be troublesome to the patient
4
Q
List 4 possible troubles to a patient because of chronic inflammation
A
- fibrosis and malfunction of the organ
- deformity e.g. rheumatoid arthritis
- gradual organ destruction e.g tuberculosis
- pain
5
Q
Host defences and response to chronic inflammation include ?
A
- natural barriers (skin , mucous membranes)
- innate immunity -> non-specific immune responses (phagocytic cells [neutrophils, macrophages], thier products)
- adaptive immunity -> specific immune responses (antibodies, lymphocytes)
6
Q
How does acute insult lead to possible resolution or repair and scarring ?
A
- acute insult
- acute inflammation
- damage slight ? -> no -> chronic inflammation -> repair & scarring
- damage slight ? -> yes -> possible resolution
7
Q
2 ways chronic inflammation arise?
A
- may ‘take over’ from acute inflammation
- may arise gradually without an obvious acute phase
8
Q
How does chronic inflammation arise if it ‘takes over’ from acute inflammation ?
A
- insult / damage is too severe to be resolved within a few days
- or following persistent or recurrent acute episodes
9
Q
How does chronic inflammation arise gradually without an obvious acute phase ?
A
- some chronic infections (e.g. hepatitis, B, C, Tuberculosis, leprosy)
- autoimmune conditions (e.g. RA)
- unknown aetiology / idiopathic
10
Q
Clinical definition of ‘chronic’
A
> 6 weeks
11
Q
Clinical features of chronic inflammation?
A
may be similar to acute inflammation :
* pain (dolor)
* loss of function
* rubor (redness)
* swelling (tumor)
* heat (calor)
12
Q
On inspection what tissue is seen in chronic inflammation
A
granulation
13
Q
what is chronic inflammation characterised by ?
A
microscopic appearances which are much more variable than acute inflammation
14
Q
An important characteristic of chronic inflammation is ?
A
the predominant type of cell present
15
Q
6 typical features of chronic inflammation in terms of microscopic appearances ?
[Question to CE are polymorphs neutrophils]
A
- 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)
16
Q
Where are macrophages derived from ?
A
blood monocytes
17
Q
Which inflammation type are macrophages important in ?
A
both acute and chronic
18
Q
Functions of macrophages
A
- 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
19
Q
What is EGF ?
A
epidermal growth factor
20
Q
what is FGF ?
A
fibroblast growth factors
21
Q
what is PDGF ?
A
platelet-derived growth factor
22
Q
What are 3 growth factors that macrophages need to release to control other cells ?
A
- EGF = epidermal growth factor
- FGF = fibroblast growth factor
- PDGF = platelet-derived growth factor
23
Q
Name 3 cells under the term ‘lymphocytes’
A
- B-cells
- T-cell
- NK cells
24
Q
% of cicrulating leukocytes that lymphocytes constitute of ?
A
25 - 33 %
25
diameter of lymphocytes ?
~ 10 µm
26
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
27
How many years can memory B-cells live for ?
many
28
How do lymphocytes appear in blood smears ?
spherical with thin strip of cytoplasm surrounding a regularly-shaped nucleus
29
How do B-lymphocytes create a repertoire of antibodies to be able to recognise a vareity of antigens ?
'shuffle' the DNA encoding their immunoglobulins
30
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
31
What a long-lived memory B-lymphocytes able to do ?
expand again following re-exposure to the antigen
32
Where do T-lymphocytes originate and mature in ?
originate -> bone marrow
mature -> thymus or in adults spleen
33
what happens to T-lymphocytes when they mature in the thymus or spleen ?
undergo rearrangement of their T-cell receptor genes
34
What do CD4+ (T helper) cell induce ?
proliferation and differentiation of T&B cells, and activate macrophages
35
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
36
NK cells produce ..1.... and are an important component of ..2...
1. a rapid response to viral infection
2. innate immunity
37
what do NK cells recognise ?
"stressed" cells like tumour cells
38
What's the mechanism of killing that NK cells have ?
similar to cytotoxic T cells but without the requirement for MHC presentation
39
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
40
Plasma cells are differentiated ....1..... lymphocytes
usually implies considerable ...2...
1. antibody - producing B
2. chronicity
41
Name some conditions in which trigger eosinophilia
* allergic reactions
* parasite infestations
* some forms of vasculitis
* some tumours
42
Fibroblasts / myofibroblasts are recruited by ..1.... and make ...2...
1. macrophages
2. collagen and elastin
43
In the bladder wall where are massive eosinophilia found ?
around schistosome eggs
44
what are giant cells ?
multinucleate cells made by fusion of macrophages
45
3 types of recognised giant cells?
* langhans giant cell -> tuberculosis
* foreign body type -> adaptive/memory immunity NOT involved
* touton type -> pale cytoplasm = lipid phagocytosed
46
In touton giant cell what does the pale cytoplasm indicate ?
lipid phagocytosed
47
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
48
What pathology do T-cell mediated immunity usually involve ?
Langhans type giant cell
49
How is the nuclei in Langhans giant cell arranged ?
around the periphery of the giant cell
50
1. How is the nuclei of foreign body type giant cell arranged ?
2. often seen when what is present e.g. ?
1. randomly in cell
2. foreign body is present e.g. surgical suture
51
How is the nuclei of a touton giant cell arranged ?
In a ring structure towards the centre of the cell
52
Where are touton giant cells often found ? [alter later]
In lesions with a high lipid content such as fat necrosis and xanthomas
53
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
54
Of most chronic inflammatory reactions what is the morphology
non-specific
55
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
56
In rheumatoid arthritis, mainly what cell type can be observed?
plasma cells
57
In chronic gastritis, mainly what cell type can be observed ?
lymphocytes and plasma cells
58
In leishmaniasis (protozoal parasite), mainly what cell type can be observed?
macrophages
59
60
61
62
63
64
Drugs that would worsen chronic peptic ulcer ? [alter after lecture !]
* NSAID (non-steroidal anti-inflammatory drugs)
* genetic
* alcohol
* cigarettes
* steroids
65
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)
66
is chronic peptic ulcer common ?
it was common a few decades ago
67
Example of fibrosis and impaired function as an effect of chronic inflammation
hepatitis and cirrhosis
68
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...
1. hepatocytes
2. hodular
3. cirrhosis
69
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
70
3 complications of liver cirrhosis
* portal hypertension
* liver failure
* hepatocellular carcinoma
71
In cirrhosis under the microscope what colour is fibrous tissue ?
blue
72
what is chronic cholecystitis ?
chronic swelling (inflammation) and irritation of the gallbladder that occurs over time
73
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...
1. universal body
2. inflammatory
3. blood vessel
4. phagocytosis
5. fibroblasts
6. fibrous tissue
7. granulates
8. granuloma
74
what features reflects the chronic inflammatory process that characterizes conditions like inflammatory bowel disease?
* oedematous mucosa
* ulceration
* scar tissue
75
1. What type of disease is inflammatory bowel disease ?
2. affecting what ?
1. idiopathic inflammatory disease
2. large and small bowel
76
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)
77
2 conditions that inflammatory bowel disease contains ?
* ulcerative colitis
* crohn's disease
78
What part of the body does Crohn's disease involve ?
may involve any part of GI tract
79
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
80
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
81
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
82
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
83
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
84
What is full-thickness inflammation ?
Full-thickness inflammation involves inflammation that extends through all layers of the intestinal wall.
85
What part of the GI tract is primarily affected by ulcerative colitis (UC)?
primarily affects the large bowel , approx 90% cases involving the rectum
86
Are granulomas typically present in the affected tissue in ulcerative colitis (UC)?
no granulomas unlike Crohn's disease
87
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.
88
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.
89
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
90
What type of disease is thyrotoxicosis (grave's disease) ?
autoimmune
91
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
92
Symptoms of thyrotoxicosis (grave's disease)
* exophthalmos (protruding eyes)
* thyrotoxic signs (palpitations, tremor)
* enlarged thyroid (multinodular toxic goitre)
93
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)
94
an example where atrophy can be observed in a disease pathogenesis is one chronic condition of the gut known as ?
autoimmune gastritis
95
An example where inappropriate immune response can be observed in a disease pathogenesis is one chronic condition of the joints known as ?
rheumatoid arthritis
96
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
97
How do immune diseases cause pathology ?
chronic inflammation
98
What does chronic inflammation overlap with ?
immune responses
99
Ratio of RA in female and males
female: male = 3:1
100
RA involves systemic immune response like what ?
* rheumatoid nodules
* splenomegaly
* amyloidosis
* pulmonary fibrosis
101
RA (rheumatoid arthritis):
* quite ..1...
* ...2... disease
* ....3... affects joints
* localised ...4.... inflammation leads to ...5.. destruction - ..6... joints
1. common
2. systemic
3. invariably
4. chronic
5. joint
6. small
102
What is granulomatous inflammation ?
chronic inflammation with granulomas
103
What is a granuloma ?
what is nuclei shape ?
organised collection of epithelioid cells which are modified/activated macrophages, often have elongated banana-like nuclei
104
granulomas mar or may not contain / be what ?
1. contain giant cells
2. be necrotic
105
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...
106
examples of foriegn body granulomas that are organisms that are difficult to eliminate
* mycobacterium tuberculosis
* mycobacterium leprae
107
what is a immune granuloma ?
granuloma caused by a variety of agents that are capable of inducing cell-mediated response ; known as tubercles
108
3 Main causes of granulomatous inflammation
1. mildly irritant 'foreign' material
2. infectious
3. unknown causes
109
example of mildly irritant 'foreign' material as a cause of granulomatous inflammation
suture material
110
examples of infections that are a cause of granulomatous inflammation
* mycobacteria: tuberculosis, leprosy
* other infections e.g. some fungi
111
name 3 unknown causes of granulomatous inflammation
* sarcoidosis
* granulomatosis with polyangiitis GPA (was Wegner's granulomatosis)
* Crohn's disease
112
What bacteria causes tuberculosis ?
mycobacterium tuberculosis
113
1. what adaptations does mycobacterium tuberculosis have to evade immune response ?
2. what stain ?
1. thick waxy wall of lipids (mycolic acid) that protects against ROS
2. Ziel-neelsen stain
114
How does M. tuberculosis cause disease ?
by persistence and induction of cell - mediated immunity
115
What is not produced by M. tuberculosis ?
toxins or lytic enzymes
116
Caseating granuloma ?
central necrosis ; characteristic of TB and fungal infections
117
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)
118
what is latent TB ?
asymptomatic, noncontagious but infected by TB - results in positive tuberculin skin test / TB blood test must be treated regardless
119
TB can erode into the bronchus leading to ?
tuberculous bronchopenumonia
120
What can haematogenous spread of tubercle bacilli lead to?
infection spreading anywhere in the body -> lead to miliary tuberculosis
121
what is miliary TB ?
* may complicate primary or reactivation disease
* hematogenous dissemination
* diffuse bilateral 2- to 3-mm pulmonary nodules
122
Miliary TB generalised symptoms ?
* malaise
* fever
* loss of appetite
* cachexia = weakness/ wasting of body due to chronic illness
123
some examples of other granulomatous infections
* leprosy
* syphilis
* chronic fungal infections
* cat-scratch disease
124
what does tumour necrosis factor (TNF) cause ?
* migration of fibroblasts
* proliferation of fibroblasts
* secretion of collagenase
125
what does vascular endothelial growth factor (VEGF) cause ?
* development of blood vessels in chronic inflammation (angiogenesis)
* wound healing
* tumours
126
what does epidermal growth factor (EGF) cause ?
mitosis in fibroblasts, epithelial cells and hepatocytes
127
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
128
sarcoidosis:
* ...1... clinical manifestations
* commoner in ....2...
* involves ...3... nodes, lungs, ....4... granulomas, ..5... cells
1. variable
2. young adult women
3. lymph
4. non-caseating
5. giant
129
3 granulomatous diseases of unknown cause
* sarcoidosis
* crohn's disease
* granulomatosis with polyangiitis (GPA)
