Week 3 - Tutorial - Immunopathology Flashcards
List 3 types of chronic inflammation which can lead to cancer. (provide specifics of both the inflammation & cancer)
Could be any 3 of the following
- Chronic Ulcerative Colitis = Colon Cancer
- Chronic Hepatitis B or C = Liver Cancer
- Chronic Obstructive Pulmonary Disease (COPD) or asthma = lung cancer
- Chronic Cystitis = Bladder Cancer
- Sjogren syndrome = lymphoma
- Chronic Thyroiditis = lymphoma
- Fibrocystic breast disease = breast cancer
- Benign Prostatic Hyperplasia = prostate cancer
How does chronic inflammation develop into a tumour?
(can enter at any stage)
- Cells transform
- Primary growth
- Metastasis
What does a loss in gut bacteria cause? (could be one of 3 reasons)
- loss in gut bacteria =
- loss of barrier function
- increase commensal penetration
- increase inflammation
- = enhanced tumour growth
- Pathobiont-mediated tumorigenesis
- potentially pathogenic commensal strains enhance tumorigenesis
- use TH17 cells
- inflammation
- Dysbiosis-mediated inflammation
- loss of host-related innate sensing platforms
- = pertubation of microbiota composition and function
- = tumour growth enhanced
How do Inflammatory Cells help tumour cells?
Inflammatory cells release;
- Growth Factors
- TNF
- IL-1
- Survival Factors
- TNF
- IL-1
- IL-6
- CXCL8
- VEGF
- CSF1
Which alter the gene expression of the cell & thus promotes its survival & makes it flourish (specifically through action of IL-2)
What are the primary sources of Chronic Liver Disease?
- 26% Hepatitis C Virus
- 24% Alcohol
- 17% Unknown
- 14% Hepatitis C virus and Alcohol
- 11% Hepatitis B Virus
- 5% Other
- 3% Hepatitis B virus & alcohol
aka Hepatitis B & C main
although data was taken in Alabama
What are the main causes of Hepatitis C?
- 60% Injecting Drug use
- 15% Sexual
- 10% Transfusion (occurred before screening)
- 10% Unknown
- 4% Occupational
- 1% other (Nosocomial, iatrogenic, prenatal)
What does iatrogenic mean?
Means diseases that occurred due to a harmful complication, or other ill effects by any medical activity, including diagnosis, intervention, error, or negligence.
What is the progression of Chronic Liver Disease (CLD)?
How quickly can the liver regenerate itself?
~2 months
What is the prognosis of CLD?
1 in 4 die (aka v bad)
What is the progression of a healthy liver to liver cancer? Describe the 4 stages. (hint 2 have been said)
- Healthy liver
- normal
- Fibrotic Liver
- continuous inflammation
- if caused by Hep B
- lead to fibrosis aka HEALING WITH SCARRING
- ie formation of scar tissue
- Cirrhotic liver
- scar tissue replaces normal, healthy tissue
- blocks flow of blood through liver
- prevents norm function
- Liver Cancer
- formation of malignant tumours in liver
What does HCC stand for?
Hepatocellular carcinoma
How is Chronic liver disease diagnosed?
- Computed Tomography
- aka ultrasound
- to see if there are any visible lesions
- If yes, a percutaneous biopsy of lesions
- examination under microscope to compare morphology
- diagnose stage & prognosis
What are some factors that may cause liver inflammation?
- HBV & HCV (more so HCV as there is no vaccine)
- Non-Alcoholic Steatohepatitis (NASH)
- Alcohol
- Diabetes
- Aflatoxins
- abnormalities in TGF-β1 pathway
- p53 family abnormalities (as v important in killing cancer)
Which one is healthy? What is the other? Why do you think this?
- Left = Healthy
- normal
- Right = cirrhosis of liver
- many lymphoid cell infiltration
- more scar tissue (white)
Which of these is infecter and which is uninfected? What disease could it be & why?
- Left = unifected
- Right = infected
- probs HCV as
- its liver
- infiltration of lymphocytes is seen
- and connective tissue is being placed down
- probs HCV as
What is AFP & what is it a marker for?
Alpha-fetoprotein (AFP)
is a marker for some cancers specifically in the liver
If a patient has Hepatocellular Carcinomas (HCC) then they have a 34% chance of getting what disease?
HCC leads to pulmonary (lung) metastasis
What are the main treatment options for Liver Cancer?
- Liver Transplant
- Trans-Catheter Arterial Chemobolisation (TACE) - for patients who are not suitable for a liver transplant
What is TACE?
Trans-catheter arterial chemobolization
What is the main aim of TACE and how does it work?
- Aim = procedure performed in intentional radiology to restrict a tumour’s blood supply
- combines chemotherapy with embolization
- small embolic particles coated with chemotherapeutic drugs are injected selectively through a catheter into an artery that is directly supplying the tumour
- Particles block blood supply & induce cytotoxicity
What are the two main mechanisms that are beneficial to TACE?
- The typical blood supply of hepatic tumours
- The ability to deliver a higher dose of chemotherapeutic drugs
How is the blood supply of hepatic tumours beneficial to TACE?
- Most tumours are supplied by the PROPER HEPATIC ARTERY
- embolisation ideally interrupts the tumours blood supply through the blockage of the vessel
- this stalls growth until neovascularisation occurs
Why can higher doses be given during TACE?
- Higher doses of chemotherapeutic drugs can be given
- as it is being delivered to a focused area
- decreases systemic exposure (which is usually the limiting factor of doses)
- occurs due to increase likeliness that drugs
- arent washed out from the tumour’s vascular bed
- higher concentration of the drug to be in contact with tumour for a longer period of time
The intra-tumour concentration of chemotherapeutic is 10 times greater in ____ than _____
a. proper hepatic artery
b. portal vein
What does embolization induce?
induces ischemic necrosis of tumour
which causes a failure of transmembrane pump = greater absorption of agents by tumour cells
What is Ulcerative colitis?
is chronic inflammation of the bowel (colon) or digestive tract which can result in formation ulcers
What is 5-ASA and what does it do?
5-ASA = 5 amino-salicylate
is used to monitor mild to moderate IBM as it is an anti-metabolite
How is ulcerative colitis (UC) diagnosed?
- After diagnosis person has annual colonoscopies to monitor condition
- If surface of lesion is irregular & margin was unclear
- Biopsy is taken & cells
- if surrounding colonic mucosa is pale and rough = quisenct phase of UC activity
- if lesion biopsy shows well differentiated tubular adenocarcinomas then
- Computed tomography is done to see extent of swelling of digestive system
What is the main problem after a colectomy is performed?
Managing every day life as faeces cannot be controlled as you cannot feel them coming out
Where does ulcerative colitis begin?
Starts at rectum & may extend for a variable distance around the colon
What are some of the hypotheses of the aetiology of ulcerative colitis?
- Psychosomatic cause
- stress is believed to exacerbate disease in some individuals
- Infective Cause
- adhesive of enteropathogenic E. coli may trigger episodes of inflammation
- Immunological cause
- lymphoid cells participate in inflammation
- antibodies & immune complexes have been seen in some cases
- steroids are effective in treatment as they’re anti-inflammatories
- infection triggers inappropriate autoimmune response = leads to destruction of colonic mucosa
- p53 involvement
In active ulcerative colitis what are the effects of;
(a) ulcerated areas
(b) crypt abscesses
a. ulcerated areas are haemorrhagic = bloody diarrhea
b. is a collection of neutrophils = increase lymphoid cells and plasma cells in lamina propria = oedema or swelling
What are the local effects of ulcerative colitis?
LOCAL
- blood and fluid loss from extensive ulceration
- may be severe
- acute disease may process rapidly to toxic dilation & perforation
- in long standing disease = dysplasia and neoplastic changes may occur
What are the Systemic effects of ulcerative colitis?
extra-intestinal manifestations e.g.
fever
inflammation of eyes or joints
ulcers of the mouth
inflamed nodules on the shins.
List 3 other conditions which may be associated with ulcerative colitis?
Can list any of the following
- migratory polyarthritis (pain, swelling & joint stiffness)
- sacroiliitis (inflammation of both sacroiliac joints)
- ankylosing spondylitis (an inflammatory disease that over time causes vertebrae to fuse)
- uveitis (inflammation of the uvea = eye redness, pain & blurred vision)
- erythema nodosum (is a panniculitis (skin inflammation) that affects the subcutaneous fat in the skin)
- primary sclerosing cholangitis (chronic disease which results in the scarring & inflammation of the gall bladder)
What are the 3 natural history (progression of the disease) patterns that patients of ulcerative colitis follow? (state %)
- 10% = develop severe disease requiring early surgery
- 10% = have persistent active disease despite treatment
- 80% = have chronic quiescent colitis with infrequent episodes of relapse
In diagnosis, what are some diseases that ulcerative colitis must be distinguished from?
- infective colitis
- Crohn’s Disease
- Ischemic Colitis
- Proctitis caused by sexually transmitted diseases
What is total ulcerative colitis?
- when the whole entire large intestine
- occurs in ~20% of people
What checks do patients with total UC do & how often do they occur?
- If patient is over 50 years then;
- have regular screening coloscopy every 2 years
- rectal biopsy every 6 months to detect dysplastic changes
The development of dysplasia in the rectal mucosa in chronic ulcerative colitis is due to?
regenerative changes
- Regenerative changes in rectal mucosa lead to the development of; -1-
- as well as the potential risk of -2-
- which is related to -3- & -4-
- dysplasia
- carcinoma of the colon
- extent of the disease (high risk for total colitis)
- Duration of illness (high risk for disease of over 10 year duration)
Which side of the colon is associated with a lower risk of cancer?
Left
What is Necrosis?
Necrosis is the death of most cells in a tissue or organ as a result of disease, injury or failure of blood supply (O2 deprivation)
What is Apoptosis?
Apoptosis is a form of programmed cell death which occurs in multicellular organisms
What are differences in the size of a cell if it has undergone necrosis or apoptosis?
Necrosis
- Cellular swelling
- Many cells are affected - diffuse
Apoptosis
- Cellular shrinkage (condensation)
- One cell is affected (individual)
What are differences in the uptake of a cell if it has undergone necrosis or apoptosis?
Apoptosis
- Cells contents ingested by macrophages
- significant inflammation
Necrosis
- cell contents ingested by neighbouring cells
- No inflammatory response
What the differences to the membrane of a cell if it has undergone necrosis or apoptosis?
Necrosis
- Loss of membrane integrity (brakes)
- Cell lysis occurs (elicits inflammatory response)
Apoptosis
- membrane blebbing but integrity is maintained (intact)
- apoptotic bodies form
What are differences in the organelles of a cell if it has undergone necrosis or apoptosis?
Necrosis
- Organelle swelling and lysosomal leakage
- fragmentation of DNA is either random or smeared
- ATP is depleted
Apoptosis
- Mitochondria release pro-apoptotic proteins
- chromatin condensation & ladder-like DNA fragmentation
- requires ATP
Is Necrosis or Apoptosis an active process? which one isn’t?
Apoptosis is active as it requires ATP
Necrosis is inactive and doesn’t need ATP to occur but does result in the depletion of ATP
