Week 3 - Tutorial - Immunopathology

Question 1

List 3 types of chronic inflammation which can lead to cancer. (provide specifics of both the inflammation & cancer)

Answer 1

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

Question 2

How does chronic inflammation develop into a tumour?

Answer 2

(can enter at any stage)

1. Cells transform
2. Primary growth
3. Metastasis

Question 3

What does a loss in gut bacteria cause? (could be one of 3 reasons)

Answer 3

• loss in gut bacteria =

1. loss of barrier function
   
   • increase commensal penetration
   • increase inflammation
   • = enhanced tumour growth
2. Pathobiont-mediated tumorigenesis
   
   • potentially pathogenic commensal strains enhance tumorigenesis
   • use T_H17 cells
   • inflammation
3. Dysbiosis-mediated inflammation
   
   • loss of host-related innate sensing platforms
   • = pertubation of microbiota composition and function
   • = tumour growth enhanced

Question 4

How do Inflammatory Cells help tumour cells?

Answer 4

Inflammatory cells release;

1. Growth Factors
   
   • TNF
   • IL-1
2. 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)

Question 5

What are the primary sources of Chronic Liver Disease?

Answer 5

• 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

Question 6

What are the main causes of Hepatitis C?

Answer 6

• 60% Injecting Drug use
• 15% Sexual
• 10% Transfusion (occurred before screening)
• 10% Unknown
• 4% Occupational
• 1% other (Nosocomial, iatrogenic, prenatal)

Question 7

What does iatrogenic mean?

Answer 7

Means diseases that occurred due to a harmful complication, or other ill effects by any medical activity, including diagnosis, intervention, error, or negligence.

Question 8

What is the progression of Chronic Liver Disease (CLD)?

Answer 8

Question 9

How quickly can the liver regenerate itself?

Answer 9

~2 months

Question 10

What is the prognosis of CLD?

Answer 10

1 in 4 die (aka v bad)

Question 11

What is the progression of a healthy liver to liver cancer? Describe the 4 stages. (hint 2 have been said)

Answer 11

1. Healthy liver
   
   • normal
2. Fibrotic Liver
   
   • continuous inflammation
   • if caused by Hep B
   • lead to fibrosis aka HEALING WITH SCARRING
   • ie formation of scar tissue
3. Cirrhotic liver
   
   • scar tissue replaces normal, healthy tissue
   • blocks flow of blood through liver
   • prevents norm function
4. Liver Cancer
   
   • formation of malignant tumours in liver

Question 12

What does HCC stand for?

Answer 12

Hepatocellular carcinoma

Question 13

How is Chronic liver disease diagnosed?

Answer 13

• 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

Question 14

What are some factors that may cause liver inflammation?

Answer 14

• 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)

Question 15

Which one is healthy? What is the other? Why do you think this?

Answer 15

• Left = Healthy
  
  • normal
• Right = cirrhosis of liver
  
  • many lymphoid cell infiltration
  • more scar tissue (white)

Question 16

Which of these is infecter and which is uninfected? What disease could it be & why?

Answer 16

• Left = unifected
• Right = infected
  
  • probs HCV as
    
    • its liver
    • infiltration of lymphocytes is seen
    • and connective tissue is being placed down

Question 17

What is AFP & what is it a marker for?

Answer 17

Alpha-fetoprotein (AFP)

is a marker for some cancers specifically in the liver

Question 18

If a patient has Hepatocellular Carcinomas (HCC) then they have a 34% chance of getting what disease?

Answer 18

HCC leads to pulmonary (lung) metastasis

Question 19

What are the main treatment options for Liver Cancer?

Answer 19

1. Liver Transplant
2. Trans-Catheter Arterial Chemobolisation (TACE) - for patients who are not suitable for a liver transplant

Question 20

What is TACE?

Answer 20

Trans-catheter arterial chemobolization

Question 21

What is the main aim of TACE and how does it work?

Answer 21

• 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

Question 22

What are the two main mechanisms that are beneficial to TACE?

Answer 22

1. The typical blood supply of hepatic tumours
2. The ability to deliver a higher dose of chemotherapeutic drugs

Question 23

How is the blood supply of hepatic tumours beneficial to TACE?

Answer 23

• 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

Question 24

Why can higher doses be given during TACE?

Answer 24

• 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

Question 25

The intra-tumour concentration of chemotherapeutic is 10 times greater in ____ than \_\_\_\_\_

Answer 25

a. proper hepatic artery b. portal vein

Question 26

What does embolization induce?

Answer 26

induces *ischemic necrosis of tumour* which causes a failure of transmembrane pump = greater absorption of agents by tumour cells

Question 27

What is Ulcerative colitis?

Answer 27

is chronic inflammation of the bowel (colon) or digestive tract which can result in formation ulcers

Question 28

What is 5-ASA and what does it do?

Answer 28

5-ASA = 5 amino-salicylate is used to monitor mild to moderate IBM as it is an anti-metabolite

Question 29

How is ulcerative colitis (UC) diagnosed?

Answer 29

* 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

Question 30

What is the main problem after a colectomy is performed?

Answer 30

Managing every day life as faeces cannot be controlled as you cannot feel them coming out

Question 31

Where does ulcerative colitis begin?

Answer 31

Starts at rectum & may extend for a variable distance around the colon

Question 32

What are some of the hypotheses of the aetiology of ulcerative colitis?

Answer 32

1. Psychosomatic cause * stress is believed to exacerbate disease in some individuals 2. Infective Cause * adhesive of enteropathogenic E. coli may trigger episodes of inflammation 3. 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

Question 33

In active ulcerative colitis what are the effects of; (a) ulcerated areas (b) crypt abscesses

Answer 33

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

Question 34

What are the local effects of ulcerative colitis?

Answer 34

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

Question 35

What are the Systemic effects of ulcerative colitis?

Answer 35

extra-intestinal manifestations e.g. fever inflammation of eyes or joints ulcers of the mouth inflamed nodules on the shins.

Question 36

List 3 other conditions which may be associated with ulcerative colitis?

Answer 36

Can list any of the following 1. **migratory polyarthritis** (pain, swelling & joint stiffness) 2. **sacroiliitis** (inflammation of both sacroiliac joints) 3. **ankylosing spondylitis** (an inflammatory disease that over time causes vertebrae to fuse) 4. **uveitis** (inflammation of the uvea = eye redness, pain & blurred vision) 5. **erythema nodosum** (is a panniculitis (skin inflammation) that affects the subcutaneous fat in the skin) 6. **primary sclerosing cholangitis** (chronic disease which results in the scarring & inflammation of the gall bladder)

Question 37

What are the 3 natural history (progression of the disease) patterns that patients of ulcerative colitis follow? (state %)

Answer 37

1. 10% = develop severe disease requiring **early** **surgery** 2. 10% = have **persistent active disease** despite treatment 3. 80% = have **chronic quiescent colitis** with infrequent episodes of relapse

Question 38

In diagnosis, what are some diseases that ulcerative colitis must be distinguished from?

Answer 38

1. infective colitis 2. Crohn's Disease 3. Ischemic Colitis 4. Proctitis caused by sexually transmitted diseases

Question 39

What is total ulcerative colitis?

Answer 39

* when the whole entire large intestine * occurs in ~20% of people

Question 40

What checks do patients with total UC do & how often do they occur?

Answer 40

* If patient is over 50 years then; * have regular screening coloscopy every 2 years * rectal biopsy every 6 months to detect dysplastic changes

Question 41

The development of dysplasia in the rectal mucosa in chronic ulcerative colitis is due to?

Answer 41

regenerative changes

Question 42

* 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-

Answer 42

1. dysplasia 2. carcinoma of the colon 3. extent of the disease (high risk for total colitis) 4. Duration of illness (high risk for disease of over 10 year duration)

Question 43

Which side of the colon is associated with a lower risk of cancer?

Answer 43

Left

Question 44

What is Necrosis?

Answer 44

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)

Question 45

What is Apoptosis?

Answer 45

Apoptosis is a form of programmed cell death which occurs in multicellular organisms

Question 46

What are differences in the size of a cell if it has undergone necrosis or apoptosis?

Answer 46

Necrosis * Cellular swelling * Many cells are affected - diffuse Apoptosis * Cellular shrinkage (condensation) * One cell is affected (individual)

Question 47

What are differences in the uptake of a cell if it has undergone necrosis or apoptosis?

Answer 47

Apoptosis * Cells contents ingested by macrophages * significant inflammation Necrosis * cell contents ingested by neighbouring cells * No inflammatory response

Question 48

What the differences to the membrane of a cell if it has undergone necrosis or apoptosis?

Answer 48

Necrosis * Loss of membrane integrity (brakes) * Cell lysis occurs (elicits inflammatory response) Apoptosis * membrane blebbing but integrity is maintained (intact) * apoptotic bodies form

Question 49

What are differences in the organelles of a cell if it has undergone necrosis or apoptosis?

Answer 49

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

Question 50

Is Necrosis or Apoptosis an active process? which one isn't?

Answer 50

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