Tutorial 3 - Inflammation, cancer & case studies

Question 1

chronic hepatitis leads to? % probabilities?

Answer 1

1. fibrotic liver (fibrous scar tissue),
2. liver cirrhosis (25% chance), which can then lead to
3. liver cancer (3-5%)

Question 2

state main causes of chronic liver disease?

Answer 2

hepatitis C 26%
alcohol 24%
hepatitis C with alcohol 14%
hepatitis B 11%

Question 3

t/f: spontaneous regression of HCC is a rare phenomena where it basically just goes away

Answer 3

true

HCC = hepatocellular carcinoma; liver cancer

Question 4

possible causes spontaenous regression?

Answer 4

1. ischaemia

2. immunologic mechanisms

Question 5

what is Trans-catheter arterial chemoembolization (TACE)?

Answer 5

• restrictive blood supply tumor
• minimally invasive
• chemotherapy + embolization = chemoembolization

Question 6

how does TACE work?

Answer 6

small embolic particles coated in therapeutic drugs injected selectively through a catheter into an artery which supplies the tumor

these particles block blood supply and induce cytotoxicity

Question 7

most tumors in liver supplied by which artery?

Answer 7

hepatic proper

Question 8

by attacking the hepatic proper artery, how does this fight off the tumor (TACE)?

Answer 8

prevents nutrient delivery over time until neovascularisation can take place

Question 9

what is (typically) the limiting factor for chemotherapy?

Answer 9

systemic exposure

Question 10

state the 2 mechanisms by which TACE works?

overall effect of this on physiological level?

Answer 10

1. block arterial blood supply until neovascularisation
2. focused chemotherapy of higher dose. This effect augmented as chemotherapeutic drug not washed out tumor vascular bed by blood flow (as its blocked). This means a higher contact time of tumor and drug

embolization -> ischaemic necrosis -> failure of transmembrane pump, resulting -> greater absoprtion by tumor cells

Question 11

how was it proven that TACE targets tumor in liver, not liver overall?

Answer 11

tumor 40x more agent then rest of liver. This proven as if inject into hepatic portal vein, only 1/10 of intra-tumoral concentration

so using hepatic artery proper gives 10x higher [drug]

Question 12

where does ulcerative colitis start?

Answer 12

starts in rectum, may extend for variable distance along colon

Question 13

define proctisis

Answer 13

anal canal inflamed

Question 14

how severe can ulcerative colitis (UC) be - how much of colon can be affected?

Answer 14

all of colon and all colonic mucosa can be affected in highly severe cases

Question 15

symptoms of UC?

Answer 15

diarrhea, blood/ mucus/ pus in faeces

Question 16

aetiology of UC?

Answer 16

not clear, several hypothesis:

1. psychosomatic - stress induced
2. infective - enteropathological form e.coli induce
3. autoimmune - lymphoid cells cause inflammation

unified explanation: infection triggers inappropriate immune response leading to destruction colonic mucosa

Question 17

in active UC, the ulcerated areas are _____

Answer 17

hemorrhagic, leading to bloody diarrhoea

Question 18

explain histology of active UC?

Answer 18

• in-tact mucosa sits above areas of ulceration as islands
• edema
• increased lymphoid cells & plasma cells in lamina propria
• neutrophils in lamina propria and gland epithelium
• neutrophils migrate through walls of glands forming crypt abscesses in gland lumen
• depletion goblet cells

Question 19

t/f: UC has only local, no systemic effects

Answer 19

false - both

Question 20

direct local complications of UC?

Answer 20

blood and fluid loss from extensive ulceration

Question 21

natural history of patients with UC?

Answer 21

10% develop severe disease, need surgery
10% have persistent active disease despite treatment
80% have chronic quiescent colitis with infrequent episodes

Question 22

In chronic UC, regeneative changes to colonic mucosa leads to?

Answer 22

dysplasia and risk of carcinoma development in colon

Question 23

There is more risk of dysplasia/ carcinoma development in chronic UC if?

Answer 23

1. disease very severe (total colitis)

2. disease duration long (had for 10 years)

Question 24

In trying to kill cancer, how are most cancer cells killed?

Answer 24

apoptosis is stimulated by drugs given

Question 25

necrosis means death by?

Answer 25

O2 deprivation

Question 26

contrast necrosis and apoptosis in terms of: | cell size change

Answer 26

necrosis - cell swells | apoptosis - cell condense

Question 27

contrast necrosis and apoptosis in terms of: | membrane

Answer 27

necrosis - membrane broken | apoptosis - membrane in tact

Question 28

contrast necrosis and apoptosis in terms of: | ATP

Answer 28

necrosis - no ATP needed | apoptosis - ATP needed

Question 29

contrast necrosis and apoptosis in terms of: | how cell destroyed

Answer 29

necrosis - cell lyses | apoptosis - cell phagocytosed

Question 30

contrast necrosis and apoptosis in terms of: | DNA

Answer 30

necrosis - random DNA fragmentation/ smearing | apoptosis - ladder-like DNA fragmentation

Question 31

contrast necrosis and apoptosis in terms of: | in vivo, what area affected?

Answer 31

necrosis - whole areas or tissue | apoptosis - individual cells

Question 32

contrast necrosis and apoptosis in terms of: | effect on inflammation?

Answer 32

necrosis - inflammation triggered | apoptosis - minimal macrophage activation

Question 33

contrast necrosis and apoptosis in terms of: | which needs protein function?

Answer 33

necrosis - nil, passive | apoptosis - requires protein use, active

Question 34

discuss relationship between inflammation and age.

Answer 34

age increases inflammation and inflammatory processes age the body (goes both ways)

Question 35

describe the relationship between chronic inflammation and cancer?

Answer 35

chronic inflammation contributes toward/ causes cancer, as the chemical mediators released during inflammation stimulate cancerous growth (assumed)

Question 36

chronic inflammation causing cancer; state the disease (which lead to inflammation) behind the following cancer: colon cancer

Answer 36

chronic ulcerative colitis

Question 37

chronic inflammation causing cancer; state the disease (which lead to inflammation) behind the following cancer: Liver cancer

Answer 37

chronic hepatitis B or C

Question 38

chronic inflammation causing cancer; state the disease (which lead to inflammation) behind the following cancer: Lung cancer

Answer 38

COPD, chronic asthma

Question 39

chronic inflammation causing cancer; state the disease (which lead to inflammation) behind the following cancer: bladder cancer

Answer 39

chronic cystitis

Question 40

chronic inflammation causing cancer; state the disease (which lead to inflammation) behind the following cancer: lymphoma

Answer 40

chronic thyroiditis, sjorgen syndrome

Question 41

chronic inflammation causing cancer; state the disease (which lead to inflammation) behind the following cancer: breast cancer

Answer 41

fibrocystic breast disease

Question 42

chronic inflammation causing cancer; state the disease (which lead to inflammation) behind the following cancer: prostate cancer

Answer 42

benign prostate hyperplasia

Question 43

expand acronym HCC

Answer 43

hepatocellular carcinoma

Question 44

main sources infection hepatitis C

Answer 44

inject drug 60% sexual 15% transfusion 10%

Question 45

t/f: gut normal flora can migrate across a degenerated gut mucosa (epithelium) and stimulate inflammation

Answer 45

true

Question 46

survival factors (cytokines) released by inflammatory cells, promoting tumor growth are?

Answer 46

SOD2 BFL1 BCL-Xl GADD45beta

Question 47

describe the relationship between IL-6 and IL-1

Answer 47

they both cause more of each other to be produced (loop)

Question 48

cirrhosis?

Answer 48

late stage of fibrosis; the progression | hep c (or others) --> fibrosis --> cirrhosis --> cancer development

Question 49

how would colon of someone with UC in quiescent phase look?

Answer 49

pale and rough

Question 50

t/f: inflammation triggers regeneration and repair

Answer 50

true (wow)

Question 51

discuss the relationship between MHC class 1 and natural killer cells?

Answer 51

if a cell does not possess MHC class 1, natural killer cells will attack (Major Histocompatability protein has protective, 'self recognising' effect TO NK CELLS)

Question 52

non-IgE asthma is driven by which cells (mainly)?

Answer 52

ILC2's and eosinophils

Question 53

Consider IgG and IgM, and IgE. a. ) Which are likely to be present in the early phase of infection? b. ) Which are likely to be present in the late phase of infection?

Answer 53

a. ) IgM, IgE | b. ) IgG

Question 54

which antibodies are the "memory antibodies"?

Answer 54

IgG

Question 55

multiple sclerosis is a type _ hypersensitivity?

Answer 55

4

Question 56

state the targets of the autoimmune response in multiple sclerosis?

Answer 56

myelin, schwann cells, oligodendrocytes

Question 57

ulcerative colitis is a major cause of ____ ____.

Answer 57

colon cancer

Question 58

t/f: apoptosis requires protein synthesis

Answer 58

true

Question 59

state 3 growth factors which control tissue repair post inflammation?

Answer 59

TFGbeta, VEGF, PDGF

Question 60

state 3 cancers linked to chronic inflammation?

Answer 60

colon, liver, lung

Question 61

state cardinal signs of acute inflammation?

Answer 61

heat, swelling, pain, redness

Question 62

state chemical mediators in the vascular inflammatory response?

Answer 62

serotonin, histamine, prostoglandins, leukotrienes

Question 63

Th2 cells are (MCQ): a. ) main player pathogenesis asthma b. ) main player cytotoxic T cell response c. ) attract macrophages d. ) lyse other cells

Answer 63

a.

Question 64

what type of hypersensitivity is an anaphylactic episode?

Answer 64

type 1