Alcohol and The Liver

Question 1

What is meant by a unit of alcohol in the UK?

Answer 1

8g or 10ml of alcohol

Question 2

At what age does alcoholic liver disease peak within the population?

Answer 2

Approximately 50 years old

Question 3

The amount, type and frequency of alcohol consumption affect the likelihood of alcoholic liver disease developing. T/F?

Answer 3

True

Question 4

The majority of heavy alcohol abusers will develop steatosis. T/F?

Answer 4

True

Question 5

Cirrhosis is reversible. T/F?

Answer 5

False

Question 6

Hepatitis is reversible. T/F?

Answer 6

True

Question 7

Most alcoholics will develop cirrhosis. T/F?

Answer 7

False - only about 10-20% will

Question 8

Which enzyme in the liver is mostly responsible for converted alcohol to acetaldehyde?

Answer 8

Alcohol dehydrogenase

Question 9

Which liver enzyme is responsible for conversion of acetaldehyde to acetate in the metabolism of alcohol?

Answer 9

Acetaldehyde dehydrogenase

Question 10

The initial conversion of alcohol to acetaldehyde occurs in which part of the cell in alcohol metabolism?

Answer 10

Cytosol

Question 11

The conversion of acetaldehyde to acetate occurs in which part of the cell in alcohol metabolism

Answer 11

Mitochondria

Question 12

Which enzyme is involved in the microsomal ethanol oxidising system?

Answer 12

Cytochrome p450 2E1

Question 13

Which alcohol metabolism pathways result in the production of reactive oxidative species?

Answer 13

Microsomal ethanol oxidising system

catalase

Question 14

What is the main pathway for the metabolism of alcohol?

Answer 14

Alcohol dehydrogenase pathway

Question 15

When the main pathway for the metabolism of alcohol because saturated in alcohol excess, which pathways are induced?

Answer 15

Catalase pathway

Micorosmal ethanol oxidising system pathway

Question 16

Acetaldehyde from alcohol metabolism binds to DNA. What effects does this have?

Answer 16

Immunogeneic

Stimulates collagen production

Question 17

Acetate from alcohol metabolism results in increased acetyl coA concentrations. How does this promote inflammation?

Answer 17

By histone acetylation

Question 18

Alcohol metabolism results in an increased NADH:NAD ratio. What effects does this have?

Answer 18

Increased fatty acid synthesis
reduced fatty acid oxidation
promotes steatosis

Question 19

Alcohol metabolism results in the production of hydrogen peroxide and superoxide ions. How does this lead to increased TNF-alpha production?

Answer 19

Activates redox sensitive transcription factors such as NF-kappaB

Question 20

What is the result of the increased TNF-alpha levels in alcohol metabolism?

Answer 20

promotion of lipid per oxidation
promotion of inflammation
damage of mitochondrial membranes causing apoptosis
activates stellate cells to produce collagen causing fibrosis
increased intestinal permeability

Question 21

Alcohol consumption results in increased intestinal permeability. How does this lead to the production of TNF-alpha?

Answer 21

Bacterial products such as endotoxins leak out of the intestines
this promotes activation of kupffer cells which promote liver injury and produce TNF-alpha

Question 22

Which cytokine is produced as a result of increased ROS in alcohol metabolism, causing recruitment of neutrophils?

Answer 22

IL-8

Question 23

How does oxidative stress in alcohol metabolism cause apoptosis of liver cells?

Answer 23

Leads to leakage of pro-apoptotic factors from the mitochondria regulated by Bcl-2 proteins. pro-apoptotic factors activate caspases leading to cell degradation

Question 24

In alcoholic liver disease, how is the extrinsic apoptotic pathway initiated?

Answer 24

By TNF-alpha

Question 25

How does TNF-alpha activated the extrinsic apoptotic pathway in alcohol metabolism?

Answer 25

Causes caspase activation via fas-associated death domain

Question 26

What is the name of the vesicles containing broken down cell components from apoptosis?

Answer 26

Apoptotic bodies

Question 27

How does apoptosis differ from necrosis?

Answer 27

Natural cell death Stimulated by cell signals Can be beneficial Produces cell fragments which can send signals that facilitate phagocytosis

Question 28

depletion of trace elements may exacerbate ROS production and promote apoptosis in alcohol metabolism. T/F?

Answer 28

True

Question 29

From what is glutathione synthesised?

Answer 29

Methionine

Question 30

Glutathione synthesis from methionine is reduced by a deficiency in...?

Answer 30

Folate | Vitamin B6

Question 31

When there is disrupted methionine metabolism there is reduced conversion of s-adenosylmethionine to s-adenosylhomocysteine. What are the results of this?

Answer 31

Reduced trans methylation and impaired gene expression Increased caspase expression causing apoptosis Increased TNF-alpha production causing inflammation Reduced cystathionine beta sythase activity

Question 32

Obesity induces the enzyme involved in the microsomal ethanol oxidising system. T/F?

Answer 32

True

Question 33

Why is AST always higher than ALT in alcoholic liver disease?

Answer 33

AST is a mitochondrial enzyme, ALT is a cytosolic enzyme In alcoholic liver disease, the mitochondria is broken down in apoptosis and there are therefore very high levels of AST in the blood

Question 34

Alcohol induces lipodystrophy. T/F?

Answer 34

True

Question 35

In which zones of the hepatic acini does steatosis usually occur predominantly?

Answer 35

Zone 2 and 3

Question 36

What are the hallmarks of alcoholic hepatitis as seen on a histological sample?

Answer 36

``` Swollen heptocytes Giant mitochondria Steatosis Mallory bodies Collagen ```

Question 37

What non-invasive technique can be used to measure the stiffness of the liver?

Answer 37

Transient elastography

Question 38

What are the non-specific symptoms of alcoholic liver disease?

Answer 38

Malaise, nausea

Question 39

What are the signs and symptoms of alcoholic liver disease?

Answer 39

Malaise, nausea, fever, jaundice, hepatomegaly, sepsis, encephalopathy, ascites, renal failure, death

Question 40

The Glasgow alcoholic hepatitis score can indicate the severity of hepatitis. What factors are assessed in this scale?

Answer 40

``` Age White blood cell count Urea Prothrombin time Bilirubin ```

Question 41

How can patients with a high Glasgow alcoholic hepatitis score be treated?

Answer 41

High dose steroid - prednisolone | ntiinflammatory

Question 42

How much fluid needs to be present in ascites to be detectable by percussion?

Answer 42

5-6L

Question 43

How much fluid needs to be present in ascites to cause the patient to have a tense, uncomfortable abdomen?

Answer 43

12L

Question 44

What are the stigmata of liver disease?

Answer 44

``` Spider nave encephalopathy prolonged prothrombin time palmar erythema hypoalbuminaemia ```

Question 45

What are the signs of portal hypertension?

Answer 45

Caput medusae hypersplenism thrombocytopenia

Question 46

The Childs-Pugh score can indicate the severity of chronic liver disease. What factors are assessed in this score?

Answer 46

``` Encephalopathy ascites bilirubin albumin prothrombin time ```

Question 47

Alcoholic cirrhosis is often found incidentally. T/F?

Answer 47

True