Alcohol and The Liver Flashcards
What is meant by a unit of alcohol in the UK?
8g or 10ml of alcohol
At what age does alcoholic liver disease peak within the population?
Approximately 50 years old
The amount, type and frequency of alcohol consumption affect the likelihood of alcoholic liver disease developing. T/F?
True
The majority of heavy alcohol abusers will develop steatosis. T/F?
True
Cirrhosis is reversible. T/F?
False
Hepatitis is reversible. T/F?
True
Most alcoholics will develop cirrhosis. T/F?
False - only about 10-20% will
Which enzyme in the liver is mostly responsible for converted alcohol to acetaldehyde?
Alcohol dehydrogenase
Which liver enzyme is responsible for conversion of acetaldehyde to acetate in the metabolism of alcohol?
Acetaldehyde dehydrogenase
The initial conversion of alcohol to acetaldehyde occurs in which part of the cell in alcohol metabolism?
Cytosol
The conversion of acetaldehyde to acetate occurs in which part of the cell in alcohol metabolism
Mitochondria
Which enzyme is involved in the microsomal ethanol oxidising system?
Cytochrome p450 2E1
Which alcohol metabolism pathways result in the production of reactive oxidative species?
Microsomal ethanol oxidising system
catalase
What is the main pathway for the metabolism of alcohol?
Alcohol dehydrogenase pathway
When the main pathway for the metabolism of alcohol because saturated in alcohol excess, which pathways are induced?
Catalase pathway
Micorosmal ethanol oxidising system pathway
Acetaldehyde from alcohol metabolism binds to DNA. What effects does this have?
Immunogeneic
Stimulates collagen production
Acetate from alcohol metabolism results in increased acetyl coA concentrations. How does this promote inflammation?
By histone acetylation
Alcohol metabolism results in an increased NADH:NAD ratio. What effects does this have?
Increased fatty acid synthesis
reduced fatty acid oxidation
promotes steatosis
Alcohol metabolism results in the production of hydrogen peroxide and superoxide ions. How does this lead to increased TNF-alpha production?
Activates redox sensitive transcription factors such as NF-kappaB
What is the result of the increased TNF-alpha levels in alcohol metabolism?
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
Alcohol consumption results in increased intestinal permeability. How does this lead to the production of TNF-alpha?
Bacterial products such as endotoxins leak out of the intestines
this promotes activation of kupffer cells which promote liver injury and produce TNF-alpha
Which cytokine is produced as a result of increased ROS in alcohol metabolism, causing recruitment of neutrophils?
IL-8
How does oxidative stress in alcohol metabolism cause apoptosis of liver cells?
Leads to leakage of pro-apoptotic factors from the mitochondria regulated by Bcl-2 proteins. pro-apoptotic factors activate caspases leading to cell degradation
In alcoholic liver disease, how is the extrinsic apoptotic pathway initiated?
By TNF-alpha
How does TNF-alpha activated the extrinsic apoptotic pathway in alcohol metabolism?
Causes caspase activation via fas-associated death domain
What is the name of the vesicles containing broken down cell components from apoptosis?
Apoptotic bodies
How does apoptosis differ from necrosis?
Natural cell death
Stimulated by cell signals
Can be beneficial
Produces cell fragments which can send signals that facilitate phagocytosis
depletion of trace elements may exacerbate ROS production and promote apoptosis in alcohol metabolism. T/F?
True
From what is glutathione synthesised?
Methionine
Glutathione synthesis from methionine is reduced by a deficiency in…?
Folate
Vitamin B6
When there is disrupted methionine metabolism there is reduced conversion of s-adenosylmethionine to s-adenosylhomocysteine. What are the results of this?
Reduced trans methylation and impaired gene expression
Increased caspase expression causing apoptosis
Increased TNF-alpha production causing inflammation
Reduced cystathionine beta sythase activity
Obesity induces the enzyme involved in the microsomal ethanol oxidising system. T/F?
True
Why is AST always higher than ALT in alcoholic liver disease?
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
Alcohol induces lipodystrophy. T/F?
True
In which zones of the hepatic acini does steatosis usually occur predominantly?
Zone 2 and 3
What are the hallmarks of alcoholic hepatitis as seen on a histological sample?
Swollen heptocytes Giant mitochondria Steatosis Mallory bodies Collagen
What non-invasive technique can be used to measure the stiffness of the liver?
Transient elastography
What are the non-specific symptoms of alcoholic liver disease?
Malaise, nausea
What are the signs and symptoms of alcoholic liver disease?
Malaise, nausea, fever, jaundice, hepatomegaly, sepsis, encephalopathy, ascites, renal failure, death
The Glasgow alcoholic hepatitis score can indicate the severity of hepatitis. What factors are assessed in this scale?
Age White blood cell count Urea Prothrombin time Bilirubin
How can patients with a high Glasgow alcoholic hepatitis score be treated?
High dose steroid - prednisolone
ntiinflammatory
How much fluid needs to be present in ascites to be detectable by percussion?
5-6L
How much fluid needs to be present in ascites to cause the patient to have a tense, uncomfortable abdomen?
12L
What are the stigmata of liver disease?
Spider nave encephalopathy prolonged prothrombin time palmar erythema hypoalbuminaemia
What are the signs of portal hypertension?
Caput medusae
hypersplenism
thrombocytopenia
The Childs-Pugh score can indicate the severity of chronic liver disease. What factors are assessed in this score?
Encephalopathy ascites bilirubin albumin prothrombin time
Alcoholic cirrhosis is often found incidentally. T/F?
True
