AS Lecture 17 - Alcohol And Lifestyle

Question 1

What is the biochemistry of ethanol?

Answer 1

It is practically insoluble in fats and oils -> C2H5OH NOT bound to plasma proteins

Question 2

What is the concentration of ethanol in the tissues dependent on?

Answer 2

The relative water content of the tissue -> it reaches equilibrium quickly with the conc of ethanol in the plasma

Question 3

What is the metabolism of ethanol?

Answer 3

Question 4

When are CYP2E1 and catalase pathways used in the body?

Answer 4

When a lot of alcohol is consumed, these 2 cycles are needed on top of ADH cycle

Question 5

What forms a reactive oxygen species in the metabolism of ethanol?

Answer 5

CYP2E1 and acetaldehyde -> form free radicals, which are implicated in cancer cell formation

Question 6

How do you determine an alcohol dependent person?

Answer 6

Audit - alcohol-use disorders identification test -> with scores from 1-7 for low risk, 8-15 for hazardous drinking, 16-19 for harmful drinking and 20+ for possible dependence on alcohol

Question 7

How does ethanol damage hepatocytes in alcohol related liver disease?

Answer 7

Question 8

What are some of the suggested mechanisms for the pathogenesis of ALD?

Answer 8

Question 9

What is steatosis?

Answer 9

Fatty liver, with fat droplets deposited in the liver. Occurs in 50-90% of heavy drinkers

Question 10

What is the main pathway for ethanol metabolism?

Answer 10

Ethanol -> ADH -> Acetaldehyde -> ALDH -> Acetate

Question 11

What are the secondary pathways for ethanol metabolism and where do they occur?

Answer 11

In cells outside of the liver -> CYP2E1 (in brain) and Catalase. Only occur when greater amounts of ethanol have been consumed

Question 12

What is the protein adduct formation in metabolism of ethanol?

Answer 12

Acetaldehyde is toxic, which binds to certain amino acids, which is recognised as foreign, produces an immune response and then causes inflammation -> hepatic cells (which it bound to) undergo cell death

Question 13

When can hypoxia occur in metabolism of ethanol?

Answer 13

When ADH converts ethanol to acetaldehyde, NAD+ is converted to NADH, resulting in state of oxidation, so the cell becomes hypoxic as no more respiration can occur due to NADH being formed

Question 14

What is the spectrum of ALD?

Answer 14

Question 15

What does steatosis lead to?

Answer 15

Steatohepatitis and abnormal liver function tests BUT can be reversed if alcohol reduced

Question 16

How many patients with ALD develop fibrosis from steatosis?

Answer 16

10-20% if no inflammation, 40-50% if inflammation (steatohepatitis)

Question 17

How is hepatic fibrosis produced?

Answer 17

Chronic inflammation leads to transformation of hepatic stellate cells (help Vit A storage) into fibroblasts which begin to lay down collagen fibres -> condense to fibrous bands, so liver becomes hard

Question 18

How many patients with ALD develop cirrhosis from steatosis and what are some risk factors?

Answer 18

Females have a higher risk, also thought to be genetic and smoking and 8-20% w/out inflammation and 40-50% with inflammation

Question 19

What is cirrhosis?

Answer 19

Irreversible scarring of liver with fibrous bands and regenerative nodules

Question 20

What does cirrhosis lead to?

Answer 20

Impaired liver function and development of HPV hypertension -> 3-5% p/annum of developing liver cancer (HCC) and death in most within 10y

Question 21

What are some symptoms of cirrhosis?

Answer 21

Morbidity common, associated with jaundice, ascites, bleeding varices, cachexia, infections and encephalopathy

Question 22

What are the 2 types of cirrhosis?

Answer 22

Compensated (asymptomatic) vs decompensated (symptomatic)

Question 23

What is encephalopathy?

Answer 23

Question 24

What is chronic pancreatitis and what can it cause?

Answer 24

45% due to alcohol (up to) -> exocrine insufficiency (steatorrhea, vitamin deficiencies, hypocalcaemia), endocrine insufficiency (diabetes), chronic pain, weight loss

Question 25

What does alcohol cause in the CVS?

Answer 25

Hypertension, alcoholic cardiomyopathy, stroke

Question 26

How does alcohol affect stroke risks?

Answer 26

High alcohol intake is associated with risk of stroke and is dose-dependent

Question 27

How does alcohol affect brain function over time?

Answer 27

Ability to perform tasks, recall information, coordinate upper limbs and maintain balance can occur

Question 28

What are the neurological effects of alcohol?

Answer 28

Wernicke’s encephalopathy, Korsakoff’s psychosis, optic toxicity, autonomic dysfunction and peripheral neuropathy

Question 29

What is fetal alcohol syndrome?

Answer 29

Specific pattern of facial features, pre/post natal growth deficiency and evidence of CNS dysfunction -> many babies aren’t born with obvious FAS but never reach full potential as result of effects of alcohol in utero

Question 30

What is the hidden impact of alcohol?

Answer 30

Social, financial, job, housing, friends, sense of well-being, self-esteem, family and social productivity