What is the biochemistry of ethanol?
It is practically insoluble in fats and oils -> C2H5OH NOT bound to plasma proteins
What is the concentration of ethanol in the tissues dependent on?
The relative water content of the tissue -> it reaches equilibrium quickly with the conc of ethanol in the plasma
What is the metabolism of ethanol?
When are CYP2E1 and catalase pathways used in the body?
When a lot of alcohol is consumed, these 2 cycles are needed on top of ADH cycle
What forms a reactive oxygen species in the metabolism of ethanol?
CYP2E1 and acetaldehyde -> form free radicals, which are implicated in cancer cell formation
How do you determine an alcohol dependent person?
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
How does ethanol damage hepatocytes in alcohol related liver disease?
What are some of the suggested mechanisms for the pathogenesis of ALD?
What is steatosis?
Fatty liver, with fat droplets deposited in the liver. Occurs in 50-90% of heavy drinkers
What is the main pathway for ethanol metabolism?
Ethanol -> ADH -> Acetaldehyde -> ALDH -> Acetate
What are the secondary pathways for ethanol metabolism and where do they occur?
In cells outside of the liver -> CYP2E1 (in brain) and Catalase. Only occur when greater amounts of ethanol have been consumed
What is the protein adduct formation in metabolism of ethanol?
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
When can hypoxia occur in metabolism of ethanol?
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
What is the spectrum of ALD?
What does steatosis lead to?
Steatohepatitis and abnormal liver function tests BUT can be reversed if alcohol reduced
How many patients with ALD develop fibrosis from steatosis?
10-20% if no inflammation, 40-50% if inflammation (steatohepatitis)
How is hepatic fibrosis produced?
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
How many patients with ALD develop cirrhosis from steatosis and what are some risk factors?
Females have a higher risk, also thought to be genetic and smoking and 8-20% w/out inflammation and 40-50% with inflammation
What is cirrhosis?
Irreversible scarring of liver with fibrous bands and regenerative nodules
What does cirrhosis lead to?
Impaired liver function and development of HPV hypertension -> 3-5% p/annum of developing liver cancer (HCC) and death in most within 10y
What are some symptoms of cirrhosis?
Morbidity common, associated with jaundice, ascites, bleeding varices, cachexia, infections and encephalopathy
What are the 2 types of cirrhosis?
Compensated (asymptomatic) vs decompensated (symptomatic)
What is encephalopathy?
What is chronic pancreatitis and what can it cause?
45% due to alcohol (up to) -> exocrine insufficiency (steatorrhea, vitamin deficiencies, hypocalcaemia), endocrine insufficiency (diabetes), chronic pain, weight loss
What does alcohol cause in the CVS?
Hypertension, alcoholic cardiomyopathy, stroke
How does alcohol affect stroke risks?
High alcohol intake is associated with risk of stroke and is dose-dependent
How does alcohol affect brain function over time?
Ability to perform tasks, recall information, coordinate upper limbs and maintain balance can occur
What are the neurological effects of alcohol?
Wernicke's encephalopathy, Korsakoff's psychosis, optic toxicity, autonomic dysfunction and peripheral neuropathy
What is fetal alcohol syndrome?
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
What is the hidden impact of alcohol?
Social, financial, job, housing, friends, sense of well-being, self-esteem, family and social productivity