Alcoholic Liver Disease Flashcards
What is alcoholic liver disease?
3 stages: fatty liver (steatosis)→ alcoholic hepatitis (inflamm and necrosis)→ alcoholic liver cirrhosis. All caused by chronic alcohol ingestion.
Fatty liver: build up of fat on liver. Rarely symptomatic. Reversible.
Alcoholic hepatitis: NOT related to infective hepatitis. Acute inflamm. Mild forms are reversible; if severe→ serious and life-threatening. May be symptomatic.
Cirrhosis: significant scarring. Symptomatic; not reversible.
What pathways exist physiologically to metabolise alcohol?
Alcohol dehydrogenase pathway and cytochrome P450
Explain the alcohol dehydrogenase pathway for metabolising alcohol.
-Alcohol→ acetaldehyde (via alcohol dehydrogenase- hepatic enzyme)→ acetate (via acetaldehyde dehydrogenase- mitochondrial enzyme)
-BOTH enzymes (alcohol dehydogenase and acetaldehyde dehydrogenase) also cause reduction reaction: NAD (nicotinamide adenine dinucleotide)→ NADH (reduced form)
Subsequent imbalance of excess NADH in relation to NAD→ inhibits gluconeogenesis and increases fatty acid oxidation→ fatty infiltrate in liver and oxidative stress→ hepatocyte necrosis and apoptosis
Explain the cytochrome P450 pathway for metabolising alcohol.
Cytochrome P450 also causes alcohol→ acetaldehyde (Part A), like alcohol dehydrogenase
Cytochrome P450 also causes an oxidation reaction: NADPH→ NADP. Free radicals generated by reaction.
Chronic alcohol→ upregulates cytochrome P450→ more oxidation reaction→ more free radicals→ lipid peroxidation→ inflammation and fibrosis
What third pathway of alcohol metabolism is activated after chronic consumption?
Hepatic macrophages→ produce TNF-alpha→ induce production of more free radicals (mitochondria)
Questionnaires for alcohol history.
CAGE and AUDIT
AUDIT results interpretation
10 questions
Score of 8 or more (≥7 for age >65 years)→ alcohol-use disorder and alcohol dependence
CAGE questions and score interpretation?
C: Have you ever felt you needed to CUT down on your drinking?
A: Have people ANNOYED you by criticising your drinking?
G: Have you ever felt GUILTY about drinking?
E: Have you ever felt you needed a drink first thing in the morning (EYE-OPENER) to steady your nerves or get rid of a hangover?
2 or more positives→ indicate alcohol dependency
Aetiology of alcoholic liver disease (2)
1) Chronic heavy alcohol ingestion
2) Cytokine and alcohol-metabolising enzyme gene polymorphisms assoc w increased risk
Risk factors for alcoholic liver disease? (6)
Chronic heavy alcohol consumption, female sex, hepatitis C, smoking and obesity, age 65+, genetic predisposition
Symptoms of alcoholic liver disease?
- RUQ pain
- N&V
- Fever
- Haematemesis, malaena
- Malnutrition, anorexia and wasting
- Fatigue
Signs of alcoholic liver disease?
- RUQ pain
- Hepatomegaly and splenomegaly
- Ascites
- Haematemeis and melaena
- Jaundice
- Caput medusa
- Palmar erythema
- Cutaneous telangiectasia
- Asterixis
- Dupuytren’s contracture
Ix: Bloods in ALD?
- AST/ ALT: elevated
- ALP: normal/ elevated
- Bilirubin: elevated (→ impaired liver metabolic funct w/ o biliary obst)
- Albumin: low
- GGT: elevated
- FBC: anaemia, leukocytosis, thrombocytopenia, raised MCV
Ix: Potential hepatic USS findings in ALD?
Perfomed in all w harmful alcohol use. May show: hepatomegaly, fatty liver, liver cirrhosis, liver mass, splenomegaly, ascites, evidence of PHTN
First line management of ALD?
Alcohol abstinence; manage withdrawal (benzodiazepine: diazepam)
Weight reduction, smoking cessation, supplements and multivitamins
Immunisation (influenza, pneumococcal, hep A, B)
CONSIDER: corticosteroids, sodium restriction w/ wo diuretics
