Alcoholic Liver Disease Flashcards
Describe the effects of alcohol on the body - the normal physiology.
- Ethanol is metabolised in the liver by 2 pathways, resulting in the increase in the NADH/NAD ratio.
- The altered redox potential causes increased hepatic fatty acid synthesis with decreased fatty acid oxidation - this results in the hepatic accumulation of fatty acids, which are then esterified to glycerides.
- The changes in oxidation-reduction also impair carbohydrate and protein metabolism and are the cause of the centrilobular necrosis of the heaptic acinus that is typical of alcohol damage.
- TNF-alpha release from Kupffer cells causes the release of reactive oxygen species (ROS), leading to tissue injury and fibrosis.
- Acetaldehyde is formed by the oxidation of ethanol, and its effect on heaptic proteins could be a factor in producing liver cell damage.
- Alcohol can also enhance the effects of the toxic metabolites of drugs e.g. paracetamol on the liver.
Give 5 complications that can arise from alcohol abuse.
- Alcoholic Liver Disease
- Cirrhosis and the complications of cirrhosis including hepatocellular carcinoma
- Alcohol Dependence and Withdrawal
- Wernicke-Korsakoff Syndrome (WKS)
- Pancreatitis
- Alcoholic Cardiomyopathy
Define alcoholic liver disease.
Results from the effects of the long term excessive consumption of alcohol on the liver.
What are the 3 phases of alcoholic liver disease?
- Fatty change: hepatocytes contain triglycerides.
- Alcohol hepatitis.
- Alcoholic cirrhosis: destruction of liver architecture and fibrosis.
Describe the 1st stage of alcoholic liver disease: Fatty change.
Fatty liver:
- Metabolism of alcohol produces fat in the liver
- This is minimal with small amounts of alcohol, but with larger amounts, the cells become swollen with fat (steatosis)
- There is no liver cell damage
- The fat disappears on stopping alcohol
- In some cases, collagen is laid down around the central hepatic veins and this can sometimes progress to cirrhosis, without a preceding hepatitis.
- Alcohol directly affects stellate cells, transforming them into collagen-producing myofibroblast cells.
What are the clinical features of fatty change (stage 1)?
Often no symptoms or signs.
- Vague abdominal symptoms of nausea, vomiting, diarrhoea are due to the more general effects of alcohol on the GI tract.
Describe the 2nd stage of alcoholic liver disease: alcoholic hepatitis.
- In addition to fatty change, there is infiltration by polymorphonuclear leucocytes and hepatocyte necrosis.
- Dense cytoplasmic inclusions called Mallory bodies are sometimes seen in hepatocytes.
- Giant mitochondria are also a feature.
- If alcohol consumption continues, alcoholic hepatitis can progress to cirrhosis.
What are the clinical features of alcoholic hepatitis (stage 2)?
- SPIDER NAEVI
- Rapid onset mild jaundice
- Signs of chronic liver disease - Ascites, Bruising, Clubbing
- Tender hepatomegaly
Describe the 3rd stage of alcoholic liver disease: alcoholic cirrhosis.
This is where the liver is made up of scar tissue rather than healthy liver tissue.
Classically of the MICRONODULAR TYPE but mixed pattern is also seen accompanying fatty change.
Evidence of pre-existing alcoholic hepatitis may be present.
This is irreversible.
Stopping drinking can prevent further damage. Continued drinking has a very poor prognosis.
What are the clinical features of alcoholic cirrhosis (stage 3)?
Patients can be very well with few symptoms.
On examination there are usually signs of chronic liver disease - ascites, bruising, clubbing and Dupuytren’s contracture.
Features of alcohol dependency.
What is the path of damage that the alcoholic liver follows?
Fatty change - alcoholic heptatitis - fibrosis - micronodular cirrhosis
Investigations for stage 1 - fatty liver.
- Bloods:
- Elevated MCV indicates heavy drinking
- Raised ALT and AST
- Serum GGT particularly elevated - Ultrasound or CT will demonstrate fatty infiltration
- Liver histology will also show any fatty infiltration
What blood test might show that someone has alcoholic liver disease?
Serum GGT (gamma-glutamyl transferase) will be elevated.
Investigations for stage 2 - alcoholic hepatitis.
- Bloods:
* Leucocytosis
- Elevated:
- Serum bilirubin
- Serum AST and ALT
- Serum GGT (gamma-glutamyl transferase)
- Serum alkaline phosphate
- Prothrombin time
What distinctive feature is often seen on biopsy in people suffering from alcoholic liver disease?
Mallory bodies.