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OutlineOutline: 1.Intro2.Definition3.Pathogenesis4.Symptoms5.Clinical signs6.Treatment7.Complications8.References
Case Study:A 36 year old man complains of fatigue, dark urine, and abdominal swelling. He admits to drinking a few beers a day since his teen years, but he has never had major medical problems. Recently, he has been drinking more heavily while unemployed. He states that he has not had blood transfusions and does not use intravenous drugs. Physical examination findings are remarkable for tachycardia and low-grade fever. Prominent scleral icterus is noted, and the abdominal examination reveals shifting dullness. The liver span is increased on percussion.
Introduction:• Most important agent that produces toxic liver injury
is alcohol.• Excessive ethanol consumption causes more than
60% of chronic liver disease in most Western countries and accounts for 40% to 50% of deaths due to cirrhosis.
• More than 10 million Americans are alcoholics.
• Alcohol abuse causes 100,000 to 200,000 deaths annually in the United States, the • fifth leading cause of death in the US.
Some Stats:• 90-100% of alcohol consumers develop
hepatic steotosis• Out of these 10-35% develop Alcoholic
hepatitis and 8-20% develop cirrhosis
Morphology of Alcoholic hepatitis:
1.Hepatocyte Swelling/Necrosis• Single or multiple cells undergo swelling
and necrosis• Due to accumulation of fat, water and
proteins that are normally exported
Morphology of Alcoholic hepatitis:2. Mallary Bodies: • Accumulation of intermediate filaments
and other proteins• Seen as eosinophilic cytoplasmic inclusions
in dying cells
Morphology of Alcoholic hepatitis:
3. Neutrophil Infiltration• Neutrophills together with lymphocytes and
macrophages enter the liver and surround the degenerating hepatocytes
Morphology of Alcoholic hepatitis:
4. Fibrosis:• Sinusoidal and Perivenular fibrosis• Liver looks mottled red with bile stained
areas• Cholestasis and mild deposition of
hemosiderrin in Kupffer cells.
Pathogenesis:Alcohol Consumed Absorbed unchanged into blood (by the stomach and small intestine
Levels of Alcohol in the blood and their effects:• 200 mg/dL will result in drowsiness• 300 mg/dL will result in stupor• >300 mg/dL can result in comaChronic Alcoholics can tolerate up to 700 mg/dL and still not enter coma
Pathogenesis:Alcohol Metabolism: There are 3 enzyme systems involved
1.Alcohol dehydrogenase in the cytosol 2.Cytochrome P-450 in the microsomes3.Catalase in peroxisomes (minor:
metabolizes only 5%)
Pathogenesis:Alcohol Metabolism: There are 3 enzyme systems involved
1.Alcohol dehydrogenase in the cytosol • Alcohol oxidation by alcohol
dehydrogenase causes a decrease in NAD+ and an increase in NADH.
• NAD+ is required for fatty acid oxidation in the liver.
• Its deficiency is a main cause of accumulation of fat in the liver of alcoholics.
Pathogenesis:• NAD+ is also required for the
conversion of lactate into pyruvate• Increase in the NADH/NAD+ ratio in
alcoholics causes metabolic acidosis resulting from Lactic acid accumulation
• Acetaldehyde has many toxic effects and may be responsible for some of the acute effects of alcohol.
Pathogenesis:
Alcohol Metabolism: There are 3 enzyme systems involved
2. Cytochrome P-450 in the microsomes• At high blood alcohol levels, the
microsomal ethanol-oxidizing system participates in the metabolism. • Involves cytochrome P-450 enzymes,
particularly the CYP2E1 isoform, located in the smooth ER.
Pathogenesis:
• P-450 enzymes metabolizes drugs (acetaminophen, cocaine), anesthetics, carcinogens, and industrial solvents. • When alcohol is present in the
blood at high concentrations, it competes with other CYP2E1 substrates• This delays the catabolism of other
drugs, thus potentiating their effects.
Pathogenesis:
• Also produces free radicals that disrupts the cytoskeleton and membrane of the haptocytes
Clinical Symptoms:• Malaise• Anorexia, weight loss, loss of appetite and
nausea and vomiting• Upper abdominal pain and tenderness• Hepatomegaly • Fever• Ascites
Lab tests:• CBC • CT, ultrasound, or MRI of the liver• Blood test to check levels of:• Bilirubin• ALT and ASTHigh levels indicate liver necrosis
Risk Factors:• Other liver diseases like Hepatitis C• Malnutrition• Obesity and genetic factors• Sex: women are 5 times more likely to
develop this condition• Type of beverage: Beer/spirits vs wine• Binge drinking • Race: African American and Hispanic
Complications:• Increased BP in portal vein that can lead to
portal HT• Varices: bleeding into stomach and
esophagus• Ascites, Jaundice, hepatic encephalopathy• Cirrhosis• Kidney failure
Treatment: 1.Stop drinking2.Get on a healthy diet to counter any
malnourishment3.Take corticosteroids for inflammation but
beware of the adverse side effects4.Last resort liver transplant.
Case Study:A 36 year old man complains of fatigue, dark urine, and abdominal swelling. He admits to drinking a few beers a day since his teen years, but he has never had major medical problems. Recently, he has been drinking more heavily while unemployed. He states that he has not had blood transfusions and does not use intravenous drugs. Physical examination findings are remarkable for tachycardia and low-grade fever. Prominent scleral icterus is noted, and the abdominal examination reveals shifting dullness. The liver span is increased on percussion.
References:
Basic Pathology By Robins 8th edition Mayo Clinic website: http://www.mayoclinic.org/diseases-conditions/alcoholic-hepatitis/basics/treatment/con-20026160
http://books.google.ca/books?id=nStxzRQlNaAC&pg