alcoholic liver disease new 20-6-2016
TRANSCRIPT
Alcoholic liver disease
Dr. Vaishali DAssistant Professor
"With ordinary talent and extraordinary perseverance, all things are attainable."
Objectives
• What is ALD?• 3 phases-steatosis,AlcoholicHepatitis&
fibrosis• Pathogenesis• Morphology• Clinical features• Lab Diagnosis
• Excessive alcohol consumption is the leading cause of liver disease.
• Alcoholic liver disease comprises of three main stages
1. Hepatic steatosis2. Alcoholic hepatitis3. Cirrhosis
Hepatic steatosisPathogenesis :• Fatty change is an acute, reversible manifestation of
ethanol ingestion.• Ethanol causes
– Increased fatty acid synthesis by causing catabolism of fat in the peripheral tissues
– Acetaldehyde which is metabolite of ethanol converts NAD+ to NADH. An excess NADH stimulates lipid biosynthesis.
– Also decreases oxidation of fatty acid by mitochondria due to reduced availability of NAD-req. for oxidation of fatty acid
– Acetaldehyde impairs the function of microtubules, resulting in decreased transport of lipoproteins from liver
• Collectively these metabolic consequences produce fatty liver.
Metabolism of ethanol. ADH, alcohol dehydrogenase; ALDH, aldehyde dehydrogenase
• Pathology:• Gross:
– The liver becomes yellow, greasy and is enlarged (up to 4 to 6 kg)
– The increase in weight is because of accumulation of fat
• Microscopy:• Following even moderate intake of alcohol,
small (microvesicular) lipid droplets accumulates in the liver
• With chronic intake of alcohol, more lipid accumulates, creating a large macrovesicular globules, compressing the nucleus the periphery.
Fatty change –liver(Steatosis)
Alcoholic Fatty Liver
• Clinical presentation of alcoholic steatosis– Hepatomegaly – Mild elevation of serum bilirubin, alkaline
phasphatase and gamma GT
Alcoholic hepatitis
• characterized by1. Hepatocyte swelling and necrosis2. Mallory bodies3. Neutrophilic inflammatory response4. Perivenular fibrosis
• Hepatocyte swelling and necrosis:– Single or scattered foci of cells undergo
swelling (ballooning degeneration) and necrosis
• Mallory bodies:– Scattered hepatocytes accumulate cytokeratin
intermediate filaments and other proteins– Visible as eosinophilic cytoplasmic inclusions
in degenerating hepatocytes
• Neutrophilic reaction:– Neutrophils accumulate around the
degenerating hepatocytes, particularly those having Mallory bodies.
– Lymphocytes and macrophages also enter portal tracts and spill into parenchyma
• Fibrosis :– Commonly seen in the form of sinusoidal and
perivenular fibrosis– Occasionaly periportal fibrosis may
predominate– Fibrosis mainly occurs because of the
activation of sinusoidal stellate cells and portal tract fibroblasts
• Clinical features:– Malaise, anorexia, weight loss, upper
abdominal discomfort, tender hepatomegaly.– Laboratory findings:
• Hyperbilirubinemia• Elevated ALP,GGT, moderate elevation of AST • Neutrophilic leucocytosis
• Alcoholic cirrhosis:– The final and irreversible form of alcoholic
liver disease– Usually evolves slowly– Gross:
• Initially the liver is yellow-tan, fatty and enlarged.• Later it is transformed into brown, shrunken,
nonfatty organ with multiple nodules.• Sometimes nodularity becomes very prominent
with scattred lager nodules creating a “hobnail” appearance on the surface of liver
Normal Liver
Cirrhosis
Alcoholic liver cirrhosis:
• Microscopy:– Initially fibrous septae are very delicate and
extend through sinusoids from central to portal regions as well as from portal tract to portal tract.
– As the fibrous septae dissect and surround nodules, the liver becomes more fibrotic, loses fat, and shrinks in size. (Laennec cirrhosis)
– Bile stasis may be seen.
Normal Liver Histology
Cirrhosis
Fibrosis
Regenerating Nodule
• Clinical features:– Features are similar to other forms of cirrhosis.– Malaise, weakness, weight loss, loss of appetite– Jaundice, ascites, and peripheral edema– Features of portal hypertension
Laboratory findings• Hematology-• HMG:Hb:Decreased• Anemia-Macrocytic• Clinical pathology-• Urine:Bile salt/pigment present• Ascitic /Peritoneal fluid-?• Biochemical-(LFTs)
– Hyperbilirubinemia – elevated serum aminotransferase (SGPT/SGOT)– Alkaline phasphatase, – Hypoproteinemia– Prothrombine time:Prolonged
• Case – 55yr/M chronic alcoholic,undernourished presented with nausea,anorexia.O/E : Pallor,icterus.P/A-distended,shifting dullness,mild tenderness.
• Features of Portal hypertension
Summary
• What is ALD?• Three phases with pathogenesis-• 1.Accumulation-steatosis-reversible• 2.Inflammation-Hepatitis• 3.Fibrosis-cirrhosis-irreversible• Morphology-• Fatty liver-Pale enlarge-initially• Later-cirrhosis-shrunkun• LFTs-deranged
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