L24 alcoholic liver disease


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  • L24 alcoholic liver disease

    1. 1. Alcoholic LiverDiseaseLecture 24ETHANOL1ETHANOL
    2. 2. ETHANOLExcessive alcohol (ethanol)consumption is the leading cause ofliver disease in mostWestern countries.2ETHANOL
    3. 3. Forms of alcoholic liver disease(1)Hepatic steatosis (fatty liverdisease)(2) Alcoholic hepatitis(3) Cirrhosis.ETHANOL 3
    4. 4. Fatty Liver /SteatosisDefinition:• Fatty liver is the collection of excessiveamounts of triglycerides and otherfats inside liver cells.ETHANOL 4
    5. 5. Description• The liver is the organ responsible for changing fats eaten in the diet to types of fat that can be stored and used by the body. • Triglycerides are one of the forms of fat stored by the body and used for energy and new cell formation.ETHANOL 5
    6. 6. The break down of fats in the liver can be disrupted by  ETHANOL 6
    7. 7. Morphology of1.Hepatic Steatosis (Fatty Liver).After even moderate intake of alcohol,microvesicular lipid dropletsaccumulate in hepatocytes.ETHANOL 71.Hepatic Steatosis (Fatty Liver).After even moderate intake of alcohol,microvesicular lipid dropletsaccumulate in hepatocytes.
    8. 8. With chronic intake of alcohol, lipidaccumulates creatingthat compress and displace the hepatocytenucleus to the periphery of the cell.ETHANOL 8
    9. 9. ETHANOL 9
    10. 10. The normal adult liver weighs 1400 -1600 gmMacroscopically, the fatty liver of chronicalcoholism is a large (as heavy as 4 to 6kg), soft organ that is yellow and greasy.The fatty change is completely reversible if there isabstention from further intake of alcohol.ETHANOL 10
    11. 11. Morphology 2. Alcoholic Hepatitis (Alcoholic Steatohepatitis).Alcoholic hepatitis is characterized by:1. Hepatocyte swelling and necrosis2. Mallory bodies:Mallory bodies are visible as eosinophilic cytoplasmic clumps in hepatocytes.3. Neutrophilic reaction4. FibrosisETHANOL 11
    12. 12. ETHANOL 12American Pathologist
    13. 13. Mallory BodiesLarge, poorly defined accumulations ofeosinophilic material in the cytoplasm ofdamaged hepatic cells in certain forms ofcirrhosis especially those due to alcoholism.• Synonym(s): alcoholic hyalin, alcoholic hyalinebodiesMallory body, Mallory-Denk body, andMallorys hyalineETHANOL 13
    14. 14. ETHANOL 14Mallory body with the characteristic twisted-rope appearance (centre of image - withina ballooning hepatocyte). H&E stain
    15. 15. ETHANOL 15
    16. 16. ETHANOL 16
    17. 17. ETHANOL 17
    18. 18. ETHANOL 18
    19. 19. ETHANOL 19
    20. 20. Alcoholic cirrhosis. A, The characteristic diffuse nodularity of the surface reflects theprocesses of nodular regeneration and scarring. The greenish tint of some nodules isdue to bile stasis. A hepatocellular carcinoma is present as a budding mass at thelower edge of the right lobe (lower left).ETHANOL 20
    21. 21. B, The microscopic view shows nodules of varying sizes entrapped in blue-stainingfibrous tissue. The liver capsule is at the top (Masson trichrome).ETHANOL 21
    22. 22. Alcoholic liver disease. The interrelationships among hepatic steatosis,hepatitis, and cirrhosis are shown, depicting key morphologicfeatures.ETHANOL 221 23
    23. 23. Pathogenesis.• Short-term ingestion of as much as 80 gm ofalcohol over one to several days generallyproduces mild, reversible hepaticsteatosis.ETHANOL 23
    24. 24. • Daily intake of 80 gm or more of ethanolgenerates significant risk for severe hepaticinjury, and daily ingestion of 160 gm or morefor 10 to 20 years is associated moreconsistently with severe injury.ETHANOL 24
    25. 25. • Only 10% to 15% of alcoholics, however,develop cirrhosis.• Thus, other factors must also influence thedevelopment and severity of alcoholic liverdisease.ETHANOL 25
    26. 26. Factors other than alcohol1. Gender. Women2. Ethnic differences3. Genetic factorsETHANOL 26
    27. 27. Hepatocellular steatosis results from(1) shunting of normal substrates away fromcatabolism and toward lipid biosynthesis(2) impaired assembly and secretion oflipoproteins;(3) increased peripheral catabolism of fat.ETHANOL 27
    28. 28. Clinical Features• 1.Hepatic steatosis (fattyliver):Hepatomegaly,• with mild elevation of serum bilirubin andalkaline phosphatase levels.• Severe hepatic dysfunction is unusual.ETHANOL 28
    29. 29. Treatment• Alcohol withdrawal and• the provision of an adequate dietaresufficient treatment.ETHANOL 29
    30. 30. 2. Alcoholic hepatitistends to appear acutely, usually following about of heavy drinking.ETHANOL 30
    31. 31. Clinical features of Alcoholic Hepatitis1. Malaise,2. Anorexia,3. Weight loss,4. Upper abdominal discomfort,5. Tender hepatomegaly,ETHANOL 31
    32. 32. Laboratory findings:hyperbilirubinemia,elevated alkaline phosphatase,neutrophilic leukocytosis.ETHANOL 32
    33. 33. • An acute cholestatic syndrome may appear,resembling large bile duct obstruction.ETHANOL 33
    34. 34. • The outlook is unpredictable; each bout ofhepatitis incurs about a 10% to 20% risk ofdeath.• With repeated bouts, cirrhosis appears inabout one third of patients within a fewyears.• Alcoholic hepatitis also may besuperimposed on established cirrhosis.ETHANOL 34
    35. 35. • With proper nutrition and total cessation ofalcohol consumption, the alcoholic hepatitismay clear slowly.• However, in some patients, thehepatitis persists, despiteabstinence, and progresses to cirrhosis.ETHANOL 35
    36. 36. Laboratory findings:• Elevated serum aminotransferase,• Hyperbilirubinemia,• Elevation of serum alkaline phosphatase,• Hypoproteinemia,• Anemia.ETHANOL 36SGOT, SGPTCholestasisDiagnosis
    37. 37. • In some instances, liver biopsy may beindicated, since in about 10% to 20% of casesof presumed alcoholic cirrhosis, anotherdisease process is found.ETHANOL 37
    38. 38. Silent Cirrhosis• Finally, cirrhosis may be clinically silent,discovered only at autopsy or• when stress such as infection or trauma tipsthe balance toward hepatic insufficiency.ETHANOL 38
    39. 39. Prognosis• Five-year survival approaches 90% inabstainers who are free of jaundice, ascites,or hematemesis;• it drops to 50% to 60% in those whocontinue to imbibe.ETHANOL 39
    40. 40. In the end-stage alcoholic the proximate causes of death are(1) hepatic coma,(2) massive gastrointestinal hemorrhage,(3) intercurrent infection(4) hepatorenal syndrome(5) hepatocellular carcinomaETHANOL 40
    41. 41. Summary• Alcoholic liver disease is a chronic disorderfeaturing steatosis, hepatitis, progressivefibrosis, cirrhosis, and marked derangementof vascular perfusion.• It can be regarded as a maladaptive state inwhich cells in the liver respond in anincreasingly pathologic manner to a stimulus(alcohol) that originally was only marginallyharmful.• For some unknown reason, cirrhosisdevelops in only a small fraction of chronicalcoholics. ETHANOL 41
    42. 42. Drug- and Toxin-Induced LiverDiseaseThe drugs and toxinswhich cause hepaticinjury along with theirspecific effects.ETHANOL 42
    43. 43. BKMC1231921
    44. 44. 4 5678 59 10111314 9
    45. 45. 10 8151617181119 20
    46. 46. 121222223 24
    47. 47. ETHANOL 47