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1. "With ordinary talent and extraordinary perseverance, all things are attainable." - Thomas E. Buxton "Achievement is connected with action, not in genes..…!” - Conrad Hilton

2. Alcoholic liver disease

3. Excessive alcohol consumption is the leading cause of liver disease. • Alcoholic liver disease comprises of three main stages • Hepatic steatosis • Alcoholic hepatitis • Cirrhosis

4. Hepatic steatosis • Pathogenesis : • 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. • Oxidation of fatty acid by mitochondria is decreased • Acetaldehyde impairs the function of microtubules, resulting in decreased transport of lipoproteins from liver • Collectively these metabolic consequences produce fatty liver.

5. 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, protein and water

6. Alcoholic Fatty Liver

7. 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.

8. Steatosis in Alcoholism

9. Alcoholic Fatty Liver

10. Clinical features of alcoholic steatosis • Hepatomegaly • Mild elevation of serum bilirubin, alkaline phasphatase and gamma GT

11. Alcoholic hepatitis • Is characterized by • Hepatocyte swelling and necrosis • Mallory bodies • Neutrophilic inflammatory response • Perivenular fibrosis

12. Hepatocyte swelling and necrosis: • Single or scattered foci of cells undergo swelling (ballooning degeneration) and necrosis

13. Mallory bodies: • Scattered hepatocytes accumulate cytokeratin intermediate filaments and other proteins • Visible as eosinophilic cytoplasmic inclusions in degenerating hepatocytes

14. Neutrophilic reaction: • Neutrophils accumulate around the degenerating hepatocytes, particularly those having Mallory bodies. • Lymphocytes and macrophages also enter portal tracts and spill into parenchyma

15. 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

16. Clinical features: • Malaise, anorexia, weight loss, upper abdominal discomfort, tender hepatomegaly. • Laboratory findings: • Hyperbilirubinemia • Elevated ALP,GGT, moderate elevation of AST • Neutrophilic leucocytosis

17. 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

18. Normal Liver

19. Cirrhosis

20. Micronodular cirrhosis:

21. Alcoholic Cirrhosis

22. 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.

23. Normal Liver Histology

24. Cirrhosis Fibrosis Regenerating Nodule

25. Liver Biopsy – Cirrhosis

26. Cirrhosis in Alcoholism

27. 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: • Hyperbilirubinemia, elevated serum aminotransferase, alkaline phasphatase, hypoproteinemia and anaemia

28. Alcoholic Liver Damage

29. Liver abscesses

30. Introduction • Liver abscesses can result from bacterial infection (pyogenic abscess) or from Entamoeba histolytica. • Pyogenic abscesses have a high mortality rate of 40%.  • Liver abscesses generally result from spread of infection from : • the digestive tract via the portal vein, • from biliary disease or • by direct extension from an adjacent infection.  • Risk factors include: • Biliary disease • Trauma • Diabetes • Malignancy. 

31. Aetiology of liver abscess • Enteric Gram-negative bacilli (aerobes and anaerobes) are frequently cultured.  • Many of the causative organisms originate in the gastrointestinal tract: • Escherichia coli • Klebsiella pneumoniae • Bacteroides spp. • Enterococcus spp. • Anaerobic Streptococcus spp. • Streptococcus ‘milleri’ group.

32. Diagnosis of liver abscess Signs and symptoms include: • Fever • Anorexia • Nausea • Weight loss • Weakness • Upper right quadrant pain • Jaundice is rare until a late stage of the infection.

33. Laboratory diagnosis • Diagnostic investigations include: • Culture of aspirated material (under ultrasound guidance) is the most useful diagnostic test • With the advent of modern systems and improved media, particularly for the recovery of anaerobic organisms, blood culture is often helpful. • Imaging • CT is the most useful imaging technique, with ultrasound effective for lesions more than a couple of centimetres in diameter.

34. Amoebic liver abscess • Amebiasis is a disease caused by a one-celled parasite called Entamoeba histolytica . • Mode of transmission: feco-oral with ingestion of amoebic cysts.

35. Symptoms of amoebic liver abscess • Pain • Enlarged liver with maximal tenderness over abscess • Intermittent fever (38-39°C) • Night sweats • Weight loss • Nausea • Vomiting • Cough • Dyspnoea

36. Symptoms of amebiasis • The symptoms often are quite mild and can include loose stools, stomach pain, and stomach cramping. • Amebic dysentery is a severe form of amebiasis associated with stomach pain, bloody stools, and fever. • Rarely, E. histolytica invades the liver and forms an abscess. • Even less commonly, it spreads to other parts of the body, such as the lungs or brain. 

37. Pathogenesis & pathology : • Amoebic liver abscess is always preceded by intestinal colonisation of the protozoan. • Trophozoites invade veins to reach the liver through the portal system. • Inoculation of amoebae into the liver results in acute inflammation & necrosis of hepatocytes. • The necrotic contents of the liver “abscess” are described as “anchovy-sauce” OR “chocolate-paste”.

38. Trophozoites of entamoeba histolytica:

39. The liver parenchyma is replaced by necrotic tissue surrounded by a thin rim of congested hepatic tissue, having a “shaggy” appearance due to fibrin.

40. Complications of amoebic liver abscess(ALA): • ALA has a high mortality rate when associated with other-organ involvement. • The abscess can rupture into : • the pleural space, • lung, • peritoneal cavity, • pericardial cavity and • the sub-phrenic space forming amoebic abscesses in these sites.

41. ‘Time’ is the best kept secret of the rich..! – Jim Rohn