pathology of liver and biliary tract.pptx

pathology of the hepato biliary tract with their management for those medial students

1. Disease of liver and biliary tract

2. VIRAL HEPATITIS Hepatitis A self-limited disease with an incubation period of 2 to 6 weeks does not cause chronic hepatitis spread by ingestion of contaminated water and foods The IgM response usually begins to decline in a few months and is followed by the appearance of IgG anti-HAV. The latter persists for years

3. Hepatitis B Virus Hepatitis B virus (HBV) can produce (1) acute hepatitis with resolution (2) chronic hepatitis, which may evolve to cirrhosis (3) fulminant hepatitis with massive liver necrosis (4) the backdrop for hepatitis D virus infection. HBV also plays an important role in the development of hepatocellular carcinoma.

4. cont.. HBV has a prolonged incubation period (4 to 26 weeks). Transfusion, blood products, dialysis, needle-stick accidents intravenous drug abuse, and homosexual activity constitute the primary risk categories for HBV infection

5. Hepatitis C Virus The major routes of transmission are inoculations and blood transfusions ,intravenous drug user The incubation period for HCV hepatitis ranges from 2 to 26 weeks In chronic HCV infection, circulating HCV RNA persists in many patients despite the presence of neutralizing antibodies

6. Hepatitis D Virus hepatitis D virus (HDV) is a unique RNA virus that is replication defective, causing infection only when it is encapsulated by HBsAg Acute coinfection occurs following exposure to serum containing both HDV and HBV. Superinfection of a chronic carrier of HBV with a new inoculum of HDV

7. Hepatitis E Virus Hepatitis E virus (HEV) hepatitis is an enterically transmitted, water-borne infection that occurs primarily in young to middle-aged adults sporadic infection and overt illness in children are rare. Epidemics have been reported from Asia and the Indian subcontinent, sub-Saharan Africa A characteristic feature of HEV infection is the high mortality rate among pregnant women, approaching 20%. In most cases, the disease is self-limiting; HEV is not associated with chronic liver disease

8. cont... Clinicopathologic Syndromes Acute asymptomatic infection with recovery: serologic evidence only Acute symptomatic hepatitis with recovery Chronic hepatitis: without or with progression to cirrhosis Fulminant hepatitis: with massive to submassive hepatic necrosis

9. Acute Hepatitis With acute hepatitis , hepatocyte injury takes the form of diffuse swelling ("ballooning degeneration") cholestasis, with bile plugs in canaliculi and brown pigmentation of hepatocytes. Two patterns of hepatocyte cell death are seen. In the first, rupture of cell membranes leads to cytolysis and focal loss of hepatocytes. The second pattern of cell death, apoptosis,It is caused by anti-viral cytotoxic T cells. .

10. Chronic Hepatitis Chronic hepatitis is defined as symptomatic, biochemical, or serologic evidence of continuing or relapsing hepatic disease for more than 6 months, with histologically documented inflammation and necrosis. the hepatitis viruses (HBV, HCV, and HBV + HDV) are responsible for most cases of chronic hepatitis

11. cont... common findings are lymphoid aggregates and bile duct damage in the portal tracts and focally mild to moderate macrovesicular steatosis. In all forms of chronic hepatitis, continued interface hepatitis and bridging necrosis are harbingers of progressive liver damage. The hallmark of irreversible liver damage is the deposition of fibrous tissue. At first, only portal tracts exhibit increased fibrosis, but with time, periportal septal fibrosis occurs, followed by linking of fibrous septa between lobules

12. cont... Continued loss of hepatocytes and fibrosis results in cirrhosis, with fibrous septae and hepatocyte regenerative nodules. This pattern of cirrhosis is characterized by irregularly sized nodules separated by variable but mostly broad scars

13. Fulminant Hepatitis When hepatic insufficiency progresses from onset of symptoms to hepatic encephalopathy within 2 to 3 weeks, it is termed fulminant hepatic failure. Much rarer causes, but just as life-threatening jaundice, encephalopathy Life-threatening extrahepatic complications. The overall mortality rate ranges from 25% to 90% in the absence of liver transplantation.

14. Autoimmune Hepatitis Autoimmune hepatitis is a chronic hepatitis with histologic features that may be indistinguishable from those of chronic viral hepatitis Female predominance (78%), particularly in young and perimenopausal women. The absence of viral serologic markers Elevated serum IgG and γ-globulin levels (>1.5 times normal) High serum titers of autoantibodies in 80% of cases, including antinuclear (ANA), antismooth muscle (SMA), and/or antiliver/kidney microsomes (anti-LKM1) antibodies Negative antimitochondrial antibody (AMA)

15. ALCOHOLIC LIVER DISEASE 1) hepatic steatosis (2) alcoholic hepatitis (3) cirrhosis

16. Hepatic Steatosis (Fatty Liver) small (microvesicular) lipid droplets accumulate in hepatocytes. With chronic intake of alcohol, lipid accumulates to the point of creating large, clear macrovesicular globules This transformation is initially centrilobular, but in severe cases, it may involve the entire lobule Although there is little or no fibrosis at the outset, with continued alcohol intake, fibrous tissue develops . The fatty change is completely reversible if there is abstention from further intake of alcohol.

17. Alcoholic Hepatitis Hepatocyte swelling and necrosis Mallory bodies: Neutrophils permeate the lobule and accumulate around degenerating hepatocytes . Lymphocytes and macrophages also enter portal tracts and spill into the parenchyma. Alcoholic hepatitis is almost always accompanied by prominent activation of sinusoidal stellate cells and portal tract fibroblasts, giving rise to fibrosis.

18. Alcoholic Cirrhosis. Cirrhosis may develop more rapidly in the setting of alcoholic hepatitis, within 1 to 2 years. Regenerative activity of entrapped parenchymal hepatocytes generates fairly uniformly sized "micronodules." With time, the nodularity becomes more prominent; scattered larger nodules As fibrous septae dissect and surround nodules, the liver becomes more fibrotic, loses fat, and shrinks progressively in size.

19. Pathogenesis. Short-term ingestion of up to 80 gm of alcohol (eight beers ) over one to several days generally produces mild, reversible hepatic changes Daily intake of 80 gm or more of ethanol generates significant risk for severe hepatic injury daily ingestion of 160 gm or more for 10 to 20 years is associated more consistently with severe injury

20. Clinical Features. The manifestations of alcoholic cirrhosis are similar to those of other forms of cirrhosis Commonly, the first signs of cirrhosis relate to complications of portal hypertension malaise, weakness, weight loss, and loss of appetite , jaundice, ascites, and peripheral edema . The stigmata of cirrhosis grossly distended abdomen, wasted extremities, caput medusae may be dramatically evident. Laboratory findings elevated serum aminotransferase, hyperbilirubinemia, variable elevation of serum alkaline phosphatase, hypoproteinemia

21. Metabolic Liver Disease HEMOCHROMATOSIS excessive accumulation of body iron, most of which is deposited in parenchymal organs such as the liver and pancreas. Because humans do not have a major excretory pathway for iron, hemochromatosis results either from a genetic defect causing excessive iron absorption or as a consequence of parenteral administration of iron The disease manifests itself typically after 20 gm of storage iron have accumulated

22. Excessive iron appears to be directly toxic to host tissues, by the following mechanisms: (1) lipid peroxidation radical reactions (2) stimulation of collagen formation (3) interactions of reactive oxygen species and of iron itself with DNA, leading to lethal injury or predisposition to hepatocellular carcinoma.

23. Clinical Features hepatomegaly, abdominal pain, skin pigmentation deranged glucose homeostasis or frank diabetes mellitus cardiac dysfunction (arrhythmias, cardiomyopathy), and atypical arthritis. A significant cause of death is hepatocellular carcinoma

24. WILSON DISEASE This autosomal-recessive disorder is marked by the accumulation of toxic levels of copper in many tissues and organs, principally the liver, brain and eye

25. Tumors MALIGNANT TUMORS Most arise from hepatocytes and are termed hepatocellular carcinoma (HCC). Much less common are carcinomas of bile duct origin, cholangiocarcinomas Hepatoblastoma is the most common liver tumor of young childhood, usually fatal within a few years if not resected

26. Hepatocellular Carcinomas More than 85% of cases of HCC occur in countries with high rates of chronic HBV infection. The largest numbers of cases are found in Asia (76% of all HCC), followed by Africa Three major etiologic associations have been established: viral infection (HBV, HCV), chronic alcoholism, and food contaminants (primarily aflatoxins)

27. Pathogenesis sex, chemicals, viruses, hormones, alcohol, and nutrition, interact in the development of HCC link chronic HBV and chronic HCV infection with liver cancer Repeated cycles of cell death and regeneration, as occurs in chronic hepatitis from any cause, are important in the pathogenesis of hepatocellular carcinomas. The accumulation of mutations during continuous cycles of cell division may damage DNA repair mechanisms and eventually transform hepatocytes.

28. CHOLELITHIASIS Risk Factors Advancing age Female sex hormones Female gender Oral contraceptives Pregnancy

29. Obesity Rapid weight reduction Gallbladder stasis Inborn disorders of bile acid metabolism Hyperlipidemia syndromes

30. Pathogenesis of Cholesterol Stones Cholesterol is rendered soluble in bile by aggregation with water-soluble bile salts and water-insoluble lecithins, both of which act as detergents. When cholesterol concentrations exceed the solubilizing capacity of bile (supersaturation), cholesterol can no longer remain dispersed and nucleates into solid cholesterol monohydrate crystals.

31. Pathogenesis of Pigment Stones Pigment gallstones are complex mixtures of abnormal insoluble calcium salts of unconjugated bilirubin along with inorganic calcium salts. Unconjugated bilirubin is normally a minor component of bile but increases when infection of the biliary tract leads to release of microbial β-glucuronidases, which hydrolyze bilirubin glucuronides. Thus, infection of the biliary tract, as with Escherichia coli or Ascaris lumbricoides , increases the likelihood of pigment stone formation

32. Clinical Features. Gallstones may be present for decades before symptoms develop, and 70% to 80% of patients remain asymptomatic throughout their lives. biliary pain More severe complications include empyema, perforation, fistulae

33. CHOLECYSTITIS Inflammation of the gallbladder may be acute, chronic, or acute superimposed on chronic. It almost always occurs in association with gallstones.

34. Acute Cholecystitis Acute calculous cholecystitis is an acute inflammation of the gallbladder Most cases of cholecystitis without gallstones occur in the following circumstances: the postoperative state after major, nonbiliary surgery; severe trauma , war injuries,severe burns; multisystem organ failure; sepsis

35. Pathogenesis. Acute calculous cholecystitis results from chemical irritation and inflammation of the obstructed gallbladder. The normally protective glycoprotein mucus layer is disrupted, exposing the mucosal epithelium to the direct detergent action of bile salts.

36. Acute acalculous cholecystitis is thought to result from ischemia. The cystic artery is an end artery with essentially no collateral circulation. Contributing factors may include Dehydration and multiple blood transfusions, leading to a pigment load Gallbladder stasis Inflammation and edema of the wall, compromising blood flow Bacterial contamination

37. Clinical Features An attack of acute cholecystitis begins with progressive right upper quadrant or epigastric pain, frequently associated with mild fever, anorexia, tachycardia, sweating, and nausea and vomiting. The upper abdomen is tender, Most patients are free of jaundice

38. Chronic Cholecystitis Chronic cholecystitis may be a sequel to repeated bouts of mild to severe acute cholecystitis, but in many instances, it develops in the apparent absence of antecedent attacks

39. Clinical Features. usually characterized by recurrent attacks of either steady or colicky epigastric or right upper quadrant pain. Nausea, vomiting, and intolerance for fatty foods are frequent accompaniments

40. compications Bacterial superinfection with cholangitis or sepsis Gallbladder perforation and local abscess formation Gallbladder rupture with diffuse peritonitis Biliary enteric (cholecystenteric) fistula,

41. CARCINOMA OF THE GALLBLADDER Carcinoma of the gallbladder is slightly more common in women and occurs most frequently in the seventh decade of life. diagnosed at late stage Gallstones are present in 60% to 90% of cases

42. Clinical Features. insidious and typically indistinguishable from those associated with cholelithiasis: abdominal pain, jaundice, anorexia, and nausea and vomiting Preoperative diagnosis of carcinoma of the gallbladder is the exception