Diseases of the Liver. Wang Lin 王琳 Department of pathology Norman Bethune College of Medicine

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1 Diseases of the Liver Wang Lin 王琳 Department of pathology Norman Bethune College of Medicine

2 Degeneration Hepatic injury Basic pathological changes Hydropic degeneration Fatty change/steatosis Inflammatory cells infiltration Regeneration Fibrosis Necrosis &Apoptosis Spotty necrosis Piecemeal necrosis Bridging necrosis Submassive necrosis Massive necrosis Acidophilic body

3 Viral Hepatitis Carrier state Acute Asymptomatic Infection infection Acute hepatitis Fulminant hepatitis Death Persistent infection Submassive necrosis Massive necrosis Chronic hepatitis mild moderate severe Cirrhosis Hepatocellular carcinoma Death

4 Viral Hepatitis

5 Severe chronic hepatitis Severe and wide piecemeal necrosis & bridging necrosis. Hepatocytic regeneration. Fibrous septae reorganize the hepatic lobules. piecemeal necrosis Bridging necrosis portal tract

6 Alcoholic Liver Disease

7 Primary hepatic disease Viral hepatitis Alcoholic liver disease cirrhosis Primary carcinoma of the liver

8 Cirrhosis normal Definition end-stage liver disease characterized by diffuse disruption of the liver architecture by bands of fibrosis that divide the liver into nodules of regenerating liver parenchyma cirrhosis normal cirrhosis

9 Liver cirrhosis Chronic liver diseases The end stage of chronic diseases irreversible liver change Hepatocyte degeneration & necrosis Inflammation cell infiltration liver fibrosis hepatocyte regeneration Reorganization of hepatic lobules and vascular architecture The central pathogenetic processes in cirrhosis are progressive fibrosis and reorganization of the vascular architecture of the liver Pseudolobule formation Liver cirrhosis

10 Activation of hepatic stellate cells in hepatic fibrosis

11 Bridging necrosis Piecemeal necrosis Formation of pseudolobule Liver fibrosis Process of fibrosis and pseudolobule

12 Cirrhosis Classification Base on morphology Base on etiology Micronodular cirrhosis most of the nodules are < 3mm Macronodular cirrhosis most of the nodules are > 3mm Mixed type cirrhosis Alcoholic cirrhosis Post-viral hepatitis cirrhosis Post-necrotic cirrhosis Biliary cirrhosis

13 Classification of liver cirrhosis Micronodular cirrhosis most of the nodules are < 3mm Macronodular cirrhosis most of the nodules are > 3mm Mixed type cirrhosis Micronodular cirrhosis Macronodular cirrhosis

14 According to etiology & morphology Macronodular & Mixed Alcoholic cirrhosis Post-necrotic cirrhosis Micronodular Biliary cirrhosis

15 Alcoholic cirrhosis 酒精性肝硬化 Portal cirrhosis 门脉性肝硬化 Laennec cirrhosis

16 Pathological change of alcoholic cirrhosis Grossly In the early and mild stages size of liver: normal or some little enlargement consistency : slightly firm In later stage size and consistency of liver: smaller and much firmer surface and cut surface: diffuse nodular, cm features of nodules: similar size, yellow or yellow- green color, fine fibrous septae around each small nodule

17 Alcoholic cirrhosis Grossly size, weight, consistency, color, surface and cut surface of the liver normal

18 Alcoholic cirrhosis On the surface and cut section of portal cirrhosis notice the fine nodularity

19 Alcoholic cirrhosis Small regenerative nodules

20 Alcoholic cirrhosis Microscopically Nodules, also called regeneration nodules or pseudolobules, substitute the normal liver lobules There is no central vein (or accentric, or 2 veins) The liver cords are confused, no radiate arrangement Degeneration or necrosis of hepatocytes Thin stroma around the nodules. There are bile ductules and lymphocytes in the fibrous septae

21 Alcoholic cirrhosis normal pseudolobules

22 Alcoholic cirrhosis pseudolobules

23 Alcoholic cirrhosis Axan mellory staining pseudolobules encircled by thin fibrous septae

24 Alcoholic cirrhosis pseudolobules

25 Postnecrotic cirrhosis 坏死后性肝硬化 Macronodular and Mixed type cirrhosis 大结节及大小结节混合型

26 Postnecrotic cirrhosis Cause: severe hepatitis Morphology In general, it is similar to alcoholic cirrhosis, but The size of liver is smaller than alcoholic cirrhosis Deformation is more markedly Varying size of pseudolobules, big and irregular, 1-6 cm in diameter Rather wide fibrous septae around pseudolobules

27 Postnecrotic cirrhosis broad scar and coarse nodular surface coarse nodularity encircled by uneven fibrous septae

28 Postnecrotic cirrhosis variable nodules in size, coarsely nodular cirrhosis

29 Morphology of post-necrotic cirrhosis uneven fibrous septae

30 Morphology of post-necrotic cirrhosis pseudolobules and fibrous septae

31 Comparison between alcoholic and postnecrotic cirrhosis postnecrotic alcoholic

32 Comparison between alcoholic and postnecrotic cirrhosis alcoholic postnecrotic broad fibrous septa and marked infiltrative of inflammation cell

33 门脉性肝硬化与坏死后性肝硬化的区别 结节 纤维间隔 肝细胞变性坏死 新生小胆管 炎细胞 汇管区集中 门脉性 坏死后性 小 大小较一致大 大小不一致 薄 均匀轻 宽 不一重

34 Biliary cirrhosis 胆汁性肝硬化 Primary Secondary Micronudular cirrhosis

35 Biliary cirrhosis Grossly Micronodules Microscopically Periportal fibrosis Inflammatory cell infiltrate in portal area Proliferation of bile ducts Marked cholestasis Feathery necrosis Micronudular pattern

36 Morphology of biliary cirrhosis The nodules are fine or not typical, and its reform is not severe. Cholestasis is very evident.

37 Secondary biliary cirrhosis regeneration nodules fibrous septa inflammatory infiltrate biliary ducts reaction

38 Secondary biliary cirrhosis bile casts or bile thrombi (brown-green, amorphous)

39 Biliary cirrhosis Bile cast Bile ductules Fibrous septae

40 Biliary cirrhosis

41 Biliary cirrhosis Bile lake Feathery necrosis

42 Cirrhosis normal Definition end-stage liver disease characterized by diffuse disruption of the liver architecture by bands of fibrosis that divide the liver into nodules of regenerating liver parenchyma cirrhosis normal cirrhosis

43 Cirrhosis Cirrhosis is the combined process of inappropriate regeneration of the parenchyma of the liver accompanied by fibrosis. New vascular architecture contains arterio-venous shunts in the portal system Normal appearing hepatocytes without function

44 Clinical features of liver cirrhosis Portal hypertension 门脉高压 --Ascites --Portosystemic venous shunts --Congesitve splenomegaly --Gastrointestinal congestion Hepatic failure 肝功能衰减 --Decrease estrogen inactivation --Hemorrhage tendency --Jaudice --Hepatic encephalopathy

45 Hepatic vein Central vein Portal tract Normal liver g Portal vein Hepatic artery

46 Formation of portal hypertension Increased resistance to portal flow at the Hepatic artery Portal vein Hepatic artery Portal vein level of sinusoids, terminal hepatic veins. Anastomoses 吻合 between the arterial and portal systems. Hepatic vein normal Hepatic vein cirrhotic

47 Clinical consequences of portal hypertesion Ascites Portosystemic venous shunts Congesitve splenomegaly : g Gastrointestinal congestion

48 Portal hypertension --- Ascites 腹水 Pressure of hepatic sinusoid albumin colloid osmotic pressure Hepatic lymph fluid infiltrate into abdominal cavity Secondary hyperaldosteronemia 高醛固酮血症

49 Portosystemic venous shunts 侧枝分流形成 Esophageal capillary beds -- esophageal varices Rectum capillary beds -- hemorrhoids 痔 Abdomal wall collaterals -- Caput Medusae 海蛇头

50 Esophageal varices 食道静脉曲张 Varices in the lower esophagus as linear blue dilated veins There is hemorrhage around one of them

51 Caput Medusae 海蛇头 Caput medusae which consists of dilated veins seen on the abdomen of patient with liver cirrhosis

52 Congesitve splenomegaly normal 300g or less Enlarged spleen between g

53 Portal hypertension gastroenteric congestion ascites portosystem shunts splenomegaly

54 Clinical features liver cirrhosis Hepatic failure Disorder of protein synthesis -- Hypoproteinemia Hemorrhagic tendency Dysmetabolism cholochrome -- jaundice Decreased catabolism 分解代谢 of estrogen Hepatic encephalopathy 肝性脑病 Hepatorenal syndrome 肝肾综合征

55 Hepatic failure Jaundice 黄疸 hemorrhage liver palm 肝掌 Gynecomastia 男性乳腺发育

56 Spider nevi 蜘蛛痣 Hepatic failure

57 Cirrhosis It refers to fibrosis of the liver that involves both central veins and portal triads. This fibrosis is the result of liver cell necrosis and regenerative hepatic nodules. These nodules consist of hyperplastic hepatocytes with enlarged, atypical nuclei, irregular hepatic plates, and distorted vasculature. There is distortion of the normal lobular architecture. These changes diffusely involve the entire liver; they are not focal. It is thought that the fibrosis is the result of fibril-forming collagens that are released by hepatic stellate cells.

58 Primary carcinoma of the liver Hepatocellular carcinoma (HCC) Cholangiocarcinoma Mixed primary carcinoma of liver

59 Etiology & Pathogenesis of HCC Hepatic virus infection: HBV and HCV Liver Cirrhosis Alcoholic liver diseases Environment carcinogens: aflatoxin B 1 Hereditary metabolic diseases

60 Pathological changes of liver cancer Early stage carcinoma/small liver carcinoma: Single nodule or the sum of two nodules less than 3cm in diameter. Moderate and later stage/advanced liver carcinoma Unifocal type: common in right lobe, diameter>15cm. Nodular type: multifocal nodules, diameter 5~10cm. Diffuse type: diffusely infiltrative, less common.

61 Pathological changes of HCC Unifocal type 巨块型

62 Pathological changes of HCC Nodular type Diffuse type

63 Hepatocellular carcinoma a unifocal, massive neoplasm replacing most of the right hepatic lobe in a noncirrhotic liver poorly differentiated well-differentiated lesion tumor cells resemble hepatocytes and are arranged in nests, sometimes with a central lumen, some of which contains bile.

64 Summary Classification and pathological changes of cirrhosis Pathogenesis of cirrhosis Clinical manifestations of cirrhosis

65 Review Viral hepatitis Alcoholic liver disease Cirrhosis Carcinoma Peptic ulcer Carcinoma Carcinoma Gastritis Peptic ulcer Carcinoma Appendicitis