1. Diseases of liver

2. By the end of the session the student should be able to: Discuss the components of the liver Discuss the components of the liver Discuss the diseases of liver Discuss the diseases of liver Define hepatitis Define hepatitis List causes of hepatitis List causes of hepatitis Describe the morphological features of hepatitis Describe the morphological features of hepatitis Define liver fibrosis, liver cirrhosis Define liver fibrosis, liver cirrhosis List causes of liver cirrhosis Discuss clinical features and complications of cirrhosis

8. The main patterns of morphologic liver injury 1-Degeneration and intracellular accumulation. 2-Necrosis and apoptosis. 3-Regeneration.4-Inflammation.5-Fibrosis.6-Cirrhosis.

9. The main patterns of morphologic liver injury (continue) 2-Necrosis and apoptosis. Cell death may be limited to scattered cells within the hepatic parenchyma or to the interface between the periportal parenchyma and inflamed portal tracts (interface hepatitis). Cell death may be limited to scattered cells within the hepatic parenchyma or to the interface between the periportal parenchyma and inflamed portal tracts (interface hepatitis). With more severe inflammatory or toxic injury, apoptosis or necrosis of contiguous hepatocytes may span adjacent lobules in a portal-to-portal, portal-to-central, or central-to-central fashion (bridging necrosis). Destruction of entire lobules (submassive necrosis) or most of the liver parenchyma (massive necrosis) is usually accompanied by hepatic failure. With more severe inflammatory or toxic injury, apoptosis or necrosis of contiguous hepatocytes may span adjacent lobules in a portal-to-portal, portal-to-central, or central-to-central fashion (bridging necrosis). Destruction of entire lobules (submassive necrosis) or most of the liver parenchyma (massive necrosis) is usually accompanied by hepatic failure.

10. The main patterns of morphologic liver injury (continue) 3-Regeneration. Cell death or tissue resection (such as in living-donor transplantation) triggers hepatocyte replication, to compensate for the cell or tissue loss. Hepatocyte proliferation is recognized by the presence of mitoses or by the detection of cell cycle markers by immunocytochemical staining. The cells of the canals of Hering constitute a reserve compartment of progenitor cells for hepatocytes and bile duct cells. Cells of this reserve compartment, known as oval cells, proliferate when hepatocytes are unable to replicate or have exhausted their replicative capacity.

11. The main patterns of morphologic liver injury 4-Inflammation. Injury to hepatocytes associated with an influx of acute or chronic inflammatory cells into the liver is termed hepatitis. Injury to hepatocytes associated with an influx of acute or chronic inflammatory cells into the liver is termed hepatitis. It is classified into acute and chronic It is classified into acute and chronic

12. Causes of acute hepatitis Viral hepatitis Viral hepatitis Hepatitis A, B, C, D, and E, Hepatitis A, B, C, D, and E, infectious mononucleosis (Epstein-Barr virus) infectious mononucleosis (Epstein-Barr virus) cytomegalovirus cytomegalovirus Yellow fever Yellow fever Alcohol Alcohol Toxins: carbon tetrachloride Toxins: carbon tetrachloride Drugs: Paracetamol, amoxycillin, antituberculosis medicines, minocycline Drugs: Paracetamol, amoxycillin, antituberculosis medicines, minocycline Ischemic hepatitis (circulatory insufficiency) Ischemic hepatitis (circulatory insufficiency) Pregnancy Pregnancy Auto immune conditions, e.g., systemic lupus erythematosus (SLE) Auto immune conditions, e.g., systemic lupus erythematosus (SLE) Metabolic diseases, e.g., Wilson's disease Metabolic diseases, e.g., Wilson's disease

13. 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. 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.

14. Causes of chronic hepatitis Causes of chronic hepatitis Viral hepatitis: Hepatitis B, hepatitis D, hepatitis C (neither hepatitis A nor hepatitis Ecauses chronic hepatitis) Viral hepatitis: Hepatitis B, hepatitis D, hepatitis C (neither hepatitis A nor hepatitis Ecauses chronic hepatitis) Autoimmune Autoimmune Autoimmune hepatitis Autoimmune hepatitis Alcohol Alcohol Drugs Drugs methyldopa methyldopa nitrofurantoin nitrofurantoin isoniazid isoniazid ketoconazole ketoconazole Non-alcoholic steatohepatitis Non-alcoholic steatohepatitis Heredity Heredity Wilson's disease Wilson's disease alpha 1-antitrypsin deficiency alpha 1-antitrypsin deficiency

15. morphological features of Acute Hepatitis Gross: Enlarged, reddened liver; greenish if cholestatic Enlarged, reddened liver; greenish if cholestaticMicroscopic Hepatocyte injury: swelling (ballooning degeneration) Hepatocyte injury: swelling (ballooning degeneration) HCV: mild fatty change of hepatocytes HCV: mild fatty change of hepatocytes Hepatocyte necrosis: isolated cells or clusters Hepatocyte necrosis: isolated cells or clusters If severe: bridging necrosis (portal-portal, central-central, portal- central) If severe: bridging necrosis (portal-portal, central-central, portal- central) Regenerative changes: hepatocyte proliferation Regenerative changes: hepatocyte proliferation Portal tracts Inflammation: predominantly mononuclear Inflammatory spillover into adjacent parenchyma, with hepatocyte necrosis Portal tracts Inflammation: predominantly mononuclear Inflammatory spillover into adjacent parenchyma, with hepatocyte necrosis

16. morphological features of Chronic Hepatitis Changes shared with acute hepatitis: Changes shared with acute hepatitis: Hepatocyte injury, necrosis, apoptosis, and regeneration Hepatocyte injury, necrosis, apoptosis, and regeneration Portal tracts Portal tracts Inflammation: Inflammation: Confined to portal tracts, or Confined to portal tracts, or Spillover into adjacent parenchyma, with necrosis of hepatocytes ("interface hepatitis"), Spillover into adjacent parenchyma, with necrosis of hepatocytes ("interface hepatitis"), Bridging inflammation and necrosis Bridging inflammation and necrosis Fibrosis: Fibrosis: Portal deposition, or Portal deposition, or Portal and periportal deposition, or Portal and periportal deposition, or Formation of bridging fibrous septa Formation of bridging fibrous septa HBV: ground-glass hepatocytes (accumulation of HBsAg) HBV: ground-glass hepatocytes (accumulation of HBsAg) HCV: bile duct epithelial cell proliferation, lymphoid aggregate formation HCV: bile duct epithelial cell proliferation, lymphoid aggregate formation

17. The main patterns of morphologic liver injury (continue) 5-Fibrosis. Fibrous tissue is formed in response to inflammation or direct toxic insult to the liver. Deposition of collagen has lasting consequences on hepatic patterns of blood flow and perfusion of hepatocytes. Fibrous tissue is formed in response to inflammation or direct toxic insult to the liver. Deposition of collagen has lasting consequences on hepatic patterns of blood flow and perfusion of hepatocytes. In the initial stages, fibrosis may develop within or around portal tracts (portal or periportal fibrosis) or around the central vein, or fibrous tissue may be deposited directly within the sinusoids around single or multiple hepatocytes (pericellular fibrosis). In the initial stages, fibrosis may develop within or around portal tracts (portal or periportal fibrosis) or around the central vein, or fibrous tissue may be deposited directly within the sinusoids around single or multiple hepatocytes (pericellular fibrosis). With time, fibrous strands link regions of the liver (portal-to-portal, portal-to-central, central-to-central), a process called bridging fibrosis. With time, fibrous strands link regions of the liver (portal-to-portal, portal-to-central, central-to-central), a process called bridging fibrosis.

18. 6-Cirrhosis. With progressive parenchymal injury and fibrosis, the liver develops nodules of regenerating hepatocytes surrounded by bands of scar tissue. In this process, the normal liver architecture is destroyed, and the condition is termed cirrhosis. 6-Cirrhosis. With progressive parenchymal injury and fibrosis, the liver develops nodules of regenerating hepatocytes surrounded by bands of scar tissue. In this process, the normal liver architecture is destroyed, and the condition is termed cirrhosis.

19. LIVER CIRRHOSIS Definition: the end stage of chronic liver disease, It is a chronic diffuse progressive and irreversible liver disease characterized by: 1) Necrosis and degeneration of liver cells. 2) Bridging fibrous septa in the form of delicate bands or broad scars linking portal tracts with one another and portal tracts with terminal hepatic veins. Fibrosis is the key feature of progressive damage to the liver. 3) 3) Regeneration of liver cells forming regenerating nodules lacking the normal lobular pattern. Parenchymal nodules containing hepatocytes encircled by fibrosis, Nodularity results from cycles of hepatocyte regeneration and scarring. nodules lacking the normal lobular pattern. Parenchymal nodules containing hepatocytes encircled by fibrosis, Nodularity results from cycles of hepatocyte regeneration and scarring. 4) Loss of the lobular architecture of the liver. 5) Interference with intrahepatic microcirculation.

20. Classification of cirrhosis I- Anatomical classification: I- Anatomical classification: 1) Micronodular cirrhosis: The liver surface is fine granular, the nodules are 1 or 3 mm in diameter and of uniform size and shape. 2) Macronodular cirrhosis: The surface of the liver is coarse granular and the nodules vary in size but usually more than 1 cm in diameter. 3) Mixed nodular cirrhosis: The outer and cut surfaces of the liver show marked variation in the diameter of the nodules.

22. II- Aetiological classification: II- Aetiological classification: 1- Post-hepatitic cirrhosis (HBV and HCV ). 2- Post-necrotic cirrhosis: Secondary to hepatotoxic liver cell necrosis due to drugs, chemicals or viruses. 3- Alcoholic cirrhosis. 4-Biliary cirrhosis (Due to intra and extra-hepatic biliary obstruction). 5- Cardiac cirrhosis. 6- Immunological (lupoid hepatitis ) 7- Metabolic cirrhosis: a- Haemochromatosis (Disturbances in iron metabolism). b- Wilson disease (Disturbances in copper metabolism). c- Alpha-1 antitrypsin deficiency. 8- Malnutrition. 9- Syphilitic cirrhosis. 10- Cryptogenic cirrhosis (unknown cause).

23. Clinical Features All forms of cirrhosis may be clinically silent. When symptomatic they lead to nonspecific manifestations: anorexia, weight loss, weakness, and, in advanced disease, frank debilitation

24. Effects and complications of liver cirrhosis: I. Portal hypertension: It is elevation of the portal blood pressure II. Hepatocellular failure: Occurs due to continuous and progressive loss of liver cells and distortion of the hepatic circulation. Occurs due to continuous and progressive loss of liver cells and distortion of the hepatic circulation. III. Liver cell carcinoma: The incidence of liver cell carcinoma in cirrhotic liver is more than that of non cirrhotic one. Carcinoma is more liable to complicate post-hepatitic cirrhosis, haemochromatosis and alcoholic cirrhosis.