Diseases of liver
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Diseases of liver
By the end of the session the student should be able to:Discuss the components of the liverDiscuss the diseases of liverDefine hepatitisList causes of hepatitisDescribe the morphological features of hepatitisDefine liver fibrosis, liver cirrhosisList causes of liver cirrhosisDiscuss clinical features and complications of cirrhosis
The main patterns of morphologic liver injury1-Degeneration and intracellular accumulation. 2-Necrosis and apoptosis. 3-Regeneration. 4-Inflammation. 5-Fibrosis. 6-Cirrhosis.
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). 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.
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.
The main patterns of morphologic liver injury4-Inflammation. 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
Causes of acute hepatitisViral hepatitisHepatitis A,B,C,D, andE, infectious mononucleosis (Epstein-Barr virus)cytomegalovirus Yellow fever
AlcoholToxins:carbon tetrachlorideDrugs:Paracetamol, amoxycillin,antituberculosis medicines,minocyclineIschemic hepatitis(circulatoryinsufficiency)PregnancyAuto immuneconditions, e.g.,systemic lupus erythematosus (SLE)Metabolic diseases, e.g.,Wilson's disease
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.
Causes of chronic hepatitis
Viral hepatitis:Hepatitis B,hepatitis D,hepatitis C(neitherhepatitis Anorhepatitis Ecauses chronic hepatitis)AutoimmuneAutoimmune hepatitisAlcoholDrugsmethyldopanitrofurantoinisoniazidketoconazoleNon-alcoholic steatohepatitisHeredityWilson's diseasealpha 1-antitrypsin deficiency
morphological features of Acute Hepatitis Gross: Enlarged, reddened liver; greenish if cholestatic MicroscopicHepatocyte injury: swelling (ballooning degeneration) HCV: mild fatty change of hepatocytes Hepatocyte necrosis: isolated cells or clusters If severe: bridging necrosis (portal-portal, central-central, portal-central) Regenerative changes: hepatocyte proliferation Portal tracts Inflammation: predominantly mononuclear Inflammatory spillover into adjacent parenchyma, with hepatocyte necrosis
morphological features of Chronic HepatitisChanges shared with acute hepatitis: Hepatocyte injury, necrosis, apoptosis, and regeneration Portal tracts Inflammation: Confined to portal tracts, or Spillover into adjacent parenchyma, with necrosis of hepatocytes ("interface hepatitis"), Bridging inflammation and necrosis Fibrosis: Portal deposition, or Portal and periportal deposition, or Formation of bridging fibrous septa HBV: ground-glass hepatocytes (accumulation of HBsAg) HCV: bile duct epithelial cell proliferation, lymphoid aggregate formation
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. 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.
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.
LIVER CIRRHOSISDefinition: 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. 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) 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.4) Loss of the lobular architecture of the liver.5) Interference with intrahepatic microcirculation.
Classification of cirrhosis
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.
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).
Clinical FeaturesAll forms of cirrhosis may be clinically silent. When symptomatic they lead to nonspecific manifestations: anorexia, weight loss, weakness, and, in advanced disease, frank debilitation
Effects and complications of liver cirrhosis:
I. Portal hypertension: It is elevation of the portal blood pressureII. Hepatocellular failure: 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.