Pathology of the Liver
• Normal anatomy:
• Microarchitecture.
• Pathology.
Hepatic injury:
1. Metabolic.
2. Toxic.
3. Microbial.
4. Circulatory.
5. Neoplastic.
Disorders of the liver:
• Primary: (Viral hepatitis, HCC)
• Secondary: More common e.g. Cardiac decompensation, Disseminated ca., alcoholism, extrahepatic infection.
Enormous functional reserve mask early infection.
General aspect of liver diseases:
Jaundice
Yellow discoloration of the
–skin
–mucous membranes
–sclera
Due to abnormal metabolism or retention of bilirubin
Bilirubin levels (icterus)> 5 mg/dL
Pathological terms regarding hepatic disease
• The limiting plate of hepatocytes around the portal tracts:
It is usually intact, presenting a sharp border.
There may also be proliferating bile ductules in the portal spaces.
• Confluent hepatic necrosis
The term confluent implies a geographic distribution, affecting regions of the lobule; in terms of severity there is bridging, submassive and massive necrosis.
• Bridging necrosis:
Bands of necrotic liver cells stretching from portal tract to portal tract, from central vein to central vein or from portal tract to central vein. This pattern is not uniform in the liver; some lobules are affected, others are not. As a result of the necrosis, the collagen stroma collapses, forming bands, which are increased by newly formed collagen. Bridging may disappear but occasionally may progress, terminating in liver failure.
• Submassive confluent necrosis:
It involves entire lobules; patients may die in hepatic failure.
• Massive hepatic necrosis:
It is a very severe form, almost always fatal. Because of the rapid clinical course it is called fulminant hepatitis. The liver weighs less than 500g, and has a soft, flabby consistency (“acute yellow atrophy”).
Virtually all liver cells are dead and there are no inflammatory cells.
Chronic hepatitis
The following are features of chronic hepatitis, affecting HBV and HCV infections.
• Piecemeal necrosis:
It is an inflammation affecting the periportal area, destroying the limiting plate, creating an irregular border between the parenchyma and the portal areas.
• Portal inflammation:
There are lymphocytes, plasma cells and macrophages. The lymphocytes form follicles in hepatitis C but only in a minority of cases. There is also bile duct damage, with necrosis of ductal cells and intraepithelial inflammation. Proliferation of bile ductules is also present as a response to injury.
• Intralobular inflammation:
There is focal necrosis and accumulation of lymphocytes in the parenchyma, with scattered apoptotic bodies and enlarged Kupffer cells.
The presence of bridging necrosis is a bad prognostic sign. In chronic hepatitis the hepatocytes may contain HBsAg particles; they have a diffuse granular surface (“ground glass hepatocytes”).
• Periportal fibrosis:
Fibrous tissue develops in the portal spaces as a result of the piecemeal necrosis, extending to the periportal area. The fibrous tissue may eventually link with other portal tracts or central veins. The end stage of this process is cirrhosis: nodules of liver tissue surrounded by fibrous tissue.
Acute Viral Hepatitis
Morphology of acute viral hepatitis is the same for all viruses, from A to E. Liver cell injury and necrosis are the main changes. The necrosis may affect single cells or groups of cells. Necrotic cells may appear as eosinophilic bodies (called Councilman or apoptotic bodies); other cells appear swollen (balloon cells), yet others differ in size and shape.
Alcoholic liver disease
Alcohol is a direct hepatotoxic agent.
15% of alcoholics can be expected to develop cirrhosis. The amount of alcohol necessary to produce chronic liver disease is about 80g/day.
Women are more susceptible to alcoholic liver damage than men.
Alcohol is metabolized by the liver to acetaldehyde and acetate; it is oxidized through the enzyme alcohol dehydrogenase. Another minor metabolic pathway is a microsomal ethanol oxidizing system (MEOS).
There are 3 main manifestations of alcoholic liver disease:
A) Fatty liver.
B) Alcoholic hepatitis.
C) Cirrhosis.
A) Fatty Liver:
Fat is accumulated in the liver in practically all chronic alcoholics. The mechanism is not precisely understood. The fat accumulated is mostly derived from the diet; in the fasting state it is from endogenous fat deposits.
Alcohol increases fatty synthesis, decreases oxidation of fatty acids, increases triglyceride production and impairs release of lipoproteins.
All these factors produce a fatty liver.
The livers are usually heavy, as much as three times the usual weight; microscopically it varies from minute fat droplets to distention of the entire cytoplasm by large droplets. The liver cells may look like fat cells. Patients with fatty livers have few symptoms and mild abnormalities of serum enzymes. It is fully reversible
B) Alcoholic hepatitis:
It is an acute inflammation, characterized by the presence of polymorph neutrophils, necrosis of liver cells, fibrosis around central veins and cytoplasmic inclusions within hepatocytes. The inclusions are called hyalin bodies or Mallory bodies; they consist of irregular masses of eosinophilic material arranged in a perinuclear fashion and are formed by aggregates of intermediate (cytokeratin)filaments. The polymorph neutrophils are clustered around cells with Mallory bodies, attracted by chemotaxis.
Cholestasis may be present, as well as steatosis. The fibrous tissue present around the central vein tends to obliterate the veins and perivenular sinusoids; the lesion has been called central hyaline sclerosis. The portal spaces in alcoholic hepatitis range from normal to distended by lymphocytes and proliferating bile ductules.
Pathogenesis:
The pathogenesis of alcoholic hepatitis is uncertain; patients usually have fatty livers for years and for unknown reasons alcohol produces an inflammatory reaction.
C) Alcoholic cirrhosis:
Fatty liver and alcoholic hepatitis may lead to cirrhosis in about 15% of alcoholics. The term denotes the formation of fibrous septa surrounding hepatocellular nodules. Alcoholic cirrhosis is one of the most common causes for liver transplantation, since it is usually considered as end stage liver disease.
Cirrhosis:
Causes:
• PRIMARY(CRYPTOGENIC CIRRHOSIS)20-30%.
• SECONDARY DUE TO:
1.Alcohol abuse.
2.Chronic viral hepatitis.
3.Autoimmune disease.
4.Heriditary disorders.
5.Drug toxicity.
6.Long standing biliary obstruction.
• Pathologic finding:
In all cases the liver is firm and nodular, owing to fibrosis.
• Gross examination: cirrhosis can be classified into micronodular and macronodular or irregular( not significant).
• Etiological classification:
• Alcoholic cirrhosis, the liver appear to be fatty (yellow)& uniformly micronodular,the • Post hepatitic cirrhosis, The liver is usually shrunken, macronodular, & transvers by irregularliver may be enlarged , of normal size or small.
fibrous scar. There are histologic sign of chronic inflammation.
• Pigmentary cirrhosis, is the charcteristic lesion of hemochromatosis.
the liver parenchyma contains nodules of variable size & is reddish-browen owing to iron pigment accumulation.
4. Biliary cirrhosis, may be primary ( autoimmune destruction of the portal bile ducts).
5. Cryptogenic cirrhosis.
6. Rare types: ( AAT, Wilson disease)
Primary biliary cirrhosis (PBC)
It is a chronic progressive cholestatic disease that destroys intrahepatic bile ducts. It occurs mainly in middle aged women, with familial predominance of 4%.
It is an autoimmune disease; many patients have other autoimmune disorders such as rheumatoid arthritis, Sj?gren syndrome or systemic lupus.
There are humoral and cellular immunity alterations; IgM is elevated and over 95% of patients have circulating antimitochondrial antibodies (AMA).
They may also have circulating antinuclear, antithyroid, antiplatelets and antiribonucleoprotein antibodies.
Primary sclerosing cholangitis (PSC)
It is also a chronic cholestatic liver disease with inflammation and fibrosis that progressively obstructs the intra and extrahepatic bile ducts. In contrast to PBC most patients are men under the age of 40 years. Over 2/3 of patients have inflammatory bowel disease (ulcerative colitis or Crohn’s).
Genetic and immunological factors have been invoked in its pathogenesis; it is associated with HLA haplotypes, such as HLA B8 and DR3.
They have circulating antineutrophil cytoplasmic antibodies (ANCA).