Hepatobiliary pathology

Disorders of the liver:
Primary: (Viral hepatitis, HCC)
Secondary: More common e.g. Cardiac decompensation, Diabetes mellitus, alcoholic liver disease, extrahepatic infection and liver involvement by disseminated ca.
Enormous functional reserve mask early impairment.
Laboratory Evaluation of Liver Disease

Bilirubin metabolism and elimination.
1. Normal bilirubin
production (0.2 to 0.3 g/day
2. Extrahepatic bilirubin is bound
to serum albumin and delivered to the liver.

3 and 4, Hepatocellular
uptake (3) and glucuronidation (4) by glucuronosyltransferase in the hepatocytes

generate bilirubin monoglucuronides and diglucuronides,
5, Gut bacteria deconjugate
the bilirubin and degrade it to colorless urobilinogens.

The urobilinogens and the residue of intact pigments are excreted in the feces, with some reabsorption and reexcretion into bile.



Morphological features of hepatic injury

Degenerative & intracellular accumulation.
Necrosis & apoptosis.
Inflammation.
Regeneration.
Fibrosis.



Chronic hepatitis
The following are features of chronic hepatitis, affecting HBV and HCV infections.
1. 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.

2. 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.
3. 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”).

4.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.

Cirrhosis
Defined as a diffuse process characterized by fibrosis and the conversion of normal liver architecture into structurally abnormal nodules.
Its major causes include chronic viral infections, alcoholic or nonalcoholic steatohepatitis (NASH), autoimmune
diseases affecting hepatocytes and/or bile ducts, and
iron overload.
Its main characteristics by definition are not focal but rather involve most (if not all) of the diseased liver and include:
Fibrous septa and formation of Parenchymal nodules.

Classification of cirrhosis:
PRIMARY(CRYPTOGENIC CIRRHOSIS) 10%.
SECONDARY DUE TO:

Alcohol abuse.
Chronic viral hepatitis.
Autoimmune disease.
Hereditary disorders.
Drug toxicity.
Long standing biliary obstruction.


The three main characteristics of cirrhosis are
(1) Involvement of most or all of the liver.
(2) bridging fibrous septa,
(3) parenchymal nodules containing a mix of senescent
and replicating (often stem/progenitor cell-derived) hepatocytes.

Cirrhosis usually is an end-stage process that may have multiple causes.
The most frequent are chronic hepatitis B and C and alcoholic and nonalcoholic steatohepatitis.
Less frequent causes are autoimmune and biliary diseases
and metabolic conditions such as hemochromatosis.
The main complications of cirrhosis are related to
decreased liver function, portal hypertension, and increased risk for development of hepatocellular carcinoma.




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.

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).


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).



Alcoholic liver disease:
A) Fatty liver.
B) Alcoholic hepatitis.
C) Cirrhosis.


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.
Gross
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.
Central hyaline sclerosis: The fibrous tissue present around the central vein tends to obliterate the veins and perivenular sinusoids.
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.


Clinical features:
Patients present with acute symptoms: right upper quadrant pain, anorexia, fever and jaundice.
Serum enzymes are abnormal and the white count may reach 25000. Mortality rate can reach up to 30%.

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.