Page 452 - Concise Pathology for Exam Preparation ( PDFDrive )

15 Diseases of the Hepatobiliary System and Pancreas 437

Alcoholic Hepatitis
• Fifteen to twenty years of alcohol intake predispose an individual to alcoholic hepatitis.
It usually presents suddenly after a bout of excessive drinking with malaise, anorexia
and upper abdominal discomfort, elevated ALT and AST with AST/ALT ratio . 1.
• Unlike fatty liver which reverses completely after alcohol withdrawal and proper
nutrition, alcoholic hepatitis may sometimes persist and progress to cirrhosis.
Pathogenesis
• Acetaldehyde, a major metabolic intermediate of alcohol, induces lipid peroxidation
and acetaldehyde–protein adduct formation, which disrupts cytoskeletal and membrane
proteins.
• Alcohol directly affects microtubule organization, mitochondrial and membrane
functions.
• Reactive oxygen species (ROS) generated during oxidation of ethanol by microsomal
ethanol oxidizing system can damage membrane and proteins.
• ROS are also generated by neutrophils infiltrating the liver.
• Under normal circumstances glutathione is transported from the cytoplasm to the mi-
tochondria where it neutralizes the ROS. There is impairment of this transport in alco-
holic liver disease leading to mitochondrial dysfunction by ROS.
• In the intestine, alcohol causes release of endotoxin (lipopolysaccharide or LPS) from
the gram-negative flora which enters portal circulation to induce production of proin-
flammatory cytokines (TNF-alfa, IL-6 and TGF-alfa) from kupffer cells. This causes
hepatocellular injury/damage.

Pathology
The liver is enlarged, yellow but firm on account of fibrosis. The following microscopic
features are seen:
• Hepatocyte swelling and necrosis: Ballooning and necrosis of single and small groups
of hepatocytes.
• Mallory–Denk bodies or Mallory hyaline: Tangled skeins of intermediate filaments vis-
ible as dense, eosinophilic inclusions in the perinuclear zone cytoplasm of hepatocytes.
Also seen in Wilson disease, chronic cholestatic syndromes and hepatocellular tumours.
• Neutrophil infiltration: Present around degenerating hepatocytes particularly those
with Mallory bodies.
• Fibrosis: Initially pericellular (chicken wire fence pattern), sinusoidal and perivenu-
lar; with prolonged bouts of alcohol intake; periportal fibrosis may also be seen.

Alcoholic (Laennec or Portal) Cirrhosis
It is the irreversible end stage of alcoholic liver disease which entails a diffuse loss of
architecture with fibrosis and nodule formation.

Pathogenesis
Activation of Stellate cells and portal fibroblasts eventually progresses to extensive central–
central, central–portal and portal–portal fibrosis.
Pathology
• Liver is yellow, fatty and enlarged in the initial stages and becomes brown, shrunken and
firm in the later stages.
• Capsular surface shows nodules (hobnail appearance – initially micronodules are seen
and they later coalesce to form macronodules to show a mixed pattern).
• There is diffuse loss of normal parenchymal and vascular architecture with formation of
regenerating nodules.
• New vascular channels form in the fibrous septae which connect the portal vessels with
the terminal hepatic veins.

mebooksfree.com