Page 455 - Concise Pathology for Exam Preparation ( PDFDrive )

440 SECTION II Diseases of Organ Systems

• Due to mutation in ATP7B, a gene located on chromosome 13 (encodes for ATPase
metal iron transporter, localized to Golgi region of hepatocytes; the deficiency of which
impairs copper excretion into bile)

Normal Copper Physiology (Flowchart 15.3)

Absorption of ingested copper in duodenum and jejunum

Transportation to portal circulation as a complex with albumin and histidine
Dissociation of free copper
Uptake by hepatocytes followed by incorporation into an
α-2 globulin (apoceruloplasmin) to form ceruloplasmin

Secretion of ceruloplasmin into plasma
(accounts for 90–95% of plasma copper)

Hepatic uptake of senescent ceruloplasmin from plasma followed by
lysosomal degradation and secretion of free copper into bile
FLOWCHART 15.3. Normal copper physiology.

Wilson disease is characterized by the following abnormalities:
• Failure of secretion of ceruloplasmin in plasma
• Failure of biliary copper excretion causing its accumulation in the body
Copper causes toxic liver injury by:
• Inducing formation of free radicals
• Binding to sulphydryl groups of cellular proteins
• Displacing other metals from hepatic metalloenzymes

Clinicopathological Features

• Presents between 5 and 30 years
• The excess copper is deposited in various tissues resulting in damage to:
Liver
• Fatty change
• Acute and chronic hepatitis with hepatocytic ballooning and presence of ‘Mallory–
Denk bodies’
• Massive liver cell necrosis
• Cirrhosis
Brain (basal ganglia)
Basal ganglia show atrophy and cavitation leading to neuropsychiatric manifestations:
• Neurological manifestations: Movement disorders, especially resting tremors. Less
commonly spasticity, rigidity, chorea, dysphagia and dysarthria may be seen.
• Psychiatric manifestations: Bizarre behavioural disturbances similar to schizophre-
nia, manic-depressive psychosis and neurosis.
Eyes: Kayser–Fleischer rings (green to brown deposits of copper in the Descemet mem-
brane in the limbus of cornea). Kayser–Fleischer rings may be associated with ‘sunflower
cataracts’.
Others: RBCs show haemolysis, deposits of copper in kidneys may cause renal tubular
damage and in the skeleton may cause osteoporosis.

Investigations
• Slit-lamp examination of the eyes for Kayser–Fleischer rings

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