Page 454 - Concise Pathology for Exam Preparation ( PDFDrive )

15 Diseases of the Hepatobiliary System and Pancreas 439

• The most common form of the disease is inherited as an autosomal recessive disorder
characterized by mutations in the HFE gene that regulates the levels of hepcidin, the
iron hormone produced by liver, which inhibits iron absorption.
• Hepcidin levels are reduced in all known forms of haemochromatosis leading to increased
absorption of dietary iron over years.
• Ninety percent of the patients are males (females are protected by the iron loss in
menstruation and pregnancy).
• Excessive iron can be directly toxic to host tissues by the following mechanisms:
• Lipid peroxidation by iron-mediated free radical reactions
• Interaction of iron and reactive oxygen species generated by the iron directly with
DNA leading to cell injury and predisposition to hepatocellular carcinoma
• Stimulation of Ito cells/hepatic stellate cells to produce more collagen

Pathology
• The excess iron deposited in various tissues results in damage to liver, pancreas, heart,
pituitary gland and skin.
• Pancreas show diffuse interstitial fibrosis and parenchymal atrophy with haemosiderin
deposits in the acinar as well as islet cells (the latter causing diabetes).
• Heart is enlarged with haemosiderin deposits in the myocardial fibres (causing arrhyth-
mias and cardiomyopathy).
• Haemosiderin deposits in the synovium leads to acute synovitis.
• Testes are small and atrophic (leading to loss of libido and infertility).

Clinical Features
• The total body iron ranges between 2 g (normal is 4 g).
• Presents in men over 40 years.
• Fully developed cases show a triad of
(i) Micronodular cirrhosis
(ii) Diabetes mellitus (bronze diabetes)
(iii) Skin pigmentation (attributed mainly to excess melanin production and partly to
haemosiderin deposits)
• Other manifestations include loss of libido, testicular atrophy, spider nevi, loss of body
hair, jaundice and ascites, heart failure and cardiac arrhythmias.
• It is associated with a high incidence of hepatocellular carcinoma.
2. Acquired (secondary) haemochromatosis (also called haemosiderosis)
Develops secondary to:
(a) Chronic anaemias:
(i) Thalassaemia major
(ii) Sideroblastic anaemia
(b) Exogenous iron overload:
(i) Multiple blood transfusions
(ii) Repeated iron injections
(iii) Prolonged oral iron intake (including African iron overload or Bantu siderosis)
(c) Chronic liver diseases
(d) Porphyria cutanea tarda
Note: In secondary iron overload, iron accumulates in Kupffer cells rather than hepatocytes
(accumulation in hepatocytes typically occurs in hereditary haemochromatosis).

Q. Write briefly on the aetiology and clinicopathological features
of Wilson disease (hepatolenticular degeneration).
Ans. The following are the salient features of Wilson disease:

Aetiology

• Hereditary disorder with autosomal recessive inheritance

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