75. Iron overload (hemochromatosis, hemosiderosis) and iron deficiency - etiology, pathogenesis, clinical manifestations.

Iron overload (hemochromatosis and hemosiderosis) and Iron deficiency – etiology, pathogenesis, and clinical manifestations.

Definitions

• Hemochromatosis: Genetic disorder with increased intestinal iron absorption, leading to parenchymal iron deposition and organ dysfunction.
• Hemosiderosis: Secondary iron overload, usually due to excess iron intake or transfusions, with iron deposited mostly in reticuloendothelial cells (macrophages).

Etiology

Hemochromatosis (primary iron overload)

• Hereditary hemochromatosis (most common form):
• Autosomal recessive.
• Mutation in HFE gene (most common: C282Y mutation).

Hemosiderosis (secondary iron overload)

• Multiple blood transfusions (e.g., in thalassemia major).
• Excess parenteral or oral iron therapy.
• Chronic hemolytic anemias (ineffective erythropoiesis with iron release).
• Chronic liver diseases (e.g., alcoholic liver disease).

Pathogenesis

1. Excess iron absorbed or received → iron accumulates in tissues.
2. Iron catalyzes formation of free radicals (via Fenton reaction) → lipid peroxidation → cell damage.
3. Progressive fibrosis and organ dysfunction, especially liver, pancreas, heart.

Clinical manifestations

Hemochromatosis (classic triad)

• Cirrhosis → hepatomegaly, risk of hepatocellular carcinoma.
• Diabetes mellitus ("bronze diabetes") → due to pancreatic islet damage.

Skin pigmentation ("bronze skin").

Other features

Cardiomyopathy (restrictive or dilated).

Arthropathy (especially of MCP joints).

Hypogonadism (pituitary or testicular iron deposition).

Fatigue, weakness.

Hemosiderosis

Usually milder; iron mainly in macrophages.

Organ dysfunction less common initially, but possible with heavy chronic iron loading.