Hemochromatosis: hepcidin, HFE and where iron settles
- Lesion
In hemochromatosis the gut absorbs too much iron for years; the iron piles up in the liver, pancreas, heart and skin.
What it is
Hemochromatosis is excess body iron deposited in parenchymal cells. The hereditary form is an autosomal recessive defect of hepcidin regulation, most often homozygous C282Y mutation of HFE. Low hepcidin leaves ferroportin active, so the gut absorbs iron without control. Secondary hemochromatosis (hemosiderosis) comes from transfusions and ineffective erythropoiesis, as in thalassemia. Iron injures cells through free radicals and drives fibrosis.
Structure
- Liver: golden-brown hemosiderin granules in periportal hepatocytes, later in all zones, bile ducts and Kupffer cells; micronodular cirrhosis; dark brown liver.
- Pancreas: dark brown, with atrophy, fibrosis and islet loss (diabetes).
- Heart: iron in myocytes, dilated or restrictive cardiomyopathy.
- Skin: pigmentation largely from melanin increase, with some iron in the dermis.
Step by step
- A mutation (HFE, or HJV, HAMP, TFR2) lowers hepcidin production.
- Ferroportin stays on enterocytes and macrophages, so iron enters plasma freely.
- Transferrin saturates and non-transferrin-bound iron is taken up by parenchymal cells.
- Iron catalyses free radical formation (Fenton reaction), causing lipid peroxidation.
- Iron also stimulates collagen synthesis by stellate cells and damages DNA.
- Over decades: cirrhosis, pancreatic islet loss, cardiomyopathy and HCC.
Markers
- Prussian blue (Perls) stain
- Hepatic iron index
- HFE genotype
In the lab
- Raised transferrin saturation is the earliest clue; ferritin reflects total iron stores.
- MRI quantifies liver iron and often replaces biopsy.
Test yourself
Think of the answer, then tap the question to see it.
How does HFE mutation lead to iron overload?
It lowers hepcidin; without hepcidin ferroportin is not degraded, so intestinal iron absorption and macrophage iron release stay high.
Which stain shows the iron in a hemochromatosis liver biopsy?
Prussian blue (Perls), which colours hemosiderin blue.
Why do women develop hemochromatosis later than men?
Physiologic iron losses through menstruation and pregnancy delay accumulation.
Which cancer is most increased in hemochromatosis with cirrhosis?
Hepatocellular carcinoma.
Elsewhere in DurgiPedia
Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Hemochromatosis: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); Hereditary hemochromatosis: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026).
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Representative model, for educational purposes only.