The organelle pathology of liver biopsy specimens from patients with either primary or secondary haemochromatosis was investigated by analytical subcellular fractionation in combination with enzymic microanalysis. The most striking changes were found in the lysosomes. Increased total activities but decreased latent activities of enzymes selectively localized to the high density population of lysosomes was demonstrated in the iron overloaded biopsies. Depletion of the iron, where possible, by venesection was accompanied by a return to normal of these changes. The other subcellular organelles, plasma membrane, endoplasmic reticulum, biliary canaliculi, mitochondria, peroxisomes and the low density population of lysosomes appear to be relatively unaffected. The minor changes demonstrated are similar to those seen in other forms of chronic liver disease. It is suggested that iron mediated lysosomal disruption is implicated in the pathogenesis of the tissue damage in haemochromatosis.
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