5.2 Mitochondriopathy

Definition: Mitochondrial abnormailies due to drugs are found in cells of the proximal tubules. The mitochondria differ in number, size (giant mitochondria / megamitochondria), shape, and structure of cristae from normal tissue. Giant mitochondria are visible by light microscopy as inclusion bodies in individual tubular cells.

Without any other pathology or on the background of other lesions (e.g. characteristic for different drugs), giant mitochondria may be seen as inclusion bodies in the cells of the proximal tubules. Giant mitochondria are seen in HE stained sections but can be better visualized in trichrome stains . However,they are negative in the PAS or silver stains.

By electron microscopy, giant mitochondria predominate in the proximal tubule, usually one per cell. Multiple tubular inclusion bodies must be considered as phagolysosomes. Giant mitochondria are distributed inhomogeneously and are rare, even in cases of severe toxicity. Whereas some tubular cross sections may contain many giant mitochondria, adjacent ones may contain none. Giant mitochondria reach about half the size or even the full size of the nuclei,They are mostly round or oval, are rarely cigar-shaped or polymophic, and lie adjacent to the nuclei. The morphology of giant mitochondria lacks any specificity. They usually have very few cristae and frequently contain paracrystalline inclusions, large matrix granules, and lipid droplets. Because of the rarity of cristae and their polymorphism, they are easily mistaken for lysosomes. The other mitochondria vary slightly in size and shape, rarely they show more prominent lesions. A depletion of mitochondria may also be present. In rare cases, auto-phagolysosomes contain fragments of mitochondria. Giant mitochondria are often found in the tubular lumen.

Enlarged and giant mitochondria are rarely seen in native kidney diseases with concomitant nephrotic syndrome, after ischemia, and due to drugs and poisons (alcohol, lead). The pathogenesis of giant mitochondria is unclear. Different pathogenetic factors may be involved according aetiological differences (swelling and/or fusion of mitochondria).