Figure 114

Ultrastructural appearance of proximal tubule cells in aminoglycoside-treated patients (4 days of therapeutic doses). Lysosomes (large arrow) contain dense lamellar and concentric structures. Brush border, mitochondria (small arrows) and peroxisomes are unaltered. At higher magnification the structures in lysosomes show a periodic pattern. The bar in A represents 1 ^m, in part B, 0.1 ^m [7].

FIGURE 11-5 (see Color Plate)

FIGURE 11-5 (see Color Plate)

Administration of aminoglycosides for days induces progression of lysosomal phospholipidosis. The overloaded lysosomes continue to swell, even if the drug is then withdrawn. In vivo this overload may result in loss of integrity of the membranes of lysosomes and release of large amounts of lysosomal enzymes, phospholipids, and aminoglycosides into the cytosol, but this has not been proven. Thus, these aminoglycosides can gain access to and injure other organelles, such as mitochondria, and disturb their functional integrity, which leads rapidly to cell death. As a consequence of cell necrosis, A, intratubular obstruction by cell debris increased intratubule pressure, a decrease in the glomerular filtration rate and cellular infiltration, B, may ensue. In parallel with these lethal processes in the kidney, a striking regeneration process is observed that is characterized by a dramatic increase in tubule cell turnover and proliferation, C, in the cortical interstitial compartment.

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