Effects of parenteral nutrition with lipids on the human liver. An electron-microscopic study.

The ultrastructural findings in the Kupffer cells of a liver biopsy of a 5-week-old baby, who had received repeated i.v. administration of Intralipid (10%) in a dose of 20 ml/kg body weight/day for 12 days, are presented. Heterophagocytosis of free lipid droplets occurs by invagination of the Kupffer cell membrane. Large, solitary or conglomerated fat droplets surrounded by a membrane (lipophagosomes) are present within the hypertrophic and most active Kupffer cells. Small, round or elongated dark bodies (primary lysosomes) are linked with and/or seem to fuse with these lipophagosomes. In addition, smaller phagosomes almost completely surrounded by a dark small rim and a less electron-dense center probably represent (further stages of the lysosomal breakdown. The latter is also expressed by the condensation from the periphery towards the center of the original lipid droplets enclosed within the lysosomes. Angular inclusion bodies, build up of lipid remnants and a granular matrix of medium electron density, constitute far advanced stages of lysosomal digestion and represent the development or transformation of the phagocytosed lipids into lipogenous pigments. On the electron-microscopic level a distinction between lipofuscin granules and ceroid pigment can hardly be made at that stage. These pigment granules can be found in various amounts within the Kupffer cells and can stay there for a long time. This accumulation probably inhibits the clearance capacity of the cellular elements of the hepatic reticuloendothelial system. The hepatocytes and spaces of Disse seem not to be directly involved in the process of fat phagocytosis and breakdown as summarized above.