The Rat Hepatocyte After Exposure to High Altitude: Structural and Chemical Changes

Abstract

One-day-old rats were exposed for 2 weeks in a low pressure chamber at a simulated altitude of 4,700 m. Then total esterified fatty acids, phospholipids and glycogen were determined in their livers, and electron microscopy of the liver cells was carried out.Normal rats of the same age were examined as controls. In the rats exposed to simulated high altitude, total esterified fatty acids were more than thrice the control value, phospholipid the same as the control value, and glycogen less than the control value. Their hepatocytes showed a marked increase in cytoplasmic lipid droplets, most pronounced near the central vein of the hepatic lobules; a marked diminution in rough endoplasmic reticulum; and generally absence of glycogen particles. Dense mitochondria of normal appearance were seen very closely apposed to the lipid droplets.Altitude appears to interfere with the normal development of the hepatocyte, which remains in a rather enzymatically immature stage.Altitudes over 3,900 m produce fatty degeneration in the liver cells of new born rats [Chiodi et al., 1952]. Similar results were obtained by Krum [1957] in rats born at 3,810 m. In Krum's report the high mortality in the new born rats was associated with a low glycogen content and an increase in liver fat, and was attributed to starvation, but Chiodi [1964] found that high altitudes produce a fatty degeneration of the liver without evidence of faulty lactation. The present report correlates the structure of the heptatocyte with the lipid and glycogen variations in response to high altitude. MATERIALS AND METHODSRats of the Holtzmann strain were used. Mothers and one-day-old litters were exposed for 14 days in a low pressure chamber to a simulated altitude of 4,700 m (424 mm Hg). Temperature and humidity of the chamber were between 22-25°C and 65-72 per cent respectively. The chamber was opened once every 48 hr for 3-5 min for cleaning and feeding. The animals were killed by cervical dislocation.

Changes in enzyme activities in tissues of rats exposed to hypoxia (Short Communication)

“…There were no changes in the activities of enzymes associated with glycolysis (lactate dehydrogenase, pyruvate kinase), and the oxidative capacity of the tissue was largely unaffected (cytochrome oxidase, succinate-cytochrome c oxidoreductase), The increases in succinate dehydrogenase activity, also noted by Ainthal & Ramasarma (1969), coupled with the decrease in cytochrome oxidase activity, may reflect the biochemical consequences of the hypoxia-induced disruption of mitochondrial structure noted in the ultrastructural work of Sulkin & Sulkin (1965) and Burgos et al (1970). It would appear that the liver moves to a greater utilization of fat (a-glycerophosphate dehydrogenase) and amino acids (aspartate aminotransferase), as might be expected from the body-weight changes, but the amino acids appear to be oxidized directly and not used for gluconeogenesis, as judged by the unchanged (or in some instances diminished; W. Whole-animal conditions.…”