Liver Sinusoid during Chronic Alcohol Consumption in the Rat: An Electron Microscopic Study

Transmission and scanning electron microscopic studies were performed on the liver sinusoid, with emphasis on sinusoidal endothelial cells, in rats fed a liquid diet containing either alcohol or dextrin (control) for 14 weeks. Animals were also treated with either Gram-negative bacterial lipopolysaccharide (LPS; 100 μg/100 g body weight, intravenously) or sterile saline (control). All specimens were prepared after perfusion fixation of the liver. Livers of rats fed dextrin-containing liquid diet displayed the ultrastructural features typical of the sinusoid and its endothelial cells. Livers from alcohol-fed animals, however, were characterized by massive loss of sieve-plate architecture of the sinusosidal endothelium, which was virtually replaced with a meshwork of enlarged openings with diameters frequently exceeding 1 urn. Morphological evidence of Kupffer cell activation could also be seen along with significant fatty infiltration of the hepatocyte. Conversely, LPS administration to dextrin-fed animals induced an apparent decrease in fenestration of the sinusoidal endothelial cell, accompanied by morphological evidence of enhanced endocytotic activity and cytoplasmic swelling. The changes seen 3 hr after LPS administration were markedly advanced at 24 hr. LPS administration to alcohol-fed rats accentuated the alterations observed after alcohol treatment alone. Additionally, the presence of platelets in the sinusoid as well as adhering to the hepatocyte microvilli in the space of Disse, along with the presence of Ito and Kupffer cell activation, greater than that observed in the alcohol-treated rats, is morphological evidence consistent with the disruption of vascular integrity in the liver. Interestingly, LPS treatment did not reverse the effects of alcohol on the sinusoidal endothelial cell fenestration. The possible functional consequences of alcohol- and LPS-induced ultrastructural alterations of the sinusoidal endothelial cell, and of the hepatic sinusoid in general, are evaluated in light of the available data on scavenging function of the sinusoidal endothelial cell.