Alcohol, hepatic sinusoidal microcirculation, and chronic liver disease.
According to the "intact cell hypothesis," ethanol (EtOH) primarily targets nonparenchymal hepatic sinusoidal and perisinusoidal cells, thereby promoting sinusoidal capillarization, which impairs microcirculatory exchange of nutrients and wastes, promotes tissue fibrosis, and only indirectly damages hepatic parenchyma. To test this hypothesis, sinusoidal ultrastructure and hepatic lymph flow and protein composition were examined in rats up to 16 weeks after intragastric EtOH (36% calories)-high fat infusion (Tsukamoto-French model) (TF). The findings were compared to dietary controls and interpreted in light of restricted transsinusoidal protein movement observed in patients with alcoholic cirrhosis. In vitro, alterations in rat hepatic sinusoidal endothelial cell (RSE) morphology, proliferative index, and transendothelial macromolecular permeability (Evans blue-albumin uptake into microcarrier beads) were determined after acute and more chronic exposure to 0.1%-5 vol% EtOH. TF displayed 75% increased liver size, perisinusoidal collagenosis, and basal lamina deposition, ascitic fluid, and doubling of hepatic lymph liquid and protein flux. In vitro, 1% EtOH retracted RSE cell margins, enhanced transendothelial Evans blue-albumin flux and suppressed proliferative index. Thus, high EtOH concentration, clinically attainable in the portal blood during an alcoholic binge, both in vivo and in vitro, promotes early structural and functional alterations in sinusoidal endothelium, which over time may be responsible for progressive restriction of free intrahepatic exchange of liquid, macromolecules, and migrating immune cells.
Witte
M H
MH
Department of Surgery, University of Arizona College of Medicine, Tucson 85724.
Borgs
P
P
Way
D L
DL
Ramirez
G
G
Bernas
M J
MJ
Witte
C L
CL
D000818:Animals; D002908:Chronic Disease; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D000431:Ethanol / Q000097:blood / Q000633:toxicity*; D005289:Ferrets; D006801:Humans; D008102:Liver Circulation / Q000187:drug effects*; D008104:Liver Cirrhosis, Alcoholic / Q000378:metabolism*; D008196:Lymph / Q000187:drug effects / Q000378:metabolism; D008833:Microcirculation / Q000187:drug effects; D051381:Rats
D000431:Ethanol