Alcohol, hepatic sinusoidal microcirculation, and chronic liver disease

Marlys H. Witte, Peter Borgs, Dennis L. Way, Geronimo Ramirez, Michael J. Bernas, Charles L. Witte

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

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 trasendothelial macromolecular permeability (Evans bluealbumin 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.

Original languageEnglish (US)
Pages (from-to)473-480
Number of pages8
JournalAlcohol
Volume9
Issue number6
DOIs
StatePublished - Jan 1 1992

Keywords

  • Alcohol
  • Capillarization
  • Endothelial culture
  • Gastric infusion model
  • Lymph
  • Microcirculation
  • Sinusoid

ASJC Scopus subject areas

  • Health(social science)
  • Biochemistry
  • Toxicology
  • Neurology
  • Behavioral Neuroscience

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