title: The lung in liver disease: old problem, new concepts.
abstract: Liver dysfunction has been recognized to influence the lung in many different clinical situations, although the mechanisms for these effects are not well understood. One increasingly recognized interaction, the hepatopulmonary syndrome (HPS) occurs in the context of cirrhosis and results when alveolar microvascular dilation causes arterial gas exchange abnormalities and hypoxemia. HPS occurs in up to 30% of patients with cirrhosis and significantly increases mortality in affected patients. Currently, liver transplantation is the only curative therapy. Experimental biliary cirrhosis induced by common bile duct ligation (CBDL) in the rat reproduces the pulmonary vascular and gas exchange abnormalities of human HPS and has been contrasted with other experimental models of cirrhosis in which HPS does not develop. Microvascular dilation, intravascular monocyte infiltration, and angiogenesis in the lung have been identified as pathologic features that drive gas exchange abnormalities in experimental HPS. Our recent studies have identified biliary epithelium and activation and interaction between the endothelin-1 (ET-1)/endothelial endothelin B (ETB) receptor and CX3CL1/CX3CR1 pathways as important mechanisms for the observed pathologic events. These studies define novel interactions between the lung and liver in cirrhosis and may lead to effective medical therapies.
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology, Hepatology & Nutrition, The University of Texas Medical School at Houston, 6431 Fannin Street, MSB 4.234, Houston, Texas 77030, USA. Michael.B.Fallon@uth.tmc.edu
authors.forename: Michael B
authors.initials: MB
authors.lastname: Fallon
authors.forename: Junlan
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D019332:Endothelin-1 / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D020065:Hepatopulmonary Syndrome / Q000473:pathology*; D006801:Humans; D051381:Rats
chemical_list: D016207:Cytokines; D019332:Endothelin-1