Hepatic Circulation: Physiology and Pathophysiology

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Morgan & Claypool Publishers, Nov 17, 2009 - Science - 174 pages
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The Hepatic circulation is unique among vascular beds. The most obvious unique features include the dual vascular supply; the mechanism of intrinsic regulation of the hepatic artery (the hepatic arterial buffer response); the fact that portal blood flow, supplying two thirds of liver blood flow, is not controlled directly by the liver; the fact that 20% of the cardiac output rushes through the most vascularized organ in the body, driven by a pressure gradient of only a few millimeters of mercury; the extremely distensible capacitance and venous resistance sites; the unidirectional acinar blood flow that regulates parenchymal cell metabolic specialization; and the high concentration of macrophagic (Kupffer) cells filtering the blood. The liver is the only organ reported to have regional blood flow monitored by the autonomic nervous system. This mechanism, when dysfunctional, accounts for the hepatorenal syndrome and offers a mechanistic therapeutic target to treat this syndrome. The trigger for liver regeneration is dependent on hepatic hemodynamics so that chronic liver blood flow regulates liver cell mass. In severe liver disease, the whole body circulation is reorganized, by forming portacaval shunts, to accommodate the increased intrahepatic venous resistance. These shunts protect the venous drainage of the splanchnic organs but lead to loss of major regulatory roles of the liver. The development of knowledge of the hepatic vasculature is presented from a historical perspective with modern concepts summarized based on the perspective of the author's four decades of devotion to this most marvelous of organs. Table of Contents: Acknowledgements / Historical Perspectives / Overview / Fluid Exchange / Capacitance / Resistance in the Hepatic Artery / Resistance in the Venous System / Fetal and Neonatal Hepatic Circulation / In Vivo Pharmacodynamic Approaches / Nitric Oxide / Adenosine / Hepatic Nerves / Hepatic Circulation and Toxicology / Hepatorenal Syndrome / Integrative Hepatic Response to Hemorrhage / Blood Flow Regulation of Hepatocyte Proliferation / Multiple Mechanisms Maintaining a Constant Hepatic Blood Flow to Liver Mass Ratio / Pathopharmacology and Repurposing Drugs as a Research Strategy / References
 

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Contents

Chapter 1Historical Perspectives
1
Chapter 2Overview
7
Chapter 3Fluid Exchange
19
Chapter 4Capacitance
27
Chapter 5Resistance in the Hepatic Artery
35
Chapter 6Resistance in the Venous System
53
Chapter 7Fetal and Neonatal Hepatic Circulation
63
Chapter 8In Vivo Pharmacodynamic Approaches
67
Chapter 11Hepatic Nerves
83
Chapter 12Hepatic Circulation and Toxicology
113
Chapter 13Hepatorenal Syndrome
125
Chapter 14Integrative Hepatic Response to Hemorrhage
129
Chapter 15Blood Flow Regulation of Hepatocyte Proliferation
133
Chapter 16Multiple Mechanisms Maintaining a Constant Hepatic Blood Flow to Liver Mass Ratio
137
Chapter 17Pathopharmacology and Repurposing Drugs as a Research Strategy
145
References
149

Chapter 9Nitric Oxide
77
Chapter 10Adenosine
81

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