Cirrhosis
Cirrhosis is the consequence of chronic liver disease. When the cause of liver damage is not removed, a chronic inflammatory reaction develops, which is typically accompanied by the accumulation of fibrillar extracellular matrix, nodular regeneration [1],
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Introduction to Cirrhosis Cirrhosis is the consequence of chronic liver disease. When the cause of liver damage is not removed, a chronic inflammatory reaction develops, which is typically accompanied by the accumulation of fibrillar extracellular matrix, nodular regeneration [1], neoangiogenesis, and the establishment of portal hypertension (PH), i.e., high blood pressure in the portal vein, its branches, and tributaries. While PH increases, the hemodynamic derangement extends beyond the splanchnic circulation due to a net increase in circulating vasodilating molecules. This increase is secondary to a systemic and sustained inflammatory reaction and leads to hyperdynamic circulation. The latter is characterized by an increased heart rate and cardiac output as well as a decreased systemic vascular resistance with low arterial blood pressure. Inflammation, altered hemodynamics, and tissue perfusion, together with parenchymal extinction, are also accompanied by a profound metabolic derangement that characterizes cirrhosis in its more advanced stages.
M. Rosselli • M. Pinzani (*) Institute for Liver and Digestive Health, Division of Medicine, University College London, Royal Free Hospital UP3, NW3 2QG London, UK e-mail: [email protected]; [email protected]
Pathophysiology of Cirrhosis and Metabolic Alterations Portal Hypertension PH is the hemodynamic consequence (and hallmark) of liver cirrhosis. It is initially caused by two main pathophysiological events. First, collagen deposition and nodular regeneration increase intrahepatic vascular resistance by mechanically compressing vessels. Second, a dysregulation of intrahepatic vasoactive molecules dynamically increases the contraction of hepatic myofibroblasts around the sinusoids, thus increasing the portal blood pressure. PH is defined by a hepatic venous pressure gradient (HVPG) above 5 mmHg. HPVG is the difference between pressure in the portal vein and the intra-abdominal portion of the inferior vena cava. Under normal conditions, substances absorbed by the intestine follow the enterohepatic circulation, flowing through the portal venous system to be processed by the liver. In cirrhosis, once PH increases beyond 10 mmHg, low-resistance vascular sites are used to create alternative circulatory pathways [2] (e.g., gastroesophageal varices, paraumbilical vein, retroperitoneal venous collaterals, splenorenal shunts) allowing a bypass of the “obstructed” liver. As a consequence, there is a reduced hepatic clearance of gut-derived vasodilating agents, such as endogenous gastrointestinal hormones (glucagon, vasoactive intestinal peptide, calcitonin gene-related peptide) and intestinal bacterial products [3].
E. Lammert, M. Zeeb (eds.), Metabolism of Human Diseases, DOI 10.1007/978-3-7091-0715-7_28, © Springer-Verlag Wien 2014
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In cirrhosis, intestinal transit time is prolonged and the intestinal mucosa is often edematous due to low oncotic pressure (as a consequence of hypoalbuminemia) and increased portal pressure. In addition, biliary secretion a
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