Portal Hypertension and Its Complications Arun J. Sanyal, Jaime Bosch, Andres Blei, Vincente Arroyo  Gastroenterology  Volume 134, Issue 6, Pages 1715-1728 (May 2008) DOI: 10.1053/j.gastro.2008.03.007 Copyright © 2008 AGA Institute Terms and Conditions

Figure 1 Pathophysiology of variceal bleeding. Bleeding occurs when the tension exerted by the thin wall of the varices exceeds the rupture point. This is facilitated by the progressive increase in the size of the varices and decreased wall thickness (A). These factors are mathematically interrelated in Laplace's law (B) and explain why an increased HVPG, the endoscopic apearance of the varices, and the degree of liver failure are associated with increased risk of variceal bleeding (C). Gastroenterology 2008 134, 1715-1728DOI: (10.1053/j.gastro.2008.03.007) Copyright © 2008 AGA Institute Terms and Conditions

Figure 2 Pathophysiology of ascites and hepatorenal syndrome. The initial event is splanchnic arterial vasodilation, which causes effective hypovolemia. This is compensated for by an increased cardiac output (hyperdynamic circulation). However, as the disease progresses, splanchnic arterial vasodilation increases and cardiac output decreases, leading to deterioration of circulatory function and stimulation of the renin-angiotensin-aldosterone system, sympathetic nervous system, and antidiuretic hormone. When circulatory dysfunction is moderate, patients develop sodium retention. When it is severe, patients develop a profound impairment in free water excretion and dilutional hyponatremia. Finally, when it is extreme, patients present with HRS. Gastroenterology 2008 134, 1715-1728DOI: (10.1053/j.gastro.2008.03.007) Copyright © 2008 AGA Institute Terms and Conditions

Figure 3 Glutamine as a “Trojan horse.” In astrocytes, glutamine is transported into mitochondria via specific transporters, where under the action of glutaminase, ammonia is regenerated. Mitochondrial dysfunction occurs, with the generation of reactive oxygen species (ROS) and the mitochondrial permeability transition. Astroglial dysfunction leads to altered glial-neuronal communications, with abnormalities in neurotransmission (eg, glutamate, GABA) and the development of encephalopathy. Gastroenterology 2008 134, 1715-1728DOI: (10.1053/j.gastro.2008.03.007) Copyright © 2008 AGA Institute Terms and Conditions

Figure 4 An algorithm for the primary prophylaxis of variceal hemorrhage. Gastroenterology 2008 134, 1715-1728DOI: (10.1053/j.gastro.2008.03.007) Copyright © 2008 AGA Institute Terms and Conditions

Figure 5 An algorithm for the management of variceal hemorrhage. Initial treatment is with endoscopic and pharmacologic treatment. Continued bleeding or severe early rebleeding can be managed with TIPS. Those who respond to first-line treatment should receive band ligation and β-blockers. A transplant evaluation should be initiated based on the standard of care locally. Varices should be ligated to obliteration, and suitable patients should undergo transplantation when an organ is available. TIPS is used as a salvage treatment for recurrent bleeding. Liver transplantation remains the only treatment that corrects both the portal hypertension and the underlying liver disease and is the definitive treatment of choice in the long-term for appropriate candidates. Gastroenterology 2008 134, 1715-1728DOI: (10.1053/j.gastro.2008.03.007) Copyright © 2008 AGA Institute Terms and Conditions

Arun J. Sanyal Gastroenterology 2008 134, 1715-1728DOI: (10.1053/j.gastro.2008.03.007) Copyright © 2008 AGA Institute Terms and Conditions

Jaime Bosch Gastroenterology 2008 134, 1715-1728DOI: (10.1053/j.gastro.2008.03.007) Copyright © 2008 AGA Institute Terms and Conditions

Andres Blei Gastroenterology 2008 134, 1715-1728DOI: (10.1053/j.gastro.2008.03.007) Copyright © 2008 AGA Institute Terms and Conditions

Vincente Arroyo Gastroenterology 2008 134, 1715-1728DOI: (10.1053/j.gastro.2008.03.007) Copyright © 2008 AGA Institute Terms and Conditions