Molecular mechanisms of circulatory dysfunction in cirrhotic portal hypertension

Abstract

Acute or chronic insults to the liver are usually followed by a tissue repairing process. Unfortunately, this action, in most cases, is not effective enough to restore the normal hepatic structure and function. Instead, fibrogenesis and regenerative nodules formation ensue, which are relatively nonfunctioning. The common final stage of the process is liver cirrhosis with increased intrahepatic resistance to portal venous blood flow. Throughout the entire course, the extrahepatic circulatory dysfunction, including increased splanchnic blood flow, elevated portal venous blood flow and pressure, decreased splanchnic and peripheral vascular resistance, tachycardia, and increased cardiac output, are noted and denoted as portal hypertension with hyperdynamic circulatory dysfunction. When such a condition is established, patients may suffer from fatal complications such as gastroesophageal variceal hemorrhage, hepatic encephalopathy, or hepatorenal syndrome. The cause of such a circulatory dysfunction is not fully elucidated. Nevertheless, clarification of the pathophysiology definitely contributes to the control of portal hypertension-related complications. Herein, the molecular mechanism of this intriguing disaster is reviewed and discussed.

Systemic hemodynamics in advanced cirrhosis: Concerns during perioperative period of liver transplantation

“…Cirrhotic hemodynamics are characterized as hyperdynamic by a high CO, large BV, low TPR, mildly tachycardic heart rate (HR), and low or normal mean arterial pressure (MAP) [1][2][3][4]6,[8][9][10] . Parameters of peripheral resistance, such as TPR, clearly reflect various vascular alterations [1][2][3]9,11,12] .…”

“…The systemic hyperdynamic state causes vessel dilation and collateral development, and the venous endothelium becomes damaged [4,65] . An intact endothelial barrier is important, especially in critical situations such as sepsis and thrombotic microangiopathy [106,107] .…”

“…Long-term PH results in various vascular alterations, such as venous dilatation, endothelial damage, collateral pathway formation, and shunt development [1][2][3] . Some pathognomonic findings (e.g., varices, splanchnic congestion, intractable ascites, hepatic encephalopathy, and hepatorenal syndrome) are directly related to PH [3,4] , and the pathophysiology of PH involves a complex of humoral and neural mechanisms [3] . These mechanisms determine hemodynamic changes and lead to a peculiar systemic circulation pattern [3] .…”

Splenic Transcriptome Profiling of the Patients with Post-Hepatitis B Liver Cirrhosis and Portal Hypertension

“…Cirrhotic portal hypertension has attracted extensive attention for its fatal complications for hundreds of years [13,14]. Its consequences include bleeding from gastroesophageal varices, portal hypertensive g a s t r o p a t h y, a s c i t e s , s p o n t a n e o u s b a c t e r i a l peritonitis, hepatorenal syndrome, hepatopulmonary/ p o r t o p u l m o n a r y s y n d r o m e s a n d h e p a t i c encephalopathy, which represent the first cause of death and liver transplantation in cirrhotic patients.…”

“…Besides, the progressive splanchnic vasodilatation increases the portal blood flow, which further aggravates the state of portal hypertension [14,18]. Although not fully elucidated, it is generally accepted that portal hypertension is involved by many etiologic factors including increased vasodilatory substance release, dys-regulated response to vasoconstrictors, changes of vascular contractile signaling, vascular remodeling, and angiogenesis [13]. Therefore, it would probably be an alternative way to explore the changes of vasoactive or some other cytokines in cirrhotic portal hypertension for better elucidation of its pathogenesis.…”