Regulatory processes interacting to maintain hepatic blood flow constancy: Vascular compliance, hepatic arterial buffer response, hepatorenal reflex, liver regeneration, escape from vasoconstriction

Abstract

Constancy of hepatic blood flow (HBF) is crucial for several homeostatic roles. The present conceptual review focuses on interrelated mechanisms that act to maintain a constant HBF per liver mass. The liver cannot directly control portal blood flow (PF); therefore, these mechanisms largely operate to compensate for PF changes. A reduction in PF leads to reduced intrahepatic distending pressure, resulting in the highly compliant hepatic vasculature passively expelling up to 50% of its blood volume, thus adding to venous return, cardiac output and HBF. Also activated immediately upon reduction of PF are the hepatic arterial buffer response and an HBF-dependent hepatorenal reflex. Adenosine is secreted at a constant rate into the small fluid space of Mall which surrounds the terminal branches of the hepatic arterioles, portal venules and sensory nerves. The concentration of adenosine is regulated by washout into the portal venules. Reduced PF reduces the washout and the accumulated adenosine causes dilation of the hepatic artery, thus buffering the PF change. Adenosine also activates hepatic sensory nerves to cause reflex renal fluid retention, thus increasing circulating blood volume and maintaining cardiac output and PF. If these mechanisms are not able to maintain total HBF, the hemodynamic imbalance results in hepatocyte proliferation, or apoptosis, by a shear stress/nitric oxide-dependent mechanism, to adjust total liver mass to match the blood supply. These mechanisms are specific to this unique vascular bed and provide an excellent example of multiple integrative regulation of a major homeostatic organ.

Perfusion CT Assessment of Tissue Hemodynamics Following Hepatic Arterial Infusion of Increasing Doses of Angiotensin II in a Rabbit Liver Tumor Model

“…These results suggest that the 2.5 m g/mL dose of angiotensin II can cause vasoconstriction in the adjacent and distant normal liver that is suffi cient to decrease the BF and BV in these regions without invoking the hepatic arterial buffer response ( 30 ) or inducing hepatic arterial vascular escape ( 31 ), which cause arterial vasodilatation in the normal liver parenchyma that is mediated by increased local levels of adenosine and nitric oxide, respectively. The combination of these two hepatic refl ex responses has been shown to give the normal liver the unique ability to escape from severe vasoconstrictive infl uences ( 30,31 ); this appears to have occurred at the higher angiotensin II doses, especially 50.0 m g/mL, in our study. Furthermore, only at the 2.5 m g/mL dose was the capillary permeabilitysurface area product of the tumor signifi cantly higher than that of the surrounding normal liver tissue.…”

Vasopressin decreases portal vein pressure and flow in the native liver during liver transplantation

“…This hepatic arterial buffer response preserves a constant total hepatic blood flow with changes in portal blood flow. [16][17][18] Because hepatic arterial tone is regulated through local adenosine washout by intrahepatic portal venules, denervation of the liver during the transplant is not going to abate the hepatic arterial buffer response.…”

Cortisol Release From Adipose Tissue by 11β-Hydroxysteroid Dehydrogenase Type 1 in Humans

“…In health, the portal vein provides ϳ80% and the hepatic artery ϳ20% of total liver blood flow (25). In cirrhosis, PBF decreases and HABF increases (26,27), such that as little as 10% of HBF may originate from the portal vein (28). To account for this unknown, we have modeled PBF to range between 10 and 80% of HBF and concordantly for HABF to range between 90 and 20% of HBF.…”