Hepatic Blood Flow: Regulation
Basic, Organ-Based and Clinical Sciences
The blood supply to the liver is provided by the portal vein (75%) and hepatic artery (25%); each vessel provides about 50% of the oxygen requirements of the liver. The mean pressure in the hepatic artery is similar to aortic pressure, whereas portal vein pressure is typically between 6 and 10 mmHg. Portal pressure is primarily dependent on the degree of vasoconstriction of the splanchnic arterioles as well as intrahepatic resistance.
Liver blood flow is controlled by mechanisms that are independent of vasoactive agents and extrinsic innervation. These mechanisms regulate hepatic arterial inflow, portal venous inflow, and the relationship between the two. Among extensive research on the relationship between mean arterial pressure and hepatic arterial blood flow, there has been considerable disagreement over whether or not the hepatic arterial vasculature exhibits autoregulation of blood flow; overall, the degree of autoregulation is considered to be small and present in only about 60% of prepared specimens. In contrast, there is less disagreement over autoregulation of blood flow in the portal venous vascular bed, as the vast majority of studies have revealed linear pressure-to-flow relationships.
The hepatic arterial buffer response (HABR) contributes to intrinsic regulation of hepatic arterial blood flow by changing flow in the hepatic artery to compensate for changes in portal venous flow. If portal blood flow is reduced, the hepatic artery dilates, and if portal blood flow is increased, the hepatic artery constricts. The HABR is able to maintain a constant overall hepatic blood flow by accommodating for 25-60% decrease in portal blood flow. Thus, the HABR minimizes the influence of portal venous changes on hepatic clearance and also maintains oxygen supply to the liver. However, the latter function is likely of minor importance as the liver typically receives more oxygen than it requires, and it can extract more oxygen from blood to compensate for reduced oxygen delivery. Of note, there is no reciprocity of the HABR; that is, alterations in hepatic arterial flow do not induce compensatory changes in portal vascular flow or resistance.
The HABR can be explained mechanistically by the adenosine washout hypothesis, which states that adenosine is released at a constant rate into fluid in the space of Mall that surrounds the hepatic resistance vessels and portal venules. The space of Mall is somewhat separated from other fluid compartments, and the concentration of adenosine in the space of Mall is regulated by washout into the portal vein and the hepatic artery. If portal blood flow is decreased, less adenosine is washed away from the space of Mall; the elevated adenosine levels lead to dilation of the hepatic artery and increased hepatic arterial blood flow. It has also been suggested that ATP, nitric oxide, H2S, calcitonin-gene related peptide receptors, and neurokinin-1 receptors may contribute to the HABR.