Extrinsic Regulation of Hepatic Blood Flow

Neural Control

Branches of the splanchnic nerves (postganglionic sympathetic fibers from T6-11), vagus nerve, and phrenic nerve enter the liver with the major blood vessels and bile ducts. These nerve fibers form an intercommunicating plexus, with synapses on the terminal arterioles and venules. Sympathetic innervation of the hepatic and splanchnic vasculature plays a major role in regulating the volume of whole blood stored in, and expelled from, the hepatic reservoir. Studies in a canine model have shown that sympathoadrenal stimulation (e.g., hypercarbia, pain, hypoxia) can abruptly decrease hepatic blood flow and splanchnic vascular capacitance. Within seconds, splanchnic nerve stimulation can autotransfuse up to 80% of the hepatic blood (400–500 mL) into the central circulation.^{[7] [23]} Other studies have shown that vagal stimulation alters the tone of presinusoidal sphincters^[24] and influences blood flow distribution within the liver rather than total hepatic blood flow.

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Figure 19-6 Blood supply of the simple liver acinus. The oxygen tension and the nutrient level of the blood in sinusoids decrease from Zone 1 through Zone 3. Note that the lower left side of the figure also depicts Zones 1, 2, and 3 in a portion of an adjacent acinar unit. BD, bile duct; HA, hepatic artery; PV, portal vein; CV, central vein. (Reprinted with permission from Jones AL: Anatomy of the normal liver. In Zakim D, Boyer T [eds]: Hepatology: A Textbook of Liver Disease, 3rd ed. Philadelphia, WB Saunders, 1996, p 3.)

Humoral Control

The hepatic arterial bed has α₁ -, α₂ -, and β₂ -adrenergic receptors, whereas the portal vein has only α-receptors (see Fig. 19-5 ).^[25] Of the adrenergic mediators, epinephrine induces the most consequential changes in the hepatic circulation. When injected directly into the hepatic artery, epinephrine initially causes vasoconstriction (α-receptor stimulation), followed by vasodilation (β-receptor stimulation). When injected into the portal vein, however, epinephrine causes only vasoconstriction (α-receptor stimulation). Dopamine is unlikely to influence the hepatic circulation during sympathoadrenal activation; its vasoactive effects are weak and dwarfed by those of epinephrine and norepinephrine.^{[17] [25]}

Glucagon induces dose-dependent relaxation of hepatic arterial smooth muscle and antagonizes vasoconstrictor responses of the hepatic artery to various physiologic stimuli-including increases in sympathoadrenal tone.^[26] Angiotensin II severely constricts hepatic arterial and portal venous beds, and markedly decreases both mesenteric blood flow and portal venous flow; blood flow to the liver may plummet.^[27] In comparison, vasopressin intensely constricts the splanchnic arterial bed, but it also lowers portal venous resistance. Therefore, vasopressin can be an effective treatment for portal hypertension. ^[28]