Hepatic nervous system and neurobiology of the liver

Abstract

The liver has a nervous system containing both afferent and efferent neurons that are involved in a number of processes. The afferent arm includes the sensation of lipids, glucose, and metabolites (after eating and drinking) and triggers the nervous system to make appropriate physiological changes. The efferent arm is essential for metabolic regulation, modulation of fibrosis and biliary function and the control of a number of other processes. Experimental models have helped us to establish how: (i) the liver is innervated by the autonomic nervous system; and (ii) the cell types that are involved in these processes. Thus, the liver acts as both a sensor and effector that is influenced by neurological signals and ablation. Understanding these processes hold significant implications in disease processes such as diabetes and obesity, which are influenced by appetite and hormonal signals.

Figure 1. Gross anatomy of the hepatic nervous system

The anterior plexus forms around the common hepatic artery, and the posterior plexus forms around the portal vein. These plexuses follow these structures to enter the liver hilus with the accompanying portal structures and carry afferent and efferent fibers of both sympathetic and parasympathetic origin.

Figure 2. Anatomy of the intrinsic sympathetic and parasympathetic nerve fibers

In all mammalian species, sympathetic and parasympathetic fibers surround the portal area. In humans and guinea pigs but not rats, sympathetic fibers course into liver sinusoids.

Figure 3. Osmosensation by hepatic afferent nerves

Afferent nerves surrounding the liver vasculature sense hypo-osmolar signals and trigger the pressor reflex via the dorsal root ganglion, and increased sympathetic activity. Like other reflexes, this process is thought to act independent of the brain.

Figure 4. Sensation of Ions by hepatic afferent nerves

Afferent nerves surrounding the liver vasculature trigger in response to hypernatremia and act on sympathetic fibers in the dorsal root ganglion to reflexively decrease sympathetic output to the kidney.

Figure 5. Lipid sensation by liver and gut

Lipid sensation by both the liver and the gut, leads to vagal afferent activation. The hypothalamus of the brain responds by signaling the liver to increase glucose production and decrease glycogenesis.

Figure 6. Effects of efferent neurotransmitters and neuropeptides on hepatic sinusoids

Release of parasympathetic neurotransmitters such as acetylcholine or vasoactive intestinal peptide causes relaxation of the sinusoids. Release of sympathetic neurotransmitters such as adrenalin or substance P causes contraction of the sinusoids. Sympathetic activation is seen during hemorrhage or physical activity, where blood is diverted from the liver to the systemic circulation.