Got nerve? Autonomic innervation of the human liver
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EDITORIAL
Got nerve? Autonomic innervation of the human liver Romil Saxena 1 Received: 13 March 2020 / Revised: 13 March 2020 / Accepted: 17 March 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Literature on innervation of the human liver is not prolific. Although much may be extrapolated from animal studies, it is well acknowledged that there are significant differences in hepatic innervation between species [1]. The lack of substantial studies is however not surprising, given the difficulty of visualizing nerve fibers in routine pathologic sections of the liver, and comparable difficulty in designing studies that may reliably elucidate the anatomical, functional, and spatial properties of innervation in the human liver. In contrast to literature on the subject, innervation of the liver itself is prolific, comprising all elements of the autonomic nervous system, including cholinergic, aminergic, peptidergic, and nitrergic fibers. That the liver is a veritable “bag of nerves” is not surprising [1, 2], given the role the autonomic nervous system plays in all aspects of mammalian function, of which the liver performs all, and then some. Postganglionic sympathetic fibers are derived from splanchnic nerves originating in the celiac and the superior mesenteric ganglia and are more abundant around the hepatic artery. Postganglionic parasympathetic fibers are derived from ganglia located in the hepatic hilum and portal tracts. Neuropeptides, representing the peptidergic component, co-localize with neurotransmitters in both aminergic and cholinergic nerves. These neuropeptides include neuropeptide Y (NPY), substance P (SP), vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP), glucagon-like peptide (GLP), somatostatin (SOM), neurotensin (NT), galanin (GAL), and serotonin. The nitrergic component is represented by intrahepatic nerves containing nitric oxide (NO), or neuronal nitric oxidase synthase (nNOS), the enzyme that catalyzes the formation of nitric oxide.
* Romil Saxena [email protected] 1
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, 350 West 11th Street, Room 4014, Indianapolis, IN 46202, USA
Autonomic nerves enter the liver through the hilum, forming an anterior plexus around the hepatic artery, and a posterior plexus around the portal vein and bile duct. This rich portal innervation maintains flow of blood and bile, directly by maintaining tone of the vascular and biliary systems and indirectly by regulating sinusoidal flow, which is an essential determinant of optimal metabolic function of the liver [3, 4]. Whereas innervation of the portal tracts is uniform across species, lobular innervation is variable. In man, aminergic and peptidergic fibers have been shown to course through the lobule along the space of Disse, coming in close contact with hepatocytes and stellate cells, which suggests direct autonomic control of sinusoidal blood flow and hepatocellular metabolism. Similar lobular innervation has not been demonstrated i
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