Physiology of Cholangiocytes

Abstract

Cholangiocytes are epithelial cells that line the intra-and extrahepatic ducts of the biliary tree. The main physiologic function of cholangiocytes is modification of hepatocyte-derived bile, an intricate process regulated by hormones, peptides, nucleotides, neurotransmitters, and other molecules through intracellular signaling pathways and cascades. The mechanisms and regulation of bile modification are reviewed herein.

Physiology of Cholangiocytes

“…An alternative mechanism involves stimulation of basolateral M3 muscarinic receptors with acetylcholine (ACh), resulting in a local increase in IP 3 . This increase in IP 3 leads to a release of Ca 2+ from basolateral (types I and II) IP 3 Rs, thus leading to apical Cl − /HCO 3 − secretion (192, 204). …”

Liver and Bile

“…The biliary tree can be divided grossly into two anatomically and functionally different compartments: the intra-and the extrahepatic compartments (Figure 4(a) and 4(b)) (Tabibian et al, 2012). The smallest (<15 mm in luminal diameter, lined by four to five cholangiocytes circumferentially) of the entirely cholangiocyte-lined conduits are the ductules (Strazzabosco and Fabris, 2008;Baiocchi et al, 1999;Boyer, 2003;Kanno et al, 2001;Ludwig, 1987;Ludwig et al, 1998;Masyuk et al, 2006aMasyuk et al, , 2001Roskams et al, 2004;Sasaki et al, 1967;Saxena and Theise, 2004;Schaffner and Popper, 1961). The smallest (<15 mm in luminal diameter, lined by four to five cholangiocytes circumferentially) of the entirely cholangiocyte-lined conduits are the ductules (Strazzabosco and Fabris, 2008;Baiocchi et al, 1999;Boyer, 2003;Kanno et al, 2001;Ludwig, 1987;Ludwig et al, 1998;Masyuk et al, 2006aMasyuk et al, , 2001Roskams et al, 2004;Sasaki et al, 1967;Saxena and Theise, 2004;Schaffner and Popper, 1961).…”

“…Extending from the apical membrane of cholangiocytes are numerous microvilli, which provide a fivefold increase in the cell surface area (Ludwig et al, 1998;Ishii et al, 1989;Vroman and LaRusso, 1996;Alpini et al, 1989) (Figure 9). Other notable subcellular features of cholangiocytes include a prominent Golgi apparatus located near the apical membrane, inconspicuous and sparse endoplasmic reticulum, small perinuclear mitochondria (Benedetti et al, 1996;Ishii et al, 1989;Marzioni et al, 2002;Masyuk et al, 2006a), and a round to oval, oftentimes notched, and typically basally located nucleus. Other notable subcellular features of cholangiocytes include a prominent Golgi apparatus located near the apical membrane, inconspicuous and sparse endoplasmic reticulum, small perinuclear mitochondria (Benedetti et al, 1996;Ishii et al, 1989;Marzioni et al, 2002;Masyuk et al, 2006a), and a round to oval, oftentimes notched, and typically basally located nucleus.…”

“…This is driven primarily by active excretion of organic solutes and ions into the canalicular space followed by osmotic entry of water, Figure 11 Overview of bile formation and modification. the details of which can be found elsewhere (Masyuk et al, 2006a;Banales et al, 2006;Boyer, 2003;Esteller, 2008;Nathanson and Boyer, 1991). As canalicular bile flows along the biliary tree, it is subjected to cholangiocyte secretory and absorptive processes, thus resulting in modified ductal bile.…”

MicroRNAs in the Cholangiopathies: Pathogenesis, Diagnosis, and Treatment

“…Area (zonal) and segmental ducts are considered large intrahepatic bile ducts, whereas septal ducts represent the transition point between the large and the interlobular biliary system. This classification is based on the diameter of the ducts: bile ductules (15 μm), interlobular ducts (15–100 μm), septal ducts (100–300 μm), area (zonal) ducts (300–400 μm), segmental ducts (400–800 μm), and hepatic ducts (800 μm) [ 1 , 2 , 3 ]. Small bile ducts are lined by 4 to 5 cuboidal cholangiocytes while larger bile ducts are lined by 10–12 cholangiocytes.…”