The accessory organs: Pancreas, liver and gallbladder
Paul Ong, Rachel Skittrall in Gastrointestinal Nursing, 2017
One of the functions of hepatocytes is to produce bile. Bile consists of water, electrolytes, bile acids, cholesterol, phospholipids and bilirubin. Bile plays a key role in the digestion of fats within the small intestine. Bile is secreted by hepatocytes into canaliculi which transport bile out of the lobule where it drains into bile ductules, interlobular bile ducts and then collects in the right and left hepatic ducts outside the liver. These then join up to form the common hepatic duct (Figure 6.11). As bile flows through the bile ducts the ductal epithelial cells (cholangiocytes) that line its surface modify the bile by secreting a watery, bicarbonate-rich secretion. This secretion plays an important role in neutralising the acid environment in the duodenum so that pancreatic and small intestine enzymes can function. The bile then either flows via the common bile duct emptying into the duodenum or it enters the cystic duct and is stored in the gallbladder. The gallbladder stores and concentrates bile between meals and overnight. Bile will remain within the gallbladder until its release is triggered by the contraction of the walls of the gallbladder. During the time that bile remains in the gallbladder, water and some electrolytes are absorbed causing the bile to become more concentrated.
Estrogen Regulation of Cholangiocyte Proliferation
Gianfranco Alpini, Domenico Alvaro, Marco Marzioni, Gene LeSage, Nicholas LaRusso in The Pathophysiology of Biliary Epithelia, 2020
Cholangiocytes are the epithelial cells which line the intrahepatic bile ducts and which participate in the process of bile formation through the manipulation of native hepato-canalicular bile.1 Cholangiocytes are the preferential target of damage in a group of chronic cholestatic liver diseases called cholangiopathies and recently classified as vanishing bile duct syndromes. 1–4 These diseases, which include primary biliary cirrhosis and primary sclerosing cholangitis, share common pathological features including the damage and disappearance of interlobular bile ducts, the proliferation of residual ducts and intralobular cholestasis.1–4 The progressive disappearance of intrahepatic bile ducts leads to a severe ductopenic condition in terminal stages. In the early stage of the disease, the disappearance of bile ducts is compensated by the proliferation of residual ducts.1–4 Thus, the course of these diseases is characterized by a balance between damage (loss) of bile ducts and compensatory proliferation of the residual ducts. In the terminal decompensated stage, the inefficacy of proliferation to balance for the loss of intrahepatic bile ducts leads to the clinical manifestations of overt cholestasis.1–4 Therefore, the design of a therapeutic strategy aimed at supporting an efficacious cholangiocyte proliferation could delay the progression to ductopenia and this represents a challenge for the future. For these reasons mechanisms and agents involved in the modulation of cholangiocyte proliferation were extensively investigated, in the last years, especially at the experimental level. To this latter regard, the experimental model of the common bile duct ligated (BDL) rat was very helpful since the selective cholangiocyte proliferation typical of BDL rats induce a marked increase in the mass of intrahepatic bile ducts and cholangiocytes which arrive to represent more than 30% of parenchymal hepatic cells (normally less than 2%).5 Thanks to recent studies, we now know that cholangiocyte proliferation is regulated by several growth factors, hormones, neuropeptides and by bile salts (BS). As far as hormones are concerned, acetylcholine and activators of adenylate cyclase (i.e., forskolin) induce cholangiocyte proliferation while somatostatin and gastrin display inhibitory effects.1,2
MiR-122 and other microRNAs as potential circulating biomarkers of drug-induced liver injury
Published in Expert Review of Molecular Diagnostics, 2018
Lawrence S. Howell, Lucy Ireland, B. Kevin Park, Christopher E. Goldring
Identification of DILI in either zone I or zone III of the liver by a circulating biomarker would be advantageous for a number or reasons. Cholangiocytes are found within the periportal region and play many important roles within the liver, such as regulating bile composition. They are targets of toxicity for numerous commonly prescribed drugs, such as the penicillins [68]. Serious damage of these cells may ultimately lead to vanish bile duct syndrome, which requires liver transplantation. Diagnosis is dependent upon liver biopsies, whereas a panel of miRNA biomarkers selective for cholangiocyte or generalized periportal injury would ensure a noninvasive, early diagnosis [69]. Liver zonation causes a marked gradient of key physiological processes across the liver, such as the expression of key drug-metabolizing phase I and II enzymes. Detection of zone-specific miRNAs in preclinical testing may ultimately aid future drug design by linking the drugs’ chemical properties to the area of DILI.
с-Met receptor can be activated by extracellular alkaline medium
Published in Journal of Receptors and Signal Transduction, 2019
Oxana V. Serova, Alexander N. Orsa, Natalia A. Chachina, Alexander G. Petrenko, Igor E. Deyev
Met is expressed in skin, liver, lung, kidney, gut, and pancreas. In particular, Met was found in secreting bile hepatocytes [18]. pH of hepatic bile is well known to be within the range of 7.4–8.5 [19,20,21]. Alongside with the kidneys and lungs, the liver has been recognized as an important regulator of acid–base homeostasis. Various complex metabolic acid-base disorders may occur with liver dysfunction [22]. Liver cells cholangiocytes and hepatocytes secrete bicarbonate (HCO3−) into the bile duct lumen. Biliary HCO3− secretion is pivotal in humans and is thought to serve a number of functions: (1) to sustain bile flow, (2) to facilitate disposal of xenobiotics and endobiotics, (3) to neutralize the acidic pH of gastric secretions for digestion of nutrients in the intestine, and (4) bile salts remain in their polar, membrane-insensitive state with an increased bile luminal pH. A defective apical HCO3− secretory apparatus would weaken the alkaline barrier, leading to partial protonation of bile salts in humans, rendering the resulting bile acids a polar and capable of crossing the cholangiocyte membrane independent from bile salt transporter activity, thereby inducing apoptosis and senescence of cholangiocytes [23].
Evaluation of noninvasive markers for the diagnosis of cystic fibrosis liver disease
Published in Scandinavian Journal of Gastroenterology, 2018
Alexandra Alexopoulou, Sophia Pouriki, Larisa Vasilieva, Theodoros Alexopoulos, Vasiliki Filaditaki, Maria Gioka, Filia Diamantea, Spyros P. Dourakis
Liver disease is a well-known manifestation of CF with a cumulative incidence of 27–35% [8,14]. The incidence of CFLD is about 2.4 per patient-years during the first decade of life declining thereafter [8,14]. The liver disease has various pathogenetic mechanisms mainly due to cholangiocyte damage leading to focal biliary cirrhosis, sclerosing cholangitis and hepatic steatosis [11]. Approximately 5–10% of CF patients will develop multilobular cirrhosis accounting for 2.5% of overall mortality. CFLD is the most frequent nonpulmonary cause of death [11,15]. Respiratory function, infection, liver disease and nutritional status appeared as independent factors associated with poor prognosis in a recent study of 285 adult CF patients [16]. The pre-symptomatic diagnosis of CFLD is therefore important in order to initiate early treatment with ursodeoxycholic acid, prevent the complications of portal hypertension and evaluate the patients for combined lung and liver transplantation. However, liver disease may remain silent until major complications of cirrhosis such as variceal bleeding develop. The latent course of the disease, its focal nature and the inconsistency of liver biopsy as reference method -owing to sampling errors and its invasive characteristics-, have ended up to the search for new methods for early CFLD diagnosis [16].
Related Knowledge Centers
- Bile Acid
- Bombesin
- Epithelium
- Hepatocyte
- Porta Hepatis
- Secretin
- Bile Duct
- Bile
- Acetylcholine
- Adenosine Triphosphate