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Comprehensive Physiology Jul 2013Bile is a unique and vital aqueous secretion of the liver that is formed by the hepatocyte and modified down stream by absorptive and secretory properties of the bile... (Review)
Review
Bile is a unique and vital aqueous secretion of the liver that is formed by the hepatocyte and modified down stream by absorptive and secretory properties of the bile duct epithelium. Approximately 5% of bile consists of organic and inorganic solutes of considerable complexity. The bile-secretory unit consists of a canalicular network which is formed by the apical membrane of adjacent hepatocytes and sealed by tight junctions. The bile canaliculi (∼1 μm in diameter) conduct the flow of bile countercurrent to the direction of portal blood flow and connect with the canal of Hering and bile ducts which progressively increase in diameter and complexity prior to the entry of bile into the gallbladder, common bile duct, and intestine. Canalicular bile secretion is determined by both bile salt-dependent and independent transport systems which are localized at the apical membrane of the hepatocyte and largely consist of a series of adenosine triphosphate-binding cassette transport proteins that function as export pumps for bile salts and other organic solutes. These transporters create osmotic gradients within the bile canalicular lumen that provide the driving force for movement of fluid into the lumen via aquaporins. Species vary with respect to the relative amounts of bile salt-dependent and independent canalicular flow and cholangiocyte secretion which is highly regulated by hormones, second messengers, and signal transduction pathways. Most determinants of bile secretion are now characterized at the molecular level in animal models and in man. Genetic mutations serve to illuminate many of their functions.
Topics: Animals; Bile; Bile Acids and Salts; Bile Ducts; Biological Transport; Gastroenterology; Hepatocytes; History, 20th Century; Humans; Liver; Membrane Transport Proteins; Signal Transduction
PubMed: 23897680
DOI: 10.1002/cphy.c120027 -
Biomolecules Apr 2022Gallstone disease is a common pathology of the digestive system with nearly a 10-20% incidence rate among adults. The mainstay of treatment is cholecystectomy, which is... (Review)
Review
Gallstone disease is a common pathology of the digestive system with nearly a 10-20% incidence rate among adults. The mainstay of treatment is cholecystectomy, which is commonly associated with physical pain and may also seriously affect a patient's quality of life. Clinical research suggests that cholelithiasis is closely related to the age, gender, body mass index, and other basic physical characteristics of patients. Clinical research further suggests that the occurrence of cholelithiasis is related to obesity, diabetes, non-alcoholic fatty liver, and other diseases. For this reason, we reviewed the following: genetic factors; excessive liver cholesterol secretion (causing cholesterol supersaturation in gallbladder bile); accelerated growth of cholesterol crystals and solid cholesterol crystals; gallbladder motility impairment; and cardiovascular factors. Herein, we summarize and analyze the causes and mechanisms of cholelithiasis, discuss its correlation with the pathogenesis of related diseases, and discuss possible mechanisms.
Topics: Adult; Bile; Bile Acids and Salts; Cholesterol; Gallstones; Humans; Quality of Life
PubMed: 35454138
DOI: 10.3390/biom12040550 -
Annals of Internal Medicine Feb 1999Biliary sludge was first described with the advent of ultrasonography in the 1970s. It is defined as a mixture of particulate matter and bile that occurs when solutes in... (Review)
Review
Biliary sludge was first described with the advent of ultrasonography in the 1970s. It is defined as a mixture of particulate matter and bile that occurs when solutes in bile precipitate. Its composition varies, but cholesterol monohydrate crystals, calcium bilirubinate, and other calcium salts are the most common components. The clinical course of biliary sludge varies, and complete resolution, a waxing and waning course, and progression to gallstones are all possible outcomes. Biliary sludge may cause complications, including biliary colic, acute pancreatitis, and acute cholecystitis. Clinical conditions and events associated with the formation of biliary sludge include rapid weight loss, pregnancy, ceftriaxone therapy, octreotide therapy, and bone marrow or solid organ transplantation. Sludge may be diagnosed on ultrasonography or bile microscopy, and the optimal diagnostic method depends on the clinical setting. This paper proposes a protocol for the microscopic diagnosis of sludge. There are no proven methods for the prevention of sludge formation, even in high-risk patients, and patients should not be routinely monitored for the development of sludge. Asymptomatic patients with sludge can be managed expectantly. If patients with sludge develop symptoms or complications, cholecystectomy should be considered as the definitive therapy. Further studies of the pathogenesis, natural history, and clinical associations of biliary sludge will be essential to our understanding of gallstones and other biliary tract abnormalities.
Topics: Acute Disease; Bile; Cholecystitis; Cholelithiasis; Colic; Disease Susceptibility; Female; Humans; Microscopy; Pancreatitis; Pregnancy; Ultrasonography
PubMed: 10068389
DOI: 10.7326/0003-4819-130-4-199902160-00016 -
Chimia Dec 2022The liver fulfills many vital functions for the body, among them bile formation and detoxification. Bile salts are organic anions, are the major constituents of bile and... (Review)
Review
The liver fulfills many vital functions for the body, among them bile formation and detoxification. Bile salts are organic anions, are the major constituents of bile and are at high concentrations cytotoxic. Detoxification exposes the liver to many harmful compounds. This function is therefore potentially damaging to the liver. Impaired bile formation may lead to hepatic accumulation of bile salts and subsequently to liver disease. Diagnosis of liver diseases involves the measurement of so-called liver function parameters. This overview aims to characterize and summarize the role of organic anion transporters in bile formation at the protein level under normal physiologic conditions and in liver function tests used for diagnosing liver diseases in pathophysiologic situations.
Topics: Humans; Bile; Bile Acids and Salts; Liver; Liver Diseases; Organic Anion Transporters
PubMed: 38069798
DOI: 10.2533/chimia.2022.1025 -
Comprehensive Physiology Jan 2013Cholangiocytes are epithelial cells that line the intra- and extrahepatic ducts of the biliary tree. The main physiologic function of cholangiocytes is modification of... (Review)
Review
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.
Topics: Animals; Bile; Biliary Tract; Epithelial Cells; Humans; Signal Transduction
PubMed: 23720296
DOI: 10.1002/cphy.c120019 -
Clinica Chimica Acta; International... Nov 2023Biliary tract cancers are heterogeneous in etiology, morphology and molecular characteristics thus impacting disease management. Diagnosis is complex and prognosis poor.... (Review)
Review
Biliary tract cancers are heterogeneous in etiology, morphology and molecular characteristics thus impacting disease management. Diagnosis is complex and prognosis poor. The advent of liquid biopsy has provided a unique approach to more thoroughly understand tumor biology in general and biliary tract cancers specifically. Due to their minimally invasive nature, liquid biopsy can be used to serially monitor disease progression and allow real-time monitoring of tumor genetic profiles as well as therapeutic response. Due to the unique anatomic location of biliary tract cancer, bile provides a promising biologic fluid for this purpose. This review focuses on the composition of bile and the use of these various components, ie, cells, extracellular vesicles, nucleic acids, proteins and metabolites as potential biomarkers. Based on the disease characteristics and research status of biliary tract cancer, considerable effort should be made to increase understanding of this disease, promote research and development into early diagnosis, develop efficient diagnostic, therapeutic and prognostic markers.
Topics: Humans; Bile; Biomarkers, Tumor; Biliary Tract Neoplasms; Prognosis; Liquid Biopsy
PubMed: 37839517
DOI: 10.1016/j.cca.2023.117593 -
Gut and Liver Sep 2016Cholangiocytes, the lining epithelial cells in bile ducts, are an important subset of liver cells. They are activated by endogenous and exogenous stimuli and are... (Review)
Review
Cholangiocytes, the lining epithelial cells in bile ducts, are an important subset of liver cells. They are activated by endogenous and exogenous stimuli and are involved in the modification of bile volume and composition. They are also involved in damaging and repairing the liver. Cholangiocytes have many functions including bile production. They are also involved in transport processes that regulate the volume and composition of bile. Cholangiocytes undergo proliferation and cell death under a variety of conditions. Cholangiocytes have functional and morphological heterogenecity. The immunobiology of cholangiocytes is important, particularly for understanding biliary disease. Secretion of different proinflammatory mediators, cytokines, and chemokines suggests the major role that cholangiocytes play in inflammatory reactions. Furthermore, paracrine secretion of growth factors and peptides mediates extensive cross-talk with other liver cells, including hepatocytes, stellate cells, stem cells, subepithelial myofibroblasts, endothelial cells, and inflammatory cells. Cholangiopathy refers to a category of chronic liver diseases whose primary disease target is the cholangiocyte. Cholangiopathy usually results in end-stage liver disease requiring liver transplant. We summarize the biology of cholangiocytes and redefine the concept of cholangiopathy. We also discuss the recent progress that has been made in understanding the pathogenesis of cholangiopathy and how such progress has influenced therapy.
Topics: Bile; Bile Ducts; Epithelial Cells; Humans; Liver; Liver Diseases
PubMed: 27563020
DOI: 10.5009/gnl16033 -
World Journal of Gastroenterology Nov 2013This review considers the physiological and molecular biochemical mechanisms of bile formation. The composition of bile and structure of a bile canaliculus, biosynthesis... (Review)
Review
This review considers the physiological and molecular biochemical mechanisms of bile formation. The composition of bile and structure of a bile canaliculus, biosynthesis and conjugation of bile acids, bile phospholipids, formation of bile micellar structures, and enterohepatic circulation of bile acids are described. In general, the review focuses on the molecular physiology of the transporting systems of the hepatocyte sinusoidal and apical membranes. Knowledge of physiological and biochemical basis of bile formation has implications for understanding the mechanisms of development of pathological processes, associated with diseases of the liver and biliary tract.
Topics: Animals; Bile; Bile Pigments; Biliary Tract; Biological Transport; Carrier Proteins; Cellulose, Oxidized; Enterohepatic Circulation; Humans; Liver; Membrane Glycoproteins; Micelles; Phospholipids
PubMed: 24259965
DOI: 10.3748/wjg.v19.i42.7341 -
Forensic Science International Feb 2016In forensic toxicology, alternative matrices to blood are useful in case of limited, unavailable or unusable blood sample, suspected postmortem redistribution or long... (Review)
Review
In forensic toxicology, alternative matrices to blood are useful in case of limited, unavailable or unusable blood sample, suspected postmortem redistribution or long drug intake-to-sampling interval. The present article provides an update on the state of knowledge for the use of bile in forensic toxicology, through a review of the Medline literature from 1970 to May 2015. Bile physiology and technical aspects of analysis (sampling, storage, sample preparation and analytical methods) are reported, to highlight specificities and consequences from an analytical and interpretative point of view. A table summarizes cause of death and quantification in bile and blood of 133 compounds from more than 200 case reports, providing a useful tool for forensic physicians and toxicologists involved in interpreting bile analysis. Qualitative and quantitative interpretation is discussed. As bile/blood concentration ratios are high for numerous molecules or metabolites, bile is a matrix of choice for screening when blood concentrations are low or non-detectable: e.g., cases of weak exposure or long intake-to-death interval. Quantitative applications have been little investigated, but small molecules with low bile/blood concentration ratios seem to be good candidates for quantitative bile-based interpretation. Further experimental data on the mechanism and properties of biliary extraction of xenobiotics of forensic interest are required to improve quantitative interpretation.
Topics: Bile; Forensic Toxicology; Humans; Sensitivity and Specificity
PubMed: 26773224
DOI: 10.1016/j.forsciint.2015.10.034 -
Journal of Hepatology Feb 2021Many epithelia secrete bicarbonate-rich fluid to generate flow, alter viscosity, control pH and potentially protect luminal and intracellular structures from chemical... (Review)
Review
Many epithelia secrete bicarbonate-rich fluid to generate flow, alter viscosity, control pH and potentially protect luminal and intracellular structures from chemical stress. Bicarbonate is a key component of human bile and impaired biliary bicarbonate secretion is associated with liver damage. Major efforts have been undertaken to gain insight into acid-base homeostasis in cholangiocytes and more can be learned from analogous secretory epithelia. Extrahepatic examples include salivary and pancreatic duct cells, duodenocytes, airway and renal epithelial cells. The cellular machinery involved in acid-base homeostasis includes carbonic anhydrase enzymes, transporters of the solute carrier family, and intra- and extracellular pH sensors. This pH-regulatory system is orchestrated by protein-protein interactions, the establishment of an electrochemical gradient across the plasma membrane and bicarbonate sensing of the intra- and extracellular compartment. In this review, we discuss conserved principles identified in analogous secretory epithelia in the light of current knowledge on cholangiocyte physiology. We present a framework for cholangiocellular acid-base homeostasis supported by expression analysis of publicly available single-cell RNA sequencing datasets from human cholangiocytes, which provide insights into the molecular basis of pH homeostasis and dysregulation in the biliary system.
Topics: Acid-Base Equilibrium; Acid-Base Imbalance; Bicarbonates; Bile; Bile Ducts; Epithelium; Humans; Hydrogen-Ion Concentration; Secretory Pathway
PubMed: 33342564
DOI: 10.1016/j.jhep.2020.10.010