Mechanisms of Bile Formation—An Introduction

Chapter Details

Pub Date: 30 Nov 2003
Pages: 8
Chapter Category: Channels and Transporters
Taken from the Book: Molecular Pathogenesis of Cholestasis
Book Series: Intelligence Unit
Edited by: Michael Trauner and Peter Jansen

Download PDF

All chapters PDFs are available for free under an Open Access license.

Mechanisms of Bile Formation—An Introduction

James L. Boyer

About this Chapter

The formation of bile is a unique and vital function of the liver. Failure to form bile results in progressive cholestatic liver injury and death. Knowledge of the mechanism of bile formation has progressed rapidly in the past decade and this introduction provides a background and historical perspective for the subsequent reviews. Bile is a complex aqueous secretion composed of ~95% water and endogenous solid constituents consisting of bile salts, phospholipid and cholesterol, amino acids, steroids, enzymes, porphyrins, vitamins, and heavy metals as well as exogenous drugs, xenobiotics and toxins.1 Bile salts are the major organic solute in bile and are necessary for the emulsification and digestive absorption of dietary lipids. Bile serves to eliminate potentially harmful organic lipophilic substances, including xenobiotics and toxins as well as endogenous substrates such as bilirubin and bile salts, not easily excreted by the kidney. Bile is also the major route of excretion for cholesterol. Disorders that impair the production of bile result in the syndrome known as cholestasis.2,3 The primary secretion of bile is generated by osmotic gradients that are formed within the bile canaliculus of the hepatocytes by energy dependent mechanisms. The creation of these osmotic gradients depends upon the function of a number of transporting polypeptides that are located on basolateral and apical plasma membrane domains. This primary secretion of bile is subsequently modified by the bile duct epithelium where transport systems in the luminal membranes of cholangiocytes both secrete and absorb certain biliary constituents.4

More chapters from the book

Bile formation involves vectorial transport of solutes from blood to bile and is dependent on coordinated activities of various solute transporters located at t...
The formation of bile is a unique and vital function of the liver. Failure to form bile results in progressive cholestatic liver injury and death. Knowledge of...
Bile formation is a regulated process and depends on the coordinated action of a number of transporter proteins in the sinusoidal (basal) and canalicular (apic...

Mutations in the coding region of BSEP which result in its absence from the bile canalicular membrane are manifested by progressive cholestasis and liver dam...

In this chapter, we first review the bile duct structure, then the intracellularmechanisms involved in ductal secretion and absorption. The modulation of ductal...
The expression and activities of hepatobiliary transporter genes is a critical component of liver function. Both sinusoidal and canalicular membrane transporte...
The liver plays an important role in the metabolism of xenobiotics and the metabolic reactions are mediated by many different kinds of enzymes. These enzymes m...
Bilirubin, the end product of heme catabolism, needs to be taken up into hepatocytes and is then glucuronidated within the cells prior to its excretion via bil...
Copper is an essential nutrient that is required in a number of critical metabolic path ways. This metal is absorbed in the stomach and duodenum, stored in the ...
Primary biliary cirrhosis (PBC) can be defined by the triad of positive PBC-specific autoantibodies (antimitochondrial antibodies (AMA) in >95%), cholestatic l...
Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disorder of the intrahepatic and/or extrahepatic bile ducts. PSC is characterized by concent...
Drug induced cholestatic liver disease is a subtype of liver injury that is characterized by predominant elevations of alkaline phosphatase and bilirubin secon...
Exposure to cholestatic injury (e.g., drugs, hormones, proinflammatory cytokines, biliary obstruction/destruction), hereditary mutations of transporter genes, ...
Patients with chronic cholestatic liver disease are especially prone to osteoporosis. Hepatic osteodystrophy typically presents as low turnover osteoporosis wit...
Fatigue and pruritus are subjective complaints which are extremely common amongst patients with cholestasis, significantly impairing the quality of life of thes...
Cholestasis and its sequelae are the hallmark of chronic cholestatic liver diseases and can be a feature of virtually all liver diseases at some point. Ursodeox...
Gap junctions are hexameric hemichannels that are inserted into the plasma membrane and allow for direct exchange of cytosolic contents among adjacent cells. Co...
In terms of solute mass, lipids are the second most important component of bile. Biliary lipids mainly consist of phospholipid (almost exclusively phosphatidylc...
The basolateral membrane of hepatocytes is equipped with efficient transport systems for uptake of bile salts (Ntcp/NTCP) and xenobiotics (Oatps/OATPs). Under ...
The liver has a central role in control of various aspects of lipid metabolism. Primarily, the liver produces bile, constituents of which are required for effi...
Genetic approaches complement functional approaches to the study of hereditary disease, and have contributed substantially to our understanding of the biology ...
The research on liver-directed gene therapy and hepatocyte transplantation has progressed in parallel. Hepatocytes, with or without genetic modification have b...
H injury by inducing apoptosis. Toxic bile acids induce apoptosis by activating cell surface membrane death receptors. The activated death receptors stimulate a...
C formation may give rise to extensive parenchymal changes, without significant alterations in biliary tree morphology. Sepsis or systemic inflammatory conditio...
Bile salts take part in a rather efficient enterohepatic circulation in which most of the secreted bile salts are reclaimed by absorption in the terminal ileum....