Apoptosis, or programmed cell death is a regulated event, which plays a major role in maintaining homeostasis in the biliary epithelium. The disruption of normal apoptotic pathways can result in different disease states: (1) increases in apoptosis result in decreasing number of biliary epithelial...

The gallbladder stores and concentrates bile between meals. Fluid secretion prevents the stagnation of bile salts after feeding, while mucins secreted in the gallbladder ensure cytoprotection. Mucin secretion in human gallbladder is stimulated predominantly by Ca 2+ dependent pathways that are...

The intrahepatic biliary tree is a major target of a diverse group of hepatobiliary diseases, the cholangiopathies, which preferentially involve specific anatomical portions or segments of the bile ducts. Microscopic computed tomography (micro-CT) is a novel technique that allows reconstruction...

Cholangiocytes, the epithelial cells that line the intrahepatic bile ducts, express water channel proteins [i.e., aquaporins (AQPs)], which are increasingly recognized to be important in ductal bile formation. In this chapter we focus on AQPs expressed in cholangiocytes, their topography and...

Cryptosporidium causes selflimited diarrhea in immunocompetent subjects and potentially life-threatening syndromes in immunocompromised individuals, primarily those with acquired immunodeficiency syndrome (AIDS). AIDS-cholangiopathy, an important biliary disorder resulting in significant...

Transepithelial transport of Cl - ions contributes importantly to the formation of bile by cholangiocytes, the epithelial cells that line the lumen of intrahepatic bile ducts. This response is mediated in part by opening of Cl - channels in the apical membrane. Recent emphasis has been placed...

Primary biliary cirrhosis (PBC) is an autoimmune liver disease that predominantly affects women and characterized by chronic progressive destruction of small intrahepatic bile ducts with portal inflammation and subsequent fibrosis. The serologic hallmark of PBC is the presence of...

Recent data demonstrate that estrogens and their receptors play an important role in modulating cholangiocyte proliferation. Rat cholangiocytes, in fact, express estrogen receptors (ER)-a and -bsubtypes, which are overexpressed in cholangiocytes proliferating after bile duct ligation (BDL)...

The sodium-dependent bile salt transporter ASBT in the apical domain of cholangiocytes allows the reabsorption of bile salts in intrahepatic bile ducts. MRP3, a transporter of glucuronide-conjugates and of bile salts, and t-ASBT, a truncated form of ASBT, are expressed in the basolateral...

Extrahepatic biliary atresia is a disorder of infancy in which there is obliteration of the hepatic or common bile ducts resulting in irreversible end-stage obstructive liver dis ease. Hepatic portoenterostomy (“Kasai procedure”) has permitted long-term survival in approximately 20% of...

Hepatic reactions to injury are an attempt to maintain functionality and regain homeo stasis while adapting to a change in the liver environment. Most reactions involve proliferation and apoptosis of hepatocytes, biliary epithelial cells (BEC), and stromal, hematolymphoid, and endothelial...

Liver transplantation (LTx) is nowadays an established treatment which has revolution ized the care of patients with end-stage chronic liver diseases. Thousands of patients with a life expectancy of few months to few years have the opportunity to extend their survival with adequate quality...

Vanishing bile duct syndromes (VBDS) are characterized by progressive destruction of intrahepatic and sometimes extrahepatic branches of the biliary tree. A common symp- tom of all VBDS is chronic cholestasis, which is often progressive and leads to biliary cirrhosis and its sequelae. VBDS...

Liver and biliary tree formation involves the systematic expression of key transcriptional activators and signaling molecules by the endoderm as well as surrounding mesoderm. Control of early hepatic growth, the coordination of bile epithelial cell and hepatocyte differentiation that is...

Cytokines are mediator molecules which coordinate communication between different cell types and tissues. Recent studies have shown that cholangiocytes can produce as well as respond to cytokines. Several cytokines such as Interleukin-6, Transforming Growth Factor beta and Tumor Necrosis...

The hallmark of cholangiopathies (i.e., diseases of the intrahepatic biliary ducts) is a chronic progressive cholestasis. Cytokines and other inflammatory mediators play a central role in the pathophysiology of cholangiopathies through stimulation of apoptotic and proliferative responses,...

The concept of extracellular nucleotides as regulatory molecules is not new; Burnstock first advanced it in the 1950’s.1-3 However, this idea did not gain widespread accep tance until distinct nucleotide receptors were first identified in the 1970’s and cloned in the 1980’s and beyond....

Cystic fibrosis (CF) is a multi-organ genetic disorder of the Caucasian population, af fecting between 1 in 2000 and 1 in 4500 newborns in different ethnic groups. Progres sive pulmonary disease limits survival and quality of life of most patients with CF. When the disease was first described...

Cholangiocytes are epithelial cells that line the intrahepatic biliary tree, a three-dimensional network of interconnecting ducts of different sizes and functions. The objectives of this chapter are to review the recent findings related to the role of nerves in the regulation of...

The structure of the peribiliary plexus (PBP) in the normal liver has been the subject of a number of studies using both light microscopy, and scanning electron microscopy observations. The PBP, that stems from the hepatic artery branches and flows into the hepatic sinusoids, nourishes the...

Primary bile is formed by the secretion to the canalicular lumen of biliary lipids, organic anions, glutathione, ions and water. Along the biliary tract canalicular bile undergoes a process of fluidification and alkalinization that is influenced by several factors including hormones,...

Vanishing Bile Duct Syndrome is a term used to describe progressive loss of small intra- hepatic ducts in a variety of different diseases. It is increasingly clear that immunopathogenetic mechanisms involving innate and adaptive immune responses contribute to ductopenia in most of these...

The human liver allograft is subject to a multitude of insults: ischaemia, reperfusion injury, acute and chronic rejection, infection (viral, bacterial and fungal), drug toxicity, outflow obstruction and recurrent disease. In the majority of these situations, the epithelial cells of the...

Much has been learned in the past few years concerning morphology and function of the intrahepatic biliary epithelium. Immunohistochemistry, together with ultrastruc tural studies has allowed a better identification of the smallest branches of the biliary tree and of subcellular components...

Bile-duct injury, or cholangiopathy, observed in hepatic graft versus host disease (GVHD) is regarded as an immune-mediated injury, although its precise mechanism is unclear. However, recent studies have suggested the involvement of Fas (CD95) -mediated cell death in this immune-mediated...

The precise relationship between cholestasis, in its broad meaning, and liver tissue fibro- sis is still poorly defined. The aim of this chapter is to identify and discuss the factors that may associate these general phenomena. For reasons of clarity, we will focus on clinical and...

Bile acids interact with cholangiocytes numerous ways. A specific bile acid transporter (ASBT) is localized on the apical membrane posed to absorb biliary bile acids. On the basolateral membrane three transport systems have been identified (t-ASBT, MDR3 and an anion exchanger system)....

The liver primordium buds off the ventral aspect of the embryonic foregut very early during development of the abdominal organs, at about 18 days of gestation. By week 16, the architectural organization of the hepatic parenchyma and vasculature is well-established, and the extrahepatic biliary...

Cholangiocyte bicarbonate secretion is highly regulated by hormones, peptides and nerves since it contributes significantly to the total bicarbonate requirement for digestive functions and is the major determinant of alkalinity and hydration of hepatic bile. During digestion secretin induces a...

Cytosolic Ca2+ is an important second messenger in virtually all cells and tissues. Ca2+ regulates a range of cell functions, from contraction to secretion to gene expression. Moreover, Ca2+ is able to regulate multiple cellular functions simultaneously. Evidence suggests that Ca2+ is able to...

The intrahepatic biliary epithelium is a simple epithelium (each cell is in contact with a basement membrane) that until relatively recently was thought to function solely as an inert lining to the biliary ductular system. Improved methods to allow adequate purification and maintenance of...

Various drugs have been implicated in the development of a particular form of liver damage, predominantly involving the bile ducts. Bile duct damage can be mild, but can also result in progressive ductopenia, posing the differential diagnostic problem with other vanishing bile duct syndromes...

Medical management of vanishing bile duct syndrome (VBDS) should be aimed at treating both the underlying disease and symptoms or complications of long-standing cholestasis. For the treatment of pruritus, the most specific symptom of VBDS, anion exchange resins represent the first-line therapy...

Regeneration of the liver begins with growth activation of the primary hepatocyte population. Although in the adult, hepatocytes are normally quiescent and fully differentiated, they retain the capacity to proliferate on demand. The other cell types in the liver, including biliary epithelium,...

In this book chapter, we discuss the latest findings related to the concept that the bile duct system is heterogeneous regarding: (i) morphological characteristics; (ii) physiological response to gastrointestinal hormones/peptides; (iii) apoptotic and proliferative activity in response to...