How should we alter our diet when our liver had stopped secreting bile juice?
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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.
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Introduction
Bile formation is a unique function of the liver which is vital to survival of the organism. Knowledge of the mechanism of bile formation has progressed rapidly in recent years and has provided the basis for further diagnosis and treatment of cholestatic disorders. Here, we review historical milestones in these developments and summarize current knowledge in this field.
Bile is a complex aqueous secretion that originates from hepatocytes and is modified distally by absorptive and secretory transport systems in the bile duct epithelium. Bile then enters the gallbladder where it is concentrated or is delivered directly to the intestinal lumen. Bile consists of ~95% water in which are dissolved a number of endogenous solid constituents including bile salts, bilirubin phospholipid, cholesterol, amino acids, steroids, enzymes, porphyrins, vitamins, and heavy metals, as well as exogenous drugs, xenobiotics and environmental toxins (76). Bile serves a number of important functions. (i) Bile is the major excretory route for potentially harmful exogenous lipophilic substances, noted above, as well as other endogenous substrates such as bilirubin and bile salts whose molecular weights are >300 to 500 daltons and not readily filtered or excreted by the kidney. (ii) Bile salts are the major organic solutes in bile and normally function to emulsify dietary fats and facilitate their intestinal absorption. (iii) Bile is the major route for elimination of cholesterol. (iv) Bile protects the organism from enteric infections by excreting immune globulin A (IgA), inflammatory cytokines, and stimulating the innate immune system in the intestine. (v) Bile is an essential component of the cholehepatic and enterohepatic circulation, and finally, (vi) many hormones and pheromones are excreted in bile, and contribute to growth and development of the intestine in some species and provide attractants for the weaning of non-human vertebrates.
The importance of bile secretion to the health of the organism becomes most evident when this secretion is impaired by developmental, genetic or acquired cholestatic diseases. This is most dramatically demonstrated by children born with biliary atresia who develop progressive cholestatic liver injury, biliary cirrhosis, and ultimately liver failure and death.
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