Reclaimed by specific transporters, useful solutes such as glucose and amino acids are essential for maintaining the balance. The exchange of chloride ions for HCO3- in bile renders it slightly alkaline, reducing the risk of calcium precipitation. Enzyme γ-glutamyl transpeptidase (GGT) breaks down glutathione into constituent amino acids on the surface of cholangiocytes, which are then reabsorbed. In response to hormones like secretin, HCO3- secretion increases, leading to the insertion of aquaporin water channels into the cholangiocyte's apical membrane, diluting the bile during the postprandial period when bile acids aid in lipid assimilation.

The sphincter of Oddi constricts between meals, blocking the outflow of bile, thereby redirecting it to the gallbladder. The gallbladder, lined with high-resistance epithelial cells, stores bile and concentrates it through active absorption of sodium ions in exchange for protons. The gallbladder epithelial tight junctions prevent the exit of bile acids, resulting in their concentration. Despite a possible 10-fold increase in bile acid concentration, bile remains isotonic as a single micelle functions as one osmotically active particle. Additional bile acid monomers immediately incorporate into existing mixed micelles, reducing the risk of cholesterol precipitation. Although antinucleating proteins inhibit cholesterol precipitation in most adults, prolonged storage of bile increases the likelihood of nucleation, contributing to the prevalence of gallstone disease in humans.
Fig. 32.10 ). Useful solutes (e.g., glucose, amino acids) are reclaimed by the activity of specific transporters. Chloride ions in bile are also exchanged for HCO3 − , rendering the bile slightly alkaline and reducing the risk of precipitation of Ca++ . Glutathione is broken down on the surface of cholangiocytes into its constituent amino acids by the enzyme γ-glutamyl transpeptidase (GGT), and the products are reabsorbed. Bile is also diluted at this site, in concert with ingestion of a meal, in response to hormones such as secretin that increase HCO3 − secretion and stimulate insertion of aquaporin water channels into the cholangiocyte’s apical membrane. Flow of bile is thereby increased during the postprandial period when bile acids are needed to aid in assimilation of lipid.
Role of the Gallbladder
Finally, bile enters the ducts and is conveyed toward the intestine. However, in the period between meals, outflow is blocked by constriction of the sphincter of Oddi, and thus bile is redirected to the gallbladder. The gallbladder is a muscular sac lined with high-resistance epithelial cells. During gallbladder storage, bile becomes concentrated because sodium ions are actively absorbed in exchange for protons, and bile acids, as the major anions, are too large to exit across the gallbladder epithelial tight junctions (Fig.
32.11 ). However, although the concentration of bile acids can rise more than 10-fold, bile remains isotonic because a •Fig. 32.11 Mechanismsaccountingforconcentrationofbileduringstorageinthegallbladder.NHE,sodium/hydrogenexchanger;BA−,bileacidanion;AQP1,aquaporin1.
single micelle acts as only one osmotically active particle. Any additional bile acid monomers that become available as a result of concentration are thus immediately incorporated into existing mixed micelles. This also reduces to some extent the risk that cholesterol will precipitate from bile. However, cholesterol is supersaturated in the bile of many adults, with precipitation normally being inhibited by the presence of antinucleating proteins. Prolonged storage of bile increases the chance that nucleation can occur, thus making a good case for never skipping breakfast and perhaps explaining why gallstone disease is relatively prevalent in humans.