The limit of intestinal absorption ranges from 0.0 to 1.25. The diet and hepatic and extra-hepatic synthesis contribute to the production of bile acids and cholesterol. In a healthy state, the input and output of cholesterol are balanced at 0.5g/day. The rate of bile acid secretion averages 30g/24h, while the synthesis rate averages 0.5g/24h. Increased secretion leads to a higher return rate of bile acids to the liver via portal blood, resulting in negative feedback on synthesis. On the other hand, interruption of the enterohepatic circulation, such as after ileal resection, can increase synthesis to values more than 10 times higher than normal. The daily cholesterol balance in healthy adult humans is shown in Figure 32.8. The entry of solutes into bile occurs through mixed micelles composed of bile acids, phosphatidylcholine, and cholesterol. These micelles are osmotically active, causing water and other plasma solutes to be drawn into the canalicular lumen. The tight junctions between hepatocytes are relatively leaky, allowing for this movement. Figure 32.9 illustrates the relative amounts of bile acids in different body pools and the enterohepatic circulation. The majority of the bile acid pool circulates between the liver, gallbladder, and small intestine. Conjugated bilirubin and various organic and xenobiotic substances are secreted into bile across the apical membrane of the hepatocyte. Figure 32.10 shows the major transport processes of cholangiocytes, which secrete an alkaline-rich fluid and reclaim useful substances. The cholangiocytes lining the biliary ductules have specialized functions in modifying the composition of bile.
Limit of intestinal absorption 0.5 30 0.0 0.25 0.5 0.75 1.0 1.25 Diet Hepatic and extra-hepatic synthesis To bile As bile acids As cholesterol In health, input = output Cholesterol (g/day) 0.5 •Fig. 32.6 Relationshipbetweenratesofbileacidsynthesisandsecretion.Thebileacidsecretionratenormallyaverages30g/24h,whereasthesynthesisrateaverages0.5g/24h.Thepairsofverticalandhorizontaldottedlinesdepictthenormalrangeforbileacidsecretionandsynthesis,respectively.Increasedsecretion(simulatedbybileacidfeeding)increasestherateofreturnofbileacidstotheliverviaportalblood,whichexertsanegativefeedbackonsynthesis.Conversely,interruptionoftheenterohepaticcirculation,suchasafterilealresection,canincreasesynthesistovaluesmorethan10-foldhigherthannormal.(FromCareyMC,CahalaneMJ.In:AriasIMetal.[eds].The Liver: Biology and Pathobiology. 2nded.NewYork:RavenPress;1988.) •Fig. 32.8 Dailycholesterolbalanceinhealthyadulthumans.
•Fig. 32.9 Pathwaysforentryofsolutesintobile.(ModifiedfromBarrettKE.Gastrointestinal Physiology. NewYork:McGraw-Hill;2006.) because mixed micelles composed of bile acids, phosphatidylcholine, and cholesterol are osmotically active and the tight junctions that link adjacent hepatocytes are relatively leaky, water is drawn into the canalicular lumen, as well as other plasma solutes (e.g., Ca++, glucose, glutathione, amino acids, urea) at concentrations essentially approximating •Fig. 32.7 Relativeamountsofbileacidsindifferentbodypoolsand theenterohepaticcirculation.Therelativeamountsareindicatedbythe widthofthegreenlines.Thusthefigureillustratesthatthemajorityof thebileacidpoolcirculatesbetweentheliver,gallbladder,andsmall
Fig. 32.9 ). Finally, conjugated bilirubin, which is water soluble, and a variety of additional organic and xenobiotics are secreted into bile across the apical intestine,ratherthanbeinginthesystemiccirculation.membrane of the hepatocyte.
•Fig. 32.10 Themajortransportprocessesofcholangiocytesthatsecreteanalkaline-richfluidandreclaimusefulsubstances.AQP,aquaporin;CFTR,cysticfibrosistransmembraneconductanceregulator;GGT,γ-glutamyltranspeptidase;NKCC1,sodium/potassium/2chloridecotransporter1;NBC,sodium/bicarbonatecotransporter;NHE1,sodium/hydrogenexchanger1,SGLT-1,sodium-glucosecotransporter1;GLUT1,glucosetransporter1.
The cholangiocytes lining the biliary ductules are specifically designed to modify the composition of bile (