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 (