Ifthecirculationoftheliver(particularlyitssinusoids)iscompressedbyfibrosis,theliverlosesitsabilitytoaccommodatetheincreasesinbloodflowthatoccurafteramealwithoutaconcomitantincreaseinpressure.Becauseofthefenestrations,albuminescapesfromthecirculationandalbumin-richfluidweepsfromthesurfaceoftheliverintotheabdominalcavity,whereitoverwhelmsthelymphaticdrainage.Thisconditionisknownasascites andisreflectedinaconsiderableincreaseinthegirthofmanypatientswithliverdisease.Aspressureintheliverbuilds,newcollateralbloodvesselsforminanattempttocircumventtheobstructionandreducetheportalhypertension.Someofthesevesselsaredirectedtoabdominalstructuresand,becauseoftheirthinweakwalls,arepronetorupture.Aparticularexampleisformationofhigh-pressurecollateralstotheesophagus,whichcanthenbecomevaricesthatbleedintothelumen.Bleedingintotheesophageallumenisveryhardtocontrolandisthusamedicalemergency.Evenintheabsenceofbleeding,moreover,theformationofcollateralbloodvesselsbypassestheremainingmetaboliccapacityoftheliver,andlevelsoftoxinssuchasammoniaareincreasedandcanexertadverseeffectselsewhereinthebody.
Infectionoftheliverwithcertainvirusesoroverexposuretotoxicsubstancessuchasalcoholkillshepatocytesandactivateshepaticstellatecells,whichsynthesizeexcessiveamountsofcollagenthatresultinthehistologicappearanceoffibrosis.Iftheinsultischronic,thefibrosiseventuallybecomesirreversible,aconditionknownascirrhosis. Thefibroticscarredareascrowdoutthehepatocytemass,therebyreducingthesynthetic,metabolic,andexcretorycapacityoftheliver.Fibroticmassespressonthesinusoidsandpreventthemfromexpandingasportalbloodflowtotheliverincreasesduringthepostprandialperiod.Edemamaydevelopinpatientswithchronicliverinjuryasaresultofreducedlevelsofalbumininblood,andascitesmaythendevelop,inwhichfluidaccumulatesintheperitonealcavitysecondarytoincreasedportalpressure.Eventually,accumulationoftoxicsubstancesinthebloodstreamcanleadtojaundice,itching,andneurologicalcomplications.Ifhepaticfunctionbecomescompromisedbeyondacertainlevel,theonlyeffectivetreatmentislivertransplantation.
Hepatocytes are also the origination point for the biliary system. Although hepatocytes are considered to be epithelial cells with basolateral and apical membranes, the spatial arrangement of these two cell domains differs from that seen in simple columnar epithelium, such as that lining the gastrointestinal tract. Rather, in the liver the apical surface of the hepatocyte occupies only a small fraction of the cell membrane, and the apical membranes of adjacent cells oppose each other to form a channel between the cells known as the canaliculus (see
Fig. 32.3 ). The role of canaliculi is to drain bile from the liver, and these canaliculi drain into biliary ductules that are lined by classic columnar epithelial cells known as cholangiocytes. Ultimately the biliary ductules drain into large bile ducts that coalesce into the right and left hepatic ducts to permit exit of bile from the liver. These in turn form the common hepatic duct, from which bile can flow into either the gallbladder (via the cystic duct) or the intestine (via the common bile duct;
Fig. 32.4 ) on the basis of prevailing pressure relationships.