Compression of the circulation of the liver, particularly the sinusoids, due to fibrosis leads to a loss of the liver's ability to handle increases in blood flow after a meal without an increase in pressure. This results in albumin escaping from the circulation and albumin-rich fluid leaking from the surface of the liver into the abdominal cavity, overwhelming the lymphatic drainage. This condition is known as ascites and causes a significant increase in the girth of patients with liver disease. As pressure in the liver builds, new collateral blood vessels form to bypass the obstruction and reduce portal hypertension. Some of these vessels are directed to abdominal structures and are prone to rupture due to their thin weak walls. A specific example is the formation of high-pressure collaterals in the esophagus, which can become varices and bleed into the lumen. Bleeding into the esophageal lumen is difficult to control and is a medical emergency. Even in the absence of bleeding, the formation of collateral blood vessels bypasses the remaining metabolic capacity of the liver, leading to increased levels of toxins such as ammonia that can have adverse effects elsewhere in the body.

Infection of the liver with certain viruses or overexposure to toxic substances such as alcohol causes hepatocyte death and activates hepatic stellate cells, which produce excessive collagen resulting in fibrosis. If the insult is chronic, the fibrosis eventually becomes irreversible, a condition known as cirrhosis. The fibrotic scarred areas crowd out the hepatocyte mass, reducing the liver's synthetic, metabolic, and excretory capacity. Fibrotic masses compress the sinusoids and prevent them from expanding as portal blood flow to the liver increases after a meal. Edema may develop in patients with chronic liver injury due to reduced levels of albumin in the blood, and ascites may then develop, with fluid accumulating in the peritoneal cavity due to increased portal pressure. Eventually, the accumulation of toxic substances in the bloodstream can lead to jaundice, itching, and neurological complications. If hepatic function becomes severely compromised, liver transplantation is the only effective treatment.

Hepatocytes also play a role in the biliary system. While hepatocytes are epithelial cells with basolateral and apical membranes, their spatial arrangement differs from simple columnar epithelium, such as the lining of the gastrointestinal tract. 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 come together to form canaliculi, which are channels between the cells. Canaliculi drain bile from the liver, and these canaliculi then drain into biliary ductules lined by columnar epithelial cells called cholangiocytes. Eventually, the biliary ductules drain into larger bile ducts that merge into the right and left hepatic ducts for bile to exit the liver. These hepatic ducts form the common hepatic duct, from which bile can flow into either the gallbladder or the intestine based on pressure relationships.
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.