Biliary atresia in lampreys.

The preceding pages have described an organism that is far removed from mammals on the taxonomic scale of vertebrates but one that has proven to have a unique and most useful system for studies of liver function and, in particular, bile product transport and excretion. It is also an organism in which iron loading can be studied in the liver and other organs and tissues. Many of the events that occur in this animal during its life cycle with regard to bile pigment metabolism as normal programmed phenomena are unparalleled among the vertebrates. In the larval (ammocoete) period of lampreys, there is an intrahepatic gallbladder and a biliary tree that is well equipped for the storage, transport, and elimination of bile products into the intestine for ultimate excretion with the feces. The importance of the patency of these bile ducts to bile excretion is illustrated in one species of lampreys in which the bile ducts of young ammocoetes become infested with larval nematodes to a degree that bile pigment regurgitation into the blood results in a green serum that is identified as biliverdin. Despite having serum levels of biliverdin that would be toxic to humans, these individuals live a complete larval life. The larvae of all lamprey species undergo a phase of metamorphosis in which they transform into adults. During this phase the larval gallbladder, the bile canaliculi of the hepatocytes, and all the intrahepatic bile ducts completely regress in a developmental process called lamprey biliary atresia. The epithelium of the extrahepatic common bile duct transforms and expands into a caudal portion of the endocrine pancreas of the adult. Many of the events of lamprey biliary atresia resemble events occurring during experimental and pathological conditions of mammalian cholestasis, including disruption to the bile-blood barrier (intercellular junctions), accumulation of bile components in the cytoplasmic inclusions, and alteration of the distribution of membrane enzymes in hepatocytes. Regression of the bile ducts and ductules is accompanied by a periductular fibrosis that seems to be a product of activity by lipocytes (Ito cells). The regurgitation of bile products into the interstitial tissue of the liver during early biliary atresia may be the stimulus for both inflammatory (granulomatous) and autoimmune responses. There are no bile ducts in adults lampreys, yet they seem to show no immediate consequences of the absence of an exocrine mechanism for the elimination of bile products.(ABSTRACT TRUNCATED AT 400 WORDS)