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332                                                        The Toxicology of Fishes


                       TABLE 7.1
                       Comparison of Rodent and Fish Hepatic Anatomical Features
                       Feature                          Rodent                        Fish
                       Liver lobes           Multiple                     Usually single; cyprinids are exception
                       Lobules               Distinct                     Indistinct or absent; implies different
                                                                          arrangement
                       Portal tracts         Classic lobule contains bile duct, portal   Absent; larger bile ducts may coexist with
                                              venule, and hepatic arteriole and defines   hepatic artery in so-called “biliary arterial
                                              sites where arterial blood enters hepatic   tract”; no portal vein branches are in
                                              microcirculation            biliary arterial tracts
                       Blood supply          Dual supply by hepatic artery and hepatic   Dual supply by hepatic artery and hepatic
                                              portal vein (major volume); capillary-  portal vein (major volume); capillary-like
                                              like sinusoids contain arterial and   sinusoids contain arterial and afferent
                                              afferent venous blood       venous blood
                       Venous drainage       Hepatic veins to caudal vena cava  Hepatic veins to sinus venosus
                       Architecture of parenchyma  Laminae of hepatocytes predominantly   Hepatic tubules comprised of five to eight
                                              one-cell thick and usually separated by   hepatocytes clustered about a lumen
                                              sinusoid from nearest neighbor; no   (biliary passageway); parenchyma often
                                              biliary epithelial cells in parenchymal   contain biliary epithelial cells (see below)
                                              compartment
                       Biliary system        Canaliculi sole component in lobules,   Canaliculi formed by lateral plasma
                                              with network extending from center of   membranes of adjacent hepatocytes; after
                                              lobule to periphery; cholangioles (ducts   short course communicate with lumen of
                                              of Hering) at lobular margin; small bile   hepatic tubule; transitional biliary
                                              ducts in portal tracts; large intrahepatic   epithelial cells and cholangioles present at
                                              ducts near hilus            center of tubules
                       Kupffer cells         Present                      Generally absent; Ameiurus species are
                                                                          exceptions
                       Perisinusoidal macrophages  Present                Present
                       Macrophage aggregates  Absent                      Present


                        In early embryonic stages, human hepatocytes form cords or tubules in which (as in a gland) multiple
                       epithelial cells appear on the cut surface to surround the lumen. The epithelial cell masses cluster around
                       a biliary vascular axis to which afferent blood is brought from hepatic arteries and portal veins, and bile
                       is secreted in the opposite direction (Arias et al., 1988). As metabolic demands rise for mammals, the
                       gland-like cords are transformed into a sponge-like wall work, or cellular mass, which is composed of
                       hepatocellular plates (or laminae) that are predominantly one hepatocyte thick; they meet at different
                       angles and surround the hepatic lacunae (microvasculature and spaces immediately surrounding the
                       capillary such as sinusoids). In the human, metamorphosis from cord or tubule to laminae of hepatocytes
                       is completed by age 5 (Arias et al., 1988). In contrast, the livers of amphibians, birds, fishes, and reptiles
                       retain the tubular architectural pattern as the adult phenotype (Hampton et al., 1985; Hinton and Couch,
                       1998; Hinton et al., 2001). This glandular arrangement of cells within the piscine liver translates into
                       an abundance of biliary  epithelial cells in close proximity to hepatocytes within the parenchymal
                       compartment (Hinton and Couch, 1998).
                        Gross inspection of the livers of fish reveals that most are in the form of a single lobe (Figure 7.1),
                       whereas livers of mammals have multiple lobes. Cyprinid fishes such as Cyprinus carpio and Danio
                       rerio have extensions from the major liver mass that extend along loops of the intestine (Amlacher,
                       1954). These may be regarded as multiple lobes (Figure 7.2). The relationships of the liver to neighboring
                       organs are shown in Figure 7.3 and Figure 7.4.
                        The classic lobule, a consistent microanatomical feature of mammalian liver, is not present in the
                       livers of fish, as has been illustrated in high-resolution light micrographs from medaka liver (Figure 7.5).
                       Mammalian portal tracts, found at corners of the classic lobule, are variably delimited in different
                       mammalian species by perilobular connective tissue containing the bile duct, portal venule, and hepatic
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