In some species (e.g., the pig; Fig. 18.4a), the classic lobule is easily recognized because the portal areas are connected by relatively thick layers of connective tissue. In humans, however, there is normally very little interlobular connective tissue, and it is necessary, when examining histologic sections of liver, to draw imaginary lines between portal areas surrounding a central vein to get some sense of the size of the classic lobule (Fig. 18.4b).
The portal lobule emphasizes the exocrine functions of the liver.
The major exocrine function of the liver is bile secretion. Thus, the morphologic axis of the portal lobule is the interlobular bile duct of the portal triad of the classic lobule. Its outer margins are imaginary lines drawn between the three central veins that are closest to that portal triad (Fig. 18.5). These lines define a roughly triangular block of tissue that includes those portions of three classic lobules that secrete the bile that drains into its axial bile duct. This concept allows a description of hepatic parenchymal structure comparable to that of other exocrine glands.
The liver acinus is the structural unit that provides the best correlation between blood perfusion, metabolic activity, and liver pathology.
The liver acinus is lozenge shaped and represents the smallest functional unit of the hepatic parenchyma. The short axis of the acinus is defined by the terminal branches of the portal triad that lie along the border between two classic lobules. The long axis of the acinus is a line drawn between the two central veins closest to the short axis. Therefore, in a two-dimensional view (Fig. 18.6) the liver acinus occupies parts of adjacent classic lobules. This concept allows a description of the exocrine secretory function of the liver comparable to that of the portal lobule.
The hepatocytes in each liver acinus are described as being arranged in three concentric elliptical zones surrounding the short axis (see Fig. 18.6).  Zone 1 is closest to the short axis and the blood supply from penetrating branches of the portal vein and hepatic artery. This zone corresponds to the periphery of the clas sic lobules.  Zone 3 is farthest from the short axis and closest to the ter minal hepatic vein (central vein). This zone corresponds to the most central part of the classic lobule that surrounds the terminal hepatic vein.  Zone 2 lies between zones 1 and 3 but has no sharp boundaries.
The zonation is important in the description and interpretation of patterns of degeneration, regeneration, and specific toxic effects in the liver parenchyma relative to the degree or quality of vascular perfusion of the hepatic cells. As a result of the sinusoidal blood ﬂow, the oxygen gradient, metabolic activity of the hepatocytes, and distribution of hepatic enzymes vary chapter 18 Digestive System III: Liver, Gallbladder, and Pancreas LIVE R 633
FIGURE 18.4 • Photomicrographs of pig and human livers. a. This photomicrograph shows a cross section of a pig liver lobule stained by the Mallory-Azan method to visualize connective tissue components. Note the relatively thick interlobular connective tissue (stained blue) surrounding the lobules. The terminal hepatic venule (central vein) is visible in the center of the lobule. 65. b. Photomicrograph of a human liver from a routine H&E preparation. Note that in contrast to the pig liver, the lobules of the human liver lack connective tissue septa. The plates of hepatocytes of one lobule merge with those of adjacent lobules. The boundaries of a lobule can be approximated, however, by drawing a line (dashed line) from one portal canal to the next, thus circumscribing the lobule. 65.