Digestion Tract: Accessory Organs

Liver has a unique blood supply. It receives blood from the small intestine, pancreas, and spleen via the hepatic portal vein. This vein carries 75% of the blood supply to the liver, essentially depleted of oxygen. It contains nutrients, noxious materials, blood cells and breakdown products of blood cells (from the spleen), and endocrine secretions of the pancreas. The hepatic artery carries oxygenated blood to the liver, making up the remaining 25% of the supply. Blood from the hepatic portal vein and hepatic artery is mixed as it perfuses hepatocytes of the parenchyma. Hepatocytes are never exposed to fully oxygenated blood. In the liver parenchyma, branches of the hepatic portal vein and hepatic artery supply the sinusoidal capillaries (sinusoids). There is also draining of the branches of the bile ducts system. These three constitute and travel as the portal triad, because the portal triad involves the lymphatic vessels as well. The liver structure includes hepatocytes (plates of cells), connective tissue stroma (blood vessels, nerves, lymphatics, and bile ducts travel within the CT), sinusoidal capillaries (sinusoids [between plates of cells]), and perisinusoidal spaces (or spaces of Disse). There are three descriptions of liver lobules:

• Classic liver lobule are hexagonal blocks of tissue. They consist of stacks of anastomosing plates of liver cells, which are 1-2 cells thick and radiate from the central vein to the periphery of the lobule. Plates are separated by the branching system of sinusoids, and the cells are perfused with mixed portal and arterial blood. The center of a classic lobule is occupied by a large venule, the terminal hepatic venule (also called central vein). Sinusoids drain into it. Each lobule is about 2.0 X 0.7 mm. At the angles of the hexagon are the portal areas (also called portal canals), and contain the portal triads. It is made of loose stromal connective tissue. Space between the hepatocytes and portal canals is the space of Mall, where lymph originates in the liver. Humans have very little interlobular connective tissue. It is useful to draw imaginary lines between portal areas in histological sections of the human liver to appreciate the size of a lobule. Classic lobules are very easy to see in some species. For example, in the liver of pigs the portal areas (canals) are connected by thick layers of connective tissue.
• Portal lobule
• Liver acinus correlates blood perfusion, metabolic activity, and liver pathology. They are described as diamond-shaped or oval-shaped. The short axis is defined by the terminal branches of the portal triad that lie along the border between two classic lobules. The long axis is the line between the two central veins closest to the short axis. The acinus concept allows description of patterns of specific toxic effects in liver parenchyma, degeneration, and regeneration. Cells in each acinus are arranged in three concentric elliptical zones surrounding the short axis:
• Zone 1 is closest to the short axis. These cells are first to receive nutrients and toxins, show degenerative changes following bile duct occlusion (bile stasis), and to regenerate. They are last to die if circulation is impaired.
• Zone 3 is farthest from the axis and closest to the terminal hepatic venule (central vein). These cells are first to show ischemic necrosis (centrilobular necrosis) during reduced perfusion, and to show fat accumulation. They are last to respond to toxins and bile stasis.
• Zone 2 lies between zone 1 and 3 but has no sharp boundaries. These cells exhibit intermediate reaction to the previously mentioned conditions.

Blood Vessels of the Parenchyma:

• Portal Vein, where the lumen is larger than that of the associated artery. It provides venous blood to the sinusoids.
• Hepatic Artery has a thick muscular wall, which is typical of arteries. It provides arterial blood to the sinusoids, connective tissue, and other structures in the portal canals.
• Central Vein has a thin wall, central position, and receives blood from hepatic sinusoids. The endothelium is surrounded by spirally arranged connective tissue fibers. They are more properly called the terminal hepatic venule because it is the terminal venule of the hepatic portal vein system.
• Sinusoids are lined with thin endothelial cells that are discontinuous (large gaps seen between the cells) and have wide open fenestrae (i.e. no diaphragm). Endothelial cells are supported by discontinuous basal lamina.

Space of Disse associated cells. In addition to the lining endothelial cells, the space of Disse is associated with:

• Kupffer cells, which form part of the sinusoid lining. They are derived from monocytes and do not form junctions with endothelial cells.
• Ito cells (hepatic stellate cells or lipocytes), which are the primary site for storage of vitamin A (transported from the liver to the retina). When depleted of lipids, these cells look like fibroblasts. They secrete reticular fibers (type III collagen).
• Anal canal, where the submucosa has terminal branches of superior rectal artery and rectal venous plexuses. Enlargements of submucosal veins constitute internal hemorrhoids, related to elevated venous pressure of the portal circulation. The inner circular layer of muscularis externa is modified to form the internal anal sphincter. Muscles of the pelvis form the external anal sphincter.

Hepatocytes are large polygonal cells with large central, spherical nuclei. Many cells are binucleate and tetraploid (have 4x amount of DNA). Each nucleus contains -12 well developed nucleoli. They have numerous mitochondria (800-1000/cell), several small Gogli complexes per cell, developed rER, and developed sER.

• Rich in peroxisomes, which are involved in the breakdown of hydrogen peroxides produced in many general cytoplasmic activities. There are 200-300/cell and are large, roughly 0.2-1.0 μm. Peroxisome enzymes in humans include catalase and alcohol dehydrogenase (½ of alcohol ingested is converted to acetaldehyde by peroxisome enzymes).
• There are extensive smooth ER in hepatocytes, but it varies with metabolic activity. They contain enzymes involved in degradation and conjugation of toxins and drugs, and synthesis of cholesterol and the lipid portion of lipoproteins. sER undergoes hypertrophy after the administration of phenobarbital, ethanol, anabolic steroids and progesterone, and certain cancer therapeutic drugs.

The biliary tree is a system of conduits of increasing diameter that carries bile from the hepatocytes to the gallbladder and intestine. The flow of bile is centrifugal (opposite the flow of blood), beginning at the region of the central vein and proceeding to the portal canal.

• Bile canaliculi are small canals formed by opposed grooves in the surface of neighbouring cells. They form a complete loop around four sides of 6-sided hepatocytes. They contain short irregular microvilli and are sealed by junctional complexes (tight, adhering, and desmosomal junctions). Near the portal canal, bile canaliculi join to form Canals of Hering. These are partially lined by hepatocytes and cholangiocytes (which are cuboidal, possess microvilli and a single cilium, and line the rest of the biliary tree where they become columnar). Canals of Hering carry bile to the bile ducts (part of the triad).