A. The sparse collagen fibers found in the perisinusoidal space (of Disse) are produced by the hepatic stellate cells (Ito cells). In certain pathologic conditions, these cells lose their storage vacuoles and differentiate into myofibroblasts that produce collagen fibers, leading to liver fibrosis. Observe that the stellate sinusoidal macrophage (Kupffer cell) forms an integral part of the sinusoidal lining.
FIGURE 18.12 • Electron micrographs of a hepatocyte. a. This electron micrograph shows organelles and other cytoplasmic structures near the nucleus (N). These include a peroxisome (P), mitochondrion (M), glycogen inclusions (Gl), smooth endoplasmic reticulum (sER), and rough endoplasmic reticulum (rER). In the lower left, the membranes of the rER have been cut in a tangential plane showing the ribosomes (encircled by a dashed line) on the cytoplasmic face of the membrane. 12,000. b. This micrograph shows a region of cytoplasm near a bile canaliculus (C). It includes a lysosome (L), mitochondria (M), and both sER and rER. Note the microvilli in the bile canaliculus. 18,000.
Peroxisomes are numerous in hepatocytes.
Hepatocytes have as many as 200 to 300 peroxisomes per cell. They are relatively large and vary in diameter from 0.2 to 1.0 m (see Fig. 18.12a). Peroxisomes are a major site of oxygen use and in this way perform a function similar to that of mitochondria. They contain a large amount of oxidase that generates toxic hydrogen peroxide, H2O2. The enzyme catalase, also residing within peroxisomes, degrades hydrogen peroxide to oxygen and water. These types of reactions are involved in many detoxification processes occurring in the liver (e.g., detoxification of alcohol). In fact, about one half of the ethanol that is ingested is converted to acetaldehyde by enzymes contained in liver peroxisomes. In humans, catalase and D-amino acid oxidase, as well as alcohol dehydrogenase, are found in peroxisomes. In addition, peroxisomes are also involved in breakdown of fatty acids ( oxidation) as well as gluconeogenesis and metabolism of purines.
sER can be extensive in hepatocytes.
The sER in hepatocytes may be extensive but varies with metabolic activity (see Fig. 18.12b). The sER contains enzymes involved in degradation and conjugation of toxins and drugs as well as enzymes responsible for synthesizing cholesterol and the lipid portion of lipoproteins. Under conditions of hepatocyte challenged by drugs, toxins, or metabolic stimulants, the sER may become the predominant organelle in the cell. In addition to stimulating sER activity, certain drugs and hormones induce synthesis of new sER membranes and their associated enzymes. The sER undergoes hypertrophy after administration of alcohol, drugs (i.e., phenobarbital, anabolic steroids, and progesterone), and certain chemotherapeutic agents used to treat cancer.
Stimulation of the sER by ethanol enhances its ability to detoxify other drugs, certain carcinogens, and some pesticides. On the other hand, metabolism by the sER can actually increase the hepatocyte-damaging effects of some toxic compounds, such as carbon tetrachloride (CCl4) and 3, 4-benzpyrene.
The large Golgi apparatus in hepatocytes consists of as many as 50 Golgi units.