As mentioned above, the liver receives a dual blood supply. The hepatic portal vein provides the majority of the incoming blood, the rest coming from the hepatic artery. The blood from the portal vein has already supplied the small intestine, pancreas, and spleen, and is largely deoxygenated. It contains nutrients and noxious materials absorbed in the intestine. The blood from the hepatic artery supplies the liver with oxygen. Because the blood from the two sources intermingles as it perfuses the liver cells, these cells must carry out their many activities under low oxygen conditions that most cells would not be able to tolerate.

The liver synthesizes a number of proteins, as suggested by its abundant rER and Golgi. One of the most important of these is albumins (responsible for several functions including colloid osmotic pressure), the protein parts of several kinds of lipoproteins, nonimmune alpha and beta globulins, prothrombin, and numerous glycoproteins, including fibronectin. These proteins are considered as endocrine secretions because they are released directly from the liver cells into the blood supply. The liver also synthesizes cholesterol and the lipid portion of lipoproteins. The enzymes for these activities are found in the sER.

The liver is involved in a wide range of metabolic activities. Among its major metabolic functions are gluconeogenesis (the formation of glucose from non-carbohydrate precursors), and the deamination of amino acids. In addition to the proteins listed above, the liver also releases a number of other products directly into the blood as endocrine secretions. These include products of carbohydrate metabolism, e.g., glucose released from stored glycogen, and modified secretions from other organs, e.g., triiodothyronine (T3).

Liver cells store large deposits of glucose in the form of glycogen, which can be stained by the periodic acid-Schiff or PAS procedure. They also store lipids in the form of droplets of varying sizes. The latter can be revealed with Sudan staining after tissue fixation. The removal of these materials in routine preparations gives liver cells a foamy or vacuolated appearance. Lysosomes within hepatocytes may be a normal storage site for iron, in a form of a ferritin complex. Excessive amounts of iron may accumulate in cells as an unusable yellowish-brown pigment called hemosiderin, a partly denatured form of ferritin. Liver lysosomes also contain pigment granules (lipofuscin) and partially digested cytoplasmic organelles. The liver also stores vitamins, especially vitamin A, which is transported from the liver to the retina to be used in the formation of visual pigments. Most of the vitamin A is not stored in the hepatocytes, however, but in special fat-storing cells, called Ito cells, within the sinusoids. Ito cells also store the other three fat-soluble vitamins, D, E, and K, as well as vitamin B12.

The liver is, after the gastrointestinal tract, the first organ to receive metabolic substrates and nutrients from the intestine, but it is also the first to receive any toxic substances, for instance carcinogens or drugs that have been ingested. The sER of liver cells contains enzymes involved in the degradation and conjugation of toxins (in addition to those responsible for synthesizing cholesterol and the lipid portion of lipoproteins). Under conditions of challenge by drugs, toxins or metabolic stimulants, the sER becomes the predominant organelle. Stimulation by one drug, e.g., alcohol, enhances its ability to detoxify some other compounds. On the other hand, some toxins can get metabolized by the liver to even more damaging compounds.

The gallbladder is a tubular organ. Its tunica mucosa is a very regular simple columnar epithelium, with no goblet cells or glands. The deep folds in the bottom of the mucosa, which are often cut in cross section, sometimes look like “glands,” but they have no secretory activity. There is a scanty lamina propria, and a thin tunica muscularis. There is no muscularis mucosae, and this is one of the “landmarks” for this organ. The gallbladder is only partially covered by a fold of peritoneum; its opposite side is seated in a pocket in the surface of the liver. Bile ducts carry bile to the gall bladder for temporary storage.

The low magnification image above shows the walls of the gallbladder (Fig. 2.3). They vary in height depending on how full the bladder is. At higher magnification, the nature of the gallbladder epithelium is revealed: a simple columnar form, containing no goblet cells. Though these cells do have a few microvilli on their free surfaces, they cannot be considered as real brush borders. There is no muscularis mucosae in these structures, and the tunica muscularis is stringy and scanty with collagen fibers. Since it has only the function of squirting bile into the duct that carries it to the duodenum, it appears little developed.

Bile is continuously formed in bile canaliculi in the liver hepatocytes, were it is collected and secreted into the hepatic bile duct. Bile is a complex fluid containing water, electrolytes, and a battery of organic molecules including bile acids (water-soluble derivatives of cholesterol), cholesterol, phospholipids, and bilirubin (Mcmaster and Elman 1926). The rate of bile fluid secretion is dependent on the circadian rhythm of the animal.