The liver is a large multilobed organ located in the abdominal cavity whose function is intimately associated with that of the gastrointestinal system. The liver serves as the first site of processing for most absorbed nutrients and also secretes bile acids, which as we learned in , play a critical role in absorption of lipids from the diet. In addition the liver is a metabolic powerhouse, critical for disposing of a variety of metabolic waste products and xenobiotics from the body by converting them to forms that can be excreted. The liver stores or produces numerous substances needed by the body, such as glucose, amino acids, and plasma proteins. In general, key functions of the liver can be divided into three areas: (1) contributions to whole-body metabolism, (2) detoxification, and (3) excretion of protein-bound/lipid-soluble waste products. In this chapter we discuss the structural and molecular features of the liver and biliary system that subserve these functions, as well as their regulation. Although the liver contributes in a pivotal way to the maintenance of whole-body biochemical status, a complete discussion of all the underpinning reactions is beyond the scope of this chapter. We will confine our discussion primarily to hepatic functions that relate to gastrointestinal physiology.
Metabolic Functions of the Liver
Hepatocytes contribute to metabolism of the major nutrients: carbohydrates, lipids, and proteins. Thus the liver plays an important role in glucose metabolism by engaging in gluconeogenesis, conversion of other sugars to glucose. The liver also stores glucose as glycogen at times of glucose excess (e.g., postprandial period) and then releases stored glucose into the bloodstream as it is needed. This process is referred to as the glucose buffer function of the liver. When hepatic function is impaired, glucose concentrations in blood may rise excessively after ingestion of carbohydrate; conversely, between meals, hypoglycemia may be seen because of an inability of the liver to contribute to carbohydrate metabolism and interconversion of one sugar to another.
Hepatocytes also participate in lipid metabolism. They are a particularly rich source of the metabolic enzymes engaged in fatty acid oxidation to supply energy for other body functions. Hepatocytes also convert products of carbohydrate metabolism to lipids that can be stored in adipose tissue and synthesize large quantities of lipoproteins, cholesterol, and phospholipids, the latter two being important in the biogenesis of cell membranes. In addition, hepatocytes convert a considerable portion of synthesized cholesterol to bile acids, which will be discussed in more detail later in this chapter.
The liver also plays a vital role in protein metabolism. The liver synthesizes all the nonessential amino acids (see ) that do not need to be supplied in the diet, in addition to participating in interconverting and deaminating amino acids so the products can enter biosynthetic pathways for carbohydrate synthesis. With the exception of immunoglobulins, the liver synthesizes almost all the proteins present in plasma (especially albumin, which determines plasma oncotic pressure) as well as most of the important clotting factors. Patients suffering from liver disease may develop peripheral edema secondary to hypoalbuminemia and are also susceptible to bleeding disorders. Finally, the liver is the critical site for disposal of the ammonia generated from protein catabolism. This is accomplished by converting ammonia to urea, which is •Fig. 32.1 Typicalbloodflowthroughthesplanchniccirculationinafastingadulthuman.
excreted by the kidneys. The details of this process will be discussed later in this chapter.
The Liver and Detoxification