Porth's Essentials of Pathophysiology, 4e

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Disorders of Hepatobiliary and Exocrine Pancreas Function

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TABLE 30-1 Functions of the Liver and Manifestations of Altered Function Function Manifestations of Altered Function

Production of bile salts Elimination of bilirubin

Malabsorption of fat and fat-soluble vitamins Elevation in serum bilirubin and jaundice

Metabolism of steroid hormones Sex hormones

Disturbances in gonadal function, including gynecomastia in the male

Glucocorticoids

Signs of increased cortisol levels (i.e., Cushing syndrome)

Aldosterone

Signs of hyperaldosteronism (e.g., sodium retention and hypokalemia) Decreased drug metabolism Decreased plasma binding of drugs owing to a decrease in albumin production

Metabolism of drugs

Carbohydrate metabolism

Hypoglycemia may develop when glycogenolysis and gluconeogenesis are impaired

Stores glycogen and synthesizes glucose from amino acids, lactic acid, and glycerol

Abnormal glucose tolerance curve may occur because of impaired uptake and release of glucose by the liver

Fat metabolism Formation of lipoproteins

Impaired synthesis of lipoproteins

Conversion of carbohydrates and proteins to fat Synthesis, recycling, and elimination of cholesterol

Altered cholesterol levels

Formation of ketones from fatty acid Protein metabolism Deamination of proteins Formation of urea from ammonia

Elevated blood ammonia levels

Synthesis of plasma proteins

Decreased levels of plasma proteins, particularly albumin, which contributes to edema formation

Synthesis of clotting factors (fibrinogen, prothrombin, factors V, VII, IX, X)

Bleeding tendency

Storage of minerals and vitamins

Signs of deficiency of fat-soluble and other vitamins that are stored in the liver Increased exposure of the body to colonic bacteria and other foreign matter

Filtration of blood and removal of bacteria and particulate matter by Kupffer cells

hormones and drugs, synthesizes plasma proteins and blood clotting factors, stores vitamins and minerals, maintains blood glucose levels, and regulates very–low- density lipoprotein (VLDL) levels. In its capacity for metabolizing drugs and hormones, the liver serves as an excretory organ. In this respect, the bile, which carries the end products of substances metabolized by the liver, is much like the urine, which carries the body wastes filtered by the kidneys. These functions, many of which are disrupted by the liver diseases discussed in this chap- ter, are summarized in Table 30-1. Metabolic Functions The liver is involved in many metabolic pathways including carbohydrate metabolism and maintenance of blood glucose, lipid metabolism, and protein synthe- sis and conversion of ammonia to urea. In addition to nutrients, several vitamins (e.g., A, D, K) are also taken up from the bloodstream and then stored or biochemi- cally converted in the liver. Carbohydrate Metabolism. The liver plays an essential role in carbohydrate metabolism and glucose homeosta- sis (Fig. 30-4A). It stores excess glucose as glycogen and synthesizes glucose from amino acids and other sub- strates as a means of maintaining blood glucose dur- ing periods of fasting or increased need. The liver also

converts excess carbohydrates to triglycerides for stor- age in adipose tissue. Pathways of Lipid Metabolism. Although most cells of the body metabolize fat, certain aspects of lipid metabolism occur mainly in the liver. These include the oxidation of free fatty acids to ketoacids; synthesis of cholesterol, phospholipids, and lipoproteins; and for- mation of triglycerides from carbohydrates and proteins (Fig. 30-4B). To derive energy from neutral fats (tri- glycerides), the molecule must first be split into glycerol and fatty acids, and then the fatty acids split into two- carbon acetyl-coenzyme A (acetyl-CoA units). Acetyl- CoA is readily channeled into the citric acid cycle to produce adenosine triphosphate ([ATP], see Chapter 1, Understanding Cell Metabolism). Because the liver can- not use all the acetyl-CoA that is formed, it converts the excess into acetoacetic acid, a highly soluble ketoacid that is released into the bloodstream and transported to other tissues, where it is used for energy. The acetyl- CoA derived from fat metabolism is also used to synthe- size cholesterol and bile acids. Cholesterol has several fates in the liver. It can be esterified and stored, exported bound to VLDLs, or converted to bile acids. Protein Synthesis and Conversion of Ammonia to Urea. In addition to its role in carbohydrate and lipid metabolism, the liver is also an important site for