ASSESSMENT OF THE LIVER Anatomic and Physiologic Overview The liver, the largest gland of the body and a major organ, can be considered a chemical factory that manufactures, stores, alters, and excretes a large number of substances involved in metabolism (Hammer & McPhee, 2019; Sanyal, Boyer, Terrault, et al., 2018). The location of the liver is essential because it receives nutrient-rich blood directly from the gastrointestinal (GI) tract and then either stores or transforms these nutrients into chemicals that are used elsewhere in the body for metabolic needs. The liver is especially important in the regulation of glucose and protein metabolism. The liver manufactures and secretes bile, which has a major role in the digestion and absorption of fats in the GI tract. The liver removes waste products from the bloodstream and secretes them into the bile. The bile produced by the liver is stored temporarily in the gallbladder until it is needed for digestion, at which time the gallbladder empties and bile enters the intestine (see Fig. 43-1). Anatomy of the Liver The liver is a large, highly vascular organ located behind the ribs in the upper right portion of the abdominal cavity. It weighs between 1200 and 1500 g in the average adult and is divided into four lobes. A thin layer of connective tissue surrounds each lobe, extending into the lobe itself and dividing the liver mass into small, functional units called lobules (Barrett, Barman, Brooks, et al., 2019; Hammer & McPhee, 2019). The circulation of the blood into and out of the liver is of major importance to liver function. The blood that perfuses the liver comes from two sources. Approximately 80% of the blood supply comes from the portal vein, which drains the GI tract and is rich in nutrients but lacks oxygen. The remainder of the blood supply enters by way of the hepatic artery and is rich in oxygen. Terminal branches of these two blood vessels join to form common capillary beds, which constitute the sinusoids of the liver (see Fig. 43-2). Thus, a mixture of venous and arterial blood bathes the hepatocytes (liver cells). The sinusoids empty into venules that occupy the center of each liver lobule and are called the central veins. The central veins join to form the hepatic vein, which constitutes the venous drainage from the liver and empties into the inferior vena cava, close to the diaphragm (Barrett et al., 2019; Hammer & McPhee, 2019; Sanyal et al., 2018). In addition to hepatocytes, phagocytic cells belonging to the reticuloendothelial system are present in the liver. Other organs that contain reticuloendothelial cells are the spleen, bone marrow, lymph nodes, and lungs. In the liver, these cells are called Kupffer cells (Barrett et al., 2019; Hammer & McPhee, 2019). As the most common phagocyte in the human body, their main function is to engulf particulate matter (e.g., bacteria) that enters the liver through the portal blood. The smallest bile ducts, called canaliculi, are located between the lobules of the liver. The canaliculi receive secretions from the hepatocytes and carry them to larger bile ducts, which eventually form the hepatic duct. The hepatic duct from the liver and the cystic duct from the gallbladder join to form the common bile duct, which empties into the small intestine. The sphincter of Oddi, located at the junction where the common bile duct enters the duodenum, controls the flow of bile into the intestine. Figure 43-1 • The liver and biliary system, including the gallbladder and bile ducts. Reprinted with permission from Norris, T. L. (2019). Porth’s pathophysiology: Concepts of altered health states (10th ed., Fig. 38.1). Philadelphia, PA: Wolters Kluwer. Figure 43-2 • A section of liver lobule showing the location of hepatic veins, hepatic cells, liver sinusoids, and branches of the portal vein and hepatic artery. Functions of the Liver Glucose Metabolism The liver plays a major role in the metabolism of glucose and the regulation of blood glucose concentration. After a meal, glucose is taken up from the portal venous blood by the liver and converted into glycogen, which is stored in the hepatocytes. Subsequently, the glycogen is converted back to glucose through a process called glycogenolysis and is released as needed into the bloodstream to maintain normal levels of blood glucose. However, this process provides a limited amount of glucose. Additional glucose can be synthesized by the liver through a process called gluconeogenesis. For this process, the liver uses amino acids from protein breakdown or lactate produced by exercising muscles. This process occurs in response to hypoglycemia (Barrett et al., 2019; Hammer & McPhee, 2019). Ammonia Conversion The use of amino acids from protein for gluconeogenesis results in the formation of ammonia as a by-product. The liver converts this metabolically generated ammonia into urea. Ammonia produced by bacteria in the intestines is also removed from portal blood for urea synthesis. In this way, the liver converts ammonia, a potential toxin, into urea, a compound that is excreted in the urine (Barrett et al., 2019; Hammer & McPhee, 2019). Protein Metabolism The liver also plays an important role in protein metabolism. It synthesizes almost all of the plasma proteins (except gamma-globulin), including albumin, alpha-globulins and beta-globulins, blood clotting factors, specific transport proteins, and most of the plasma lipoproteins. Vitamin K is required by the liver for synthesis of prothrombin and some of the other clotting factors. Amino acids are used by the liver for protein synthesis (Barrett et al., 2019; Hammer & McPhee, 2019). Fat Metabolism The liver is also active in fat metabolism. Fatty acids can be broken down for the production of energy and ketone bodies (acetoacetic acid, beta-hydroxybutyric acid, and acetone). Ketone bodies are small compounds that can enter the bloodstream and provide a source of energy for muscles and other tissues. Breakdown of fatty acids into ketone bodies occurs primarily when the availability of glucose for metabolism is limited, as in starvation or in uncontrolled diabetes. Fatty acids and their metabolic products are also used for the synthesis of cholesterol, lecithin, lipoproteins, and other complex lipids (Hammer & McPhee, 2019; Sanyal et al., 2018). Vitamin and Iron Storage Vitamins A, B, and D and several of the B-complex vitamins are stored in large amounts in the liver. Certain substances, such as iron and copper, are also stored in the liver. Bile Formation Bile is continuously formed by the hepatocytes and collected in the canaliculi and bile ducts. It is composed mainly of water and electrolytes such as sodium, potassium, calcium, chloride, and bicarbonate, and it also contains significant amounts of lecithin, fatty acids, cholesterol, bilirubin, and bile salts. Bile is collected and stored in the gallbladder and is emptied into the intestine as needed for digestion. The functions of bile are excretory, as in the excretion of bilirubin; bile also serves as an aid to digestion through the emulsification of fats by bile salts. Bile salts are synthesized by the hepatocytes from cholesterol. After conjugation or binding with amino acids (taurine and glycine), bile salts are excreted into the bile. The bile salts, together with cholesterol and lecithin, are required for emulsification of fats in the intestine, which is necessary for efficient digestion and absorption. Bile salts are then reabsorbed, primarily in the distal ileum, into portal blood for return to the liver and are again excreted into the bile. This pathway from hepatocytes to bile to intestine and back to the hepatocytes is called the enterohepatic circulation. Because of the enterohepatic circulation, only a small fraction of the bile salts that enter the intestine are excreted in the feces. This decreases the need for active synthesis of bile salts by the liver cells (Hammer & McPhee, 2019). Bilirubin Excretion Bilirubin is a pigment derived from the breakdown of hemoglobin by cells of the reticuloendothelial system, including the Kupffer cells of the liver. Hepatocytes remove bilirubin from the blood and chemically modify it through conjugation to glucuronic acid, which makes the bilirubin more soluble in aqueous solutions. The conjugated bilirubin is secreted by the hepatocytes into the adjacent bile canaliculi and is eventually carried in the bile into the duodenum. p. 1366 p. 1367 In the small intestine, bilirubin is converted into urobilinogen, which is partially excreted in the feces and partially absorbed through the intestinal mucosa into the portal blood. Much of this reabsorbed urobilinogen is removed by the hepatocytes and secreted into the bile once again (enterohepatic circulation). Some of the urobilinogen enters the systemic circulation and is excreted by the kidneys in the urine. Elimination of bilirubin in the bile represents the major route of its excretion. Drug Metabolism The liver metabolizes many medications, such as barbiturates, opioids, sedatives, anesthetics, and amphetamines (Goldman & Schafer, 2019; Hammer & McPhee, 2019; Sanyal et al., 2018). Metabolism generally results in drug inactivation, although activation may also occur. One of the important pathways for medication metabolism involves conjugation (binding) of the medication with a variety of compounds, such as glucuronic acid or acetic acid, to form more soluble substances. These substances may be excreted in the feces or urine, similar to bilirubin excretion. Bioavailability is the fraction of the given medication that actually reaches the systemic circulation. The bioavailability of an oral medication (absorbed from the GI tract) can be decreased if the medication is metabolized to a great extent by the liver before it reaches the systemic circulation; this is known as first-pass effect. Some medications have such a large first-pass effect that their use is essentially limited to the parenteral route, or oral doses must be substantially larger than parenteral doses to achieve the same effect. Gerontologic Considerations Chart 43-1 summarizes age-related changes in the liver. In the older adult, the most common change in the liver is a decrease in size and weight, accompanied by a decrease in total hepatic blood flow. However, in general, these decreases are proportional to the decreases in body size and weight seen in normal aging. Results of liver function tests do not normally change with age; abnormal results in older patients indicate abnormal liver function and are not a result of the aging process itself. Chart 43-1 Age-Related Changes of the Hepatobiliary System •Atypical clinical presentation of biliary disease •Decreases in the following: •Clearance of hepatitis B surface antigen •Drug metabolism and clearance capabilities •Intestinal and portal vein blood flow •Gallbladder contraction after a meal •Rate of replacement and or repair of liver cells after injury •Size and weight of the liver, particularly in women •Increased prevalence of gallstones due to the increase in cholesterol secretion in bile •More rapid progression of hepatitis C infection and lower response rate to therapy •More severe complications of biliary tract disease Adapted from Townsend, C. M., Beauchamp, R. D., Evers, B. M., et al. (2016). Sabiston’s textbook of surgery: The biological basis of modern surgical practice. Philadelphia, PA: Elsevier. Metabolism of medications by the liver decreases in the older adult, but such changes are usually accompanied by changes in intestinal absorption, renal excretion, and altered body distribution of some medications secondary to changes in fat deposition. These alterations necessitate careful medication administration and monitoring; if appropriate, reduced dosages may be needed to prevent medication toxicity
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