Porth's Essentials of Pathophysiology, 4e

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Disorders of Hepatobiliary and Exocrine Pancreas Function

C h a p t e r 3 0

where it is converted to urea before being released into the systemic circulation. Intestinal production of ammo- nia is increased after ingestion of high-protein foods and gastrointestinal bleeding, a process that becomes impaired in persons with advanced liver disease. Bile Formation and Flow The secretion of bile is essential for digestion and absorption of dietary fats and fat-soluble vitamins from the intestine. The liver produces approximately 600 to 1200 mL of yellow-green bile daily. 1 Bile contains water, bile salts, bilirubin, cholesterol, and certain by-products of metabolism. Of these, only bile salts, which are formed from cholesterol, are important in digestion. The other components of bile depend on the secretion of sodium, chloride, bicarbonate, and potassium by the bile ducts. Bile salts serve an important function in digestion; they aid in emulsifying dietary fats, and they are necessary for the formation of the micelles that transport fatty acids and fat-soluble vitamins to the surface of the intestinal mucosa for absorption. Approximately 94% of bile salts that enter the intestine are reabsorbed into the portal cir- culation by an active transport process that takes place in the distal ileum. From the portal circulation, the bile salts move into the liver cells and are recycled. Normally, bile salts travel this entire circuit approximately 18 times before being expelled in the feces. 1 The system for recir- culation of bile is called the enterohepatic circulation. Bilirubin Formation and Jaundice Bilirubin is the substance that gives bile its color. It is formed from aging red blood cells. In the process of deg- radation, the hemoglobin from the red blood cell is bro- ken down to form biliverdin, which is rapidly converted to free bilirubin (Fig. 30-5). Free bilirubin (unconju- gated), which is insoluble in plasma, is transported in the blood attached to plasma albumin. As it passes through the liver, unconjugated bilirubin is absorbed through the hepatocytes’ cell membrane and released from its albumin carrier molecule. Once inside the hepatocyte, unconjugated bilirubin combines with glucuronic acid (a molecule similar to glucose) to create a water-soluble form called conjugated bilirubin , which is secreted as a constituent of bile. In this form, it passes through the bile ducts into the small intestine. In the intestine, approximately one half of the bilirubin is converted into a highly soluble substance called urobilinogen by the intestinal flora. Urobilinogen is either absorbed into the portal circulation or excreted in the feces. Most of the urobilinogen that is absorbed is returned to the liver to be reexcreted into the bile. A small amount of urobi- linogen, approximately 5%, is absorbed into the general circulation and then excreted by the kidneys. Usually, only a small amount of bilirubin is found in the blood; the normal level of total serum bilirubin is 0.1 to 1.2 mg/dL (2 to 21 μ mol/L). 3 Laboratory measure- ments of bilirubin usually determine the unconjugated and conjugated bilirubin as well as the total bilirubin. These are reported as the direct (conjugated) bilirubin and the indirect (unconjugated) bilirubin.

Senescent Red Blood Cell Hemoglobin Heme + Globin

Plasma Free bilirubin (protein bound)

Biliverdin

Liver

Conjugated bilirubin

Portal circulation

Bile duct

Intestine (bacterial flora) urobilinogen

General circulation

Feces

Kidney

Urine

FIGURE 30-5. The process of bilirubin formation, circulation, and elimination.

Jaundice (i.e., icterus) is a yellowish discoloration of the skin and deep tissues resulting from abnormally high levels of bilirubin in the blood. Jaundice becomes evident when the serum bilirubin levels rise above 2 to 2.5 mg/dL (34.2 to 42.8 μ mol/L). 3,4 Because normal skin has a yellow cast, the early signs of jaundice often are difficult to detect, especially in persons with dark skin. Bilirubin has a special affinity for elastic tissue. The sclera of the eye, which contains a high proportion of elastic fibers, usually is one of the first structures in which jaundice can be detected (Fig. 30-6). The four major causes of jaundice are excessive destruction of red blood cells, impaired uptake of bili- rubin by the liver cells, decreased conjugation of bili- rubin, and obstruction of bile flow in the canaliculi of the hepatic lobules or in the intrahepatic or extrahepatic bile ducts. From an anatomic standpoint, jaundice can be categorized as prehepatic, intrahepatic, and posthe- patic. Chart 30-1 lists the common causes of prehepatic, intrahepatic, and posthepatic jaundice. The major cause of prehepatic jaundice is exces- sive hemolysis of red blood cells. Hemolytic jaundice occurs when red blood cells are destroyed at a rate in excess of the liver’s ability to remove the bilirubin from the blood. It may follow a hemolytic blood transfusion reaction or may occur in diseases such as hereditary