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The liver has the ability to process and eliminate more than 3,000 mg of bilirubin per day, although the normal production of bilirubin is only 300 mg per day. This extra capacity allows the liver to respond to increased breakdown of heme by increasing the conjugation and secretion of conjugated bilirubin. However, excessive hemolysis, such as in individuals with sickle cell anemia or deficiencies of pyruvate kinase or glucose 6-phosphate dehydrogenase, can lead to bilirubin being produced faster than it can be conjugated. As a result, levels of unconjugated bilirubin in the blood rise, causing jaundice. Hemolysis also results in increased production and excretion of conjugated bilirubin into the bile, leading to an increased amount of urobilinogen entering the enterohepatic circulation and elevated levels of urinary urobilinogen.

Damage to liver cells, as seen in patients with cirrhosis or hepatitis, can cause unconjugated hyperbilirubinemia due to decreased conjugation. The damage also reduces the enterohepatic circulation of urobilinogen, allowing more of it to enter the bloodstream, where it is eventually filtered into the urine. This leads to darkening of the urine, while the stools may appear pale and clay-colored. Elevated levels of alanine and aspartate transaminases (ALT and AST, respectively) are found in the blood. In cases where conjugated bilirubin is produced but not efficiently secreted into the bile (intrahepatic cholestasis), it may leak into the bloodstream, causing a condition known as conjugated hyperbilirubinemia.

Obstructive jaundice, also known as posthepatic jaundice, is not a result of excessive bilirubin production or decreased conjugation, but rather occurs due to obstruction of the common bile duct (extrahepatic cholestasis). Obstruction can be caused by the presence of a tumor or bile stones, which prevent conjugated bilirubin from entering the intestine. Patients with obstructive jaundice experience gastrointestinal pain and nausea, and their stools may become pale and clay-colored. The conjugated bilirubin regurgitates into the bloodstream, leading to conjugated hyperbilirubinemia. Over time, the conjugated bilirubin is excreted in the urine, causing it to darken. This form of bilirubin in the urine is referred to as urinary bilirubin, while urinary urobilinogen is absent.

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a. Hemolytic (prehepatic): The liver has the capacity to conjugate and excrete >3,000 mg of bilirubin/day, whereas the normal production of bilirubin is only 300 mg/day. This excess capacity allows the liver to respond to increased heme degradation with a corresponding increase in conjugation and secretion of CB. However, extensive hemolysis (for example, in patients with sickle cell anemia or deficiency of pyruvate kinase or glucose 6-phosphate dehydrogenase) may produce bilirubin faster than it can be conjugated. UCB levels in the blood become elevated (unconjugated hyperbilirubinemia), causing jaundice (Fig. 21.12A). [Note: With hemolysis, more CB is made and excreted into the bile, the amount of urobilinogen entering the enterohepatic circulation is increased, and urinary urobilinogen is increased.] b.
Hepatocellular (hepatic): Damage to liver cells (for example, in patients with cirrhosis or hepatitis) can cause unconjugated hyperbilirubinemia as a result of decreased conjugation. Urobilinogen is increased in the urine because hepatic damage decreases the enterohepatic circulation of this compound, allowing more to enter the blood, from which it is filtered into the urine. The urine consequently darkens, whereas stools may be a pale, clay color. Plasma levels of alanine and aspartate transaminases (ALT and AST, respectively; see p. 251) are elevated. If CB is made but is not efficiently secreted from the liver into bile (intrahepatic cholestasis), it can leak into the blood (regurgitation), causing a conjugated hyperbilirubinemia.
c.
Obstructive (posthepatic): In this instance, jaundice is not caused by overproduction of bilirubin or decreased conjugation but, instead, results from obstruction of the common bile duct (extrahepatic cholestasis). For example, the presence of a tumor or bile stones may block the duct, preventing passage of CB into the intestine. Patients with obstructive jaundice experience GI pain and nausea and produce stools that are a pale, clay color. The CB regurgitates into the blood (conjugated hyperbilirubinemia). The CB is eventually excreted in the urine (which darkens over time) and is referred to as urinary bilirubin. Urinary urobilinogen is absent.