Hyperbilirubinemia refers to elevated bilirubin levels in the blood plasma. Bilirubin comes in two forms, water-soluble and water-insoluble. Water-soluble bilirubin is called conjugated bilirubin, and water-insoluble bilirubin is called unconjugated bilirubin, according to "Pathophysiology 3rd Edition." The nomenclature is derived from the concept of bilirubin metabolism.
Bilirubin Metabolism
According to "Pathophysiology 3rd Edition," red blood cells are produced by the bone marrow and released into circulation. At the end of their life span of 120 days, they become fragile and burst, releasing hemoglobin. Specialized cells called macrophages capture hemoglobin and degrade it into heme and globin. The heme portion is converted into a greenish-yellow pigment called bilirubin and released into systemic circulation. At this stage, the bilirubin is water-insoluble or unconjugated, and must bind to a protein carrier, albumin, to reach the liver. At the liver, bilirubin separates from albumin to enter liver cells. It undergoes modification to become water-soluble or conjugated bilirubin. In this form, liver cells excrete bilirubin into the liver bile ducts to flow through the biliary tree into the small intestine.
Unconjugated Hyperbilirubinemia
Unconjugated hyperbilirubinemia results from increased unconjugated bilirubin levels in blood plasma from excessive red blood cell destruction, or hemolysis. Liver cells become overwhelmed and unable to excrete conjugated bilirubin at the rate they are being produced from destroyed red blood cells. Consequently, the unconjugated form increases in concentration beyond normal levels and gradually deposits in skin, causing jaundice. In the absence of hemolysis, other factors should be considered, according to "Harrison's Principles of Internal Medicine 17th Edition."
Certain medications will interfere with the uptake of bilirubin into the liver cells and may cause unconjugated hyperbilirubinemia. These include rifampicin and probenecid, according to "Harrison's Principles of Internal Medicine 17th Edition".
Genetic conditions impair bilirubin conjugation. A defective gene in liver cells is inherited that affects the expression of an enzyme called bilirubin-UDPGT. The gene abnormally produces a reduced amount of enzyme or no enzyme. The absence or insufficient enzyme activity interferes with bilirubin conjugation and result in mild to high, unconjugated hyperbilirubinemia, according to "Harrison's Principles of Internal Medicine 17th Edition".
Conjugated Hyperbilirubinemia
Conjugated hyperbilirubinemia indicates that the liver cells conjugated bilirubin, but that excretion was unsuccessful as a consequence of biliary obstruction or intrahepatic disorders. Obstruction in the biliary tree secondary to a stone or a pancreatic head carcinoma obstructs the flow of bile through the biliary tree and causes back flow into the liver cells and back into systemic circulation. Since the conjugated form of bilirubin does not require a protein carrier, it enters the kidney and causes dark or tea-colored urine, according to "Harrison's Principles of Internal Medicine 17th Edition." In biliary obstruction, the liver cells are functional and continue to accept unconjugated bilirubin, but return the conjugated form back into circulation since the biliary ducts are blocked or narrowed.
Intrahepatic or hepatocellular causes of conjugated hyperbilirubinemia include liver inflammation or hepatitis related to viral infection, excessive alcohol consumption or acetaminophen medication, according to "Pathophysiology 3rd Edition."
References
- "Harrison's Principles of Internal Medicine 17th Edition"; Fauci, et al.; 2008
- "Pathophysiology Third Edition"; Copstead, et al.; 2005
