TAILIEUCHUNG - Chapter 043. Jaundice (Part 4)

Hemolytic disorders that cause excessive heme production may be either inherited or acquired. Inherited disorders include spherocytosis, sickle cell anemia, thalassemia, and deficiency of red cell enzymes such as pyruvate kinase and glucose-6-phosphate dehydrogenase. In these conditions, the serum bilirubin rarely exceeds 86 µmol/L (5 mg/dL). Higher levels may occur when there is coexistent renal or hepatocellular dysfunction or in acute hemolysis such as a sickle cell crisis. In evaluating jaundice in patients with chronic hemolysis, it is important to remember the high incidence of pigmented (calcium bilirubinate) gallstones found in these patients, which increases the likelihood of choledocholithiasis. | Chapter 043. Jaundice Part 4 Hemolytic disorders that cause excessive heme production may be either inherited or acquired. Inherited disorders include spherocytosis sickle cell anemia thalassemia and deficiency of red cell enzymes such as pyruvate kinase and glucose-6-phosphate dehydrogenase. In these conditions the serum bilirubin rarely exceeds 86 iimoi l 5 mg dL . Higher levels may occur when there is coexistent renal or hepatocellular dysfunction or in acute hemolysis such as a sickle cell crisis. In evaluating jaundice in patients with chronic hemolysis it is important to remember the high incidence of pigmented calcium bilirubinate gallstones found in these patients which increases the likelihood of choledocholithiasis as an alternative explanation for hyperbilirubinemia. Acquired hemolytic disorders include microangiopathic hemolytic anemia . hemolytic-uremic syndrome paroxysmal nocturnal hemoglobinuria spur cell anemia and immune hemolysis. Ineffective erythropoiesis occurs in cobalamin folate and iron deficiencies. In the absence of hemolysis the physician should consider a problem with the hepatic uptake or conjugation of bilirubin. Certain drugs including rifampicin and probenecid may cause unconjugated hyperbilirubinemia by diminishing hepatic uptake of bilirubin. Impaired bilirubin conjugation occurs in three genetic conditions Crigler-Najjar syndrome types I and II and Gilbert s syndrome. CriglerNajjar type I is an exceptionally rare condition found in neonates and characterized by severe jaundice bilirubin 342 iimoi l 20 mg dL and neurologic impairment due to kernicterus frequently leading to death in infancy or childhood. These patients have a complete absence of bilirubin UDPGT activity usually due to mutations in the critical 3 domain of the UDPGT gene and are totally unable to conjugate hence cannot excrete bilirubin. The only effective treatment is orthotopic liver transplantation. Use of gene therapy and allogeneic hepatocyte infusion are .

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