A 37-year-old woman visits her primary care physician after developing jaundice and scleral icterus. She is diagnosed with paroxysmal nocturnal hemoglobinuria. Which of the following metabolites would you expect to be increased in her urine?

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In paroxysmal nocturnal hemoglobinuria, there is increased hemolysis leading to elevated levels of hemoglobin breakdown products. Urobilinogen, a product of bilirubin reduction, is increased in the urine due to increased hemolysis and subsequent increased bilirubin processing. Paroxysmal nocturnal hemoglobinuria is a hemolytic anemia in which an acquired cell membrane defect increases red blood cell susceptibility to lysis by endogenous complement. Intravascular hemolysis overwhelms hepatic enzyme conjugation capability and leads to an increase in unconjugated bilirubin (water-insoluble) in serum. The liver enzyme glucuronyl transferase converts unconjugated bilirubin into conjugated bilirubin (now water-soluble), which is then excreted by hepatocytes into the bile. After secretion of bile into the intestine, ileal and colonic bacteria convert conjugated bilirubin into urobilinogen. A fraction of urobilinogen is oxidized to stercobilin and directly excreted in feces (and hence, would not be a urinary metabolite). The remaining urobilinogen is reabsorbed from the intestine and reenters the portal circulation where a portion is taken up by the liver and reexcreted into bile, while the rest bypasses the liver and is excreted by the kidney. Therefore, in hemolytic anemias, increased liver excretion of conjugated bilirubin will lead to an increase in urinary urobilinogen levels. Note that this is in contrast to biliary tract obstruction in which failure of conjugated bilirubin to enter the intestine would lead to decreased levels of both fecal and urinary urobilinogen.

A 37-Year-Old Woman Visits Her Primary Care Physician After Developing