Pathology Answer-11

(E) 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 (choice C)
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. In biliary tract obstruction,
conjugated bilirubin will accumulate
proximal to the point of obstruction and will
reflux back into the circulation, leading to an
increase in urinary conjugated bilirubin
(choice B), a process that does not occur in
hemolytic anemia. Unconjugated bilirubin
(choice D) is not water soluble .

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