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CASE FILES: BIOCHEMISTRY
Intrahepatic cholestasis of pregnancy is a syndrome of unknown etiology
characterized by a 100-fold increase in maternal and fetal blood bile salt lev-
els. Bile salts are produced in both the fetal and maternal liver. The fetus trans-
fers the bile salts across the placenta for disposal. When the function of the
maternal gallbladder is slowed, bile salts can accumulate in the liver and
bloodstream, ultimately resulting in the classical pruritus symptom. It is
believed that pregnancy-related hormones may slow bile salt excretion from
the gallbladder.
The most successful therapy for cholestasis of pregnancy has been
ursodeoxycholic acid (Figure 33-1). Ursodeoxycholic acid is a naturally
occurring bile acid, which, when administered, relieves both pruritus and liver
function abnormalities. Experimental evidence suggests that it protects hepa-
tocytes and cholangiocytes from bile acid-induced cytotoxicity and improves
hepatobiliary excretion. Additionally, it decreases bile salt transfer to the fetus
and improves
the
secretory
function
of placental
trophoblast
cells.
Ursodeoxycholic acid is recycled through the enterohepatic circulation.
Cholestyramine is another treatment option for cholestasis of pregnancy.
It is an oral medication that binds bile salts in the intestine and promotes their
excretion in the feces. As this drug is not absorbed, it most likely has little
effect on the fetus. Effects on the fetus are still under evaluation. However,
cholestyramine can interfere with the absorption of fat soluble vitamins, such
as vitamins A, D, E, and K. In rare cases, drug-induced vitamin K deficiency
is believed to contribute to hemorrhaging during childbirth.
Figure 33-1. Comparison of the structures of isomers of deoxycholate.
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