Bile Acids
Tau ro - a n d glyco-
T a u ro - a n d glyco-
D eoxych olic acid
Lithocholic acid
FIGURE 19-19
Conversion of primary to secondary bile acids by microbial enzymes.
through a biliary fistula, to administration of bile acid-
complexing resins (e.g., cholestyramine), or to ileal ex-
clusion, activity of 7a-hydroxylase increases several fold,
with consequent increase in bile acid formation. The lat-
ter two methods are used to reduce cholesterol levels in
hypercholesterolemic patients (Chapter 20).
Disposition of Bile Acids in the Intestines and
Their Enterohepatic Circulation
Bile is stored and concentrated in the gallbladder, a saccu-
lar, elongated, pear-shaped organ attached to the hepatic
duct. Bile contains bile acids, bile pigments (i.e., bilirubin
glucuronides; see Chapter 29), cholesterol, and lecithin.
The pH of gallbladder bile is
.9-7.7. Cholesterol is sol-
ubilized in bile by the formation of micelles with bile
acids and lecithin. Cholesterol gallstones can form as a
result of excessive secretion of cholesterol or of insuffi-
cient amounts of bile acids and lecithin relative to choles-
terol in bile. Inadequate amounts of bile acids result from
decreased hepatic synthesis, decreased uptake from the
portal blood by hepatocytes, or increased loss from the
gastrointestinal tract.
With ingestion of food, cholecystokinin (Chapter 12)
is released into the blood and causes contraction of the
gallbladder, whose contents are rapidly emptied into the
duodenum by way of the common bile duct. In the duo-
denal wall, the bile duct fuses with the pancreatic duct
at the ampulla of Vater. Bile functions include absorption
of lipids and the lipid-soluble vitamins A, D, E, and K
by the emulsifying action of bile salts (Chapter 12), neu-
tralization of acid chyme, and excretion of toxic metabo-
lites (e.g., bile pigments, some drugs and toxins) in the
The secondary bile acids, deoxycholic and lithocholic
acids, are derived by 7-dehydroxylation from the decon-
jugated primary bile acids, cholic and chenodeoxycholic
acids, respectively (Figure 19-19), through action of bac-
terial enzymes primarily in the large intestine. The major
portion (> 90%) of bile acids in the intestines is reabsorbed
by an active transport system into the portal circulation at
the distal ileum and transported bound to albumin. They
are taken up by the liver, promptly reconjugated with tau-
rine and glycine, and resecreted into bile. Both ileal ab-
sorption and hepatic uptake of bile acids may be mediated
by Na+-dependent (carrier) transport mechanisms. This
cyclic transport of bile acids from intestine to liver and
back to the intestine is known as the enterohepatic cir-
culation (Figure 19-20). During a single passage of portal
blood through the liver, about 90% of the bile acids are ex-
tracted. The bile acid pool size in the enterohepatic circu-
lation is
2 ^ 1
g and circulates about twice during digestion
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