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U N I T 8
Gastrointestinal and Hepatobiliary Function
spherocytosis, in which the red cell membranes are
defective, or in hemolytic disease of the newborn. In
prehepatic jaundice, there is mild jaundice, the uncon-
jugated bilirubin is elevated, the stools are of normal
color, and there is no bilirubin in the urine. Because
the hepatic mechanisms for conjugating and excreting
bilirubin are not fully mature during the first 2 weeks
of life, many newborn infants develop a transient and
mild unconjugated hyperbilirubinemia, termed
neonatal
or
physiologic jaundice of the newborn
.
3
Abnormally
high or sustained levels of unconjugated bilirubin are
abnormal, however, and require investigation and treat-
ment (see Chapter 13).
Intrahepatic
or
hepatocellular jaundice
is caused
by disorders that directly affect the ability of the liver
to remove bilirubin from the blood or conjugate it so
it can be eliminated in the bile. Liver diseases such as
hepatitis and cirrhosis are the most common causes
of intrahepatic jaundice. Drugs such as the anesthetic
agent halothane, oral contraceptives, estrogen, anabolic
steroids, isoniazid, trimethoprim-sulfamethoxazole,
amoxicillin-clavulanic acid, and chlorpromazine may
also be implicated in this type of jaundice. Because
intrahepatic jaundice usually interferes with all phases
of bilirubin metabolism—uptake, conjugation, and
excretion—both conjugated and unconjugated bilirubin
are elevated, the urine often is dark because of bilirubin
in the urine, and the serum alkaline phosphatase (ALP),
an enzyme present in the bile duct epithelium and cana-
licular membrane of hepatocytes, is slightly elevated.
Posthepatic
or
obstructive jaundice
, also called
cho-
lestatic jaundice,
occurs when bile flow is obstructed
between the liver and the intestine, with the obstruction
located at any point between the junction of the right
or left hepatic duct and the point where the common
bile duct opens into the intestine. Among the causes are
strictures of the bile duct, gallstones, and tumors of the
bile duct or the pancreas. Conjugated bilirubin levels
usually are elevated, the stools are clay colored because
of the lack of bilirubin in the bile, the urine is dark, the
levels of serum ALP are markedly elevated, and the ami-
notransferase levels are slightly increased. Blood levels
of bile acids often are elevated in obstructive jaundice.
As the bile acids accumulate in the blood, pruritus devel-
ops. A history of pruritus preceding jaundice is common
in obstructive jaundice.
Cholestasis
Cholestasis represents a pathologic condition of impaired
bile formation and bile flow, leading to accumulation of
bile pigment in the parenchymal tissues of the liver. As a
result, materials normally transferred to the bile, includ-
ing bilirubin, cholesterol, and bile acids, accumulate in
the blood.
3,4
The condition may be caused by intrinsic
liver disease affecting the intrahepatic canaliculi and bile
ducts, in which case it is referred to as intrahepatic cho-
lestasis. Alternatively, it can by caused by obstruction of
the large bile ducts, for example by strictures, gallstones,
or neoplasms, a condition known as extrahepatic cho-
lestasis. Genetic disorders involving the transport of bile
into the canaliculi also can result in cholestasis.
The morphologic features of cholestasis depend on
the underlying cause. Common to all types of obstruc-
tive and hepatocellular cholestasis is the accumulation
of bile pigment in the liver. Elongated green-brown
plugs of bile are visible in the dilated bile canaliculi.
Rupture of the canaliculi leads to extravasation of bile
and subsequent degenerative changes in the surround-
ing hepatocytes. Prolonged obstructive cholestasis leads
not only to fatty changes in the hepatocytes but also
to destruction of the supporting connective tissue.
3
FIGURE 30-6.
Jaundice in a person with hepatitis A. (From
the Centers for Disease Control and Prevention. Public Health
Image Library No. 2860. Courtesy ofThomas F. Sellers.)
CHART 30-1
Causes of Jaundice
Prehepatic (Excessive Red Blood Cell
Destruction)
Hemolytic blood transfusion reaction
Hereditary disorders of the red blood cell
Sickle cell disease
Thalassemia
Spherocytosis
Acquired hemolytic disorders
Hemolytic disease of the newborn
Autoimmune hemolytic anemias
Intrahepatic
Decreased bilirubin uptake by the liver
Decreased conjugation of bilirubin
Hepatocellular liver damage
Hepatitis
Cirrhosis
Cancer of the liver
Drug-induced cholestasis
Posthepatic (Obstruction of Bile Flow)
Structural disorders of the bile duct
Cholelithiasis
Congenital atresia of the extrahepatic bile ducts
Bile duct obstruction caused by tumors
