C h a p t e r 3 0
Disorders of Hepatobiliary and Exocrine Pancreas Function
729
where it is converted to urea before being released into
the systemic circulation. Intestinal production of ammo-
nia is increased after ingestion of high-protein foods
and gastrointestinal bleeding, a process that becomes
impaired in persons with advanced liver disease.
Bile Formation and Flow
The secretion of bile is essential for digestion and
absorption of dietary fats and fat-soluble vitamins from
the intestine. The liver produces approximately 600 to
1200 mL of yellow-green bile daily.
1
Bile contains water,
bile salts, bilirubin, cholesterol, and certain by-products
of metabolism. Of these, only bile salts, which are formed
from cholesterol, are important in digestion. The other
components of bile depend on the secretion of sodium,
chloride, bicarbonate, and potassium by the bile ducts.
Bile salts serve an important function in digestion; they
aid in emulsifying dietary fats, and they are necessary for
the formation of the micelles that transport fatty acids
and fat-soluble vitamins to the surface of the intestinal
mucosa for absorption. Approximately 94% of bile salts
that enter the intestine are reabsorbed into the portal cir-
culation by an active transport process that takes place
in the distal ileum. From the portal circulation, the bile
salts move into the liver cells and are recycled. Normally,
bile salts travel this entire circuit approximately 18 times
before being expelled in the feces.
1
The system for recir-
culation of bile is called the
enterohepatic circulation.
Bilirubin Formation and Jaundice
Bilirubin is the substance that gives bile its color. It is
formed from aging red blood cells. In the process of deg-
radation, the hemoglobin from the red blood cell is bro-
ken down to form biliverdin, which is rapidly converted
to free bilirubin (Fig. 30-5). Free bilirubin (unconju-
gated), which is insoluble in plasma, is transported in the
blood attached to plasma albumin. As it passes through
the liver, unconjugated bilirubin is absorbed through
the hepatocytes’ cell membrane and released from its
albumin carrier molecule. Once inside the hepatocyte,
unconjugated bilirubin combines with
glucuronic acid
(a molecule similar to glucose) to create a water-soluble
form called
conjugated bilirubin
, which is secreted as
a constituent of bile. In this form, it passes through
the bile ducts into the small intestine. In the intestine,
approximately one half of the bilirubin is converted into
a highly soluble substance called
urobilinogen
by the
intestinal flora. Urobilinogen is either absorbed into
the portal circulation or excreted in the feces. Most of
the urobilinogen that is absorbed is returned to the liver
to be reexcreted into the bile. A small amount of urobi-
linogen, approximately 5%, is absorbed into the general
circulation and then excreted by the kidneys.
Usually, only a small amount of bilirubin is found in
the blood; the normal level of total serum bilirubin is 0.1
to 1.2 mg/dL (2 to 21
μ
mol/L).
3
Laboratory measure-
ments of bilirubin usually determine the unconjugated
and conjugated bilirubin as well as the total bilirubin.
These are reported as the direct (conjugated) bilirubin
and the indirect (unconjugated) bilirubin.
Jaundice
(i.e., icterus) is a yellowish discoloration
of the skin and deep tissues resulting from abnormally
high levels of bilirubin in the blood. Jaundice becomes
evident when the serum bilirubin levels rise above 2 to
2.5 mg/dL (34.2 to 42.8
μ
mol/L).
3,4
Because normal
skin has a yellow cast, the early signs of jaundice often
are difficult to detect, especially in persons with dark
skin. Bilirubin has a special affinity for elastic tissue.
The sclera of the eye, which contains a high proportion
of elastic fibers, usually is one of the first structures in
which jaundice can be detected (Fig. 30-6).
The four major causes of jaundice are excessive
destruction of red blood cells, impaired uptake of bili-
rubin by the liver cells, decreased conjugation of bili-
rubin, and obstruction of bile flow in the canaliculi of
the hepatic lobules or in the intrahepatic or extrahepatic
bile ducts. From an anatomic standpoint, jaundice can
be categorized as prehepatic, intrahepatic, and posthe-
patic. Chart 30-1 lists the common causes of prehepatic,
intrahepatic, and posthepatic jaundice.
The major cause of
prehepatic jaundice
is exces-
sive hemolysis of red blood cells. Hemolytic jaundice
occurs when red blood cells are destroyed at a rate in
excess of the liver’s ability to remove the bilirubin from
the blood. It may follow a hemolytic blood transfusion
reaction or may occur in diseases such as hereditary
Senescent Red Blood Cell
Hemoglobin Heme + Globin
Biliverdin
Plasma
Free bilirubin
(protein bound)
Liver
Conjugated
bilirubin
Bile
duct
Portal
circulation
Feces
General
circulation
Intestine
(bacterial flora)
urobilinogen
Kidney
Urine
FIGURE 30-5.
The process of bilirubin formation, circulation,
and elimination.
