Ganong's Review of Medical Physiology, 23rd Edition

484
SECTION V
Gastrointestinal Physiology

extrahepatic bile duct obstruction. When it is due to one of the
first three processes, the free bilirubin rises. When it is due to
disturbed secretion of conjugated bilirubin or bile duct obstruc-
tion, bilirubin glucuronide regurgitates into the blood, and it is
predominantly the conjugated bilirubin in the plasma that is
elevated.

OTHER SUBSTANCES CONJUGATED

BY GLUCURONYL TRANSFERASE

The glucuronyl transferase system in the smooth endoplasmic
reticulum catalyzes the formation of the glucuronides of a variety
of substances in addition to bilirubin. As discussed above, the list
includes steroids (see Chapter 22) and various drugs. These other
compounds can compete with bilirubin for the enzyme system
when they are present in appreciable amounts. In addition, sev-
eral barbiturates, antihistamines, anticonvulsants, and other
compounds cause marked proliferation of the smooth endoplas-
mic reticulum in the hepatic cells, with a concurrent increase in
hepatic glucuronyl transferase activity. Phenobarbital has been
used successfully for the treatment of a congenital disease in
which there is a relative deficiency of glucuronyl transferase (type
2 UDP-glucuronosyltransferase deficiency).

OTHER SUBSTANCES

EXCRETED IN THE BILE

Cholesterol and alkaline phosphatase are excreted in the bile.

In patients with jaundice due to intra- or extrahepatic obstruc-

tion of the bile duct, the blood levels of these two substances

usually rise. A much smaller rise is generally seen when the

jaundice is due to nonobstructive hepatocellular disease.

Adrenocortical and other steroid hormones and a number of

drugs are excreted in the bile and subsequently reabsorbed

(enterohepatic circulation).

AMMONIA METABOLISM & EXCRETION

The liver is critical for ammonia handling in the body. Ammo-

nia levels must be carefully controlled because it is toxic to the

central nervous system (CNS), and freely permeable across the

blood–brain barrier. The liver is the only organ in which the

complete urea cycle (also known as the Krebs-Henseleit cycle)

is expressed (Figure 29–6). This converts circulating ammonia

to urea, which can then be excreted in the urine (Figure 29–7).

Ammonia in the circulation comes primarily from the

colon and kidneys with lesser amounts deriving from the

breakdown of red blood cells and from metabolism in the

muscles. As it passes through the liver, the vast majority of

FIGURE 29–6
The urea cycle, which converts ammonia to urea, takes place in the mitochondria and cytosol of hepatocytes.

To circulation

ATP

HCO 3 −

NH 4 + H 2 NC

O

OPO−

O−

ADP O

Carbamoyl

Mitochondrionphosphate

H 2 NC

O

NH (CH 2 ) 3 CH COO−

NH 3 +

Citrulline

COO− NH 2 + NH 3 +

OOC CH 2 CH NH C NH (CH 2 ) 3 CH COO−

Aspartate

AMP

2

3

4

Arginine succinate

H 2 NCNH(CH 2 ) 3 CH COO−

NH 2 + NH 3 +

Arginine

H 3 N(CH 2 ) 2 CH COO−

NH 3 +

+

NH 3

H 2 NC

O

NH 2

Fumarate

H 2 O

1 Carbamoyl synthetase 3 Arginine succinate lyase Arginase

Hepatocyte

Net reaction

2NH 3 + CO 2 = Urea + H 2 O

2 Arginosuccinate synthetase

Cytosol

Urea cycle

Urea

Ornithine

1

4

1

P