694
U N I T 8
Gastrointestinal and Hepatobiliary Function
The act of vomiting is integrated in the vomiting cen-
ter, which is located in the dorsal portion of the reticular
formation of the medulla near the sensory nuclei of the
vagus (Fig. 28-13). The vomiting center can be activated
directly by irritants or indirectly following input from
four different sources: (1) the GI tract and other abdom-
inal organs; (2) higher central nervous system centers
that respond to certain sights, sounds, or emotions that
induce vomiting; (3) the vestibular apparatus, which is
responsible for motion sickness; and (4) the chemorecep-
tor trigger zone, which is activated by chemical agents
such as drugs and toxins. Hypoxia exerts a direct effect
on the vomiting center, producing nausea and vomiting.
This direct effect probably accounts for the vomiting
that occurs during periods of decreased cardiac out-
put, shock, environmental hypoxia, and brain ischemia
caused by increased intracranial pressure. Inflammation
of any of the intra-abdominal organs, including the liver,
gallbladder, or urinary tract, can cause vomiting because
of the stimulation of the visceral afferent pathways that
communicate with the vomiting center. Distention or
irritation of the GI tract also causes vomiting through
the stimulation of visceral afferent neurons. The chemo-
receptor trigger zone is located outside the blood–brain
barrier in a small area between the medulla and the floor
of the fourth ventricle, where it is exposed to both blood
and cerebrospinal fluid. This region may be stimulated
by drugs, chemotherapeutic agents, toxins, uremia, aci-
dosis, and pregnancy.
Several neurotransmitters and receptor subtypes are
implicated as neuromediators in nausea and vomiting.
Dopamine, serotonin, and opioid receptors are found
in the GI tract and in the vomiting center and chemo-
receptor trigger zone. Dopamine antagonists, such as
prochlorperazine, depress vomiting caused by stimu-
lation of the chemoreceptor trigger zone. Serotonin is
believed to be involved in the nausea and emesis associ-
ated with cancer chemotherapy and radiation therapy.
Serotonin (5-hydroxytryptamine [5HT]) antagonists
(e.g., granisetron, ondansetron) are often effective in
treating the nausea and vomiting associated with these
stimuli. The recently developed neurokinin-1 (NK-1)
receptor antagonists (e.g., aprepitant) may also be used
for the treatment of acute and delayed chemotherapy-
induced nausea and vomiting. These drugs act cen-
trally to block the activation of the NK-1 receptors in
the vomiting center. Motion sickness appears to be a
CNS response to vestibular stimuli. Norepinephrine
and acetylcholine receptors are located in the vestibu-
lar center. The acetylcholine receptors are thought to
mediate the impulses responsible for exciting the vom-
iting center. Many of the motion sickness drugs (e.g.,
meclizine, dimenhydrinate, transdermal scopalamine)
have a strong CNS anticholinergic effect and act on the
receptors in the vomiting center and areas related to the
vestibular system.
Higher cortical
centers
Gastrointestinal
tract
Chemoreceptor
trigger zone
Vomiting center
Flow of CSF
CSF
(4th ventricle)
Vestibular
apparatus
Salivary
center
Abdominal
muscles
Respiratory
center
FIGURE 28-13.
Physiologic events involved in vomiting. CSF,
cerebrospinal fluid.
SUMMARY CONCEPTS
■■
The signs and symptoms of many GI tract
disorders are manifested by anorexia, nausea,
and vomiting.
■■
Anorexia, or loss of appetite, may occur alone or
may accompany nausea and vomiting.
■■
Nausea, which is an ill-defined, unpleasant
sensation, signals the stimulation of the
medullary vomiting center. It often precedes
vomiting and frequently is accompanied by
autonomic responses, such as salivation and
vasoconstriction with pallor, sweating, and
tachycardia.
■■
Vomiting, which is integrated by the vomiting
center, involves the sudden and forceful oral
expulsion of the gastric contents.The vomiting
center can be activated directly by irritants or
indirectly following input from the GI tract and
other abdominal organs; higher central nervous
system centers; the vestibular apparatus,
which is responsible for motion sickness; or the
chemoreceptor trigger zone, which is activated by
chemical agents such as drugs and toxins.
