Porth's Essentials of Pathophysiology, 4e

694

Gastrointestinal and Hepatobiliary Function

U N I T 8

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. ■■ 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. SUMMARY CONCEPTS

Higher cortical centers

Vestibular apparatus

Chemoreceptor trigger zone CSF (4th ventricle)

Gastrointestinal tract

Flow of CSF

Vomiting center

Salivary center

Abdominal muscles

Respiratory center

FIGURE 28-13. Physiologic events involved in vomiting. CSF, cerebrospinal fluid.

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.