Nausea and Vomiting
Lisa Lohr
Nausea and vomiting are unpleasant symptoms caused by self-limiting disorders or serious conditions such as cancer. These symptoms can range from mild, short-lived nausea to continuing severe emesis and retching. In addition to the suffering involved, uncontrolled vomiting can lead to dehydration, electrolyte imbalances, malnutrition, aspiration pneumonia, and esophageal tears. Nausea and vomiting often reduce food intake and can impair a person's ability to care for themselves. Significant reductions in quality-of-life scores have been demonstrated in cancer patients with chemotherapy-induced nausea and vomiting compared with patients who did not have those symptoms. Clinicians can improve the care of patients by recommending appropriate preventive medications in situations where nausea and vomiting can be predicted (e.g., postoperative, chemotherapy-induced and radiation-induced symptoms). In addition, by assuring appropriate use of rescue antiemetics, clinicians can help reduce existing symptoms.
Pathophysiology and Neurotransmitters
The neurophysiology of the emetic response is complex, with multiple organs and neurotransmitters involved. The emetic response can be described in three phases: nausea, vomiting, and retching. Nausea is the subjective feeling of the need to vomit. It includes an unpleasant sensation in the mouth and stomach and can be associated with salivation, sweating, dizziness, and tachycardia. Vomiting is the forceful expulsion of the stomach contents through the mouth, but is preceded by the relaxation of the esophageal sphincter, contraction of the abdominal muscles, and temporary suspension of breathing. Retching is the rhythmic contraction of the abdominal muscles without actual emesis. It can accompany nausea, or occur before or after emesis.
Nausea and vomiting are caused by many disorders. Central nervous system (CNS) causes include increased intracranial pressure, migraine, brain metastases, vestibular dysfunction, alcohol intoxication, and anxiety. Infectious disease causes include viral gastroenteritis, food poisoning, peritonitis, meningitis, and urinary tract infections. Metabolic causes include hypercalcemia, uremia, hyperglycemia, and hyponatremia. Gastrointestinal disorders, such as gastroparesis, bowel obstruction, distention, and mechanical irritation, can cause nausea and vomiting. Among the many medications that can cause nausea and vomiting are cancer chemotherapy, antibiotics, antifungals, and opiate analgesics.
The CNS, the peripheral nervous system, and the gastrointestinal (GI) tract are all involved in initiating and coordinating the emetic response. In the CNS, the vomiting center (VC) receives incoming signals from other parts of the brain and the GI tract and then coordinates the emetic response by sending signals to the effector organs. The VC is located in the medulla oblongata of the brain, near the nucleus tractus solitarius (NTS). The VC is stimulated by neurotransmitters released from the chemoreceptor trigger zone (CTZ), the GI tract, the cerebral cortex, the limbic system, and the vestibular system (Fig. 7-1). The major neurotransmitter receptors associated with the emetic response include serotonin (the 5-hydroxytryptamine type 3) receptors, neurokinin-1 receptors, and dopamine receptors. Other receptors involved include corticosteroid, acetylcholine, histamine, cannabinoid, gabaminergic, and opiate receptors. Many of these receptors are targets for antiemetic therapy.
In the CNS, the CTZ is located in the area postrema on the floor of the fourth ventricle in the brainstem; it lies outside the blood–brain barrier. When the CTZ senses toxins and noxious substances in the blood and cerebrospinal fluid, it triggers the emetic response by releasing neurotransmitters that travel to the VC and the NTS. The major neurotransmitter receptors involved in this pathway include serotonin, dopamine, and neurokinin-1.
The GI system also plays a large part in the initiation of the emetic response. The GI tract contains enterochromaffin cells in the GI mucosa. When these cells are damaged by chemotherapy, radiation, or mechanical irritation, serotonin is released, which can stimulate the vagal afferents as well as directly stimulate the VC and NTS. The vomiting center then propagates the emetic response.
The cerebral cortex and limbic system can stimulate the emetic center in response to emotional states such as anxiety, pain, and conditioned responses (anticipatory nausea and vomiting). The neurotransmitters involved in this pathway are less well understood. Disorders of the vestibular system, such as vertigo and motion sickness, stimulate the VC through acetylcholine and histamine release.
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