Physiology of Vomiting
Vomiting is a coordinated reflex controlled by the medullary vomiting center, which receives afferent signals from four primary sources—the chemoreceptor trigger zone, gastrointestinal tract via vagal fibers, pharynx, and cerebral cortex—and then transmits efferent impulses to execute the forceful expulsion of gastric contents through activation of respiratory muscles, abdominal muscles, salivation center, and cranial nerves. 1
Neural Control Architecture
The Vomiting Center and Afferent Pathways
The vomiting center is located in the medulla and serves as the central coordinator of the emetic reflex 1. This center receives input through four distinct afferent pathways:
Chemoreceptor trigger zone (CTZ): Located in the area postrema, this structure detects circulating toxins, drugs, metabolites, and chemotherapeutic agents in the blood 2. The CTZ lies outside the blood-brain barrier, allowing it to monitor blood-borne emetic stimuli 1.
Gastrointestinal tract: Vagal afferent fibers transmit signals from the GI tract in response to mucosal irritation, distension, inflammation, or enterochromaffin cell activation 1, 2. Cytotoxic chemotherapy triggers serotonin release from enterochromaffin cells in the small intestine, which stimulates vagal afferents through 5-HT3 receptors 3.
Pharynx: Direct pharyngeal stimulation can trigger the vomiting reflex 1.
Cerebral cortex: Higher brain centers mediate psychogenic vomiting, anticipatory nausea and vomiting, and the subjective sensation of nausea 1, 2. The cortex is essential for the conscious perception of nausea, which is thought to be a more complex phenomenon than vomiting itself 4.
Anatomical Localization
The emetic circuitry extends from the nucleus of the solitary tract through the lateral tegmental field of the reticular formation to the ventrolateral medulla, spanning the region between the obex and retrofacial nucleus 4. The area postrema and medullary midline structures are also critical components 4.
Neurotransmitter Systems
Primary Receptor Systems
Multiple neurotransmitter receptors mediate the emetic response, with the principal systems being:
Serotonin (5-HT3) receptors: Present both peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zone 3. These receptors are activated when chemotherapy causes enterochromaffin cells to release serotonin, initiating the vomiting reflex 3.
Dopamine receptors: Dopamine stimulates nausea and vomiting by activating the medullary chemoreceptor trigger zone 1, 5. Dopamine antagonists like metoclopramide block this stimulation 5.
Secondary receptor systems: Include acetylcholine, corticosteroid, histamine, cannabinoid, opiate, and neurokinin-1 (NK-1) receptors located in the vomiting and vestibular centers 1, 2.
Receptor Distribution
The chemoreceptor trigger zone, vomiting center, and gastrointestinal tract contain high concentrations of these neurotransmitter receptors 1. Activation of these receptors by chemotherapeutic agents or their metabolites is responsible for chemotherapy-induced emesis 1.
Efferent Motor Response
Execution of Vomiting
Once the vomiting center is activated, it sends efferent impulses to multiple target organs to coordinate the act of vomiting 1:
Salivation center: Produces increased saliva production (ptyalism), often the first clinical sign preceding vomiting 2, 6.
Abdominal muscles: Generate forceful contractions that create the pressure needed to expel gastric contents 1, 2.
Respiratory center: Coordinates respiratory muscle activity, including closure of the glottis to protect the airway 1, 2.
Cranial nerves: Execute pharyngeal and esophageal motor responses necessary for expulsion 1.
Gastrointestinal Motor Changes
The vomiting reflex involves coordinated changes in GI motility 1, 5:
Gastric changes: Increased tone and amplitude of gastric (especially antral) contractions occur 5.
Pyloric relaxation: The pyloric sphincter and duodenal bulb relax 5.
Retrograde peristalsis: Duodenal and jejunal peristalsis may reverse direction 5.
Lower esophageal sphincter: Relaxes to allow passage of gastric contents 1.
Nausea Versus Vomiting
Distinct but Related Phenomena
Nausea and vomiting are related but distinct processes that may occur via different mechanisms, with nausea being a subjective sensation involving the cerebral cortex that is considerably more difficult to control than vomiting itself. 2
Nausea is a conscious perception requiring cortical involvement, making it harder to study in animal models and more resistant to treatment 2, 4.
Patients receiving effective antiemetic regimens often experience more nausea than vomiting, particularly younger patients and women 2.
Vomiting can be prevented in approximately 70% of patients receiving highly emetogenic chemotherapy with prophylactic antiemetics, but nausea remains much harder to control 1.
Clinical Implications
Protective Function
Vomiting serves as a defense mechanism when threatening toxins, drugs, bacteria, viruses, or fungi enter the body through enteral or parenteral routes 7. The reflex provides forceful removal of potentially harmful substances from the gastrointestinal tract 6, 8.
Distinction from Related Phenomena
Vomiting must be distinguished from regurgitation (passive return of gastric contents without forceful expulsion) and rumination (voluntary regurgitation, mastication, and reswallowing of recently ingested food) 1. These distinctions are important for accurate diagnosis and appropriate management 1.