What are the pathophysiological mechanisms and different pathways involved in the evaluation of nausea and vomiting?

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From the Guidelines

Nausea and vomiting are complex processes involving multiple pathways and neurotransmitters, including serotonin, dopamine, acetylcholine, and histamine, which stimulate the vomiting center in the brain, leading to the emetic response.

Pathophysiological Mechanisms

The chemoreceptor trigger zone, vomiting center, and gastrointestinal tract have many neurotransmitter receptors that can be activated by chemotherapeutic agents or their metabolites, leading to chemotherapy-induced emesis 1.

Different Pathways Involved

The emetic response involves a multistep reflex pathway controlled by the brain, triggered by afferent impulses to the vomiting center from the:

  • Chemoreceptor trigger zone
  • Pharynx and gastrointestinal tract (by way of vagal afferent fibers)
  • Cerebral cortex 1

Evaluation of Nausea and Vomiting

Evaluation of nausea and vomiting should consider various causes, including:

  • Gastric outlet obstruction
  • Bowel obstruction
  • Constipation
  • Opioid use
  • Hypercalcemia 1
  • Chemotherapy and radiation therapy 1 Treatment options may include:
  • Proton pump inhibitors and histamine-2 (H2) receptor antagonists for gastritis or gastroesophageal reflux
  • Corticosteroids for gastric outlet obstruction
  • Dopamine receptor antagonists (e.g., prochlorperazine, haloperidol, metoclopramide, olanzapine) or benzodiazepines for nonspecific nausea and vomiting
  • 5-HT3 receptor antagonists and/or anticholinergic agents and/or antihistamines for persistent nausea and vomiting 1

From the Research

Pathophysiological Mechanisms

The pathophysiology of nausea and vomiting is complex and involves multiple mechanisms, including:

  • Defense mechanisms to remove toxins or irritants from the gastrointestinal tract 2, 3
  • Stimulation of emetic pathways through activation of various receptor subtypes 4, 3
  • Brain-gut interactions, gastrointestinal neurophysiologic, motor, sensory, and hormonal factors 5

Pathways Involved

Several pathways are involved in the evaluation of nausea and vomiting, including:

  • Vagal and non-vagal pathways 4
  • Brainstem nuclei, such as the nucleus tractus solitarii 6
  • Autonomic nervous system, including the vagus nerve and spinal cord neurons 4, 6
  • Central nervous system areas, including the anterior insular cortex, anterior cingulate cortex, and amygdala 6

Neurochemical Mechanisms

Neurochemical mechanisms play a crucial role in the pathophysiology of nausea and vomiting, including:

  • Neurotransmitters and mediators, such as serotonin and dopamine 2, 3
  • Corresponding receptors, such as 5-HT3 and D2 receptors 3
  • Intracellular emetic signaling pathways, including postreceptor signal transduction mechanisms 3

Current Understanding and Future Directions

While significant progress has been made in understanding the mechanisms of nausea and vomiting, there is still much to be discovered, particularly in the area of chronic nausea and vomiting 5, 6. Future research should focus on elucidating the complex interactions between various mechanisms and pathways, as well as developing effective treatments for nausea and vomiting 2, 3, 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Pathology of emesis: its autonomic basis.

Handbook of clinical neurology, 2013

Research

Chronic nausea and vomiting: insights into underlying mechanisms.

Neurogastroenterology and motility, 2016

Research

Revisiting the physiology of nausea and vomiting-challenging the paradigm.

Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, 2020

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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