What is the pathophysiology of nausea and vomiting?

Pathophysiology of Nausea and Vomiting

Nausea and vomiting result from a complex multistep reflex pathway controlled by the brain, involving multiple neurotransmitters and receptors across various anatomical structures. 1

Anatomical Structures Involved

• Vomiting Center: Located in the medulla, this is the central coordinator of the emetic response 1
• Chemoreceptor Trigger Zone (CTZ): Located in the area postrema of the fourth ventricle, outside the blood-brain barrier 1
• Gastrointestinal Tract: Sends afferent signals via vagal fibers 1
• Cerebral Cortex: Involved in anticipatory and psychogenic nausea/vomiting 1
• Vestibular System: Mediates motion-induced nausea/vomiting 1

Neural Pathways

1. Afferent Pathways:

   • Vagal afferent fibers from the GI tract to the vomiting center 1
   • Direct stimulation of the CTZ by blood-borne substances 1
   • Vestibular input through cranial nerve VIII 1
   • Cortical inputs from higher brain centers 1, 2

2. Efferent Pathways:

   • Signals from the vomiting center to:
     • Salivation center
     • Respiratory center
     • Abdominal muscles
     • Cranial nerves controlling the pharynx, larynx, and GI tract 1

Key Neurotransmitters and Receptors

• Serotonin (5-HT3) Receptors: Principal mediators, especially in chemotherapy-induced nausea and vomiting 1
• Dopamine Receptors: Important in the CTZ, targeted by many antiemetics 1, 3
• Neurokinin-1 (NK-1) Receptors: Mediate substance P effects, particularly important in delayed emesis 1
• Acetylcholine Receptors: Involved in vestibular-mediated nausea/vomiting 1
• Histamine Receptors: Contribute to motion sickness 1
• Cannabinoid Receptors: Modulate emetic response 1
• Opiate Receptors: Can both induce and inhibit nausea/vomiting 1

Physiological Sequence of Vomiting

1. Pre-ejection Phase:

   • Salivation increases
   • Pallor develops due to vasomotor changes
   • Tachycardia may occur
   • Relaxation of the gastric fundus

2. Retching Phase:

   • Rhythmic contractions of respiratory muscles against a closed glottis
   • Reverse peristalsis in the proximal small intestine
   • Relaxation of the lower esophageal sphincter

3. Ejection Phase:

   • Coordinated contraction of abdominal muscles
   • Elevation of the diaphragm
   • Opening of the upper esophageal sphincter
   • Expulsion of gastric contents 1, 4

Common Triggers and Mechanisms

• Chemotherapy: Direct stimulation of the CTZ and release of serotonin from enterochromaffin cells in the GI tract 1
• Gastrointestinal Disorders: Distension, inflammation, or obstruction activating vagal afferents 1, 5
• Medications: Direct stimulation of the CTZ or irritation of the GI tract 5
• Motion Sickness: Conflicting sensory inputs between vestibular system and visual cues 1
• Pregnancy: Hormonal changes affecting the CTZ and GI motility 5
• Psychological Factors: Cortical activation of the vomiting center 1, 5

Clinical Implications

• Understanding the multiple pathways involved explains why combination antiemetic therapy targeting different receptors is often more effective than monotherapy 1, 5
• The distinction between acute, delayed, and anticipatory nausea/vomiting reflects different underlying mechanisms and neurotransmitter involvement 1
• Gastroparesis can cause chronic nausea/vomiting through abnormal gastric emptying and vagal dysfunction 1
• The complexity of the pathophysiology explains why some forms of nausea (especially chronic nausea) are more difficult to treat than vomiting 1, 6

Diagnostic Considerations

When evaluating patients with nausea and vomiting, consider potential causes based on the underlying pathophysiology:

• Mechanical obstruction
• Vestibular dysfunction
• Brain metastases or increased intracranial pressure
• Electrolyte imbalances
• Uremia
• Medication effects
• Gastroparesis
• Psychophysiologic factors 1, 5

Understanding the complex pathophysiology of nausea and vomiting is essential for selecting appropriate antiemetic therapy that targets the specific receptors and pathways involved in individual clinical scenarios.