What is the pathophysiology of vomiting?

Pathophysiology of Vomiting

Vomiting results from stimulation of a multistep reflex pathway controlled by the brain, triggered by afferent impulses to the vomiting center (located in the medulla) from the chemoreceptor trigger zone, pharynx, gastrointestinal tract (via vagal afferent fibers), and cerebral cortex. 1

Neural Pathways of the Vomiting Reflex

The vomiting process involves a complex coordination of neural pathways:

1. Afferent Pathways - Stimuli reach the vomiting center through:

   • Chemoreceptor trigger zone (CTZ) in the area postrema
   • Vagal afferents from the gastrointestinal tract
   • Vestibular system inputs
   • Higher cortical centers (emotions, sights, smells, pain)

2. Central Processing - Occurs primarily in:

   • Vomiting center in the medulla oblongata
   • Area postrema (CTZ) which lacks a complete blood-brain barrier
   • Nucleus tractus solitarius

3. Efferent Pathways - Vomiting occurs when efferent impulses are sent from the vomiting center to:

   • Salivation center
   • Abdominal muscles
   • Respiratory center
   • Cranial nerves controlling relevant muscles

Neurotransmitters and Receptors

The vomiting reflex involves multiple neurotransmitters and receptors:

• Principal neuroreceptors:

  • Serotonin (5-HT3) receptors - particularly important in chemotherapy-induced emesis 1
  • Dopamine receptors - significant in various forms of nausea and vomiting 1

• Other important receptors:

  • Neurokinin-1 (NK-1) receptors
  • Acetylcholine receptors
  • Histamine receptors
  • Cannabinoid receptors (CB1) - located in the brain and throughout the gut 1
  • Opiate receptors
  • Corticosteroid receptors

Physiological Sequence of Vomiting

The act of vomiting follows a specific physiological sequence:

1. Pre-ejection phase:

   • Salivation increases
   • Tachycardia may develop
   • Cutaneous vasoconstriction occurs
   • Relaxation of the gastric fundus

2. Retching phase:

   • Synchronous contractions of diaphragm and abdominal muscles against a closed glottis
   • Intrathoracic pressure increases
   • Intragastric pressure increases

3. Ejection phase:

   • Relaxation of the lower esophageal sphincter
   • Powerful contraction of abdominal muscles
   • Descent of the diaphragm
   • Forceful expulsion of gastric contents

Common Triggers of the Vomiting Reflex

Various stimuli can trigger the vomiting reflex through different pathways:

• Chemotherapy and radiation - primarily via 5-HT3 receptors when these treatments cause release of serotonin from enterochromaffin cells in the GI tract 1
• Motion sickness - via vestibular inputs
• Toxins and medications - via CTZ stimulation
• Gastrointestinal disorders - via vagal afferents
• Increased intracranial pressure - direct pressure on vomiting center
• Psychological factors - via cortical inputs

Clinical Implications

Understanding the pathophysiology of vomiting is crucial for effective antiemetic therapy:

• Antiemetic medications target specific receptors in the vomiting pathway:

  • 5-HT3 antagonists (ondansetron) block serotonin receptors 2
  • Dopamine antagonists (metoclopramide) block dopamine receptors and also stimulate upper GI motility 3
  • NK-1 receptor antagonists block substance P effects
  • Antihistamines block H1 receptors
  • Anticholinergics block muscarinic receptors

• Combination therapy targeting multiple receptors is often more effective than monotherapy for complex causes of vomiting, particularly in chemotherapy-induced nausea and vomiting 1

Special Considerations

• Cannabinoid hyperemesis syndrome represents a paradoxical effect where chronic cannabis use leads to cyclic vomiting episodes, possibly due to dysregulation of the endocannabinoid system and CB1 receptors 1

• Anticipatory nausea and vomiting involves learned responses and psychological conditioning, highlighting the importance of cortical inputs in the vomiting reflex 1

Understanding this complex pathophysiology allows for targeted antiemetic therapy based on the specific mechanisms involved in different clinical scenarios.