What causes nausea?

Common Causes of Nausea

Nausea is caused by a diverse range of pathophysiological processes involving both gastrointestinal and non-gastrointestinal mechanisms, with the most common causes being gastrointestinal disorders, medication side effects, metabolic disturbances, and central nervous system pathology.

Major Categories of Nausea Causes

Gastrointestinal Causes

• Gastroparesis: Delayed gastric emptying affects 20-40% of diabetes patients and 25-40% of functional dyspepsia patients 1
• Gastroesophageal reflux disease (GERD): Treated with proton pump inhibitors or H2 receptor antagonists 1
• Gastric outlet obstruction: May benefit from corticosteroids or endoscopic interventions 1
• Bowel obstruction: Requires prompt evaluation and treatment 1
• Constipation: Occurs in approximately 50% of patients with advanced cancer 1
• Functional dyspepsia: Affects approximately 20% of the general population 1

Medication-Related Causes

• Chemotherapy: 70-80% of cancer patients on chemotherapy experience nausea/vomiting 1
• Opioids: Common cause of nausea, especially when initiating therapy 1
• Other medications: Antibiotics, antifungals, antidepressants, phenothiazines, haloperidol 1

Metabolic/Endocrine Causes

• Hypercalcemia: Can cause nausea and requires specific treatment 1
• Electrolyte disturbances: Particularly hypokalemia 1
• Hyperglycemia: Can cause antral hypomotility and delayed gastric emptying 1
• Pregnancy: Common cause of nausea, especially in early stages 2

Neurological Causes

• Brain metastases: Particularly important to consider in cancer patients 1
• Increased intracranial pressure: Can trigger the chemoreceptor trigger zone (CTZ) 3
• Vestibular disorders: Motion sickness and other vestibular disturbances 2, 4
• Migraines: Acute migraine headaches commonly present with nausea 2

Other Causes

• Psychological factors: Anxiety can lower the threshold for nausea perception 4
• Radiation therapy: Particularly when directed at abdominal or brain regions 1
• Infections: Viral gastroenteritis and other infectious syndromes 2
• Cyclic vomiting syndrome: Characterized by episodic vomiting with symptom-free intervals 1

Pathophysiological Mechanisms

Nausea involves multiple neurotransmitter pathways and receptors:

1. Dopamine receptors: Stimulation of the medullary chemoreceptor trigger zone (CTZ) by dopamine can produce nausea 3
2. Serotonin (5-HT3) receptors: Important in chemotherapy-induced and other forms of nausea 1
3. Neurokinin-1 receptors: Play a role in the emetic response 1
4. Autonomic nervous system changes: Nausea is accompanied by increased sympathetic and decreased parasympathetic activity 4

Evaluation Approach

When evaluating nausea, consider:

• Duration: Acute (≤7 days) vs. chronic (≥4 weeks) 2, 5
• Associated symptoms: Vomiting, pain, headache, neurological symptoms
• Timing: Relationship to meals, time of day, cyclical patterns
• Triggers: Foods, medications, positional changes
• Alarm symptoms: Dehydration, weight loss, hematemesis, focal neurological signs

Treatment Considerations

Treatment should target the underlying cause when possible:

• Gastroparesis: Prokinetic agents like metoclopramide which increases gastric motility 3
• Chemotherapy-induced: Combination of 5-HT3 antagonists, corticosteroids, and neurokinin-1 antagonists based on emetogenic potential 1
• Nonspecific nausea: Dopamine receptor antagonists (prochlorperazine, haloperidol, metoclopramide) 1
• Anxiety-related: Benzodiazepines may be helpful 1
• Persistent nausea: Consider adding 5-HT3 antagonists, anticholinergic agents, antihistamines, or corticosteroids 1

Clinical Pearls and Pitfalls

• Always consider medication side effects as a potential cause of nausea
• Nausea without vomiting may indicate a different pathophysiology than nausea with vomiting
• Chronic nausea is often more difficult to treat than acute nausea 2
• Individual thresholds for nausea vary based on inherent factors (age, gender, race) and psychological factors (anxiety, expectation) 4
• For cancer patients, multiple causes of nausea may coexist, requiring a comprehensive approach 1

Understanding the diverse causes of nausea is essential for appropriate evaluation and targeted treatment to improve patient quality of life and reduce morbidity.