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Nausea & Vomiting - Harrison's Principles of Internal Medicine (22nd Ed, 2025)

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DEFINITIONS

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MECHANISMS

Brainstem Coordination of Vomiting

• Coordinated by brainstem nuclei:
  • Nucleus tractus solitarius
  • Dorsal vagal and phrenic nuclei
  • Medullary respiratory nuclei
  • Nuclei controlling pharyngeal, facial, and tongue movements
• Neurotransmitters involved: NK1, 5-HT1, endocannabinoids, vasopressin

Nausea - Cortical Component

• Requires cognitive and emotional input
• Involves: insula, anterior cingulate cortex, amygdala (on functional brain imaging)
• Associated with autonomic responses: diaphoresis, pallor, altered heart rate

Somatic/Visceral Muscle Response During Emesis

• Inspiratory thoracic and abdominal wall muscles contract
• Raises intrathoracic and intraabdominal pressures
• Propulsive gastroduodenal motility replaced by retrograde contractions

Sites of Emetic Stimuli

Neurotransmitter-Receptor Specificity (Key for Drug Targets)

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DIFFERENTIAL DIAGNOSIS

Intraperitoneal Causes

• Obstruction: Ulcers/malignancy (gastric outlet), adhesions, volvulus, intussusception, Crohn's disease
• Enteric infections: Bacterial, viral gastroenteritis
• Inflammatory: Cholecystitis, pancreatitis, appendicitis, hepatitis
• Motility disorders: Gastroparesis, intestinal pseudo-obstruction, functional dyspepsia

Extraperitoneal Causes

• CNS: Migraine, increased intracranial pressure, CNS tumors, meningitis, seizures
• Labyrinthine: Vestibular neuritis, Meniere's disease, motion sickness
• Cardiac: Inferior MI (vagal response)
• Metabolic/Endocrine: Pregnancy, uremia, diabetic ketoacidosis, Addison's disease, hyperthyroidism, hypercalcemia, hyponatremia

Medications and Toxins

• Opioids, NSAIDs, antibiotics, chemotherapy (especially cisplatin)
• Digoxin, colchicine
• Radiation therapy
• Alcohol, tobacco

Functional Causes

• Cyclic vomiting syndrome (CVS)
• Cannabinoid hyperemesis syndrome (CHS)
• Functional nausea/vomiting (part of DGBI spectrum)

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CLINICAL APPROACH / HISTORY

• Acute onset (<1 week): infection, drug, obstruction, MI
• Chronic/recurrent: gastroparesis, functional, CNS, metabolic

• Immediately postprandial: psychogenic, gastric outlet obstruction
• 1-4 hours after meals: gastroparesis, gastric obstruction
• Vomiting undigested food hours after eating: gastroparesis or pyloric obstruction

• Bilious: distal to pylorus (rules out pyloric obstruction)
• Feculent: small bowel obstruction or gastrocolic fistula
• Blood: Mallory-Weiss tear, peptic ulcer, malignancy

• Abdominal pain, fever, jaundice, weight loss
• Vertigo/tinnitus (labyrinthine cause)
• Headache/visual changes (CNS cause)
• Amenorrhea (pregnancy)

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INVESTIGATIONS

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TREATMENT OF NAUSEA AND VOMITING

General Measures

• Correct fluid and electrolyte deficits (IV fluids if needed)
• NPO or clear liquids initially; advance diet as tolerated
• Identify and remove the offending cause

Antiemetic Drug Classes

Chemotherapy-Induced Nausea and Vomiting (CINV)

• Acute CINV (0-24h): 5-HT3 antagonist + NK1 antagonist + dexamethasone
• Delayed CINV (>24h): NK1 antagonist (aprepitant) + dexamethasone ± metoclopramide
• Highly emetogenic regimens (e.g., cisplatin): triple therapy (5-HT3 + NK1 + dex) + olanzapine (quadruple therapy)
• Anticipatory CINV: Lorazepam; best prevented by good control in prior cycles

Gastroparesis

• Dietary modification: small, frequent, low-fat, low-fiber meals; avoid carbonated drinks
• Prokinetics: Metoclopramide (first-line, but risk of tardive dyskinesia with long-term use), domperidone, erythromycin (motilin agonist)
• Refractory: gastric electrical stimulation (Enterra device)

Cyclic Vomiting Syndrome (CVS)

• Prophylaxis: tricyclic antidepressants (amitriptyline), topiramate, cyproheptadine (children)
• Acute attack: sumatriptan, ondansetron, benzodiazepines, IV fluids

Cannabinoid Hyperemesis Syndrome (CHS)

• Classic triad: chronic cannabis use, cyclic vomiting, compulsive hot bathing
• Treatment: cessation of cannabis; topical capsaicin to abdomen (depletes substance P); haloperidol in acute setting

Motion Sickness

• Scopolamine patch (most effective, applied behind ear 4h prior)
• Antihistamines: meclizine, dimenhydrinate
• Avoid reading; focus on horizon

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KEY TABLES FROM HARRISON

1. Intraperitoneal - obstructive, inflammatory, motility, functional
2. Extraperitoneal - CNS, cardiac, metabolic/endocrine
3. Medications and toxins
4. Postoperative
5. Pregnancy-related

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IMPORTANT HIGH-YIELD POINTS

1. Area postrema = CTZ - responds to bloodborne emetogenic stimuli; outside blood-brain barrier; targeted by D2 blockers and 5-HT3 antagonists
2. NK1 receptors mediate both nausea AND vomiting centrally - NK1 antagonists (aprepitant) are critical for delayed CINV
3. 5-HT3 receptors on vagal afferents are the primary trigger for chemotherapy/radiation N&V
4. Metoclopramide crosses BBB - risk of tardive dyskinesia; domperidone does not cross BBB
5. Gastroparesis gold standard = 4-hour gastric emptying scintigraphy (solid meal, 10% retained at 4h = diagnostic)
6. Vomiting vs. regurgitation vs. rumination: Only vomiting is truly involuntary; regurgitation and rumination have volitional control
7. Feculent vomitus = distal bowel obstruction or gastrocolic fistula
8. Morning vomiting with no nausea preceding it = classic CNS (increased ICP) - projectile, effortless
9. CHS: Hot compulsive bathing is pathognomonic; topical capsaicin works acutely

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