Nausea, Vomiting, and Indigestion¶
Chapter 48 | Part 2: Cardinal Manifestations and Presentation of Diseases
KEY CLINICAL POINTS¶
- Nausea and vomiting are caused by intracranial, gastrointestinal, metabolic, and medication-related factors.
- GERD is the most common cause of chronic heartburn and regurgitation, with 18–28% of the population experiencing weekly symptoms.
- Functional dyspepsia affects 7.2% of the population and is characterized by postprandial fullness, early satiety, or epigastric pain without organic disease.
- Eosinophilic esophagitis is an increasingly recognized cause of dysphagia requiring dietary allergen elimination and proton pump inhibitors.
- PPIs are first-line therapy for GERD and functional dyspepsia, with long-term use associated with risks like nutrient deficiencies and Clostridioides difficile infection.
1. DEFINITION & OVERVIEW¶
Nausea is the feeling of needing to vomit; vomiting is the forceful expulsion of gastric contents. Indigestion encompasses symptoms like nausea, vomiting, heartburn, and dyspepsia. Dysphagia refers to difficulty swallowing, which may involve oral, pharyngeal, or esophageal dysfunction.
Table 48-1 Causes of Nausea and Vomiting¶
| INTRAPERITONEAL | EXTRAPERITONEAL | MEDICATIONS/METABOLIC DISORDERS |
|---|---|---|
| Pyloric obstruction | Cardiomyopathy | Cancer chemotherapy |
| Small-bowel obstruction | Myocardial infarction | Opioids |
| Colonic obstruction | Labyrinthine disease | Analgesics |
| Superior mesenteric artery syndrome | Motion sickness | Glucagon-like peptide-1 (GLP-1) receptor agonists |
| Enteric infections | Labyrinthitis | Oral hypoglycemics |
| Inflammatory diseases | Malignancy | Parkinson’s disease/restless legs therapies |
| Gastroparesis | Psychiatric illness | Antidepressants |
| Intestinal pseudoobstruction | Anorexia and bulimia nervosa | Smoking cessation agents |
| Gastroesophageal reflux | Depression | Antibiotics |
| Chronic nausea vomiting syndrome | Postoperative vomiting | Cardiac antiarrhythmics/antihypertensives |
| Gastroparesis-like symptoms | Pregnancy | Oral contraceptives |
| INTRAPERITONEAL | EXTRAPERITONEAL | MEDICATIONS/METABOLIC DISORDERS |
|---|---|---|
| Cyclic vomiting syndrome | Uremia | Endocrine/metabolic disease |
| Cannabinoid hyperemesis syndrome | Ketoacidosis | Toxins |
| Rumination syndrome | Thyroid and parathyroid disease | Liver failure |
| Mesenteric insufficiency | Adrenal insufficiency | Ethanol |
1.1 Neurotransmitter Pathways¶
Vomiting is coordinated by the brainstem and involves pathways including 5-HT3, NK1, dopamine D2, and muscarinic receptors. The area postrema acts as a chemoreceptor trigger zone for bloodborne toxins.
1.2 Mechanisms of Vomiting¶
Vomiting is triggered by central (CNS), peripheral (gastrointestinal), and chemoreceptor pathways. Neurotransmitters like 5-HT3, NK1, and dopamine mediate vomiting, while anticholinergics and dopamine antagonists are key therapeutic targets.
2. EPIDEMIOLOGY¶
Nausea alone occurs in 1.9% of the population weekly, with nausea plus vomiting in 1.1%. GERD affects 18–28% with weekly symptoms. Functional dyspepsia has a prevalence of 7.2%. Cyclic vomiting syndrome (CVS) occurs in 1.4% of the population.
2.1 Risk Factors¶
Risk factors include obesity, NSAID use, H. pylori infection, pregnancy, and metabolic disorders like diabetes. Smoking, caffeine, and alcohol exacerbate GERD.
2.2 Demographics¶
GERD and functional dyspepsia are more common in adults, with increased prevalence in older age. CVS and CHS are more prevalent in adolescents and young adults.
3. ETIOLOGY & PATHOPHYSIOLOGY¶
Nausea/vomiting arise from CNS, gastrointestinal, metabolic, or medication-induced causes. GERD results from LES dysfunction and acid reflux. Functional dyspepsia involves altered motility, hypersensitivity, or microbiome dysbiosis.
3.1 Neurotransmitter Pathways¶
Vomiting is mediated by 5-HT3, NK1, dopamine D2, and muscarinic receptors. The area postrema responds to bloodborne toxins, while the vestibular system mediates motion sickness.
3.2 Mechanisms of GERD¶
Reduced LES tone, transient LES relaxations (TLESRs), and delayed gastric emptying contribute to reflux. Hiatal hernias and obesity exacerbate symptoms.
4. CLINICAL FEATURES¶
Symptoms include heartburn, regurgitation, epigastric pain, bloating, and early satiety. Alarm features (Table 48-3) indicate serious pathology like malignancy or ischemia.
Table 48-3 Alarm Symptoms in Gastroesophageal Reflux Disease¶
| Symptoms |
|---|
| Odynophagia or dysphagia |
| Unexplained weight loss |
| Recurrent vomiting |
| Occult or gross gastrointestinal bleeding |
| Jaundice |
| Palpable mass or adenopathy |
| Family history of gastroesophageal malignancy |
4.1 GERD Presentation¶
Heartburn (substernal warmth), regurgitation, and water brash. Atypical symptoms include asthma, cough, and chest pain.
4.2 Functional Dyspepsia¶
Postprandial fullness, early satiety, or epigastric pain without organic cause. Subtypes include postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS).
5. DIFFERENTIAL DIAGNOSIS¶
Differential diagnoses include GERD, functional dyspepsia, peptic ulcer disease, esophageal strictures, cyclic vomiting syndrome (CVS), cannabinoid hyperemesis syndrome (CHS), and malignancy.
5.1 Esophageal Disorders¶
Esophageal strictures, achalasia, Zenker’s diverticulum, and eosinophilic esophagitis. Symptoms include dysphagia, odynophagia, and regurgitation.
5.2 Gastrointestinal Obstruction¶
Small-bowel or colonic obstruction, intestinal pseudoobstruction, and mesenteric ischemia present with vomiting, abdominal pain, and distension.
6. INVESTIGATIONS & DIAGNOSIS¶
Diagnostic tests include upper endoscopy, esophageal pH/impedance monitoring, gastric emptying studies, and imaging. Endoscopy is critical for ruling out malignancy or structural causes.
6.1 Diagnostic Algorithms¶
For uninvestigated dyspepsia: Test for H. pylori (urea breath/fecal antigen). Endoscopy is indicated for patients >60 years, with alarm symptoms, or refractory to PPI therapy.
6.2 Imaging and Functional Tests¶
CT/MRI for bowel obstruction, esophageal manometry for motility disorders, and FLIP (functional lumen imaging probe) for esophagogastric junction dysfunction.
7. MANAGEMENT & TREATMENT¶
Treatment includes lifestyle modifications, acid suppression, prokinetics, and targeted therapies. PPIs are first-line for GERD, while H2 blockers are used for mild cases.
Table 48-2 Treatment of Nausea and Vomiting¶
| TREATMENT | MECHANISM | CLINICAL INDICATIONS |
|---|---|---|
| Antiemetic agents | Antihistaminergic | Motion sickness, inner ear disease |
| Antiemetic agents | Anticholinergic | Motion sickness, inner ear disease |
| Antiemetic agents | Antidopaminergic | Medication-, toxin-, or metabolic-induced emesis |
| Antiemetic agents | 5-HT antagonist | Chemotherapy- and radiation-induced emesis |
| Antiemetic agents | Cannabinoids | Chemotherapy-induced emesis, gastroparesis |
| Antiemetic agents | Tricyclic antidepressant | Chronic nausea vomiting syndrome |
| Antiemetic agents | Other antidepressant/atypical antipsychotic | Functional dyspepsia |
| Antiemetic agents | Neuropathic modulator | Chemotherapy-induced emesis |
| Antiemetic agents | Neurokinin (NK) receptor antagonists | Chemotherapy-induced emesis |
| Antiemetic agents | 5-HT agonist and antidopaminergic | Gastroparesis |
| Antiemetic agents | Motilin agonist | Gastroparesis |
| Antiemetic agents | Peripheral antidopaminergic | Gastroparesis |
| Antiemetic agents | Pure 5-HT agonist | Idiopathic gastroparesis |
| Antiemetic agents | Somatostatin analogue | Intestinal pseudoobstruction |
| Antiemetic agents | Acetylcholinesterase inhibitor | Small-intestinal dysmotility/pseudoobstruction |
| Special settings | Benzodiazepines | Anticipatory nausea and vomiting with chemotherapy |
| Special settings | 5-HT agonist | Functional dyspepsia |
| Special settings | Glucocorticoids | Chemotherapy-induced emesis |
| Special settings | Anticonvulsants | Cyclic vomiting syndrome |
| Special settings | Antimigraine agents | Cyclic vomiting syndrome |
| Special settings | Topical analgesic | Cannabinoid hyperemesis syndrome |
7.1 Pharmacologic Therapy¶
PPIs (omeprazole, esomeprazole) for GERD; prokinetics (metoclopramide, domperidone) for gastroparesis; and antiemetics (ondansetron, aprepitant) for chemotherapy-induced vomiting.
7.2 Nonpharmacologic Interventions¶
Dietary modifications (low-fat meals, avoidance of caffeine/alcohol), weight management, and elevating the head of the bed for GERD.
8. PROGNOSIS & COMPLICATIONS¶
GERD may progress to Barrett’s esophagus and esophageal adenocarcinoma. Prolonged vomiting can lead to dehydration, electrolyte imbalances, and aspiration pneumonia. Gastroparesis may result in malnutrition and weight loss.
8.1 Complications of GERD¶
Barrett’s esophagus (10–15% of GERD patients), esophageal strictures, and aspiration pneumonia. Long-term PPI use increases risk of nutrient deficiencies.
8.2 Gastroparesis Outcomes¶
Chronic nausea, weight loss, and malnutrition. Surgical options like gastric electrical stimulation may improve symptoms in refractory cases.
9. SPECIAL CONSIDERATIONS¶
Pregnancy-related nausea (hyperemesis gravidarum) requires hydration and thiamine. Elderly patients are at higher risk for aspiration and drug interactions. Cyclic vomiting syndrome (CVS) may require prophylactic anticonvulsants.
9.1 Pregnancy¶
Nausea of pregnancy is common; hyperemesis gravidarum may require intravenous fluids and corticosteroids. Avoid NSAIDs and antihistamines in early pregnancy.
9.2 Elderly Patients¶
Increased risk of aspiration and drug interactions. Use caution with prokinetics (e.g., metoclopramide) due to risk of extrapyramidal symptoms.
10. KEY POINTS & CLINICAL PEARLS¶
- PPIs are first-line for GERD and functional dyspepsia. 2. Rule out malignancy in patients >60 years or with alarm symptoms. 3. Avoid NSAIDs and anticholinergics in patients with gastroparesis. 4. Use gastric emptying tests for suspected intestinal pseudoobstruction. 5. Monitor for complications of long-term PPI use (e.g., vitamin deficiencies).