Causes of Dyspepsia
Primary Etiologic Categories
Functional dyspepsia accounts for approximately 80% of all dyspepsia cases in the community, making it by far the most common cause. 1 The remaining 20% have identifiable organic pathology that includes peptic ulcer disease (8%), erosive esophagitis (13%), and gastroesophageal cancer (<0.5%). 1
Organic Causes
The most common structural causes of dyspepsia include:
- Peptic ulcer disease - responsible for approximately 8-10% of cases, primarily caused by Helicobacter pylori infection or NSAID use 1
- Gastroesophageal reflux disease (GERD) - accounts for approximately 20% of cases, though significant symptom overlap exists with functional dyspepsia 1
- Erosive esophagitis - found in approximately 13% of patients undergoing endoscopy for dyspepsia 1
- Gastric or esophageal malignancy - rare (<0.5%) but critical to exclude in high-risk patients 1
- Biliary tract disease - a less common but important organic cause 2
- Medication-induced - particularly NSAIDs, which directly damage gastroduodenal mucosa 1
Less common organic causes include pancreatic disease, malabsorption syndromes, metabolic disorders, and ischemic heart disease. 2
Functional Dyspepsia
Functional dyspepsia is caused by disorders of gut-brain interaction, not psychological factors alone. 1 The underlying pathophysiologic mechanisms include:
- Visceral hypersensitivity - abnormal nerve signaling makes the stomach and duodenum more sensitive to normal digestive processes 1, 3
- Delayed gastric emptying - contributes to feelings of early fullness and postprandial distress 1, 3
- Impaired gastric accommodation - the stomach fails to relax properly after meals 3
- Altered duodenal sensitivity - to lipids or acids 3
- Gastric dysrhythmias - abnormal electrical activity in the stomach 3
- Autonomic nervous system dysregulation - disrupted communication between the gut and central nervous system 3
Contributing and Risk Factors
Risk factors that increase the likelihood of dyspepsia include:
- Female sex - consistently associated with higher prevalence 1
- Smoking - modest but consistent association 1
- NSAID use - both a risk factor and direct cause 1
- H. pylori infection - causes peptic ulcers and may contribute to functional dyspepsia in a minority of cases 1
- Psychological factors - stress, anxiety, and depression are associated with symptom onset and severity 1
- Dietary triggers - certain foods may precipitate symptoms in susceptible individuals 1
- Alterations in gut microbiota - emerging evidence suggests changes in intestinal bacteria may play a role 1, 4
Critical Diagnostic Distinctions
The key clinical challenge is distinguishing GERD from dyspepsia, as management differs substantially. 1 Patients with predominant heartburn or acid regurgitation occurring more than once weekly should be classified as having GERD rather than dyspepsia. 1 However, significant symptom overlap occurs in clinical practice, and many physicians fail to identify the predominant symptom. 1
Age is the most important risk stratification factor for organic disease. 1 Patients over 55 years (or over 40 years in high-risk populations for gastric cancer) require prompt endoscopy due to substantially higher rates of serious pathology. 1, 5
Common Pitfalls
- Failing to test for H. pylori - all dyspeptic patients should undergo non-invasive testing, as eradication cures underlying peptic ulcer disease and prevents future gastroduodenal complications 1
- Misclassifying GERD as dyspepsia - carefully identify whether heartburn or epigastric pain is the predominant symptom 1
- Over-investigating young patients without alarm features - endoscopy has very low diagnostic yield in this population 1
- Attributing all symptoms to functional dyspepsia without excluding organic causes - maintain clinical vigilance for red flag features 1, 5