Causes of Gastroparesis
Gastroparesis has three primary etiologies: diabetic (approximately 25% of cases), idiopathic, and post-surgical, with additional causes including post-infectious, medication-induced (particularly opioids), endocrine disorders, and connective tissue diseases. 1, 2
Primary Etiologies
Diabetic Gastroparesis
- Diabetes accounts for approximately 25% of all gastroparesis cases, making it the most common identifiable cause 1
- Affects 20-40% of patients with long-standing type 1 diabetes, particularly those with other diabetic complications 2, 3
- The pathophysiology involves damage to interstitial cells of Cajal (ICC), which generate the underlying rhythmicity within gastrointestinal smooth muscle 2
- Diabetic neuropathy leads to antral hypomotility and pylorospasm, characterized by prolonged intermittent contractions and marked increases in baseline pyloric tone 1
- The mechanism is multifactorial: reduced ICC numbers, deficiencies in inhibitory neurotransmission, reduced extrinsic autonomic neurons, smooth muscle abnormalities, and reduced intraneuronal nitric oxide levels 2
Idiopathic Gastroparesis
- Represents a substantial proportion of cases when no identifiable cause is found after thorough evaluation 4, 5
- G-POEM (gastric peroral endoscopic myotomy) has been found efficacious for idiopathic gastroparesis 1
Post-Surgical Gastroparesis
- Typically results from partial or complete vagotomy, which may be intended or unintended 1
- Common surgical procedures associated with gastroparesis include esophagectomy, Billroth II gastrectomy, fundoplication, and hernia repair 1
- Endoscopic sleeve gastroplasty can cause symptomatic gastroparesis as a common adverse event 1
Secondary and Less Common Causes
Post-Infectious Gastroparesis
- Occurs following viral infections affecting the gastrointestinal tract 6, 7
- Most patients with post-infectious gastroparesis should NOT be offered G-POEM, as this etiology often has a different natural history 1
Medication-Induced
- Opioid dependence is a critical reversible cause - patients should be weaned off opioids whenever possible and have gastric emptying re-evaluated 1
- Opioids worsen gastric emptying and symptoms, and their use should be avoided in gastroparesis management 8
Post-Transplant
- Symptomatic gastroparesis is a common adverse event after lung or heart-lung transplantation 1
Other Endocrine Disorders
- Various endocrine abnormalities beyond diabetes can cause delayed gastric emptying 1
Connective Tissue Diseases
- Scleroderma can cause neuropathic or myopathic abnormalities leading to gastroparesis 6
Pathophysiological Mechanisms
The underlying mechanisms involve:
- Failure of antral contractions and/or pyloric relaxation impeding gastric emptying 1
- Loss or dysfunction of ICC appears central to pathogenesis, affecting 30-50% of patients with longstanding diabetes 2
- Pyloric dysfunction with prolonged intermittent contractions and increased baseline tone 1
- The pyloric sphincter (approximately 1.2 cm wide zone of thickened muscularis propria) depends on neural signal transduction by ICC and conduction to smooth muscle cells 1
Clinical Caveat
Acute hyperglycemia can directly impair GI motility, so blood glucose should be optimized and controlled during diagnostic testing to avoid false positive results 2, 8. Even within physiological postprandial range, gastric emptying is slower at higher blood glucose levels 2.