What causes gastroparesis?

Causes of Gastroparesis

Gastroparesis is primarily caused by diabetes, post-surgical complications, medication effects, post-viral infections, and idiopathic factors, with diabetes accounting for approximately 25% of cases. 1, 2

Major Etiologies of Gastroparesis

Endocrine/Metabolic Causes

• Diabetes mellitus: Most common identifiable cause 2
  • Accounts for approximately 25% of gastroparesis cases
  • More common in type 1 diabetes (cumulative incidence of 5%) than type 2 diabetes (1%) 3
  • Mechanism: Autonomic diabetic neuropathy affecting the gastrointestinal tract
  • Diabetic neuropathy linked to antral hypomotility and pylorospasm 1

Post-Surgical Causes

• Typically due to partial or complete vagotomy 1
  • Intended or unintended during procedures such as:
    • Esophagectomy
    • Billroth II gastrectomy
    • Fundoplication
    • Hernia repair
• Post-transplantation gastroparesis
  • Common after lung or heart-lung transplantation 1
  • May promote microaspiration into lung allograft

Medication-Induced Gastroparesis

• Several medications can delay gastric emptying 1, 2:
  • Anticholinergics
  • Glucagon-like peptide-1 (GLP-1) receptor agonists
  • Opioids (common iatrogenic and potentially reversible cause)

Post-Viral/Post-Infectious Gastroparesis

• Usually self-limited but can be prolonged in some patients 1
• Not typically responsive to G-POEM (gastric peroral endoscopic myotomy) 1

Malignancy-Related Gastroparesis

• Can occur with several cancers 4:
  • Gastric cancer
  • Pancreatic cancer
  • Gallbladder cancer
  • Esophageal cancer
  • Lung cancer
  • Leiomyosarcoma
• Mechanisms include:
  • Malignant infiltration of the autonomic nervous system
  • Paraneoplastic dysmotility with autoantibody-mediated destruction of the enteric nervous system 4

Idiopathic Gastroparesis

• Most common form of gastroparesis 1
• Diagnosis of exclusion after ruling out other causes

Pathophysiological Mechanisms

1. Interstitial Cells of Cajal (ICC) Dysfunction:

   • ICCs are the pacemaker cells of the GI tract 4
   • Damage to ICCs disrupts normal gastric motility 5

2. Autonomic Neuropathy:

   • Particularly in diabetic gastroparesis
   • Affects vagal nerve function controlling gastric emptying 2

3. Pyloric Dysfunction:

   • Pylorospasm characterized by prolonged intermittent contractions
   • Marked increases in baseline tone at the pylorus 1

4. Innate Immune Dysregulation:

   • Injury to enteric nervous system components through:
     • Paracrine effects
     • Oxidative stress mediators 5

5. Failure of Antral Contractions:

   • Impedes gastric emptying
   • Main pathophysiological disturbance in gastroparesis 1

Clinical Pitfalls to Avoid

• Not discontinuing interfering medications before diagnostic testing 2
• Treating based on symptoms alone without confirming delayed gastric emptying 2
• Prescribing opioids for abdominal pain in gastroparesis (worsens condition) 2
• Overlooking nutritional status in severe cases 2
• Failing to rule out mechanical obstruction before diagnosing gastroparesis 1, 2
• Not recognizing the overlap between gastroparesis and functional dyspepsia symptoms 6

Gastroparesis represents a spectrum of gastric neuromuscular dysfunction that includes impaired gastric accommodation and requires a confirmed diagnosis of delayed gastric emptying via appropriate testing such as gastric scintigraphy or breath testing 6.