What is the pathophysiology of gastroparesis?

Pathophysiology of Gastroparesis

Gastroparesis is characterized by delayed gastric emptying in the absence of mechanical obstruction, resulting from a complex interplay of neuromuscular dysfunction affecting gastric motility, accommodation, and sensory function. 1

Core Pathophysiological Mechanisms

Gastric Motor Dysfunction

• Antral hypomotility: Reduced contractility of the gastric antrum impairs the grinding and propulsion of food particles 1
• Pyloric dysfunction: Pylorospasm characterized by prolonged intermittent contractions and increased baseline tone impedes gastric emptying 1
• Antroduodenal and pyloric dyscoordination: Disrupted coordination between antral contractions and pyloric relaxation prevents proper food passage 1

Impaired Gastric Accommodation

• Reduced ability of the proximal stomach (fundus) to relax and accommodate food
• Associated with early satiety, postprandial fullness, and weight loss 1
• Contributes to symptoms independently of delayed emptying 1

Altered Visceral Sensitivity

• Visceral hypersensitivity: Increased perception of gastric stimuli, including distension and chemical stimuli 1
• Mechanical sensitivity to balloon distension is increased following meals and associates with postprandial pain 1
• Chemical sensitivity to acid infusion worsens symptoms, particularly nausea 1

Neural Dysfunction

• Vagal nerve injury: Disruption of vagal afferent and efferent pathways 1
• Enteric nervous system damage: Loss of interstitial cells of Cajal (ICC), which are pacemaker cells that regulate gastric motility 1
• Autonomic neuropathy: Particularly relevant in diabetic gastroparesis 1

Etiology-Specific Pathophysiology

Diabetic Gastroparesis

• Accounts for approximately 25% of gastroparesis cases 1
• Diabetic neuropathy linked to antral hypomotility and pylorospasm 1
• Hyperglycemia directly impairs gastric motility and increases perception of gastrointestinal sensations 1
• Loss of ICC and CD206+ macrophages in the gastric wall 1

Post-Surgical Gastroparesis

• Typically due to partial or complete vagotomy (intended or unintended) 1
• Common after procedures like esophagectomy, gastrectomy, and fundoplication 1

Idiopathic Gastroparesis

• Most common form, often following viral infections 1
• May involve immune-mediated damage to the enteric nervous system 1

Pathophysiological Impact on Symptoms

• Nausea and vomiting: Related to gastric dysrhythmias, antral hypomotility, and increased visceral sensitivity 1
• Early satiety and postprandial fullness: Associated with impaired gastric accommodation and delayed emptying 1
• Abdominal pain: Linked to visceral hypersensitivity and altered central processing of sensory signals 1
• Bloating: Result of impaired gastric emptying and intestinal dysmotility 1

Metabolic and Nutritional Consequences

• Disrupted coordination between nutrient delivery and insulin action in diabetic patients 1
• "Gastric hypoglycemia" in insulin-treated patients due to mismatched insulin action and delayed nutrient absorption 1
• Malnutrition and weight loss due to reduced oral intake and malabsorption 1

Emerging Concepts

• Gastroparesis and functional dyspepsia may represent a spectrum of the same pathophysiological disorder rather than distinct entities 1
• Altered intestinal permeability and changes in the gastric and small bowel microbiome may contribute to symptom generation 1
• Central nervous system processing abnormalities affect symptom perception and intensity 1

Understanding these complex and often overlapping pathophysiological mechanisms is essential for developing targeted therapeutic approaches for patients with gastroparesis.