Gastroparesis

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 Gastroparesis

Definition
Gastroparesis is a chronic motility disorder characterized by delayed gastric emptying without evidence of mechanical obstruction. It frequently presents with a constellation of upper gastrointestinal symptoms such as nausea, vomiting, bloating, and early satiety.

1. Causes and Etiology

Gastroparesis may result from various causes, including idiopathic origins, systemic diseases, surgical complications, and medications.

Major Causes:

  • Idiopathic Gastroparesis (~30–40%): No identifiable underlying etiology.
  • Diabetic Gastroparesis: A well-recognized secondary cause, particularly in patients with long-standing type 1 or type 2 diabetes.
  • Post-surgical Gastroparesis: Occurs due to vagal nerve injury during procedures such as fundoplication, esophagectomy, or gastric bypass.
  • Neurological Disorders: Parkinson’s disease, multiple sclerosis, and autonomic neuropathy.
  • Connective Tissue Disorders: Systemic sclerosis (scleroderma), amyloidosis.
  • Medications: Opioids, anticholinergics, calcium channel blockers, GLP-1 receptor agonists (e.g., semaglutide), and certain antidepressants.
  • Infectious Etiologies: Often post-viral, including norovirus and cytomegalovirus (CMV).
  • Autoimmune and Paraneoplastic Syndromes
  • Post-viral or Inflammatory Mechanisms: Hypothesized in many idiopathic cases.

2. Pathophysiology

Gastroparesis results from dysfunction in any component of the gastric motility apparatus.

Normal Gastric Motility

  • Coordinated action of the enteric nervous system, autonomic nervous system, interstitial cells of Cajal (ICCs), and smooth muscle.
  • Food is stored in the fundus, mixed in the antrum, and emptied into the duodenum in a regulated manner.

Pathophysiological Mechanisms

  • Vagal Nerve Dysfunction: Impairs parasympathetic regulation, disrupting fundic relaxation and antral contractions.
  • Smooth Muscle Dysfunction: Reduces antral contractile force.
  • Loss or Dysfunction of ICCs: These pacemaker cells mediate electrical slow waves and neuronal input; their loss results in uncoordinated motility.
  • Autonomic Neuropathy: Common in diabetes, disrupts the regulation of gastric emptying.
  • Pylorospasm or Pyloric Dysfunction: Functional outflow obstruction due to impaired relaxation.
  • Hormonal and Metabolic Factors: Acute hyperglycemia can delay gastric emptying by affecting motility and smooth muscle function.

3. Epidemiology

  • Prevalence: Estimated at 10–40 per 100,000 individuals, though likely underdiagnosed.
  • Gender Distribution: Marked female predominance (up to 80% of diagnosed cases).
  • Age of Onset: Most common in individuals aged 30–60 years.
  • Diabetic Gastroparesis:
    • Affects approximately 20–50% of patients with long-standing type 1 diabetes.
    • Affects 10–20% of those with type 2 diabetes.
  • Hospitalization Rates: Increasing in recent years due to greater awareness and diagnostic capabilities.

4. Clinical Presentation

Symptoms can vary in severity and may not correlate directly with the degree of gastric emptying delay.

Common Symptoms:

  • Early satiety (feeling full soon after starting a meal)
  • Nausea
  • Vomiting (often undigested food several hours post-meal)
  • Abdominal bloating
  • Epigastric pain or discomfort
  • Postprandial fullness
  • Weight loss (in severe cases)
  • Loss of appetite (anorexia)
  • Heartburn or GERD-like symptoms

5. Imaging and Diagnostic Features

A. Gastric Emptying Scintigraphy (GES) – Gold Standard


  • Utilizes a standardized radiolabeled meal.
  • Imaging is conducted over 4 hours.
  • Delayed gastric emptying is defined as:

o    60% gastric retention at 2 hours, or

o    10% retention at 4 hours.

B. Wireless Motility Capsule (SmartPill)


  • Measures intraluminal pH, pressure, and temperature during transit.
  • Provides gastric emptying time and overall gastrointestinal transit metrics.

C. Upper Endoscopy (EGD)

  • Excludes mechanical obstructions, peptic ulcer disease, or malignancy.
  • May reveal retained food despite fasting.

D. Cross-sectional Imaging (CT/MRI)

Computed tomography scan (coronal view) of the abdomen of a 65-year-old woman showing marked distention of the stomach (arrows), no obvious obstructing lesion and retention of food products secondary to gastroparesis. doi:10.1503/cmaj.160335

  • Used to exclude structural abnormalities such as tumors or strictures.
  • May show a distended stomach containing residual food.

E. Gastric Manometry

  • Measures intragastric motility patterns.
  • Useful in complex or treatment-refractory cases.

6. Treatment

Goals of Treatment:

  • Alleviate symptoms
  • Maintain nutritional status
  • Improve gastric emptying

A. Dietary and Lifestyle Modifications

  • Frequent, small meals
  • Low-fat, low-fiber diet (to reduce delay in gastric emptying)
  • Pureed or liquid meals are often better tolerated.
  • Avoid carbonated beverages, alcohol, and smoking.
  • Tight glycemic control is essential in diabetic patients.

B. Pharmacologic Therapy

1. Prokinetic Agents

  • Metoclopramide: D2 receptor antagonist; the only FDA-approved drug for gastroparesis. Black box warning for tardive dyskinesia and extrapyramidal symptoms.
  • Domperidone: D2 receptor antagonist with fewer central side effects; not FDA-approved but available through an IND protocol.
  • Erythromycin: Motilin receptor agonist; effective short-term but limited by tachyphylaxis.
  • Prucalopride: 5-HT4 agonist, studied off-label for gastroparesis.
  • Cisapride: Withdrawn in the U.S. due to the risk of cardiac arrhythmias.

2. Antiemetics

  • Ondansetron (5-HT3 antagonist)
  • Promethazine, Prochlorperazine

3. Investigational Therapies

  • Relamorelin: Ghrelin receptor agonist
  • Tradipitant: NK1 receptor antagonist
  • Aprepitant: Also used off-label for nausea control

C. Endoscopic Interventions

1. Gastric Peroral Endoscopic Myotomy (G-POEM)

  • Minimally invasive endoscopic pyloromyotomy
  • Demonstrates promising results in refractory cases

2. Botulinum Toxin Injection to the Pylorus

  • Evidence is inconsistent; it may be used diagnostically or for short-term relief

D. Surgical Interventions

  • Gastric Electrical Stimulation (GES): An Implantable device for refractory diabetic gastroparesis with severe nausea and vomiting.
  • Feeding Tubes: Jejunostomy feeding tubes for patients with severe malnutrition or intractable vomiting.
  • Partial Gastrectomy or Pyloroplasty: Rarely used; reserved as a last resort.

7. Prognosis

General Outlook:

  • Chronic, relapsing nature with variable disease course depending on etiology and treatment response.

Prognostic Factors:

  • Idiopathic cases tend to have a better prognosis than diabetic gastroparesis.
  • Severe gastric retention, poor glycemic control, and malnutrition are associated with worse outcomes.
  • Quality of life is often significantly impaired due to chronic symptoms.

Mortality:

  • Direct mortality is rare.
  • However, complications such as malnutrition, electrolyte imbalances, or aspiration may be life-threatening in severe or unmanaged cases.

Conclusion
Gastroparesis is a debilitating motility disorder with diverse etiologies and complex pathophysiology. Accurate diagnosis requires a high index of suspicion and confirmation via specialized motility testing. Management involves a multifaceted approach including dietary measures, pharmacological agents, and in selected cases, endoscopic or surgical interventions. Individualized, multidisciplinary care is essential for optimizing patient outcomes and quality of life. 

 

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