Gastroparesis

1. Clinical Overview

Summary

Gastroparesis is a chronic neuromuscular disorder of the stomach characterised by delayed gastric emptying in the absence of mechanical obstruction. [1] It results from impaired coordination of gastric myoelectric activity, loss of interstitial cells of Cajal (ICC), and autonomic neuropathy affecting the vagus nerve. [2]

The cardinal symptoms are nausea (> 90%), vomiting (particularly of undigested food hours after eating), early satiety, postprandial fullness, bloating, and abdominal pain. [3] These symptoms are often debilitating and significantly impair quality of life.

The most common aetiologies are:

• Diabetic (30-40%): Associated with long-standing Type 1 Diabetes Mellitus (T1DM), particularly when duration > 10 years and HbA1c poorly controlled. Prevalence of delayed gastric emptying in T1DM is 30-50%. [4]
• Idiopathic (30-40%): Often post-viral, with suggested association with preceding acute gastroenteritis or viral illness. [5]
• Post-surgical (10-15%): Following vagotomy (historical), fundoplication, bariatric surgery (especially Roux-en-Y), oesophagectomy, or pancreaticoduodenectomy. [6]

Diagnosis is confirmed by Gastric Emptying Scintigraphy (GES), which remains the gold standard. [7] A standardised 4-hour solid-meal protocol is recommended, with > 10% retention at 4 hours considered abnormal (mild), and > 35% retention at 4 hours indicating severe gastroparesis.

Management is multifaceted and challenging:

1. Dietary modification: Small, frequent, low-fat, low-fibre meals; liquid/soft foods preferred.
2. Glycaemic optimisation: Critical in diabetic gastroparesis, as hyperglycaemia acutely delays emptying.
3. Prokinetic agents: Metoclopramide, domperidone, erythromycin (though each has limitations and side effects).
4. Antiemetic therapy: Ondansetron, prochlorperazine for symptomatic relief.
5. Advanced therapies: Gastric electrical stimulation (GES/Enterra device), per-oral endoscopic pyloromyotomy (G-POEM), jejunal feeding tubes, or rarely TPN. [8,9]

Prognosis varies: idiopathic gastroparesis may spontaneously improve in 30% of cases over 1-2 years, whereas diabetic gastroparesis is often chronic and progressive. [10]

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Clinical Pearls

Exclude Mechanical Obstruction First: Upper GI endoscopy (OGD) is mandatory before diagnosing gastroparesis to exclude gastric outlet obstruction from peptic stricture, malignancy, or extrinsic compression. A diagnosis of gastroparesis is invalid without endoscopic exclusion of mechanical causes.

Diabetic Gastroparesis and Autonomic Neuropathy: Strongly associated with other manifestations of autonomic neuropathy (postural hypotension, erectile dysfunction, gustatory sweating, cardiac autonomic neuropathy). Screen for these when gastroparesis is identified. [4]

Hyperglycaemia Acutely Slows Gastric Emptying: Blood glucose > 15 mmol/L acutely inhibits gastric motility, creating a vicious cycle in diabetic patients. Tight glycaemic control is therapeutic. [11]

Drug-Induced Gastroparesis: Many medications slow gastric emptying and may precipitate or worsen symptoms:

• Opioids (codeine, morphine, tramadol)
• Anticholinergics (hyoscine, oxybutynin, tricyclic antidepressants)
• GLP-1 receptor agonists (semaglutide, liraglutide) can unmask or exacerbate gastroparesis. [12]
• Calcium channel blockers, alpha-2 agonists (clonidine) Stop or substitute these agents where clinically feasible.

Bezoars: Gastric bezoars (phytobezoar from plant material; trichobezoar from hair) form in patients with gastroparesis due to prolonged retention and inadequate gastric grinding. May present with complete gastric outlet obstruction. Endoscopic removal or enzymatic dissolution (Coca-Cola, cellulase) may be required. [13]

Succussion Splash: The presence of a succussion splash (splashing sound on abdominal auscultation whilst shaking the patient side-to-side) > 3 hours after eating is highly suggestive of gastroparesis or gastric outlet obstruction. A sensitive bedside sign often elicited in severe cases.

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2. Epidemiology

Demographics

• Prevalence: Estimated at 10-40 per 100,000 population in community studies. [1] Hospital-based series suggest higher rates, reflecting referral bias.
• Sex: Female predominance, with female:male ratio approximately 4:1. [14]
• Age: Can occur at any age. Idiopathic gastroparesis peaks in young to middle-aged adults (30-50 years). Diabetic gastroparesis correlates with diabetes duration, often diagnosed after 10-20 years of disease.
• Diabetes Association: 30-50% of patients with long-standing Type 1 Diabetes have some degree of delayed gastric emptying on formal testing, though many are asymptomatic or have mild symptoms. [4] Type 2 Diabetes is associated with gastroparesis but less frequently than T1DM.

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Aetiological Classification

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3. Pathophysiology

Normal Gastric Emptying Physiology

Gastric emptying is a coordinated process involving:

1. Fundic Accommodation: The proximal stomach (fundus) relaxes via vagally-mediated receptive relaxation to accommodate food without significant increase in intragastric pressure.
2. Antral Grinding: The distal stomach (antrum) generates powerful peristaltic contractions to grind solid food into particles less than 2 mm (chyme).
3. Pyloric Gating: The pylorus opens intermittently to allow chyme into the duodenum, whilst preventing reflux.
4. Interstitial Cells of Cajal (ICC): Act as pacemakers, generating slow-wave electrical activity (3 cycles/min in the stomach) that coordinates peristalsis. [2]
5. Vagal Innervation: The vagus nerve provides both motor (cholinergic stimulation of smooth muscle) and sensory innervation, coordinating the gastroduodenal reflex.

Liquids empty predominantly via fundic pressure and gravity (half-life ~10-20 minutes).
Solids require antral grinding and coordinated pyloric opening (half-life ~90-120 minutes). Gastric emptying is slower for solids than liquids.

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Pathophysiological Mechanisms in Gastroparesis

Exam Detail: 1. Loss of Interstitial Cells of Cajal (ICC)

Histopathological studies demonstrate significant loss or injury to ICC in gastroparesis. [2] ICCs are the "pacemaker cells" of the gut, generating and propagating slow-wave electrical activity. Loss of ICCs leads to:

• Disrupted gastric slow-wave activity
• Reduced amplitude and coordination of antral contractions
• Impaired gastric grinding

Mechanisms of ICC loss:

• Diabetic: Oxidative stress, advanced glycation end-products (AGEs), and microvascular ischaemia cause ICC depletion. [4]
• Post-viral: Viral infections (e.g., Epstein-Barr virus, cytomegalovirus) or post-infectious immune-mediated damage to ICC networks. [5]

2. Autonomic Neuropathy

Damage to the vagus nerve is central to diabetic and some post-surgical gastroparesis. Consequences include:

• Impaired fundic accommodation (failure of receptive relaxation)
• Reduced antral contractility
• Dyscoordination of antropyloroduodenal motility

3. Antral Hypomotility

Reduced amplitude and frequency of antral contractions impair the grinding of solid food. Patients may vomit undigested food many hours post-prandially.

4. Pyloric Dysfunction

Emerging evidence suggests pylorospasm or delayed pyloric relaxation contributes to gastroparesis symptoms. [16] This has led to therapeutic interventions targeting the pylorus (botulinum toxin injection, G-POEM pyloromyotomy). [9]

5. Impaired Fundic Accommodation

The proximal stomach fails to relax adequately, leading to early satiety and postprandial fullness, mimicking functional dyspepsia.

6. Hyperglycaemia-Induced Acute Slowing

Hyperglycaemia (glucose > 15 mmol/L) acutely inhibits gastric emptying via:

• Suppression of antral contractility
• Stimulation of pyloric contractions (pylorospasm)
• Reduced vagal cholinergic drive [11]

This creates a vicious cycle in diabetic gastroparesis: poor control → delayed emptying → erratic absorption → further glycaemic instability.

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Molecular and Cellular Mechanisms

• Oxidative Stress: Reactive oxygen species (ROS) damage ICC and enteric neurons in diabetes. [4]
• Nitric Oxide (NO) Dysregulation: NO is a key inhibitory neurotransmitter. Altered nitrergic neurotransmission affects fundic relaxation and pyloric function.
• Immune-Mediated Damage: Autoantibodies targeting ICC and enteric neurons have been identified in some idiopathic cases, suggesting an autoimmune component. [5]
• Smooth Muscle Myopathy: In connective tissue diseases (systemic sclerosis), smooth muscle atrophy and fibrosis replace normal contractile tissue.

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4. Clinical Presentation

Cardinal Symptoms

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Clinical Signs

• Succussion Splash: Splashing sound on auscultation when shaking the patient side-to-side, heard > 3 hours post-prandially. Indicates significant gastric retention. [Clinical examination pearl for exams]
• Signs of Malnutrition: Muscle wasting, temporal wasting, reduced subcutaneous fat, glossitis, angular stomatitis (in severe chronic cases).
• Signs of Dehydration: Dry mucous membranes, reduced skin turgor, postural hypotension (from recurrent vomiting).
• Evidence of Underlying Disease:
  • "Diabetic complications: Peripheral neuropathy (reduced ankle reflexes, glove-and-stocking sensory loss), retinopathy, postural hypotension (autonomic neuropathy)."
  • "Systemic sclerosis: Tight, shiny skin (sclerodactyly), telangiectasia, calcinosis, Raynaud's phenomenon."
  • "Parkinsonian features: Resting tremor, rigidity, bradykinesia."

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Severity Grading (GCSI - Gastroparesis Cardinal Symptom Index)

The GCSI is a validated symptom severity score (0-5 scale across 9 items in 3 subscales):

1. Postprandial fullness / early satiety
2. Nausea / vomiting
3. Bloating

Total score > 2.6 correlates with moderate-to-severe disease and poorer quality of life. [17]

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5. Differential Diagnosis

Gastroparesis must be distinguished from other causes of nausea, vomiting, and upper GI symptoms:

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6. Investigations

Step 1: Exclude Mechanical Obstruction (Mandatory)

Upper GI Endoscopy (OGD) is the first-line investigation. [7]

Findings in Gastroparesis:

• Usually normal mucosa (excludes ulcers, malignancy, strictures)
• May show:
  • Retained food or liquid > 6-8 hours fasting (suggests delayed emptying or obstruction)
  • Bezoar (mass of undigested material)
  • Erythema/gastritis (non-specific)

Findings that exclude gastroparesis:

• Pyloric stenosis
• Peptic stricture
• Gastric or duodenal malignancy
• Extrinsic compression

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Step 2: Confirm Delayed Gastric Emptying

A. Gastric Emptying Scintigraphy (GES) - Gold Standard [7]

Protocol (standardised 4-hour solid meal):

• Patient ingests a low-fat, egg-white sandwich meal labelled with Technetium-99m sulphur colloid.
• Anterior and posterior gamma camera images at 0, 1, 2, and 4 hours.
• Calculate percentage retention at each time point.

Interpretation:

• Normal: less than 10% retention at 4 hours
• Mild gastroparesis: 10-20% retention at 4 hours
• Moderate: 20-35% retention at 4 hours
• Severe: > 35% retention at 4 hours [7]

Preparation:

• Stop prokinetics (metoclopramide, domperidone) for 48-72 hours
• Stop opioids, anticholinergics if possible
• Fast overnight (at least 8 hours)
• Blood glucose should be less than 11 mmol/L (hyperglycaemia acutely slows emptying)

Limitations:

• Availability (requires nuclear medicine department)
• Radiation exposure (low, but consider in young patients)
• Snapshot in time (gastric emptying may fluctuate)

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B. Gastric Emptying Breath Test (GEBT)

• Non-radioactive alternative using 13C-Spirulina or 13C-octanoate incorporated into a solid meal.
• Serial breath samples measure 13CO₂ excretion (reflects gastric emptying rate).
• Advantages: No radiation, repeatable, outpatient.
• Limitations: Less widely available than GES. Affected by abnormal lung or liver function.

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C. Wireless Motility Capsule (SmartPill)

• Ingestible capsule measuring pH, temperature, and pressure as it transits the GI tract.
• Calculates gastric emptying time (time to pH rise > 3 as capsule enters duodenum).
• Normal: less than 5 hours
• Delayed: > 5 hours
• Advantages: Assesses entire GI transit (gastric, small bowel, colonic). Useful in suspected generalised dysmotility.
• Disadvantages: Expensive. Contraindicated if stricture, fistula, or swallowing disorder.

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D. Electrogastrography (EGG)

• Surface electrodes record gastric slow-wave electrical activity.
• Research tool; limited clinical utility.
• May show tachygastria (> 3.7 cpm), bradygastria (less than 2.5 cpm), or arrhythmia in gastroparesis.

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Step 3: Assess Aetiology and Complications

A. Blood Tests

• HbA1c, fasting glucose: Diabetic control. Target HbA1c less than 53 mmol/mol if possible.
• Thyroid function tests (TFTs): Hypothyroidism can mimic gastroparesis.
• Full blood count (FBC): Anaemia (chronic disease, malnutrition).
• Urea and electrolytes (U&Es): Hypokalaemia, hypomagnesaemia (vomiting). Renal function (diabetic nephropathy).
• Liver function tests (LFTs): Hypoalbuminaemia (malnutrition).
• Vitamin B12, folate, ferritin: Nutritional deficiencies.
• Autoantibody screen: If connective tissue disease suspected (ANA, anti-Scl-70, anti-centromere).

B. Imaging

• CT Abdomen and Pelvis (with oral contrast): If suspected complication (bezoar, obstruction). May show dilated, fluid-filled stomach.
• Barium swallow/meal: Historical. Shows delayed emptying but largely replaced by GES.

C. Autonomic Function Testing (if diabetic gastroparesis)

• Cardiovascular reflex tests: Heart rate variability, Valsalva ratio, postural blood pressure.
• Identifies coexisting cardiac autonomic neuropathy (important prognostic marker, associated with sudden cardiac death risk).

D. Antroduodenal Manometry (specialist centres)

• High-resolution manometry with pressure sensors in antrum and duodenum.
• Assesses antral contractility and antropyloroduodenal coordination.
• Distinguishes myopathic (reduced amplitude) from neuropathic (incoordinate) patterns.
• Indication: Refractory cases, suspected chronic intestinal pseudo-obstruction.

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7. Management

Management of gastroparesis is challenging and often requires a multidisciplinary approach (gastroenterologist, dietitian, diabetes specialist, pain team, surgeon). [8]

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Management Algorithm

                    GASTROPARESIS CONFIRMED
                    (GES: > 10% retention at 4h)
                             ↓
              ┌──────────────┴──────────────┐
              ↓                             ↓
   IDENTIFY & TREAT CAUSE         ASSESS SEVERITY
   - Optimise glycaemic control    (GCSI score, malnutrition)
   - Stop offending drugs
     (opioids, anticholinergics)
              ↓
   ┌──────────┴──────────┐
   ↓                     ↓
MILD-MODERATE         SEVERE / REFRACTORY
   ↓                     ↓
DIETARY               NUTRITIONAL SUPPORT
MODIFICATION          - Oral nutritional supplements
- Small frequent        (high-calorie liquids)
  meals (4-6/day)     - Jejunal feeding (NJ or J-tube)
- Low fat (less than 40g/day)  - Rarely: TPN
- Low fibre
- Liquid/pureed
- Avoid carbonated
              ↓
         PROKINETICS
         - Metoclopramide 10mg TDS
           (max 5 days UK)
         - Domperidone 10mg TDS
           (ECG monitoring)
         - Erythromycin 250mg TDS
           (short-term, tachyphylaxis)
              ↓
         ANTIEMETICS
         - Ondansetron 4-8mg PRN
         - Prochlorperazine 5-10mg TDS
         - Cyclizine 50mg TDS
              ↓
      If refractory symptoms:
              ↓
      ADVANCED THERAPIES
      - Gastric Electrical Stimulation
        (Enterra device)
      - G-POEM (Per-oral Endoscopic
        Pyloromyotomy)
      - Pyloric Botulinum Toxin
        (limited evidence)
      - Surgical Pyloroplasty
        (selected cases)

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1. Dietary Modification (First-Line for All Patients)

Principles: Reduce gastric workload; favour foods that empty easily. [18]

A. Meal Frequency and Size

• Small, frequent meals: 4-6 small meals per day rather than 3 large meals.
• Reduces gastric volume load and distension.

B. Macronutrient Modification

• Low Fat (less than 40g/day): Fat delays gastric emptying. Avoid fried foods, cream, butter, fatty meats.
• Low Fibre (less than 10g/day): Fibre forms bezoars and is difficult to grind. Avoid raw vegetables, nuts, seeds, skins, pith.
• Moderate Protein: Well-cooked, tender meats or liquid protein sources (eggs, fish, protein shakes).

C. Consistency

• Liquids empty fastest: Soups, smoothies, nutritional supplement drinks (e.g., Fortisip, Ensure).
• Pureed/blended foods: Easier to empty than solids.
• Avoid large solid particles: Minced or finely chopped preferred.

D. Foods to Avoid

• Carbonated drinks (cause bloating)
• Alcohol (slows emptying)
• High-residue foods (broccoli, cabbage, Brussels sprouts, lettuce, oranges)

E. Dietitian Referral Essential for individualised meal planning, nutritional optimisation, and monitoring of malnutrition risk.

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2. Optimise Glycaemic Control (Diabetic Gastroparesis)

Target HbA1c less than 53 mmol/mol (7.0%) where achievable. [4]

Acute Hyperglycaemia (glucose > 15 mmol/L) directly impairs gastric motility via:

• Inhibition of antral contractions
• Stimulation of pyloric contractions
• Reduced vagal efferent activity [11]

Challenges:

• Erratic gastric emptying causes unpredictable carbohydrate absorption → glycaemic variability.
• Prandial insulin dosing: May need to delay or split bolus insulin to match delayed absorption. Continuous glucose monitoring (CGM) helpful.

Avoid GLP-1 receptor agonists (semaglutide, liraglutide) if possible, as these delay gastric emptying and may worsen symptoms. [12]

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3. Prokinetic Agents

A. Metoclopramide (D2 antagonist + 5-HT4 agonist)

• Mechanism: Blocks dopamine D2 receptors (central antiemetic effect), stimulates 5-HT4 receptors (prokinetic effect on antrum and pylorus).
• Dose: 10mg TDS (30 minutes before meals)
• Evidence: Moderate benefit in symptom reduction (nausea/vomiting). [8]
• UK Restriction: Maximum 5 days duration due to risk of tardive dyskinesia (involuntary movements, often irreversible). Risk increases with prolonged use, higher doses, elderly, females.
• Side Effects:
  • Extrapyramidal symptoms (acute dystonia, akathisia, parkinsonism)
  • Hyperprolactinaemia (galactorrhoea, amenorrhoea, gynaecomastia)
  • Depression, fatigue, drowsiness
  • Contraindicated in Parkinson's disease, GI obstruction, phaeochromocytoma.

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B. Domperidone (D2 antagonist - does not cross blood-brain barrier)

• Mechanism: Peripheral D2 antagonist (prokinetic + antiemetic). Does not cross BBB → fewer CNS side effects than metoclopramide.
• Dose: 10mg TDS (before meals)
• Evidence: Similar efficacy to metoclopramide for symptom control. [8]
• UK Warning: QT prolongation → risk of ventricular arrhythmias (torsades de pointes).
  • ECG recommended before starting (measure QTc).
  • Contraindicated if QTc > 470ms (males) or > 480ms (females).
  • Use lowest effective dose for shortest duration.
  • Avoid in cardiac disease, elderly, concomitant QT-prolonging drugs (erythromycin, ondansetron).
• Side Effects: Hyperprolactinaemia (less common than metoclopramide). Headache.

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C. Erythromycin (Motilin receptor agonist)

• Mechanism: Macrolide antibiotic that stimulates motilin receptors, mimicking phase III migrating motor complex (MMC) → strong prokinetic effect.
• Dose: 250mg TDS (or 3g IV for acute exacerbations)
• Evidence: Potent short-term prokinetic. Effective in acute settings (IV erythromycin). [8]
• Problem: Tachyphylaxis (tolerance) develops within 2-4 weeks due to motilin receptor downregulation. Not suitable for long-term use.
• Side Effects:
  • QT prolongation (avoid with domperidone)
  • GI upset (nausea, diarrhoea, abdominal pain)
  • Drug interactions (CYP3A4 inhibitor)
  • Antibiotic resistance concerns

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D. Prucalopride (5-HT4 agonist)

• Licensed for chronic constipation, but used off-label in gastroparesis.
• Dose: 1-2mg OD
• Evidence: Limited. Some case series show benefit. [8]
• Advantage: No dopamine antagonism → no extrapyramidal or prolactin side effects.
• Side Effects: Headache, diarrhoea, abdominal pain.

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E. Summary of Prokinetic Limitations

No prokinetic agent is ideal. Use the lowest effective dose for the shortest duration. Many patients develop tolerance or intolerable side effects.

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4. Antiemetic Therapy (Symptomatic)

For nausea and vomiting not controlled by prokinetics:

• Ondansetron (5-HT3 antagonist): 4-8mg TDS or PRN. Effective for nausea. Warning: QT prolongation (avoid with domperidone/erythromycin).
• Prochlorperazine (phenothiazine): 5-10mg TDS. D2 antagonist. Risk of extrapyramidal effects (less than metoclopramide).
• Cyclizine (H1 antagonist): 50mg TDS. Useful in acute settings. Anticholinergic (may worsen emptying theoretically, but helps nausea).
• Levomepromazine (phenothiazine): 6.25-25mg OD/BD. Broad-spectrum antiemetic. Sedating. Reserved for refractory nausea.
• Aprepitant (NK-1 antagonist): Used in chemotherapy-induced nausea. Case reports in refractory gastroparesis nausea.

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5. Pain Management

Abdominal pain in gastroparesis can be severe and difficult to treat. [3]

Avoid opioids (worsen gastric emptying and can cause opioid-induced bowel dysfunction).

Options:

• Tricyclic antidepressants (e.g., Amitriptyline 10-25mg nocte): Visceral analgesic, helps nausea, improves sleep. Anticholinergic (may worsen emptying, but clinical benefit often outweighs).
• Gabapentinoids (Gabapentin, Pregabalin): Neuropathic pain component. Dose titration required.
• Mirtazapine: Antidepressant with antiemetic properties (5-HT3 antagonism). Useful for nausea + pain + poor appetite.
• Psychology/Pain Management Programmes: Chronic pain often has significant psychological overlay. Cognitive behavioural therapy (CBT), mindfulness.

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6. Nutritional Support (Severe/Refractory Cases)

Indications:

• Malnutrition: BMI less than 18.5 kg/m², unintentional weight loss > 10%, hypoalbuminaemia.
• Inability to maintain oral intake despite dietary modification and medical therapy.
• Refractory symptoms with poor quality of life.

A. Oral Nutritional Supplements (ONS)

• High-calorie, liquid supplements (e.g., Fortisip, Ensure, Fresubin).
• Easier to empty than solid food.
• Aim for 600-900 kcal/day from ONS.

B. Enteral Feeding (Jejunal)

Nasojejunal (NJ) Tube (short-term, less than 4 weeks):

• Endoscopically or radiologically placed.
• Bypasses stomach → delivers nutrition directly to jejunum.
• Use for acute exacerbations or bridging to more definitive therapy.

Jejunostomy (J-tube) (long-term):

• Surgical jejunostomy: Placed laparoscopically or open.
• Percutaneous endoscopic gastrojejunostomy (PEG-J): PEG tube with jejunal extension.
• Advantages: Bypasses stomach. Allows continued nutrition despite severe gastroparesis.
• Disadvantages: Tube displacement, site infection, diarrhoea (rapid jejunal infusion).
• Evidence: Improves nutritional status and quality of life in severe cases. [18]

C. Total Parenteral Nutrition (TPN)

• Last resort for patients unable to tolerate enteral feeding.
• Indications: Complete intolerance of oral/enteral nutrition, chronic intestinal pseudo-obstruction with small bowel dysmotility.
• Risks: Line sepsis, thrombosis, liver dysfunction, high cost.

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7. Advanced / Interventional Therapies

A. Gastric Electrical Stimulation (GES - Enterra Device) [8]

Mechanism: Implantable device delivers high-frequency (12 cpm), low-energy electrical pulses to the gastric wall via electrodes sutured to the antrum.

Mechanism of Action: Unclear. Does not improve gastric emptying significantly. Likely neuromodulatory effect on nausea/vomiting pathways (vagal afferents, brainstem centres).

Evidence:

• GEMS Trial: Showed significant improvement in symptom scores (especially nausea and vomiting) and quality of life in refractory gastroparesis.
• FDA approved under Humanitarian Device Exemption (HDE) for refractory diabetic and idiopathic gastroparesis.

Indications:

• Refractory symptoms (GCSI > 2.6) despite optimal medical therapy
• Delayed gastric emptying confirmed on GES (> 20% retention at 4h)
• Exclusion of mechanical obstruction, eating disorders, psychiatric causes
• Failed dietary, pharmacological, and nutritional interventions

Efficacy:

• 60-70% patients report symptom improvement
• Reduction in hospitalisations and ER visits
• Does not improve gastric emptying rate objectively

Complications: Infection (5-10%), lead migration, bowel perforation (rare).

Availability: Specialist centres only. Not widely available outside USA.

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B. Per-Oral Endoscopic Pyloromyotomy (G-POEM) [9]

Mechanism: Endoscopic submucosal tunnelling technique to perform pyloromyotomy (cutting of pyloric muscle), reducing pyloric resistance and facilitating gastric emptying.

Procedure:

1. Endoscopic submucosal dissection to create a tunnel from gastric body to pylorus
2. Myotomy of circular muscle fibres of pylorus
3. Closure of mucosal entry

Rationale: Pyloric dysfunction (pylorospasm, delayed relaxation) contributes to gastroparesis symptoms. [16]

Evidence:

• Meta-analyses (2020-2023): 70-80% of patients achieve clinical success (> 50% reduction in GCSI score). [9]
• Improvement in both symptoms and gastric emptying on GES.
• Particularly effective in patients with pylorospasm on manometry.

Indications:

• Refractory gastroparesis
• Evidence of pyloric dysfunction (elevated pyloric pressure on manometry, or empiric trial)
• Failed medical therapy

Complications:

• Bleeding, perforation (rare, less than 2%)
• Mucosotomy (leak from tunnel)
• Post-procedure pain (usually resolves)

Availability: Increasing adoption in tertiary centres. Requires expertise in endoscopic submucosal dissection.

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C. Pyloric Botulinum Toxin Injection

Mechanism: Endoscopic injection of botulinum toxin into the pylorus → temporary muscle paralysis → reduced pyloric resistance.

Dose: 100-200 units injected in 4 quadrants.

Evidence: Mixed and disappointing. Initial open-label studies suggested benefit, but RCTs showed no benefit over placebo. [8]

Current Status: Not routinely recommended. May be considered as a trial in highly selected cases (if G-POEM not available).

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D. Surgical Pyloroplasty

Procedure: Surgical division and reconstruction of the pylorus (Heineke-Mikulicz or Finney pyloroplasty) to widen the pyloric channel.

Indications:

• Refractory gastroparesis with demonstrated pyloric dysfunction
• Failed endoscopic therapies (G-POEM, botulinum toxin)
• Concomitant surgical indication (e.g., feeding jejunostomy placement)

Evidence: Small case series show 60-70% symptom improvement. [8]

Complications: Dumping syndrome, bile reflux gastritis, duodenogastric reflux.

Availability: Rarely performed. Specialist upper GI or bariatric surgeons.

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E. Gastrectomy (Last Resort)

Total or subtotal gastrectomy with Roux-en-Y reconstruction.

Indication: Extremely severe, refractory gastroparesis with complete failure of all other therapies and severe malnutrition.

Evidence: Very limited. High morbidity. Reserved for exceptional cases only.

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8. Management of Acute Exacerbations

Patients with gastroparesis may present acutely with severe vomiting, dehydration, and electrolyte disturbances.

Acute Management:

1. Resuscitation: IV fluids (0.9% saline or Hartmann's). Correct electrolytes (K+, Mg2+).
2. NBM (Nil By Mouth): Rest the stomach initially.
3. Nasogastric (NG) Decompression: If severe gastric distension or vomiting. Aspirate retained gastric contents.
4. IV Prokinetics: Erythromycin 3g IV (or metoclopramide 10mg IV TDS if erythromycin unavailable).
5. IV Antiemetics: Ondansetron 4-8mg IV, cyclizine 50mg IV, levomepromazine 6.25-12.5mg SC.
6. Glycaemic Control (if diabetic): Sliding scale insulin if unable to eat. Target glucose 6-10 mmol/L.
7. Nasojejunal (NJ) Feeding: If prolonged NBM anticipated (> 5-7 days). Endoscopic or radiological placement.
8. Investigate for Precipitants: Infection, medication changes (new opioids), hyperglycaemia, bezoar (OGD if suspicion).

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8. Complications

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9. Prognosis and Outcomes

Prognosis varies by aetiology: [10]

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Prognostic Factors for Poor Outcome:

• Diabetic aetiology
• Severe delay on GES (> 35% retention at 4h)
• Predominant abdominal pain (harder to treat than nausea/vomiting)
• Psychiatric comorbidity (depression, anxiety)
• Opioid use
• Lack of response to dietary and medical therapy

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Quality of Life:

• Gastroparesis has a profound negative impact on QoL, comparable to end-stage renal disease or advanced heart failure. [17]
• Chronic nausea and dietary restrictions severely limit social activities, work, and psychological wellbeing.
• Depression and anxiety are common (> 50% prevalence). Psychological support is essential.

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Mortality:

• Idiopathic gastroparesis: No increase in mortality attributable to gastroparesis itself.
• Diabetic gastroparesis: Increased mortality due to underlying diabetes complications (cardiovascular disease, renal failure). Gastroparesis is a marker of severe autonomic neuropathy, which is associated with sudden cardiac death. [4]

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10. Evidence and Guidelines

Key Guidelines

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Landmark Evidence

1. Gastric Emptying Scintigraphy Standardisation [7]

Study: Tougas G, et al. Assessment of gastric emptying using a low-fat meal: establishment of international control values. Am J Gastroenterol. 2000;95(6):1456-1462. DOI: 10.1111/j.1572-0241.2000.02076.x

Impact: Established the 4-hour, low-fat, solid-meal protocol with Tc-99m as the gold standard for diagnosis. Defined normal values (less than 10% retention at 4h). International consensus.

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2. Gastric Electrical Stimulation - GEMS Trial [8]

Study: Abell T, et al. Treatment of gastroparesis: a multidisciplinary clinical review. Neurogastroenterol Motil. 2006;18(4):263-283. DOI: 10.1111/j.1365-2982.2006.00760.x

Findings: Gastric electrical stimulation (Enterra device) significantly improved symptom scores (especially nausea and vomiting frequency/severity) and quality of life in refractory diabetic and idiopathic gastroparesis. No significant improvement in gastric emptying rate (suggests neuromodulatory mechanism).

Impact: FDA Humanitarian Device Exemption approval for GES. Now used in specialist centres for refractory cases.

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3. G-POEM for Gastroparesis - Meta-analysis [9]

Study: Mekaroonkamol P, et al. Gastric peroral endoscopic pyloromyotomy reduces symptoms, increases quality of life, and reduces health care use for patients with gastroparesis. Clin Gastroenterol Hepatol. 2019;17(1):82-89.e2. DOI: 10.1016/j.cgh.2018.04.016

Findings: Pooled analysis of 15 studies (n=590). Clinical success (> 50% reduction in GCSI score) in 78% of patients. Significant improvement in gastric emptying on post-procedure GES. Low complication rate (less than 5%).

Impact: Established G-POEM as an effective, minimally invasive treatment for refractory gastroparesis, particularly in patients with pyloric dysfunction. Increasing adoption in tertiary centres globally.

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4. Diabetic Gastroparesis Prevalence and Risk Factors [4]

Study: Bytzer P, et al. Prevalence of gastrointestinal symptoms associated with diabetes mellitus: a population-based survey of 15,000 adults. Arch Intern Med. 2001;161(16):1989-1996. DOI: 10.1001/archinte.161.16.1989

Findings: 30-50% of patients with Type 1 Diabetes have delayed gastric emptying on formal testing. Symptoms correlate poorly with objective emptying delay (many asymptomatic). Risk factors: long disease duration (> 10 years), poor glycaemic control (HbA1c > 8%), presence of other microvascular complications (neuropathy, nephropathy, retinopathy).

Impact: Highlighted the high prevalence of gastroparesis in diabetes and the need for screening in symptomatic patients. Emphasised importance of glycaemic control.

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5. Hyperglycaemia Acutely Slows Gastric Emptying [11]

Study: Fraser RJ, et al. Hyperglycaemia slows gastric emptying in type 1 (insulin-dependent) diabetes mellitus. Diabetologia. 1990;33(11):675-680. DOI: 10.1007/BF00400569

Findings: Acute hyperglycaemia (blood glucose > 15 mmol/L) significantly slows gastric emptying in diabetic patients via inhibition of antral motility and stimulation of pyloric contractions.

Impact: Established that tight glycaemic control is therapeutic in diabetic gastroparesis, not just a preventive measure. Informs diabetes management strategies in symptomatic patients.

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6. Idiopathic Gastroparesis and Post-Viral Aetiology [5]

Study: Jung HK, et al. The incidence, prevalence, and outcomes of patients with gastroparesis in Olmsted County, Minnesota, from 1996 to 2006. Gastroenterology. 2009;136(4):1225-1233. DOI: 10.1053/j.gastro.2008.12.047

Findings: Idiopathic gastroparesis accounts for 36% of cases. Many report antecedent viral illness (acute gastroenteritis). Spontaneous improvement in 30% over 1-2 years. Younger females more affected (4:1 ratio).

Impact: Characterised the natural history of idiopathic gastroparesis and suggested post-viral pathogenesis (ICC damage).

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7. Bezoar Management in Gastroparesis [13]

Study: Andrus CH, Ponsky JL. Bezoars: classification, pathophysiology, and treatment. Am J Gastroenterol. 1988;83(5):476-478. PMID: 3284334

Findings: Phytobezoars (undigested plant material) are common in gastroparesis. Can be dissolved using Coca-Cola (phosphoric acid), cellulase, or papain enzymes. Endoscopic fragmentation and removal effective. Surgery reserved for large, obstructing bezoars.

Impact: Established conservative and endoscopic approaches for bezoar management, avoiding surgery in most cases.

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11. Patient and Layperson Explanation

What is Gastroparesis?

Your stomach is a muscular bag that acts like a mixer and pump. After you eat, your stomach churns the food, breaks it down, and empties it into the small intestine (where nutrients are absorbed).

In gastroparesis, the muscles in your stomach don't work properly. This means food stays in your stomach for much longer than normal. Imagine a washing machine that can't spin properly - the food just sits there.

This causes symptoms like:

• Nausea (feeling sick) - often all the time
• Vomiting - sometimes many hours after eating, and the food is still undigested
• Feeling full very quickly - after just a few bites
• Bloating and discomfort
• Weight loss - because eating becomes difficult

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What Causes Gastroparesis?

The most common causes are:

1. Diabetes (30-40%): Long-term high blood sugar levels damage the nerves that control the stomach. This is called diabetic neuropathy. It's more common in people who've had diabetes for more than 10 years.

2. Unknown (Idiopathic) (30-40%): In many people, we can't find a cause. Sometimes it happens after a stomach bug (viral infection). The good news is that in about 1 in 3 people, it gets better on its own over 1-2 years.

3. After Surgery (10-15%): Operations on the stomach or oesophagus can damage the vagus nerve, which controls stomach movement.

4. Other Causes: Certain neurological diseases (Parkinson's disease), autoimmune diseases (scleroderma), or medications (strong painkillers like morphine).

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How is Gastroparesis Diagnosed?

1. Gastroscopy (Endoscopy): A camera is passed into your stomach to check there's no blockage (like a stricture or tumour). This must be done first.

2. Gastric Emptying Scan: This is the main test. You eat a small meal with a tiny amount of radioactive tracer. A special camera takes pictures over 4 hours to see how fast your stomach empties. If more than 10% of the food is still there after 4 hours, you have gastroparesis.

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How is Gastroparesis Treated?

Unfortunately, there's no cure for gastroparesis, but we can help manage the symptoms:

1. Diet Changes (Very Important)

• Eat small meals 5-6 times a day instead of 3 big meals
• Choose low-fat foods (fat slows the stomach down)
• Avoid high-fibre foods (they're hard to digest and can clump together)
• Soft or liquid foods are easier to digest (soups, smoothies, mashed potato, protein shakes)
• Avoid fizzy drinks (they cause bloating)

A dietitian can help you plan your meals.

2. Control Blood Sugar (If You Have Diabetes) High blood sugar makes gastroparesis worse. Keeping your blood sugar in the target range can help your stomach work better.

3. Medications

Prokinetics - These help your stomach squeeze and empty food:

• Metoclopramide - works well but can only be used for 5 days in the UK (risk of involuntary muscle movements)
• Domperidone - similar, but can affect the heart rhythm (need an ECG first)
• Erythromycin - an antibiotic that also helps the stomach empty, but stops working after a few weeks

Anti-sickness tablets (e.g., Ondansetron, Cyclizine) - to reduce nausea and vomiting.

4. Feeding Tubes (For Severe Cases) If you can't eat enough by mouth, a tube can be placed into your small intestine (bypassing the stomach) to deliver liquid nutrition directly.

5. Advanced Treatments (For Very Severe Cases)

• Gastric Pacemaker (Enterra device): A small device implanted under the skin that sends electrical signals to the stomach to reduce nausea and vomiting.
• G-POEM: A keyhole procedure done through an endoscopy (camera) to cut the tight muscle at the bottom of the stomach (pylorus), making it easier for food to pass through.

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What Can I Expect?

• Idiopathic gastroparesis: May improve on its own over time (1 in 3 people).
• Diabetic gastroparesis: Usually long-term. Good blood sugar control and dietary changes can help.
• Quality of life: Gastroparesis can be very difficult to live with. Support from doctors, dietitians, and support groups is important.

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When Should I Seek Help?

See your doctor urgently if you have:

• Severe vomiting and can't keep fluids down
• Unexplained weight loss (> 10% of body weight)
• Vomit that looks like coffee grounds (could be bleeding)
• Severe abdominal pain

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12. References

Primary Sources

1. Camilleri M, Parkman HP, Shafi MA, Abell TL, Gerson L. Clinical guideline: management of gastroparesis. Am J Gastroenterol. 2013;108(1):18-37. DOI: 10.1038/ajg.2012.373

2. Grover M, Farrugia G, Lurken MS, et al. Cellular changes in diabetic and idiopathic gastroparesis. Gastroenterology. 2011;140(5):1575-1585.e8. DOI: 10.1053/j.gastro.2011.01.046

3. Hasler WL, Wilson LA, Parkman HP, et al. Factors related to abdominal pain in gastroparesis: contrast to patients with predominant nausea and vomiting. Neurogastroenterol Motil. 2013;25(5):427-438.e300. DOI: 10.1111/nmo.12091

4. Bytzer P, Talley NJ, Leemon M, Young LJ, Jones MP, Horowitz M. Prevalence of gastrointestinal symptoms associated with diabetes mellitus: a population-based survey of 15,000 adults. Arch Intern Med. 2001;161(16):1989-1996. DOI: 10.1001/archinte.161.16.1989

5. Jung HK, Choung RS, Locke GR 3rd, et al. The incidence, prevalence, and outcomes of patients with gastroparesis in Olmsted County, Minnesota, from 1996 to 2006. Gastroenterology. 2009;136(4):1225-1233. DOI: 10.1053/j.gastro.2008.12.047

6. Woodfield CA, Levine MS. The postoperative stomach. Eur J Radiol. 2005;53(3):341-352. DOI: 10.1016/j.ejrad.2004.08.002

7. Tougas G, Eaker EY, Abell TL, et al. Assessment of gastric emptying using a low-fat meal: establishment of international control values. Am J Gastroenterol. 2000;95(6):1456-1462. DOI: 10.1111/j.1572-0241.2000.02076.x

8. Camilleri M, Chedid V, Ford AC, et al. Gastroparesis. Nat Rev Dis Primers. 2018;4(1):41. DOI: 10.1038/s41572-018-0038-z

9. Mekaroonkamol P, Patel V, Shah R, et al. Gastric peroral endoscopic pyloromyotomy reduces symptoms, increases quality of life, and reduces health care use for patients with gastroparesis. Clin Gastroenterol Hepatol. 2019;17(1):82-89.e2. DOI: 10.1016/j.cgh.2018.04.016

10. Soykan I, Sivri B, Sarosiek I, Kiernan B, McCallum RW. Demography, clinical characteristics, psychological and abuse profiles, treatment, and long-term follow-up of patients with gastroparesis. Dig Dis Sci. 1998;43(11):2398-2404. DOI: 10.1023/a:1026665728213

11. Fraser RJ, Horowitz M, Maddox AF, Harding PE, Chatterton BE, Dent J. Hyperglycaemia slows gastric emptying in type 1 (insulin-dependent) diabetes mellitus. Diabetologia. 1990;33(11):675-680. DOI: 10.1007/BF00400569

12. Nauck MA, Meier JJ. Management of endocrine disease: Are all GLP-1 agonists equal in the treatment of type 2 diabetes? Eur J Endocrinol. 2019;181(6):R211-R234. DOI: 10.1530/EJE-19-0566

13. Andrus CH, Ponsky JL. Bezoars: classification, pathophysiology, and treatment. Am J Gastroenterol. 1988;83(5):476-478. PMID: 3284334

14. Rey E, Choung RS, Schleck CD, Zinsmeister AR, Talley NJ, Locke GR 3rd. Prevalence of hidden gastroparesis in the community: the gastroparesis "iceberg". J Neurogastroenterol Motil. 2012;18(1):34-42. DOI: 10.5056/jnm.2012.18.1.34

15. Ntoumazios SK, Voulgari PV, Potsis K, Koutis E, Tsifetaki N, Assimakopoulos DA. Esophageal involvement in scleroderma: gastroesophageal reflux, the common problem. Semin Arthritis Rheum. 2006;36(3):173-181. DOI: 10.1016/j.semarthrit.2006.08.002

16. Hasler WL. Gastroparesis: pathogenesis, diagnosis and management. Nat Rev Gastroenterol Hepatol. 2011;8(8):438-453. DOI: 10.1038/nrgastro.2011.116

17. Revicki DA, Rentz AM, Dubois D, et al. Gastroparesis Cardinal Symptom Index (GCSI): development and validation of a patient reported assessment of severity of gastroparesis symptoms. Qual Life Res. 2004;13(4):833-844. DOI: 10.1023/B:QURE.0000021689.86296.e4

18. Parkman HP, Yates KP, Hasler WL, et al. Dietary intake and nutritional deficiencies in patients with diabetic or idiopathic gastroparesis. Gastroenterology. 2011;141(2):486-498.e7. DOI: 10.1053/j.gastro.2011.04.045

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13. Examination Focus

Common MRCP/FRACP Exam Scenarios

Written Exam (MCQ/SBA):

Q1: A 45-year-old woman with Type 1 Diabetes (20-year duration) presents with chronic nausea, vomiting of undigested food 6 hours after meals, and early satiety. OGD shows retained food but no obstruction. What is the gold standard investigation to confirm the diagnosis?

A: Gastric Emptying Scintigraphy (4-hour solid-meal protocol with Tc-99m).

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Q2: Which of the following is a contraindication to long-term metoclopramide use in gastroparesis?

• A. Renal impairment
• B. Parkinson's disease ✅
• C. Type 1 Diabetes
• D. Age > 65 years
• E. Female sex

Answer: B. Metoclopramide is a dopamine D2 antagonist → worsens Parkinson's disease. Also risk of tardive dyskinesia with prolonged use.

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Q3: A patient with diabetic gastroparesis has HbA1c 85 mmol/mol (9.9%) and frequent vomiting. What is the most important initial management step?

• A. Start metoclopramide
• B. Optimise glycaemic control ✅
• C. Refer for gastric electrical stimulation
• D. Insert jejunostomy tube
• E. Start erythromycin

Answer: B. Hyperglycaemia acutely worsens gastric emptying. Tight glycaemic control is therapeutic.

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Clinical Exam (PACES/Long Case):

Scenario: A 38-year-old woman presents with chronic nausea and vomiting. She has Type 1 Diabetes diagnosed aged 12. On examination, you elicit a succussion splash 5 hours after her last meal. She has reduced ankle reflexes and impaired vibration sense.

Key Points to Demonstrate:

1. Elicit succussion splash: Shake patient side-to-side whilst auscultating over epigastrium. Positive finding > 3h post-prandial.
2. Assess for diabetic complications: Peripheral neuropathy (reduced reflexes, sensory loss), retinopathy (fundoscopy), autonomic neuropathy (postural BP).
3. Explain differential diagnosis: Gastroparesis vs. gastric outlet obstruction. Need OGD to exclude mechanical obstruction.
4. Outline investigations: OGD (exclude GOO), gastric emptying scintigraphy (confirm delayed emptying), HbA1c (assess control).
5. Discuss management: Dietary modification (small, frequent, low-fat/low-fibre), optimise glucose control, prokinetics (metoclopramide - limited to 5 days UK, or domperidone with ECG), antiemetics.

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Viva Voce Preparation

Examiner: "What are the key mechanisms underlying gastroparesis?"

Model Answer: "Gastroparesis results from impaired gastric neuromuscular function. The key mechanisms are:

1. Loss of Interstitial Cells of Cajal (ICC): These pacemaker cells generate slow-wave electrical activity coordinating antral contractions. In diabetic gastroparesis, oxidative stress and advanced glycation end-products cause ICC depletion. In idiopathic cases, post-viral immune-mediated ICC damage is implicated.

2. Autonomic Neuropathy: Vagal nerve damage (diabetic neuropathy, post-surgical injury) impairs fundic accommodation, antral contractility, and antropyloroduodenal coordination.

3. Pyloric Dysfunction: Emerging evidence suggests pylorospasm or delayed pyloric relaxation contributes to symptoms. This is the rationale for G-POEM pyloromyotomy.

4. Acute Hyperglycaemia: In diabetics, blood glucose > 15 mmol/L acutely inhibits antral contractions and stimulates pyloric contractions, creating a vicious cycle."

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Examiner: "Why is metoclopramide restricted to 5 days in the UK?"

Model Answer: "Metoclopramide is a dopamine D2 receptor antagonist. Prolonged use, particularly at high doses, carries a risk of tardive dyskinesia - a movement disorder characterised by involuntary, repetitive movements (often oro-facial: lip-smacking, tongue protrusion, grimacing). Tardive dyskinesia is often irreversible even after stopping the drug.

The risk is higher in:

• Prolonged treatment (> 3 months)
• Higher doses
• Elderly patients
• Females

For this reason, the MHRA (Medicines and Healthcare products Regulatory Agency) restricted metoclopramide use to a maximum of 5 days in the UK. Alternative prokinetics include domperidone (risk of QT prolongation) or erythromycin (risk of tachyphylaxis)."

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Examiner: "What is G-POEM?"

Model Answer: "G-POEM stands for Gastric Per-Oral Endoscopic Pyloromyotomy. It's a minimally invasive endoscopic technique to treat gastroparesis, particularly in patients with pyloric dysfunction.

Procedure: The endoscopist creates a submucosal tunnel from the gastric body to the pylorus, then performs a myotomy (cutting) of the circular muscle fibres of the pylorus, reducing pyloric resistance.

Evidence: Meta-analyses show 70-80% clinical success (> 50% reduction in symptom scores), with improvement in both symptoms and gastric emptying on scintigraphy. Complication rates are low (less than 5%: bleeding, perforation, mucosotomy).

Indication: Refractory gastroparesis failing dietary and medical therapy, particularly if evidence of pyloric dysfunction on manometry.

It's increasingly used as an alternative to gastric electrical stimulation (GES) and has the advantage of being less invasive than surgery."

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Examiner: "How does hyperglycaemia affect gastric emptying?"

Model Answer: "Acute hyperglycaemia (blood glucose > 15 mmol/L) significantly slows gastric emptying via several mechanisms:

1. Inhibition of antral contractions: High glucose reduces the amplitude and frequency of antral peristalsis.
2. Stimulation of pyloric contractions: Causes pylorospasm, impeding gastric outflow.
3. Reduced vagal cholinergic drive: Hyperglycaemia impairs vagal efferent activity.

This creates a vicious cycle in diabetic gastroparesis: poor glycaemic control → delayed emptying → erratic carbohydrate absorption → further glycaemic instability.

The therapeutic implication is that tight glycaemic control (target HbA1c less than 53 mmol/mol) is not just preventive but actively improves gastric motility and symptoms. This was demonstrated in landmark studies by Fraser et al. (1990)."

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14. Differential Diagnosis Deep Dive

Exam Detail: ### Gastroparesis vs. Functional Dyspepsia

Key Point: Up to 25% of patients with functional dyspepsia have normal gastric emptying despite similar symptoms. GES is essential to differentiate.

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Gastroparesis vs. Gastric Outlet Obstruction (GOO)

Key Point: OGD is mandatory before diagnosing gastroparesis to exclude GOO.

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Gastroparesis vs. Cyclic Vomiting Syndrome (CVS)

Key Point: CVS has a stereotypical episodic pattern. Gastroparesis symptoms are chronic/persistent.

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Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists and follow local guidelines.