Understanding GERD & Endoscopic Findings

• Gastrointestinal (GI) symptoms have significant economic and social consequences
• In the United States, approximately 11% of the population has a chronic digestive disease
• The prevalence rate of chronic digestive disease as high as 35% in people who are 65 years of age and older
• Functional gastrointestinal disorders (FGIDs) are also relatively common
• Functional dyspepsia (FD) and irritable bowel syndrome (IBS) include differing combinations of chronic or acute GI symptoms with no apparent structural or biochemical cause.
• Worldwide rates of dyspepsia/FD are 5.3-20.4% and IBS are 1.1–29.2%

Gastro-oesophageal Reflux Disease (GERD)

• GERD occurs when reflux triggers troublesome symptoms or esophageal injury/complications
• GERD symptoms include heartburn or regurgitation
• A common endoscopic finding associated with esophageal mucosal injury is reflux esophagitis
• NERD (non-erosive reflux disease) presents with characteristic symptoms of gastroesophageal reflux disease without esophageal injury, but may show reflux esophagitis on endoscopy in 50-70% of GERD patients
• ERD (erosive reflux disease) shows gastroesophageal reflux with evidence of esophageal injury
• Reflux esophagitis may be present on endoscopy for people with ERD, about 30-50% of GERD patients

Anti-Reflux Mechanisms

• The lower esophageal sphincter is typically closed but relaxes when bolus moves to the stomach during swallowing The esophagus enters the stomach in the abdominal cavity
• Pressure in the abdominal cavity is higher than in the thoracic cavity
• The right crus of the diaphragm acts as a sling around the lower esophagus
• GORD clinical features arise from the failure of antireflux mechanisms.
• Prolonged contact of gastric juices with the lower esophageal mucosa is a sign of GORD

Clinical Features of Dyspepsia

• Dyspepsia means indigestion, a symptom including epigastric pain, heartburn, distension, nausea or 'an acid feeling' after eating or drinking
• Potential causes of dyspepsia include:
• Functional dyspepsia
• Reflux or ulcer disease
• Gastric cancer
• Biliary tract disease
• Chronic pancreatitis
• Hepatic problems
• Diabetes mellitus
• Medication (antibiotics, iron, NSAIDs, etc)

Investigations and Diagnosis

• Clinical diagnosis made without investigation on symptoms alone is usually sufficient
• Investigation is needed for alarming symptoms like dysphagia or suspected hiatus hernia, investigated by endoscopy

Management

• Lifestyle changes include:
• Losing weight
• Stopping smoking
• Reducing alcohol consumption
• Reducing consumption of foods that aggravate symptoms (chocolate, fatty foods, coffee)
• Eating smaller meals
• Medications include:
• Simple antacids such as calcium carbonate that neutralise acid
• Raft antacids like Gaviscon liquid create a protective layer on top of stomach contents post-eating to prevents reflux
• PPIs like omeprazole reduce acid secretion by parietal cells
• H2 antagonists like ranitidine block H2 receptors to reduce acid secretion

Complications

• Continual contact of gastric juices with esophageal mucosa can cause a metaplastic change
• This condition is known as Barrett's esophagus
• Additional complications
• Reflux esophagitis
• Erosive esophagitis
• Iron deficiency anemia
• Esophageal stricture
• Aspiration of gastric contents
• Reflux laryngitis

Peptic Ulcer Disease (PUD)

• A peptic ulcer is a break in superficial epithelial cells penetrating down into the Muscularis mucosa of either stomach (GU) or duodenum (DU)
• Most DUs are found in the duodenal cap, and GUs are most commonly seen in the lesser curvature of stomach.
• Ulcer disease affects mainly older adults, peaking between 55 and 65 years of age

Pathogenesis

• Gastric hyperacidity leads to PUD
• Acidity driving PUD can result from H. pylori infection
• Acidity driving PUD can result from parietal cell hyperplasia.
• Zollinger-Ellison syndrome, characterized by multiple peptic ulcerations in the stomach, duodenum, and even jejunum, is the result of Excessive secretory responses or impaired inhibition of stimulatory mechanisms, like gastrin release

Cofactors in Peptic Ulcerogenesis

• Chronic NSAID use

• Cigarette smoking

• High-dose corticosteroids

• Alcoholic cirrhosis

• Chronic obstructive pulmonary disease

• Chronic renal failure

• Hyperparathyroidism

• Psychologic stress

• Gastric and duodenal mucosa injury occurs when the deleterious effects of gastric acid overwhelm the defensive properties of the mucosa

• Inhibition of endogenous prostaglandin synthesis decreases epithelial mucus, bicarbonate secretion, mucosal blood flow, epithelial proliferation, and mucosal resistance to injury

• Lowered mucosal resistance increases injury due to endogenous factors like acid, pepsin, and bile salts or exogenous factors like NSAIDs and ethanol

Epidemiology

• Duodenal ulcers are found in ~10% of the adult population, and are 2-3 times more common than GUs
• Developed countries show increased NSAID-associated GU prevalence, and decreasing H pylori-associated ulceration

Clinical Features

• Recurrent, burning epigastric pain, typically worse at night and when hungry with Duodenal Ulcers and relieved when eating
• Persistent, severe pain suggests ulcer penetration into other organs
• Back pain suggests penetrating posterior ulcer
• Nausea, with vomiting
• Weight loss and anorexia in GUs
• Asymptomatic presentation with hematemesis when ulcer has perforated a blood vessel

Investigations

• Test for H pylori diagnosis
• Endoscopy for older patients (over 55) or with other alarming symptoms to exclude cancer

Management of therapy for peptic ulcer

• Relieving symptoms
• Healing craters
• Preventing recurrence
• Preventing complications
• Medical therapy should include treatment with drugs, and attempt to accomplish the following:
• Reduce gastric acidity, achieved through mechanisms that inhibit or neutralize acid secretion
• Provide a prostaglandin analog
• Coat ulcer craters to prevent acid and pepsin penetration
• Remove environmental factors such as NSAIDs and smoking
• Reduce emotional stresses to the patient
• Triple therapy is used if PUD is due to H pylori infection:
• A proton pump inhibitor (e.g. Omeprazole)
• Antibiotics (e.g. Clarithromycin, Amoxicillin)
• A H2 antagonist (e.g. Cimetidine)
• Stop or review NSAID use, as well as using alternatives with lower PUD risk, or prophylactic PPIs
• Surgical therapy is also an option Management

Complications

• Possible haemorrhage for eroded ulcers with hematemesis and melena
• Perforation of the ulcer, more common in DUs than GUs, typically perforating into the peritoneal cavity
• Gastric outlet obstruction happens when the active ulcer has oedema, or is healing with associated fibrosis (scarring); may be pre-pyloric, pyloric or duodenal
• Presents as vomiting without pain
• GU = high malignant potential (5-10% of cases), always rule out malignancy with biopsy
• DU = usually benign, routine biopsy not required

Helicobacter Pylori and Chronic Gastritis

• H pylori is a gram negative, urease-producing bacterium that resides in the stomach of infected individuals
• Production of urease produces ammonia, which neutralises an acidic environment

Pathogenesis

• H. pylori secretes urease which converts urea to NH3 to alkalinize the acidic environment This allows for bacteria survival in the gastric lumen
• Bacterial colonization and attachment to epithelial cells leads to the release of cytotoxins (e.g., cagA toxin) that disrupt the mucosal barrier and damage underlying cells
• H. pylori inhibits somatostatin secretion
• Increased gastrin and H+ secretion occur
• Excess H+ delivery to the duodenum occurs
• The bacterium directly spreads to the duodenum, inhibiting duodenal HCO3- secretion
• This leads to acidification and insufficient neutralization of duodenal contents

Diagnosis

• IgG in serum show good sensitivity and specificity
• 13C-urea breath test: 13C-urea is ingested, and if H. pylori produces urease that then breaks down 13C-urea to NH3 and CO2, CO2 (carbon is 13C) will be exhaled on breath and can be detected
• Gastric sample taken by endoscopy can show histology and culture
• Rapid urease test is also an effective tool for diagnosis

Treatment

• Triple therapy helps against H. pylori
• A proton pump inhibitor (e.g. Omeprazole)
• Two antibiotics (e.g. Clarithromycin/Amoxicillin)
• H2 Antagonist (if severe)
• Treatment should last 7-14 days to be effective
• Side-effects of treatment makes people not finish the two week course

H Pylori Gastric Diseases:

• Gastritis is common in H pylori infection, which is usually asymptomatic
• The prevalence of duodenal ulcers (DUs) due to H pylori is falling due to decreased rates of H pylori infection
• Eradication of H pylori relieves symptoms and decreases chances of recurrence
• Gastric ulcers can occur due to reduction in gastric mucosal resistance due to cytokine production as a result of infection
• H pylori can also cause gastric cancer

Principles of Modern Ulcer Treatment

• Treat H pylori infection with Triple Therapy
• Proton Pump Inhibitor (e.g. Omeprazole)
• Two Antibiotics: Clarithromycin/Amoxicillin
• H₂ Antagonist (if severe)
• Stop and review NSAIDs (use alternatives with lower PUD risk) or use prophylactic PPIs as well

Reducing Gastric Acid Secretion

• Acid secretion may be reduced by inhibition of histamine at H₂ Receptors
• H₂ Receptors antagonists reduce gastric acid production by blocking the H2 receptor on the parietal cell
• Cimetidine, ranitidine, famotidine, and nizatidine
• These medications remove the amplification of Gastrin/Ach signal
• Proton Pump Inhibitors (PPIs)
• Omeprazole, lansoprazole, pantoprazole, rabeprazole, and esomeprazole
• They inactivate the parietal cell hydrogen-potassium ATPase located on the lumenal surface
• ATPase constitutes the final common pathway in the secretion of hydrogen ions
• This class of medicines is now considered the gold standard in medical therapy of peptic ulcer disease