Gastroduodenal Disorders Flashcards
Describe the stomach divisions and the different functions assigned to each area.
5 basic functions: o Storage o Mixing and mechanical breakdown o Proteolytic digestion o Absorption of water, salts, alcohol, and some drugs o Secretion of digestive hormones
2 main functional divisions:
o Body and fundus = exocrine stomach and adaptive/storage region
o Antrum = endocrine stomach and propulsive region
Exocrine vs. endocrine stomach
Exocrine stomach (body) o Lined with columnar epithelial cells o Contains functional glandular units 4 main kinds of cells: • Mucus cells = mucus, HCO3- • Parietal cells = HCl, intrinsic factor • Chief cell (primarily in fundus) = pepsinogen • Enterochromaffin-like cells (ECL); primarily in body = histamine
Endocrine stomach (antrum)
o Mucous epithelial cells
o G cells (antrum) = gastrin
o D cells (throughout stomach) = inhibitory somatostatin
Gastric acid secretion: phases
Basal rate = diurnal (greatest in evening; least in early morning)
Phases:
Cephalic
• Stimulated by eating or thought of food
• Via vagus nerve
Gastric phase
• Stimulated by gastrin
• Stimulated by antral distention and presence of protein
Intestinal phase
• Modulates acid secretion via endocrine pathways as food is digested and absorbed in intestine
State the mechanisms behind ulcer formation and the balance between aggressive and protective factors.
Mucosal cytoprotection:
o Buffered Surface Mucous Layer
• “Unstirred layer”
o Gastric epithelial cells = rapid turnover, tight junctions
o Rich blood flow maintains oxygenation for HCO3- transport during acid production
Prostaglandins
• THE primary factor mediating cytoprotection
• Stimulate bicarbonate and mucus production
• Help maintain adequate mucosal blood flow
• Inhibit histamine and H+ production
Prostaglandin deficiency is final common pathway to injury
Ulcer etiology = from disruption in balance: Factors contributing to ulcer production: • H. pylori • NSAIDs: inhibit PGE production, local irritant • Acid (Old dictum “No acid, no ulcer”) • Pepsin • Bile acids • Pancreatic enzymes • Tobacco, caffeine, alcohol • Heredity • Delayed emptying • Stress, steroids
Protective factors: • Mucus • Bicarbonate • Mucosal blood flow • Prostaglandins
Analyze the actions of H. pylori in its role in ulcer disease
H. pylori characteristics o Gram negative rod o Microaerophilic o Flagellated o Urease producing (cloud of urea) o Lives beneath mucus layer
Associated with: o Chronic active gastritis o Duodenal ulcers o Gastric ulcers o Gastric adenocarcinoma o Gastric MALToma (lymphoma)= Mucosa Associated Lymphoid Tissue tumor
Oral Transmission of H. pylori: o By families in early childhood o Person to person in saliva, vomitus, feces o Overcrowded living situations o Poor water sanitation o Higher incidence in GI lab workers
Pathogenesis
Adapted to the niche of the gastric environment
• Urease converts urea to CO2 and NH3 = allows survival in acidic environment
• Flagella = allows motility to get under mucus layer
Continuously changing genome
• Imports DNA fragments from other strains
Able to shift between 32 different outer membrane proteins (adhesins) for adherence
Creates a chronic infection/inflammation
• TH1 based immune response
• Paradoxical (TH1 usually to intracellular pathogens)
• Causes apoptosis of epithelial cells
• Increases gastrin release
• Increased IL-8 → activates neutrophils
• Strong humoral response
• Does NOT lead to eradication
Analyze the role of NSAIDs in ulcer disease
Prostaglandins = protective o Maintain blood flow o Stimulate mucus and HCO3- production o Inhibit histamine and H+ production NSAIDs inhibit cyclooxygenase → inhibits prostaglandin production → erosion and ulcer formation
Determine when testing for H. pylori is appropriate and distinguish between the different diagnostic tests available.
When to test: o Dyspepsia without "alarm” signs o Peptic ulcer disease o Gastric cancer o Gastric lymphoma
Diagnostic tests:
Histopathology
• Biopsy
Urease testing
• Biopsy
• Place small sample of stomach lining in agar gel with urea and pH sensitive dye
• If urea present → turns into ammonia and CO2 → dye turns from yellow to red
Urea breath test
• Patient eats radiolabeled urea meal
• If urea present in stomach = broken down = labeled CO2 breathed out = collect and analyze
Stool antigen
• Inexpensive, accurate
• Non-invasive
Serology
• Accurate BUT does not distinguish between active vs. past infections
• Serum Ab testing remains positive even after clearing infection
Propose treatment regimens for different types of ulcers; both medical and surgical.
Medical therapy
Acid suppression:
• PPI (almost always used)
• H2 receptor antagonists (weaker agents)
Continue for 8 weeks
Discontinue NSAIDs
Eradication of H. pylori:
• Multiple antibiotics
• Usually combination of 2, sometimes 3
• Clarithromycin + amoxicillin OR metronidazole
• Take with food to prolong contact time with gastric mucosa
• 10 – 14 days
• Need to be retested after treatment
• No antibiotics, Pepto-Bismol, or PPI within 2 weeks of testing
Surgery Indicated: • Refractory outlet obstruction • Unresponsive GI bleeding • Perforation • Malignancy • Recurrent ulcers Procedures: • Antrectomy with vagotomy • Truncal vagotomy with pyloroplasty • Highly selective vagotomy
Peptic Ulcer disease: epidemiology
Location: o Stomach (typically body, antrum, pylorus) o Duodenum (bulb ONLY)
Epidemiology
o Affects 10% of men; 5% of women
o 500,000 new cases/year and 4 million recurrences
o Low mortality (<15,000/year)
Peptic Ulcer disease: symptoms
Dyspepsia: epigastric burning, severe “hunger” pains, nausea sensation
• May be improved by eating or taking antacids
May be asymptomatic (present with bleeding)
Alarm symptoms = early endoscopy required: • Bleeding • Anemia • Early satiety • Unexplained weight loss • Progressive dysphagia • Odynophagia • Recurrent vomiting • Family history of GI cancer • Previous esophagogastric malignancy • Age > 50 years (more susceptible to complications)
Peptic Ulcer disease: complications
Bleeding
• Most common complication (10-20%)
• Mortality: 8-10%
• Hematemesis or melena
Gastric outlet obstruction (<2%)
• May lead to free perforation
• May have posterior perforation into pancreas with secondary pancreatitis
Duodenal ulcers = special considerations • More common than gastric ulcers • Always benign • Almost always in bulb (1st part) • Except for hypersecretory states (hypergastrinemia due to Zollinger Ellison Syndrome or gastrinoma) Posterior wall ulcers • Overly gastroduodenal artery • Much higher risk of fatal hemorrhage
Gastric ulcers = special considerations
• Almost always benign BUT have malignant potential
• So = repeat endoscopy after course of acid suppression
• Document healing and biopsy for malignancy
Peptic Ulcer disease: diagnosis
o Upper endoscopy (preferred since able to perform biopsy) or upper GI x-ray series
o Need to re-endoscope gastric ulcers after complete therapy
Describe the relationship between H. pylori and gastric malignancy.
Treating H. pylori → decreases ulcer recurrence rates from 60-70% to less than 5-10%
Describe and explain why proton pump inhibitors are more effective than histamine-2 receptor antagonists at suppressing acid secretion.
PPIs
o Ex: Omeprazole, pantoprazole, lansoprazole, esomeprazole, rabeprazole, dexlansoprazole
o Inhibit the final step of acid secretion
• Bind to and inhibit the parietal cell H+/K+ ATPase (“proton pump”)
o Most potent acid suppressing medication available
o Uses: peptic ulcer disease, GERD, and part of therapy to eradicate H. pylori
Histamine receptor antagonists (H2 blockers)
o Ex: Ranitidine, famotidine, cimetidine, nizatidine
o Histamine = binds to H2 receptors on parietal cell H+K+ATPase = acts as paracrine stimulator for acid secretion
o Less potent acid suppression when compared to PPIs
• Only one of many pathways to induce acid secretion
o Uses: Much less effective than PPIs, but still effective in treating peptic ulcer disease and GERD
