1. Peptic Ulcer Disease Lerma, Daniel Joseph M.

2. Peptic Ulcer Disease Ulcer - disruption of the mucosal integrity of the stomach and/or duodenum leading to a local defect or excavation due to active inflammation; breaks in the mucosal surface >5 mm in size, with depth to the submucosa. Burning epigastric pain exacerbated by fasting and improved with meals is a symptom complex associated with PUD

3. Gastric Anatomy gastric epithelial lining - rugae that contain microscopic gastric pits, each branching into four or five gastric glands made up of highly specialized epithelial cells. gastric cardia comprise <5% of the gastric gland area and contain mucous and endocrine cells The 75% of gastric glands are found within the oxyntic mucosa and contain mucous neck, parietal, chief, endocrine, and enterochromaffin cells. Pyloric glands contain mucous and endocrine cells (including gastrin cells) and are found in the antrum.

4. The parietal cell (aka oxyntic cell)- found in the neck, or isthmus, or in the oxyntic gland. The resting, or unstimulated, parietal cell has prominent cytoplasmic tubulovesicles and intracellular canaliculi containing short microvilli along its apical surface. H +,K + -ATPase is expressed in the tubulovesicle membrane; upon cell stimulation, this membrane, along with apical membranes, transforms into a dense network of apical intracellular canaliculi containing long microvilli. Acid secretion, a process requiring high energy, occurs at the apical canalicular surface. Numerous mitochondria (30– 40% of total cell volume) generate the energy required for secretion.

5. Gastroduodenal Defense can be envisioned as a three-level barrier, composed of preepithelial, epithelial, and subepithelial elements Preepithelial – mucus, bicarbonate, surface active phospholipids Epithelial – Cellular resistance, restitution, growth factors & prostaglandins, cell proliferation Subepithelial – Blood flow, leucocyte

6. Epidemiology/Incidence Duodenal Ulcer – occur in 6–15% of the Western population – incidence of DUs declined steadily from 1960 to 1980 and has remained stable since then – death rates, need for surgery, and physician visits have decreased by >50% over the past 30 years; reason for the reduction in the frequency of DUs is likely related to the decreasing frequency of Helicobacter pylori. Gastric Ulcer – tend to occur later in life than duodenal lesions, peak incidence in 6 th decade of life – More than half occur in males; higher likelihood of being “silent” and presenting only after a complication develops

7. Pathology Duodenal Ulcer – occur first portion of duodenum (>95%), with ~90% located within 3 cm of the pylorus. – usually 1 cm in diameter; can reach 3–6 cm (giant ulcer). – sharply demarcated, sometimesreaching the muscularis propria; base of the ulcer often consists of a zone of eosinophilic necrosis with surrounding fibrosis. Malignant DUs are extremely rare. Gastric Ulcer – In contrast to DUs, GUs can represent a malignancy – Benign GUs  often found distal to the junction between the antrum and the acid secretory mucosa; quite rare in the gastric fundus and are histologically similar to DUs. – Benign GUs associated with H. pylori are also associated with antral gastritis

8. Pathophysiology Duodenal Ulcer – H. pylori and NSAID-induced injury account for the majority – acid secretory abnormalities have been described in patients; average basal and nocturnal gastric acid secretion is increased in DU patients as compared to controls – H. pylori infection may contribute to decreased bicarbonate secretion in the duodenal bulb of patients with an active DU Gastric Ulcer – majority of GUs can be attributed to either H. pylori or NSAID- induced mucosal damage – Gastric acid output (basal and stimulated) tends to be normal or decreased in GU patients

9. Helicobacter pylori Gram (-) microaerophilic rod found most commonly in the deeper portions of the mucous gel coating the gastric mucosa or between the mucous layer and the gastric epithelium may attach to gastric epithelium but normally does not appear to invade cells. designed to live within the aggressive environment of the stomach. It is S-shaped (~0.5 x 3 m in size) and contains multiple sheathed flagella. Initially resides in the antrum, then migrates toward the more proximal segments of the stomach. Can transform into a coccoid form(dormant state) that may facilitate survival in adverse conditions. Infection initially dependent on the bacteria's motility and its ability to produce urease. Urease produces ammonia from urea, an essential step in alkalinizing the surrounding pH. Additional bacterial factors include catalase, lipase, adhesins, platelet-activating factor, and pic B (induces cytokines). Multiple strains of H. pylori exist and are characterized by their ability to express several of these factors (Cag A, Vac A, etc.). It is possible that the different diseases related to H. pylori infection can be attributed to different strains of the organism with distinct pathogenic features.

10. UGI Bleeding due to PUD Peptic ulcers are the most common cause of UGIB (50% of cases) increasing proportion is due to NSAIDs, with the prevalence of H. pylori decreasing. Ulcer characteristics at endoscopy provide important prognostic information. 1/3 of patients with active bleeding or a nonbleeding visible vessel have further bleeding that requires urgent surgery if they are treated conservatively.* In contrast, patients with clean-based ulcers have rates of recurrent bleeding approaching zero. **

11. One-third of patients with a bleeding ulcer will rebleed within the next 1–2 years. Prevention of recurrent bleeding focuses on the three main factors in ulcer pathogenesis – H. pylori eradication – NSAIDs should be discontinued if a bleeding ulcer develops, and if NSAIDs must be continued, initial treatment should be with a PPI. Long-term preventive strategies to decrease NSAID- associated ulcers include use of a cyclooxygenase 2 (COX-2) selective inhibitor (coxib) or addition of GI co-therapy to a traditional NSAID – Patients with bleeding ulcers unrelated to H. pylori or NSAIDs should remain on full-dose antisecretory therapy indefinitely. Peptic ulcers are discussed in Chap. 287.